WorldWideScience

Sample records for boeing e-3 sentry

  1. 78 FR 47778 - The Boeing Company Boeing Commercial Aircraft (BCA) Auburn, Washington; The Boeing Company Boeing...

    Science.gov (United States)

    2013-08-06

    ...; TA-W-82,705E] The Boeing Company Boeing Commercial Aircraft (BCA) Auburn, Washington; The Boeing Company Boeing Commercial Aircraft (BCA) Everett, Washington; The Boeing Company Boeing Commercial Aircraft (BCA) Puyallup, Washington; The Boeing Company Boeing Commercial Aircraft (BCA) Including Four...

  2. Control of Multiple Robotic Sentry Vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Feddema, J.; Klarer, P.; Lewis, C.

    1999-04-01

    As part of a project for the Defense Advanced Research Projects Agency, Sandia National Laboratories is developing and testing the feasibility of using of a cooperative team of robotic sentry vehicles to guard a perimeter and to perform surround and diversion tasks. This paper describes on-going activities in the development of these robotic sentry vehicles. To date, we have developed a robotic perimeter detection system which consists of eight ''Roving All Terrain Lunar Explorer Rover'' (RATLER{trademark}) vehicles, a laptop-based base-station, and several Miniature Intrusion Detection Sensors (MIDS). A radio frequency receiver on each of the RATLER vehicles alerts the sentry vehicles of alarms from the hidden MIDS. When an alarm is received, each vehicle decides whether it should investigate the alarm based on the proximity of itself and the other vehicles to the alarm. As one vehicle attends an alarm, the other vehicles adjust their position around the perimeter to better prepare for another alarm. We have also demonstrated the ability to drive multiple vehicles in formation via tele-operation or by waypoint GPS navigation. This is currently being extended to include mission planning capabilities. At the base-station, the operator can draw on an aerial map the goal regions to be surrounded and the repulsive regions to be avoided. A potential field path planner automatically generates a path from the vehicles' current position to the goal regions while avoiding the repulsive regions and the other vehicles. This path is previewed to the operator before the regions are downloaded to the vehicles. The same potential field path planner resides on the vehicle, except additional repulsive forces from on-board proximity sensors guide the vehicle away from unplanned obstacles.

  3. Cooperative sentry vehicles and differential GPS leapfrog

    Energy Technology Data Exchange (ETDEWEB)

    FEDDEMA,JOHN T.; LEWIS,CHRISTOPHER L.; LAFARGE,ROBERT A.

    2000-06-07

    As part of a project for the Defense Advanced Research Projects Agency, Sandia National Laboratories Intelligent Systems and Robotics Center is developing and testing the feasibility of using a cooperative team of robotic sentry vehicles to guard a perimeter, perform a surround task, and travel extended distances. This paper describes the authors most recent activities. In particular, this paper highlights the development of a Differential Global Positioning System (DGPS) leapfrog capability that allows two or more vehicles to alternate sending DGPS corrections. Using this leapfrog technique, this paper shows that a group of autonomous vehicles can travel 22.68 kilometers with a root mean square positioning error of only 5 meters.

  4. E3 Staff Database

    Data.gov (United States)

    US Agency for International Development — E3 Staff database is maintained by E3 PDMS (Professional Development & Management Services) office. The database is Mysql. It is manually updated by E3 staff as...

  5. Vigilance: A Review of the Literature and Applications to Sentry Duty

    Energy Technology Data Exchange (ETDEWEB)

    See, Judi E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-09-01

    Vigilance , or sustained attention, involves the ability to maintain focus and remain alert for prolonged periods of time. Problems associated with the ability to sustain attention were first identified in real-world combat situations during World War II, and they continue to abound and evolve as new and different types of situations requiring vigilance arise. This paper provides a review of the vigilance literature that describes the primary psychophysical, task, environmental, pharmacological, and individual factors that impact vigilance performance. The paper also describes how seminal findings from vigilance research apply specifically to the task of sentry duty. The strengths and weaknesses of a human sentry and options to integrate human and automated functions for vigilance tasks are discussed. Finally, techniques that may improve vigilance performance for sentry duty tasks are identified.

  6. Vigilance: A Review of the Literature and Applications to Sentry Duty

    Energy Technology Data Exchange (ETDEWEB)

    See, Judi E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-09-01

    Vigilance, or sustained attention, involves the ability to maintain focus and remain alert for prolonged periods of time. Problems associated with the ability to sustain attention were first identified in real-world combat situations during World War II, and they continue to abound and evolve as new and different types of situations requiring vigilance arise. This paper provides a review of the vigilance literature that describes the primary psychophysical, task, environmental, pharmacological, and individual factors that impact vigilance performance. The paper also describes how seminal findings from vigilance research apply specifically to the task of sentry duty. The strengths and weaknesses of a human sentry and options to integrate human and automated functions for vigilance tasks are discussed. Finally, techniques that may improve vigilance performance for sentry duty tasks are identified.

  7. Valuation of the Boeing Company

    OpenAIRE

    Khan, Mohammed Masud

    2015-01-01

    In this paper I have conducted a comprehensive analysis of the Boeing Company based on popular valuation methods to determine if the share price of Boeing is undervalued, overvalued, or correctly valued. My initial finding is that, the equity price of Boeing differs slightly from the current market price. According to the discounted cash flow analysis, a fair price of Boeing is USD 101.893 which is approximately 26 % lower than the current market price (USD 128,358 as per 31/12/2014). Rather ...

  8. The Android smartphone as an inexpensive sentry ground sensor

    Science.gov (United States)

    Schwamm, Riqui; Rowe, Neil C.

    2012-06-01

    A key challenge of sentry and monitoring duties is detection of approaching people in areas of little human traffic. We are exploring smartphones as easily available, easily portable, and less expensive alternatives to traditional military sensors for this task, where the sensors are already integrated into the package. We developed an application program for the Android smartphone that uses its sensors to detect people passing nearby; it takes their pictures for subsequent transmission to a central monitoring station. We experimented with the microphone, light sensor, vibration sensor, proximity sensor, orientation sensor, and magnetic sensor of the Android. We got best results with the microphone (looking for footsteps) and light sensor (looking for abrupt changes in light), and sometimes good results with the vibration sensor. We ran a variety of tests with subjects walking at various distances from the phone under different environmental conditions to measure limits on acceptable detection. We got best results by combining average loudness over a 200 millisecond period with a brightness threshold adjusted to the background brightness, and we set our phones to trigger pictures no more than twice a second. Subjects needed to be within ten feet of the phone for reliable triggering, and some surfaces gave poorer results. We primarily tested using the Motorola Atrix 4G (Android 2.3.4) and HTC Evo 4G (Android 2.3.3) and found only a few differences in performance running the same program, which we attribute to differences in the hardware. We also tested two older Android phones that had problems with crashing when running our program. Our results provide good guidance for when and where to use this approach to inexpensive sensing.

  9. Home Sentry: servicio al cliente en la práctica

    Directory of Open Access Journals (Sweden)

    Mauricio Nieto Potes

    2006-07-01

    Full Text Available Presenta la experiencia exitosa de Home SEntry, empresa comercial de grandes superficies dedicada a la venta de productos de una amplia gama para el hogar, con base en su sistema de atención y servicio al cliente

  10. 75 FR 58417 - Agency Information Collection Activities: Application-Alternative Inspection Services (SENTRI...

    Science.gov (United States)

    2010-09-24

    ... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: Application-- Alternative Inspection Services (SENTRI Application and FAST Commercial Driver Application) AGENCY: U.S.... Customs and Border Protection (CBP) encourages the general public and affected Federal agencies to...

  11. 75 FR 38821 - Agency Information Collection Activities: Application-Alternative Inspection Services (SENTRI...

    Science.gov (United States)

    2010-07-06

    ... Doc No: 2010-16314] DEPARTMENT OF HOMELAND SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: Application-- Alternative Inspection Services (SENTRI Application and FAST Commercial Driver Application) AGENCY: U.S. Customs and Border Protection, Department of Homeland...

  12. Will Boeing Change Health Care?

    Science.gov (United States)

    Stempniak, Marty

    2015-12-01

    Big employers like Boeing and Intel are directly contracting with hospitals in an effort to control health care prices. Some hospital CEOs see direct contracting as the future, while others wonder how they can participate.

  13. RING E3 ligases

    DEFF Research Database (Denmark)

    Cho, Seok Keun; Ryu, Moon Young; Kim, Jong Hum

    2017-01-01

    response pathways of plants through various molecular and genetic studies. In particular, it was recently discovered that ubiquitin proteasome system (UPS), a regulatory mechanism for protein turn over, is greatly involved in the stress responsive pathways. In the UPS, many E3 ligases play key roles...... in recognizing and tethering poly-ubiquitins on target proteins for subsequent degradation by the 26S proteasome. Here we discuss the roles of RING ligases that have been defined in related to abiotic stress responses in plants....

