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Sample records for allowable resistance requirements

  1. 46 CFR 310.62 - Allowances and expenses; required deposit.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Allowances and expenses; required deposit. (a) Items furnished. Each midshipman shall receive: Free tuition... deposit, as established by Academy regulations, to help defray the cost of items and services generally...

  2. 46 CFR 310.62 - Allowances and expenses; required deposit.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Allowances and expenses; required deposit. (a) Items furnished. Each midshipman shall receive: Free tuition... deposit, as established by Academy regulations, to help defray the cost of items and services generally...

  3. 46 CFR 310.62 - Allowances and expenses; required deposit.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Allowances and expenses; required deposit. (a) Items furnished. Each midshipman shall receive: Free tuition... deposit, as established by Academy regulations, to help defray the cost of items and services generally...

  4. 46 CFR 310.62 - Allowances and expenses; required deposit.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Allowances and expenses; required deposit. (a) Items furnished. Each midshipman shall receive: Free tuition... deposit, as established by Academy regulations, to help defray the cost of items and services generally...

  5. 46 CFR 310.62 - Allowances and expenses; required deposit.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Allowances and expenses; required deposit. 310.62 Section 310.62 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION TRAINING MERCHANT MARINE TRAINING Admission and Training of Midshipmen at the United States Merchant Marine Academy §...

  6. 40 CFR 97.41 - Timing requirements for NOX allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Timing requirements for NOX allowance... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS NOX Allowance Allocations § 97.41 Timing requirements for NOX allowance allocations. (a) The NOX allowance...

  7. 40 CFR 97.41 - Timing requirements for NOX allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Timing requirements for NOX allowance... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS NOX Allowance Allocations § 97.41 Timing requirements for NOX allowance allocations. (a) The NOX allowance...

  8. 40 CFR 97.41 - Timing requirements for NOX allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Timing requirements for NOX allowance... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS NOX Allowance Allocations § 97.41 Timing requirements for NOX allowance allocations. (a) The NOX allowance...

  9. 40 CFR 97.41 - Timing requirements for NOX allowance allocations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Timing requirements for NOX allowance... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS NOX Allowance Allocations § 97.41 Timing requirements for NOX allowance allocations. (a) The NOX allowance...

  10. 40 CFR 96.41 - Timing requirements for NOX allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Timing requirements for NOX allowance... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.41 Timing requirements for NOX allowance allocations. (a)...

  11. 40 CFR 96.41 - Timing requirements for NOX allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Timing requirements for NOX allowance... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.41 Timing requirements for NOX allowance allocations. (a)...

  12. 40 CFR 96.41 - Timing requirements for NOX allowance allocations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Timing requirements for NOX allowance... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.41 Timing requirements for NOX allowance allocations. (a)...

  13. 40 CFR 96.41 - Timing requirements for NOX allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Timing requirements for NOX allowance... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO 2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.41 Timing requirements for NOX allowance allocations. (a)...

  14. 40 CFR 96.41 - Timing requirements for NOX allowance allocations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Timing requirements for NOX allowance... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.41 Timing requirements for NOX allowance allocations. (a)...

  15. 40 CFR 96.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Timing requirements for CAIR NOX Ozone... PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Ozone Season Allowance Allocations § 96.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) By October 31, 2006, the permitting...

  16. 40 CFR 96.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Timing requirements for CAIR NOX Ozone... PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Ozone Season Allowance Allocations § 96.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) By October 31, 2006, the permitting...

  17. 40 CFR 97.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Timing requirements for CAIR NOX Ozone... TRADING PROGRAMS CAIR NOX Ozone Season Allowance Allocations § 97.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) The Administrator will determine by order the CAIR NOX...

  18. 40 CFR 97.511 - Timing requirements for TR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Timing requirements for TR NOX Ozone... TRADING PROGRAMS TR NOX Ozone Season Trading Program § 97.511 Timing requirements for TR NOX Ozone Season allowance allocations. (a) Existing units. (1) TR NOX Ozone Season allowances are allocated, for the...

  19. 40 CFR 97.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Timing requirements for CAIR NOX Ozone... TRADING PROGRAMS CAIR NOX Ozone Season Allowance Allocations § 97.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) The Administrator will determine by order the CAIR NOX...

  20. 40 CFR 97.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Timing requirements for CAIR NOX Ozone... TRADING PROGRAMS CAIR NOX Ozone Season Allowance Allocations § 97.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) The Administrator will determine by order the CAIR NOX...

  1. 40 CFR 97.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Timing requirements for CAIR NOX Ozone... TRADING PROGRAMS CAIR NOX Ozone Season Allowance Allocations § 97.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) The Administrator will determine by order the CAIR NOX...

  2. 40 CFR 96.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Timing requirements for CAIR NOX Ozone... PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Ozone Season Allowance Allocations § 96.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) By October 31, 2006, the permitting...

  3. 40 CFR 97.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Timing requirements for CAIR NOX Ozone... TRADING PROGRAMS CAIR NOX Ozone Season Allowance Allocations § 97.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) The Administrator will determine by order the CAIR NOX...

  4. 40 CFR 96.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Timing requirements for CAIR NOX Ozone... PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Ozone Season Allowance Allocations § 96.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) By October 31, 2006, the permitting...

  5. 40 CFR 96.341 - Timing requirements for CAIR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Timing requirements for CAIR NOX Ozone... PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Ozone Season Allowance Allocations § 96.341 Timing requirements for CAIR NOX Ozone Season allowance allocations. (a) By October 31, 2006, the permitting...

  6. 40 CFR 97.511 - Timing requirements for TR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Timing requirements for TR NOX Ozone... TRADING PROGRAMS TR NOX Ozone Season Trading Program § 97.511 Timing requirements for TR NOX Ozone Season allowance allocations. (a) Existing units. (1) TR NOX Ozone Season allowances are allocated, for the...

  7. 40 CFR 97.511 - Timing requirements for TR NOX Ozone Season allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Timing requirements for TR NOX Ozone... TRADING PROGRAMS TR NOX Ozone Season Trading Program § 97.511 Timing requirements for TR NOX Ozone Season allowance allocations. (a) Existing units. (1) TR NOX Ozone Season allowances are allocated, for the...

  8. 40 CFR 97.141 - Timing requirements for CAIR NOX allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Timing requirements for CAIR NOX... (CONTINUED) AIR PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS CAIR NOX Allowance Allocations § 97.141 Timing requirements for CAIR NOX allowance allocations. (a)...

  9. 40 CFR 97.141 - Timing requirements for CAIR NOX allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Timing requirements for CAIR NOX... (CONTINUED) AIR PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS CAIR NOX Allowance Allocations § 97.141 Timing requirements for CAIR NOX allowance allocations. (a)...

  10. 40 CFR 97.141 - Timing requirements for CAIR NOX allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Timing requirements for CAIR NOX... (CONTINUED) AIR PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS CAIR NOX Allowance Allocations § 97.141 Timing requirements for CAIR NOX allowance allocations. (a)...

  11. 40 CFR 97.141 - Timing requirements for CAIR NOX allowance allocations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Timing requirements for CAIR NOX... (CONTINUED) AIR PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS CAIR NOX Allowance Allocations § 97.141 Timing requirements for CAIR NOX allowance allocations. (a)...

  12. 40 CFR 97.141 - Timing requirements for CAIR NOX allowance allocations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Timing requirements for CAIR NOX... (CONTINUED) AIR PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS CAIR NOX Allowance Allocations § 97.141 Timing requirements for CAIR NOX allowance allocations. (a)...

  13. 45 CFR 1310.12 - Required use of School Buses or Allowable Alternate Vehicles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...-appropriate child restraint systems, and that have reverse beepers. As provided in 45 CFR 1310.2(a), this... 45 Public Welfare 4 2014-10-01 2014-10-01 false Required use of School Buses or Allowable... § 1310.12 Required use of School Buses or Allowable Alternate Vehicles. (a) Effective December 30,...

  14. 40 CFR 96.141 - Timing requirements for CAIR NOX allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Timing requirements for CAIR NOX... (CONTINUED) AIR PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Allowance Allocations § 96.141 Timing requirements for CAIR...

  15. 40 CFR 96.141 - Timing requirements for CAIR NOX allowance allocations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Timing requirements for CAIR NOX... (CONTINUED) AIR PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Allowance Allocations § 96.141 Timing requirements for CAIR...

  16. 40 CFR 96.141 - Timing requirements for CAIR NOX allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Timing requirements for CAIR NOX... (CONTINUED) AIR PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO 2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Allowance Allocations § 96.141 Timing requirements for CAIR...

  17. 40 CFR 96.141 - Timing requirements for CAIR NOX allowance allocations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Timing requirements for CAIR NOX... (CONTINUED) AIR PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Allowance Allocations § 96.141 Timing requirements for CAIR...

  18. 40 CFR 96.141 - Timing requirements for CAIR NOX allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Timing requirements for CAIR NOX... (CONTINUED) AIR PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Allowance Allocations § 96.141 Timing requirements for CAIR...

  19. 40 CFR 97.41 - Timing requirements for NOX allowance allocations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Timing requirements for NOX allowance allocations. 97.41 Section 97.41 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS NOX...

  20. 40 CFR 97.611 - Timing requirements for TR SO2 Group 1 allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... new unit set-aside after promulgation of each notice of data availability required in paragraph (b)(1... Group 1 allowances to the new unit set-aside for such control period; or (B) If the State has a SIP... each year thereafter, as provided in a notice of data availability issued by the...

  1. 40 CFR 97.611 - Timing requirements for TR SO2 Group 1 allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... new unit set-aside after promulgation of each notice of data availability required in paragraph (b)(1... Group 1 allowances to the new unit set-aside for such control period; or (B) If the State has a SIP... each year thereafter, as provided in a notice of data availability issued by the...

  2. 40 CFR 97.611 - Timing requirements for TR SO2 Group 1 allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... new unit set-aside after promulgation of each notice of data availability required in paragraph (b)(1... Group 1 allowances to the new unit set-aside for such control period; or (B) If the State has a SIP... each year thereafter, as provided in a notice of data availability issued by the...

  3. Trehalose Glycopolymer Resists Allow Direct Writing of Protein Patterns by Electron-Beam Lithography

    PubMed Central

    Bat, Erhan; Lee, Juneyoung; Lau, Uland Y.; Maynard, Heather D.

    2015-01-01

    Direct-write patterning of multiple proteins on surfaces is of tremendous interest for a myriad of applications. Precise arrangement of different proteins at increasingly smaller dimensions is a fundamental challenge to apply the materials in tissue engineering, diagnostics, proteomics and biosensors. Herein we present a new resist that protects proteins during electron beam exposure and its application in direct-write patterning of multiple proteins. Polymers with pendant trehalose units are shown to effectively cross-link to surfaces as negative resists, while at the same time providing stabilization to proteins during the vacuum and electron beam irradiation steps. In this manner, arbitrary patterns of several different classes of proteins such as enzymes, growth factors and immunoglobulins are realized. Utilizing the high precision alignment capability of electron-beam lithography, surfaces with complex patterns of multiple proteins are successfully generated at the micrometer and nanometer scale without requiring cleanroom conditions. PMID:25791943

  4. Trehalose glycopolymer resists allow direct writing of protein patterns by electron-beam lithography

    NASA Astrophysics Data System (ADS)

    Bat, Erhan; Lee, Juneyoung; Lau, Uland Y.; Maynard, Heather D.

    2015-03-01

    Direct-write patterning of multiple proteins on surfaces is of tremendous interest for a myriad of applications. Precise arrangement of different proteins at increasingly smaller dimensions is a fundamental challenge to apply the materials in tissue engineering, diagnostics, proteomics and biosensors. Herein, we present a new resist that protects proteins during electron-beam exposure and its application in direct-write patterning of multiple proteins. Polymers with pendant trehalose units are shown to effectively crosslink to surfaces as negative resists, while at the same time providing stabilization to proteins during the vacuum and electron-beam irradiation steps. In this manner, arbitrary patterns of several different classes of proteins such as enzymes, growth factors and immunoglobulins are realized. Utilizing the high-precision alignment capability of electron-beam lithography, surfaces with complex patterns of multiple proteins are successfully generated at the micrometre and nanometre scale without requiring cleanroom conditions.

  5. Trehalose glycopolymer resists allow direct writing of protein patterns by electron-beam lithography.

    PubMed

    Bat, Erhan; Lee, Juneyoung; Lau, Uland Y; Maynard, Heather D

    2015-03-20

    Direct-write patterning of multiple proteins on surfaces is of tremendous interest for a myriad of applications. Precise arrangement of different proteins at increasingly smaller dimensions is a fundamental challenge to apply the materials in tissue engineering, diagnostics, proteomics and biosensors. Herein, we present a new resist that protects proteins during electron-beam exposure and its application in direct-write patterning of multiple proteins. Polymers with pendant trehalose units are shown to effectively crosslink to surfaces as negative resists, while at the same time providing stabilization to proteins during the vacuum and electron-beam irradiation steps. In this manner, arbitrary patterns of several different classes of proteins such as enzymes, growth factors and immunoglobulins are realized. Utilizing the high-precision alignment capability of electron-beam lithography, surfaces with complex patterns of multiple proteins are successfully generated at the micrometre and nanometre scale without requiring cleanroom conditions.

  6. 42 CFR 84.122 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Breathing resistance test; minimum requirements. 84... Masks § 84.122 Breathing resistance test; minimum requirements. (a) Resistance to airflow will be... each test conducted in accordance with §§ 84.124, 84.125, and 84.126, with air flowing at a...

  7. 42 CFR 84.203 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Breathing resistance test; minimum requirements. 84... Chemical Cartridge Respirators § 84.203 Breathing resistance test; minimum requirements. (a) Resistance to... mounted on a test fixture with air flowing at a continuous rate of 85 liters per minute, both before...

  8. 42 CFR 84.203 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Breathing resistance test; minimum requirements. 84... Chemical Cartridge Respirators § 84.203 Breathing resistance test; minimum requirements. (a) Resistance to... mounted on a test fixture with air flowing at a continuous rate of 85 liters per minute, both before...

  9. 42 CFR 84.203 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Breathing resistance test; minimum requirements. 84... Chemical Cartridge Respirators § 84.203 Breathing resistance test; minimum requirements. (a) Resistance to... mounted on a test fixture with air flowing at a continuous rate of 85 liters per minute, both before...

  10. 42 CFR 84.203 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Breathing resistance test; minimum requirements. 84... Chemical Cartridge Respirators § 84.203 Breathing resistance test; minimum requirements. (a) Resistance to... mounted on a test fixture with air flowing at a continuous rate of 85 liters per minute, both before...

  11. 42 CFR 84.122 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Breathing resistance test; minimum requirements. 84... Masks § 84.122 Breathing resistance test; minimum requirements. (a) Resistance to airflow will be... each test conducted in accordance with §§ 84.124, 84.125, and 84.126, with air flowing at a...

  12. 42 CFR 84.122 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Breathing resistance test; minimum requirements. 84... Masks § 84.122 Breathing resistance test; minimum requirements. (a) Resistance to airflow will be... each test conducted in accordance with §§ 84.124, 84.125, and 84.126, with air flowing at a...

  13. 42 CFR 84.203 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing resistance test; minimum requirements. 84... Chemical Cartridge Respirators § 84.203 Breathing resistance test; minimum requirements. (a) Resistance to... mounted on a test fixture with air flowing at a continuous rate of 85 liters per minute, both before...

  14. 49 CFR 236.552 - Insulation resistance; requirement.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Insulation resistance; requirement. 236.552... Insulation resistance; requirement. When periodic test prescribed in § 236.588 is performed, insulation... intermittent inductive automatic train stop system, not less than 250,000 ohms. Insulation resistance...

  15. 49 CFR 236.552 - Insulation resistance; requirement.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Insulation resistance; requirement. 236.552... Insulation resistance; requirement. When periodic test prescribed in § 236.588 is performed, insulation... intermittent inductive automatic train stop system, not less than 250,000 ohms. Insulation resistance...

  16. 49 CFR 236.552 - Insulation resistance; requirement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Insulation resistance; requirement. 236.552... Insulation resistance; requirement. When periodic test prescribed in § 236.588 is performed, insulation... intermittent inductive automatic train stop system, not less than 250,000 ohms. Insulation resistance...

  17. 49 CFR 236.552 - Insulation resistance; requirement.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Insulation resistance; requirement. 236.552... Insulation resistance; requirement. When periodic test prescribed in § 236.588 is performed, insulation... intermittent inductive automatic train stop system, not less than 250,000 ohms. Insulation resistance...

  18. 49 CFR 236.552 - Insulation resistance; requirement.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Insulation resistance; requirement. 236.552... Insulation resistance; requirement. When periodic test prescribed in § 236.588 is performed, insulation... intermittent inductive automatic train stop system, not less than 250,000 ohms. Insulation resistance...

  19. 30 CFR 1206.179 - What general requirements regarding processing allowances apply to me?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... allowances apply to me? 1206.179 Section 1206.179 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT VALUATION Indian Gas Processing Allowances... separate processing allowance for each gas plant product and processing plant relationship. Natural...

  20. 30 CFR 1206.179 - What general requirements regarding processing allowances apply to me?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... allowances apply to me? 1206.179 Section 1206.179 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT VALUATION Indian Gas Processing Allowances... separate processing allowance for each gas plant product and processing plant relationship. Natural...

  1. Density-dependent adaptive resistance allows swimming bacteria to colonize an antibiotic gradient.

    PubMed

    Hol, Felix J H; Hubert, Bert; Dekker, Cees; Keymer, Juan E

    2016-01-01

    During antibiotic treatment, antibiotic concentration gradients develop. Little is know regarding the effects of antibiotic gradients on populations of nonresistant bacteria. Using a microfluidic device, we show that high-density motile Escherichia coli populations composed of nonresistant bacteria can, unexpectedly, colonize environments where a lethal concentration of the antibiotic kanamycin is present. Colonizing bacteria establish an adaptively resistant population, which remains viable for over 24 h while exposed to the antibiotic. Quantitative analysis of multiple colonization events shows that collectively swimming bacteria need to exceed a critical population density in order to successfully colonize the antibiotic landscape. After colonization, bacteria are not dormant but show both growth and swimming motility under antibiotic stress. Our results highlight the importance of motility and population density in facilitating adaptive resistance, and indicate that adaptive resistance may be a first step to the emergence of genetically encoded resistance in landscapes of antibiotic gradients.

  2. 42 CFR 84.192 - Cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Chemical Cartridge Respirators § 84.192 Cartridges in parallel; resistance requirements. Where two or...

  3. 42 CFR 84.192 - Cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Chemical Cartridge Respirators § 84.192 Cartridges in parallel; resistance requirements. Where two or...

  4. 30 CFR 1206.179 - What general requirements regarding processing allowances apply to me?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ENFORCEMENT, DEPARTMENT OF THE INTERIOR Natural Resources Revenue PRODUCT VALUATION Indian Gas Processing... separate processing allowance for each gas plant product and processing plant relationship. Natural gas... production that is not royalty bearing. (e) You will be allowed a reasonable amount of residue gas...

  5. 30 CFR 206.179 - What general requirements regarding processing allowances apply to me?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... allowances apply to me? 206.179 Section 206.179 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT PRODUCT VALUATION Indian Gas Processing Allowances § 206.179... 30 CFR part 206. In those situations where a processing plant processes gas from more than one...

  6. 49 CFR 192.112 - Additional design requirements for steel pipe using alternative maximum allowable operating...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Additional design requirements for steel pipe...: MINIMUM FEDERAL SAFETY STANDARDS Pipe Design § 192.112 Additional design requirements for steel pipe using... segment must meet the following additional design requirements. Records for alternative MAOP must...

  7. Corrosion-resistant fuel cladding allow for liquid metal fast breeder reactors

    DOEpatents

    Brehm, Jr., William F.; Colburn, Richard P.

    1982-01-01

    An aluminide coating for a fuel cladding tube for LMFBRs (liquid metal fast breeder reactors) such as those using liquid sodium as a heat transfer agent. The coating comprises a mixture of nickel-aluminum intermetallic phases and presents good corrosion resistance to liquid sodium at temperatures up to 700.degree. C. while additionally presenting a barrier to outward diffusion of .sup.54 Mn.

  8. 40 CFR 97.711 - Timing requirements for TR SO2 Group 2 allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... new unit set-aside after promulgation of each notice of data availability required in paragraph (b)(1... new unit set-aside after promulgation of each notice of data availability required in paragraph (b)(2... each year thereafter, as provided in a notice of data availability issued by the...

  9. 40 CFR 97.711 - Timing requirements for TR SO2 Group 2 allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... new unit set-aside after promulgation of each notice of data availability required in paragraph (b)(1... new unit set-aside after promulgation of each notice of data availability required in paragraph (b)(2... each year thereafter, as provided in a notice of data availability issued by the...

  10. 40 CFR 97.711 - Timing requirements for TR SO2 Group 2 allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... new unit set-aside after promulgation of each notice of data availability required in paragraph (b)(1... new unit set-aside after promulgation of each notice of data availability required in paragraph (b)(2... each year thereafter, as provided in a notice of data availability issued by the...

  11. 45 CFR 1310.12 - Required use of School Buses or Allowable Alternate Vehicles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-appropriate child restraint systems, and that have reverse beepers. As provided in 45 CFR 1310.2(a), this... reverse beeper. (c) As provided in 45 CFR 1310.2(a), paragraph (b) of this section does not apply to... 45 Public Welfare 4 2010-10-01 2010-10-01 false Required use of School Buses or...

  12. 45 CFR 1310.12 - Required use of School Buses or Allowable Alternate Vehicles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...-appropriate child restraint systems, and that have reverse beepers. As provided in 45 CFR 1310.2(a), this... reverse beeper. (c) As provided in 45 CFR 1310.2(a), paragraph (b) of this section does not apply to... 45 Public Welfare 4 2011-10-01 2011-10-01 false Required use of School Buses or...

  13. 40 CFR 97.411 - Timing requirements for TR NOX Annual allowance allocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... new unit set-aside after promulgation of each notice of data availability required in paragraph (b)(1... each year thereafter, as provided in a notice of data availability issued by the Administrator..., if a unit provided an allocation in the notice of data availability issued under paragraph (a)(1)...

  14. 40 CFR 97.411 - Timing requirements for TR NOX Annual allowance allocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... new unit set-aside after promulgation of each notice of data availability required in paragraph (b)(1... each year thereafter, as provided in a notice of data availability issued by the Administrator..., if a unit provided an allocation in the notice of data availability issued under paragraph (a)(1)...

  15. 40 CFR 97.411 - Timing requirements for TR NOX Annual allowance allocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... new unit set-aside after promulgation of each notice of data availability required in paragraph (b)(1... each year thereafter, as provided in a notice of data availability issued by the Administrator..., if a unit provided an allocation in the notice of data availability issued under paragraph (a)(1)...

  16. 41 CFR 102-74.290 - May Federal agencies allow employees to use parking spaces not required for official needs?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false May Federal agencies allow employees to use parking spaces not required for official needs? 102-74.290 Section 102-74.290 Public Contracts and Property Management Federal Property Management Regulations System...

  17. 41 CFR 102-74.290 - May Federal agencies allow employees to use parking spaces not required for official needs?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false May Federal agencies allow employees to use parking spaces not required for official needs? 102-74.290 Section 102-74.290 Public Contracts and Property Management Federal Property Management Regulations System...

  18. 21 CFR 1311.45 - Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... attorney to obtain CSOS digital certificates under their DEA registration. 1311.45 Section 1311.45 Food and... PRESCRIPTIONS (Eff. 6-1-10) Obtaining and Using Digital Certificates for Electronic Orders § 1311.45 Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates under their...

  19. 42 CFR 84.122 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing resistance test; minimum requirements. 84.122 Section 84.122 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES...

  20. 42 CFR 84.122 - Breathing resistance test; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Breathing resistance test; minimum requirements. 84.122 Section 84.122 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES...

  1. HIGH RESOLUTION RESISTIVITY LEAK DETECTION DATA PROCESSING & EVALUATION MEHTODS & REQUIREMENTS

    SciTech Connect

    SCHOFIELD JS

    2007-10-04

    This document has two purposes: {sm_bullet} Describe how data generated by High Resolution REsistivity (HRR) leak detection (LD) systems deployed during single-shell tank (SST) waste retrieval operations are processed and evaluated. {sm_bullet} Provide the basic review requirements for HRR data when Hrr is deployed as a leak detection method during SST waste retrievals.

  2. Using the written description requirement to limit broad patent scope, allow competition, and encourage innovation in biotechnology.

    PubMed

    Mull, William C

    2004-01-01

    The biotechnology research and development process is extremely expensive and companies must attract investors to this high-risk industry to pay for these costs. Biotechnology companies rely on their ability to exclude others from exploiting the benefits of their research through patent protection to attract these investors. Consequently, they seek strong patent protection for their inventions by claiming a broad scope of patent protection for their inventions. Biotechnology is an industry where the scope of protection should be limited. Science-based technologies exploit the perceived technological opportunities from recent scientific developments, concentrating the attention of many inventors on the same areas. This poses several unique problems. First, only the first of several inventors will receive a patent to the invention. Second, due to publicly available, basic techniques, the actual contribution made by the inventor may be relatively small. Finally, there is a significant risk that permitting an overbroad patent scope may permit original patentees to control a variety of improvements and a number of applications. Additionally, a broad scope of protection for an invention tends to cause underutilization of many potential inventions or improvements. By limiting the scope of protection, one allows competitors to utilize these potential inventions or improvements and encourages the advancement of the technology. Traditionally, courts have used the scope of the disclosure to limit a patent with an overly broad scope of protection. The Federal Circuit is correctly applying the written description requirement as part of the disclosure to limit broad claim scope in biotechnology patents. The written description requirement is separate from the enablement requirement and applies to all claims. By requiring a written description to allow a PHOSITA to determine the structural characteristics of the claimed invention, the Federal Circuit is able limit biotechnology

  3. Race Against Antimicrobial Resistance Requires Coordinated Action – An Overview

    PubMed Central

    Premanandh, J.; Samara, B. S.; Mazen, A. N.

    2016-01-01

    Resistance developed by microbes is challenging success stories of treatment of infectious diseases with anti-microbials. Developing new antimicrobials against these resistant organisms does not progress at the same speed. In an effort to address this key issue, this work overviews the role of different stakeholders and discusses preventative and control measures for effective management of available resources. Roles and concerns of physicians, pharmacists and the public are also discussed. More than anything, this situation requires immediate action to establish antimicrobial stewardship program, control over the counter sale and promote public awareness. The paper also confronts the idea of curbing the use of antimicrobials using mass media, while detailing the consequences of non-therapeutic use. The role of policy makers in taking global action is essential to establishing authority or agency for formulating national guidelines and regulations for prudently using antimicrobials. To do this, this paper recommend the establishment of a global fund. In conclusion, the race against resistance is a collective responsibility requiring coordinated action at local, national, regional and international levels to ensure sustained utilization of antimicrobials. PMID:26869998

  4. Global warming mitigation by sulphur loading in the stratosphere: dependence of required emissions on allowable residual warming rate

    NASA Astrophysics Data System (ADS)

    Eliseev, Alexey V.; Chernokulsky, Alexandr V.; Karpenko, Andrey A.; Mokhov, Igor I.

    2010-07-01

    An approach to mitigate global warming via sulphur loading in the stratosphere (geoengineering) is studied, employing a large ensemble of numerical experiments with the climate model of intermediate complexity IAP RAS CM. The model is forced by the historical+SRES A1B anthropogenic greenhouse gases+tropospheric sulphates scenario for 1860-2100 with additional sulphur emissions in the stratosphere in the twenty-first century. Different ensemble members are constructed by varying values of the parameters governing mass, horizontal distribution and radiative forcing of the stratospheric sulphates. It is obtained that, given a global loading of the sulphates in the stratosphere, among those studied in this paper latitudinal distributions of geoengineering aerosols, the most efficient one at the global basis is that peaked between 50° N and 70° N and with a somewhat smaller burden in the tropics. Uniform latitudinal distribution of stratospheric sulphates is a little less efficient. Sulphur emissions in the stratosphere required to stop the global temperature at the level corresponding to the mean value for 2000-2010 amount to more than 10 TgS/year in the year 2100. These emissions may be reduced if some warming is allowed to occur in the twenty-first century. For instance, if the global temperature trend S g in every decade of this century is limited not to exceed 0.10 K/decade (0.15 K/decade), geoengineering emissions of 4-14 TgS/year (2-7 TgS/year) would be sufficient. Even if the global warming is stopped, temperature changes in different regions still occur with a magnitude up to 1 K. Their horizontal pattern depends on implied latitudinal distribution of stratospheric sulphates. In addition, for the stabilised global mean surface air temperature, global precipitation decreases by about 10%. If geoengineering emissions are stopped after several decades of implementation, their climatic effect is removed within a few decades. In this period, surface air

  5. 48 CFR 211.170 - Requiring the use of fire-resistant rayon fiber.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...-resistant rayon fiber. 211.170 Section 211.170 Federal Acquisition Regulations System DEFENSE ACQUISITION... Developing Requirements Documents 211.170 Requiring the use of fire-resistant rayon fiber. See 225.7016 for the statutory prohibition on requiring the use of fire-resistant rayon fiber....

  6. 48 CFR 211.170 - Requiring the use of fire-resistant rayon fiber.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...-resistant rayon fiber. 211.170 Section 211.170 Federal Acquisition Regulations System DEFENSE ACQUISITION... Developing Requirements Documents 211.170 Requiring the use of fire-resistant rayon fiber. See 225.7016 for the statutory prohibition on requiring the use of fire-resistant rayon fiber....

  7. 48 CFR 211.170 - Requiring the use of fire-resistant rayon fiber.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...-resistant rayon fiber. 211.170 Section 211.170 Federal Acquisition Regulations System DEFENSE ACQUISITION... Developing Requirements Documents 211.170 Requiring the use of fire-resistant rayon fiber. See 225.7016 for the statutory prohibition on requiring the use of fire-resistant rayon fiber....

  8. Interfamilial recombination between viruses led to acquisition of a novel translation-enhancing RNA element that allows resistance breaking

    PubMed Central

    Miras, Manuel; Sempere, Raquel N.; Kraft, Jelena J.; Miller, W. Allen; Aranda, Miguel A.; Truniger, Veronica

    2015-01-01

    Summary Many plant viruses depend on functional RNA elements, called 3′-UTR cap-independent translation enhancers (3′-CITEs), for translation of their RNAs. In this manuscript we provide direct proof for the existing hypothesis that 3′-CITEs are modular and transferable by recombination in nature, and that this is associated with an advantage for the created virus. By characterizing a newly identified Melon necrotic spot virus (MNSV; Tombusviridae) isolate, which is able to overcome eukaryotic translation initiation factor 4E (eIF4E)-mediated resistance, we found that it contains a 55 nucleotide insertion in its 3′-UTR. We provide strong evidence that this insertion was acquired by interfamilial recombination with the 3′-UTR of an Asiatic Cucurbit aphid-borne yellows virus (CABYV; Luteoviridae). By constructing chimeric viruses, we showed that this recombined sequence is responsible for resistance breaking. Analysis of the translational efficiency of reporter constructs showed that this sequence functions as a novel 3′-CITE in both resistant and susceptible plants, being essential for translation control in resistant plants. In conclusion, we showed that a recombination event between two clearly identified viruses from different families led to the transfer of exactly the sequence corresponding to a functional RNA element, giving rise to a new isolate with the capacity to infect an otherwise non-susceptible host. PMID:24372390

  9. 21 CFR 1311.45 - Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... attorney to obtain CSOS digital certificates under their DEA registration. 1311.45 Section 1311.45 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE REQUIREMENTS FOR ELECTRONIC ORDERS AND PRESCRIPTIONS Obtaining and Using Digital Certificates for Electronic Orders § 1311.45 Requirements...

  10. Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance.

    PubMed

    Frise, Rebecca; Bradley, Konrad; van Doremalen, Neeltje; Galiano, Monica; Elderfield, Ruth A; Stilwell, Peter; Ashcroft, Jonathan W; Fernandez-Alonso, Mirian; Miah, Shahjahan; Lackenby, Angie; Roberts, Kim L; Donnelly, Christl A; Barclay, Wendy S

    2016-07-19

    Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution.

  11. Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance

    PubMed Central

    Frise, Rebecca; Bradley, Konrad; van Doremalen, Neeltje; Galiano, Monica; Elderfield, Ruth A.; Stilwell, Peter; Ashcroft, Jonathan W.; Fernandez-Alonso, Mirian; Miah, Shahjahan; Lackenby, Angie; Roberts, Kim L.; Donnelly, Christl A.; Barclay, Wendy S.

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution. PMID:27430528

  12. 21 CFR 1311.45 - Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... attorney to obtain CSOS digital certificates under their DEA registration. 1311.45 Section 1311.45 Food and... registrants that allow powers of attorney to obtain CSOS digital certificates under their DEA registration. (a) A registrant that grants power of attorney must report to the DEA Certification Authority within...

  13. 21 CFR 1311.45 - Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... attorney to obtain CSOS digital certificates under their DEA registration. 1311.45 Section 1311.45 Food and... registrants that allow powers of attorney to obtain CSOS digital certificates under their DEA registration. (a) A registrant that grants power of attorney must report to the DEA Certification Authority within...

  14. 21 CFR 1311.45 - Requirements for registrants that allow powers of attorney to obtain CSOS digital certificates...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... attorney to obtain CSOS digital certificates under their DEA registration. 1311.45 Section 1311.45 Food and... registrants that allow powers of attorney to obtain CSOS digital certificates under their DEA registration. (a) A registrant that grants power of attorney must report to the DEA Certification Authority within...

  15. 30 CFR 75.1107-2 - Approved fire-resistant hydraulic fluids; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Approved fire-resistant hydraulic fluids... Protection Fire Suppression Devices and Fire-Resistant Hydraulic Fluids on Underground Equipment § 75.1107-2 Approved fire-resistant hydraulic fluids; minimum requirements. Fire-resistant hydraulic fluids...

  16. 20 CFR 641.850 - Are there other specific allowable and unallowable cost requirements for the SCSEP?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Lobbying costs. In addition to the prohibition contained in 29 CFR part 93, SCSEP funds must not be used to... housing occupied by persons with low incomes who are declared eligible for such services by authorized... unallowable cost requirements for the SCSEP? 641.850 Section 641.850 Employees' Benefits EMPLOYMENT...

  17. 41 CFR 102-39.80 - What are the accounting requirements for exchange allowances or proceeds of sale?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the general finance and accounting rules applicable to you. Except as otherwise authorized by law, all... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What are the accounting... Exchange/Sale Methods and Reports § 102-39.80 What are the accounting requirements for exchange...

  18. 41 CFR 102-39.80 - What are the accounting requirements for exchange allowances or proceeds of sale?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... the general finance and accounting rules applicable to you. Except as otherwise authorized by law, all... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What are the accounting... Exchange/Sale Methods and Reports § 102-39.80 What are the accounting requirements for exchange...

  19. 41 CFR 102-39.80 - What are the accounting requirements for exchange allowances or proceeds of sale?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the general finance and accounting rules applicable to you. Except as otherwise authorized by law, all... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false What are the accounting... Exchange/Sale Methods and Reports § 102-39.80 What are the accounting requirements for exchange...

  20. 41 CFR 102-39.80 - What are the accounting requirements for exchange allowances or proceeds of sale?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the general finance and accounting rules applicable to you. Except as otherwise authorized by law, all... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false What are the accounting... Exchange/Sale Methods and Reports § 102-39.80 What are the accounting requirements for exchange...

  1. 41 CFR 102-39.80 - What are the accounting requirements for exchange allowances or proceeds of sale?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the general finance and accounting rules applicable to you. Except as otherwise authorized by law, all... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false What are the accounting... Exchange/Sale Methods and Reports § 102-39.80 What are the accounting requirements for exchange...

  2. 48 CFR 225.7016 - Prohibition on requiring the use of fire-resistant rayon fiber.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... the use of fire-resistant rayon fiber. 225.7016 Section 225.7016 Federal Acquisition Regulations... 225.7016 Prohibition on requiring the use of fire-resistant rayon fiber. In accordance with section... include the use of fire-resistant rayon fiber. However, this does not preclude issuing a solicitation...

  3. 48 CFR 225.7016 - Prohibition on requiring the use of fire-resistant rayon fiber.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... the use of fire-resistant rayon fiber. 225.7016 Section 225.7016 Federal Acquisition Regulations... 225.7016 Prohibition on requiring the use of fire-resistant rayon fiber. In accordance with section... include the use of fire-resistant rayon fiber. However, this does not preclude issuing a solicitation...

  4. 48 CFR 225.7016 - Prohibition on requiring the use of fire-resistant rayon fiber.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the use of fire-resistant rayon fiber. 225.7016 Section 225.7016 Federal Acquisition Regulations... 225.7016 Prohibition on requiring the use of fire-resistant rayon fiber. In accordance with section... include the use of fire-resistant rayon fiber. However, this does not preclude issuing a solicitation...

  5. 32 CFR 37.680 - Must I require a participant to report when it enters into a subaward allowing a for-profit firm...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... INVESTMENT AGREEMENTS Award Terms Affecting Participants' Financial, Property, and Purchasing Systems Financial Matters § 37.680 Must I require a participant to report when it enters into a subaward allowing a... does not itself have to be reported again. Property...

  6. 32 CFR 37.680 - Must I require a participant to report when it enters into a subaward allowing a for-profit firm...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... INVESTMENT AGREEMENTS Award Terms Affecting Participants' Financial, Property, and Purchasing Systems Financial Matters § 37.680 Must I require a participant to report when it enters into a subaward allowing a... does not itself have to be reported again. Property...

  7. 32 CFR 37.680 - Must I require a participant to report when it enters into a subaward allowing a for-profit firm...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... INVESTMENT AGREEMENTS Award Terms Affecting Participants' Financial, Property, and Purchasing Systems Financial Matters § 37.680 Must I require a participant to report when it enters into a subaward allowing a... does not itself have to be reported again. Property...

  8. 32 CFR 37.680 - Must I require a participant to report when it enters into a subaward allowing a for-profit firm...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... INVESTMENT AGREEMENTS Award Terms Affecting Participants' Financial, Property, and Purchasing Systems Financial Matters § 37.680 Must I require a participant to report when it enters into a subaward allowing a... does not itself have to be reported again. Property...

  9. 32 CFR 37.680 - Must I require a participant to report when it enters into a subaward allowing a for-profit firm...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... INVESTMENT AGREEMENTS Award Terms Affecting Participants' Financial, Property, and Purchasing Systems Financial Matters § 37.680 Must I require a participant to report when it enters into a subaward allowing a... does not itself have to be reported again. Property...

  10. An NB-LRR protein required for HR signalling mediated by both extra- and intracellular resistance proteins.

    PubMed

    Gabriëls, Suzan H E J; Vossen, Jack H; Ekengren, Sophia K; van Ooijen, Gerben; Abd-El-Haliem, Ahmed M; van den Berg, Grardy C M; Rainey, Daphne Y; Martin, Gregory B; Takken, Frank L W; de Wit, Pierre J G M; Joosten, Matthieu H A J

    2007-04-01

    Tomato (Solanum lycopersicum) Cf resistance genes confer hypersensitive response (HR)-associated resistance to strains of the pathogenic fungus Cladosporium fulvum that express the matching avirulence (Avr) gene. Previously, we identified an Avr4-responsive tomato (ART) gene that is required for Cf-4/Avr4-induced HR in Nicotiana benthamiana as demonstrated by virus-induced gene silencing (VIGS). The gene encodes a CC-NB-LRR type resistance (R) protein analogue that we have designated NRC1 (NB-LRR protein required for HR-associated cell death 1). Here we describe that knock-down of NRC1 in tomato not only affects the Cf-4/Avr4-induced HR but also compromises Cf-4-mediated resistance to C. fulvum. In addition, VIGS using NRC1 in N. benthamiana revealed that this protein is also required for the HR induced by the R proteins Cf-9, LeEix, Pto, Rx and Mi. Transient expression of NRC1(D481V), which encodes a constitutively active NRC1 mutant protein, triggers an elicitor-independent HR. Subsequently, we transiently expressed this auto-activating protein in N. benthamiana silenced for genes known to be involved in HR signalling, thereby allowing NRC1 to be positioned in an HR signalling pathway. We found that NRC1 requires RAR1 and SGT1 to be functional, whereas it does not require NDR1 and EDS1. As the Cf-4 protein requires EDS1 for its function, we hypothesize that NRC1 functions downstream of EDS1. We also found that NRC1 acts upstream of a MAP kinase pathway. We conclude that Cf-mediated resistance signalling requires a downstream NB-LRR protein that also functions in cell death signalling pathways triggered by other R proteins.

  11. RUNX3 plays an important role in As2O3‑induced apoptosis and allows cells to overcome MSC‑mediated drug resistance.

    PubMed

    Pan, Guo-Zheng; Zhai, Feng-Xian; Lu, Yin; Fang, Zhi-Gang; Fan, Rui-Fang; Liu, Xiang-Fu; Lin, Dong-Jun

    2016-10-01

    The interaction between bone marrow stromal cells and leukemia cells is critical for the persistence and progression of leukemia, and this interaction may account for residual disease. However, the link between leukemia cells and their environment is still poorly understood. In our study, runt‑related transcription factor 3 (RUNX3) was identified as a novel target gene affected by As2O3 and involved in mesenchymal stem cell (MSC)‑mediated protection of leukemia cells from As2O3‑induced apoptosis. We observed induction of RUNX3 expression and the translocation of RUNX3 into the nucleus after As2O3 treatment in leukemia cells. In K562 chronic myeloid leukemia cells, downregulation of endogenous RUNX3 compromised As2O3‑induced growth inhibition, cell cycle arrest, and apoptosis. In the presence of MSC, As2O3‑induced expression of RUNX3 was reduced significantly and this reduction was modulated by CXCL12/CXCR4 signaling. Furthermore, overexpression of RUNX3 restored, at least in part, the sensitivity of leukemic cells to As2O3. We conclude that RUNX3 plays an important role in As2O3‑induced cellular responses and allows cells to overcome MSC‑mediated drug resistance. Therefore, RUNX3 is a promising target for therapeutic approaches to overcome MSC‑mediated drug resistance. PMID:27498627

  12. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... cosmetic products. 700.25 Section 700.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS GENERAL Requirements for Specific Cosmetic Products § 700.25 Tamper-resistant packaging requirements for cosmetic products. (a) General. Because most cosmetic...

  13. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... cosmetic products. 700.25 Section 700.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS GENERAL Requirements for Specific Cosmetic Products § 700.25 Tamper-resistant packaging requirements for cosmetic products. (a) General. Because most cosmetic...

  14. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... cosmetic products. 700.25 Section 700.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS GENERAL Requirements for Specific Cosmetic Products § 700.25 Tamper-resistant packaging requirements for cosmetic products. (a) General. Because most cosmetic...

  15. Identification of a New Locus, Ptr(t), Required for Rice Blast Resistance Gene Pi-ta-Mediated Resistance

    SciTech Connect

    Jia, Yulin; Martin, Rodger Carl

    2008-01-01

    Resistance to the blast pathogen Magnaporthe oryzae is proposed to be initiated by physical binding of a putative cytoplasmic receptor encoded by a NBS type resistance gene Pi-ta to the processed elicitor encoded by the corresponding avirulence gene AVR-Pita. Here we report the identification of a new locus Ptr(t) that is required for Pi-ta-mediated signal recognition. A Pi-ta expressing susceptible mutant was identified using a genetic screen. Putative mutations at Ptr(t) does not alter recognition specificity to another resistance gene Pi-ks in the Pi-ta homozygote indicate that Ptr(t) is more likely specific to Pi-ta-mediated signal recognition. Genetic crosses of Pi-ta Ptr(t) and Pi-ta ptr(t) homozygotes suggest that Ptr(t) segregate at single dominant nuclear gene. A ratio of 1 resistant: 1 susceptible of a BC1 using Pi-ta Ptr(t) with pi-ta ptr(t) homozygotes indicates that Pi-ta and Ptr(t) are linked and co-segregated. Genotyping of mutants of pi-ta ptr(t) and Pi-ta Ptr(t) homozygotes using ten simple sequence repeat markers spanning 9 megabase of Pi-ta determines that Pi-ta and Ptr(t) are of indica origin. Identification of Ptr(t) is a significant advancement in studying Pi-ta-mediated signal recognition and transduction.

  16. Directly observed treatment, short-course strategy and multidrug-resistant tuberculosis: are any modifications required?

    PubMed Central

    Bastian, I.; Rigouts, L.; Van Deun, A.; Portaels, F.

    2000-01-01

    Multidrug-resistant tuberculosis (MDRTB) should be defined as tuberculosis with resistance to at least isoniazid and rifampicin because these drugs are the cornerstone of short-course chemotherapy, and combined isoniazid and rifampicin resistance requires prolonged treatment with second-line agents. Short-course chemotherapy is a key ingredient in the tuberculosis control strategy known as directly observed treatment, short-course (DOTS). For populations in which multidrug-resistant tuberculosis is endemic, the outcome of the standard short-course chemotherapy regimen remains uncertain. Unacceptable failure rates have been reported and resistance to additional agents may be induced. As a consequence there have been calls for well-functioning DOTS programmes to provide additional services in areas with high rates of multidrug-resistant tuberculosis. These "DOTS-plus for MDRTB programmes" may need to modify all five elements of the DOTS strategy: the treatment may need to be individualized rather than standardized; laboratory services may need to provide facilities for on-site culture and antibiotic susceptibility testing; reliable supplies of a wide range of expensive second-line agents would have to be supplied; operational studies would be required to determine the indications for and format of the expanded programmes; financial and technical support from international organizations and Western governments would be needed in addition to that obtained from local governments. PMID:10743297

  17. An EDS1 orthologue is required for N-mediated resistance against tobacco mosaic virus.

    PubMed

    Peart, Jack R; Cook, Graeme; Feys, Bart J; Parker, Jane E; Baulcombe, David C

    2002-03-01

    In Arabidopsis, EDS1 is essential for disease resistance conferred by a structural subset of resistance (R) proteins containing a nucleotide-binding site, leucine-rich-repeats and amino-terminal similarity to animal Toll and Interleukin-1 (so-called TIR-NBS-LRR proteins). EDS1 is not required by NBS-LRR proteins that possess an amino-terminal coiled-coil motif (CC-NBS-LRR proteins). Using virus-induced gene silencing (VIGS) of a Nicotiana benthaminana EDS1 orthologue, we investigated the role of EDS1 in resistance specified by structurally distinct R genes in transgenic N. benthamiana. Resistance against tobacco mosaic virus mediated by tobacco N, a TIR-NBS-LRR protein, was EDS1-dependent. Two other R proteins, Pto (a protein kinase), and Rx (a CC-NBS-LRR protein) recognizing, respectively, a bacterial and viral pathogen did not require EDS1. These data, together with the finding that expression of N. benthamiana and Arabidopsis EDS1 mRNAs are similarly regulated, lead us to conclude that recruitment of EDS1 by TIR-NBS-LRR proteins is evolutionarily conserved between dicotyledenous plant species in resistance against bacterial, oomycete and viral pathogens. We further demonstrate that VIGS is a useful approach to dissect resistance signaling pathways in a genetically intractable plant species.

  18. The Toll-Dorsal Pathway Is Required for Resistance to Viral Oral Infection in Drosophila

    PubMed Central

    Ferreira, Álvaro Gil; Naylor, Huw; Esteves, Sara Santana; Pais, Inês Silva; Martins, Nelson Eduardo; Teixeira, Luis

    2014-01-01

    Pathogen entry route can have a strong impact on the result of microbial infections in different hosts, including insects. Drosophila melanogaster has been a successful model system to study the immune response to systemic viral infection. Here we investigate the role of the Toll pathway in resistance to oral viral infection in D. melanogaster. We show that several Toll pathway components, including Spätzle, Toll, Pelle and the NF-kB-like transcription factor Dorsal, are required to resist oral infection with Drosophila C virus. Furthermore, in the fat body Dorsal is translocated from the cytoplasm to the nucleus and a Toll pathway target gene reporter is upregulated in response to Drosophila C Virus infection. This pathway also mediates resistance to several other RNA viruses (Cricket paralysis virus, Flock House virus, and Nora virus). Compared with control, viral titres are highly increased in Toll pathway mutants. The role of the Toll pathway in resistance to viruses in D. melanogaster is restricted to oral infection since we do not observe a phenotype associated with systemic infection. We also show that Wolbachia and other Drosophila-associated microbiota do not interact with the Toll pathway-mediated resistance to oral infection. We therefore identify the Toll pathway as a new general inducible pathway that mediates strong resistance to viruses with a route-specific role. These results contribute to a better understanding of viral oral infection resistance in insects, which is particularly relevant in the context of transmission of arboviruses by insect vectors. PMID:25473839

  19. 42 CFR 84.112 - Canisters and cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Canisters and cartridges in parallel; resistance requirements. 84.112 Section 84.112 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY...

  20. 42 CFR 84.112 - Canisters and cartridges in parallel; resistance requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Canisters and cartridges in parallel; resistance requirements. 84.112 Section 84.112 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY...

  1. 30 CFR 75.1107-2 - Approved fire-resistant hydraulic fluids; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...; minimum requirements. 75.1107-2 Section 75.1107-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection Fire Suppression Devices and Fire-Resistant Hydraulic Fluids on Underground Equipment §...

  2. 30 CFR 75.1107-2 - Approved fire-resistant hydraulic fluids; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...; minimum requirements. 75.1107-2 Section 75.1107-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection Fire Suppression Devices and Fire-Resistant Hydraulic Fluids on Underground Equipment §...

  3. 30 CFR 75.1107-2 - Approved fire-resistant hydraulic fluids; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...; minimum requirements. 75.1107-2 Section 75.1107-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection Fire Suppression Devices and Fire-Resistant Hydraulic Fluids on Underground Equipment §...

  4. 30 CFR 75.1107-2 - Approved fire-resistant hydraulic fluids; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...; minimum requirements. 75.1107-2 Section 75.1107-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Fire Protection Fire Suppression Devices and Fire-Resistant Hydraulic Fluids on Underground Equipment §...

  5. Meta-analysis and time series modeling allow a systematic review of primary HIV-1 drug-resistant prevalence in Latin America and Caribbean.

    PubMed

    Coelho, Antonio Victor Campos; De Moura, Ronald Rodrigues; Da Silva, Ronaldo Celerino; Kamada, Anselmo Jiro; Guimarães, Rafael Lima; Brandão, Lucas André Cavalcanti; Coelho, Hemílio Fernandes Campos; Crovella, Sergio

    2015-01-01

    Here we review the prevalence of HIV-1 primary drug resistance in Latin America and Caribbean using meta-analysis as well as time-series modeling. We also discuss whether there could be a drawback to HIV/AIDS programs due to drug resistance in Latin America and Caribbean in the next years. We observed that, although some studies report low or moderate primary drug resistance prevalence in Caribbean countries, this evidence needs to be updated. In other countries, such as Brazil and Argentina, the prevalence of drug resistance appears to be rising. Mutations conferring resistance against reverse transcriptase inhibitors were the most frequent in the analyzed populations (70% of all mutational events). HIV-1 subtype B was the most prevalent in Latin America and the Caribbean, although subtype C and B/F recombinants have significant contributions in Argentina and Brazil. Thus, we suggest that primary drug resistance in Latin America and the Caribbean could have been underestimated. Clinical monitoring should be improved to offer better therapy, reducing the risk for HIV-1 resistance emergence and spread, principally in vulnerable populations, such as men who have sex with men transmission group, sex workers and intravenous drug users.

  6. Nucleoporins Nup160 and Seh1 are required for disease resistance in Arabidopsis.

    PubMed

    Roth, Charlotte; Wiermer, Marcel

    2012-10-01

    Arabidopsis Nup160 and Seh1, encoding two predicted nucleoporins of the Nup107-160 nuclear pore sub-complex, were identified in a reverse genetics screen based on their requirement for basal disease resistance. Both genes also contribute to immunity conferred by Toll interleukin 1 receptor/nucleotide-binding/leucine-rich repeat (TNL)-type R proteins and constitutive resistance activated in the deregulated TNL mutant, snc1. Protein amounts of EDS1, a central regulator of TNL-triggered resistance, are reduced in seh1 and severely depleted in nup160 single mutants. Here, we investigate the impact of mutations in Nup160, Seh1 and a third complex member, MOS3/Nup96, on EDS1 protein accumulation in the snc1 auto-immune mutant background. In addition, we examine the subcellular localization of Seh1 in root tissues.

  7. 42 CFR 84.154 - Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.154 Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements. (a) Airflow resistance shall be... diameter. (b) Airflow resistance shall not exceed 38 mm. (1.5 inches) of water-column height to air...

  8. 42 CFR 84.156 - Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Airflow resistance test; Type C supplied-air... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.156 Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements. (a) Inhalation resistance shall...

  9. 42 CFR 84.154 - Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.154 Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements. (a) Airflow resistance shall be... diameter. (b) Airflow resistance shall not exceed 38 mm. (1.5 inches) of water-column height to air...

  10. 42 CFR 84.156 - Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Airflow resistance test; Type C supplied-air... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.156 Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements. (a) Inhalation resistance shall...

  11. 42 CFR 84.154 - Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.154 Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements. (a) Airflow resistance shall be... diameter. (b) Airflow resistance shall not exceed 38 mm. (1.5 inches) of water-column height to air...

  12. 42 CFR 84.153 - Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.153 Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements. (a) Airflow resistance will be... 42 Public Health 1 2013-10-01 2013-10-01 false Airflow resistance test, Type A and Type...

  13. 42 CFR 84.154 - Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.154 Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements. (a) Airflow resistance shall be... diameter. (b) Airflow resistance shall not exceed 38 mm. (1.5 inches) of water-column height to air...

  14. 42 CFR 84.153 - Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.153 Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements. (a) Airflow resistance will be... 42 Public Health 1 2014-10-01 2014-10-01 false Airflow resistance test, Type A and Type...

  15. 42 CFR 84.156 - Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Airflow resistance test; Type C supplied-air... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.156 Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements. (a) Inhalation resistance shall...

  16. 42 CFR 84.156 - Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Airflow resistance test; Type C supplied-air... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.156 Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements. (a) Inhalation resistance shall...

  17. 42 CFR 84.153 - Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.153 Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements. (a) Airflow resistance will be... 42 Public Health 1 2012-10-01 2012-10-01 false Airflow resistance test, Type A and Type...

  18. 42 CFR 84.154 - Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air Respirators § 84.154 Airflow resistance test; Type B and Type BE supplied-air respirators; minimum requirements. (a) Airflow resistance shall be... diameter. (b) Airflow resistance shall not exceed 38 mm. (1.5 inches) of water-column height to air...

  19. 42 CFR 84.153 - Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements. 84.153 Section 84.153 Public Health PUBLIC HEALTH SERVICE... A and Type AE supplied-air respirators; minimum requirements. (a) Airflow resistance will...

  20. 42 CFR 84.153 - Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Airflow resistance test, Type A and Type AE supplied-air respirators; minimum requirements. 84.153 Section 84.153 Public Health PUBLIC HEALTH SERVICE... A and Type AE supplied-air respirators; minimum requirements. (a) Airflow resistance will...

  1. ABA is required for Leptosphaeria maculans resistance via ABI1- and ABI4-dependent signaling.

    PubMed

    Kaliff, Maria; Staal, Jens; Myrenås, Mattias; Dixelius, Christina

    2007-04-01

    Abscisic acid (ABA) is a defense hormone with influence on callose-dependent and -independent resistance against Leptosphaeria maculans acting in the RLMcol pathway. ABA-deficient and -insensitive mutants in Ler-0 background (abal-3 and abil-1) displayed susceptibility to L. maculans, along with a significantly decreased level of callose depositions, whereas abi2-1 and abi3-1 remained resistant, together with the abi5-1 mutant of Ws-0 background. Suppressor mutants of abil-1 confirmed that the L. maculans-susceptible response was due to the dominant negative nature of the abil-1 mutant. Highly induced camalexin levels made ABA mutants in Col-0 background (aba2-1, aba3-1, and abi4-1) appear resistant, but displayed enhanced susceptibility as double mutants with pad3-1, impaired in camalexin biosynthesis. beta-Aminobutyric acid (BABA) pretreatment of Ler-0 contributed to an elevated level of endogenous ABA after L. maculans inoculation. Comparisons between (RLM1co1)pad3 and rlmlLerpad3 showed that ABA and BABA enhancement of callose deposition requires induction from RLM1col. ABII, but not ABI2, was found to be involved in a feedback mechanism that modulates RLM1co, expression. Genetic analysis showed further that this feedback occurs upstream of ABI4 and that components downstream of ABI4 modulate ABIJ activity. ABA and BABA treatments of the L. maculans-susceptible callose synthase mutant pmr4 showed that ABA also induces a callose-independent resistance. Similar treatments enhanced callose depositions and induced resistance to L. maculans in oilseed rape, and BABA-induced resistance was found to be independent of salicylic acid.

  2. Genetic Studies of Sulfadiazine-resistant and Methionine-requiring Neisseria Isolated From Clinical Material

    PubMed Central

    Catlin, B. Wesley

    1967-01-01

    Deoxyribonucleate (DNA) preparations were extracted from Neisseria meningitidis (four isolates from spinal fluid and blood) and N. gonorrhoeae strains, all of which were resistant to sulfadiazine upon primary isolation. These DNA preparations, together with others from in vitro mutants of N. meningitidis and N. perflava, were examined in transformation tests by using as recipient a drug-susceptible strain of N. meningitidis (Ne 15 Sul-s Met+) which was able to grow in a methionine-free defined medium. The sulfadiazine resistance typical of each donor was introduced into the uniform constitution of this recipient. Production of p-aminobenzoic acid was not significantly altered thereby. Transformants elicited by DNA from the N. meningitidis clinical isolates were resistant to at least 200 μg of sulfadiazine/ml, and did not show a requirement for methionine (Sul-r Met+). DNA from six strains of N. gonorrhoeae, which were isolated during the period of therapeutic use of sulfonamides, conveyed lower degrees of resistance and, invariably, a concurrent methionine requirement (Sul-r/Met−). The requirement of these transformants, and that of in vitro mutants selected on sulfadiazine-agar, was satisfied by methionine, but not by vitamin B12, homocysteine, cystathionine, homoserine, or cysteine. Sul-r Met+ and Sul-r/Met− loci could coexist in the same genome, but were segregated during transformation. On the other hand, the dual Sul-r/Met− properties were not separated by recombination, but were eliminated together. DNA from various Sul-r/Met− clones tested against recipients having nonidentical Sul-r/Met− mutant sites yielded Sul-s Met+ transformants. The met locus involved is genetically complex, and will be a valuable tool for studies of genetic fine structure of members of Neisseria, and of genetic homology between species. Images PMID:4962305

  3. Chaperones of the endoplasmic reticulum are required for Ve1-mediated resistance to Verticillium.

    PubMed

    Liebrand, Thomas W H; Kombrink, Anja; Zhang, Zhao; Sklenar, Jan; Jones, Alexandra M E; Robatzek, Silke; Thomma, Bart P H J; Joosten, Matthieu H A J

    2014-01-01

    The tomato receptor-like protein (RLP) Ve1 mediates resistance to the vascular fungal pathogen Verticillium dahliae. To identify the proteins required for Ve1 function, we transiently expressed and immunopurified functional Ve1-enhanced green fluorescent protein (eGFP) from Nicotiana benthamiana leaves, followed by mass spectrometry. This resulted in the identification of peptides originating from the endoplasmic reticulum (ER)-resident chaperones HSP70 binding proteins (BiPs) and a lectin-type calreticulin (CRT). Knock-down of the different BiPs and CRTs in tomato resulted in compromised Ve1-mediated resistance to V. dahliae in most cases, showing that these chaperones play an important role in Ve1 functionality. Recently, it has been shown that one particular CRT is required for the biogenesis of the RLP-type Cladosporium fulvum resistance protein Cf-4 of tomato, as silencing of CRT3a resulted in a reduced pool of complex glycosylated Cf-4 protein. In contrast, knock-down of the various CRTs in N. benthamiana or N. tabacum did not result in reduced accumulation of mature complex glycosylated Ve1 protein. Together, this study shows that the BiP and CRT ER chaperones differentially contribute to Cf-4- and Ve1-mediated immunity. PMID:24015989

  4. The Flagellum of Pseudomonas aeruginosa Is Required for Resistance to Clearance by Surfactant Protein A

    PubMed Central

    Zhang, Shiping; McCormack, Francis X.; Levesque, Roger C.; O'Toole, George A.; Lau, Gee W.

    2007-01-01

    Surfactant protein A (SP-A) is an important lung innate immune protein that kills microbial pathogens by opsonization and membrane permeabilization. We investigated the basis of SP-A-mediated pulmonary clearance of Pseudomonas aeruginosa using genetically-engineered SP-A mice and a library of signature-tagged P. aeruginosa mutants. A mutant with an insertion into flgE, the gene that encodes flagellar hook protein, was preferentially cleared by the SP-A+/+ mice, but survived in the SP-A−/− mice. Opsonization by SP-A did not play a role in flgE clearance. However, exposure to SP-A directly permeabilized and killed the flgE mutant, but not the wild-type parental strain. P. aeruginosa strains with mutation in other flagellar genes, as well as mucoid, nonmotile isolates from cystic fibrosis patients, were also permeabilized by SP-A. Provision of the wild-type fliC gene restored the resistance to SP-A-mediated membrane permeabilization in the fliC-deficient bacteria. In addition, non-mucoid, motile revertants of CF isolates reacquired resistance to SP-A-mediated membrane permeability. Resistance to SP-A was dependent on the presence of an intact flagellar structure, and independent of flagellar-dependent motility. We provide evidence that flagellar-deficient mutants harbor inadequate amounts of LPS required to resist membrane permeabilization by SP-A and cellular lysis by detergent targeting bacterial outer membranes. Thus, the flagellum of P. aeruginosa plays an indirect but important role resisting SP-A-mediated clearance and membrane permeabilization. PMID:17593964

  5. Castration-Resistant Lgr5+ Cells Are Long-Lived Stem Cells Required for Prostatic Regeneration

    PubMed Central

    Wang, Bu-er; Wang, Xi; Long, Jason E.; Eastham-Anderson, Jeff; Firestein, Ron; Junttila, Melissa R.

    2015-01-01

    Summary The adult prostate possesses a significant regenerative capacity that is of great interest for understanding adult stem cell biology. We demonstrate that leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is expressed in a rare population of prostate epithelial progenitor cells, and a castration-resistant Lgr5+ population exists in regressed prostate tissue. Genetic lineage tracing revealed that Lgr5+ cells and their progeny are primarily luminal. Lgr5+ castration-resistant cells are long lived and upon regeneration, both luminal Lgr5+ cells and basal Lgr5+ cells expand. Moreover, single Lgr5+ cells can generate multilineage prostatic structures in renal transplantation assays. Additionally, Lgr5+ cell depletion revealed that the regenerative potential of the castrated adult prostate depends on Lgr5+ cells. Together, these data reveal insights into the cellular hierarchy of castration-resistant Lgr5+ cells, indicate a requirement for Lgr5+ cells during prostatic regeneration, and identify an Lgr5+ adult stem cell population in the prostate. PMID:25937372

  6. A Multicopper Oxidase Is Required for Copper Resistance in Mycobacterium tuberculosis

    PubMed Central

    Rowland, Jennifer L.

    2013-01-01

    Mycobacterium tuberculosis, the causative agent of tuberculosis, is one of the most important bacterial pathogens. Recent work has revealed that the natural bactericidal properties of copper are utilized by the host immune system to combat infections with bacteria, including M. tuberculosis. However, M. tuberculosis employs multiple mechanisms to reduce the internal copper amount by efflux and sequestration, which are required for virulence of M. tuberculosis. Here, we describe an alternative mechanism of copper resistance by M. tuberculosis. Deletion of the rv0846c gene increased the susceptibility of M. tuberculosis to copper at least 10-fold, establishing Rv0846c as a major component of copper resistance in M. tuberculosis. In vitro assays showed that Rv0846c oxidized organic substrates and Fe(II). Importantly, mutation of the predicted copper-coordinating cysteine 486 resulted in inactive Rv0846c protein which did not protect M. tuberculosis against copper stress. Hence, Rv0846c is a multicopper oxidase of M. tuberculosis and was renamed mycobacterial multicopper oxidase (MmcO). MmcO is membrane associated, probably by lipidation after export across the inner membrane by the twin-arginine translocation system. However, mutation of the lipidation site did not affect the oxidase activity or the copper protective function of MmcO. Our study revealed MmcO as an important copper resistance mechanism of M. tuberculosis, which possibly acts by oxidation of toxic Cu(I) in the periplasm. PMID:23772064

  7. Optimal level of purple acid phosphatase5 is required for maintaining complete resistance to Pseudomonas syringae

    PubMed Central

    Ravichandran, Sridhar; Stone, Sophia L.; Benkel, Bernhard; Zhang, Junzeng; Berrue, Fabrice; Prithiviraj, Balakrishnan

    2015-01-01

    Plants possess an exceedingly complex innate immune system to defend against most pathogens. However, a relative proportion of the pathogens overcome host's innate immunity and impair plant growth and productivity. We previously showed that mutation in purple acid phosphatase (PAP5) lead to enhanced susceptibility of Arabidopsis to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). Here, we report that an optimal level of PAP5 is crucial for mounting complete basal resistance. Overexpression of PAP5 impaired ICS1, PR1 expression and salicylic acid (SA) accumulation similar to pap5 knockout mutant plants. Moreover, plant overexpressing PAP5 was impaired in H2O2 accumulation in response to Pst DC3000. PAP5 is localized in to peroxisomes, a known site of generation of reactive oxygen species for activation of defense responses. Taken together, our results demonstrate that optimal levels of PAP5 is required for mounting resistance against Pst DC3000 as both knockout and overexpression of PAP5 lead to compromised basal resistance. PMID:26300891

  8. Functional diversification of hsp40: distinct j-protein functional requirements for two prions allow for chaperone-dependent prion selection.

    PubMed

    Harris, Julia M; Nguyen, Phil P; Patel, Milan J; Sporn, Zachary A; Hines, Justin K

    2014-07-01

    Yeast prions are heritable amyloid aggregates of functional yeast proteins; their propagation to subsequent cell generations is dependent upon fragmentation of prion protein aggregates by molecular chaperone proteins. Mounting evidence indicates the J-protein Sis1 may act as an amyloid specificity factor, recognizing prion and other amyloid aggregates and enabling Ssa and Hsp104 to act in prion fragmentation. Chaperone interactions with prions, however, can be affected by variations in amyloid-core structure resulting in distinct prion variants or 'strains'. Our genetic analysis revealed that Sis1 domain requirements by distinct variants of [PSI+] are strongly dependent upon overall variant stability. Notably, multiple strong [PSI+] variants can be maintained by a minimal construct of Sis1 consisting of only the J-domain and glycine/phenylalanine-rich (G/F) region that was previously shown to be sufficient for cell viability and [RNQ+] prion propagation. In contrast, weak [PSI+] variants are lost under the same conditions but maintained by the expression of an Sis1 construct that lacks only the G/F region and cannot support [RNQ+] propagation, revealing mutually exclusive requirements for Sis1 function between these two prions. Prion loss is not due to [PSI+]-dependent toxicity or dependent upon a particular yeast genetic background. These observations necessitate that Sis1 must have at least two distinct functional roles that individual prions differentially require for propagation and which are localized to the glycine-rich domains of the Sis1. Based on these distinctions, Sis1 plasmid-shuffling in a [PSI+]/[RNQ+] strain permitted J-protein-dependent prion selection for either prion. We also found that, despite an initial report to the contrary, the human homolog of Sis1, Hdj1, is capable of [PSI+] prion propagation in place of Sis1. This conservation of function is also prion-variant dependent, indicating that only one of the two Sis1-prion functions may have

  9. Comparison of genes required for H2O2 resistance in Streptococcus gordonii and Streptococcus sanguinis.

    PubMed

    Xu, Yifan; Itzek, Andreas; Kreth, Jens

    2014-12-01

    Hydrogen peroxide (H2O2) is produced by several members of the genus Streptococcus mainly through the pyruvate oxidase SpxB under aerobic growth conditions. The acute toxic nature of H2O2 raises the interesting question of how streptococci cope with intrinsically produced H2O2, which subsequently accumulates in the microenvironment and threatens the closely surrounding population. Here, we investigate the H2O2 susceptibility of oral Streptococcus gordonii and Streptococcus sanguinis and elucidate potential mechanisms of how they protect themselves from the deleterious effect of H2O2. Both organisms are considered primary colonizers and occupy the same intraoral niche making them potential targets for H2O2 produced by other species. We demonstrate that S. gordonii produces relatively more H2O2 and has a greater ability for resistance to H2O2 stress. Functional studies show that, unlike in Streptococcus pneumoniae, H2O2 resistance is not dependent on a functional SpxB and confirms the important role of the ferritin-like DNA-binding protein Dps. However, the observed increased H2O2 resistance of S. gordonii over S. sanguinis is likely to be caused by an oxidative stress protection machinery present even under anaerobic conditions, while S. sanguinis requires a longer period of time for adaptation. The ability to produce more H2O2 and be more resistant to H2O2 might aid S. gordonii in the competitive oral biofilm environment, since it is lower in abundance yet manages to survive quite efficiently in the oral biofilm.

  10. Contemporary Issues in Protein Requirements and Consumption for Resistance Trained Athletes

    PubMed Central

    Wilson, Jacob; Wilson, Gabriel J

    2006-01-01

    In recent years an explosion of research papers concerning protein consumption has been published. The need to consolidate this information has become critical from both practical and future research standpoints. For this reason, the following paper presents an in depth analysis of contemporary issues in protein requirements and consumption for resistance trained athletes. Specifically, the paper covers: 1.) protein requirements for resistance trained athletes; 2.) the effect of the digestion rate of protein on muscular protein balance; 3.) the optimal timing of protein intake relative to exercise; 4.) the optimal pattern of protein ingestion, relative to how an individual should consume their protein throughout a 24 hour period, and what sources are utilized during this time frame; 5.) protein composition and its interaction with measures of protein balance and strength performance; 6.) the combination of protein and carbohydrates on plasma insulin levels and protein balance; 7.) the efficacy of protein supplements and whole food protein sources. Our goal is to provide the reader with practical information in optimizing protein intake as well as for provision of sound advice to their clients. Finally, special care was taken to provide future research implications. PMID:18500966

  11. Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes.

    PubMed

    Labenski, Verena; Suerth, Julia D; Barczak, Elke; Heckl, Dirk; Levy, Camille; Bernadin, Ornellie; Charpentier, Emmanuelle; Williams, David A; Fehse, Boris; Verhoeyen, Els; Schambach, Axel

    2016-08-01

    Primary human T lymphocytes represent an important cell population for adoptive immunotherapies, including chimeric-antigen and T-cell receptor applications, as they have the capability to eliminate non-self, virus-infected and tumor cells. Given the increasing numbers of clinical immunotherapy applications, the development of an optimal vector platform for genetic T lymphocyte engineering, which allows cost-effective high-quality vector productions, remains a critical goal. Alpharetroviral self-inactivating vectors (ARV) have several advantages compared to other vector platforms, including a more random genomic integration pattern and reduced likelihood for inducing aberrant splicing of integrated proviruses. We developed an ARV platform for the transduction of primary human T lymphocytes. We demonstrated functional transgene transfer using the clinically relevant herpes-simplex-virus thymidine kinase variant TK.007. Proof-of-concept of alpharetroviral-mediated T-lymphocyte engineering was shown in vitro and in a humanized transplantation model in vivo. Furthermore, we established a stable, human alpharetroviral packaging cell line in which we deleted the entry receptor (SLC1A5) for RD114/TR-pseudotyped ARVs to prevent superinfection and enhance genomic integrity of the packaging cell line and viral particles. We showed that superinfection can be entirely prevented, while maintaining high recombinant virus titers. Taken together, this resulted in an improved production platform representing an economic strategy for translating the promising features of ARVs for therapeutic T-lymphocyte engineering. PMID:27162078

  12. Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes.

    PubMed

    Labenski, Verena; Suerth, Julia D; Barczak, Elke; Heckl, Dirk; Levy, Camille; Bernadin, Ornellie; Charpentier, Emmanuelle; Williams, David A; Fehse, Boris; Verhoeyen, Els; Schambach, Axel

    2016-08-01

    Primary human T lymphocytes represent an important cell population for adoptive immunotherapies, including chimeric-antigen and T-cell receptor applications, as they have the capability to eliminate non-self, virus-infected and tumor cells. Given the increasing numbers of clinical immunotherapy applications, the development of an optimal vector platform for genetic T lymphocyte engineering, which allows cost-effective high-quality vector productions, remains a critical goal. Alpharetroviral self-inactivating vectors (ARV) have several advantages compared to other vector platforms, including a more random genomic integration pattern and reduced likelihood for inducing aberrant splicing of integrated proviruses. We developed an ARV platform for the transduction of primary human T lymphocytes. We demonstrated functional transgene transfer using the clinically relevant herpes-simplex-virus thymidine kinase variant TK.007. Proof-of-concept of alpharetroviral-mediated T-lymphocyte engineering was shown in vitro and in a humanized transplantation model in vivo. Furthermore, we established a stable, human alpharetroviral packaging cell line in which we deleted the entry receptor (SLC1A5) for RD114/TR-pseudotyped ARVs to prevent superinfection and enhance genomic integrity of the packaging cell line and viral particles. We showed that superinfection can be entirely prevented, while maintaining high recombinant virus titers. Taken together, this resulted in an improved production platform representing an economic strategy for translating the promising features of ARVs for therapeutic T-lymphocyte engineering.

  13. P53- and mevalonate pathway–driven malignancies require Arf6 for metastasis and drug resistance

    PubMed Central

    Hashimoto, Ari; Oikawa, Tsukasa; Hashimoto, Shigeru; Sugino, Hirokazu; Yoshikawa, Ayumu; Otsuka, Yutaro; Handa, Haruka; Onodera, Yasuhito; Nam, Jin-Min; Oneyama, Chitose; Okada, Masato; Fukuda, Mitsunori

    2016-01-01

    Drug resistance, metastasis, and a mesenchymal transcriptional program are central features of aggressive breast tumors. The GTPase Arf6, often overexpressed in tumors, is critical to promote epithelial–mesenchymal transition and invasiveness. The metabolic mevalonate pathway (MVP) is associated with tumor invasiveness and known to prenylate proteins, but which prenylated proteins are critical for MVP-driven cancers is unknown. We show here that MVP requires the Arf6-dependent mesenchymal program. The MVP enzyme geranylgeranyl transferase II (GGT-II) and its substrate Rab11b are critical for Arf6 trafficking to the plasma membrane, where it is activated by receptor tyrosine kinases. Consistently, mutant p53, which is known to support tumorigenesis via MVP, promotes Arf6 activation via GGT-II and Rab11b. Inhibition of MVP and GGT-II blocked invasion and metastasis and reduced cancer cell resistance against chemotherapy agents, but only in cells overexpressing Arf6 and components of the mesenchymal program. Overexpression of Arf6 and mesenchymal proteins as well as enhanced MVP activity correlated with poor patient survival. These results provide insights into the molecular basis of MVP-driven malignancy. PMID:27044891

  14. Transportin-SR Is Required for Proper Splicing of Resistance Genes and Plant Immunity

    PubMed Central

    Xu, Shaohua; Zhang, Zhibin; Jing, Beibei; Gannon, Patrick; Ding, Jinmei; Xu, Fang; Li, Xin; Zhang, Yuelin

    2011-01-01

    Transportin-SR (TRN-SR) is a member of the importin-β super-family that functions as the nuclear import receptor for serine-arginine rich (SR) proteins, which play diverse roles in RNA metabolism. Here we report the identification and cloning of mos14 (modifier of snc1-1, 14), a mutation that suppresses the immune responses conditioned by the auto-activated Resistance (R) protein snc1 (suppressor of npr1-1, constitutive 1). MOS14 encodes a nuclear protein with high similarity to previously characterized TRN-SR proteins in animals. Yeast two-hybrid assays showed that MOS14 interacts with AtRAN1 via its N-terminus and SR proteins via its C-terminus. In mos14-1, localization of several SR proteins to the nucleus was impaired, confirming that MOS14 functions as a TRN-SR. The mos14-1 mutation results in altered splicing patterns of SNC1 and another R gene RPS4 and compromised resistance mediated by snc1 and RPS4, suggesting that nuclear import of SR proteins by MOS14 is required for proper splicing of these two R genes and is important for their functions in plant immunity. PMID:21738492

  15. Differential Requirement of Oryza sativa RAR1 in Immune Receptor-Mediated Resistance of Rice to Magnaporthe oryzae

    PubMed Central

    Song, Min-Young; Kim, Chi-Yeol; Han, Muho; Ryu, Hak-Seung; Lee, Sang-Kyu; Sun, Li; He, Zuhua; Seo, Young-Su; Canal, Patrick; Ronald, Pamela C.; Jeon, Jong-Seong

    2013-01-01

    The required for Mla12 resistance (RAR1) protein is essential for the plant immune response. In rice, a model monocot species, the function of Oryza sativa RAR1 (OsRAR1) has been little explored. In our current study, we characterized the response of a rice osrar1 T-DNA insertion mutant to infection by Magnaporthe oryzae, the causal agent of rice blast disease. osrar1 mutants displayed reduced resistance compared with wild type rice when inoculated with the normally virulent M. oryzae isolate PO6-6, indicating that OsRAR1 is required for an immune response to this pathogen. We also investigated the function of Os-RAR1 in the resistance mechanism mediated by the immune receptor genes Pib and Pi5 that encode nucleotide binding-leucine rich repeat (NB-LRR) proteins. We inoculated progeny from Pib/osrar1 and Pi5/osrar1 heterozygous plants with the avirulent M. oryzae isolates, race 007 and PO6-6, respectively. We found that only Pib-mediated resistance was compromised by the osrar1 mutation and that the introduction of the OsRAR1 cDNA into Pib/osrar1 rescued Pib-mediated resistance. These results indicate that OsRAR1 is required for Pib-mediated resistance but not Pi5-mediated resistance to M. oryzae. PMID:23563801

  16. Lower body versus whole body resistive exercise training and energy requirements of older men and women.

    PubMed

    Campbell, Wayne W; Kruskall, Laura J; Evans, William J

    2002-08-01

    A person's energy requirement is defined as the metabolizable energy intake (MEI) consumed over a period of body weight stability. Controversy exists regarding whether resistive exercise training (RT) influences the energy requirement of older people. The aim of this study was to assess the effect of RT on the energy requirement of older people. The subjects were 11 men (M) and 17 women (W); age range, 55 to 78 years. During a 14-week precisely controlled diet study, each subject consumed foods and beverages portioned to provide sufficient MEI to match their energy requirement and to keep body weight stable at +/- 0.5 kg of their starting weight. MEI was determined from bomb calorimeter analyses of the gross energy (GE) content of food, urine, and feces samples collected during 4-day intake-balance periods at study weeks 2, 8, and 14 (baseline, week RT6, and week RT12, respectively). MEI = GE(food)-GE(urine) - GE(feces). Resting energy expenditure (REE) was measured using an indirect calorimeter. From study weeks 3 to 14, 10 subjects (4 M, 6 W) remained sedentary (SED), 9 subjects (4 M, 5 W) performed lower body RT (LBRT) 3 times/week, and 9 subjects (3 M, 6 W) performed whole body RT (WBRT) 3 times/week. Body weight was not different among the SED, LBRT, and WBRT groups at baseline and were not changed over time or influenced by RT. At baseline, MEI was not different among the 3 groups. From weeks RT1 to RT12, MEI had to be increased by 17% +/- 5% (mean +/- SEM), 14% +/- 7%, and 12% +/- 7% in the SED, LBRT, and WBRT groups, respectively, to maintain stable body weights. At week RT12, the MEI required to maintain stable body weight was not significantly different among the SED, LBRT, and WBRT groups (9.45 +/- 0.95, 9.40 +/- 0.83, and 8.64 +/-0.53 MJ/d, respectively). At week RT12, the MEI and MEI/REE ratio were higher in men versus women, independent of group assignment. These data suggest that RT, whether performed using the lower body only or the whole body, does

  17. Requirement of MrpH for Mannose-Resistant Proteus-Like Fimbria-Mediated Hemagglutination by Proteus mirabilis

    PubMed Central

    Li, Xin; Johnson, David E.; Mobley, Harry L. T.