  14. Approaching BOE%初识"京东方(BOE)"

    Institute of Scientific and Technical Information of China (English)

    编辑部

    2006-01-01

    @@ "京东方"是京东方科技集团股份有限公司(Bejing Orient Electron Technology Group CO., LTD)的简称,其英文名称缩写为BOE.京东方的前身是享有"中国电子工业摇篮"美誉的北京电子管厂.该厂在20世纪80年代陷入重重危机,濒临破产.

  15. Factors associated to the imposition of types of violence against women informed in sentry services

    Directory of Open Access Journals (Sweden)

    Luiza Jane Eyre de Souza Vieira

    2013-07-01

    Full Text Available OBJECTIVE: to identify the prevalence and the factors associated to the imposition of the different types of violence against women informed in sentry services. METHOD: transversal study accomplished through 939 notification forms of cases of violence against women, referring to the three years from 2006 to 2008 in Fortaleza, Ceará. Univariate and multiple analyses by logistic regression were realized. RESULT: the results showed a positive association between the imposition of types of violence against women with a schooling varying from illiterate to basic education and the aggression which had occurred other times. CONCLUSION: this knowledge contributes to the delineation of specific actions that aim at facing this problem, as well as generates subsidies for adequate attendance proposals and guidance for the victims who call on health services.

  16. 78 FR 25662 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-02

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for all The Boeing Company Model 727... Federal holidays. For Boeing service information identified in this proposed AD, contact Boeing...

  17. Boeing Technology Exposition & Exchange Brochure & Flyer

    OpenAIRE

    Phantom Works and Integrated Defense Systems / Advanced Systems

    2008-01-01

    Not open to the public - No foreign Nationals, Attendance Restricted by U.S. Export Regulations. The Expo is open only to Active Duty U.S. Military, U.S. GOvernment Civilian Personnel and Boeing invited Support Contractors, who are U.S. persons, will be required to sign a Proprietary Information Agreement with The Boeing Company. For more information visit: http://www.boeing.com/techexpo The documents attached include a NPS tri-fold brochure and a Tech Expo Flyer. Brochure regarding ...

  18. E3 Portfolio Review Database

    Data.gov (United States)

    US Agency for International Development — The E3 Portfolio Review Database houses operational and performance data for all activities that the Bureau funds and/or manages. Activity-level data is collected by...

  19. E3 Sustainable Manufacturing Curriculum

    Science.gov (United States)

    A short E3 course containing three modules on Environmental Sustainability; Lean Manufacturing and Pollution Prevention; and Energy and Carbon. Each module includes slides, a facilitator's guide with handouts, activities, quizzes, and facilitator's notes.

  20. 77 FR 58330 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-09-20

    ..., email: rse.boecom@boeing.com . The report must include the inspection results including a description of..., Attention: Manager, Airline Support, email: rse.boecom@boeing.com . The report must include the...

  1. 78 FR 76047 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-12-16

    ...-074-AD; Amendment 39-17695; AD 2013-24-18] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 747-200B, -200C, -200F, -300... (AD): 2013-24-18 The Boeing Company: Amendment 39-17695; Docket No. FAA- 2013-0704;...

  2. 78 FR 53078 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-08-28

    ... Directives; The Boeing Company Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice... certain The Boeing Company Model 747-200B, -200C, -200F, -300, and 747SR series airplanes. This proposed... directive (AD): The Boeing Company: Docket No. FAA-2013-0704; Directorate Identifier 2013-NM-074-AD....

  3. 78 FR 21569 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-04-11

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for all The Boeing Company Model 727... the following new airworthiness directive (AD): The Boeing Company: Docket No....

  4. 78 FR 57053 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-09-17

    ...-243-AD; Amendment 39-17572; AD 2013-17-08] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... superseding airworthiness directive (AD) 2010-20-08, which applied to certain The Boeing Company Model 747-100... (75 ] FR 61337, October 5, 2010), and adding the following new AD: 2013-17-08 The Boeing...

  5. 78 FR 13463 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-02-28

    ...-042-AD; Amendment 39-17284; AD 2012-25-03] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... applies to certain The Boeing Company Model 757 airplanes. That AD incorrectly identified certain actions... windshield. For certain The Boeing Company Model 757 airplanes, AD 2012-25-03 also specifies...

  6. 77 FR 42962 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-07-23

    ...-255-AD; Amendment 39-17117; AD 2012-14-03] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 777-200 and -300 series... the following new airworthiness directive (AD): 2012-14-03 The Boeing Company: Amendment...

  7. 78 FR 25898 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-03

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... Boeing Company Model 747 series airplanes. The existing AD currently requires inspection of the fuselage... Boeing Company Model 747 series airplanes. AD 90-23-14 superseded AD 85-17-05, Amendment 39-5123...

  8. 78 FR 28764 - Airworthiness Directives; The Boeing Company

    Science.gov (United States)

    2013-05-16

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 737-300... the following new airworthiness directive (AD): The Boeing Company: Docket No....

  9. 78 FR 27001 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-09

    ...-277-AD; Amendment 39-17442; AD 2013-09-01] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... superseding an existing airworthiness directive (AD) for certain The Boeing Company Model 737-200, -200C, -300...), and adding the following new AD: 2013-09-01 The Boeing Company: Amendment 39-17442; Docket No....

  10. 76 FR 78574 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2011-12-19

    ... Directives; The Boeing Company Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice... all The Boeing Company Model 767 airplanes. This proposed AD was prompted by reports of cracks of the... fitting, and contacting The Boeing Company for repair instructions and doing the repair. The...

  11. 77 FR 23166 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-04-18

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for all The Boeing Company Model DC-10-10.... 39.13 by adding the following new airworthiness directive (AD): The Boeing Company: Docket No....

  12. 78 FR 59293 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-09-26

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 777... directive (AD): The Boeing Company: Docket No. FAA-2013-0830; Directorate Identifier 2013-NM-128-AD. ]...

  13. 77 FR 76230 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-12-27

    ...-268-AD; Amendment 39-17286; AD 2012-25-05] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 737-600, -700, -700C, -800, -900... airworthiness directive (AD): 2012-25-05 The Boeing Company: Amendment 39-17286; Docket No. FAA-...

  14. 78 FR 73744 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-12-09

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... proposed rulemaking (SNPRM) for all The Boeing Company Model 737-600, -700, - 700C, -800, -900 and -900ER... stabilizer; hence, this SNPRM should apply to all The Boeing Company Model 737-600, -700, -700C, -800,...

  15. 77 FR 71723 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-12-04

    ... Directives; The Boeing Company Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice... (AD) that applies to certain The Boeing Company Model 737-200, -200C, - 300, and -400 series airplanes...-13 R1, Amendment 39-12317 (66 FR 36146, July 11, 2001), for certain The Boeing Company Model...

  16. 78 FR 26233 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-06

    ...-17418; AD 2013-08-01] RIN 2120-AA64 Airworthiness Directives; The Boeing Company Airplanes AGENCY... airworthiness directive (AD) for certain The Boeing Company Model 737-600, -700, -700C, -800, -900, and -900ER...): 2013-08-01 The Boeing Company: Amendment 39-17418; Docket No. FAA- 2011-1231; Directorate...

  17. 78 FR 46540 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-08-01

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 747... FAA amends Sec. 39.13 by adding the following new airworthiness directive (AD): The Boeing...

  18. 78 FR 27020 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-09

    ... revising an existing airworthiness directive (AD) for all The Boeing Company Model 737-100, -200, -200C..., January 9, 2013) and the FAA's response to each comment. Supportive Comment The Boeing Company stated that..., 2012), and adding the following new AD: 2012-18-13 R1 The Boeing Company: Amendment 39-17429; Docket...

  19. 78 FR 4042 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-01-18

    ...-181-AD; Amendment 39-17299; AD 2012-26-04] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... superseding an existing airworthiness directive (AD) for certain The Boeing Company Model 757-200, -200PF, and...), and adding the following new AD: 2012-26-04 The Boeing Company: Amendment 39-17299; Docket No....

  20. 77 FR 61550 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-10

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... would have superseded an existing AD that applies to certain The Boeing Company Model 737-200, -200C... FR 54206, September 8, 2004), and adding the following new AD: The Boeing Company: Docket No....

  1. 78 FR 4047 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-01-18

    ...-029-AD; Amendment 39-17295; AD 2012-25-13] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 747-100, 747-200B, 747-200C, 747... The Boeing Company: Amendment 39-17295; Docket No. FAA- 2012-0299; Directorate Identifier...

  2. 78 FR 40060 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-07-03

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... Boeing Company Model 777-200 and -300 series airplanes equipped with Rolls-Royce engines. The existing AD... 2006-26-06, Amendment 39-14864 (71 FR 77586, December 27, 2006), for certain The Boeing Company...

  3. 78 FR 37497 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-06-21

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... to rescind an existing airworthiness directive (AD) that applies to certain The Boeing Company Model...'s response. Requests To Clarify ``Different Unsafe Condition'' UPS and Boeing...

  4. 77 FR 49708 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-17

    ...-066-AD; Amendment 39-17159; AD 2012-16-12] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for all The Boeing Company Model 707 airplanes, and Model 720 and... airworthiness directive (AD): 2012-16-12 The Boeing Company: Amendment 39-17159; Docket No. FAA-...

  5. 77 FR 47329 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-08

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... propose to rescind an existing airworthiness directive (AD) that applies to certain The Boeing Company...), for certain The Boeing Company Model 767-200, -300, -300F, and -400ER series airplanes. That...

  6. 78 FR 68345 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-11-14

    ...-187-AD; Amendment 39-17658; AD 2013-23-03] RIN 2120-AA64 Airworthiness Directives; The Boeing Company.... SUMMARY: We are adopting a new airworthiness directive (AD) for certain The Boeing Company Model 747-100....13 by adding the following new airworthiness directive (AD): 2013-23-03 The Boeing Company:...

  7. 77 FR 34876 - Airworthiness Directives; The Boeing Company

    Science.gov (United States)

    2012-06-12

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 777.... 39.13 by adding the following new airworthiness directive (AD): The Boeing Company: Docket No....

  8. 77 FR 24355 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-04-24

    ...-265-AD; Amendment 39-17026; AD 2012-08-09] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 777-200, -200LR, -300, -300ER... to The Boeing Company Model 777-200, -200LR, - 300, -300ER, and 777F series airplanes,...

  9. 78 FR 4051 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-01-18

    ... superseding an existing airworthiness directive (AD) for certain The Boeing Company Model 747-100, 747-100B..., 2009), and adding the following new AD: 2013-01-02 The Boeing Company: Amendment 39-17316; Docket No...-16059 (74 FR 55763, October 29, 2009). (c) Applicability This AD applies to The Boeing Company Model...

  10. 77 FR 41041 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-07-12

    ...-17111; AD 2012-13-09] RIN 2120-AA64 Airworthiness Directives; The Boeing Company Airplanes AGENCY... airworthiness directive (AD) for certain The Boeing Company Model 747-100, 747-100B, 747-100B SUD, 747-200B, 747...): 2012-13-09 The Boeing Company: Amendment 39-17111; Docket No. FAA- 2010-1115; Directorate...

  11. 78 FR 43839 - Airworthiness Directives; the Boeing Company

    Science.gov (United States)

    2013-07-22

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; the Boeing Company..., 1994), and adding the following new AD: The Boeing Company: Docket No. FAA-2013-0625; Directorate..., 1994). (c) Applicability This AD applies to The Boeing Company Model 747-100, 747-200B, and...

  12. 77 FR 46340 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-03

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... FR 71212, December 17, 2007), and adding the following new AD: The Boeing Company: Docket No. FAA... 39-15307 (72 FR 71212, December 17, 2007). (c) Applicability This AD applies to The Boeing...

  13. 78 FR 46532 - Airworthiness Directives; the Boeing Company Airplanes

    Science.gov (United States)

    2013-08-01

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; the Boeing Company... directive (AD) for all The Boeing Company Model 767 airplanes. That NPRM proposed to require repetitive... directive (AD): The Boeing Company: Docket No. FAA-2008-0616; Directorate Identifier 2007-NM-353-AD....

  14. 78 FR 21576 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-04-11

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 757... directive (AD): The Boeing Company: Docket No. FAA-2013-0300; Directorate Identifier 2011-NM-163-AD....

  15. 78 FR 12231 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-02-22

    ...-016-AD; Amendment 39-17366; AD 2013-02-51] RIN 2120-AA64 Airworthiness Directives; The Boeing Company.... SUMMARY: We are adopting a new airworthiness directive (AD) for all The Boeing Company Model 787-8... airworthiness directive (AD): 2013-02-51 The Boeing Company: Amendment 39-17366; Docket No. FAA-...

  16. 77 FR 43547 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-07-25

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 737... amends Sec. 39.13 by adding the following new airworthiness directive (AD): The Boeing Company: Docket...

  17. 78 FR 55662 - Airworthiness Directives; the Boeing Company Airplanes

    Science.gov (United States)

    2013-09-11

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; the Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain the Boeing Company Model DC-9.... 39.13 by adding the following new airworthiness directive (AD): The Boeing Company: Docket No....

  18. 78 FR 35749 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-06-14

    ...-151-AD; Amendment 39-17474; AD 2013-11-14] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 777-200 and -300 series...): 2013-11-14 The Boeing Company: Amendment 39-17474; Docket No. FAA- 2012-1221; Directorate...

  19. 78 FR 25905 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-03

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 727... the following new airworthiness directive (AD): The Boeing Company: Docket No....

  20. 78 FR 68693 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-11-15

    ...-087-AD; Amendment 39-17659; AD 2013-23-04] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 737-600, -700, -800, -900, and...): 2013-23-04 The Boeing Company: Amendment 39-17659; Docket No. FAA- 2012-0426; Directorate...

  1. 78 FR 57542 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-09-19

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... Boeing Company Model 777-200 and -300 series airplanes. AD 2012-12-08 requires an inspection for the part..., 2012) (``AD 2012-12-08''), for certain The Boeing Company Model 777-200 and -300 series airplanes....

  2. 78 FR 73739 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-12-09

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... all The Boeing Company Model MD-90- 30 airplanes. AD 97-11-07 and AD 99-18-23 currently require..., 1997), for all The Boeing Company Model MD-90-30 airplanes. AD 97-11-07 requires revising...

  3. 77 FR 33619 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-06-07

    ...-087-AD; Amendment 39-17074; AD 2012-11-11] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... superseding an existing airworthiness directive (AD) for certain The Boeing Company Model 767-200, -300, and... (74 FR 8717, February 26, 2009), and adding the following new AD: 2012-11-11 The Boeing...

  4. 77 FR 40307 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-07-09

    ... Directives; The Boeing Company Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... earlier proposed airworthiness directive (AD) for certain The Boeing Company Model 747-400, -400D, and... directive (AD): The Boeing Company: Docket No. FAA-2008-0620; Directorate Identifier 2007-NM-357-AD....

  5. 78 FR 72836 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-12-04

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for all The Boeing Company Model 717-200... FAA amends Sec. 39.13 by adding the following new airworthiness directive (AD): The Boeing...

  6. 77 FR 55159 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-09-07

    ... Directives; The Boeing Company Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... earlier proposed airworthiness directive (AD) for certain The Boeing Company Model 737-700, -700C, -800... certain The Boeing Company Model 737-700, -700C, -800, and -900ER series airplanes, Model 747-400F...

  7. 78 FR 78703 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-12-27

    ...-067-AD; Amendment 39-17708; AD 2013-25-12] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model DC-9-10, DC-9-30, and DC-9-40... The Boeing Company: Amendment 39-17708; Docket No. FAA-2013-0706; Directorate Identifier...

  8. 77 FR 24831 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-04-26

    ...-148-AD; Amendment 39-17034; AD 2012-08-17] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 737-100, -200, -200C, -300, -400... airworthiness directive (AD): 2012-08-17 The Boeing Company: Amendment 39-17034; Docket No. FAA-...

  9. 77 FR 6518 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-02-08

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 777... directive (AD): The Boeing Company: Docket No. FAA-2012-0104; Directorate Identifier 2011-NM-279-AD....

  10. 77 FR 61548 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-10

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 727... directive (AD): The Boeing Company: Docket No. FAA-2012-1041; Directorate Identifier 2011-NM-272-AD....

  11. 77 FR 6522 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-02-08

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 777... directive (AD): The Boeing Company: Docket No. FAA-2012-0105; Directorate Identifier 2011-NM-123-AD....

  12. 77 FR 24357 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-04-24

    ...-002-AD; Amendment 39-17030; AD 2012-08-13] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 777-200 and -300 series... Boeing Company and United Airlines both support the NPRM (76 FR 68366, November 4, 2011). Request...

  13. 78 FR 21854 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-04-12

    ... Directives; The Boeing Company Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice... certain The Boeing Company Model 747-400 and -400F series airplanes. This proposed AD was prompted by a... FAA amends Sec. 39.13 by adding the following new airworthiness directive (AD): The Boeing...

  14. 78 FR 20229 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-04-04

    ...-119-AD; Amendment 39-17402; AD 2013-06-05] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... superseding an existing airworthiness directive (AD) for all The Boeing Company Model 737-600, -700, -700C... AD: 2013-06-05 The Boeing Company: Amendment 39-17402; Docket No. FAA- 2012-0994;...