    1999-01-01

    Two new genes, mrpH and mrpJ, were identified downstream of mrpG in the mrp gene cluster encoding mannose-resistant Proteus-like (MR/P) fimbriae of uropathogenic Proteus mirabilis. Since the predicted MrpH has 30% amino acid sequence identity to PapG, the Galα(1-4)Gal-binding adhesin of Escherichia coli P fimbriae, we hypothesized that mrpH encodes the functional MR/P hemagglutinin. MR/P fimbriae, expressed in E. coli DH5α, conferred on bacteria both the ability to cause mannose-resistant hemagglutination and the ability to aggregate to form pellicles on the broth surface. Both a ΔmrpH mutant expressed in E. coli DH5α and an isogenic mrpH::aphA mutant of P. mirabilis were unable to produce normal MR/P fimbriae efficiently, suggesting that MrpH was involved in fimbrial assembly. Amino acid residue substitution of the N-terminal cysteine residues (C66S and C128S) of MrpH abolished the receptor-binding activity (hemagglutinating ability) of MrpH but allowed normal fimbrial assembly, supporting the notion that MrpH was the functional MR/P hemagglutinin. Immunogold electron microscopy of P. mirabilis HI4320 revealed that MrpH was located at the tip of MR/P fimbriae, also consistent with its role in receptor binding. The isogenic mrpH::aphA mutant of HI4320 was less able to colonize the urine, bladder, and kidneys in a mouse model of ascending urinary tract infection (P < 0.01), and therefore MR/P fimbriae contribute significantly to bacterial colonization in mice. While there are similarities between P. mirabilis MR/P and E. coli P fimbriae, there are more notable differences: (i) synthesis of the MrpH adhesin is required to initiate fimbrial assembly, (ii) MR/P fimbriae confer an aggregation phenotype, (iii) site-directed mutation of specific residues can abolish receptor binding but allows fimbrial assembly, and (iv) mutation of the adhesin gene abolishes virulence in a mouse model of ascending urinary tract infection. PMID:10338487

  18. A peroxiredoxin, PRDX-2, is required for insulin secretion and insulin/IIS-dependent regulation of stress resistance and longevity.

    PubMed

    Oláhová, Monika; Veal, Elizabeth A

    2015-08-01

    Peroxiredoxins (Prx) are abundant thiol peroxidases with a conserved anti-ageing role. In contrast to most animals, the nematode worm, Caenorhabditis elegans, encodes a single cytosolic 2-Cys Prx, PRDX-2, rendering it an excellent model for examining how peroxiredoxins affect animal physiology and ageing. Our previous work revealed that, although PRDX-2 protects against the toxicity of peroxides, enigmatically, prdx-2-mutant animals are hyper-resistant to other forms of oxidative stress. Here, we have investigated the basis for this increased resistance. Mammalian FOXO and Nrf2 transcription factors directly promote the expression of a range of detoxification enzymes. We show that the FOXO orthologue, DAF-16, and the Nrf2 orthologue, SKN-1, are required for the increased stress resistance of prdx-2-mutant worms. Our data suggest that PRDX-2 is required for normal levels of insulin secretion and hence the inhibition of DAF-16 and SKN-1 by insulin/IGF-1-like signalling (IIS) under nutrient-rich conditions. Intriguingly, loss of PRDX-2 increases DAF-16 and SKN-1 activities sufficiently to increase arsenite resistance without initiating other IIS-inhibited processes. Together, these data suggest that loss of peroxiredoxin function may increase stress resistance by reducing insulin secretion, but that further changes in insulin signalling are required for the reprogramming of development and fat metabolism. In addition, we reveal that the temperature-dependent prolongevity function of PRDX-2 is required for the extended lifespan associated with several pathways, including further reductions in IIS.

  19. A peroxiredoxin, PRDX-2, is required for insulin secretion and insulin/IIS-dependent regulation of stress resistance and longevity

    PubMed Central

    Oláhová, Monika; Veal, Elizabeth A

    2015-01-01

    Peroxiredoxins (Prx) are abundant thiol peroxidases with a conserved anti-ageing role. In contrast to most animals, the nematode worm, Caenorhabditis elegans, encodes a single cytosolic 2-Cys Prx, PRDX-2, rendering it an excellent model for examining how peroxiredoxins affect animal physiology and ageing. Our previous work revealed that, although PRDX-2 protects against the toxicity of peroxides, enigmatically, prdx-2-mutant animals are hyper-resistant to other forms of oxidative stress. Here, we have investigated the basis for this increased resistance. Mammalian FOXO and Nrf2 transcription factors directly promote the expression of a range of detoxification enzymes. We show that the FOXO orthologue, DAF-16, and the Nrf2 orthologue, SKN-1, are required for the increased stress resistance of prdx-2-mutant worms. Our data suggest that PRDX-2 is required for normal levels of insulin secretion and hence the inhibition of DAF-16 and SKN-1 by insulin/IGF-1-like signalling (IIS) under nutrient-rich conditions. Intriguingly, loss of PRDX-2 increases DAF-16 and SKN-1 activities sufficiently to increase arsenite resistance without initiating other IIS-inhibited processes. Together, these data suggest that loss of peroxiredoxin function may increase stress resistance by reducing insulin secretion, but that further changes in insulin signalling are required for the reprogramming of development and fat metabolism. In addition, we reveal that the temperature-dependent prolongevity function of PRDX-2 is required for the extended lifespan associated with several pathways, including further reductions in IIS. PMID:25808059

  20. Glutamate Dehydrogenase Is Required by Mycobacterium bovis BCG for Resistance to Cellular Stress

    PubMed Central

    Gallant, James L.; Viljoen, Albertus J.; van Helden, Paul D.; Wiid, Ian J. F.

    2016-01-01

    We recently reported on our success to generate deletion mutants of the genes encoding glutamate dehydrogenase (GDH) and glutamine oxoglutarate aminotransferase (GOGAT) in M. bovis BCG, despite their in vitro essentiality in M. tuberculosis. We could use these mutants to delineate the roles of GDH and GOGAT in mycobacterial nitrogen metabolism by using M. bovis BCG as a model for M. tuberculosis specifically. Here, we extended our investigation towards the involvement of GDH and GOGAT in other aspects of M. bovis BCG physiology, including the use of glutamate as a carbon source and resistance to known phagosomal stresses, as well as in survival inside macrophages. We find that gdh is indispensable for the utilization of glutamate as a major carbon source, in low pH environments and when challenged with nitric oxide. On the other hand, the gltBD mutant had increased viability under low pH conditions and was unaffected by a challenge with nitric oxide. Strikingly, GDH was required to sustain M. bovis BCG during infection of both murine RAW 264.7 and bone-marrow derived and macrophages, while GOGAT was not. We conclude that the catabolism of glutamate in slow growing mycobacteria may be a crucial function during infection of macrophage cells and demonstrate a novel requirement for M. bovis BCG GDH in the protection against acidic and nitrosative stress. These results provide strong clues on the role of GDH in intracellular survival of M. tuberculosis, in which the essentiality of the gdh gene complicates knock out studies making the study of the role of this enzyme in pathogenesis difficult. PMID:26824899

  1. Learned stressor resistance requires extracellular signal-regulated kinase in the prefrontal cortex

    PubMed Central

    Christianson, John P.; Flyer-Adams, Johanna G.; Drugan, Robert C.; Amat, Jose; Daut, Rachel A.; Foilb, Allison R.; Watkins, Linda R.; Maier, Steven F.

    2014-01-01

    Behaviorally controllable stressors confer protection from the neurochemical and behavioral consequences of future uncontrollable stressors, a phenomenon termed “behavioral immunization”. Recent data implicate protein synthesis within the ventromedial prefrontal cortex (mPFC) as critical to behavioral immunization. Adult, male Sprague-Dawley rats were exposed to a series of controllable tailshocks and 1 week later to uncontrollable tailshocks, followed 24 h later by social exploration and shuttlebox escape tests. To test the involvement of N-methyl-D-aspartate receptors (NMDARs) and the extracellular signal-regulated kinase (ERK) cascade in behavioral immunization, either D-AP5 or the MEK inhibitor U0126 was injected to the prelimbic (PL) or infralimbic (IL) mPFC prior to controllable stress exposure. Phosphorylated ERK and P70S6K, regulators of transcription and translation, were quantified by Western blot or immunohistochemistry after controllable or uncontrollable tailshocks. Prior controllable stress prevented the social exploration and shuttlebox performance deficits caused by the later uncontrollable stressor, and this effect was blocked by injections of D-AP5 into mPFC. A significant increase in phosphorylated ERK1 and ERK2, but not P70S6K, occurred within the PL and IL in rats exposed to controllable stress, but not to uncontrollable stress. However, U0126 only prevented behavioral immunization when injected to the PL. We provide evidence that NMDAR and ERK dependent signaling within the PL region is required for behavioral immunization, a learned form of stressor resistance. PMID:25324750

  2. Lipopolysaccharide core phosphates are required for viability and intrinsic drug resistance in Pseudomonas aeruginosa.

    PubMed

    Walsh, A G; Matewish, M J; Burrows, L L; Monteiro, M A; Perry, M B; Lam, J S

    2000-02-01

    Pseudomonas aeruginosa is an opportunistic pathogen that is notorious for its intrinsic drug resistance. We have used chemical and genetic techniques to characterize three putative kinase genes that are involved in the addition of phosphate to the inner core region of P. aeruginosa lipopolysaccharide. The first gene is a waaP homologue, whereas the other two (wapP and wapQ) are unique to P. aeruginosa. Repeated attempts using a variety of membrane-stabilizing conditions to generate waaP:Gm (Gm, gentamicin) or wapP:Gm mutants were unsuccessful. We were able to generate a chromosomal waaP mutant that had a wild-type copy of either waaPPa or waaPEc in trans, but were unable to cure this plasmid-borne copy of the gene. These results are consistent with the fact that P. aeruginosa mutants lacking inner core heptose (Hep) or phosphate have never been isolated and demonstrate the requirement of Hep-linked phosphate for P. aeruginosa viability. A wapQ:Gm mutant was isolated and it had an unaltered minimum inhibitory concentration (MIC) for novobiocin and only a small decrease in the MIC for sodium dodecyl sulphate (SDS), suggesting that the loss of a phosphate group transferred by WapQ may only be having a small impact on outer-membrane permeability. Nuclear magnetic resonance and methylation linkage analysis showed that WaaPPa could add one phosphate to O4 of HepI in a Salmonella typhimurium waaP mutant. The expression of WaaPPa increased the outer-membrane integrity of these complemented mutants, as evidenced by 35-fold and 75-fold increases in the MIC for novobiocin and SDS respectively. The S. typhimurium waaP mutant transformed with both waaP and wapP had over 250-fold and 1000-fold increases, respectively, in these MICs. The inner core phosphates of P. aeruginosa appear to be playing a key role in the intrinsic drug resistance of this bacterium.

  3. 42 CFR 84.1149 - Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Airflow resistance tests; all dust, fume, and mist... RESPIRATORY PROTECTIVE DEVICES Dust, Fume, and Mist; Pesticide; Paint Spray; Powered Air-Purifying High Efficiency Respirators and Combination Gas Masks § 84.1149 Airflow resistance tests; all dust, fume, and...

  4. 42 CFR 84.1149 - Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Airflow resistance tests; all dust, fume, and mist... RESPIRATORY PROTECTIVE DEVICES Dust, Fume, and Mist; Pesticide; Paint Spray; Powered Air-Purifying High Efficiency Respirators and Combination Gas Masks § 84.1149 Airflow resistance tests; all dust, fume, and...

  5. 42 CFR 84.1149 - Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Airflow resistance tests; all dust, fume, and mist... RESPIRATORY PROTECTIVE DEVICES Dust, Fume, and Mist; Pesticide; Paint Spray; Powered Air-Purifying High Efficiency Respirators and Combination Gas Masks § 84.1149 Airflow resistance tests; all dust, fume, and...

  6. 42 CFR 84.1149 - Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Airflow resistance tests; all dust, fume, and mist... RESPIRATORY PROTECTIVE DEVICES Dust, Fume, and Mist; Pesticide; Paint Spray; Powered Air-Purifying High Efficiency Respirators and Combination Gas Masks § 84.1149 Airflow resistance tests; all dust, fume, and...

  7. 42 CFR 84.1149 - Airflow resistance tests; all dust, fume, and mist respirators; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Airflow resistance tests; all dust, fume, and mist... RESPIRATORY PROTECTIVE DEVICES Dust, Fume, and Mist; Pesticide; Paint Spray; Powered Air-Purifying High Efficiency Respirators and Combination Gas Masks § 84.1149 Airflow resistance tests; all dust, fume, and...

  8. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... reasonable manner during manufacture, distribution, and retail display. (c) Labeling. Each retail package of... oral hygiene products and vaginal products are not now packaged in tamper-resistant retail packages... retail sale that is not packaged in a tamper-resistant package or that is not properly labeled under...

  9. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... reasonable manner during manufacture, distribution, and retail display. (c) Labeling. Each retail package of... oral hygiene products and vaginal products are not now packaged in tamper-resistant retail packages... retail sale that is not packaged in a tamper-resistant package or that is not properly labeled under...

  10. A signaling protease required for melanization in Drosophila affects resistance and tolerance of infections.

    PubMed

    Ayres, Janelle S; Schneider, David S

    2008-12-01

    Organisms evolve two routes to surviving infections-they can resist pathogen growth (resistance) and they can endure the pathogenesis of infection (tolerance). The sum of these two properties together defines the defensive capabilities of the host. Typically, studies of animal defenses focus on either understanding resistance or, to a lesser extent, tolerance mechanisms, thus providing little understanding of the relationship between these two mechanisms. We suggest there are nine possible pairwise permutations of these traits, assuming they can increase, decrease, or remain unchanged in an independent manner. Here we show that by making a single mutation in the gene encoding a protease, CG3066, active in the melanization cascade in Drosophila melanogaster, we observe the full spectrum of changes; these mutant flies show increases and decreases in their resistance and tolerance properties when challenged with a variety of pathogens. This result implicates melanization in fighting microbial infections and shows that an immune response can affect both resistance and tolerance to infections in microbe-dependent ways. The fly is often described as having an unsophisticated and stereotypical immune response where single mutations cause simple binary changes in immunity. We report a level of complexity in the fly's immune response that has strong ecological implications. We suggest that immune responses are highly tuned by evolution, since selection for defenses that alter resistance against one pathogen may change both resistance and tolerance to other pathogens.

  11. Impact resistance of materials for guards on cutting machine tools--requirements in future European safety standards.

    PubMed

    Mewes, D; Trapp, R P

    2000-01-01

    Guards on machine tools are meant to protect operators from injuries caused by tools, workpieces, and fragments hurled out of the machine's working zone. This article presents the impact resistance requirements, which guards according to European safety standards for machine tools must satisfy. Based upon these standards the impact resistance of different guard materials was determined using cylindrical steel projectiles. Polycarbonate proves to be a suitable material for vision panels because of its high energy absorption capacity. The impact resistance of 8-mm thick polycarbonate is roughly equal to that of a 3-mm thick steel sheet Fe P01. The limited ageing stability, however, makes it necessary to protect polycarbonate against cooling lubricants by means of additional panes on both sides.

  12. Cryptococcus neoformans Yap1 is required for normal fluconazole and oxidative stress resistance.

    PubMed

    Paul, Sanjoy; Doering, Tamara L; Moye-Rowley, W Scott

    2015-01-01

    Cryptococcus neoformans is a pathogen that is the most common cause of fungal meningitis. As with most fungal pathogens, the most prevalent clinical antifungal used to treat Cryptococcosis is orally administered fluconazole. Resistance to this antifungal is an increasing concern in treatment of fungal disease in general. Our knowledge of the specific determinants involved in fluconazole resistance in Cryptococcus is limited. Here we report the identification of an important genetic determinant of fluconazole resistance in C. neoformans that encodes a basic region-leucine zipper transcription factor homologous to Saccharomyces cerevisiae Yap1. Expression of a codon-optimized form of the Cn YAP1 cDNA in S. cerevisiae complemented defects caused by loss of the endogenous S. cerevisiae YAP1 gene and activated transcription from a reporter gene construct. Mutant strains of C. neoformans lacking YAP1 were hypersensitive to a range of oxidative stress agents but importantly also to fluconazole. Loss of Yap1 homologues from other fungal pathogens like Candida albicans or Aspergillus fumigatus was previously found to cause oxidant hypersensitivity but had no detectable effect on fluconazole resistance. Our data provide evidence for a unique biological role of Yap1 in wild-type fluconazole resistance in C. neoformans.

  13. Energy requirements for methods improving gas detection by modulating physical properties of resistive gas sensors

    NASA Astrophysics Data System (ADS)

    Trawka, M.; Kotarski, M.

    2016-01-01

    One of the most important disadvantage of resistive gas sensors is their limited gas selectivity. Therefore, various methods modulating their physical properties are used to improve gas detection. These methods are usually limited to temperature modulation or UV light irradiation for the layers exhibiting photocatalytic effect. These methods cause increased energy consumption. In our study we consider how much energy has to be supplied to utilize such methods and what kind of additional information can be gathered. We present experimental results of selected resistive gas sensors, including commercial and prototype constructions, and practical solutions of modulating their physical properties.

  14. Increase in family allowances.

    PubMed

    1989-01-01

    In July 1989 the family allowance structure in Australia was changed from a 4-rate to a 2-rate structure. The new rates were increased to $A9 a week for the 1st 3 children and $A12 for each additional child. The Family Allowance Supplment rate for children 13-15 years old was raised from $A31 to $A34.10/week. PMID:12344544

  15. High-Level Chromate Resistance in Arthrobacter sp. strain FB24 Requires Previously Uncharacterized Accessory Genes

    SciTech Connect

    Henne, Kristene L.; Nakatsu, Cindy N.; Thompson, Dorothea K.; Konopka, Allan

    2009-09-24

    The annotated genome sequence of Arthrobacter sp. strain FB24 revealed a chromate resistance determinant (CRD): a cluster of 8 genes located on a 10.6 kb fragment of a 96 kb plasmid. The CRD includes chrA, which encodes a putative chromate efflux protein, and three genes with amino acid similarities to the amino and carboxy termini of ChrB, a putative regulatory protein. There are also three novel genes that have not been previously associated with chromate resistance in other bacteria; they encode an oxidoreductase (most similar to malate:quinone oxidoreductase), a functionally unknown protein with a WD40 repeat domain and a lipoprotein. A chromate-sensitive mutant (strain D11) was generated by curing FB24 of its 96-kb plasmid. Elemental analysis indicated that chromate-exposed cells of strain D11 accumulated three times more chromium than strain FB24. Introduction of the CRD into strain D11 conferred chromate resistance comparable to wild-type levels, whereas deletion of specific regions of the CRD led to decreased resistance. Using real-time reverse transcriptase PCR, we show that expression of each gene within the CRD is specifically induced in response to chromate but not by lead, hydrogen peroxide or arsenate. Higher levels of chrA expression were achieved when the chrB orthologs and the WD40 repeat domain genes were present, suggesting their regulatory roles. Collectively, our findings indicate that chromate resistance in strain FB24 is primarily achieved by plasmid-mediated chromate efflux with the contribution of previously unrecognized accessory genes.

  16. Sterol biosynthesis is required for heat resistance but not extracellular survival in leishmania.

    PubMed

    Xu, Wei; Hsu, Fong-Fu; Baykal, Eda; Huang, Juyang; Zhang, Kai

    2014-10-01

    Sterol biosynthesis is a crucial pathway in eukaryotes leading to the production of cholesterol in animals and various C24-alkyl sterols (ergostane-based sterols) in fungi, plants, and trypanosomatid protozoa. Sterols are important membrane components and precursors for the synthesis of powerful bioactive molecules, including steroid hormones in mammals. Their functions in pathogenic protozoa are not well characterized, which limits the development of sterol synthesis inhibitors as drugs. Here we investigated the role of sterol C14α-demethylase (C14DM) in Leishmania parasites. C14DM is a cytochrome P450 enzyme and the primary target of azole drugs. In Leishmania, genetic or chemical inactivation of C14DM led to a complete loss of ergostane-based sterols and accumulation of 14-methylated sterols. Despite the drastic change in lipid composition, C14DM-null mutants (c14dm(-)) were surprisingly viable and replicative in culture. They did exhibit remarkable defects including increased membrane fluidity, failure to maintain detergent resistant membrane fraction, and hypersensitivity to heat stress. These c14dm(-) mutants showed severely reduced virulence in mice but were highly resistant to itraconazole and amphotericin B, two drugs targeting sterol synthesis. Our findings suggest that the accumulation of toxic sterol intermediates in c14dm(-) causes strong membrane perturbation and significant vulnerability to stress. The new knowledge may help improve the efficacy of current drugs against pathogenic protozoa by exploiting the fitness loss associated with drug resistance.

  17. Sterol biosynthesis is required for heat resistance but not extracellular survival in leishmania.

    PubMed

    Xu, Wei; Hsu, Fong-Fu; Baykal, Eda; Huang, Juyang; Zhang, Kai

    2014-10-01

    Sterol biosynthesis is a crucial pathway in eukaryotes leading to the production of cholesterol in animals and various C24-alkyl sterols (ergostane-based sterols) in fungi, plants, and trypanosomatid protozoa. Sterols are important membrane components and precursors for the synthesis of powerful bioactive molecules, including steroid hormones in mammals. Their functions in pathogenic protozoa are not well characterized, which limits the development of sterol synthesis inhibitors as drugs. Here we investigated the role of sterol C14α-demethylase (C14DM) in Leishmania parasites. C14DM is a cytochrome P450 enzyme and the primary target of azole drugs. In Leishmania, genetic or chemical inactivation of C14DM led to a complete loss of ergostane-based sterols and accumulation of 14-methylated sterols. Despite the drastic change in lipid composition, C14DM-null mutants (c14dm(-)) were surprisingly viable and replicative in culture. They did exhibit remarkable defects including increased membrane fluidity, failure to maintain detergent resistant membrane fraction, and hypersensitivity to heat stress. These c14dm(-) mutants showed severely reduced virulence in mice but were highly resistant to itraconazole and amphotericin B, two drugs targeting sterol synthesis. Our findings suggest that the accumulation of toxic sterol intermediates in c14dm(-) causes strong membrane perturbation and significant vulnerability to stress. The new knowledge may help improve the efficacy of current drugs against pathogenic protozoa by exploiting the fitness loss associated with drug resistance. PMID:25340392

  18. Nanobatteries in redox-based resistive switches require extension of memristor theory.

    PubMed

    Valov, I; Linn, E; Tappertzhofen, S; Schmelzer, S; van den Hurk, J; Lentz, F; Waser, R

    2013-01-01

    Redox-based nanoionic resistive memory cells are one of the most promising emerging nanodevices for future information technology with applications for memory, logic and neuromorphic computing. Recently, the serendipitous discovery of the link between redox-based nanoionic-resistive memory cells and memristors and memristive devices has further intensified the research in this field. Here we show on both a theoretical and an experimental level that nanoionic-type memristive elements are inherently controlled by non-equilibrium states resulting in a nanobattery. As a result, the memristor theory must be extended to fit the observed non-zero-crossing I-V characteristics. The initial electromotive force of the nanobattery depends on the chemistry and the transport properties of the materials system but can also be introduced during redox-based nanoionic-resistive memory cell operations. The emf has a strong impact on the dynamic behaviour of nanoscale memories, and thus, its control is one of the key factors for future device development and accurate modelling.

  19. γ-Secretase inhibitor-resistant glioblastoma stem cells require RBPJ to propagate.

    PubMed

    Fan, Xing

    2016-07-01

    Targeting glioblastoma stem cells with γ-secretase inhibitors (GSIs) disrupts the Notch pathway and has shown some benefit in both pre-clinical models and in patients during phase I/II clinical trials. However, it is largely unknown why some glioblastoma (GBM) does not respond to GSI treatment. In this issue of the JCI, Xie et al. determined that GSI-resistant brain tumor-initiating cells (BTICs) from GBM express a higher level of the gene RBPJ, which encodes a mediator of canonical Notch signaling, compared to non-BTICs. Knockdown of RBPJ in BTICs decreased propagation in vitro and in vivo by inducing apoptosis. Interestingly, RBPJ was shown to regulate a different transcription program than Notch in BTICs by binding CDK9, thereby affecting Pol II-regulated transcript elongation. Targeting CDK9 or c-MYC, an upstream regulator of RBPJ, with small molecules also decreased BTIC propagation, and prolonged survival in mice bearing orthotopic GBM xenografts. This study not only provides a mechanism for GSI treatment resistance, but also identifies two potential therapeutic strategies to target GSI-resistant BTICs.

  20. Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells.

    PubMed

    Samanta, Debangshu; Gilkes, Daniele M; Chaturvedi, Pallavi; Xiang, Lisha; Semenza, Gregg L

    2014-12-16

    Triple negative breast cancers (TNBCs) are defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 expression, and are treated with cytotoxic chemotherapy such as paclitaxel or gemcitabine, with a durable response rate of less than 20%. TNBCs are enriched for the basal subtype gene expression profile and the presence of breast cancer stem cells, which are endowed with self-renewing and tumor-initiating properties and resistance to chemotherapy. Hypoxia-inducible factors (HIFs) and their target gene products are highly active in TNBCs. Here, we demonstrate that HIF expression and transcriptional activity are induced by treatment of MDA-MB-231, SUM-149, and SUM-159, which are human TNBC cell lines, as well as MCF-7, which is an ER(+)/PR(+) breast cancer line, with paclitaxel or gemcitabine. Chemotherapy-induced HIF activity enriched the breast cancer stem cell population through interleukin-6 and interleukin-8 signaling and increased expression of multidrug resistance 1. Coadministration of HIF inhibitors overcame the resistance of breast cancer stem cells to paclitaxel or gemcitabine, both in vitro and in vivo, leading to tumor eradication. Increased expression of HIF-1α or HIF target genes in breast cancer biopsies was associated with decreased overall survival, particularly in patients with basal subtype tumors and those treated with chemotherapy alone. Based on these results, clinical trials are warranted to test whether treatment of patients with TNBC with a combination of cytotoxic chemotherapy and HIF inhibitors will improve patient survival.

  1. Nanobatteries in redox-based resistive switches require extension of memristor theory

    PubMed Central

    Valov, I.; Linn, E.; Tappertzhofen, S.; Schmelzer, S.; van den Hurk, J.; Lentz, F.; Waser, R.

    2013-01-01

    Redox-based nanoionic resistive memory cells are one of the most promising emerging nanodevices for future information technology with applications for memory, logic and neuromorphic computing. Recently, the serendipitous discovery of the link between redox-based nanoionic-resistive memory cells and memristors and memristive devices has further intensified the research in this field. Here we show on both a theoretical and an experimental level that nanoionic-type memristive elements are inherently controlled by non-equilibrium states resulting in a nanobattery. As a result, the memristor theory must be extended to fit the observed non-zero-crossing I–V characteristics. The initial electromotive force of the nanobattery depends on the chemistry and the transport properties of the materials system but can also be introduced during redox-based nanoionic-resistive memory cell operations. The emf has a strong impact on the dynamic behaviour of nanoscale memories, and thus, its control is one of the key factors for future device development and accurate modelling. PMID:23612312

  2. Trastuzumab resistance induces EMT to transform HER2+ PTEN− to a triple negative breast cancer that requires unique treatment options

    PubMed Central

    Burnett, Joseph P.; Korkaya, Hasan; Ouzounova, Maria D.; Jiang, Hui; Conley, Sarah J.; Newman, Bryan W.; Sun, Lichao; Connarn, Jamie N.; Chen, Ching-Shih; Zhang, Ning; Wicha, Max S.; Sun, Duxin

    2015-01-01

    Although trastuzumab is an effective treatment in early stage HER2+ breast cancer the majority of advanced HER2+ breast cancers develop trastuzumab resistance, especially in the 40% of breast cancers with loss of PTEN. However, HER2+ breast cancer patients continue to receive trastuzumab regardless PTEN status and the consequence of therapy in these patients is unknown. We demonstrate that continued use of trastuzumab in HER2+ cells with loss of PTEN induces the epithelial-mesenchymal transition (EMT) and transform HER2+ to a triple negative breast cancer. These transformed cells exhibited mesenchymal morphology and gene expression markers, while parent HER2+ cells showed epithelial morphology and markers. The transformed cells exhibited loss of dependence on ERBB family signaling (such as HER2, HER3, HER4, BTC, HRG, EGF) and reduced estrogen and progesterone receptors. Continued use of trastuzumab in HER2+ PTEN− cells increased the frequency of cancer stem cells (CSCs) and metastasis potential. Strikingly, parental HER2+ cells and transformed resistant cells respond to treatment differently. Transformed resistant cells were sensitive to chemical probe (sulforaphane) through inhibition of IL-6/STAT3/NF-κB positive feedback loop whereas parental HER2+ cells did not respond. This data suggests that trastuzumab resistance in HER2+ PTEN− breast cancer induces EMT and subtype switching, which requires unique treatment options. PMID:26522776

  3. SGT1 interacts with the Prf resistance protein and is required for Prf accumulation and Prf-mediated defense signaling.

    PubMed

    Kud, Joanna; Zhao, Zhulu; Du, Xinran; Liu, Yule; Zhao, Yun; Xiao, Fangming

    2013-02-15

    The highly conserved eukaryotic co-chaperone SGT1 (suppressor of the G2 allele of skp1) is an important signaling component of plant defense responses and positively regulates disease resistance conferred by many resistance (R) proteins. In this study, we investigated the contribution of SGT1 in the Prf-mediated defense responses in both Nicotiana benthamiana and tomato (Solanum lycopersicum). SGT1 was demonstrated to interact with Prf in plant cells by co-immunoprecipitation. The requirement of SGT1 in the accumulation of Prf or autoactive Prf(D1416V) was determined by the degradation of these proteins in N. benthamiana, in which SGT1 was repressed by virus-induced gene silencing (VIGS). Pseudomonas pathogen assay on the SGT1-silenced tomato plants implicates SGT1 is required for the Prf-mediated full resistance to Pseudomonas syringae pv. tomato (Pst). These results suggest that, in both N. benthamiana and tomato, SGT1 contributes to the Prf-mediated defense responses by stabilizing Prf protein via its co-chaperone activity.

  4. 46 CFR 154.440 - Allowable stress.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Allowable stress. 154.440 Section 154.440 Shipping COAST... Tank Type A § 154.440 Allowable stress. (a) The allowable stresses for an independent tank type A must... Commandant (CG-522). (b) A greater allowable stress than required in paragraph (a)(1) of this section may...

  5. 46 CFR 154.440 - Allowable stress.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Allowable stress. 154.440 Section 154.440 Shipping COAST... Tank Type A § 154.440 Allowable stress. (a) The allowable stresses for an independent tank type A must... Commandant (CG-ENG). (b) A greater allowable stress than required in paragraph (a)(1) of this section may...

  6. 46 CFR 154.440 - Allowable stress.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Allowable stress. 154.440 Section 154.440 Shipping COAST... Tank Type A § 154.440 Allowable stress. (a) The allowable stresses for an independent tank type A must... Commandant (CG-ENG). (b) A greater allowable stress than required in paragraph (a)(1) of this section may...

  7. 46 CFR 154.440 - Allowable stress.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Allowable stress. 154.440 Section 154.440 Shipping COAST... Tank Type A § 154.440 Allowable stress. (a) The allowable stresses for an independent tank type A must... Commandant (CG-ENG). (b) A greater allowable stress than required in paragraph (a)(1) of this section may...

  8. Extracellular DNA is required for root tip resistance to fungal infection.

    PubMed

    Wen, Fushi; White, Gerard J; VanEtten, Hans D; Xiong, Zhongguo; Hawes, Martha C

    2009-10-01

    Plant defense involves a complex array of biochemical interactions, many of which occur in the extracellular environment. The apical 1- to 2-mm root tip housing apical and root cap meristems is resistant to infection by most pathogens, so growth and gravity sensing often proceed normally even when other sites on the root are invaded. The mechanism of this resistance is unknown but appears to involve a mucilaginous matrix or "slime" composed of proteins, polysaccharides, and detached living cells called "border cells." Here, we report that extracellular DNA (exDNA) is a component of root cap slime and that exDNA degradation during inoculation by a fungal pathogen results in loss of root tip resistance to infection. Most root tips (>95%) escape infection even when immersed in inoculum from the root-rotting pathogen Nectria haematococca. By contrast, 100% of inoculated root tips treated with DNase I developed necrosis. Treatment with BAL31, an exonuclease that digests DNA more slowly than DNase I, also resulted in increased root tip infection, but the onset of infection was delayed. Control root tips or fungal spores treated with nuclease alone exhibited normal morphology and growth. Pea (Pisum sativum) root tips incubated with [(32)P]dCTP during a 1-h period when no cell death occurs yielded root cap slime containing (32)P-labeled exDNA. Our results suggest that exDNA is a previously unrecognized component of plant defense, an observation that is in accordance with the recent discovery that exDNA from white blood cells plays a key role in the vertebrate immune response against microbial pathogens.

  9. Extracellular DNA Is Required for Root Tip Resistance to Fungal Infection1[W][OA

    PubMed Central

    Wen, Fushi; White, Gerard J.; VanEtten, Hans D.; Xiong, Zhongguo; Hawes, Martha C.

    2009-01-01

    Plant defense involves a complex array of biochemical interactions, many of which occur in the extracellular environment. The apical 1- to 2-mm root tip housing apical and root cap meristems is resistant to infection by most pathogens, so growth and gravity sensing often proceed normally even when other sites on the root are invaded. The mechanism of this resistance is unknown but appears to involve a mucilaginous matrix or “slime” composed of proteins, polysaccharides, and detached living cells called “border cells.” Here, we report that extracellular DNA (exDNA) is a component of root cap slime and that exDNA degradation during inoculation by a fungal pathogen results in loss of root tip resistance to infection. Most root tips (>95%) escape infection even when immersed in inoculum from the root-rotting pathogen Nectria haematococca. By contrast, 100% of inoculated root tips treated with DNase I developed necrosis. Treatment with BAL31, an exonuclease that digests DNA more slowly than DNase I, also resulted in increased root tip infection, but the onset of infection was delayed. Control root tips or fungal spores treated with nuclease alone exhibited normal morphology and growth. Pea (Pisum sativum) root tips incubated with [32P]dCTP during a 1-h period when no cell death occurs yielded root cap slime containing 32P-labeled exDNA. Our results suggest that exDNA is a previously unrecognized component of plant defense, an observation that is in accordance with the recent discovery that exDNA from white blood cells plays a key role in the vertebrate immune response against microbial pathogens. PMID:19700564

  10. Cofilin regulator 14-3-3zeta is an evolutionarily conserved protein required for phagocytosis and microbial resistance.

    PubMed

    Ulvila, Johanna; Vanha-aho, Leena-Maija; Kleino, Anni; Vähä-Mäkilä, Mari; Vuoksio, Milka; Eskelinen, Sinikka; Hultmark, Dan; Kocks, Christine; Hallman, Mikko; Parikka, Mataleena; Rämet, Mika

    2011-05-01

    Phagocytosis is an ancient cellular process that plays an important role in host defense. In Drosophila melanogaster phagocytic, macrophage-like hemocytes recognize and ingest microbes. We performed an RNAi-based in vitro screen in the Drosophila hemocyte cell line S2 and identified Abi, cpa, cofilin regulator 14-3-3ζ, tlk, CG2765, and CG15609 as mediators of bacterial phagocytosis. Of these identified genes, 14-3-3ζ had an evolutionarily conserved role in phagocytosis: bacterial phagocytosis was compromised when 14-3-3ζ was targeted with RNAi in primary Drosophila hemocytes and when the orthologous genes Ywhab and Ywhaz were silenced in zebrafish and mouse RAW 264.7 cells, respectively. In Drosophila and zebrafish infection models, 14-3-3ζ was required for resistance against Staphylococcus aureus. We conclude that 14-3-3ζ is essential for phagocytosis and microbial resistance in insects and vertebrates. PMID:21208897

  11. The Rhizobium etli opt operon is required for symbiosis and stress resistance.

    PubMed

    Vos, K; Braeken, K; Fauvart, M; Ndayizeye, M; Verhaert, J; Zachurzok, S; Lambrichts, I; Michiels, J

    2007-07-01

    Rhizobium etli is a Gram-negative root-colonizing soil bacterium capable of fixing nitrogen while living in symbiosis with its leguminous host Phaseolus vulgaris. A genome-wide screening for R. etli symbiotic mutants revealed a R. etli operon encoding an oligopeptide ABC-transporter (Opt), two redA homologous genes and one redB gene. Expression analysis showed this opt operon to be transcribed both under free-living and symbiotic conditions and expression levels were demonstrated to be growth-phase-dependent. Plants nodulated by R. etli opt mutants showed a reduced symbiotic nitrogen fixation activity (approximately 50% reduction). Growth experiments with opt mutants in the presence of oligopeptides as the sole nitrogen source confirmed the involvement of the opt genes in oligopeptide uptake. Further phenotypic analysis of the opt mutants revealed them to display an enhanced resistance to the oligopeptide antibiotic bacitracin, an increased susceptibility to the beta-lactam antibiotic ampicillin and a decreased osmotolerance. In conclusion, our results demonstrate that the opt operon plays a crucial role during symbiosis and stress resistance. PMID:17564602

  12. Leptospira interrogans Catalase Is Required for Resistance to H2O2 and for Virulence

    PubMed Central

    Eshghi, Azad; Lourdault, Kristel; Murray, Gerald L.; Bartpho, Thanatchaporn; Sermswan, Rasana W.; Picardeau, Mathieu; Adler, Ben; Snarr, Brendan; Zuerner, Richard L.

    2012-01-01

    Pathogenic Leptospira spp. are likely to encounter higher concentrations of reactive oxygen species induced by the host innate immune response. In this study, we characterized Leptospira interrogans catalase (KatE), the only annotated catalase found within pathogenic Leptospira species, by assessing its role in resistance to H2O2-induced oxidative stress and during infection in hamsters. Pathogenic L. interrogans bacteria had a 50-fold-higher survival rate under H2O2-induced oxidative stress than did saprophytic L. biflexa bacteria, and this was predominantly catalase dependent. We also characterized KatE, the only annotated catalase found within pathogenic Leptospira species. Catalase assays performed with recombinant KatE confirmed specific catalase activity, while protein fractionation experiments localized KatE to the bacterial periplasmic space. The insertional inactivation of katE in pathogenic Leptospira bacteria drastically diminished leptospiral viability in the presence of extracellular H2O2 and reduced virulence in an acute-infection model. Combined, these results suggest that L. interrogans KatE confers in vivo resistance to reactive oxygen species induced by the host innate immune response. PMID:22927050

  13. Allele characterization of genes required for rpg4-mediated wheat stem rust resistance identifies Rpg5 as the R gene.