  15. 77 FR 41045 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-07-12

    ...-279-AD; Amendment 39-17107; AD 2012-13-05] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 777-200, -200LR, -300, -300ER... airworthiness directive (AD): 2012-13-05 The Boeing Company: Amendment 39-17107; Docket No. FAA-...

  16. 78 FR 28128 - Airworthiness Directives; the Boeing Company Airplanes

    Science.gov (United States)

    2013-05-14

    ...-351-AD; Amendment 39-17450; AD 2013-09-08] RIN 2120-AA64 Airworthiness Directives; the Boeing Company... new airworthiness directive (AD) for all The Boeing Company Model 737-300, -400, and -500 series... the Boeing Company: Amendment 39-17450; Docket No. FAA- 2008-0614; Directorate Identifier...

  17. 78 FR 78701 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-12-27

    ...-003-AD; Amendment 39-17701; AD 2013-25-05] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 737-300, -400, and -500 series... airworthiness directive (AD): 2013-25-05 The Boeing Company: Amendment 39-17701; Docket No. FAA-...

  18. 77 FR 42964 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-07-23

    ...-103-AD; Amendment 39-17095; AD 2012-12-15] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... superseding an existing airworthiness directive (AD) for The Boeing Company Model 757 Airplanes. That AD... (73 FR 25974, May 8, 2008), and adding the following new AD: 2012-12-15 The Boeing Company:...

  19. 77 FR 75827 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-12-26

    ...-190-AD; Amendment 39-17292; AD 2012-25-11] RIN 2120-AA64 Airworthiness Directives; The Boeing Company.... SUMMARY: We are superseding an existing airworthiness directive (AD) for certain The Boeing Company Model... certain The Boeing Company Model 757-200, -200CB, and -300 series airplanes. AD 2012-15-15...

  20. 77 FR 65506 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-29

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... Boeing Company Model 757-200 and - 200PF series airplanes. The existing AD currently requires... 11, 2003), and adding the following new AD: The Boeing Company: Docket No. FAA-2012-1109;...

  1. 77 FR 11789 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-02-28

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 737.... 39.13 by adding the following new airworthiness directive (AD): The Boeing Company: Docket No....

  2. 78 FR 26286 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-06

    ... airworthiness directive (AD) for all The Boeing Company Model 717-200 airplanes. That NPRM proposed requiring... rulemaking (NPRM) to amend 14 CFR part 39 to include an AD that would apply to all The Boeing Company Model... directive (AD): The Boeing Company: Docket No. FAA-2012-0425; Directorate Identifier 2011-NM-273-AD....

  3. 78 FR 4055 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-01-18

    ...-130-AD; Amendment 39-17317; AD 2013-01-03] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 737-300, 737-400, 737-500, and... airworthiness directive (AD): 2013-01-03 The Boeing Company: Amendment 39-17317; Docket No. ]...

  4. 77 FR 31167 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-05-25

    ...-17059; AD 2012-10-10] RIN 2120-AA64 Airworthiness Directives; The Boeing Company Airplanes AGENCY... airworthiness directive (AD) for certain The Boeing Company Model 777 airplanes. This AD was prompted by reports... airworthiness directive (AD): 2012-10-10 The Boeing Company: Amendment 39-17059; Docket No. FAA-...

  5. 78 FR 14469 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-03-06

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... Boeing Company Model 747-100, 747- 100B, 747-100B SUD, 747-200B, 747-200C, 747-200F, 747-300, 747-400... 61337, October 5, 2010), and adding the following new AD: The Boeing Company: Docket No....

  6. 77 FR 71485 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-12-03

    ... adopting a new airworthiness directive (AD) for certain The Boeing Company Model 737-100, -200, -200C, -300... airworthiness directive (AD): 2012-23-14 The Boeing Company: Amendment 39-17270; Docket No. FAA- 2012-0857... ADs None. (c) Applicability (1) This AD applies to The Boeing Company Model 737-100, -200, -...

  7. 77 FR 29857 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-05-21

    ...-009-AD; Amendment 39-17052; AD 2012-10-03] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... superseding an existing airworthiness directive (AD) for certain The Boeing Company Model 747 series airplanes... following new AD: 2012-10-03 The Boeing Company: Amendment 39-17052; Docket No. FAA- 2011-0645;...

  8. 77 FR 48423 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-14

    ...-213-AD; Amendment 39-17154; AD 2012-16-07] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 737-500 series airplanes. This... The Boeing Company: Amendment 39-17154; Docket No. FAA- 2012-0336; Directorate Identifier...

  9. 77 FR 60296 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-03

    ...-074-AD; Amendment 39-17206; AD 2012-19-11] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 737 airplanes. This AD was... the Latest Service Information Delta (DAL), AAL, and The Boeing Company requested that the proposed...

  10. 77 FR 22686 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-04-17

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 737.... 39.13 by adding the following new airworthiness directive (AD): The Boeing Company: Docket No....

  11. 77 FR 47267 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-08

    ...-17142; AD 2012-15-13] RIN 2120-AA64 Airworthiness Directives; The Boeing Company Airplanes AGENCY... following new AD: 2012-15-13 The Boeing Company: Amendment 39-17142; Docket No. FAA- 2009-0607; Directorate..., 2007). (c) Applicability This AD applies to all The Boeing Company Model 747-100B SUD, 747-300,...

  12. 78 FR 15332 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-03-11

    ... Directives; The Boeing Company Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice... (AD) that applies to all The Boeing Company Model 737-300, -400, and - 500 series airplanes. The... (73 FR 15397, March 24, 2008), for all The Boeing Company Model 737-300, - 400, and -500...

  13. 78 FR 63130 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-10-23

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 777F.... 39.13 by adding the following new airworthiness directive (AD): The Boeing Company: Docket No....

  14. 77 FR 54856 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-09-06

    ... respect to maintaining fail-safe design and damage tolerance of the structure of The Boeing Company Model... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for all The Boeing Company Model 727,...

  15. 78 FR 52875 - Airworthiness Directives; the Boeing Company Airplanes

    Science.gov (United States)

    2013-08-27

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; the Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for all the Boeing Company Model 727.... For service information identified in this proposed AD, contact Boeing Commercial Airplanes,...

  16. 77 FR 59728 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-01

    ...-125-AD; Amendment 39-17198; AD 2012-19-03] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... superseding an existing airworthiness directive (AD) for certain The Boeing Company Model DC-10-10, DC-10-10F..., August 3, 2006). ADDRESSES: For service information identified in this AD, contact Boeing...

  17. 78 FR 56182 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-09-12

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... to rescind airworthiness directive (AD) 2008-06-03, which applies to certain The Boeing Company Model..., American Airlines, and Boeing requested clarification of the different unsafe condition introduced by...

  18. 77 FR 21426 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-04-10

    ...-020-AD; Amendment 39-17013; AD 2012-07-07] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for all The Boeing Company Model 747 airplanes. This AD was prompted..., contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC...

  19. 78 FR 49217 - Airworthiness Directives; the Boeing Company Airplanes

    Science.gov (United States)

    2013-08-13

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; the Boeing Company... directive (AD), for all The Boeing Company Model 727 airplanes, which proposed to supersede an existing AD... information identified in this AD, contact Boeing Commercial Airplanes, Attention: Data & Services...

  20. 78 FR 58982 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-09-25

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to supersede airworthiness directive (AD) 2013-07- 07, which applies to all The Boeing... information identified in this AD, contact Boeing Commercial Airplanes, Attention: Data & Services...

  1. 78 FR 49229 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-08-13

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... Boeing Company Model 737-600, -700, - 700C, and -800 series airplanes. AD 2009-24-07 currently requires... holidays. For service information identified in this proposed AD, contact Boeing Commercial...

  2. 78 FR 58962 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-09-25

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... Boeing Company Model 747 series airplanes. ] AD 89-12-10 currently requires replacement of certain... information identified in this proposed AD, contact Boeing Commercial Airplanes, Attention: Data &...

  3. 77 FR 21429 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-04-10

    ...-208-AD; Amendment 39-17012; AD 2012-07-06] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 777 airplanes. This AD was...: For service information identified in this AD, contact Boeing Commercial Airplanes, Attention:...

  4. 78 FR 73460 - Airworthiness Directives; the Boeing Company Airplanes

    Science.gov (United States)

    2013-12-06

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; the Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 767... Federal holidays. For service information identified in this proposed AD, contact Boeing...

  5. 77 FR 24835 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-04-26

    ...-217-AD; Amendment 39-17031; AD 2012-08-14] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 767 airplanes. This AD was... this AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707,...

  6. 78 FR 3365 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-01-16

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Airplanes... holidays. For service information identified in this proposed AD, contact Boeing Commercial...

  7. 78 FR 49237 - Airworthiness Directives; the Boeing Company Airplanes

    Science.gov (United States)

    2013-08-13

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; the Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 707... Federal holidays. For service information identified in this proposed AD, contact Boeing...

  8. 78 FR 52838 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-08-27

    ...-354-AD; Amendment 39-17533; AD 2013-15-17] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 737-600, -700, -700C, -800, -900... information identified in this AD, contact Boeing Commercial Airplanes, Attention: Data & Services...

  9. 78 FR 52836 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-08-27

    ...-352-AD; Amendment 39-17529; AD 2013-15-13] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for all The Boeing Company Model 757 airplanes. This AD was prompted... October 1, 2013. ADDRESSES: For service information identified in this AD, contact Boeing...

  10. 78 FR 24037 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-04-24

    ...-257-AD; Amendment 39-17441; AD 2013-08-23] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for all The Boeing Company Model DC-10-10, DC-10-10F, DC-10-15, DC-10... Service Information Two commenters requested that we delay issuing the AD until Boeing has...

  11. 77 FR 731 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-01-06

    ...-256-AD; Amendment 39-16904; AD 2011-27-03] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... publications listed in the AD as of February 10, 2012. ADDRESSES: For Boeing service information identified in this AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707,...

  12. 78 FR 61388 - TA-W-82,705, the Boeing Company Boeing Commercial Aircraft, (BCA) Including On-Site Leased...

    Science.gov (United States)

    2013-10-03

    ... Employment and Training Administration TA-W-82,705, the Boeing Company Boeing Commercial Aircraft, (BCA..., Washington; TA-W-82,705A, the Boeing Company Boeing Commercial Aircraft, (BCA) Including On-Site Leased... International, Volt Services and Yoh Services Everett, Washington; TA-W-82,705B, The Boeing Company...

  13. Resistance to beta-lactams among blood isolates of Salmonella spp. in European hospitals : results from the SENTRY Antimicrobial Surveillance Program 1997-98

    NARCIS (Netherlands)

    Tzouvelekis, LS; Lukova, [No Value; Tassios, PT; Fluit, AC; Jones, RN; Legakis, NJ

    2003-01-01

    The susceptibility to beta -lactams and the beta -lactamase content of 110 Salmonella spp. blood isolates collected during 1997-98 in 19 European centers participating in the SENTRY Surveillance Program were studied. Thirty-one isolates (28%) were resistant to penicillins, due to production of TEM-1

  14. Resistance to beta-lactams among blood isolates of Salmonella spp. in European hospitals : results from the SENTRY Antimicrobial Surveillance Program 1997-98

    NARCIS (Netherlands)

    Tzouvelekis, LS; Lukova, [No Value; Tassios, PT; Fluit, AC; Jones, RN; Legakis, NJ

    2003-01-01

    The susceptibility to beta -lactams and the beta -lactamase content of 110 Salmonella spp. blood isolates collected during 1997-98 in 19 European centers participating in the SENTRY Surveillance Program were studied. Thirty-one isolates (28%) were resistant to penicillins, due to production of TEM-1

  15. Telepresence field research experience for undergraduate and graduate students: An R/V Okeanos Explorer/AUV Sentry success story

    Science.gov (United States)

    Van Dover, C. L.; German, C. R.; Yoerger, D. R.; Kaiser, C. L.; Brothers, L.

    2012-12-01

    Telepresence and ocean exploration are generally perceived as rich visual experiences informed by streaming video of ocean environments from ship to shore. In an NSF/NOAA-funded partnership, our team of engineers, scientists, and students pushed the boundary of what it means to engage in a telepresence research experience. Instead of using a tethered ROV as our data-gathering platform, we used the autonomous underwater vehicle Sentry on science missions to explore the Blake Ridge and Cape Fear Diapirs off the Carolina coast. The shore-based team included one senior engineer, two senior scientists, the talented support staff of the Inner Space Center at the University of Rhode Island, three PhD students, four undergraduate interns, and one MFA graduate student. The ship-based team included an engineer, a scientist, and extremely capable NOAA personnel. Sentry was deployed nightly on science missions designed from shore with input from shipboard science and engineering. The vehicle was recovered and data was downloaded and sent to shore each morning, where the data was 'attacked' by student teams. Within three days of the start of the field program, the student teams had developed their research questions under the mentorship of the senior scientists and identified the priority data streams required from Sentry. Students initially were audience to science mission planning discussions, but less than halfway through the 11-mission program, student teams were providing key data to inform planning decisions. Their entrepreneurial engagement with the research was so complete that the last two missions were designed by the students in collaboration with the engineers who programmed each mission. This scientific maturation of the students was markedly swift by usual standards and is attributed in large part to the data-sharing and data-processing capacity of the Inner Space Center. Post-cruise analysis of the data by students continued with the same avidity, resulting in

  16. 78 FR 15281 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-03-11

    ... adopting a new airworthiness directive (AD) for all The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD... airworthiness directive (AD): 2013-05-02 The Boeing Company: Amendment 39-17374; Docket No. FAA- 2011-0909... ADs None. (c) Applicability This AD applies to The Boeing Company Model DC-9-81 (MD-81), DC- 9-82...

  17. 77 FR 46343 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-03

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... Boeing Company Model 747-100, 747-100B, 747-100B SUD, 747-200B, 747-200C, 747-200F, 747-300, 747-400, 747... 2009-22-08, Amendment 39-16059 (74 FR 55763, October 29, 2009), for certain The Boeing Company...

  18. Air Canada Selects Boeing 777s and 787 Dreamliners

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

      ACE Aviation Holdings Inc.,the parent company of Air Canada, and Boeing today announced a wide-body fleet renewal plan for the airline that includes up to 36 Boeing 777s and up to 60 Boeing 787Dreamliners. Air Canada will use the airplanes to modernize its existing fleet and improve operating efficiencies, creating one of the world's youngest and most simplified airline fleets.……

  19. Air Canada Selects Boeing 777s and 787 Dreamliners

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ ACE Aviation Holdings Inc.,the parent company of Air Canada, and Boeing today announced a wide-body fleet renewal plan for the airline that includes up to 36 Boeing 777s and up to 60 Boeing 787Dreamliners. Air Canada will use the airplanes to modernize its existing fleet and improve operating efficiencies, creating one of the world's youngest and most simplified airline fleets.

  20. Boeing-AX Jet-Effects Model

    Science.gov (United States)

    1994-01-01

    This model of the Boeing A/FX (Advanced Attack/Fighter) Aircraft was photographed between test runs in NASA Langley Research Center's 16-Foot Transonic Tunnel. Testing was conducted to determine the effects of the jet exhaust on the aerodynamic characteristics of the aircraft afterbody. The A/FX program was a Navy effort to obtain a next-generation replacement for the A-6 and F/A-18. The A/FX program evolved into the current multi-service JSF (Joint Strike Fighter) program.

  1. 77 FR 46943 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-07

    ... thread between ST Aerospace and The Boeing Company was forwarded to the FAA by The Boeing Company as an.... \\1\\ Depending on work package. Authority for This Rulemaking Title 49 of the United States Code... Code 25, Equipment/Furnishings. (e) Unsafe Condition This AD was prompted by a report of an...

  2. 78 FR 59304 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-09-26

    ... the following new airworthiness directive (AD): The Boeing Company: Docket No. FAA-2013-0831...) Affected ADs None. (c) Applicability This AD applies to The Boeing Company Model 737-100, -200, - 200C... TRANSPORTATION Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The...

  3. 77 FR 65501 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-29

    ... certain The Boeing Company Model 707 airplanes, and Model 720 and 720B series airplanes. The existing AD... Boeing Company Model 707-100 long body, - 200, -100B long body, and -100B short body series airplanes... TRANSPORTATION Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The...

  4. 77 FR 47330 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-08

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... to supersede an existing airworthiness directive (AD) that applies to certain The Boeing...

  5. 78 FR 63135 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-10-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company... a new airworthiness directive (AD) for certain The Boeing Company Model 767 airplanes equipped...

  6. 77 FR 37770 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-06-25

    .... Request To Clarify the Applicability Regarding the Installation of Winglets American Airlines (American... for airplanes covered by the applicability of the NPRM are affected by the installation of winglets... winglets. Aviation Partners Boeing (APB) stated it has reviewed Boeing Alert Service Bulletin...

  7. 78 FR 60679 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-10-02

    ...-273-AD; Amendment 39-17604; AD 2013-19-22] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for all The Boeing Company Model 717-200 airplanes. This AD was... result in damage to the adjacent structure and consequent loss of structural integrity of the...

  8. 77 FR 54848 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-09-06

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 737... not electrically bonded to primary structure of the airplane. This proposed AD would...

  9. 78 FR 17290 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-03-21

    ...-056-AD; Amendment 39-17375; AD 2013-05-03] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 777-200, -200LR, -300, and... measuring the electrical resistance of the bond from the adapter plate to the airplane structure, and...

  10. 77 FR 69744 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-11-21

    ... NPRM (76 FR 69685, November 9, 2011) to clarify that structural inspections of fuselage structure are...-239-AD; Amendment 39-17255; AD 2012-22-17] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 767-200 and -300...