    PubMed

    Arora, D; Gross, T; Brueggeman, R

    2013-11-01

    A highly virulent form of the wheat stem rust pathogen Puccinia graminis f. sp. tritici race TTKSK is virulent on both wheat and barley, presenting a major threat to world food security. The recessive and temperature-sensitive rpg4 gene is the only effective source of resistance identified in barley (Hordeum vulgare) against P. graminis f. sp. tritici race TTKSK. Efforts to position clone rpg4 localized resistance to a small interval on barley chromosome 5HL, tightly linked to the rye stem rust (P. graminis f. sp. secalis) resistance (R) gene Rpg5. High-resolution genetic analysis and post-transcriptional gene silencing of the genes at the rpg4/Rpg5 locus determined that three tightly linked genes (Rpg5, HvRga1, and HvAdf3) are required together for rpg4-mediated wheat stem rust resistance. Alleles of the three genes were analyzed from a diverse set of 14 domesticated barley lines (H. vulgare) and 8 wild barley accessions (H. vulgare subsp. spontaneum) to characterize diversity that may determine incompatibility (resistance). The analysis determined that HvAdf3 and HvRga1 code for predicted functional proteins that do not appear to contain polymorphisms determining the compatible (susceptible) interactions with the wheat stem rust pathogen and were expressed at the transcriptional level from both resistant and susceptible barley lines. The HvAdf3 alleles shared 100% amino acid identity among all 22 genotypes examined. The P. graminis f. sp. tritici race QCCJ-susceptible barley lines with HvRga1 alleles containing the limited amino acid substitutions unique to the susceptible varieties also contained predicted nonfunctional rpg5 alleles. Thus, susceptibility in these lines is likely due to the nonfunctional RPG5 proteins. The Rpg5 allele analysis determined that 9 of the 13 P. graminis f. sp. tritici race QCCJ-susceptible barley lines contain alleles that either code for predicted truncated proteins as the result of a single nucleotide substitution, resulting in a

  14. The MAP kinase Pmk1 and protein kinase A are required for rotenone resistance in the fission yeast, Schizosaccharomyces pombe

    SciTech Connect

    Wang, Yiwei; Gulis, Galina; Buckner, Scott; Johnson, P. Connor; Sullivan, Daniel; Busenlehner, Laura; Marcus, Stevan

    2010-08-20

    Research highlights: {yields} Rotenone induces generation of ROS and mitochondrial fragmentation in fission yeast. {yields} The MAPK Pmk1 and PKA are required for rotenone resistance in fission yeast. {yields} Pmk1 and PKA are required for ROS clearance in rotenone treated fission yeast cells. {yields} PKA plays a role in ROS clearance under normal growth conditions in fission yeast. -- Abstract: Rotenone is a widely used pesticide that induces Parkinson's disease-like symptoms in rats and death of dopaminergic neurons in culture. Although rotenone is a potent inhibitor of complex I of the mitochondrial electron transport chain, it can induce death of dopaminergic neurons independently of complex I inhibition. Here we describe effects of rotenone in the fission yeast, Schizosaccharomyces pombe, which lacks complex I and carries out rotenone-insensitive cellular respiration. We show that rotenone induces generation of reactive oxygen species (ROS) as well as fragmentation of mitochondrial networks in treated S. pombe cells. While rotenone is only modestly inhibitory to growth of wild type S. pombe cells, it is strongly inhibitory to growth of mutants lacking the ERK-type MAP kinase, Pmk1, or protein kinase A (PKA). In contrast, cells lacking the p38 MAP kinase, Spc1, exhibit modest resistance to rotenone. Consistent with these findings, we provide evidence that Pmk1 and PKA, but not Spc1, are required for clearance of ROS in rotenone treated S. pombe cells. Our results demonstrate the usefulness of S. pombe for elucidating complex I-independent molecular targets of rotenone as well as mechanisms conferring resistance to the toxin.

  15. Blue light photoreceptors are required for the stability and function of a resistance protein mediating viral defense in Arabidopsis

    PubMed Central

    Jeong, Rae-Dong; Kachroo, Aardr

    2010-01-01

    This light-perceiving ability of plants requires the activities of proteins termed photoreceptors. In addition to various growth and developmental processes, light also plays a role in plant defense against pathogens and is required for activation of several defense genes and regulation of the cell death response. However, the molecular or biochemical basis of light modulated regulation of defense signaling is largely unclear. We demonstrate a direct role for blue-light photoreceptors in resistance (R) protein-mediated plant defense against Turnip Crinkle Virus (TCV) in Arabidopsis. The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are specifically required for maintaining the stability of the R protein HRT, and thereby resistance to TCV. Exogenous application of the phytohormone salicylic acid elevates HRT levels in phot2 but not in cry2 background. These data indicate that CRY2 and PHOT2 function distinctly in maintaining post-transcriptional stability of HRT. HRT-mediated resistance is also dependent on CRY1 and PHOT1 proteins, but these do not contribute to the stability of HRT. HRT interacts with the CRY2/PHOT2-interacting protein COP1, a E3 ubiquitin ligase. Exogenous application of a proteasome inhibitor prevents blue-light-dependent degradation of HRT, suggesting that HRT is degraded via the 26S proteasome. These and the fact that PHOT2 interacts directly with the R protein RPS2 suggest that blue-light photoreceptors might be involved in regulation and/or signaling mediated by several R proteins. PMID:21057210

  16. Mitochondrial localization of fission yeast manganese superoxide dismutase is required for its lysine acetylation and for cellular stress resistance and respiratory growth

    SciTech Connect

    Takahashi, Hidekazu; Shirai, Atsuko; Matsuyama, Akihisa; Yoshida, Minoru

    2011-03-04

    Research highlights: {yields} Fission yeast manganese superoxide dismutase (MnSOD) is acetylated. {yields} The mitochondrial targeting sequence (MTS) is required for the acetylation of MnSOD. {yields} The MTS is not crucial for MnSOD activity, but is important for respiratory growth. {yields} Posttranslational regulation of MnSOD differs between budding and fission yeast. -- Abstract: Manganese-dependent superoxide dismutase (MnSOD) is localized in the mitochondria and is important for oxidative stress resistance. Although transcriptional regulation of MnSOD has been relatively well studied, much less is known about the protein's posttranslational regulation. In budding yeast, MnSOD is activated after mitochondrial import by manganese ion incorporation. Here we characterize posttranslational modification of MnSOD in the fission yeast Schizosaccharomyces pombe. Fission yeast MnSOD is acetylated at the 25th lysine residue. This acetylation was diminished by deletion of N-terminal mitochondrial targeting sequence, suggesting that MnSOD is acetylated after import into mitochondria. Mitochondrial localization of MnSOD is not essential for the enzyme activity, but is crucial for oxidative stress resistance and growth under respiratory conditions of fission yeast. These results suggest that, unlike the situation in budding yeast, S. pombe MnSOD is already active even before mitochondrial localization; nonetheless, mitochondrial localization is critical to allow the cell to cope with reactive oxygen species generated inside or outside of mitochondria.

  17. Arabidopsis WRKY33 transcription factor is required for resistance to necrotrophic fungal pathogens.

    PubMed

    Zheng, Zuyu; Qamar, Synan Abu; Chen, Zhixiang; Mengiste, Tesfaye

    2006-11-01

    Plant WRKY transcription factors are key regulatory components of plant responses to microbial infection. In addition to regulating the expression of defense-related genes, WRKY transcription factors have also been shown to regulate cross-talk between jasmonate- and salicylate-regulated disease response pathways. The two pathways mediate resistance against different types of microbial pathogens, and there are numerous reports of antagonistic interactions between them. Here we show that mutations of the Arabidopsis WRKY33 gene encoding a WRKY transcription factor cause enhanced susceptibility to the necrotrophic fungal pathogens Botrytis cinerea and Alternaria brassicicola concomitant with reduced expression of the jasmonate-regulated plant defensin PDF1.2 gene. Ectopic over-expression of WRKY33, on the other hand, increases resistance to the two necrotrophic fungal pathogens. The wrky33 mutants do not show altered responses to a virulent strain of the bacterial pathogen Pseudomonas syringae, although the ectopic expression of WRKY33 results in enhanced susceptibility to this pathogen. The susceptibility of WRKY33-over-expressing plants to P. syringae is associated with reduced expression of the salicylate-regulated PR-1 gene. The WRKY33 transcript is induced in response to pathogen infection, or treatment with salicylate or the paraquat herbicide that generates activated oxygen species in exposed cells. WRKY33 is localized to the nucleus of plant cells and recognizes DNA molecules containing the TTGACC W-box sequence. Together, these results indicate that pathogen-induced WRKY33 is an important transcription factor that regulates the antagonistic relationship between defense pathways mediating responses to P. syringae and necrotrophic pathogens.

  18. MACROAUTOPHAGY AND CHAPERONE-MEDIATED AUTOPHAGY ARE REQUIRED FOR HEPATOCYTE RESISTANCE TO OXIDANT STRESS

    PubMed Central

    Wang, Yongjun; Singh, Rajat; Xiang, Youqing; Czaja, Mark J.

    2010-01-01

    The function of the lysosomal degradative pathway of autophagy in cellular injury is unclear as findings in nonhepatic cells have implicated autophagy as both a mediator of cell death and as a survival response. Autophagic function is impaired in steatotic and aged hepatocytes, suggesting that in these settings hepatocellular injury may be altered by the decrease in autophagy. To delineate the specific function of autophagy in the hepatocyte injury response, the effects of menadione-induced oxidative stress were examined in the RALA255-10G rat hepatocyte line when macroautophagy was inhibited by an shRNA-mediated knockdown of the autophagy gene atg5. Inhibition of macroautophagy sensitized cells to apoptotic and necrotic death from normally nontoxic concentrations of menadione. Inhibition of macroautophagy led to overactivation of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway that induced cell death. Death occurred from activation of the mitochondrial death pathway with cellular ATP depletion, mitochondrial cytochrome c release and caspase activation. Sensitization to death from menadione occurred despite up regulation of other forms of autophagy in compensation for the loss of macroautophagy. Chaperone-mediated autophagy (CMA) also mediated resistance to menadione as CMA inhibition sensitized cells to death from menadione through a mechanism different from that of a loss of macroautophagy as death occurred in the absence of JNK/c-Jun overactivation or ATP depletion. Conclusion Hepatocyte resistance to injury from menadione-induced oxidative stress is mediated by distinct functions of both macroautophagy and CMA, indicating that impaired function of either form of autophagy may promote oxidant-induced liver injury. PMID:20578144

  19. The TCA cycle is not required for selection or survival of multidrug-resistant Salmonella

    PubMed Central

    Ricci, Vito; Loman, Nick; Pallen, Mark; Ivens, Alasdair; Fookes, Maria; Langridge, Gemma C.; Wain, John; Piddock, Laura J. V.

    2012-01-01

    Objectives The initial aim of this study was to use a systems biology approach to analyse a ciprofloxacin-selected multidrug-resistant (MDR) Salmonella enterica serotype Typhimurium, L664. Methods The whole genome sequence and transcriptome of L664 were analysed. Site-directed mutagenesis to recreate each mutation was carried out, followed by phenotypic characterization and mutation frequency analysis. As a mutation in the TCA cycle was detected we tested the controversial hypothesis regarding the bacterial response to bactericidal antibiotics, put forward by Kohanski et al. (Cell 2007; 130: 797–810 and Mol Cell 2010; 37: 311–20), that exposure of bacteria to agents such as ciprofloxacin produces reactive oxygen species (ROS), which transiently increase the mutation rate giving rise to MDR bacteria. Results L664 contained a mutation in ramR that conferred MDR. A mutation in tctA affected the TCA cycle and conferred the inability to grow on minimal agar. The virulence of L664 was not attenuated. Ciprofloxacin exposure produced ROS in L664 and SL1344 (tctA::aph), but it was reduced and occurred later. There were no significant differences in the rates of killing or mutations per generation to antibiotic resistance between the strains. Conclusions Whilst we confirm production of ROS in response to ciprofloxacin, we have no data to support the hypothesis that this leads to selection of MDR strains. Our results indicate that the mutations in tctA and glgA were random as they did not pre-exist in the parental strain, and that the mutation in tctA did not provide a survival advantage or disadvantage in the presence of antibiotic. PMID:22186876

  20. The ABC transporter YejABEF is required for resistance to antimicrobial peptides and the virulence of Brucella melitensis.

    PubMed

    Wang, Zhen; Bie, Pengfei; Cheng, Jie; Lu, Lin; Cui, Buyun; Wu, Qingmin

    2016-01-01

    The ability to resist the killing effects of host antimicrobial peptides (AMPs) plays a vital role in the virulence of pathogens. The Brucella melitensis NI genome has a gene cluster that encodes ABC transport. In this study, we constructed yejA1, yejA2, yejB, yejE, yejF, and whole yej operon deletion mutants, none of which exhibited discernible growth defect in TSB or minimal medium. Unlike their parental strain, the mutants showed a significantly increased sensitivity to acidic stress. The NIΔyejE and NIΔyejABEF mutants were also more sensitive than B. melitensis NI to polymyxin B, and the expression of yej operon genes was induced by polymyxin B. Moreover, cell and mouse infection assays indicated that NIΔyejE and NIΔyejABEF have restricted invasion and replication abilities inside macrophages and are rapidly cleared from the spleens of infected mice. These findings indicate that the ABC transporter YejABEF is required for the virulence of Brucella, suggesting that resistance to host antimicrobials is a key mechanism for Brucella to persistently survive in vivo. This study provided insights that led us to further investigate the potential correlation of AMP resistance with the mechanisms of immune escape and persistent infection by pathogens. PMID:27550726

  1. The ABC transporter YejABEF is required for resistance to antimicrobial peptides and the virulence of Brucella melitensis

    PubMed Central

    Wang, Zhen; Bie, Pengfei; Cheng, Jie; Lu, Lin; Cui, Buyun; Wu, Qingmin

    2016-01-01

    The ability to resist the killing effects of host antimicrobial peptides (AMPs) plays a vital role in the virulence of pathogens. The Brucella melitensis NI genome has a gene cluster that encodes ABC transport. In this study, we constructed yejA1, yejA2, yejB, yejE, yejF, and whole yej operon deletion mutants, none of which exhibited discernible growth defect in TSB or minimal medium. Unlike their parental strain, the mutants showed a significantly increased sensitivity to acidic stress. The NIΔyejE and NIΔyejABEF mutants were also more sensitive than B. melitensis NI to polymyxin B, and the expression of yej operon genes was induced by polymyxin B. Moreover, cell and mouse infection assays indicated that NIΔyejE and NIΔyejABEF have restricted invasion and replication abilities inside macrophages and are rapidly cleared from the spleens of infected mice. These findings indicate that the ABC transporter YejABEF is required for the virulence of Brucella, suggesting that resistance to host antimicrobials is a key mechanism for Brucella to persistently survive in vivo. This study provided insights that led us to further investigate the potential correlation of AMP resistance with the mechanisms of immune escape and persistent infection by pathogens. PMID:27550726

  2. Histone Acetylation and CREB Binding Protein Are Required for Neuronal Resistance against Ischemic Injury

    PubMed Central

    Yildirim, Ferah; Ji, Shengbo; Kronenberg, Golo; Barco, Angel; Olivares, Roman; Benito, Eva; Dirnagl, Ulrich; Gertz, Karen; Endres, Matthias

    2014-01-01

    Epigenetic transcriptional regulation by histone acetylation depends on the balance between histone acetyltransferase (HAT) and deacetylase activities (HDAC). Inhibition of HDAC activity provides neuroprotection, indicating that the outcome of cerebral ischemia depends crucially on the acetylation status of histones. In the present study, we characterized the changes in histone acetylation levels in ischemia models of focal cerebral ischemia and identified cAMP-response element binding protein (CREB)–binding protein (CBP) as a crucial factor in the susceptibility of neurons to ischemic stress. Both neuron-specific RNA interference and neurons derived from CBP heterozygous knockout mice showed increased damage after oxygen-glucose deprivation (OGD) in vitro. Furthermore, we demonstrated that ischemic preconditioning by a short (5 min) subthreshold occlusion of the middle cerebral artery (MCA), followed 24 h afterwards by a 30 min occlusion of the MCA, increased histone acetylation levels in vivo. Ischemic preconditioning enhanced CBP recruitment and histone acetylation at the promoter of the neuroprotective gene gelsolin leading to increased gelsolin expression in neurons. Inhibition of CBP's HAT activity attenuated neuronal ischemic preconditioning. Taken together, our findings suggest that the levels of CBP and histone acetylation determine stroke outcome and are crucially associated with the induction of an ischemia-resistant state in neurons. PMID:24748101

  3. Peroxidase-dependent apoplastic oxidative burst in Arabidopsis required for pathogen resistance

    PubMed Central

    Bindschedler, Laurence V.; Dewdney, Julia; Blee, Kris A.; Stone, Julie M.; Asai, Tsuneaki; Plotnikov, Julia; Denoux, Carine; Hayes, Tezni; Gerrish, Chris; Davies, Dewi R.; Ausubel, Frederick M.; Bolwell, G. Paul

    2011-01-01

    Summary The oxidative burst is an early response to pathogen attack leading to the production of reactive oxygen species (ROS) including hydrogen peroxide. Two major mechanisms involving either NADPH oxidases or peroxidases that may exist singly or in combination in different plant species have been proposed for the generation of ROS. We identified an Arabidopsis thaliana azide-sensitive but diphenylene iodonium-insensitive apoplastic oxidative burst that generates H2O2 in response to a Fusarium oxysporum cell-wall preparation. Transgenic Arabidopsis plants expressing an anti-sense cDNA encoding a type III peroxidase, French bean peroxidase type 1 (FBP1) exhibited an impaired oxidative burst and were more susceptible than wild-type plants to both fungal and bacterial pathogens. Transcriptional profiling and RT-PCR analysis showed that the anti-sense (FBP1) transgenic plants had reduced levels of specific peroxidase-encoding mRNAs, including mRNAs corresponding to Arabidopsis genes At3g49120 (AtPCb) and At3g49110 (AtPCa) that encode two class III peroxidases with a high degree of homology to FBP1. These data indicate that peroxidases play a significant role in generating H2O2 during the Arabidopsis defense response and in conferring resistance to a wide range of pathogens. PMID:16889645

  4. Delineating the requirements for spontaneous DNA damage resistance pathways in genome maintenance and viability in Saccharomyces cerevisiae.

    PubMed Central

    Morey, Natalie J; Doetsch, Paul W; Jinks-Robertson, Sue

    2003-01-01

    Cellular metabolic processes constantly generate reactive species that damage DNA. To counteract this relentless assault, cells have developed multiple pathways to resist damage. The base excision repair (BER) and nucleotide excision repair (NER) pathways remove damage whereas the recombination (REC) and postreplication repair (PRR) pathways bypass the damage, allowing deferred removal. Genetic studies in yeast indicate that these pathways can process a common spontaneous lesion(s), with mutational inactivation of any pathway increasing the burden on the remaining pathways. In this study, we examine the consequences of simultaneously compromising three or more of these pathways. Although the presence of a functional BER pathway alone is able to support haploid growth, retention of the NER, REC, or PRR pathway alone is not, indicating that BER is the key damage resistance pathway in yeast and may be responsible for the removal of the majority of either spontaneous DNA damage or specifically those lesions that are potentially lethal. In the diploid state, functional BER, NER, or REC alone can support growth, while PRR alone is insufficient for growth. In diploids, the presence of PRR alone may confer a lethal mutation load or, alternatively, PRR alone may be insufficient to deal with potentially lethal, replication-blocking lesions. PMID:12807766

  5. Superdormant spores of Bacillus species have elevated wet-heat resistance and temperature requirements for heat activation.

    PubMed

    Ghosh, Sonali; Zhang, Pengfei; Li, Yong-qing; Setlow, Peter

    2009-09-01

    Purified superdormant spores of Bacillus cereus, B. megaterium, and B. subtilis isolated after optimal heat activation of dormant spores and subsequent germination with inosine, d-glucose, or l-valine, respectively, germinate very poorly with the original germinants used to remove dormant spores from spore populations, thus allowing isolation of the superdormant spores, and even with alternate germinants. However, these superdormant spores exhibited significant germination with the original or alternate germinants if the spores were heat activated at temperatures 8 to 15 degrees C higher than the optimal temperatures for the original dormant spores, although the levels of superdormant spore germination were not as great as those of dormant spores. Use of mixtures of original and alternate germinants lowered the heat activation temperature optima for both dormant and superdormant spores. The superdormant spores had higher wet-heat resistance and lower core water content than the original dormant spore populations, and the environment of dipicolinic acid in the core of superdormant spores as determined by Raman spectroscopy of individual spores differed from that in dormant spores. These results provide new information about the germination, heat activation optima, and wet-heat resistance of superdormant spores and the heterogeneity in these properties between individual members of dormant spore populations.

  6. Venezuelan equine encephalitis virus entry mechanism requires late endosome formation and resists cell membrane cholesterol depletion

    SciTech Connect

    Kolokoltsov, Andrey A.; Fleming, Elisa H.; Davey, Robert A. . E-mail: radavey@utmb.edu

    2006-04-10

    Virus envelope proteins determine receptor utilization and host range. The choice of receptor not only permits specific targeting of cells that express it, but also directs the virus into specific endosomal trafficking pathways. Disrupting trafficking can result in loss of virus infectivity due to redirection of virions to non-productive pathways. Identification of the pathway or pathways used by a virus is, thus, important in understanding virus pathogenesis mechanisms and for developing new treatment strategies. Most of our understanding of alphavirus entry has focused on the Old World alphaviruses, such as Sindbis and Semliki Forest virus. In comparison, very little is known about the entry route taken by more pathogenic New World alphaviruses. Here, we use a novel contents mixing assay to identify the cellular requirements for entry of a New World alphavirus, Venezuelan equine encephalitis virus (VEEV). Expression of dominant negative forms of key endosomal trafficking genes shows that VEEV must access clathrin-dependent endocytic vesicles for membrane fusion to occur. Unexpectedly, the exit point is different from Old World alphaviruses that leave from early endosomes. Instead, VEEV also requires functional late endosomes. Furthermore, unlike the Old World viruses, VEEV entry is insensitive to cholesterol sequestration from cell membranes and may reflect a need to access an endocytic compartment that lacks cholesterol. This indicates fundamental differences in the entry route taken by VEEV compared to Old World alphaviruses.

  7. 50 CFR 80.15 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., see 5 CFR 1310.3.). (b) What is required to determine the allowability of costs? Source documents or... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Allowable costs. 80.15 Section 80.15... WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.15 Allowable costs. (a) What...

  8. 44 CFR 206.439 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Allowable costs. 206.439... Allowable costs. (a) General requirements for determining allowable costs are established in 44 CFR 13.22... section. (b) Administrative and management costs for major disasters will be paid in accordance with...

  9. [Resistant hypertension].

    PubMed

    Feldstein, Carlos A

    2008-04-01

    Resistant hypertension, defined as a persistent blood pressure over 140/90 mmHg despite the use of three antihypertensive drugs including a diuretic, is unusual. The diagnosis requires ruling out initially pseudoresistance and a lack of compliance with treatment. Ambulatory blood pressure recording allow the recognition of white coat hypertension. When there is a clinical or laboratory suspicion, secondary causes of hypertension should be discarded. Excessive salt intake, the presence of concomitant diseases such as diabetes mellitus, chronic renal disease, obesity, and psychiatric conditions such as panic attacks, anxiety and depression, should also be sought. The presence of target organ damage requires a more aggressive treatment of hypertension. Recent clinical studies indicate that the administration of aldosterone antagonists as a fourth therapeutic line provides significant additional blood pressure reduction, when added to previous antihypertensive regimens in subjects with resistant hypertension. The possible blood pressure lowering effects of prolonged electrical activation of carotid baroreceptors is under investigation. PMID:18769797

  10. [Resistant hypertension].

    PubMed

    Feldstein, Carlos A

    2008-04-01

    Resistant hypertension, defined as a persistent blood pressure over 140/90 mmHg despite the use of three antihypertensive drugs including a diuretic, is unusual. The diagnosis requires ruling out initially pseudoresistance and a lack of compliance with treatment. Ambulatory blood pressure recording allow the recognition of white coat hypertension. When there is a clinical or laboratory suspicion, secondary causes of hypertension should be discarded. Excessive salt intake, the presence of concomitant diseases such as diabetes mellitus, chronic renal disease, obesity, and psychiatric conditions such as panic attacks, anxiety and depression, should also be sought. The presence of target organ damage requires a more aggressive treatment of hypertension. Recent clinical studies indicate that the administration of aldosterone antagonists as a fourth therapeutic line provides significant additional blood pressure reduction, when added to previous antihypertensive regimens in subjects with resistant hypertension. The possible blood pressure lowering effects of prolonged electrical activation of carotid baroreceptors is under investigation.

  11. Different requirements for EDS1 and NDR1 by disease resistance genes define at least two R gene-mediated signaling pathways in Arabidopsis.

    PubMed

    Aarts, N; Metz, M; Holub, E; Staskawicz, B J; Daniels, M J; Parker, J E

    1998-08-18

    The Arabidopsis genes EDS1 and NDR1 were shown previously by mutational analysis to encode essential components of race-specific disease resistance. Here, we examined the relative requirements for EDS1 and NDR1 by a broad spectrum of Resistance (R) genes present in three Arabidopsis accessions (Columbia, Landsberg-erecta, and Wassilewskija). We show that there is a strong requirement for EDS1 by a subset of R loci (RPP2, RPP4, RPP5, RPP21, and RPS4), conferring resistance to the biotrophic oomycete Peronospora parasitica, and to Pseudomonas bacteria expressing the avirulence gene avrRps4. The requirement for NDR1 by these EDS1-dependent R loci is either weak or not measurable. Conversely, three NDR1-dependent R loci, RPS2, RPM1, and RPS5, operate independently of EDS1. Another RPP locus, RPP8, exhibits no strong exclusive requirement for EDS1 or NDR1 in isolate-specific resistance to P. parasitica, although resistance is compromised weakly by eds1. Similarly, resistance conditioned by two EDS1-dependent RPP genes, RPP4 and RPP5, is impaired partially by ndr1, implicating a degree of pathway cross-talk. Our results provide compelling evidence for the preferential utilization of either signaling component by particular R genes and thus define at least two disease resistance pathways. The data also suggest that strong dependence on EDS1 or NDR1 is governed by R protein structural type rather than pathogen class.

  12. Proliferation of Double-Strand Break-Resistant Polyploid Cells Requires Drosophila FANCD2.

    PubMed

    Bretscher, Heidi S; Fox, Donald T

    2016-06-01

    Conserved DNA-damage responses (DDRs) sense genome damage and prevent mitosis of broken chromosomes. How cells lacking DDRs cope with broken chromosomes during mitosis is poorly understood. DDRs are frequently inactivated in cells with extra genomes (polyploidy), suggesting that study of polyploidy can reveal how cells with impaired DDRs/genome damage continue dividing. Here, we show that continued division and normal organ development occurs in polyploid, DDR-impaired Drosophila papillar cells. As papillar cells become polyploid, they naturally accumulate broken acentric chromosomes but do not apoptose/arrest the cell cycle. To survive mitosis with acentric chromosomes, papillar cells require Fanconi anemia proteins FANCD2 and FANCI, as well as Blm helicase, but not canonical DDR signaling. FANCD2 acts independently of previous S phases to promote alignment and segregation of acentric DNA produced by double-strand breaks, thus avoiding micronuclei and organ malformation. Because polyploidy and impaired DDRs can promote cancer, our findings provide insight into disease-relevant DNA-damage tolerance mechanisms. PMID:27270041

  13. Tobacco Rar1, EDS1 and NPR1/NIM1 like genes are required for N-mediated resistance to tobacco mosaic virus.

    PubMed

    Liu, Yule; Schiff, Michael; Marathe, Rajendra; Dinesh-Kumar, S P

    2002-05-01

    The tobacco N gene confers resistance to tobacco mosaic virus (TMV) and encodes a Toll-interleukin-1 receptor/nucleotide binding site/leucine-rich repeat (TIR-NBS-LRR) class protein. We have developed and used a tobacco rattle virus (TRV) based virus induced gene silencing (VIGS) system to investigate the role of tobacco candidate genes in the N-mediated signalling pathway. To accomplish this we generated transgenic Nicotiana benthamiana containing the tobacco N gene. The transgenic lines exhibit hypersensitive response (HR) to TMV and restrict virus spread to the inoculated site. This demonstrates that the tobacco N gene can confer resistance to TMV in heterologous N. benthamiana. We have used this line to study the role of tobacco Rar1-, EDS1-, and NPR1/NIM1- like genes in N-mediated resistance to TMV using a TRV based VIGS approach. Our VIGS analysis suggests that these genes are required for N function. EDS1-like gene requirement for the N function suggests that EDS1 could be a common component of bacterial, fungal and viral resistance signalling mediated by the TIR-NBS-LRR class of resistance proteins. Requirement of Rar1- like gene for N-mediated resistance to TMV and some powdery mildew resistance genes in barley provide the first example of converging points in the disease resistance signalling pathways mediated by TIR-NBS-LRR and CC-NBS-LRR proteins. The TRV based VIGS approach as described here to study N-mediated resistance signalling will be useful for the analysis of not only disease resistance signalling pathways but also of other signalling pathways in genetically intractable plant systems.

  14. FIBRILLIN4 Is Required for Plastoglobule Development and Stress Resistance in Apple and Arabidopsis1[W][OA

    PubMed Central

    Singh, Dharmendra K.; Maximova, Siela N.; Jensen, Philip J.; Lehman, Brian L.; Ngugi, Henry K.; McNellis, Timothy W.

    2010-01-01

    The fibrillins are a large family of chloroplast proteins that have been linked with stress tolerance and disease resistance. FIBRILLIN4 (FIB4) is found associated with the photosystem II light-harvesting complex, thylakoids, and plastoglobules, which are chloroplast compartments rich in lipophilic antioxidants. For this study, FIB4 expression was knocked down in apple (Malus 3 domestica) using RNA interference. Plastoglobule osmiophilicity was decreased in fib4 knockdown (fib4 KD) tree chloroplasts compared with the wild type, while total plastoglobule number was unchanged. Compared with the wild type, net photosynthetic CO2 fixation in fib4 KD trees was decreased at high light intensity but was increased at low light intensity. Furthermore, fib4 KD trees produced more anthocyanins than the wild type when transferred from low to high light intensity, indicating greater sensitivity to high light stress. Relative to the wild type, fib4 KD apples were more sensitive to methyl viologen and had higher superoxide levels during methyl viologen treatment. Arabidopsis (Arabidopsis thaliana) fib4 mutants and fib4 KD apples were more susceptible than their wild-type counterparts to the bacterial pathogens Pseudomonas syringae pathovar tomato and Erwinia amylovora, respectively, and were more sensitive to ozone-induced tissue damage. Following ozone stress, plastoglobule osmiophilicity decreased in wild-type apple and remained low in fib4 KD trees; total plastoglobule number increased in fib4 KD apples but not in the wild type. These results indicate that FIB4 is required for plastoglobule development and resistance to multiple stresses. This study suggests that FIB4 is involved in regulating plastoglobule content and that defective regulation of plastoglobule content leads to broad stress sensitivity and altered photosynthetic activity. PMID:20813909

  15. 40 CFR 35.2025 - Allowance and advance of allowance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... advance of allowance. (a) Allowance. Step 2+3 and Step 3 grant agreements will include an allowance for facilities planning and design of the project and Step 7 agreements will include an allowance for facility... would receive under paragraph (a) of this section. (5) In the event a Step 2+3, Step 3 or Step 7...

  16. 45 CFR 34.4 - Allowable claims.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... occurred. (7) Claims for automobiles, only when required to perform official business or parked on a... amount allowed is the value of the vehicle at the time of loss as determined by the National...

  17. 36 CFR 1207.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Circular A-122 as not subject to that circular 48 CFR part 31. Contract Cost Principles and Procedures, or... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Allowable costs. 1207.22... GOVERNMENTS Post-Award Requirements Financial Administration § 1207.22 Allowable costs. (a) Limitation on...

  18. 7 CFR 3016.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Circular A-122 as not subject to that circular 48 CFR part 31. Contract Cost Principles and Procedures, or... 7 Agriculture 15 2011-01-01 2011-01-01 false Allowable costs. 3016.22 Section 3016.22 Agriculture... GOVERNMENTS Post-Award Requirements Financial Administration § 3016.22 Allowable costs. (a) Limitation on...

  19. 24 CFR 85.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Circular A-122 as not subject to that circular 48 CFR part 31. Contract Cost Principles and Procedures, or... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Allowable costs. 85.22 Section 85... TRIBAL GOVERNMENTS Post-Award Requirements Financial Administration § 85.22 Allowable costs....

  20. 38 CFR 43.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... not subject to that circular 48 CFR part 31. Contract Cost Principles and Procedures, or uniform cost... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Allowable costs. 43.22... Requirements Financial Administration § 43.22 Allowable costs. (a) Limitation on use of funds. Grant funds...

  1. 45 CFR 602.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CFR part 31. Contract Cost Principles and Procedures, or uniform cost accounting standards that comply... 45 Public Welfare 3 2010-10-01 2010-10-01 false Allowable costs. 602.22 Section 602.22 Public... Requirements § 602.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for:...

  2. 24 CFR 85.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Circular A-122 as not subject to that circular 48 CFR part 31. Contract Cost Principles and Procedures, or... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Allowable costs. 85.22 Section 85... TRIBAL GOVERNMENTS Post-Award Requirements Financial Administration § 85.22 Allowable costs....

  3. 45 CFR 2541.220 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... not subject to that circular 48 CFR Part 31. Contract Cost Principles and Procedures, or uniform cost... 45 Public Welfare 4 2010-10-01 2010-10-01 false Allowable costs. 2541.220 Section 2541.220 Public... Post-Award Requirements § 2541.220 Allowable costs. (a) Limitation on use of funds. Grant funds may...

  4. 75 FR 4098 - Utility Allowance Adjustments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-26

    ... URBAN DEVELOPMENT Utility Allowance Adjustments AGENCY: Office of the Chief Information Officer, HUD... are required to advise the Secretary of the need for and request of a new utility allowance for... whether the information will have practical utility; (2) Evaluate the accuracy of the agency's estimate...

  5. 32 CFR 32.27 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of allowable costs that are in accordance with uniform cost accounting standards and comply with cost... NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management § 32.27 Allowable... contractors is determined in accordance with the provisions of Appendix E to 45 CFR part 74, “Principles...

  6. 28 CFR 70.27 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management § 70.27 Allowable costs. (a... bids, proposals, and applications. Bid and proposal costs of the current accounting period are all allowable as indirect costs. Bid and proposal costs of past accounting periods are unallowable in...

  7. 32 CFR 32.27 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... of allowable costs that are in accordance with uniform cost accounting standards and comply with cost... NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management § 32.27 Allowable... contractors is determined in accordance with the provisions of Appendix E to 45 CFR part 74, “Principles...

  8. 28 CFR 70.27 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management § 70.27 Allowable costs. (a... bids, proposals, and applications. Bid and proposal costs of the current accounting period are all allowable as indirect costs. Bid and proposal costs of past accounting periods are unallowable in...

  9. 28 CFR 70.27 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management § 70.27 Allowable costs. (a... bids, proposals, and applications. Bid and proposal costs of the current accounting period are all allowable as indirect costs. Bid and proposal costs of past accounting periods are unallowable in...

  10. 32 CFR 32.27 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... of allowable costs that are in accordance with uniform cost accounting standards and comply with cost... NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management § 32.27 Allowable... contractors is determined in accordance with the provisions of Appendix E to 45 CFR part 74, “Principles...

  11. 40 CFR 30.27 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management § 30.27 Allowable..., “Cost Principles for State and Local Governments.” The allowability of costs incurred by non-profit... organizations and those non-profit organizations listed in Attachment C to Circular A-122 is determined...

  12. 38 CFR 49.27 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management § 49.27 Allowable... for State, Local, and Indian Tribal Governments.” The allowability of costs incurred by non-profit... organizations and those non-profit organizations listed in Attachment C to Circular A-122 is determined...

  13. EDS1 in tomato is required for resistance mediated by TIR-class R genes and the receptor-like R gene Ve.

    PubMed

    Hu, Gongshe; deHart, Amy K A; Li, Yansu; Ustach, Carolyn; Handley, Vanessa; Navarre, Roy; Hwang, Chin-Feng; Aegerter, Brenna J; Williamson, Valerie M; Baker, Barbara

    2005-05-01

    In tobacco and other Solanaceae species, the tobacco N gene confers resistance to tobacco mosaic virus (TMV), and leads to induction of standard defense and resistance responses. Here, we report the use of N-transgenic tomato to identify a fast-neutron mutant, sun1-1 (suppressor of N), that is defective in N-mediated resistance. Induction of salicylic acid (SA) and expression of pathogenesis-related (PR) genes, each signatures of systemic acquired resistance, are both dramatically suppressed in sun1-1 plants after TMV treatment compared to wild-type plants. Application of exogenous SA restores PR gene expression, indicating that SUN1 acts upstream of SA. Upon challenge with additional pathogens, we found that the sun1-1 mutation impairs resistance mediated by certain resistance (R) genes, (Bs4, I, and Ve), but not others (Mi-1). In addition, sun1-1 plants exhibit enhanced susceptibility to TMV, as well as to virulent pathogens. sun1-1 has been identified as an EDS1 homolog present on chromosome 6 of tomato. The discovery of enhanced susceptibility in the sun1-1 (Le_eds1-1) mutant plant, which contrasts to reports in Nicotiana benthamiana using virus-induced gene silencing, provides evidence that the intersection of R gene-mediated pathways with general resistance pathways is conserved in a Solanaceous species. In tomato, EDS1 is important for mediating resistance to a broad range of pathogens (viral, bacterial, and fungal pathogens), yet shows specificity in the class of R genes that it affects (TIR-NBS-LRR as opposed to CC-NBS-LRR). In addition, a requirement for EDS1 for Ve-mediated resistance in tomato exposes that the receptor-like R gene class may also require EDS1.