  11. 77 FR 50414 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-21

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 737... structure, which could result in uncontrolled decompression of the airplane. DATES: We must receive...

  12. 77 FR 40481 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-07-10

    ...-134-AD; Amendment 39-17110; AD 2012-13-08] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... superseding an existing airworthiness directive (AD) for certain The Boeing Company Model 747-100, 747-100B... of each affected tension tie and of the surrounding structure, and related investigative...

  13. 77 FR 37793 - Airworthiness Directives; the Boeing Company Airplanes

    Science.gov (United States)

    2012-06-25

    ...-124-AD; Amendment 39-17099; AD 2012-12-19] RIN 2120-AA64 Airworthiness Directives; the Boeing Company... new airworthiness directive (AD) for certain the Boeing Company Model 777-200, -200LR, and -300ER... ceiling support structure of Section 41, in airplanes incorporating the overhead space utilization...

  14. 78 FR 52419 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-08-23

    ...-128-AD; Amendment 39-17555; AD 2013-16-17] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for all The Boeing Company Model 727, 727C, 727-100, 727-100C, 727... any cracked structure. We are issuing this AD to detect and correct fatigue cracking of the...

  15. 78 FR 49906 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-08-16

    ...-026-AD; Amendment 39-17527; AD 2013-15-11] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for all The Boeing Company Model 727 airplanes. This AD was prompted... structure and result in loss of airplane control due to lack of horizontal stabilizer support. DATES:...

  16. 77 FR 65803 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-31

    ...-050-AD; Amendment 39-17234; AD 2012-21-18] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model MD-90-30 airplanes. This AD was... AD to detect and correct such cracking, which could result in the wing structure not supporting...

  17. 77 FR 65611 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-30

    ...-17229; AD 2012-21-13] RIN 2120-AA64 Airworthiness Directives; The Boeing Company Airplanes AGENCY... airworthiness directive (AD) for certain The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD... result in the wing structure not supporting the limit load condition, which could lead to loss...

  18. 77 FR 45515 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-01

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model MD-90... could result in the wing structure not supporting the limit load condition, which could lead to loss...

  19. 78 FR 17294 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-03-21

    ...-054-AD; Amendment 39-17377; AD 2013-05-05] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 777-200, -200LR, -300, and... smoke and heat damage to airplane structure and equipment during ground operations, and...

  20. 78 FR 73457 - Airworthiness Directives; the Boeing Company Airplanes

    Science.gov (United States)

    2013-12-06

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; the Boeing Company... Boeing Company Model 747-100, 747-200B, 747-200F series airplanes. AD 84-19-01 requires repetitive... Friday, except Federal holidays. For service information identified in this proposed AD, contact...

  1. 78 FR 11972 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-02-21

    ...-077-AD; Amendment 39-17362; AD 2013-04-05] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... new airworthiness directive (AD) for certain The Boeing Company Model 737-200, -200C, -300, -400, and... the AD as of March 28, 2013. ADDRESSES: For service information identified in this AD, contact...

  2. 78 FR 27315 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-10

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for all The Boeing Company Model 757... Friday, except Federal holidays. For service information identified in this proposed AD, contact...

  3. 77 FR 58325 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-09-20

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 737... Friday, except Federal holidays. For service information identified in this proposed AD, contact...

  4. 78 FR 24673 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-04-26

    ...-080-AD; Amendment 39-17436; AD 2013-08-12] RIN 2120-AA64 Airworthiness Directives; The Boeing Company.... SUMMARY: We are superseding an existing airworthiness directive (AD) for The Boeing Company Model 787-8... through Friday, except Federal holidays. For service information identified in this AD, contact...

  5. "Air Queen" Boeing 747’s Anniversary

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    <正>The world’s well-known Boeing 747 aircraft completed its maiden flight on February 9, 1969, rewriting the history of the world’s civil aviation.Since 1970 when it was put into operation, Boeing 747s,dubbed as "air queen," have carried 3.6 billion passengers by flying for 64.8

  6. 78 FR 75512 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-12-12

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 737... Friday, except Federal holidays. For service information identified in this proposed AD, contact...

  7. 78 FR 31867 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-28

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 747... Friday, except Federal holidays. For service information identified in this proposed AD, contact...

  8. 77 FR 58334 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-09-20

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company...). SUMMARY: We propose to adopt a new airworthiness directive (AD) for certain The Boeing Company Model 737... Friday, except Federal holidays. For service information identified in this proposed AD, contact...

  9. With US$5 Billion,China Purchases 42 Boeing Planes

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ On August 8, Air China, China Eastern Airlines, Shanghai Airlines, Xiamen Airlines signed the final Purchase agreement of 42 Boeing planes with Boeing. The price in catalogue is US$5.04 billion. The first plane will be delivered in 2008.

  10. With US$5 Billion,China Purchases 42 Boeing Planes

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

      On August 8, Air China, China Eastern Airlines, Shanghai Airlines, Xiamen Airlines signed the final Purchase agreement of 42 Boeing planes with Boeing. The price in catalogue is US$5.04 billion. The first plane will be delivered in 2008.……

  11. 78 FR 43763 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-07-22

    ... warranty, thereby reducing the cost impact on affected individuals. We do not control warranty coverage for... inclusive. We revised paragraph (i)(3) in this final rule to include text similar to that proposed by Boeing... the longeron extension fitting had been redesigned at line number 1097. Boeing suggested that the text...

  12. Final Technical Report. Project Boeing SGS

    Energy Technology Data Exchange (ETDEWEB)

    Bell, Thomas E. [The Boeing Company, Seattle, WA (United States)

    2014-12-31

    Boeing and its partner, PJM Interconnection, teamed to bring advanced “defense-grade” technologies for cyber security to the US regional power grid through demonstration in PJM’s energy management environment. Under this cooperative project with the Department of Energy, Boeing and PJM have developed and demonstrated a host of technologies specifically tailored to the needs of PJM and the electric sector as a whole. The team has demonstrated to the energy industry a combination of processes, techniques and technologies that have been successfully implemented in the commercial, defense, and intelligence communities to identify, mitigate and continuously monitor the cyber security of critical systems. Guided by the results of a Cyber Security Risk-Based Assessment completed in Phase I, the Boeing-PJM team has completed multiple iterations through the Phase II Development and Phase III Deployment phases. Multiple cyber security solutions have been completed across a variety of controls including: Application Security, Enhanced Malware Detection, Security Incident and Event Management (SIEM) Optimization, Continuous Vulnerability Monitoring, SCADA Monitoring/Intrusion Detection, Operational Resiliency, Cyber Range simulations and hands on cyber security personnel training. All of the developed and demonstrated solutions are suitable for replication across the electric sector and/or the energy sector as a whole. Benefits identified include; Improved malware and intrusion detection capability on critical SCADA networks including behavioral-based alerts resulting in improved zero-day threat protection; Improved Security Incident and Event Management system resulting in better threat visibility, thus increasing the likelihood of detecting a serious event; Improved malware detection and zero-day threat response capability; Improved ability to systematically evaluate and secure in house and vendor sourced software applications; Improved ability to continuously monitor

  13. Boeing infrared sensor (BIRS) calibration facility

    Science.gov (United States)

    Hazen, John D.; Scorsone, L. V.

    1990-01-01

    The Boeing Infrared Sensor (BIRS) Calibration Facility represents a major capital investment in optical and infrared technology. The facility was designed and built for the calibration and testing of the new generation large aperture long wave infrared (LWIR) sensors, seekers, and related technologies. Capability exists to perform both radiometric and goniometric calibrations of large infrared sensors under simulated environmental operating conditions. The system is presently configured for endoatmospheric calibrations with a uniform background field which can be set to simulate the expected mission background levels. During calibration, the sensor under test is also exposed to expected mission temperatures and pressures within the test chamber. Capability exists to convert the facility for exoatmospheric testing. The configuration of the system is described along with hardware elements and changes made to date are addressed.

  14. Advanced composite elevator for Boeing 727 aircraft

    Science.gov (United States)

    1979-01-01

    Detail design activities are reported for a program to develop an advanced composites elevator for the Boeing 727 commercial transport. Design activities include discussion of the full scale ground test and flight test activities, the ancillary test programs, sustaining efforts, weight status, and the production status. Prior to flight testing of the advanced composites elevator, ground, flight flutter, and stability and control test plans were reviewed and approved by the FAA. Both the ground test and the flight test were conducted according to the approved plan, and were witnessed by the FAA. Three and one half shipsets have now been fabricated without any significant difficulty being encountered. Two elevator system shipsets were weighed, and results validated the 26% predicted weight reduction. The program is on schedule.

  15. 78 FR 22185 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-04-15

    ...), British Airways, Boeing, and Emirates Airlines requested that we change paragraph (l) of the NPRM (77 FR...: Information Collection Clearance Officer, AES-200. (q) Alternative Methods of Compliance (AMOCs) (1) The...

  16. Engineering student takes third place in Boeing competition

    OpenAIRE

    Nystrom, Lynn A.

    2010-01-01

    Onur Bilgen of Ankara, Turkey, a recent Ph.D. recipient in the mechanical engineering department at Virginia Tech, has won third place in the Boeing competition for Engineering Student of the Year 2010.

  17. 77 FR 70355 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-11-26

    ... Federal Regulations is sold by the Superintendent of Documents. #0;Prices of new books are listed in the... the airline or by Boeing engineering, could either be approved by the Manager of the Seattle...

  18. Boeing and EGAT Unveil World's First Large Cargo Freighter——Evergreen Aviation Technologies transforms Boeing747-400 for 787 Dreamliner cargo

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Evergreen Aviation Technologies Corporation (EGAT), a subsidiary of the Evergreen Group, and The Boeing Company unveiled the first of three Boeing 747-400 Large Cargo Freighters (LCF) modified to exacting specifications to transport giant-sized Boeing 787 "Dreamliner" assemblages.Boeing selected EGAT to perform the specialized aircraft conversions and work began in 2005. The three-aircraft conversion program will be completed in 2007.

  19. Boeing's Marc Sheffler receives College of Engineering Service Award

    OpenAIRE

    Nystrom, Lynn A.

    2009-01-01

    In 2007, Marc Sheffler arranged for his company, Boeing, to present a $50,000 check to the Design Team Endowment Fund, founded by the Student Engineers' Council at Virginia Tech. A few months later he supplemented that check with another $15,000 check from Boeing for the same cause. In 2009, he presented the Student Engineers' Council with yet another $20,000 for the Design Team Endowment.

  20. Contemporary prevalence of BRO beta-lactamases in Moraxella catarrhalis: report from the SENTRY antimicrobial surveillance program (North America, 1997 to 2004).

    Science.gov (United States)

    Deshpande, Lalitagauri M; Sader, Helio S; Fritsche, Thomas R; Jones, Ronald N

    2006-10-01

    A total of 7,860 community-acquired Moraxella catarrhalis isolates (SENTRY Antimicrobial Surveillance Program, 1997 to 2004) were tested by broth microdilution methods, and 399 randomly selected strains from North American sites were tested for BRO-1 and BRO-2 by PCR methods. Several antimicrobials remained very active, including amoxicillin-clavulanate (MIC90s, BRO-2 incidence rates by year were 3 to 4% overall (96 to 97% for BRO-1) and were the highest in Canada (7.9%), with the incidence in the United States being only 2.0%.

  1. On Generalized Euler Spirals in E^3

    OpenAIRE

    Saracoglu, Semra

    2012-01-01

    The Cornu spirals on plane are the curves whose curvatures are linear. Generalized planar cornu spirals and Euler spirals in E^3, the curves whose curvatures are linear are defined in [1,5]. In this study, these curves are presented as the ratio of two rational linear functions. Also here, generalized Euler spirals in E^3 has been defined and given their some various characterizations. The approach I used in this paper is useful in understanding the role of Euler spirals in E^3 in differentia...

  2. E3: Extreme Energy Event monitoring

    CERN Document Server

    CERN. Geneva

    2015-01-01

    World peace through CERN technology: Use of explosives especially in urban areas is the defining phenomenon of the last and current century. E3 aims to reduce such excesses of violence by collecting scientific hard evidence.

  3. Freezing E3-brane instantons with fluxes

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, M.; Martucci, L. [Dipartimento di Fisica, Universita di Roma Tor Vergata (Italy); I.N.F.N., Sezione di Roma Tor Vergata (Italy); Collinucci, A. [Theory Group, Physics Department, CERN, Geneva (Switzerland); Physique Theorique et Mathematique Universite Libre de Bruxelles (Belgium)

    2012-07-15

    E3-instantons that generate non-perturbative superpotentials in IIB N = 1 compactifications have a much more frequent occurrence than currently believed. Worldvolume fluxes will typically lift the E3-brane geometric moduli and their fermionic superpartners, leaving only the two required universal fermionic zero-modes. We consistently incorporate SL(2,Z) monodromies and world-volume fluxes in the effective theory of the E3-brane fermions and study the resulting zero modes spectrum, highlighting the relation between F-theory and perturbative IIB results. This leads us to a IIB derivation of the index for generation of superpotential terms, which reproduces and generalizes available results. Furthermore, we show how E3 worldvolume fluxes can be explicitly constructed in a one-modulus compactification, such that the instanton has exactly two fermonic zero-modes. This construction is readily applicable to numerous scenarios. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  4. E3 Travel & Mission Support System

    Data.gov (United States)

    US Agency for International Development — ETRAMS is a travel data collection system developed by the CKM team in E3 that collects information on both the basic details of an employee's trips (destination,...

  5. E3: Economy, Energy and Environment

    Science.gov (United States)

    E3 is a technical assistance framework helping communities, manufacturers, and manufacturing supply chains adapt and thrive in today's green economy. Find information on pollution prevention, sustainable business practices, and energy efficiency.

  6. HECT E3s and human disease

    Directory of Open Access Journals (Sweden)

    Staub Olivier

    2007-11-01

    Full Text Available Abstract In a simplified view, members of the HECT E3 family have a modular structure consisting of the C-terminal HECT domain, which is catalytically involved in the attachment of ubiquitin to substrate proteins, and N-terminal extensions of variable length and sequence that mediate the substrate specificity of the respective HECT E3. Although the physiologically relevant substrates of most HECT E3s have remained elusive, it is becoming increasingly clear that HECT E3s play an important role in sporadic and hereditary human diseases including cancer, cardiovascular (Liddle's syndrome and neurological (Angelman syndrome disorders, and/or in disease-relevant processes including bone homeostasis, immune response and retroviral budding. Thus, molecular approaches to target the activity of distinct HECT E3s, regulators thereof, and/or of HECT E3 substrates could prove valuable in the treatment of the respective diseases. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com.

  7. Antimicrobial resistance among Gram-negative bacilli isolated from Latin America: results from SENTRY Antimicrobial Surveillance Program (Latin America, 2008-2010).

    Science.gov (United States)

    Gales, Ana C; Castanheira, Mariana; Jones, Ronald N; Sader, Hélio S

    2012-08-01

    This study updates the frequency and resistance rates of Gram-negative bacilli isolated from Latin American medical centers enrolled in the SENTRY Antimicrobial Surveillance Program. A total of 12,811 bacterial organisms, including 5704 Gram-negative bacilli (44.5%), were consecutively collected (1 per patient) between January 2008 and December 2010 from 10 Latin American medical centers located in Argentina, Brazil, Chile, and Mexico. Antimicrobial susceptibility testing was performed and interpreted by the Clinical and Laboratory Standards Institute broth microdilution method at a central laboratory. All Gram-negative organisms with reduced susceptibility to imipenem or meropenem (MIC, ≥ 2 μg/mL) were screened for carbapenemase production by the modified Hodge test and by polymerase chain reaction. ESBL rates were 18.1%, 12.8%, 23.8%, and 48.4% among Escherichia coli and 60.4%, 49.9%, 59.2%, and 33.3% among Klebsiella spp. from Argentina, Brazil, Chile, and Mexico, respectively. Meropenem-nonsusceptible Klebsiella spp. rate was highest in Brazil (11.1%), followed by Argentina (8.2%), Chile (5.0%), and Mexico (0.8%). Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae was not detected in 2008, but emerged in 2009 (10 strains) and increased significantly in 2010 (44; P 77% overall coverage against the 5 most frequently isolated Gram-negative bacilli from Latin American Medical centers participating in the SENTRY Program. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Dissection of the sentry ganglion by laparoscopic boarding in patients with cervix uterine cancer clinical stages IA2 at IIB; Diseccion de ganglio centinela por abordaje laparoscopico en pacientes con cancer cervicouterino etapas clinicas IA2 a IIB

    Energy Technology Data Exchange (ETDEWEB)

    Valdez U, J.J.; Pichardo M, P.A.; Cortes M, G.; Escudero de los Rios, P. [Hospital de Oncologia. Centro Medico Nacional Siglo XXI. IMSS, Mexico D.F. (Mexico)

    2005-07-01

    The obtained results in presently study demonstrate that the feasibility of the detection of the sentry ganglion in cervix uterine cancer using a boarding by laparoscopic via, being necessary the use of twice labelled as much with patent blue and radioisotope (colloid of labelled rhenium with {sup 99m}Tc, total dose of 3 MCi) to achieve the identification of the ganglion. (Author)

  9. 智能视频监控技术在哨位安全威胁智能识别中的应用%Application of Intelligent Video Surveillance Technology in Sentry Safety Threat Intelligent Recognition

    Institute of Scientific and Technical Information of China (English)

    刘治红; 骆云志

    2011-01-01

    针对以人工为主的传统监控系统的缺点,对智能视频监控技术在哨位安全威胁智能识别中的应用进行研究.介绍智能监控技术及发展趋势,分析智能分析技术在哨位安全监控预警中的作用.结合目前哨位安全面临的复杂形势和现有安全监控报警手段之间的差异,提出典型应用场景的哨位安全威胁智能识别系统解决方案,阐述了其系统架构、关健设备和关健技术.该研究可为哨位开展安全防护工作提供参考.%Aiming at the limitation of the traditional manual video surveillance system, discuss the applying of intelligent video analysis technology in sentry safety threat intelligent recognition. Introduces the intelligent video analysis technology and developing trend, and analyzes the effect of applying it to sentry safety threat alarm. According to the incongruity between sentry faced with safety position and usable safety defend methods, presents a solution for typical scene of sentry, describe its system framework, key device and key technology. The study may offer reference to sentry safety defend.