  14. Hippocampal UCP2 is essential for cognition and resistance to anxiety but not required for the benefits of exercise.

    PubMed

    Wang, D; Zhai, X; Chen, P; Yang, M; Zhao, J; Dong, J; Liu, H

    2014-09-26

    Uncoupling protein-2 (UCP2) reduces oxidative stress by facilitating the influx of protons into mitochondrial matrix, thus dissociating mitochondrial oxidation from ATP synthesis. UCP2 is expressed abundantly in brain areas and plays a key role in neuroprotection. Here, we sought to determine if UCP2 deficiency produces cognitive impairment and anxiety in young mice, and to determine if hippocampal UCP2 is essential for the beneficial effects of voluntary exercise. Antisense oligonucleotide (ASO) was used to produce UCP2 knockdown in mice. Our results firstly showed that UCP2-targeted ASO significantly reduced UCP2 mRNA and protein expression in the hippocampus. ASO treatment impaired learning and memory of the mice in Y-maze, T-maze, and object recognition tests (ORT). ASO-treated mice exhibited more anxiously in OPT, light/dark box test, and elevated plus maze (EPM) than the control mice. We also found that wheel running ameliorated cognitive dysfunction and anxiety-like behaviors in ASO-treated mice. Furthermore, voluntary exercise reversed ASO-induced changes in hippocampal levels of serotonin (5-HT), dopamine (DA), and norepinephrine (NE). However, UCP2 protein in the hippocampus was not correlated with cognitive and anxiolytic benefits of exercise. These findings suggest that hippocampal UCP2 is essential for cognitive function and the resistance to anxiety of mice, but not required for the beneficial effects of exercise. PMID:25003714

  15. Hippocampal UCP2 is essential for cognition and resistance to anxiety but not required for the benefits of exercise.

    PubMed

    Wang, D; Zhai, X; Chen, P; Yang, M; Zhao, J; Dong, J; Liu, H

    2014-09-26

    Uncoupling protein-2 (UCP2) reduces oxidative stress by facilitating the influx of protons into mitochondrial matrix, thus dissociating mitochondrial oxidation from ATP synthesis. UCP2 is expressed abundantly in brain areas and plays a key role in neuroprotection. Here, we sought to determine if UCP2 deficiency produces cognitive impairment and anxiety in young mice, and to determine if hippocampal UCP2 is essential for the beneficial effects of voluntary exercise. Antisense oligonucleotide (ASO) was used to produce UCP2 knockdown in mice. Our results firstly showed that UCP2-targeted ASO significantly reduced UCP2 mRNA and protein expression in the hippocampus. ASO treatment impaired learning and memory of the mice in Y-maze, T-maze, and object recognition tests (ORT). ASO-treated mice exhibited more anxiously in OPT, light/dark box test, and elevated plus maze (EPM) than the control mice. We also found that wheel running ameliorated cognitive dysfunction and anxiety-like behaviors in ASO-treated mice. Furthermore, voluntary exercise reversed ASO-induced changes in hippocampal levels of serotonin (5-HT), dopamine (DA), and norepinephrine (NE). However, UCP2 protein in the hippocampus was not correlated with cognitive and anxiolytic benefits of exercise. These findings suggest that hippocampal UCP2 is essential for cognitive function and the resistance to anxiety of mice, but not required for the beneficial effects of exercise.

  16. Constitutive disease resistance requires EDS1 in the Arabidopsis mutants cpr1 and cpr6 and is partially EDS1-dependent in cpr5.

    PubMed

    Clarke, J D; Aarts, N; Feys, B J; Dong, X; Parker, J E

    2001-05-01

    The systemic acquired resistance (SAR) response in Arabidopsis is characterized by the accumulation of salicylic acid (SA), expression of the pathogenesis-related (PR) genes, and enhanced resistance to virulent bacterial and oomycete pathogens. The cpr (constitutive expressor of PR genes) mutants express all three SAR phenotypes. In addition, cpr5 and cpr6 induce expression of PDF1.2, a defense-related gene associated with activation of the jasmonate/ethylene-mediated resistance pathways. cpr5 also forms spontaneous lesions. In contrast, the eds1 (enhanced disease susceptibility) mutation abolishes race-specific resistance conferred by a major subclass of resistance (R) gene products in response to avirulent pathogens. eds1 plants also exhibit increased susceptibility to virulent pathogens. Epistasis experiments were designed to explore the relationship between the cpr- and EDS1-mediated resistance pathways. We found that a null eds1 mutation suppresses the disease resistance phenotypes of both cpr1 and cpr6. In contrast, eds1 only partially suppresses resistance in cpr5, leading us to conclude that cpr5 expresses both EDS1-dependent and EDS1-independent components of plant disease resistance. Although eds1 does not prevent lesion formation on cpr5 leaves, it alters their appearance and reduces their spread. This phenotypic difference is associated with increased pathogen colonization of cpr5 eds1 plants compared to cpr5. The data allow us to place EDS1 as a necessary downstream component of cpr1- and cpr6-mediated responses, but suggest a more complex relationship between EDS1 and cpr5 in plant defense.

  17. Downy mildew (Peronospora parasitica) resistance genes in Arabidopsis vary in functional requirements for NDR1, EDS1, NPR1 and salicylic acid accumulation.

    PubMed

    McDowell, J M; Cuzick, A; Can, C; Beynon, J; Dangl, J L; Holub, E B

    2000-06-01

    To better understand the genetic requirements for R gene-dependent defense activation in Arabidopsis, we tested the effect of several defense response mutants on resistance specified by eight RPP genes (for resistance to Peronospora parasitica) expressed in the Col-0 background. In most cases, resistance was not suppressed by a mutation in the SAR regulatory gene NPR1 or by expression of the NahG transgene. Thus, salicylic acid accumulation and NPR1 function are not necessary for resistance mediated by these RPP genes. In addition, resistance conferred by two of these genes, RPP7 and RPP8, was not significantly suppressed by mutations in either EDS1 or NDR1. RPP7 resistance was also not compromised by mutations in EIN2, JAR1 or COI1 which affect ethylene or jasmonic acid signaling. Double mutants were therefore tested. RPP7 and RPP8 were weakly suppressed in an eds1-2/ndr1-1 background, suggesting that these RPP genes operate additively through EDS1, NDR1 and as-yet-undefined signaling components. RPP7 was not compromised in coi1/npr1 or coi1/NahG backgrounds. These observations suggest that RPP7 initiates resistance through a novel signaling pathway that functions independently of salicylic acid accumulation or jasmonic acid response components.

  18. 40 CFR 280.33 - Repairs allowed.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... STANDARDS AND CORRECTIVE ACTION REQUIREMENTS FOR OWNERS AND OPERATORS OF UNDERGROUND STORAGE TANKS (UST) General Operating Requirements § 280.33 Repairs allowed. Owners and operators of UST systems must ensure... operating properly. (f) UST system owners and operators must maintain records of each repair for...

  19. 40 CFR 280.33 - Repairs allowed.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... STANDARDS AND CORRECTIVE ACTION REQUIREMENTS FOR OWNERS AND OPERATORS OF UNDERGROUND STORAGE TANKS (UST) General Operating Requirements § 280.33 Repairs allowed. Owners and operators of UST systems must ensure... operating properly. (f) UST system owners and operators must maintain records of each repair for...

  20. GRL-04810 and GRL-05010, Difluoride-Containing Nonpeptidic HIV-1 Protease Inhibitors (PIs) That Inhibit the Replication of Multi-PI-Resistant HIV-1 In Vitro and Possess Favorable Lipophilicity That May Allow Blood-Brain Barrier Penetration

    PubMed Central

    Salcedo Gómez, Pedro Miguel; Yashchuk, Sofiya; Mizuno, Akira; Das, Debananda; Ghosh, Arun K.; Mitsuya, Hiroaki

    2013-01-01

    We designed, synthesized, and identified two novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs), GRL-04810 and GRL-05010, containing the structure-based designed privileged cyclic ether-derived nonpeptide P2 ligand, bis-tetrahydrofuranylurethane (bis-THF), and a difluoride moiety, both of which are active against the laboratory strain HIV-1LAI (50% effective concentrations [EC50s], 0.0008 and 0.003 μM, respectively) with minimal cytotoxicity (50% cytotoxic concentrations [CC50s], 17.5 and 37.0 μM, respectively, in CD4+ MT-2 cells). The two compounds were active against multi-PI-resistant clinical HIV-1 variants isolated from patients who had no response to various antiviral regimens. GRL-04810 and GRL-05010 also blocked the infectivity and replication of each of the HIV-1NL4-3 variants selected by up to 5 μM lopinavir (EC50s, 0.03 and 0.03 μM, respectively) and atazanavir (EC50s, 0.02 and 0.04 μM, respectively). Moreover, they were active against darunavir (DRV)-resistant variants (EC50 in 0.03 to 0.034 μM range for GRL-04810 and 0.026 to 0.043 μM for GRL-05010), while DRV had EC50s between 0.02 and 0.174 μM. GRL-04810 had a favorable lipophilicity profile as determined with the partition (log P) and distribution (log D) coefficients of −0.14 and −0.29, respectively. The in vitro blood-brain barrier (BBB) permeability assay revealed that GRL-04810 and GRL-05010 may have a greater advantage in terms of crossing the BBB than the currently available PIs, with apparent penetration indexes of 47.8 × 10−6 and 61.8 × 10−6 cm/s, respectively. The present data demonstrate that GRL-04810 and GRL-05010 exert efficient activity against a wide spectrum of HIV-1 variants in vitro and suggest that two fluorine atoms added to their bis-THF moieties may well enhance their penetration across the BBB. PMID:24080647

  1. 42 CFR 84.156 - Airflow resistance test; Type C supplied-air respirator, demand class; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... exceed 50 millimeters (2 inches) of water at an air flow of 115 liters (4 cubic feet) per minute. (b) The exhalation resistance to a flow of air at a rate of 85 liters (3 cubic feet) per minute shall not exceed 25... 42 Public Health 1 2010-10-01 2010-10-01 false Airflow resistance test; Type C...

  2. The Tangle of Student Allowances.

    ERIC Educational Resources Information Center

    Thomson, Norman J.

    1980-01-01

    A discussion of the distribution of student financial aid in Australia focuses on these issues: direct vs. indirect payment to students; inequality in living allowances given to secondary and postsecondary students; and distribution of expense allowances by state government and living allowances by the Commonwealth. (MSE)

  3. UDP-glucosyltransferase UGT84A2/BRT1 is required for Arabidopsis nonhost resistance to the Asian soybean rust pathogen Phakopsora pachyrhizi.

    PubMed

    Langenbach, Caspar; Campe, Ruth; Schaffrath, Ulrich; Goellner, Katharina; Conrath, Uwe

    2013-04-01

    Nonhost resistance (NHR) of plants to fungal pathogens comprises different defense layers. Epidermal penetration resistance of Arabidopsis to Phakopsora pachyrhizi requires functional PEN1, PEN2 and PEN3 genes, whereas post-invasion resistance in the mesophyll depends on the combined functionality of PEN2, PAD4 and SAG101. Other genetic components of Arabidopsis post-invasion mesophyll resistance remain elusive. We performed comparative transcriptional profiling of wild-type, pen2 and pen2 pad4 sag101 mutants after inoculation with P. pachyrhizi to identify a novel trait for mesophyll NHR. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) analysis and microscopic analysis confirmed the essential role of the candidate gene in mesophyll NHR. UDP-glucosyltransferase UGT84A2/bright trichomes 1 (BRT1) is a novel component of Arabidopsis mesophyll NHR to P. pachyrhizi. BRT1 is a putative cytoplasmic enzyme in phenylpropanoid metabolism. BRT1 is specifically induced in pen2 with post-invasion resistance to P. pachyrhizi. Silencing or mutation of BRT1 increased haustoria formation in pen2 mesophyll. Yet, the brt1 mutation did not affect NHR to P. pachyrhizi in wild-type plants. We assign a novel function to BRT1, which is important for post-invasion NHR of Arabidopsis to P. pachyrhizi. BRT1 might serve to confer durable resistance against P. pachyrhizi to soybean.

  4. SAG101 forms a ternary complex with EDS1 and PAD4 and is required for resistance signaling against turnip crinkle virus.

    PubMed

    Zhu, Shifeng; Jeong, Rae-Dong; Venugopal, Srivathsa C; Lapchyk, Ludmila; Navarre, DuRoy; Kachroo, Aardra; Kachroo, Pradeep

    2011-11-01

    EDS1, PAD4, and SAG101 are common regulators of plant immunity against many pathogens. EDS1 interacts with both PAD4 and SAG101 but direct interaction between PAD4 and SAG101 has not been detected, leading to the suggestion that the EDS1-PAD4 and EDS1-SAG101 complexes are distinct. We show that EDS1, PAD4, and SAG101 are present in a single complex in planta. While this complex is preferentially nuclear localized, it can be redirected to the cytoplasm in the presence of an extranuclear form of EDS1. PAD4 and SAG101 can in turn, regulate the subcellular localization of EDS1. We also show that the Arabidopsis genome encodes two functionally redundant isoforms of EDS1, either of which can form ternary complexes with PAD4 and SAG101. Simultaneous mutations in both EDS1 isoforms are essential to abrogate resistance (R) protein-mediated defense against turnip crinkle virus (TCV) as well as avrRps4 expressing Pseudomonas syringae. Interestingly, unlike its function as a PAD4 substitute in bacterial resistance, SAG101 is required for R-mediated resistance to TCV, thus implicating a role for the ternary complex in this defense response. However, only EDS1 is required for HRT-mediated HR to TCV, while only PAD4 is required for SA-dependent induction of HRT. Together, these results suggest that EDS1, PAD4 and SAG101 also perform independent functions in HRT-mediated resistance.

  5. Pseudomonas aeruginosa High-Level Resistance to Polymyxins and Other Antimicrobial Peptides Requires cprA, a Gene That Is Disrupted in the PAO1 Strain

    PubMed Central

    Gutu, Alina D.; Rodgers, Nicole S.; Park, Jihye

    2015-01-01

    The arn locus, found in many Gram-negative bacterial pathogens, mediates resistance to polymyxins and other cationic antimicrobial peptides through 4-amino-l-arabinose modification of the lipid A moiety of lipopolysaccharide. In Pseudomonas aeruginosa, several two-component regulatory systems (TCSs) control the arn locus, which is necessary but not sufficient for these resistance phenotypes. A previous transposon mutagenesis screen to identify additional polymyxin resistance genes that these systems regulate implicated an open reading frame designated PA1559 in the genome of the P. aeruginosa PAO1 strain. Resequencing of this chromosomal region and bioinformatics analysis for a variety of P. aeruginosa strains revealed that in the sequenced PAO1 strain, a guanine deletion at the end of PA1559 results in a frameshift and truncation of a full-length open reading frame that also encompasses PA1560 in non-PAO1 strains, such as P. aeruginosa PAK. Deletion analysis in the PAK strain showed that this full-length open reading frame, designated cprA, is necessary for polymyxin resistance conferred by activating mutations in the PhoPQ, PmrAB, and CprRS TCSs. The cprA gene was also required for PmrAB-mediated resistance to other cationic antimicrobial peptides in the PAK strain. Repair of the mutated cprA allele in the PAO1 strain restored polymyxin resistance conferred by an activating TCS mutation. The deletion of cprA did not affect the arn-mediated lipid A modification, indicating that the CprA protein is necessary for a different aspect of polymyxin resistance. This protein has a domain structure with a strong similarity to the extended short-chain dehydrogenase/reductase family that comprises isomerases, lyases, and oxidoreductases. These results suggest a new avenue through which to pursue targeted inhibition of polymyxin resistance. PMID:26100714

  6. Riboflavin-Induced Disease Resistance Requires the Mitogen-Activated Protein Kinases 3 and 6 in Arabidopsis thaliana

    PubMed Central

    Nie, Shengjun; Xu, Huilian

    2016-01-01

    As a resistance elicitor, riboflavin (vitamin B2) protects plants against a wide range of pathogens. At molecular biological levels, it is important to elucidate the signaling pathways underlying the disease resistance induced by riboflavin. Here, riboflavin was tested to induce resistance against virulent Pseudomonas syringae pv. Tomato DC3000 (Pst DC3000) in Arabidopsis. Results showed that riboflavin induced disease resistance based on MAPK-dependent priming for the expression of PR1 gene. Riboflavin induced transient expression of PR1 gene. However, following Pst DC3000 inoculation, riboflavin potentiated stronger PR1 gene transcription. Further was suggested that the transcript levels of mitogen-activated protein kinases, MPK3 and MPK6, were primed under riboflavin. Upon infection by Pst DC3000, these two enzymes were more strongly activated. The elevated activation of both MPK3 and MPK6 was responsible for enhanced defense gene expression and resistance after riboflavin treatment. Moreover, riboflavin significantly reduced the transcript levels of MPK3 and MPK6 by application of AsA and BAPTA, an H2O2 scavenger and a calcium (Ca2+) scavenger, respectively. In conclusion, MPK3 and MPK6 were responsible for riboflavin-induced resistance, and played an important role in H2O2- and Ca2+-related signaling pathways, and this study could provide a new insight into the mechanistic study of riboflavin-induced defense responses. PMID:27054585

  7. Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance

    PubMed Central

    Bonapace, Laura; Bornhauser, Beat C.; Schmitz, Maike; Cario, Gunnar; Ziegler, Urs; Niggli, Felix K.; Schäfer, Beat W.; Schrappe, Martin; Stanulla, Martin; Bourquin, Jean-Pierre

    2010-01-01

    In vivo resistance to first-line chemotherapy, including to glucocorticoids, is a strong predictor of poor outcome in children with acute lymphoblastic leukemia (ALL). Modulation of cell death regulators represents an attractive strategy for subverting such drug resistance. Here we report complete resensitization of multidrug-resistant childhood ALL cells to glucocorticoids and other cytotoxic agents with subcytotoxic concentrations of obatoclax, a putative antagonist of BCL-2 family members. The reversal of glucocorticoid resistance occurred through rapid activation of autophagy-dependent necroptosis, which bypassed the block in mitochondrial apoptosis. This effect was associated with dissociation of the autophagy inducer beclin-1 from the antiapoptotic BCL-2 family member myeloid cell leukemia sequence 1 (MCL-1) and with a marked decrease in mammalian target of rapamycin (mTOR) activity. Consistent with a protective role for mTOR in glucocorticoid resistance in childhood ALL, combination of rapamycin with the glucocorticoid dexamethasone triggered autophagy-dependent cell death, with characteristic features of necroptosis. Execution of cell death, but not induction of autophagy, was strictly dependent on expression of receptor-interacting protein (RIP-1) kinase and cylindromatosis (turban tumor syndrome) (CYLD), two key regulators of necroptosis. Accordingly, both inhibition of RIP-1 and interference with CYLD restored glucocorticoid resistance completely. Together with evidence for a chemosensitizing activity of obatoclax in vivo, our data provide a compelling rationale for clinical translation of this pharmacological approach into treatments for patients with refractory ALL. PMID:20200450

  8. AIB1 is required for the acquisition of epithelial growth factor receptor-mediated tamoxifen resistance in breast cancer cells

    SciTech Connect

    Zhao Wenhui; Zhang Qingyuan Kang Xinmei; Jin Shi; Lou Changjie

    2009-03-13

    Acquired resistance to tamoxifen has become a serious obstacle in breast cancer treatment. The underlying mechanism responsible for this condition has not been completely elucidated. In this study, a tamoxifen-resistant (Tam-R) MCF-7 breast cancer cell line was developed to mimic the occurrence of acquired tamoxifen resistance as seen in clinical practice. Increased expression levels of HER1, HER2 and the estrogen receptor (ER)-AIB1 complex were found in tamoxifen-resistant cells. EGF stimulation and gefitinib inhibition experiments further demonstrated that HER1/HER2 signaling and AIB1 were involved in the proliferation of cells that had acquired Tam resistance. However, when AIB1 was silenced with AIB1-siRNA in Tam-R cells, the cell growth stimulated by the HER1/HER2 signaling pathway was significantly reduced, and the cells were again found to be inhibited by tamoxifen. These results suggest that the AIB1 protein could be a limiting factor in the HER1/HER2-mediated hormone-independent growth of Tam-R cells. Thus, AIB1 may be a new therapeutic target, and the removal of AIB1 may decrease the crosstalk between ER and the HER1/HER2 pathway, resulting in the restoration of tamoxifen sensitivity in tamoxifen-resistant cells.

  9. Riboflavin-Induced Disease Resistance Requires the Mitogen-Activated Protein Kinases 3 and 6 in Arabidopsis thaliana.

    PubMed

    Nie, Shengjun; Xu, Huilian

    2016-01-01

    As a resistance elicitor, riboflavin (vitamin B2) protects plants against a wide range of pathogens. At molecular biological levels, it is important to elucidate the signaling pathways underlying the disease resistance induced by riboflavin. Here, riboflavin was tested to induce resistance against virulent Pseudomonas syringae pv. Tomato DC3000 (Pst DC3000) in Arabidopsis. Results showed that riboflavin induced disease resistance based on MAPK-dependent priming for the expression of PR1 gene. Riboflavin induced transient expression of PR1 gene. However, following Pst DC3000 inoculation, riboflavin potentiated stronger PR1 gene transcription. Further was suggested that the transcript levels of mitogen-activated protein kinases, MPK3 and MPK6, were primed under riboflavin. Upon infection by Pst DC3000, these two enzymes were more strongly activated. The elevated activation of both MPK3 and MPK6 was responsible for enhanced defense gene expression and resistance after riboflavin treatment. Moreover, riboflavin significantly reduced the transcript levels of MPK3 and MPK6 by application of AsA and BAPTA, an H2O2 scavenger and a calcium (Ca2+) scavenger, respectively. In conclusion, MPK3 and MPK6 were responsible for riboflavin-induced resistance, and played an important role in H2O2- and Ca2+-related signaling pathways, and this study could provide a new insight into the mechanistic study of riboflavin-induced defense responses. PMID:27054585

  10. Long-term strength and allowable stresses of grade 10Kh9MFB and X10CrMoVNb9-1 (T91/P91) chromium heat-resistant steels

    NASA Astrophysics Data System (ADS)

    Skorobogatykh, V. N.; Danyushevskiy, I. A.; Schenkova, I. A.; Prudnikov, D. A.

    2015-04-01

    Currently, grade X10CrMoVNb9-1 (T91, P91) and 10Kh9MFB (10Kh9MFB-Sh) chromium steels are widely applied in equipment manufacturing for thermal power plants in Russia and abroad. Compilation and comparison of tensile, impact, and long-term strength tests results accumulated for many years of investigations of foreign grade X10CrMoVNb9-1, T91, P91, and domestic grade 10Kh9MFB (10Kh9MFB-Sh) steels is carried out. The property identity of metals investigated is established. High strength and plastic properties of steels, from which pipes and other products are made, for operation under creep conditions are confirmed. Design characteristics of long-term strength on the basis of tests with more than one million of hour-samples are determined ( and at temperatures of 500-650°C). The table of recommended allowable stresses for grade 10Kh9MFB, 10Kh9MFB-SH, X10CrMoVNb9-1, T91, and P91 steels is developed. The long-time properties of pipe welded joints of grade 10Kh9MFB+10Kh9MFB, 10Kh9MFB-Sh+10Kh9MFB-Sh, X10CrMoVNb9-1+X10CrMoVNb9-1, P91+P91, T91+T91, 10Kh9MFB (10Kh9MFB-Sh)+X10CrMoVNb9-1(T/P91) steels is researched. The welded joint reduction factor is experimentally determined.

  11. 40 CFR 35.2025 - Allowance and advance of allowance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... facilities planning and design of the project and Step 7 agreements will include an allowance for facility... grant applicants for facilities planning and project design. (2) The State may request that the right...

  12. 40 CFR 35.2025 - Allowance and advance of allowance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... facilities planning and design of the project and Step 7 agreements will include an allowance for facility... grant applicants for facilities planning and project design. (2) The State may request that the right...

  13. 40 CFR 35.2025 - Allowance and advance of allowance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... facilities planning and design of the project and Step 7 agreements will include an allowance for facility... grant applicants for facilities planning and project design. (2) The State may request that the right...

  14. 40 CFR 35.2025 - Allowance and advance of allowance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... facilities planning and design of the project and Step 7 agreements will include an allowance for facility... grant applicants for facilities planning and project design. (2) The State may request that the right...

  15. 76 FR 70883 - Clothing Allowance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-16

    ... published in the Federal Register on February 2, 2011 (76 FR 5733-5734), VA proposed to amend its... appliances affecting different articles of clothing. 76 FR 5733; Sursely, 551 F.3d at 1356. VA will make the... allowances. The amendment provides for an annual clothing allowance for each qualifying prosthetic...

  16. Enhanced Locomotor Activity Is Required to Exert Dietary Restriction-Dependent Increase of Stress Resistance in Drosophila.

    PubMed

    Ghimire, Saurav; Kim, Man Su

    2015-01-01

    Dietary restriction (DR) is known to be one of the most effective interventions to increase stress resistance, yet the mechanisms remain elusive. One of the most obvious DR-induced changes in phenotype is an increase in locomotor activity. Although it is conceptually perceivable that nutritional scarcity should prompt enhanced foraging behavior to garner additional dietary resources, the significance of enhanced movement activity has not been associated with the DR-dependent increase of stress resistance. In this study, we confirmed that flies raised on DR exhibited enhanced locomotive activity and increased stress resistance. Excision of fly wings minimized the DR-induced increase in locomotive activity, which resulted in attenuation of the DR-dependent increase of stress resistance. The possibility that wing clipping counteracts the DR by coercing flies to have more intake was ruled out since it did not induce any weight gain. Rather it was found that elimination of reactive oxygen species (ROS) that is enhanced by DR-induced upregulation of expression of antioxidant genes was significantly reduced by wing clipping. Collectively, our data suggests that DR increased stress resistance by increasing the locomotor activity, which upregulated expression of protective genes including, but not limited to, ROS scavenger system.

  17. Infectious Bronchitis Coronavirus Inhibits STAT1 Signaling and Requires Accessory Proteins for Resistance to Type I Interferon Activity

    PubMed Central

    Kint, Joeri; Dickhout, Annemiek; Kutter, Jasmin; Maier, Helena J.; Britton, Paul; Koumans, Joseph; Pijlman, Gorben P.; Fros, Jelke J.; Wiegertjes, Geert F.

    2015-01-01

    ABSTRACT The innate immune response is the first line of defense against viruses, and type I interferon (IFN) is a critical component of this response. Similar to other viruses, the gammacoronavirus infectious bronchitis virus (IBV) has evolved under evolutionary pressure to evade and counteract the IFN response to enable its survival. Previously, we reported that IBV induces a delayed activation of the IFN response. In the present work, we describe the resistance of IBV to IFN and the potential role of accessory proteins herein. We show that IBV is fairly resistant to the antiviral state induced by IFN and identify that viral accessory protein 3a is involved in resistance to IFN, as its absence renders IBV less resistant to IFN treatment. In addition to this, we found that independently of its accessory proteins, IBV inhibits IFN-mediated phosphorylation and translocation of STAT1. In summary, we show that IBV uses multiple strategies to counteract the IFN response. IMPORTANCE In the present study, we show that infectious bronchitis virus (IBV) is resistant to IFN treatment and identify a role for accessory protein 3a in the resistance against the type I IFN response. We also demonstrate that, in a time-dependent manner, IBV effectively interferes with IFN signaling and that its accessory proteins are dispensable for this activity. This study demonstrates that the gammacoronavirus IBV, similar to its mammalian counterparts, has evolved multiple strategies to efficiently counteract the IFN response of its avian host, and it identifies accessory protein 3a as multifaceted antagonist of the avian IFN system. PMID:26401035

  18. Genetic characterization of the vaccinia virus DNA polymerase: cytosine arabinoside resistance requires a variable lesion conferring phosphonoacetate resistance in conjunction with an invariant mutation localized to the 3'-5' exonuclease domain.

    PubMed

    Taddie, J A; Traktman, P

    1993-07-01

    In this report, we describe the isolation, molecular genetic mapping, and phenotypic characterization of vaccinia virus mutants resistant to cytosine arabinoside (araC) and phosphonoacetic acid (PAA). At 37 degrees C, 8 microM araC was found to prevent macroscopic plaque formation by wild-type virus and to cause a 10(4)-fold reduction in viral yield. Mutants resistant to 8 microM araC were selected by serial passage of a chemically mutagenized viral stock in the presence of drug. Because recovery of mutants required that initial passages be performed under less stringent selective conditions, and because plaque-purified isolates were found to be cross-resistant to 200 micrograms of PAA per ml, it seemed likely that resistance to araC required more than one genetic lesion. This hypothesis was confirmed by genetic and physical mapping of the responsible mutations. PAAr was accorded by the acquisition of one of three G-A transitions in the DNA polymerase gene which individually alter cysteine 356 to tyrosine, glycine 372 to aspartic acid, or glycine 380 to serine. AraCr was found to require one of these substitutions plus an additional T-C transition within codon 171 of the DNA polymerase gene, a change which replaces the wild-type phenylalanine with serine. Congenic viral stocks carrying one of the three PAAr lesions, either alone or in conjunction with the upstream araCr lesion, in an otherwise wild-type background were generated. The PAAr mutations conferred nearly complete resistance to PAA, a slight degree of resistance to araC, hypersensitivity to aphidicolin, and decreased spontaneous mutation frequency. Addition of the mutation at codon 171 significantly augmented araC resistance and aphidicolin hypersensitivity but caused no further change in mutation frequency. Several lines of evidence suggest that the PAAr mutations primarily affect the deoxynucleoside triphosphate-binding site, whereas the codon 171 mutation, lying within a conserved motif associated with

  19. 24 CFR 84.27 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Allowable costs. 84.27 Section 84.27 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER...

  20. 24 CFR 84.27 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Allowable costs. 84.27 Section 84.27 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER...

  1. 24 CFR 84.27 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Allowable costs. 84.27 Section 84.27 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER...

  2. 14 CFR 1260.127 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Allowable costs. 1260.127 Section 1260.127 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS Uniform Administrative Requirements for Grants and Cooperative Agreements With Institutions of Higher...

  3. 14 CFR 1260.127 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Allowable costs. 1260.127 Section 1260.127 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS Uniform Administrative Requirements for Grants and Cooperative Agreements With Institutions of Higher...

  4. 14 CFR 1260.127 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Allowable costs. 1260.127 Section 1260.127 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS Uniform Administrative Requirements for Grants and Cooperative Agreements With Institutions of Higher...

  5. 14 CFR 1260.127 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Allowable costs. 1260.127 Section 1260.127 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS Uniform Administrative Requirements for Grants and Cooperative Agreements With Institutions of Higher...

  6. 21 CFR 1403.22 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Allowable costs. 1403.22 Section 1403.22 Food and... COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 1403... the applicable cost principles. For the costs of a— Use the principles in— State, local or...

  7. 21 CFR 1403.22 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Allowable costs. 1403.22 Section 1403.22 Food and... COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 1403... the applicable cost principles. For the costs of a— Use the principles in— State, local or...

  8. 21 CFR 1403.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Allowable costs. 1403.22 Section 1403.22 Food and... COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 1403... the applicable cost principles. For the costs of a— Use the principles in— State, local or...

  9. 21 CFR 1403.22 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Allowable costs. 1403.22 Section 1403.22 Food and... COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 1403... the applicable cost principles. For the costs of a— Use the principles in— State, local or...

  10. 44 CFR 13.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Circular A-122 as not subject to that circular 48 CFR part 31. Contract Cost Principles and Procedures, or... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Allowable costs. 13.22... HOMELAND SECURITY GENERAL UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS...

  11. 43 CFR 12.62 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Circular A-122 as not subject to that circular 48 CFR Part 31. Contract Cost Principles and Procedures, or... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Allowable costs. 12.62 Section 12.62... COST PRINCIPLES FOR ASSISTANCE PROGRAMS Uniform Administrative Requirements for Grants and...

  12. 45 CFR 74.27 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... costs of the current accounting period are allowable as indirect costs. Bid and proposal costs of past..., AND COMMERCIAL ORGANIZATIONS Post-Award Requirements Financial and Program Management § 74.27... determined in accordance with the provisions of the Federal Acquisition Regulation (FAR) at 48 CFR part...

  13. 45 CFR 74.27 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... costs of the current accounting period are allowable as indirect costs. Bid and proposal costs of past..., AND COMMERCIAL ORGANIZATIONS Post-Award Requirements Financial and Program Management § 74.27... determined in accordance with the provisions of the Federal Acquisition Regulation (FAR) at 48 CFR part...

  14. Aluminium resistance requires resistance to acid stress: a case study with spinach that exudes oxalate rapidly when exposed to Al stress.

    PubMed

    Yang, Jian Li; Zheng, Shao Jian; He, Yun Feng; Matsumoto, Hideaki

    2005-04-01

    Spinach is a vegetable with a high oxalate concentration in its tissues. Oxalate efflux from spinach (Spinacia oleracea L. cv. Quanneng) roots was rapidly stimulated (within 30 min) by aluminium (Al) treatment. The efflux was constant within 6 h, but increased with increasing Al concentration. The efflux was confined to the root tip (0-5 mm), which showed a 5-fold greater efflux than the root zone distal to the tip (5-10 mm). Oxalate efflux could not be triggered by treatment with the trivalent cation lanthanum or by phosphorus deficiency, indicating that the efflux was specific to the Al treatment. All this evidence suggested that spinach possesses Al-resistance mechanisms. However, spinach was found to be as sensitive to Al toxicity as the Al-sensitive wheat line ES8, which had no Al-dependent organic acids efflux. The Al accumulated in the apical 5 mm of the roots of spinach which was also similar to that in the Al-sensitive wheat after 24 h treatment with 50 microM AlCl(3), indicating a non-exclusion mechanism. In addition, root elongation in spinach was significantly inhibited at pH 4.5, compared with that at pH 6.5. Based on this evidence, it is concluded that the sensitivity to acid stress in spinach could mask the potential role for oxalate to protect the plant roots from Al toxicity.

  15. CFP, the putative cercosporin transporter of Cercospora kikuchii, is required for wild type cercosporin production, resistance, and virulence on soybean.

    PubMed

    Callahan, T M; Rose, M S; Meade, M J; Ehrenshaft, M; Upchurch, R G

    1999-10-01

    Many species of the fungal genus Cercospora, including the soybean pathogen C. kikuchii, produce the phytotoxic polyketide cercosporin. Cercosporin production is induced by light. Previously, we identified several cDNA clones of mRNA transcripts that exhibited light-enhanced accumulation in C. kikuchii. Targeted disruption of the genomic copy of one of these, now designated CFP (cercosporin facilitator protein), results in a drastic reduction in cercosporin production, greatly reduced virulence of the fungus to soybean, and increased sensitivity to exogenous cercosporin. Sequence analysis of CFP reveals an 1,821-bp open reading frame encoding a 65.4-kDa protein similar to several members of the major facilitator superfamily (MFS) of integral membrane transporter proteins known to confer resistance to various antibiotics and toxins in fungi and bacteria. We propose that CFP encodes a cercosporin transporter that contributes resistance to cercosporin by actively exporting cercosporin, thus maintaining low cellular concentrations of the toxin.

  16. The dlt Operon of Bacillus cereus Is Required for Resistance to Cationic Antimicrobial Peptides and for Virulence in Insects▿

    PubMed Central

    Abi Khattar, Z.; Rejasse, A.; Destoumieux-Garzón, D.; Escoubas, J. M.; Sanchis, V.; Lereclus, D.; Givaudan, A.; Kallassy, M.; Nielsen-Leroux, C.; Gaudriault, S.

    2009-01-01

    The dlt operon encodes proteins that alanylate teichoic acids, the major components of cell walls of gram-positive bacteria. This generates a net positive charge on bacterial cell walls, repulsing positively charged molecules and conferring resistance to animal and human cationic antimicrobial peptides (AMPs) in gram-positive pathogenic bacteria. AMPs damage the bacterial membrane and are the most effective components of the humoral immune response against bacteria. We investigated the role of the dlt operon in insect virulence by inactivating this operon in Bacillus cereus, which is both an opportunistic human pathogen and an insect pathogen. The ΔdltBc mutant displayed several morphological alterations but grew at a rate similar to that for the wild-type strain. This mutant was less resistant to protamine and several bacterial cationic AMPs, such as nisin, polymyxin B, and colistin, in vitro. It was also less resistant to molecules from the insect humoral immune system, lysozyme, and cationic AMP cecropin B from Spodoptera frugiperda. ΔdltBc was as pathogenic as the wild-type strain in oral infections of Galleria mellonella but much less virulent when injected into the hemocoels of G. mellonella and Spodoptera littoralis. We detected the dlt operon in three gram-negative genera: Erwinia (Erwinia carotovora), Bordetella (Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica), and Photorhabdus (the entomopathogenic bacterium Photorhabdus luminescens TT01, the dlt operon of which did not restore cationic AMP resistance in ΔdltBc). We suggest that the dlt operon protects B. cereus against insect humoral immune mediators, including hemolymph cationic AMPs, and may be critical for the establishment of lethal septicemia in insects and in nosocomial infections in humans. PMID:19767427

  17. Characterization of a mitogen-activated protein kinase gene from cucumber required for trichoderma-conferred plant resistance.

    PubMed

    Shoresh, Michal; Gal-On, Amit; Leibman, Diana; Chet, Ilan

    2006-11-01

    The fungal biocontrol agent Trichoderma asperellum has been recently shown to induce systemic resistance in plants through a mechanism that employs jasmonic acid and ethylene signal transduction pathways. Mitogen-activated protein kinase (MAPK) proteins have been implicated in the signal transduction of a wide variety of plant stress responses. Here we report the identification and characterization of a Trichoderma-induced MAPK (TIPK) gene function in cucumber (Cucumis sativus). Similar to its homologs, wound-induced protein kinase, MPK3, and MPK3a, TIPK is also induced by wounding. Normally, preinoculation of roots with Trichoderma activates plant defense mechanisms, which result in resistance to the leaf pathogen Pseudomonas syringae pv lachrymans. We used a unique attenuated virus vector, Zucchini yellow mosaic virus (ZYMV-AGII), to overexpress TIPK protein and antisense (AS) RNA. Plants overexpressing TIPK were more resistant to pathogenic bacterial attack than control plants, even in the absence of Trichoderma preinoculation. On the other hand, plants expressing TIPK-AS revealed increased sensitivity to pathogen attack. Moreover, Trichoderma preinoculation could not protect these AS plants against subsequent pathogen attack. We therefore demonstrate that Trichoderma exerts its protective effect on plants through activation of the TIPK gene, a MAPK that is involved in signal transduction pathways of defense responses.

  18. The S2 Cu(i) site in CupA from Streptococcus pneumoniae is required for cellular copper resistance.

    PubMed

    Fu, Yue; Bruce, Kevin E; Wu, Hongwei; Giedroc, David P

    2016-01-01

    Pathogenic bacteria have evolved copper homeostasis and resistance systems for fighting copper toxicity imposed by the human immune system. Streptococcus pneumoniae is a respiratory pathogen that encodes an obligatorily membrane-anchored Cu(i) binding protein, CupA, and a P1B-type ATPase efflux transporter, CopA. The soluble, cytoplasmic domain of CupA (sCupA) contains a binuclear Cu(i) cluster consisting of S1 and S2 Cu(i) ions. The NMR solution structure of apo-sCupA reveals the same cupredoxin fold of Cu2-sCupA, except that the Cu(i) binding loop (residues 112-116, harboring S2 Cu ligands M113 and M115) is highly dynamic as documented by both backbone and side chain methionine methyl order parameters. In contrast to the more solvent exposed, lower affinity S2 Cu site, the high affinity S1 Cu-coordinating cysteines (C74, C111) are pre-organized in the apo-sCupA structure. Biological experiments reveal that the S1 site is largely dispensable for cellular Cu resistance and may be involved in buffering low cytoplasmic Cu(i). In contrast, the S2 site is essential for Cu resistance. Expression of a chimeric CopZ chaperone fused to the CupA transmembrane helix does not protect S. pneumoniae from copper toxicity and substitution of a predicted cytoplasm-facing Cu(i) entry metal-binding site (MBS) on CopA also gives rise to a Cu-sensitivity phenotype. These findings suggest that CupA and CopA may interact and filling of the CupA S2 site with Cu(i) results in stimulation of cellular copper efflux by CopA.

  19. Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs

    PubMed Central

    Pehrsson, Erica C.; Forsberg, Kevin J.; Gibson, Molly K.; Ahmadi, Sara; Dantas, Gautam

    2013-01-01

    Rates of infection with antibiotic-resistant bacteria have increased precipitously over the past several decades, with far-reaching healthcare and societal costs. Recent evidence has established a link between antibiotic resistance genes in human pathogens and those found in non-pathogenic, commensal, and environmental organisms, prompting deeper investigation of natural and human-associated reservoirs of antibiotic resistance. Functional metagenomic selections, in which shotgun-cloned DNA fragments are selected for their ability to confer survival to an indicator host, have been increasingly applied to the characterization of many antibiotic resistance reservoirs. These experiments have demonstrated that antibiotic resistance genes are highly diverse and widely distributed, many times bearing little to no similarity to known sequences. Through unbiased selections for survival to antibiotic exposure, functional metagenomics can improve annotations by reducing the discovery of false-positive resistance and by allowing for the identification of previously unrecognizable resistance genes. In this review, we summarize the novel resistance functions uncovered using functional metagenomic investigations of natural and human-impacted resistance reservoirs. Examples of novel antibiotic resistance genes include those highly divergent from known sequences, those for which sequence is entirely unable to predict resistance function, bifunctional resistance genes, and those with unconventional, atypical resistance mechanisms. Overcoming antibiotic resistance in the clinic will require a better understanding of existing resistance reservoirs and the dissemination networks that govern horizontal gene exchange, informing best practices to limit the spread of resistance-conferring genes to human pathogens. PMID:23760651

  20. Allowance trading: Market operations and regulatory response

    SciTech Connect

    Bailey, K.A.; South, D.W.; McDermott, K.A.

    1992-12-31

    The use of the SO{sub 2} allowance system as defined by Title IV of the 1990 Clean Air Act Amendments offers utilities greater compliance flexibility than EPA technology standards, State Implementation Plan (SEP) performance standards, or EPA bubble/offset strategies. Traditional methods at best offered the utility the ability to trade emissions between different units at a particular plant. The SO{sub 2} emissions trading system advocated under Title IV will allow a utility to trade emissions across its utility system, and/or trade emissions between utilities to take advantage of interfirm control cost differences. The use of transferable emission allowances offers utilities greater flexibility in the choice of how to control emissions: the choices include fuel switching, flue gas scrubbing, environmental dispatch, repowering, and even the choice not to control emissions [as long as the New Source Performance Standards (NSPS) and Prevention of Significant Deterioration (PSD) requirements are met]. The added flexibility allows utilities to choose the least cost manner of compliance with Title IV requirements. It is hoped (intended) that pollution control cost-minimization by individual utilities will in turn reduce the cost of controlling SO{sub 2} for the electric utility industry in aggregate. In addition, through the use of NO{sub x} emission averaging, the utility would average NO{sub x} emissions from different point sources in order to comply with the prescribed emission standard.

  1. Allowance trading: Market operations and regulatory response

    SciTech Connect

    Bailey, K.A.; South, D.W.; McDermott, K.A.

    1992-01-01

    The use of the SO[sub 2] allowance system as defined by Title IV of the 1990 Clean Air Act Amendments offers utilities greater compliance flexibility than EPA technology standards, State Implementation Plan (SEP) performance standards, or EPA bubble/offset strategies. Traditional methods at best offered the utility the ability to trade emissions between different units at a particular plant. The SO[sub 2] emissions trading system advocated under Title IV will allow a utility to trade emissions across its utility system, and/or trade emissions between utilities to take advantage of interfirm control cost differences. The use of transferable emission allowances offers utilities greater flexibility in the choice of how to control emissions: the choices include fuel switching, flue gas scrubbing, environmental dispatch, repowering, and even the choice not to control emissions [as long as the New Source Performance Standards (NSPS) and Prevention of Significant Deterioration (PSD) requirements are met]. The added flexibility allows utilities to choose the least cost manner of compliance with Title IV requirements. It is hoped (intended) that pollution control cost-minimization by individual utilities will in turn reduce the cost of controlling SO[sub 2] for the electric utility industry in aggregate. In addition, through the use of NO[sub x] emission averaging, the utility would average NO[sub x] emissions from different point sources in order to comply with the prescribed emission standard.

  2. The Burkholderia cenocepacia K56-2 pleiotropic regulator Pbr, is required for stress resistance and virulence.

    PubMed

    Ramos, Christian G; Sousa, Silvia A; Grilo, André M; Eberl, Leo; Leitão, Jorge H

    2010-05-01

    Burkholderia cenocepacia is one of the most virulent species of the Burkholderia cepacia complex, a group of bacteria that emerged as important pathogens, especially to cystic fibrosis (CF) patients. In this study, we report the identification and characterization of a mutant strain derived form the CF isolate Burkholderia cenocepacia K56-2, carrying a plasposon insertion in a gene, located in a 3516 bp chromosomal region with an atypical G+C content, encoding a 80 amino acid putative regulatory protein named Pbr. Besides its inability to produce phenazines, the B. cenocepacia K56-2 pbr mutant exhibited a pleiotropic phenotype, including impaired survival to oxidative and osmotic stress, aromatic amino acid and prolonged nutrient starvation periods. In addition, the pbr mutant exhibited decreased virulence the nematode Caenorhabditis elegans. Altogether, our results demonstrate the involvement of Pbr on the regulation of phenazine biosynthesis, and an important role for this regulatory protein on several cellular processes related to stress resistance and virulence.

  3. Requirement of JIP1-mediated c-Jun N-terminal kinase activation for obesity-induced insulin resistance.

    PubMed

    Morel, Caroline; Standen, Claire L; Jung, Dae Young; Gray, Susan; Ong, Helena; Flavell, Richard A; Kim, Jason K; Davis, Roger J

    2010-10-01

    The c-Jun NH(2)-terminal kinase (JNK) interacting protein 1 (JIP1) has been proposed to act as a scaffold protein that mediates JNK activation. However, recent studies have implicated JIP1 in multiple biochemical processes. Physiological roles of JIP1 that are related to the JNK scaffold function of JIP1 are therefore unclear. To test the role of JIP1 in JNK activation, we created mice with a germ line point mutation in the Jip1 gene (Thr(103) replaced with Ala) that selectively blocks JIP1-mediated JNK activation. These mutant mice exhibit a severe defect in JNK activation caused by feeding of a high-fat diet. The loss of JIP1-mediated JNK activation protected the mutant mice against obesity-induced insulin resistance. We conclude that JIP1-mediated JNK activation plays a critical role in metabolic stress regulation of the JNK signaling pathway.

  4. Requirement for CD4+ T Lymphocytes in Host Resistance against Cryptococcus neoformans in the Central Nervous System of Immunized Mice

    PubMed Central

    Buchanan, Kent L.; Doyle, Hester A.

    2000-01-01

    The importance of cell-mediated immunity (CMI) and CD4+ T lymphocytes in host resistance against Cryptococcus neoformans is well documented and is exemplified by the high susceptibility to progressive infection with this pathogen of AIDS patients with reduced CD4+ T-cell numbers. Although much has been learned about the role of CMI in the clearance of C. neoformans from the lungs and other internal organs, less is known about the protective mechanisms in the brain, the organ most frequently involved with a fatal outcome of cryptococcosis. We hypothesized that host resistance mechanisms against C. neoformans in the central nervous system (CNS) were similar to those outside the CNS (i.e., gamma interferon [IFN-γ], CD4+ T cells, and others). To test this hypothesis, we used a murine model of cryptococcal meningitis whereby cryptococci are introduced directly into the CNS. In experiments where mice were immunized to mount an anticryptococcal CMI response, our results indicate that immunization induced protective mechanisms that could be detected in the CNS by inhibition of the growth of viable yeast cells. Flow cytometric analyses of leukocytes in brain and spinal cord homogenates revealed that T lymphocytes, macrophages, and neutrophils accumulated in C. neoformans-infected brains of immune mice. In vivo depletion of CD4+ T cells, but not CD8+ T cells, resulted in significantly reduced leukocyte accumulation in the brains of immune mice. Furthermore, depletion of CD4+ T cells or neutralization of IFN-γ exacerbated CNS infection in immune mice, suggesting a critical role for CMI mechanisms in acquired protection in the CNS. PMID:10639404

  5. Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome oncogenic PIK3CA resistance.

    PubMed

    Oikonomou, Eftychia; Koc, Michal; Sourkova, Vladimira; Andera, Ladislav; Pintzas, Alexander

    2011-01-01

    Documented sensitivity of melanoma cells to PLX4720, a selective BRAFV600E inhibitor, is based on the presence of mutant BRAF(V600E) alone, while wt-BRAF or mutated KRAS result in cell proliferation. In colon cancer appearance of oncogenic alterations is complex , since BRAF, like KRAS mutations, tend to co-exist with those in PIK3CA and mutated PI3K has been shown to interfere with the successful application of MEK inhibitors. When PLX4720 was used to treat colon tumours, results were not encouraging and herein we attempt to understand the cause of this recorded resistance and discover rational therapeutic combinations to resensitize oncogene driven tumours to apoptosis. Treatment of two genetically different BRAF(V600E) mutant colon cancer cell lines with PLX4720 conferred complete resistance to cell death. Even though p-MAPK/ ERK kinase (MEK) suppression was achieved, TRAIL, an apoptosis inducing agent, was used synergistically in order to achieve cell death by apoptosis in RKO(BRAFV600E/PIK3CAH1047) cells. In contrast, for the same level of apoptosis in HT29(BRAFV600E/PIK3CAP449T) cells, TRAIL was combined with 17-AAG, an Hsp90 inhibitor. For cells where PLX4720 was completely ineffective, 17-AAG was alternatively used to target mutant BRAF(V600E). TRAIL dependence on the constitutive activation of BRAF(V600E) is emphasised through the overexpression of BRAF(V600E) in the permissive genetic background of colon adenocarcinoma Caco-2 cells. Pharmacological suppression of the PI3K pathway further enhances the synergistic effect between TRAIL and PLX4720 in RKO cells, indicating the presence of PIK3CA(MT) as the inhibitory factor. Another rational combination includes 17-AAG synergism with TRAIL in a BRAF(V600E) mutant dependent manner to commit cells to apoptosis, through DR5 and the amplification of the apoptotic pathway. We have successfully utilised combinations of two chemically unrelated BRAF(V600E) inhibitors in combination with TRAIL in a BRAF(V600E

  6. Arabidopsis COPPER MODIFIED RESISTANCE1/PATRONUS1 is essential for growth adaptation to stress and required for mitotic onset control.

    PubMed

    Juraniec, Michal; Heyman, Jefri; Schubert, Veit; Salis, Pietrino; De Veylder, Lieven; Verbruggen, Nathalie

    2016-01-01

    The mitotic checkpoint (MC) guards faithful sister chromatid segregation by monitoring the attachment of spindle microtubules to the kinetochores. When chromosome attachment errors are detected, MC delays the metaphase-to-anaphase transition through the inhibition of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. In contrast to yeast and mammals, our knowledge on the proteins involved in MC in plants is scarce. Transient synchronization of root tips as well as promoter-reporter gene fusions were performed to analyze temporal and spatial expression of COPPER MODIFIED RESISTANCE1/PATRONUS1 (CMR1/PANS1) in developing Arabidopsis thaliana seedlings. Functional analysis of the gene was carried out, including CYCB1;2 stability in CMR1/PANS1 knockout and overexpressor background as well as metaphase-anaphase chromosome status. CMR1/PANS1 is transcriptionally active during M phase. Its deficiency provokes premature cell cycle exit and in consequence a rapid consumption of the number of meristematic cells in particular under stress conditions that are known to affect spindle microtubules. Root growth impairment is correlated with a failure to delay the onset of anaphase, resulting in anaphase bridges and chromosome missegregation. CMR1/PANS1 overexpression stabilizes the mitotic CYCB1;2 protein. Likely, CMR1/PANS1 coordinates mitotic cell cycle progression by acting as an APC/C inhibitor and plays a key role in growth adaptation to stress.

  7. NF-kappa B1 is required for optimal CD4+ Th1 cell development and resistance to Leishmania major.

    PubMed

    Artis, David; Speirs, Kendra; Joyce, Karen; Goldschmidt, Michael; Caamaño, Jorge; Hunter, Christopher A; Scott, Phillip

    2003-02-15

    The NF-kappaB family of transcription factors regulates the expression of a wide range of immune response genes involved in immunity to pathogens. However, the need for individual family members in regulating innate and adaptive immune responses in vivo has yet to be clearly defined. We investigated the role of NF-kappaB1 in the induction of protective IL-12-dependent Th1 cell responses following infection with the intracellular protozoan parasite Leishmania major. Whereas wild-type C57BL/6 mice controlled parasite replication, NF-kappaB1 knockout (KO) mice were susceptible to infection, developing chronic unresolving lesions associated with persistent parasites. There was a profound defect in Ag-specific CD4(+) T cell proliferation and IFN-gamma production in infected KO mice, although innate responses-including IL-12 production and control of intracellular parasite replication by macrophages-were intact. In vitro polyclonal stimulation of purified naive KO T cells revealed an intrinsic defect in CD4(+) T cell proliferation associated with reduced IL-2 receptor expression, but operating independently of APC function and IL-2 production. Critically, the frequency of proliferating KO CD4(+) T cells secreting IFN-gamma matched that of wild-type cells, suggesting that NF-kappaB1 was not required for efficient transcription of the IFN-gamma gene. Taken together, these results identify a novel role for NF-kappaB1 in CD4(+) T cell proliferation and the development of Th1 cell responses required for protective immunity against intracellular pathogens. PMID:12574369

  8. 46 CFR 54.25-5 - Corrosion allowance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-5 Corrosion allowance. The corrosion allowance must be as required in 46 CFR 54.01-35. ... 46 Shipping 2 2012-10-01 2012-10-01 false Corrosion allowance. 54.25-5 Section 54.25-5...

  9. 46 CFR 54.25-5 - Corrosion allowance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-5 Corrosion allowance. The corrosion allowance must be as required in 46 CFR 54.01-35. ... 46 Shipping 2 2013-10-01 2013-10-01 false Corrosion allowance. 54.25-5 Section 54.25-5...

  10. 46 CFR 54.25-5 - Corrosion allowance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-5 Corrosion allowance. The corrosion allowance must be as required in 46 CFR 54.01-35. ... 46 Shipping 2 2011-10-01 2011-10-01 false Corrosion allowance. 54.25-5 Section 54.25-5...

  11. 46 CFR 54.25-5 - Corrosion allowance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-5 Corrosion allowance. The corrosion allowance must be as required in 46 CFR 54.01-35. ... 46 Shipping 2 2014-10-01 2014-10-01 false Corrosion allowance. 54.25-5 Section 54.25-5...

  12. 46 CFR 54.25-5 - Corrosion allowance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Construction With Carbon, Alloy, and Heat Treated Steels § 54.25-5 Corrosion allowance. The corrosion allowance must be as required in 46 CFR 54.01-35. ... 46 Shipping 2 2010-10-01 2010-10-01 false Corrosion allowance. 54.25-5 Section 54.25-5...

  13. Inhibition of seed germination and induction of systemic disease resistance by Pseudomonas chlororaphis O6 requires phenazine production regulated by the global regulator, gacS.

    PubMed

    Kang, Beom Ryong; Han, Song Hee; Zdor, Rob E; Anderson, Anne J; Spencer, Matt; Yang, Kwang Yeol; Kim, Yong Hwan; Lee, Myung Chul; Cho, Baik Ho; Kim, Young Cheol

    2007-04-01

    Seed coating by a phenazine-producing bacterium, Pseudomonas chlororaphis O6, induced dose-dependent inhibition of germination in wheat and barley seeds, but did not inhibit germination of rice or cucumber seeds. In wheat seedlings grown from inoculated seeds, phenazine production levels near the seed were higher than in the roots. Deletion of the gacS gene reduced transcription from the genes required for phenazine synthesis, the regulatory phzI gene and the biosynthetic phzA gene. The inhibition of seed germination and the induction of systemic disease resistance against a bacterial soft-rot pathogen, Erwinia carotovora subsp. carotovora, were impaired in the gacS and phzA mutants of P chlororaphis O6. Culture filtrates of the gacS and phzA mutants of P chlororaphis 06 did not inhibit seed germination of wheat, whereas that of the wild-type was inhibitory. Our results showed that the production of phenazines by P chlororaphis O6 was correlated with reduced germination of barley and wheat seeds, and the level of systemic resistance in tobacco against E. carotovora.

  14. The small heat shock protein 20 RSI2 interacts with and is required for stability and function of tomato resistance protein I-2.

    PubMed

    Van Ooijen, Gerben; Lukasik, Ewa; Van Den Burg, Harrold A; Vossen, Jack H; Cornelissen, Ben J C; Takken, Frank L W

    2010-08-01

    Race-specific disease resistance in plants depends on the presence of resistance (R) genes. Most R genes encode NB-ARC-LRR proteins that carry a C-terminal leucine-rich repeat (LRR). Of the few proteins found to interact with the LRR domain, most have proposed (co)chaperone activity. Here, we report the identification of RSI2 (Required for Stability of I-2) as a protein that interacts with the LRR domain of the tomato R protein I-2. RSI2 belongs to the family of small heat shock proteins (sHSPs or HSP20s). HSP20s are ATP-independent chaperones that form oligomeric complexes with client proteins to prevent unfolding and subsequent aggregation. Silencing of RSI2-related HSP20s in Nicotiana benthamiana compromised the hypersensitive response that is normally induced by auto-active variants of I-2 and Mi-1, a second tomato R protein. As many HSP20s have chaperone properties, the involvement of RSI2 and other R protein (co)chaperones in I-2 and Mi-1 protein stability was examined. RSI2 silencing compromised the accumulation of full-length I-2 in planta, but did not affect Mi-1 levels. Silencing of heat shock protein 90 (HSP90) and SGT1 led to an almost complete loss of full-length I-2 accumulation and a reduction in Mi-1 protein levels. In contrast to SGT1 and HSP90, RSI2 silencing led to accumulation of I-2 breakdown products. This difference suggests that RSI2 and HSP90/SGT1 chaperone the I-2 protein using different molecular mechanisms. We conclude that I-2 protein function requires RSI2, either through direct interaction with, and stabilization of I-2 protein or by affecting signalling components involved in initiation of the hypersensitive response. PMID:20497382

  15. The extent to which methyl salicylate is required for signaling systemic acquired resistance is dependent on exposure to light after infection.

    PubMed

    Liu, Po-Pu; von Dahl, Caroline C; Klessig, Daniel F

    2011-12-01

    Systemic acquired resistance (SAR) is a state of heightened defense to a broad spectrum of pathogens that is activated throughout a plant following local infection. Development of SAR requires the translocation of one or more mobile signals from the site of infection through the vascular system to distal (systemic) tissues. The first such signal identified was methyl salicylate (MeSA) in tobacco (Nicotiana tabacum). Subsequent studies demonstrated that MeSA also serves as a SAR signal in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum). By contrast, another study suggested that MeSA is not required for SAR in Arabidopsis and raised questions regarding its signaling role in tobacco. Differences in experimental design, including the developmental age of the plants, the light intensity, and/or the strain of bacterial pathogen, were proposed to explain these conflicting results. Here, we demonstrate that the length of light exposure that plants receive after the primary infection determines the extent to which MeSA is required for SAR signaling. When the primary infection occurred late in the day and as a result infected plants received very little light exposure before entering the night/dark period, MeSA and its metabolizing enzymes were essential for SAR development. In contrast, when infection was done in the morning followed by 3.5 h or more of exposure to light, SAR developed in the absence of MeSA. However, MeSA was generally required for optimal SAR development. In addition to resolving the conflicting results concerning MeSA and SAR, this study underscores the importance of environmental factors on the plant's response to infection.

  16. Methods of airway resistance assessment.

    PubMed

    Urbankowski, Tomasz; Przybyłowski, Tadeusz

    2016-01-01

    Airway resistance is the ratio of driving pressure to the rate of the airflow in the airways. The most frequent methods used to measure airway resistance are whole-body plethysmography, the interrupter technique and the forced oscillation technique. All these methods allow to measure resistance during respiration at the level close to tidal volume, they do not require forced breathing manoeuvres or deep breathing during measurement. The most popular method for measuring airway resistance is whole-body plethysmography. The results of plethysmography include among others the following parameters: airway resistance (Raw), airway conductance (Gaw), specific airway resistance (sRaw) and specific airway conductance (sGaw). The interrupter technique is based on the assumption that at the moment of airway occlusion, air pressure in the mouth is equal to the alveolar pressure . In the forced oscillation technique (FOT), airway resistance is calculated basing on the changes in pressure and flow caused by air vibration. The methods for measurement of airway resistance that are described in the present paper seem to be a useful alternative to the most common lung function test - spirometry. The target group in which these methods may be widely used are particularly the patients who are unable to perform spirometry.

  17. Resistant Hypertension.

    PubMed

    Doroszko, Adrian; Janus, Agnieszka; Szahidewicz-Krupska, Ewa; Mazur, Grzegorz; Derkacz, Arkadiusz

    2016-01-01

    Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension.

  18. FBN-1, a fibrillin-related protein, is required for resistance of the epidermis to mechanical deformation during C. elegans embryogenesis

    PubMed Central

    Kelley, Melissa; Yochem, John; Krieg, Michael; Calixto, Andrea; Heiman, Maxwell G; Kuzmanov, Aleksandra; Meli, Vijaykumar; Chalfie, Martin; Goodman, Miriam B; Shaham, Shai; Frand, Alison; Fay, David S

    2015-01-01

    During development, biomechanical forces contour the body and provide shape to internal organs. Using genetic and molecular approaches in combination with a FRET-based tension sensor, we characterized a pulling force exerted by the elongating pharynx (foregut) on the anterior epidermis during C. elegans embryogenesis. Resistance of the epidermis to this force and to actomyosin-based circumferential constricting forces is mediated by FBN-1, a ZP domain protein related to vertebrate fibrillins. fbn-1 was required specifically within the epidermis and FBN-1 was expressed in epidermal cells and secreted to the apical surface as a putative component of the embryonic sheath. Tiling array studies indicated that fbn-1 mRNA processing requires the conserved alternative splicing factor MEC-8/RBPMS. The conserved SYM-3/FAM102A and SYM-4/WDR44 proteins, which are linked to protein trafficking, function as additional components of this network. Our studies demonstrate the importance of the apical extracellular matrix in preventing mechanical deformation of the epidermis during development. DOI: http://dx.doi.org/10.7554/eLife.06565.001 PMID:25798732

  19. The association of Shiga-like toxin with detergent-resistant membranes is modulated by glucosylceramide and is an essential requirement in the endoplasmic reticulum for a cytotoxic effect.

    PubMed

    Smith, Daniel C; Sillence, Daniel J; Falguières, Thomas; Jarvis, Rosemary M; Johannes, Ludger; Lord, J Michael; Platt, Frances M; Roberts, Lynne M

    2006-03-01

    Receptor-mediated internalization to the endoplasmic reticulum (ER) and subsequent retro-translocation to the cytosol are essential sequential processes required for the productive intoxication of susceptible mammalian cells by Shiga-like toxin-1 (SLTx). Recently, it has been proposed that the observed association of certain ER-directed toxins and viruses with detergent-resistant membranes (DRM) may provide a general mechanism for their retrograde transport to endoplasmic reticulum (ER). Here, we show that DRM recruitment of SLTx bound to its globotriosylceramide (Gb(3)) receptor is mediated by the availability of other glycosphingolipids. Reduction in glucosylceramide (GlcCer) levels led to complete protection against SLTx and a reduced cell surface association of bound toxin with DRM. This reduction still allowed efficient binding and transport of the toxin to the ER. However, toxin sequestration within DRM of the ER was abolished under reduced GlcCer conditions, suggesting that an association of toxin with lipid microdomains or rafts in the ER (where these are defined by detergent insolubility) is essential for a later step leading to or involving retro-translocation of SLTx across the ER membrane. In support of this, we show that a number of ER residents, proteins intimately involved in the process of ER dislocation of misfolded proteins, are present in DRM.

  20. The rpg4-mediated resistance to wheat stem rust (Puccinia graminis) in barley (Hordeum vulgare) requires Rpg5, a second NBS-LRR gene, and an actin depolymerization factor.

    PubMed

    Wang, X; Richards, J; Gross, T; Druka, A; Kleinhofs, A; Steffenson, B; Acevedo, M; Brueggeman, R

    2013-04-01

    The rpg4 gene confers recessive resistance to several races of wheat stem rust (Puccinia graminis f. sp. tritici) and Rpg5 provides dominant resistance against isolates of the rye stem rust (P. graminis f. sp. secalis) in barley. The rpg4 and Rpg5 genes are tightly linked on chromosome 5H, and positional cloning using high-resolution populations clearly separated the genes, unambiguously identifying Rpg5; however, the identity of rpg4 remained unclear. High-resolution genotyping of critical recombinants at the rpg4/Rpg5 locus, designated here as rpg4-mediated resistance locus (RMRL) delimited two distinct yet tightly linked loci required for resistance, designated as RMRL1 and RMRL2. Utilizing virus-induced gene silencing, each gene at RMRL1, i.e., HvRga1 (a nucleotide-binding site leucine-rich repeat [NBS-LRR] domain gene), Rpg5 (an NBS-LRR-protein kinase domain gene), and HvAdf3 (an actin depolymerizing factor-like gene), was individually silenced followed by inoculation with P. graminis f. sp. tritici race QCCJ. Silencing each gene changed the reaction type from incompatible to compatible, indicating that all three genes are required for rpg4-mediated resistance. This stem rust resistance mechanism in barley follows the emerging theme of unrelated pairs of genetically linked NBS-LRR genes required for specific pathogen recognition and resistance. It also appears that actin cytoskeleton dynamics may play an important role in determining resistance against several races of stem rust in barley.

  1. 30 CFR 33.33 - Allowable limits of dust concentration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS DUST COLLECTORS FOR USE IN CONNECTION WITH ROCK DRILLING IN COAL MINES Test Requirements § 33.33 Allowable limits of dust concentration. (a) The concentration of dust... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Allowable limits of dust concentration....

  2. 30 CFR 33.33 - Allowable limits of dust concentration.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Allowable limits of dust concentration. 33.33... MINES Test Requirements § 33.33 Allowable limits of dust concentration. (a) The concentration of dust determined by the control sample shall be subtracted from the average concentration of dust determined by...

  3. 30 CFR 33.33 - Allowable limits of dust concentration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Allowable limits of dust concentration. 33.33... MINES Test Requirements § 33.33 Allowable limits of dust concentration. (a) The concentration of dust determined by the control sample shall be subtracted from the average concentration of dust determined by...

  4. 30 CFR 33.33 - Allowable limits of dust concentration.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Allowable limits of dust concentration. 33.33... MINES Test Requirements § 33.33 Allowable limits of dust concentration. (a) The concentration of dust determined by the control sample shall be subtracted from the average concentration of dust determined by...

  5. 42 CFR 409.46 - Allowable administrative costs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Allowable administrative costs. 409.46 Section 409... MEDICARE PROGRAM HOSPITAL INSURANCE BENEFITS Home Health Services Under Hospital Insurance § 409.46... supervising home health aides as required at § 484.36(d) of this chapter are allowable administrative...

  6. 42 CFR 409.46 - Allowable administrative costs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Allowable administrative costs. 409.46 Section 409... MEDICARE PROGRAM HOSPITAL INSURANCE BENEFITS Home Health Services Under Hospital Insurance § 409.46... supervising home health aides as required at § 484.36(d) of this chapter are allowable administrative...

  7. 42 CFR 409.46 - Allowable administrative costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Allowable administrative costs. 409.46 Section 409... MEDICARE PROGRAM HOSPITAL INSURANCE BENEFITS Home Health Services Under Hospital Insurance § 409.46... supervising home health aides as required at § 484.36(d) of this chapter are allowable administrative...

  8. 32 CFR 534.3 - Allowable expenses for witnesses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... MILITARY COURT FEES § 534.3 Allowable expenses for witnesses. (a) Military members—(1) On active duty. Members in the military service, on active duty, when required to appear as witnesses before courts will... fees and mileage allowed to wintesses attending courts of the United States. (Article 47, Uniform...

  9. 32 CFR 534.3 - Allowable expenses for witnesses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... MILITARY COURT FEES § 534.3 Allowable expenses for witnesses. (a) Military members—(1) On active duty. Members in the military service, on active duty, when required to appear as witnesses before courts will... fees and mileage allowed to wintesses attending courts of the United States. (Article 47, Uniform...

  10. 24 CFR 882.510 - Adjustment of utility allowance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Adjustment of utility allowance... Moderate Rehabilitation-Program Development and Operation § 882.510 Adjustment of utility allowance. The PHA must determine, at least annually, whether an adjustment is required in the Utility...

  11. 24 CFR 891.645 - Adjustment of utility allowances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Adjustment of utility allowances... Handicapped-Section 8 Assistance § 891.645 Adjustment of utility allowances. In connection with adjustments of contract rents as provided in § 891.640(a), the requirements for the adjustment of utility...

  12. 45 CFR 2400.50 - Allowances and Summer Institute costs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...' round-trip transportation to and from the Institute site. The costs of tuition, required fees, books... 45 Public Welfare 4 2014-10-01 2014-10-01 false Allowances and Summer Institute costs. 2400.50... Institute costs. At the Foundation's discretion, Fellows may be paid an allowance to help offset...

  13. 45 CFR 2400.50 - Allowances and Summer Institute costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...' round-trip transportation to and from the Institute site. The costs of tuition, required fees, books... 45 Public Welfare 4 2011-10-01 2011-10-01 false Allowances and Summer Institute costs. 2400.50... Institute costs. At the Foundation's discretion, Fellows may be paid an allowance to help offset...

  14. 45 CFR 2400.50 - Allowances and Summer Institute costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...' round-trip transportation to and from the Institute site. The costs of tuition, required fees, books... 45 Public Welfare 4 2010-10-01 2010-10-01 false Allowances and Summer Institute costs. 2400.50... Institute costs. At the Foundation's discretion, Fellows may be paid an allowance to help offset...

  15. 45 CFR 2400.50 - Allowances and Summer Institute costs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...' round-trip transportation to and from the Institute site. The costs of tuition, required fees, books... 45 Public Welfare 4 2013-10-01 2013-10-01 false Allowances and Summer Institute costs. 2400.50... Institute costs. At the Foundation's discretion, Fellows may be paid an allowance to help offset...

  16. Cephalosporin Resistance in Neisseria gonorrhoeae

    PubMed Central

    Bala, Manju; Sood, Seema

    2010-01-01

    Gonorrhea, a disease of public health importance, not only leads to high incidence of acute infections and complications but also plays a major role in facilitating human immunodeficiency virus (HIV) acquisition and transmission. One of the major public health needs for gonorrhea control is appropriate, effective treatment. However, treatment options for gonorrhea are diminishing as Neisseria gonorrhoeae have developed resistance to several antimicrobial drugs such as sulfonamides, penicillin, tetracyclines and quinolones. Antimicrobial resistance (AMR) surveillance of N. gonorrhoeae helps establish and maintain the efficacy of standard treatment regimens. AMR surveillance should be continuous to reveal the emergence of new resistant strains, monitor the changing patterns of resistance, and be able to update treatment recommendations so as to assist in disease control. Current treatment guidelines recommend the use of single dose injectable or oral cephalosporins. The emergence and spread of cephalosporin resistant and multi drug resistant N. gonorrhoeae strains, represents a worrying trend that requires monitoring and investigation. Routine clinical laboratories need to be vigilant for the detection of such strains such that strategies for control and prevention could be reviewed and revised from time to time. It will be important to elucidate the genetic mechanisms responsible for decreased susceptibility and future resistance. There is also an urgent need for research of safe, alternative anti-gonococcal compounds that can be administered orally and have effective potency, allowing high therapeutic efficacy (greater than 95.0% cure rate). PMID:20927291

  17. A Second Two-Component Regulatory System of Bordetella bronchiseptica Required for Bacterial Resistance to Oxidative Stress, Production of Acid Phosphatase, and In Vivo Persistence

    PubMed Central

    Jungnitz, Heidrun; West, Nicholas P.; Walker, Mark J.; Chhatwal, Gursharan S.; Guzmán, Carlos A.

    1998-01-01

    Random minitransposon mutagenesis was used to identify genes involved in the survival of Bordetella bronchiseptica within eukaryotic cells. One of the mutants which exhibited a reduced ability to survive intracellularly harbored a minitransposon insertion in a locus (ris) which displays a high degree of homology to two-component regulatory systems. This system exhibited less than 25% amino acid sequence homology to the only other two-component regulatory system described in Bordetella spp., the bvg locus. A risA′-′lacZ translational fusion was constructed and integrated into the chromosome of B. bronchiseptica. Determination of β-galactosidase activity under different environmental conditions suggested that ris is regulated independently of bvg and is optimally expressed at 37°C, in the absence of Mg2+, and when bacteria are in the intracellular niche. This novel regulatory locus, present in all Bordetella spp., is required for the expression of acid phosphatase by B. bronchiseptica. Although catalase and superoxide dismutase production were unaffected, the ris mutant was more sensitive to oxidative stress than the wild-type strain. Complementation of bvg-positive and bvg-negative ris mutants with the intact ris operon incorporated as a single copy into the chromosome resulted in the reestablishment of the ability of the bacterium to produce acid phosphatase and to resist oxidative stress. Mouse colonization studies demonstrated that the ris mutant is cleared by the host much earlier than the wild-type strain, suggesting that ris-regulated products play a significant role in natural infections. The identification of a second two-component system in B. bronchiseptica highlights the complexity of the regulatory network needed for organisms with a life cycle requiring adaptation to both the external environment and a mammalian host. PMID:9746560

  18. Iron-regulated metabolites produced by Pseudomonas fluorescens WCS374r are not required for eliciting induced systemic resistance against Pseudomonas syringae pv. tomato in Arabidopsis

    PubMed Central

    Djavaheri, Mohammad; Mercado-Blanco, Jesús; Versluis, C; Meyer, J-M; Loon, L C; Bakker, Peter A H M

    2012-01-01

    The plant growth-promoting rhizobacterium Pseudomonas fluorescens WCS374r produces several iron-regulated metabolites, including the fluorescent siderophore pseudobactin (Psb374), salicylic acid (SA), and pseudomonine (Psm), a siderophore that contains a SA moiety. After purification of Psb374 from culture supernatant of WCS374r, its structure was determined following isoelectrofocusing and tandem mass spectrometry, and found to be identical to the fluorescent siderophore produced by P. fluorescens ATCC 13525. To study the role of SA and Psm production in colonization of Arabidopsis thaliana roots and in induced systemic resistance (ISR) against Pseudomonas syringae pv. tomato (Pst) by strain WCS374r, mutants disrupted in the production of these metabolites were obtained by homologous recombination. These mutants were further subjected to transposon Tn5 mutagenesis to generate mutants also deficient in Psb374 production. The mutants behaved similar to the wild type in both their Arabidopsis rhizosphere-colonizing capacity and their ability to elicit ISR against Pst. We conclude that Psb374, SA, and Psm production by P. fluorescens WCS374r are not required for eliciting ISR in Arabidopsis. PMID:23170230

  19. ABC transporter PEN3/PDR8/ABCG36 interacts with calmodulin that, like PEN3, is required for Arabidopsis nonhost resistance.

    PubMed

    Campe, Ruth; Langenbach, Caspar; Leissing, Franz; Popescu, George V; Popescu, Sorina C; Goellner, Katharina; Beckers, Gerold J M; Conrath, Uwe

    2016-01-01

    Nonhost resistance (NHR) is the most prevalent form of plant immunity. In Arabidopsis, NHR requires membrane-localized ATP-binding cassette (ABC) transporter PENETRATION (PEN) 3. Upon perception of pathogen-associated molecular patterns, PEN3 becomes phosphorylated, suggestive of PEN3 regulation by post-translational modification. Here, we investigated the PEN3 protein interaction network. We probed the Arabidopsis protein microarray AtPMA-5000 with the N-terminal cytoplasmic domain of PEN3. Several of the proteins identified to interact with PEN3 in vitro represent cellular Ca(2+) sensors, including calmodulin (CaM) 3, CaM7 and several CaM-like proteins, pointing to the importance of Ca(2+) sensing to PEN3-mediated NHR. We demonstrated co-localization of PEN3 and CaM7, and we confirmed PEN3-CaM interaction in vitro and in vivo by PEN3 pull-down with CaM Sepharose, CaM overlay assay and bimolecular fluorescence complementation. We also show that just like in pen3, NHR to the nonadapted fungal pathogens Phakopsora pachyrhizi and Blumeria graminis f.sp. hordei is compromised in the Arabidopsis cam7 and pen3 cam7 mutants. Our study discloses CaM7 as a PEN3-interacting protein crucial to Arabidopsis NHR and emphasizes the importance of Ca(2+) sensing to plant immunity. PMID:26315018

  20. 49 CFR 266.11 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Allowable costs. 266.11 Section 266.11... TRANSPORTATION ACT § 266.11 Allowable costs. Allowable costs include only the following costs which are properly allocable to the work performed: Planning and program operation costs which are allowed under...

  1. 46 CFR 154.421 - Allowable stress.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Allowable stress. 154.421 Section 154.421 Shipping COAST... § 154.421 Allowable stress. The allowable stress for the integral tank structure must meet the American Bureau of Shipping's allowable stress for the vessel's hull published in “Rules for Building and...

  2. 46 CFR 154.421 - Allowable stress.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Allowable stress. 154.421 Section 154.421 Shipping COAST... § 154.421 Allowable stress. The allowable stress for the integral tank structure must meet the American Bureau of Shipping's allowable stress for the vessel's hull published in “Rules for Building and...

  3. 46 CFR 154.421 - Allowable stress.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Allowable stress. 154.421 Section 154.421 Shipping COAST... § 154.421 Allowable stress. The allowable stress for the integral tank structure must meet the American Bureau of Shipping's allowable stress for the vessel's hull published in “Rules for Building and...

  4. 46 CFR 154.421 - Allowable stress.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Allowable stress. 154.421 Section 154.421 Shipping COAST... § 154.421 Allowable stress. The allowable stress for the integral tank structure must meet the American Bureau of Shipping's allowable stress for the vessel's hull published in “Rules for Building and...

  5. 46 CFR 154.421 - Allowable stress.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Allowable stress. 154.421 Section 154.421 Shipping COAST... § 154.421 Allowable stress. The allowable stress for the integral tank structure must meet the American Bureau of Shipping's allowable stress for the vessel's hull published in “Rules for Building and...

  6. Evolving spiking networks with variable resistive memories.

    PubMed

    Howard, Gerard; Bull, Larry; de Lacy Costello, Ben; Gale, Ella; Adamatzky, Andrew

    2014-01-01

    Neuromorphic computing is a brainlike information processing paradigm that requires adaptive learning mechanisms. A spiking neuro-evolutionary system is used for this purpose; plastic resistive memories are implemented as synapses in spiking neural networks. The evolutionary design process exploits parameter self-adaptation and allows the topology and synaptic weights to be evolved for each network in an autonomous manner. Variable resistive memories are the focus of this research; each synapse has its own conductance profile which modifies the plastic behaviour of the device and may be altered during evolution. These variable resistive networks are evaluated on a noisy robotic dynamic-reward scenario against two static resistive memories and a system containing standard connections only. The results indicate that the extra behavioural degrees of freedom available to the networks incorporating variable resistive memories enable them to outperform the comparative synapse types. PMID:23614774

  7. 9 CFR 73.10 - Permitted dips; substances allowed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... IN CATTLE § 73.10 Permitted dips; substances allowed. (a) The dips at present permitted by the Department for the treatment, as required in this part, of cattle affected with or exposed to scabies, are as... of scabies in cattle, the APHIS 3 will require that the product be registered under the provisions...

  8. 9 CFR 73.10 - Permitted dips; substances allowed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... IN CATTLE § 73.10 Permitted dips; substances allowed. (a) The dips at present permitted by the Department for the treatment, as required in this part, of cattle affected with or exposed to scabies, are as... of scabies in cattle, the APHIS 3 will require that the product be registered under the provisions...

  9. 9 CFR 73.10 - Permitted dips; substances allowed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... IN CATTLE § 73.10 Permitted dips; substances allowed. (a) The dips at present permitted by the Department for the treatment, as required in this part, of cattle affected with or exposed to scabies, are as... of scabies in cattle, the APHIS 3 will require that the product be registered under the provisions...

  10. 9 CFR 73.10 - Permitted dips; substances allowed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... IN CATTLE § 73.10 Permitted dips; substances allowed. (a) The dips at present permitted by the Department for the treatment, as required in this part, of cattle affected with or exposed to scabies, are as... of scabies in cattle, the APHIS 3 will require that the product be registered under the provisions...

  11. 9 CFR 73.10 - Permitted dips; substances allowed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... IN CATTLE § 73.10 Permitted dips; substances allowed. (a) The dips at present permitted by the Department for the treatment, as required in this part, of cattle affected with or exposed to scabies, are as... of scabies in cattle, the APHIS 3 will require that the product be registered under the provisions...

  12. Assessing allowable take of migratory birds

    USGS Publications Warehouse

    Runge, M.C.; Sauer, J.R.; Avery, M.L.; Blackwell, B.F.; Koneff, M.D.

    2009-01-01

    Legal removal of migratory birds from the wild occurs for several reasons, including subsistence, sport harvest, damage control, and the pet trade. We argue that harvest theory provides the basis for assessing the impact of authorized take, advance a simplified rendering of harvest theory known as potential biological removal as a useful starting point for assessing take, and demonstrate this approach with a case study of depredation control of black vultures (Coragyps atratus) in Virginia, USA. Based on data from the North American Breeding Bird Survey and other sources, we estimated that the black vulture population in Virginia was 91,190 (95% credible interval = 44,520?212,100) in 2006. Using a simple population model and available estimates of life-history parameters, we estimated the intrinsic rate of growth (rmax) to be in the range 7?14%, with 10.6% a plausible point estimate. For a take program to seek an equilibrium population size on the conservative side of the yield curve, the rate of take needs to be less than that which achieves a maximum sustained yield (0.5 x rmax). Based on the point estimate for rmax and using the lower 60% credible interval for population size to account for uncertainty, these conditions would be met if the take of black vultures in Virginia in 2006 was <3,533 birds. Based on regular monitoring data, allowable harvest should be adjusted annually to reflect changes in population size. To initiate discussion about how this assessment framework could be related to the laws and regulations that govern authorization of such take, we suggest that the Migratory Bird Treaty Act requires only that take of native migratory birds be sustainable in the long-term, that is, sustained harvest rate should be requirements of the National Environmental Protection Act.

  13. The emergence of extensively drug-resistant tuberculosis: a global health crisis requiring new interventions: Part II: scientific advances that may provide solutions.

    PubMed

    Ellner, Jerrold J

    2009-02-01

    The need for new tuberculosis (TB) diagnostics has never been greater as TB in the HIV-infected is often sputum smear negative or extrapulmonary and may progress rapidly unless diagnosed and treated appropriately. In addition, the empirical treatment of patients with drug-resistant TB leads to the acquisition of additional resistance. Fortunately there is a robust and adequately funded developments pipeline including investigational rapid diagnostics that may replace smear, culture, and drug susceptibility testing. The dogma that drug resistance usually develops as a consequence of patient nonadherence has never been entirely plausible. Recent observations indicate that certain mutations in drug resistance genes promote the acquisition of additional resistance. Further, Mycobacterium tuberculosis (MTB) may demonstrate tolerant phenotypes due to induction of a multidrug-resistant like pump. It will be difficult to "treat our way" out of the problem of extensively drug-resistant (XDR)-TB without access to new interventions. Vaccines in development offer a distant hope. Promising new therapeutics in clinical trials may shorten the duration of treatment of TB, which will lessen the development of drug resistance or provide potent new and MTB specific agents that should be effective in treatment of XDR-TB.

  14. SWI/SNF factors required for cellular resistance to DNA damage include ARID1A and ARID1B and show interdependent protein stability.

    PubMed

    Watanabe, Reiko; Ui, Ayako; Kanno, Shin-Ichiro; Ogiwara, Hideaki; Nagase, Takahiro; Kohno, Takashi; Yasui, Akira

    2014-05-01

    The SWI/SNF chromatin-remodeling family contains various protein complexes, which regulate gene expression during cellular development and influence DNA damage response in an ATP- and complex-dependent manner, of which details remain elusive. Recent human genome sequencing of various cancer cells revealed frequent mutations in SWI/SNF factors, especially ARID1A, a variant subunit in the BRG1-associated factor (BAF) complex of the SWI/SNF family. We combined live-cell analysis and gene-suppression experiments to show that suppression of either ARID1A or its paralog ARID1B led to reduced nonhomologous end joining activity of DNA double-strand breaks (DSB), decreased accumulation of KU70/KU80 proteins at DSB, and sensitivity to ionizing radiation, as well as to cisplatin and UV. Thus, in contrast to transcriptional regulation, both ARID1 proteins are required for cellular resistance to various types of DNA damage, including DSB. The suppression of other SWI/SNF factors, namely SNF5, BAF60a, BAF60c, BAF155, or BAF170, exhibits a similar phenotype. Of these factors, ARID1A, ARID1B, SNF5, and BAF60c are necessary for the immediate recruitment of the ATPase subunit of the SWI/SNF complex to DSB, arguing that both ARID1 proteins facilitate the damage response of the complex. Finally, we found interdependent protein stability among the SWI/SNF factors, suggesting their direct interaction within the complex and the reason why multiple factors are frequently lost in parallel in cancer cells. Taken together, we show that cancer cells lacking in the expression of certain SWI/SNF factors, including ARID1A, are deficient in DNA repair and potentially vulnerable to DNA damage.

  15. Functional metagenomics for the investigation of antibiotic resistance.

    PubMed

    Mullany, Peter

    2014-04-01

    Antibiotic resistance is a major threat to human health and well-being. To effectively combat this problem we need to understand the range of different resistance genes that allow bacteria to resist antibiotics. To do this the whole microbiota needs to be investigated. As most bacteria cannot be cultivated in the laboratory, the reservoir of antibiotic resistance genes in the non-cultivatable majority remains relatively unexplored. Currently the only way to study antibiotic resistance in these organisms is to use metagenomic approaches. Furthermore, the only method that does not require any prior knowledge about the resistance genes is functional metagenomics, which involves expressing genes from metagenomic clones in surrogate hosts. In this review the methods and limitations of functional metagenomics to isolate new antibiotic resistance genes and the mobile genetic elements that mediate their spread are explored.

  16. 10 CFR 600.317 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... OMB Circular A-122 is determined in accordance with the for-profit costs principles in 48 CFR part 31... Organizations.” (iii) Hospitals. Allowability is determined in accordance with the provisions of 45 CFR part 74... Allowable costs. (a) DOE determines allowability of costs in accordance with the cost principles...

  17. 7 CFR 550.25 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... at 2 CFR part 230. The allowability of costs incurred by institutions of higher education is... at 2 CFR part 225. The allowability of costs incurred by non-profit organizations is determined in... Institutions” codified at 2 CFR 220. The allowability of costs incurred by hospitals is determined...

  18. 20 CFR 211.8 - Displacement allowance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Displacement allowance. 211.8 Section 211.8 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT CREDITABLE RAILROAD COMPENSATION § 211.8 Displacement allowance. An allowance paid to an employee because he has...

  19. 20 CFR 211.8 - Displacement allowance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Displacement allowance. 211.8 Section 211.8 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT CREDITABLE RAILROAD COMPENSATION § 211.8 Displacement allowance. An allowance paid to an employee because he has...

  20. 20 CFR 211.8 - Displacement allowance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Displacement allowance. 211.8 Section 211.8 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT CREDITABLE RAILROAD COMPENSATION § 211.8 Displacement allowance. An allowance paid to an employee because he has...

  1. 20 CFR 211.8 - Displacement allowance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Displacement allowance. 211.8 Section 211.8 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT CREDITABLE RAILROAD COMPENSATION § 211.8 Displacement allowance. An allowance paid to an employee because he has...

  2. 20 CFR 211.8 - Displacement allowance.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Displacement allowance. 211.8 Section 211.8 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT CREDITABLE RAILROAD COMPENSATION § 211.8 Displacement allowance. An allowance paid to an employee because he has...

  3. 44 CFR 206.228 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Allowable costs. General policies for determining allowable costs are established in 44 CFR 13.22. Exceptions to those policies as allowed in 44 CFR 13.4 and 13.6 are explained below. (a) Eligible direct... accordance with 44 CFR part 207. (b)...

  4. 44 CFR 204.63 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....63 Allowable costs. 44 CFR 13.22 establishes general policies for determining allowable costs. (a) We will reimburse direct costs for the administration of a fire management assistance grant under 44 CFR... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Allowable costs....

  5. 50 CFR 85.41 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... applicable Federal cost principles in 43 CFR 12.60(b). Purchase of informational signs, program signs, and... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Allowable costs. 85.41 Section 85.41... Use/Acceptance of Funds § 85.41 Allowable costs. (a) Allowable grant costs are limited to those...

  6. 34 CFR 675.33 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false Allowable costs. 675.33 Section 675.33 Education... costs. (a)(1) Allowable and unallowable costs. Except as provided in paragraph (a)(2) of this section, costs reasonably related to carrying out the programs described in § 675.32 are allowable. (2)...

  7. 42 CFR 417.534 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Allowable costs. 417.534 Section 417.534 Public... PLANS Medicare Payment: Cost Basis § 417.534 Allowable costs. (a) Definition—Allowable costs means the direct and indirect costs, including normal standby costs incurred by the HMO or CMP, that are proper...

  8. 42 CFR 417.802 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Allowable costs. 417.802 Section 417.802 Public... PLANS Health Care Prepayment Plans § 417.802 Allowable costs. (a) General rule. The costs that are considered allowable for HCPP reimbursement are the same as those for reasonable cost HMOs and CMPs...

  9. 45 CFR 1180.56 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Allowable costs. 1180.56 Section 1180.56 Public... by a Grantee General Administrative Responsibilities § 1180.56 Allowable costs. (a) Determination of costs allowable under a grant is made in accordance with government-wide cost principles in...

  10. 34 CFR 304.21 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Grantee § 304.21 Allowable costs. In addition to the allowable costs established in the Education Department General Administrative Regulations in 34 CFR 75.530 through 75.562, the following items are... 34 Education 2 2011-07-01 2010-07-01 true Allowable costs. 304.21 Section 304.21...

  11. 34 CFR 80.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CFR part 31. Contract Cost Principles and Procedures, or uniform cost accounting standards that comply... 34 Education 1 2010-07-01 2010-07-01 false Allowable costs. 80.22 Section 80.22 Education Office... Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable...

  12. 34 CFR 80.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CFR part 31. Contract Cost Principles and Procedures, or uniform cost accounting standards that comply... 34 Education 1 2011-07-01 2011-07-01 false Allowable costs. 80.22 Section 80.22 Education Office... Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable...

  13. 42 CFR 417.802 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Allowable costs. 417.802 Section 417.802 Public... PLANS Health Care Prepayment Plans § 417.802 Allowable costs. (a) General rule. The costs that are considered allowable for HCPP reimbursement are the same as those for reasonable cost HMOs and CMPs...

  14. 34 CFR 304.21 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Grantee § 304.21 Allowable costs. In addition to the allowable costs established in the Education Department General Administrative Regulations in 34 CFR 75.530 through 75.562, the following items are... 34 Education 2 2010-07-01 2010-07-01 false Allowable costs. 304.21 Section 304.21...

  15. 42 CFR 417.534 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Allowable costs. 417.534 Section 417.534 Public... PLANS Medicare Payment: Cost Basis § 417.534 Allowable costs. (a) Definition—Allowable costs means the direct and indirect costs, including normal standby costs incurred by the HMO or CMP, that are proper...

  16. 45 CFR 1157.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... named in OBM Circular A-122 as not subject to that circular 48 CFR part 31. Contract Cost Principles and... 45 Public Welfare 3 2010-10-01 2010-10-01 false Allowable costs. 1157.22 Section 1157.22 Public... Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1) The allowable...

  17. 24 CFR 17.43 - Allowable claims.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Allowable claims. (a) A claim may be allowed only if: (1) The damage or loss was not caused wholly or partly...) of this section, and the other provisions of this subpart, any claim for damage to, or loss of... types of claims may be allowed, unless excluded by §§ 17.44 and 17.45: (1) Property loss or damage...

  18. 44 CFR 206.228 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Allowable costs. 206.228... Allowable costs. General policies for determining allowable costs are established in 44 CFR 13.22... costs for major disasters and emergencies will be paid in accordance with 44 CFR part 207. (b)...

  19. 46 CFR 154.447 - Allowable stress.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Allowable stress. 154.447 Section 154.447 Shipping COAST... Tank Type B § 154.447 Allowable stress. (a) An independent tank type B designed from bodies of revolution must have allowable stresses 3 determined by the following formulae: 3 See Appendix B for...

  20. 46 CFR 154.447 - Allowable stress.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Allowable stress. 154.447 Section 154.447 Shipping COAST... Tank Type B § 154.447 Allowable stress. (a) An independent tank type B designed from bodies of revolution must have allowable stresses 3 determined by the following formulae: 3 See Appendix B for...

  1. 46 CFR 154.447 - Allowable stress.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Allowable stress. 154.447 Section 154.447 Shipping COAST... Tank Type B § 154.447 Allowable stress. (a) An independent tank type B designed from bodies of revolution must have allowable stresses 3 determined by the following formulae: 3 See Appendix B for...

  2. 46 CFR 154.428 - Allowable stress.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Allowable stress. 154.428 Section 154.428 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS FOR... § 154.428 Allowable stress. The membrane tank and the supporting insulation must have allowable...

  3. 46 CFR 154.428 - Allowable stress.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Allowable stress. 154.428 Section 154.428 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS FOR... § 154.428 Allowable stress. The membrane tank and the supporting insulation must have allowable...

  4. 46 CFR 154.428 - Allowable stress.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Allowable stress. 154.428 Section 154.428 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS FOR... § 154.428 Allowable stress. The membrane tank and the supporting insulation must have allowable...

  5. 46 CFR 154.428 - Allowable stress.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Allowable stress. 154.428 Section 154.428 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS FOR... § 154.428 Allowable stress. The membrane tank and the supporting insulation must have allowable...

  6. 46 CFR 154.428 - Allowable stress.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Allowable stress. 154.428 Section 154.428 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS FOR... § 154.428 Allowable stress. The membrane tank and the supporting insulation must have allowable...

  7. 46 CFR 154.447 - Allowable stress.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Allowable stress. 154.447 Section 154.447 Shipping COAST... Tank Type B § 154.447 Allowable stress. (a) An independent tank type B designed from bodies of revolution must have allowable stresses 3 determined by the following formulae: 3 See Appendix B for...

  8. 46 CFR 154.447 - Allowable stress.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Allowable stress. 154.447 Section 154.447 Shipping COAST... Tank Type B § 154.447 Allowable stress. (a) An independent tank type B designed from bodies of revolution must have allowable stresses 3 determined by the following formulae: 3 See Appendix B for...

  9. 34 CFR 304.21 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 2 2012-07-01 2012-07-01 false Allowable costs. 304.21 Section 304.21 Education... Grantee § 304.21 Allowable costs. In addition to the allowable costs established in the Education Department General Administrative Regulations in 34 CFR 75.530 through 75.562, the following items...

  10. 34 CFR 304.21 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 2 2014-07-01 2013-07-01 true Allowable costs. 304.21 Section 304.21 Education... Grantee § 304.21 Allowable costs. In addition to the allowable costs established in the Education Department General Administrative Regulations in 34 CFR 75.530 through 75.562, the following items...

  11. 34 CFR 304.21 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 2 2013-07-01 2013-07-01 false Allowable costs. 304.21 Section 304.21 Education... Grantee § 304.21 Allowable costs. In addition to the allowable costs established in the Education Department General Administrative Regulations in 34 CFR 75.530 through 75.562, the following items...

  12. Candida albicans AGE3, the Ortholog of the S. cerevisiae ARF-GAP-Encoding Gene GCS1, Is Required for Hyphal Growth and Drug Resistance

    PubMed Central

    Lettner, Thomas; Zeidler, Ute; Gimona, Mario; Hauser, Michael; Breitenbach, Michael; Bito, Arnold

    2010-01-01

    Background Hyphal growth and multidrug resistance of C. albicans are important features for virulence and antifungal therapy of this pathogenic fungus. Methodology/Principal Findings Here we show by phenotypic complementation analysis that the C. albicans gene AGE3 is the functional ortholog of the yeast ARF-GAP-encoding gene GCS1. The finding that the gene is required for efficient endocytosis points to an important functional role of Age3p in endosomal compartments. Most C. albicans age3Δ mutant cells which grew as cell clusters under yeast growth conditions showed defects in filamentation under different hyphal growth conditions and were almost completely disabled for invasive filamentous growth. Under hyphal growth conditions only a fraction of age3Δ cells shows a wild-type-like polarization pattern of the actin cytoskeleton and lipid rafts. Moreover, age3Δ cells were highly susceptible to several unrelated toxic compounds including antifungal azole drugs. Irrespective of the AGE3 genotype, C-terminal fusions of GFP to the drug efflux pumps Cdr1p and Mdr1p were predominantly localized in the plasma membrane. Moreover, the plasma membranes of wild-type and age3Δ mutant cells contained similar amounts of Cdr1p, Cdr2p and Mdr1p. Conclusions/Significance The results indicate that the defect in sustaining filament elongation is probably caused by the failure of age3Δ cells to polarize the actin cytoskeleton and possibly of inefficient endocytosis. The high susceptibility of age3Δ cells to azoles is not caused by inefficient transport of efflux pumps to the cell membrane. A possible role of a vacuolar defect of age3Δ cells in drug susceptibility is proposed and discussed. In conclusion, our study shows that the ARF-GAP Age3p is required for hyphal growth which is an important virulence factor of C. albicans and essential for detoxification of azole drugs which are routinely used for antifungal therapy. Thus, it represents a promising antifungal drug target

  13. Novel transparent electrodes allow sustainable production of electronic devices

    SciTech Connect

    Constant, Kristen

    2010-12-27

    -particle-count clean-room facilities and multimillion-dollar equipment. On the other hand, the novel process we developed uses a method that makes use of polymer molds and standard deposition techniques in an ambient laboratory environment. The final structure consists of tall ribbons of metal (standing on edge) that are so thin that they do not block light but are very good conductors. The advantage of this design is that it avoids the competition between conductivity and transparency inherent in transparent oxide electrodes. By making the structure taller, conductivity can be increased without impacting transparency. We have measured both electrical conductivity and transparency for these structures. We performed two-wire electrical measurements to quantify the structures resistance using metal contacts deposited on each end. The total sample area was 4 x 4mm{sup 2}. We measured a resistance of structures with 40nm gold sidewalls of 7.3{Omega}, which is lower than that of ITO glass (which has a sheet resistance around 10O/square). We investigated the structures optical properties based on both specular- and total-transmission measurements. Specular transmission is measured by collecting the transmitted light at normal incidence, while total transmission is obtained by collecting transmitted light at normal incidence and diffracted light using an integrating sphere. Figure 3 shows the total transmission of a grating with 40nm gold or silver sidewalls on a glass substrate compared to that of ITO. Additionally, the transparency changes very little within 30{sup o} off normal incidence. This high visible-light transmission of our metal-patterned structures is very promising for their application as transparent electrodes, because most visible light was allowed to propagate through the patterned metallic/polymeric structures. Researchers in our group continue to refine the fabrication methods and are investigating methods to make large-scale structures for use in a variety of

  14. Concurrent MEK and autophagy inhibition is required to restore cell death associated danger-signalling in Vemurafenib-resistant melanoma cells.

    PubMed

    Martin, S; Dudek-Perić, A M; Maes, H; Garg, A D; Gabrysiak, M; Demirsoy, S; Swinnen, J V; Agostinis, P

    2015-02-01

    Vemurafenib (PLX4032), an inhibitor of BRAF(V600E), has demonstrated significant clinical anti-melanoma effects. However, the majority of treated patients develop resistance, due to a variety of molecular mechanisms including MAPK reactivation through MEK. The induction of a cancer cell death modality associated with danger-signalling resulting in surface mobilization of crucial damage-associated-molecular-patterns (DAMPs), e.g. calreticulin (CRT) and heat shock protein-90 (HSP90), from dying cells, is emerging to be crucial for therapeutic success. Both cell death and danger-signalling are modulated by autophagy, a key adaptation mechanism stimulated during melanoma progression. However, whether melanoma cell death induced by MAPK inhibition is associated with danger-signalling, and the reliance of these mechanisms on autophagy, has not yet been scrutinized. Using a panel of isogenic PLX4032-sensitive and resistant melanoma cell lines we show that PLX4032-induced caspase-dependent cell death and DAMPs exposure in the drug-sensitive cells, but failed to do so in the drug-resistant cells, displaying heightened MEK activation. MEK inhibitor, U0126, treatment sensitized PLX4032-resistant cells to death and re-established their danger-signalling capacity. Only melanoma cells exposing death-induced danger-signals were phagocytosed and induced DC maturation. Although the PLX4032-resistant melanoma cells displayed higher basal and drug-induced autophagy, compromising autophagy, pharmacologically or by ATG5 knockdown, was insufficient to re-establish their PLX4032 sensitivity. Interestingly, autophagy abrogation was particularly efficacious in boosting cell death and ecto-CRT/ecto-HSP90 in PLX4032-resistant cells upon blockage of MEK hyper-activation by U0126. Thus combination of MEK inhibitors with autophagy blockers may represent a novel treatment regime to increase both cell death and danger-signalling in Vemurafenib-resistant metastatic melanoma.

  15. 20 CFR 631.84 - Allowable projects.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Allowable projects. 631.84 Section 631.84... THE JOB TRAINING PARTNERSHIP ACT Disaster Relief Employment Assistance § 631.84 Allowable projects...) Shall be used exclusively to provide employment on projects that provide food, clothing, shelter...

  16. 27 CFR 28.334 - Credit allowance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Credit allowance. 28.334... OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Action on Claims § 28.334 Credit allowance. Where the credit relates to internal revenue taxes on beer that have been determined but not yet paid by...

  17. 27 CFR 28.334 - Credit allowance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Credit allowance. 28.334... OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Action on Claims § 28.334 Credit allowance. Where the credit relates to internal revenue taxes on beer that have been determined but not yet paid by...

  18. 27 CFR 28.334 - Credit allowance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Credit allowance. 28.334... OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Action on Claims § 28.334 Credit allowance. Where the credit relates to internal revenue taxes on beer that have been determined but not yet paid by...

  19. 27 CFR 28.334 - Credit allowance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Credit allowance. 28.334... OF THE TREASURY ALCOHOL EXPORTATION OF ALCOHOL Action on Claims § 28.334 Credit allowance. Where the credit relates to internal revenue taxes on beer that have been determined but not yet paid by...

  20. 27 CFR 28.334 - Credit allowance.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Credit allowance. 28.334... OF THE TREASURY ALCOHOL EXPORTATION OF ALCOHOL Action on Claims § 28.334 Credit allowance. Where the credit relates to internal revenue taxes on beer that have been determined but not yet paid by...

  1. 20 CFR 437.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... CFR Part 31. Contract Cost Principles and Procedures, or uniform cost accounting standards that comply... allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to cost-type...

  2. 34 CFR 642.40 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Allowable costs. 642.40 Section 642.40 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION TRAINING PROGRAM FOR FEDERAL TRIO PROGRAMS What Conditions Must Be Met by a Grantee? § 642.40 Allowable costs....

  3. 10 CFR 600.222 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... than a hospital and an organization named in OBM Circular A-122 as not subject to that circular 48 CFR... organization named in OMB Circular A-122 as not subject to that circular. 48 CFR 931.2 Hospitals 45 CFR part 74... allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in...

  4. 45 CFR 92.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... to that circular 48 CFR Part 31. Contract Cost Principles and Procedures, or uniform cost accounting... grantee or subgrantee. (b) Applicable cost principles. For each kind of organization, there is a set of Federal principles for determining allowable costs. Allowable costs will be determined in accordance...

  5. 15 CFR 24.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Part 31. Contract Cost Principles and Procedures, or uniform cost accounting standards that comply with...) Applicable cost principles. For each kind of organization, there is a set of Federal principles for determining allowable costs. Allowable costs will be determined in accordance with the cost...

  6. 20 CFR 617.46 - Travel allowance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... mile at the prevailing mileage rate authorized under the Federal travel regulations (see 41 CFR part... the same trip in the same vehicle. (2) Lodging and meals. The cost allowable for lodging and meals for... prevailing per diem allowance rate authorized under the Federal travel regulations (see 41 CFR part...

  7. 20 CFR 617.46 - Travel allowance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... mile at the prevailing mileage rate authorized under the Federal travel regulations (see 41 CFR part... the same trip in the same vehicle. (2) Lodging and meals. The cost allowable for lodging and meals for... prevailing per diem allowance rate authorized under the Federal travel regulations (see 41 CFR part...

  8. 30 CFR 206.160 - Operating allowances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Operating allowances. 206.160 Section 206.160 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT PRODUCT VALUATION Federal Gas § 206.160 Operating allowances. Notwithstanding any other provisions...

  9. Moral Appraisals Affect Doing/Allowing Judgments

    ERIC Educational Resources Information Center

    Cushman, Fiery; Knobe, Joshua; Sinnott-Armstrong, Walter

    2008-01-01

    An extensive body of research suggests that the distinction between doing and allowing plays a critical role in shaping moral appraisals. Here, we report evidence from a pair of experiments suggesting that the converse is also true: moral appraisals affect doing/allowing judgments. Specifically, morally bad behavior is more likely to be construed…

  10. Allocation of Allowances and Associated Family Practices.

    ERIC Educational Resources Information Center

    Kerr, M. Kaye; Cheadle, Tannis

    This study gathered information on general family practices concerning allowances given to children, parental reasons for the provision of allowances, the bases for their administration, and the frequency of conflicts generated around them. The subjects were 81 parents of elementary school children in a midwest Canadian city. Subjects completed…

  11. 20 CFR 632.258 - Allowable activities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR INDIAN AND NATIVE AMERICAN EMPLOYMENT AND TRAINING PROGRAMS Summer Youth Employment and Training Programs § 632.258 Allowable activities. Allowable activities are those listed in § 632.78-80 except that community service employment is...

  12. 20 CFR 632.258 - Allowable activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR INDIAN AND NATIVE AMERICAN EMPLOYMENT AND TRAINING PROGRAMS Summer Youth Employment and Training Programs § 632.258 Allowable activities. Allowable activities are those listed in § 632.78-80 except that community service employment is...

  13. 42 CFR 417.802 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) MEDICARE PROGRAM (CONTINUED) HEALTH MAINTENANCE ORGANIZATIONS, COMPETITIVE MEDICAL PLANS, AND HEALTH CARE PREPAYMENT PLANS Health Care Prepayment Plans § 417.802 Allowable costs. (a) General rule. The costs that are... 42 Public Health 3 2014-10-01 2014-10-01 false Allowable costs. 417.802 Section 417.802...

  14. 4 CFR 5.6 - Allowances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Allowances. 5.6 Section 5.6 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM COMPENSATION § 5.6 Allowances. The provisions of chapter 59 of title 5, U.S. Code and the implementing regulations for the Executive Branch apply to Government...

  15. 20 CFR 617.46 - Travel allowance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... mile at the prevailing mileage rate authorized under the Federal travel regulations (see 41 CFR part... prevailing per diem allowance rate authorized under the Federal travel regulations (see 41 CFR part 101-7... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Travel allowance. 617.46 Section...

  16. 28 CFR 66.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... applicable to the organization incurring the costs. The following chart lists the kinds of organizations and... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Allowable costs. 66.22 Section 66.22... Administration § 66.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1)...

  17. 44 CFR 208.33 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Allowable costs. 208.33... HOMELAND SECURITY DISASTER ASSISTANCE NATIONAL URBAN SEARCH AND RESCUE RESPONSE SYSTEM Response Cooperative Agreements § 208.33 Allowable costs. (a) Cost neutrality. DHS policy is that an Alert or Activation should...

  18. 30 CFR 1206.160 - Operating allowances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Operating allowances. 1206.160 Section 1206.160 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR Natural Resources Revenue PRODUCT VALUATION Federal Gas § 1206.160 Operating allowances. Notwithstanding any...

  19. 21 CFR 1403.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... and an organization named in OMB Circular A-122 as not subject to that circular 48 CFR part 31... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Allowable costs. 1403.22 Section 1403.22 Food and....22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1)...

  20. 45 CFR 1183.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... than a hospital and an organization named in OBM Circular A-122 as not subject to that circular 48 CFR... 45 Public Welfare 3 2010-10-01 2010-10-01 false Allowable costs. 1183.22 Section 1183.22 Public....22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1)...

  1. 20 CFR 633.303 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... otherwise indicated below, direct and indirect costs shall be charged in accordance with 41 CFR part 29-70... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Allowable costs. 633.303 Section 633.303... FARMWORKER PROGRAMS Program Design and Administrative Procedures § 633.303 Allowable costs. (a) General....

  2. 29 CFR 1470.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... to that circular 48 CFR part 31. Contract Cost Principles and Procedures, or uniform cost accounting... 29 Labor 4 2010-07-01 2010-07-01 false Allowable costs. 1470.22 Section 1470.22 Labor Regulations... Financial Administration § 1470.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be...

  3. 45 CFR 74.27 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... determined in accordance with the provisions of the Federal Acquisition Regulation (FAR) at 48 CFR part 31... 45 Public Welfare 1 2011-10-01 2011-10-01 false Allowable costs. 74.27 Section 74.27 Public... Allowable costs. (a) For each kind of recipient, there is a particular set of Federal principles...

  4. 45 CFR 1174.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... than a hospital and an organization named in OBM Circular A-122 as not subject to that circular 48 CFR... 45 Public Welfare 3 2010-10-01 2010-10-01 false Allowable costs. 1174.22 Section 1174.22 Public....22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1)...

  5. 2 CFR 215.27 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CFR part 230, “Cost Principles for Non-Profit Organizations (OMB Circular A-122).” The allowability of... CFR part 220, “Cost Principles for Educational Institutions (OMB Circular A-21).” The allowability of costs incurred by hospitals is determined in accordance with the provisions of appendix E of 45 CFR...

  6. 45 CFR 92.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... to that circular 48 CFR Part 31. Contract Cost Principles and Procedures, or uniform cost accounting... 45 Public Welfare 1 2011-10-01 2011-10-01 false Allowable costs. 92.22 Section 92.22 Public... Financial Administration § 92.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be...

  7. 10 CFR 600.317 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Organizations.” (iii) Hospitals. Allowability is determined in accordance with the provisions of 45 CFR part 74... OMB Circular A-122 is determined in accordance with the for-profit costs principles in 48 CFR part 31... Contracts with Hospitals.” (iv) Governmental organizations. Allowability for State, local, or...

  8. 33 CFR 136.211 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.211 Compensation allowable. (a) The amount of compensation allowable is the reasonable cost of assessing damages, and...

  9. 21 CFR 1303.24 - Inventory allowance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Inventory allowance. 1303.24 Section 1303.24 Food... Quotas § 1303.24 Inventory allowance. (a) For the purpose of determining individual manufacturing quotas... sufficient to maintain an inventory equal to, (1) For current manufacturers, 50 percent of his...

  10. 10 CFR 600.127 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... recipient, there is a set of Federal principles for determining allowable costs. Allowability of costs shall... incurred by hospitals is determined in accordance with the provisions of Appendix E of 45 CFR part 74... Federal Acquisition Regulation (FAR) at 48 CFR part 31. (b) Indirect costs. Unless restricted by...

  11. 10 CFR 600.127 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... recipient, there is a set of Federal principles for determining allowable costs. Allowability of costs shall... incurred by hospitals is determined in accordance with the provisions of Appendix E of 45 CFR part 74... Federal Acquisition Regulation (FAR) at 48 CFR part 31. (b) Indirect costs. Unless restricted by...

  12. 10 CFR 600.127 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... recipient, there is a set of Federal principles for determining allowable costs. Allowability of costs shall... incurred by hospitals is determined in accordance with the provisions of Appendix E of 45 CFR part 74... Federal Acquisition Regulation (FAR) at 48 CFR part 31. (b) Indirect costs. Unless restricted by...

  13. 10 CFR 600.127 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... recipient, there is a set of Federal principles for determining allowable costs. Allowability of costs shall... incurred by hospitals is determined in accordance with the provisions of Appendix E of 45 CFR part 74... Federal Acquisition Regulation (FAR) at 48 CFR part 31. (b) Indirect costs. Unless restricted by...

  14. 30 CFR 1206.160 - Operating allowances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Operating allowances. 1206.160 Section 1206.160 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT VALUATION Federal Gas § 1206.160 Operating allowances. Notwithstanding any...

  15. 30 CFR 1206.160 - Operating allowances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Operating allowances. 1206.160 Section 1206.160 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT VALUATION Federal Gas § 1206.160 Operating allowances. Notwithstanding any...

  16. 30 CFR 1206.160 - Operating allowances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Operating allowances. 1206.160 Section 1206.160 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE PRODUCT VALUATION Federal Gas § 1206.160 Operating allowances. Notwithstanding any...

  17. The Role of Allowances in Adolescent Socialization.

    ERIC Educational Resources Information Center

    Miller, Joanne; Yung, Susan

    1990-01-01

    Examines high school student perceptions of allowances and the conditions under which they are received. Finds that, contrary to adult conceptions, students perceive allowances as an entitlement or earned income rather than as an educational opportunity promoting financial decision making and money management. (FMW)

  18. 45 CFR 602.22 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION UNIFORM...) The allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to...

  19. 45 CFR 602.22 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION UNIFORM...) The allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to...

  20. 45 CFR 602.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION UNIFORM...) The allowable costs of the grantees, subgrantees and cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to...

  1. Tomato SlRbohB, a member of the NADPH oxidase family, is required for disease resistance against Botrytis cinerea and tolerance to drought stress.

    PubMed

    Li, Xiaohui; Zhang, Huijuan; Tian, Limei; Huang, Lei; Liu, Shixia; Li, Dayong; Song, Fengming

    2015-01-01

    NADPH oxidases (also known as respiratory burst oxidase homologs, Rbohs) are key enzymes that catalyze the generation of reactive oxygen species (ROS) in plants. In the present study, eight SlRboh genes were identified in tomato and their possible involvement in resistance to Botrytis cinerea and drought tolerance was examined. Expression of SlRbohs was induced by B. cinerea and Pseudomonas syringae pv. tomato but displayed distinct patterns. Virus-induced gene silencing based silencing of SlRbohB resulted in reduced resistance to B. cinerea but silencing of other SlRbohs did not affect the resistance. Compared to non-silenced plants, the SlRbohB-silenced plants accumulated more ROS and displayed attenuated expression of defense genes after infection with B. cinerea. Silencing of SlRbohB also suppressed flg22-induced ROS burst and the expression of SlLrr22, a marker gene related to PAMP-triggered immunity (PTI). Transient expression of SlRbohB in Nicotiana benthamiana led to enhanced resistance to B. cinerea. Furthermore, silencing of SlRbohB resulted in decreased drought tolerance, accelerated water loss in leaves and the altered expression of drought-responsive genes. Our data demonstrate that SlRbohB positively regulates the resistance to B. cinerea, flg22-induced PTI, and drought tolerance in tomato. PMID:26157450

  2. Identification of amino acids of the beet necrotic yellow vein virus p25 protein required for induction of the resistance response in leaves of Beta vulgaris plants.

    PubMed

    Chiba, Soutaro; Miyanishi, Masaki; Andika, Ida Bagus; Kondo, Hideki; Tamada, Tetsuo

    2008-05-01

    The RNA3-encoded p25 protein of beet necrotic yellow vein virus (BNYVV) is responsible for the production of rhizomania symptoms of sugar beet roots (Beta vulgaris subsp. vulgaris). Here, it was found that the presence of the p25 protein is also associated with the resistance response in rub-inoculated leaves of sugar beet and wild beet (Beta vulgaris subsp. maritima) plants. The resistance phenotype displayed a range of symptoms from no visible lesions to necrotic or greyish lesions at the inoculation site, and only very low levels of virus and viral RNA accumulated. The susceptible phenotype showed large, bright yellow lesions and developed high levels of virus accumulation. In roots after Polymyxa betae vector inoculation, however, no drastic differences in virus and viral RNA accumulation levels were found between plants with susceptible and resistant phenotypes, except at an early stage of infection. There was a genotype-specific interaction between BNYVV strains and two selected wild beet lines (MR1 and MR2) and sugar beet cultivars. Sequence analysis of natural BNYVV isolates and site-directed mutagenesis of the p25 protein revealed that 3 aa residues at positions 68, 70 and 179 are important in determining the resistance phenotype, and that host-genotype specificity is controlled by single amino acid changes at position 68. The mechanism of the occurrence of resistance-breaking BNYVV strains is discussed.

  3. The Arabidopsis downy mildew resistance gene, RPP13-Nd, functions independently of NDR1 and EDS1 and does not require the accumulation of salicylic acid.

    PubMed

    Bittner-Eddy, P D; Beynon, J L

    2001-03-01

    RPP13-Nd-mediated resistance prevents parasitism by five isolates of Peronospora parasitica (At) in a transgenic Arabidopsis. Columbia background. We tested the effect of a number of known disease resistance mutations on the RPP13-Nd function and found that resistance remained unaltered in plants carrying mutations in either EDS1 or NDR1 and in double ndr1-1/eds1-2 mutant lines. Furthermore, we found that pbs2, pad4-1, npr1-1, and rps5-1, which compromise resistance to a number of P. parasitica (At) isolates, had no affect on RPP13-Nd function. In addition, RPP13-Nd-mediated resistance remained unchanged in a background of salicylic acid depletion (nahG). We conclude that RPP13-Nd is the first Arabidopsis R gene product reported to act via a novel signaling pathway that is independent of salicylic acid-mediated responses and is completely independent of NDR1 and EDS1.

  4. Tomato SlRbohB, a member of the NADPH oxidase family, is required for disease resistance against Botrytis cinerea and tolerance to drought stress

    PubMed Central

    Li, Xiaohui; Zhang, Huijuan; Tian, Limei; Huang, Lei; Liu, Shixia; Li, Dayong; Song, Fengming

    2015-01-01

    NADPH oxidases (also known as respiratory burst oxidase homologs, Rbohs) are key enzymes that catalyze the generation of reactive oxygen species (ROS) in plants. In the present study, eight SlRboh genes were identified in tomato and their possible involvement in resistance to Botrytis cinerea and drought tolerance was examined. Expression of SlRbohs was induced by B. cinerea and Pseudomonas syringae pv. tomato but displayed distinct patterns. Virus-induced gene silencing based silencing of SlRbohB resulted in reduced resistance to B. cinerea but silencing of other SlRbohs did not affect the resistance. Compared to non-silenced plants, the SlRbohB-silenced plants accumulated more ROS and displayed attenuated expression of defense genes after infection with B. cinerea. Silencing of SlRbohB also suppressed flg22-induced ROS burst and the expression of SlLrr22, a marker gene related to PAMP-triggered immunity (PTI). Transient expression of SlRbohB in Nicotiana benthamiana led to enhanced resistance to B. cinerea. Furthermore, silencing of SlRbohB resulted in decreased drought tolerance, accelerated water loss in leaves and the altered expression of drought-responsive genes. Our data demonstrate that SlRbohB positively regulates the resistance to B. cinerea, flg22-induced PTI, and drought tolerance in tomato. PMID:26157450

  5. Family allowances and fertility: socioeconomic differences.

    PubMed

    Schellekens, Jona

    2009-08-01

    This article explores socioeconomic differences in the effect of family allowances on fertility. Although several studies have examined the relationship between cash benefits and fertility, few studies have addressed the possible differential effects of cash benefits on families of different income or education levels. I reconstructed the birth histories of women in the past two Israeli censuses of 1983 and 1995 to study socioeconomic differences in the effect of family allowances up to the seventh parity. The results indicate that family allowances have a significant effect at every parity. Using female education as an indicator of socioeconomic status, I find that socioeconomic status is a significant modifier of the effect of family allowances. Family allowances seem to have a relatively large impact on more-educated women.

  6. Role of Resistant Starch in Improving Gut Health, Adiposity, and Insulin Resistance1234

    PubMed Central

    Keenan, Michael J; Zhou, June; Hegsted, Maren; Pelkman, Christine; Durham, Holiday A; Coulon, Diana B; Martin, Roy J

    2015-01-01

    The realization that low–glycemic index diets were formulated using resistant starch led to more than a decade of research on the health effects of resistant starch. Determination of the metabolizable energy of the resistant starch product allowed for the performance of isocaloric studies. Fermentation of resistant starch in rodent studies results in what appears to be a healthier gut, demonstrated by increased amounts of short-chain fatty acids, an apparent positive change in the microbiota, and increased gene expression for gene products involved in normal healthy proliferation and apoptosis of potential cancer cells. Additionally, consumption of resistant starch was associated with reduced abdominal fat and improved insulin sensitivity. Increased serum glucagon-like peptide 1 (GLP-1) likely plays a role in promoting these health benefits. One rodent study that did not use isocaloric diets demonstrated that the use of resistant starch at 8% of the weight of the diet reduced body fat. This appears to be approximately equivalent to the human fiber requirement. In human subjects, insulin sensitivity is increased with the feeding of resistant starch. However, only 1 of several studies reports an increase in serum GLP-1 associated with resistant starch added to the diet. This means that other mechanisms, such as increased intestinal gluconeogenesis or increased adiponectin, may be involved in the promotion of improved insulin sensitivity. Future research may confirm that there will be improved health if human individuals consume the requirement for dietary fiber and a large amount of the fiber is fermentable. PMID:25770258

  7. Role of resistant starch in improving gut health, adiposity, and insulin resistance.

    PubMed

    Keenan, Michael J; Zhou, June; Hegsted, Maren; Pelkman, Christine; Durham, Holiday A; Coulon, Diana B; Martin, Roy J

    2015-03-01

    The realization that low-glycemic index diets were formulated using resistant starch led to more than a decade of research on the health effects of resistant starch. Determination of the metabolizable energy of the resistant starch product allowed for the performance of isocaloric studies. Fermentation of resistant starch in rodent studies results in what appears to be a healthier gut, demonstrated by increased amounts of short-chain fatty acids, an apparent positive change in the microbiota, and increased gene expression for gene products involved in normal healthy proliferation and apoptosis of potential cancer cells. Additionally, consumption of resistant starch was associated with reduced abdominal fat and improved insulin sensitivity. Increased serum glucagon-like peptide 1 (GLP-1) likely plays a role in promoting these health benefits. One rodent study that did not use isocaloric diets demonstrated that the use of resistant starch at 8% of the weight of the diet reduced body fat. This appears to be approximately equivalent to the human fiber requirement. In human subjects, insulin sensitivity is increased with the feeding of resistant starch. However, only 1 of several studies reports an increase in serum GLP-1 associated with resistant starch added to the diet. This means that other mechanisms, such as increased intestinal gluconeogenesis or increased adiponectin, may be involved in the promotion of improved insulin sensitivity. Future research may confirm that there will be improved health if human individuals consume the requirement for dietary fiber and a large amount of the fiber is fermentable.

  8. 12/15-Lipoxygenase Is Required for the Early Onset of High Fat Diet-Induced Adipose Tissue Inflammation and Insulin Resistance in Mice

    PubMed Central

    Sears, Dorothy D.; Miles, Philip D.; Chapman, Justin; Ofrecio, Jachelle M.; Almazan, Felicidad; Thapar, Divya; Miller, Yury I.

    2009-01-01

    Background Recent understanding that insulin resistance is an inflammatory condition necessitates searching for genes that regulate inflammation in insulin sensitive tissues. 12/15-lipoxygenase (12/15LO) regulates the expression of proinflammatory cytokines and chemokines and is implicated in the early development of diet-induced atherosclerosis. Thus, we tested the hypothesis that 12/15LO is involved in the onset of high fat diet (HFD)-induced insulin resistance. Methodology/Principal Findings Cells over-expressing 12/15LO secreted two potent chemokines, MCP-1 and osteopontin, implicated in the development of insulin resistance. We assessed adipose tissue inflammation and whole body insulin resistance in wild type (WT) and 12/15LO knockout (KO) mice after 2–4 weeks on HFD. In adipose tissue from WT mice, HFD resulted in recruitment of CD11b+, F4/80+ macrophages and elevated protein levels of the inflammatory markers IL-1β, IL-6, IL-10, IL-12, IFNγ, Cxcl1 and TNFα. Remarkably, adipose tissue from HFD-fed 12/15LO KO mice was not infiltrated by macrophages and did not display any increase in the inflammatory markers compared to adipose tissue from normal chow-fed mice. WT mice developed severe whole body (hepatic and skeletal muscle) insulin resistance after HFD, as measured by hyperinsulinemic euglycemic clamp. In contrast, 12/15LO KO mice exhibited no HFD-induced change in insulin-stimulated glucose disposal rate or hepatic glucose output during clamp studies. Insulin-stimulated Akt phosphorylation in muscle tissue from HFD-fed mice was significantly greater in 12/15LO KO mice than in WT mice. Conclusions These results demonstrate that 12/15LO mediates early stages of adipose tissue inflammation and whole body insulin resistance induced by high fat feeding. PMID:19787041

  9. Dual disease resistance mediated by the immune receptor Cf-2 in tomato requires a common virulence target of a fungus and a nematode

    PubMed Central

    Lozano-Torres, Jose L.; Wilbers, Ruud H. P.; Gawronski, Piotr; Boshoven, Jordi C.; Finkers-Tomczak, Anna; Cordewener, Jan H. G.; America, Antoine H. P.; Overmars, Hein A.; Van ‘t Klooster, John W.; Baranowski, Lukasz; Sobczak, Miroslaw; Ilyas, Muhammad; van der Hoorn, Renier A. L.; Schots, Arjen; de Wit, Pierre J. G. M.; Bakker, Jaap; Goverse, Aska; Smant, Geert

    2012-01-01

    Plants lack the seemingly unlimited receptor diversity of a somatic adaptive immune system as found in vertebrates and rely on only a relatively small set of innate immune receptors to resist a myriad of pathogens. Here, we show that disease-resistant tomato plants use an efficient mechanism to leverage the limited nonself recognition capacity of their innate immune system. We found that the extracellular plant immune receptor protein Cf-2 of the red currant tomato (Solanum pimpinellifolium) has acquired dual resistance specificity by sensing perturbations in a common virulence target of two independently evolved effectors of a fungus and a nematode. The Cf-2 protein, originally identified as a monospecific immune receptor for the leaf mold fungus Cladosporium fulvum, also mediates disease resistance to the root parasitic nematode Globodera rostochiensis pathotype Ro1-Mierenbos. The Cf-2–mediated dual resistance is triggered by effector-induced perturbations of the apoplastic Rcr3pim protein of S. pimpinellifolium. Binding of the venom allergen-like effector protein Gr-VAP1 of G. rostochiensis to Rcr3pim perturbs the active site of this papain-like cysteine protease. In the absence of the Cf-2 receptor, Rcr3pim increases the susceptibility of tomato plants to G. rostochiensis, thus showing its role as a virulence target of these nematodes. Furthermore, both nematode infection and transient expression of Gr-VAP1 in tomato plants harboring Cf-2 and Rcr3pim trigger a defense-related programmed cell death in plant cells. Our data demonstrate that monitoring host proteins targeted by multiple pathogens broadens the spectrum of disease resistances mediated by single plant immune receptors. PMID:22675118

  10. 38 CFR 3.810 - Clothing allowance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... a wheelchair) because of such disability and such disability is the loss or loss of use of a hand or... wheelchair. (b) Effective August 1, 1972, the initial lump sum clothing allowance is due and payable...

  11. 38 CFR 3.810 - Clothing allowance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... a wheelchair) because of such disability and such disability is the loss or loss of use of a hand or... wheelchair. (b) Effective August 1, 1972, the initial lump sum clothing allowance is due and payable...

  12. Higher Education Tax Allowances: An Analysis

    ERIC Educational Resources Information Center

    Leslie, Larry L.

    1976-01-01

    Tax allowances are receiving renewed attention at the federal level. Various forms are evaluated that would aid middle-income students and private institutions, and specific bills and proposals are examined. (Editor/LBH)

  13. EmrA1 Membrane Fusion Protein of Francisella tularensis LVS is required for Resistance to Oxidative Stress, Intramacrophage Survival and Virulence in Mice

    PubMed Central

    Ma, Zhuo; Banik, Sukalyani; Rane, Harshita; Mora, Vanessa T.; Rabadi, Seham M.; Doyle, Christopher R.; Thanassi, David G.; Bakshi, Chandra Shekhar; Malik, Meenakshi

    2014-01-01

    Francisella tularensis is a Category A Biodefense agent that causes a fatal human disease known as tularemia. The pathogenicity of F. tularensis depends on its ability to persist inside host immune cells primarily by resisting an attack from host-generated reactive oxygen and nitrogen species (ROS/RNS). Based on the ability of F. tularensis to resist high ROS/RNS levels, we have hypothesized that additional unknown factors act in conjunction with known antioxidant defenses to render ROS resistance. By screening a transposon insertion library of F. tularensis LVS in the presence of hydrogen peroxide, we have identified an oxidant sensitive mutant in putative EmrA1 (FTL_0687) secretion protein. The results demonstrate that the emrA1 mutant is highly sensitive to oxidants and several antimicrobial agents, and exhibits diminished intramacrophage growth that can be restored to wild type F. tularensis LVS levels either by transcomplementation, inhibition of ROS generation, or infection in NADPH oxidase deficient (gp91Phox−/−) macrophages. The emrA1 mutant is attenuated for virulence, which is restored by infection in gp91Phox−/− mice. Further, EmrA1 contributes to oxidative stress resistance by affecting secretion of Francisella antioxidant enzymes SodB and KatG. This study exposes unique links between transporter activity and the antioxidant defense mechanisms of F. tularensis. PMID:24397487

  14. Pseudomonas lini Strain ZBG1 Revealed Carboxylic Acid Utilization and Copper Resistance Features Required for Adaptation to Vineyard Soil Environment: A Draft Genome Analysis

    PubMed Central

    Chan, Kok-Gan; Chong, Teik-Min; Adrian, Tan-Guan-Sheng; Kher, Heng Leong; Grandclément, Catherine; Faure, Denis; Yin, Wai-Fong; Dessaux, Yves; Hong, Kar-Wai

    2016-01-01

    Pseudomonas lini strain ZBG1 was isolated from the soil of vineyard in Zellenberg, France and the draft genome was reported in this study. Bioinformatics analyses of the genome revealed presence of genes encoding tartaric and malic acid utilization as well as copper resistance that correspond to the adaptation this strain in vineyard soil environment. PMID:27512520

  15. Characterization of an Arabidopsis-Phytophthora pathosystem: resistance requires a functional PAD2 gene and is independent of salicylic acid, ethylene and jasmonic acid signalling.

    PubMed

    Roetschi, A; Si-Ammour, A; Belbahri, L; Mauch, F; Mauch-Mani, B

    2001-11-01

    Arabidopsis accessions were screened with isolates of Phytophthora porri originally isolated from other crucifer species. The described Arabidopsis-Phytophthora pathosystem shows the characteristics of a facultative biotrophic interaction similar to that seen in agronomically important diseases caused by Phytophthora species. In susceptible accessions, extensive colonization of the host tissue occurred and sexual and asexual spores were formed. In incompatible combinations, the plants reacted with a hypersensitive response (HR) and the formation of papillae at the sites of attempted penetration. Defence pathway mutants such as jar1 (jasmonic acid-insensitive), etr1 (ethylene receptor mutant) and ein2 (ethylene-insensitive) remained resistant towards P. porri. However, pad2, a mutant with reduced production of the phytoalexin camalexin, was hyper-susceptible. The accumulation of salicylic acid (SA) and PR1 protein was strongly reduced in pad2. Surprisingly, this lack of SA accumulation does not appear to be the cause of the hyper-susceptibility because interference with SA signalling in nahG plants or sid2 or npr1 mutants had only a minor effect on resistance. In addition, the functional SA analogue benzothiadiazol (BTH) did not induce resistance in susceptible plants including pad2. Similarly, the complete blockage of camalexin biosynthesis in pad3 did not cause susceptibility. Resistance of Arabidopsis against P. porri appears to depend on unknown defence mechanisms that are under the control of PAD2.

  16. Identification and Characterization of a Novel Issatchenkia orientalis GPI-Anchored Protein, IoGas1, Required for Resistance to Low pH and Salt Stress

    PubMed Central

    Matsushika, Akinori; Negi, Kanako; Suzuki, Toshihiro; Goshima, Tetsuya; Hoshino, Tamotsu

    2016-01-01

    The use of yeasts tolerant to acid (low pH) and salt stress is of industrial importance for several bioproduction processes. To identify new candidate genes having potential roles in low-pH tolerance, we screened an expression genomic DNA library of a multiple-stress-tolerant yeast, Issatchenkia orientalis (Pichia kudriavzevii), for clones that allowed Saccharomyces cerevisiae cells to grow under highly acidic conditions (pH 2.0). A genomic DNA clone containing two putative open reading frames was obtained, of which the putative protein-coding gene comprising 1629 bp was retransformed into the host. This transformant grew significantly at pH 2.0, and at pH 2.5 in the presence of 7.5% Na2SO4. The predicted amino acid sequence of this new gene, named I. orientalis GAS1 (IoGAS1), was 60% identical to the S. cerevisiae Gas1 protein, a glycosylphosphatidylinositol-anchored protein essential for maintaining cell wall integrity, and 58–59% identical to Candida albicans Phr1 and Phr2, pH-responsive proteins implicated in cell wall assembly and virulence. Northern hybridization analyses indicated that, as for the C. albicans homologs, IoGAS1 expression was pH-dependent, with expression increasing with decreasing pH (from 4.0 to 2.0) of the medium. These results suggest that IoGAS1 represents a novel pH-regulated system required for the adaptation of I. orientalis to environments of diverse pH. Heterologous expression of IoGAS1 complemented the growth and morphological defects of a S. cerevisiae gas1Δ mutant, demonstrating that IoGAS1 and the corresponding S. cerevisiae gene play similar roles in cell wall biosynthesis. Site-directed mutagenesis experiments revealed that two conserved glutamate residues (E161 and E262) in the IoGas1 protein play a crucial role in yeast morphogenesis and tolerance to low pH and salt stress. Furthermore, overexpression of IoGAS1 in S. cerevisiae remarkably improved the ethanol fermentation ability at pH 2.5, and at pH 2.0 in the presence of

  17. Identification and Characterization of a Novel Issatchenkia orientalis GPI-Anchored Protein, IoGas1, Required for Resistance to Low pH and Salt Stress.

    PubMed

    Matsushika, Akinori; Negi, Kanako; Suzuki, Toshihiro; Goshima, Tetsuya; Hoshino, Tamotsu

    2016-01-01

    The use of yeasts tolerant to acid (low pH) and salt stress is of industrial importance for several bioproduction processes. To identify new candidate genes having potential roles in low-pH tolerance, we screened an expression genomic DNA library of a multiple-stress-tolerant yeast, Issatchenkia orientalis (Pichia kudriavzevii), for clones that allowed Saccharomyces cerevisiae cells to grow under highly acidic conditions (pH 2.0). A genomic DNA clone containing two putative open reading frames was obtained, of which the putative protein-coding gene comprising 1629 bp was retransformed into the host. This transformant grew significantly at pH 2.0, and at pH 2.5 in the presence of 7.5% Na2SO4. The predicted amino acid sequence of this new gene, named I. orientalis GAS1 (IoGAS1), was 60% identical to the S. cerevisiae Gas1 protein, a glycosylphosphatidylinositol-anchored protein essential for maintaining cell wall integrity, and 58-59% identical to Candida albicans Phr1 and Phr2, pH-responsive proteins implicated in cell wall assembly and virulence. Northern hybridization analyses indicated that, as for the C. albicans homologs, IoGAS1 expression was pH-dependent, with expression increasing with decreasing pH (from 4.0 to 2.0) of the medium. These results suggest that IoGAS1 represents a novel pH-regulated system required for the adaptation of I. orientalis to environments of diverse pH. Heterologous expression of IoGAS1 complemented the growth and morphological defects of a S. cerevisiae gas1Δ mutant, demonstrating that IoGAS1 and the corresponding S. cerevisiae gene play similar roles in cell wall biosynthesis. Site-directed mutagenesis experiments revealed that two conserved glutamate residues (E161 and E262) in the IoGas1 protein play a crucial role in yeast morphogenesis and tolerance to low pH and salt stress. Furthermore, overexpression of IoGAS1 in S. cerevisiae remarkably improved the ethanol fermentation ability at pH 2.5, and at pH 2.0 in the presence of

  18. 15 CFR 24.22 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... than a hospital and an organization named in OBM Circular A-122 as not subject to that circular 48 CFR... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Allowable costs. 24.22 Section 24.22... Administration § 24.22 Allowable costs. (a) Limitation on use of funds. Grant funds may be used only for: (1)...

  19. Regulatory treatment of allowances and compliance costs

    SciTech Connect

    Rose, K.

    1993-07-01

    The Clean Air Act Amendments of 1990 (CAAA) established a national emission allowance trading system, a market-based form of environmental regulation designed to reduce and limit sulfur dioxide emissions. However, the allowance trading system is being applied primarily to an economically regulated electric utility industry. The combining of the new form of environmental regulation and economic regulation of electric utilities has raised a number of questions including what the role should be of the federal and state utility regulating commissions and how those actions will affect the decision making process of the utilities and the allowance market. There are several dimensions to the regulatory problems that commissions face. Allowances and utility compliance expenditures have implications for least-cost/IPR (integrated resource planning), prudence review procedures, holding company and multistate utility regulation and ratemaking treatment. The focus of this paper is on the ratemaking treatment. The following topics are covered: ratemaking treatment of allowances and compliance costs; Traditional cost-recovery mechanisms; limitations to the traditional approach; traditional approach and the allowance trading market; market-based cost recovery mechanisms; methods of determining the benchmark; determining the split between ratepayers and the utility; other regulatory approaches; limitations of incentive mechanisms.

  20. The WRKY45-2 WRKY13 WRKY42 Transcriptional Regulatory Cascade Is Required for Rice Resistance to Fungal Pathogen1[OPEN

    PubMed Central

    Cheng, Hongtao; Liu, Hongbo; Deng, Yong; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2015-01-01

    Blast caused by fungal Magnaporthe oryzae is a devastating disease of rice (Oryza sativa) worldwide, and this fungus also infects barley (Hordeum vulgare). At least 11 rice WRKY transcription factors have been reported to regulate rice response to M. oryzae either positively or negatively. However, the relationships of these WRKYs in the rice defense signaling pathway against M. oryzae are unknown. Previous studies have revealed that rice WRKY13 (as a transcriptional repressor) and WRKY45-2 enhance resistance to M. oryzae. Here, we show that rice WRKY42, functioning as a transcriptional repressor, suppresses resistance to M. oryzae. WRKY42-RNA interference (RNAi) and WRKY42-overexpressing (oe) plants showed increased resistance and susceptibility to M. oryzae, accompanied by increased or reduced jasmonic acid (JA) content, respectively, compared with wild-type plants. JA pretreatment enhanced the resistance of WRKY42-oe plants to M. oryzae. WRKY13 directly suppressed WRKY42. WRKY45-2, functioning as a transcriptional activator, directly activated WRKY13. In addition, WRKY13 directly suppressed WRKY45-2 by feedback regulation. The WRKY13-RNAi WRKY45-2-oe and WRKY13-oe WRKY42-oe double transgenic lines showed increased susceptibility to M. oryzae compared with WRKY45-2-oe and WRKY13-oe plants, respectively. These results suggest that the three WRKYs form a sequential transcriptional regulatory cascade. WRKY42 may negatively regulate rice response to M. oryzae by suppressing JA signaling-related genes, and WRKY45-2 transcriptionally activates WRKY13, whose encoding protein in turn transcriptionally suppresses WRKY42 to regulate rice resistance to M. oryzae. PMID:25624395

  1. 34 CFR 644.30 - What are allowable costs?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... program are in 34 CFR part 74, subpart Q. Allowable costs include the following if they are reasonably...) Purchase of testing materials. (c) Fees required for college admissions of entrance examinations if— (1) A... site of the grantee; and (2) The rented space is not owned by the grantee. (f) Purchase of...

  2. 7 CFR 3560.205 - Rent and utility allowance changes.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... a fully documented request to the Agency to effect any rent or utility allowance change. (1... change requests in conjunction with the annual budget submission as required under § 3560.303(d). The... the start of the season for seasonally occupied farm labor housing. However, the Agency will...

  3. 7 CFR 3560.205 - Rent and utility allowance changes.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... a fully documented request to the Agency to effect any rent or utility allowance change. (1... change requests in conjunction with the annual budget submission as required under § 3560.303(d). The... the start of the season for seasonally occupied farm labor housing. However, the Agency will...

  4. 7 CFR 3560.205 - Rent and utility allowance changes.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... a fully documented request to the Agency to effect any rent or utility allowance change. (1... change requests in conjunction with the annual budget submission as required under § 3560.303(d). The... the start of the season for seasonally occupied farm labor housing. However, the Agency will...

  5. 7 CFR 3560.205 - Rent and utility allowance changes.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... a fully documented request to the Agency to effect any rent or utility allowance change. (1... change requests in conjunction with the annual budget submission as required under § 3560.303(d). The... the start of the season for seasonally occupied farm labor housing. However, the Agency will...

  6. 40 CFR 35.2205 - Maximum allowable project cost.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... adjustments for differing site conditions will be exempt, provided the requirements of 40 CFR part 35, subpart... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Maximum allowable project cost. 35.2205 Section 35.2205 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER...

  7. 40 CFR 35.2205 - Maximum allowable project cost.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... adjustments for differing site conditions will be exempt, provided the requirements of 40 CFR part 35, subpart... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Maximum allowable project cost. 35.2205 Section 35.2205 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER...

  8. 40 CFR 35.2205 - Maximum allowable project cost.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... adjustments for differing site conditions will be exempt, provided the requirements of 40 CFR part 35, subpart... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Maximum allowable project cost. 35.2205 Section 35.2205 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER...

  9. 40 CFR 35.2205 - Maximum allowable project cost.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... adjustments for differing site conditions will be exempt, provided the requirements of 40 CFR part 35, subpart... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Maximum allowable project cost. 35.2205 Section 35.2205 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER...

  10. 14 CFR § 1260.127 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Allowable costs. § 1260.127 Section § 1260.127 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE... Higher Education, Hospitals, and Other Non-Profit Organizations Post-Award Requirements...

  11. 48 CFR 31.201-2 - Determining allowability.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... principles in this subpart are mandatory unless the contract is CAS-covered (see 48 CFR 9903). Business units... the following requirements: (1) Reasonableness. (2) Allocability. (3) Standards promulgated by the CAS... selected CAS and limit the allowability of costs to the amounts determined using the criteria in...

  12. 48 CFR 31.201-2 - Determining allowability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... principles in this subpart are mandatory unless the contract is CAS-covered (see 48 CFR 9903). Business units... the following requirements: (1) Reasonableness. (2) Allocability. (3) Standards promulgated by the CAS... selected CAS and limit the allowability of costs to the amounts determined using the criteria in...

  13. 48 CFR 31.201-2 - Determining allowability.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... principles in this subpart are mandatory unless the contract is CAS-covered (see 48 CFR 9903). Business units... the following requirements: (1) Reasonableness. (2) Allocability. (3) Standards promulgated by the CAS... selected CAS and limit the allowability of costs to the amounts determined using the criteria in...

  14. 40 CFR 264.113 - Closure; time allowed for closure.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... health and the environment, including compliance with all applicable permit requirements. (b) The owner... (2) He has taken and will continue to take all steps to prevent threats to human health and the... Administrator may allow an owner or operator to receive only non-hazardous wastes in a landfill, land...

  15. 40 CFR 264.113 - Closure; time allowed for closure.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... health and the environment, including compliance with all applicable permit requirements. (b) The owner... (2) He has taken and will continue to take all steps to prevent threats to human health and the... Administrator may allow an owner or operator to receive only non-hazardous wastes in a landfill, land...

  16. Analysis of Student Loan Special Rate Allowances and Servicing Costs.

    ERIC Educational Resources Information Center

    Technology Management, Inc., Cambridge, MA.

    This document addresses two separate, though related aspects of the operation of the Guaranteed Student Loan Program (GSLP): (1) the mechanism for setting the special rate allowance (SRA); and (2) the effect of the operating requirements of the program on lender servicing costs. The study develops recommendations for improving both aspects of the…

  17. [Resistant fungi].

    PubMed

    Vehreschild, M J G T; Cornely, O A

    2015-11-01

    Particularly in the area of hematology/oncology and intensive care medicine, infections due to resistant fungi are to be expected. Emergence of resistance in fungi is a less dynamic process than in bacteria; it can, however, have an equally important impact on treatment strategies. In the following article, the most important resistance patterns of yeasts and molds (Candida albicans , Aspergillus fumigatus, the order Mucorales and the genus Fusarium) will be presented and discussed. Their diagnosis mostly being based on blood cultures, resistance testing for yeasts is usually readily available. Culture-based therapeutic adjustments in mold infections are, however, only rarely possible, as most antifungal therapies for these infections are initiated on an empirical basis after identification of typical infiltrates on a CT scan. Response to therapy is then evaluated on the basis of clinical signs and symptoms in combination with follow-up CT scans. In case of therapeutic failure or appearance of suspicious infiltrates under antifungal prophylaxis, an open or CT-guided biopsy is recommended to allow efficient adaptation of antifungal treatment. In individual cases, particularly in patients diagnosed with mucormycosis, resection of the focus of infection may be necessary to achieve a satisfactory treatment response.

  18. Protein Requirements during Aging.

    PubMed

    Courtney-Martin, Glenda; Ball, Ronald O; Pencharz, Paul B; Elango, Rajavel

    2016-01-01

    Protein recommendations for elderly, both men and women, are based on nitrogen balance studies. They are set at 0.66 and 0.8 g/kg/day as the estimated average requirement (EAR) and recommended dietary allowance (RDA), respectively, similar to young adults. This recommendation is based on single linear regression of available nitrogen balance data obtained at test protein intakes close to or below zero balance. Using the indicator amino acid oxidation (IAAO) method, we estimated the protein requirement in young adults and in both elderly men and women to be 0.9 and 1.2 g/kg/day as the EAR and RDA, respectively. This suggests that there is no difference in requirement on a gender basis or on a per kg body weight basis between younger and older adults. The requirement estimates however are ~40% higher than the current protein recommendations on a body weight basis. They are also 40% higher than our estimates in young men when calculated on the basis of fat free mass. Thus, current recommendations may need to be re-assessed. Potential rationale for this difference includes a decreased sensitivity to dietary amino acids and increased insulin resistance in the elderly compared with younger individuals. PMID:27529275

  19. Protein Requirements during Aging

    PubMed Central

    Courtney-Martin, Glenda; Ball, Ronald O.; Pencharz, Paul B.; Elango, Rajavel

    2016-01-01

    Protein recommendations for elderly, both men and women, are based on nitrogen balance studies. They are set at 0.66 and 0.8 g/kg/day as the estimated average requirement (EAR) and recommended dietary allowance (RDA), respectively, similar to young adults. This recommendation is based on single linear regression of available nitrogen balance data obtained at test protein intakes close to or below zero balance. Using the indicator amino acid oxidation (IAAO) method, we estimated the protein requirement in young adults and in both elderly men and women to be 0.9 and 1.2 g/kg/day as the EAR and RDA, respectively. This suggests that there is no difference in requirement on a gender basis or on a per kg body weight basis between younger and older adults. The requirement estimates however are ~40% higher than the current protein recommendations on a body weight basis. They are also 40% higher than our estimates in young men when calculated on the basis of fat free mass. Thus, current recommendations may need to be re-assessed. Potential rationale for this difference includes a decreased sensitivity to dietary amino acids and increased insulin resistance in the elderly compared with younger individuals. PMID:27529275

  20. Resistance-resistant antibiotics.

    PubMed

    Oldfield, Eric; Feng, Xinxin

    2014-12-01

    New antibiotics are needed because drug resistance is increasing while the introduction of new antibiotics is decreasing. We discuss here six possible approaches to develop 'resistance-resistant' antibiotics. First, multitarget inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy owing to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, repurposing existing drugs can lead to combinations of multitarget therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and, in some cases, suggest that sensitivity to existing antibiotics may be restored in otherwise drug-resistant organisms.

  1. 40 CFR 258.74 - Allowable mechanisms.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... second half of the corrective action period), CV is the current value of the trust fund, and Y is the... waste management facilities under this part 258, cost estimates required for UIC facilities under 40 CFR... under 40 CFR part 280, if applicable, cost estimates required for PCB storage facilities under 40...

  2. 40 CFR 258.74 - Allowable mechanisms.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...; or (B) The owner or operator must satisfy each of the following financial ratios based on the owner... to the financial ratios required by paragraph (f)(1)(i)(B) of this section, if applicable, and the... waste management facilities under this part 258, cost estimates required for UIC facilities under 40...

  3. Quantum theory allows for absolute maximal contextuality

    NASA Astrophysics Data System (ADS)

    Amaral, Barbara; Cunha, Marcelo Terra; Cabello, Adán

    2015-12-01

    Contextuality is a fundamental feature of quantum theory and a necessary resource for quantum computation and communication. It is therefore important to investigate how large contextuality can be in quantum theory. Linear contextuality witnesses can be expressed as a sum S of n probabilities, and the independence number α and the Tsirelson-like number ϑ of the corresponding exclusivity graph are, respectively, the maximum of S for noncontextual theories and for the theory under consideration. A theory allows for absolute maximal contextuality if it has scenarios in which ϑ /α approaches n . Here we show that quantum theory allows for absolute maximal contextuality despite what is suggested by the examination of the quantum violations of Bell and noncontextuality inequalities considered in the past. Our proof is not constructive and does not single out explicit scenarios. Nevertheless, we identify scenarios in which quantum theory allows for almost-absolute-maximal contextuality.

  4. Using EPA`s allowance tracking system to assess the allowance market

    SciTech Connect

    Dean, M.; Kruger, J.

    1997-12-31

    The development of a credible framework for analyzing private allowance transfers recorded in EPA`s Allowance Tracking System (ATS) is essential for effective assessment of the sulfur dioxide (SO{sub 2}) allowance market. The ATS began recording transfers of allowances in March, 1994, and since then has served as an automated record of allowance holdings and transfers of ownership. Though primarily concerned with determining compliance, the ATS contains details of private allowance transfers representing what is believed to be a significant portion of overall SO{sub 2} allowance market activity. This paper will analyze these private transfers recorded in ATS and will develop relevant categories for classification purposes. The resulting categorization will enable consistent analysis of the SO{sub 2} allowance market and provide substantial insight into the level and type of allowance trading activity under the Acid Rain Program.

  5. A novel strategy to isolate cell-envelope mutants resistant to phage infection: bacteriophage mEp213 requires lipopolysaccharides in addition to FhuA to enter Escherichia coli K-12.

    PubMed

    Reyes-Cortés, Ruth; Martínez-Peñafiel, Eva; Martínez-Pérez, Francisco; de la Garza, Mireya; Kameyama, Luis

    2012-12-01

    We have developed a direct and efficient strategy, based on a three-step method, to select bacterial cell-envelope mutants resistant to bacteriophage infection. Escherichia coli K-12 strain W3110 underwent classical transposon mutagenesis followed by replica plating and selection for mutants resistant to infection by coliphage mEp213. To verify that phage resistance was due to mutations in the cell envelope, we transformed host cells with the viral genome using electroporation and selected those in which virions were subsequently detected in the supernatant. Among the nine mutants resistant to coliphage infection that we selected, six were in the fhuA gene, two were mutated in the waaC gene, and one was mutated in the gmhD gene. The latter two gene products are involved in the synthesis of lipopolysaccharide (LPS). The efficiency of plating and adsorption of phage mEp213 was affected in these mutants. We verified that LPS is required for the efficient infection of phage λ as well. We propose that this mutation-and-selection strategy can be used to find host factors involved in the initial steps of phage infection for any cognate pair of phage and bacteria.

  6. 44 CFR 208.41 - Administrative allowance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Administrative allowance. 208.41 Section 208.41 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE NATIONAL URBAN SEARCH AND RESCUE RESPONSE SYSTEM Response Cooperative Agreements § 208.41...

  7. 7 CFR 3016.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Circular A-122 as not subject to that circular 48 CFR part 31. Contract Cost Principles and Procedures, or... cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to cost-type contractors but not any fee or profit (or...

  8. 49 CFR 18.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... named in OBM Circular A-122 as not subject to that circular 48 CFR part 31. Contract Cost Principles and... of the grantees, subgrantees and cost-type contractors, including allowable costs in the form of payments to fixed-price contractors; and (2) Reasonable fees or profit to cost-type contractors but not...

  9. Manpower Training Allowances: Financial Assistance or Investment?

    ERIC Educational Resources Information Center

    Latour, Georges

    1975-01-01

    The author compares the differing approaches of Germany, Sweden, France, and Australia for providing financial support to adults enrolled in vocational training programs, focusing on training allowances for recurrent education. He concludes that without some governmental maintenance program, it is unlikely that adults can utilize even tuition-free…

  10. 32 CFR 33.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... not subject to that circular 48 CFR part 31. Contract Cost Principles and Procedures, or uniform cost accounting standards that comply with cost principles acceptable to the Federal agency. ... allowable costs) to the grantee or subgrantee. (b) Applicable cost principles. For each kind of...

  11. 32 CFR 32.27 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... contractors is determined in accordance with the provisions of Appendix E to 45 CFR part 74, “Principles for... contractor receiving a. cost-type contract under an assistance award, there is a set of Federal principles... principles applicable to the entity incurring the costs. (b) Governmental organizations. Allowability...

  12. 40 CFR 258.74 - Allowable mechanisms.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... located in the United States amounting to at least the sum of current closure, post-closure care... MUNICIPAL SOLID WASTE LANDFILLS Financial Assurance Criteria § 258.74 Allowable mechanisms. The mechanisms... and examined by a Federal or State agency. A copy of the trust agreement must be placed in...

  13. 40 CFR 258.74 - Allowable mechanisms.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... located in the United States amounting to at least the sum of current closure, post-closure care... MUNICIPAL SOLID WASTE LANDFILLS Financial Assurance Criteria § 258.74 Allowable mechanisms. The mechanisms... and examined by a Federal or State agency. A copy of the trust agreement must be placed in...

  14. 40 CFR 258.74 - Allowable mechanisms.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... located in the United States amounting to at least the sum of current closure, post-closure care... MUNICIPAL SOLID WASTE LANDFILLS Financial Assurance Criteria § 258.74 Allowable mechanisms. The mechanisms... and examined by a Federal or State agency. A copy of the trust agreement must be placed in...

  15. 42 CFR 405.2468 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Allowable costs. 405.2468 Section 405.2468 Public... FEDERAL HEALTH INSURANCE FOR THE AGED AND DISABLED Rural Health Clinic and Federally Qualified Health... 413 of this subchapter. (b) Typical rural health clinic and Federally qualified health center...

  16. 33 CFR 136.217 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.217 Section 136.217 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  17. 33 CFR 136.235 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.235 Section 136.235 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  18. 33 CFR 136.223 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.223 Section 136.223 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  19. 33 CFR 136.211 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.211 Section 136.211 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  20. 33 CFR 136.205 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.205 Section 136.205 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  1. 33 CFR 136.229 - Compensation allowable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Compensation allowable. 136.229 Section 136.229 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND;...

  2. 29 CFR 15.22 - Allowable claims.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... service with the Department and: (l) The damage or loss was not caused wholly or partly by the negligent... the other provisions of this subpart, any claim for damage to, or loss, of personal property incident... authorized places. Claims may be allowable for damage to, or loss of, property arising from fire,...

  3. 33 CFR 136.241 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.241...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.241...

  4. 33 CFR 136.217 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.217...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.217...

  5. 33 CFR 136.205 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.205...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.205...

  6. 33 CFR 136.223 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.223...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.223...

  7. 33 CFR 136.235 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.235...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.235...

  8. 33 CFR 136.229 - Compensation allowable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.229...) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; CLAIMS PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.229...

  9. 29 CFR 15.41 - Allowable claims.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... if the claim is cognizable under the Federal Tort Claims Act (28 U.S.C. 2677). (c) A claim for damage... Secretary of Labor ADMINISTRATIVE CLAIMS UNDER THE FEDERAL TORT CLAIMS ACT AND RELATED STATUTES Claims Arising Out of the Operation of the Job Corps § 15.41 Allowable claims. (a)(1) A claim for damage...

  10. 38 CFR 21.5822 - Subsistence allowance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CFR Sections Affected, which appears in the Finding Aids section of the printed volume and on GPO... will make payments of subsistence allowance on the first day of the month following the month for which... enrollment certification so late that payment cannot be made on the first day of the month following...

  11. 40 CFR 30.27 - Allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Allowable costs. 30.27 Section 30.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM...-recognized Indian tribal governments is determined in accordance with the provisions of OMB Circular...

  12. 40 CFR 30.27 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Allowable costs. 30.27 Section 30.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM...-recognized Indian tribal governments is determined in accordance with the provisions of OMB Circular...

  13. 40 CFR 30.27 - Allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Allowable costs. 30.27 Section 30.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM...-recognized Indian tribal governments is determined in accordance with the provisions of OMB Circular...

  14. 40 CFR 30.27 - Allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Allowable costs. 30.27 Section 30.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM...-recognized Indian tribal governments is determined in accordance with the provisions of OMB Circular...

  15. 30 CFR 1220.012 - Overhead allowance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Overhead allowance. 1220.012 Section 1220.012 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES... under § 1220.011(c) that are salvaged, returned, or used for the benefit of non-NPSL operations....

  16. 30 CFR 1220.012 - Overhead allowance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Overhead allowance. 1220.012 Section 1220.012 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES... under § 1220.011(c) that are salvaged, returned, or used for the benefit of non-NPSL operations....

  17. 30 CFR 1220.012 - Overhead allowance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Overhead allowance. 1220.012 Section 1220.012 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES... under § 1220.011(c) that are salvaged, returned, or used for the benefit of non-NPSL operations....

  18. 30 CFR 1220.012 - Overhead allowance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Overhead allowance. 1220.012 Section 1220.012 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR Natural Resources Revenue ACCOUNTING PROCEDURES FOR DETERMINING NET PROFIT SHARE PAYMENT FOR OUTER CONTINENTAL...

  19. 30 CFR 220.012 - Overhead allowance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Overhead allowance. 220.012 Section 220.012 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT ACCOUNTING PROCEDURES FOR DETERMINING NET PROFIT SHARE PAYMENT FOR OUTER CONTINENTAL SHELF OIL AND GAS...

  20. 14 CFR 1273.22 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... principles applicable to the organization incurring the costs. The following chart lists the kinds of... CFR part 31, Contract Cost Principles and Procedures, or uniform cost accounting standards that comply... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Allowable costs. 1273.22 Section...