  10. 77 FR 52212 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-29

    ..., ``a repair doubler, tripler, or quadrupler is installed;'' to ``a repair doubler; a doubler and a tripler; or a doubler, tripler, and quadrupler.'' Boeing stated that a tripler installation also has a doubler installed, and a quadrupler installation also has a doubler and a tripler installed. Each...

  11. Boeing vallandas ebaeetilise finantsjuhi / Annika Matson, Raivo Sormunen

    Index Scriptorium Estoniae

    Matson, Annika, 1976-

    2003-01-01

    USA lennukitootja Boeing finantsjuht Mike Sears vallandati USA Õhujõududes hankespetsialistina töötanud Darleen Druyuni palkamise ning sel viisil Boeingut puudutavate lepingute mõjutamise tõttu. Diagramm: Boeingu käive kannatab skandaali tõttu

  12. 78 FR 61164 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-10-03

    ... bushings, and inner cylinder bushings. For all airplanes, this AD requires a maintenance program revision... proposed to require a maintenance program revision, one-time inspections of the MLG truck beam, and related..., 2013) to specify the repetitive interval for the lubrication schedule (as referenced in Boeing...

  13. Gezondheidsrisico's brand EL AL-Boeing

    NARCIS (Netherlands)

    van Bruggen M; Janssen PJCM; Kliest JJG; Meulenbelt J; Smetsers RCGM; Uijt de Haag PAM; de Mik G; Elzinga G; IEM; CSR; VIC; LSO; SB4; DIR

    1998-01-01

    Op verzoek van het ministerie van VWS heeft het RIVM onderzoek verricht naar mogelijke gezondheidsrisico's van de verbranding of verspreiding van stoffen en goederen die zich aan boord bevonden van de in 1992 verongelukte El Al-Boeing. Allereerst heeft het RIVM de in de ladinglijst genoemde st

  14. 78 FR 42895 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-07-18

    ... Federal Aviation Administration 14 CFR Part 39 RIN 2120-AA64 Airworthiness Directives; The Boeing Company Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking (NPRM... to detect WFD before it becomes a hazard to flight. We will not grant any extensions of...

  15. Boeing vallandas ebaeetilise finantsjuhi / Annika Matson, Raivo Sormunen

    Index Scriptorium Estoniae

    Matson, Annika, 1976-

    2003-01-01

    USA lennukitootja Boeing finantsjuht Mike Sears vallandati USA Õhujõududes hankespetsialistina töötanud Darleen Druyuni palkamise ning sel viisil Boeingut puudutavate lepingute mõjutamise tõttu. Diagramm: Boeingu käive kannatab skandaali tõttu

  16. The Boeing Company's Manufacturing Technology Student Internship. Evaluation Report.

    Science.gov (United States)

    Owens, Thomas R.

    The Boeing Company contracted with the Northwest Regional Educational Laboratory to evaluate its student internship program, part of a "school-to-work" effort modeled after the nationally recognized Tech Prep initiative. The company's involvement in the Tech Prep Program has been implemented in three phases: (1) the initial phase helped…

  17. Boeing Company gives again to engineering design team endowment

    OpenAIRE

    Owczarski, Mark

    2008-01-01

    In 2007 Virginia Tech's Student Engineers' Council announced the creation of an endowment to benefit student design teams at the university. During the fall semester of 2007, The Boeing Company increased the size of this endowment with a gift of $50,000 from its Global Corporate Citizenship disaster relief team budget and a second gift of $15,000 from its grants program.

  18. 77 FR 36139 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-06-18

    ... significant economic impact, positive or negative, on a substantial number of small entities under the... current inspections for cracking of the frame, HFEC inspections for cracking of the reinforcement angle..., and reinforcement angle, in accordance with the Accomplishment Instructions of Boeing Alert...

  19. 77 FR 46932 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-07

    .... Request To Address Effects of NPRM (76 FR 78574, December 19, 2011) on Winglets Aviation Partners Boeing... Service Bulletin 767-57A0126, dated August 12, 2011, and has determined that the installation of winglets... the installation of these winglets does not affect accomplishing the NPRM. American Airlines...

  20. 78 FR 21236 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-04-10

    ..., August 16, 2012) on Winglets Aviation Partners Boeing (APB) stated that it has reviewed the NPRM (77 FR... that the installation of winglets, per Supplemental Type Certificate (STC) ST01518SE, ``does not affect them.'' We infer that APB means the installation of these winglets does not affect accomplishing...

  1. 78 FR 28729 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-16

    ... Regarding the Installation of Winglets Aviation Partners Boeing (APB) stated that it has reviewed the NPRM... installation of winglets per Supplemental Type Certificate (STC) ST01518SE (http://rgl.faa.gov/Regulatory--and... commenter's statement that the installation of winglets as specified in STC ST01518SE...

  2. 77 FR 12166 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-02-29

    ... superseding an existing airworthiness directive (AD) for certain Model 757-200, -200PF, -200CB, and -300... number six auxiliary slat track, causing electrical wires in the bundle to arc, which damaged both the..., contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H-65...

  3. 77 FR 61542 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-10

    ... flange of the inboard track at the rear spar attachment of each outboard flap, and eventual rework of the... the rear spar attachment of each outboard flap, and eventual rework of the flap track assembly and..., repair or rework the flap track per the ``Repair and Rework Instructions'' specified in Boeing AOM...

  4. 78 FR 22439 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-04-16

    ... Company Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed... all The Boeing Company Model 737-100, -200, -200C, -300, -400, and -500 series airplanes. The existing... around the galley service doorway hinge cutouts, add inspections of certain repaired structure at...

  5. Boeing to Rank Colleges by Measuring Graduates' Job Success

    Science.gov (United States)

    Basken, Paul

    2008-01-01

    Boeing Company, the Chicago-based aerospace giant, has spent the past year matching internal data from employee evaluations with information about the colleges its engineers attended. It has used that analysis to create a ranking system, which it plans to unveil in the coming month, that will show which colleges have produced the workers it…

  6. 76 FR 81879 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2011-12-29

    ... available in the AD docket shortly after receipt. FOR FURTHER INFORMATION CONTACT: Ivan Li, Aerospace...., Renton, Washington 98057-3356; phone: (425) 917-6437; fax: (425) 917-6590; email: ivan.li@faa.gov... clips, and contacting Boeing for repair instructions and doing the repair for main upper sill web...

  7. Antimicrobial susceptibility patterns of unusual nonfermentative gram-negative bacilli isolated from Latin America: report from the SENTRY Antimicrobial Surveillance Program (1997-2002

    Directory of Open Access Journals (Sweden)

    Ana C Gales

    2005-10-01

    Full Text Available The antimicrobial susceptibility of 176 unusual non-fermentative gram-negative bacilli (NF-GNB collected from Latin America region through the SENTRY Program between 1997 and 2002 was evaluated by broth microdilution according to the National Committee for Clinical Laboratory Standards (NCCLS recommendations. Nearly 74% of the NF-BGN belonged to the following genera/species: Burkholderia spp. (83, Achromobacter spp. (25, Ralstonia pickettii (16, Alcaligenes spp. (12, and Cryseobacterium spp. (12. Generally, trimethoprim/sulfamethoxazole (MIC50, 16 µg/ml; 18.8% susceptible and meropenem (MIC50, 8 µg/ml; 50% susceptible against Ralstonia pickettii. Since selection of the most appropriate antimicrobial agents for testing and reporting has not been established by the NCCLS for many of NF-GNB species, results from large multicenter studies may help to guide the best empiric therapy.

  8. Scaling laws in (e,3e) processes

    Energy Technology Data Exchange (ETDEWEB)

    Gasaneo, G; Rodriguez, K V [Departamento de Fisica - Universidad Nacional del Sur and CONICET, 8000 BahIa Blanca, Buenos Aires (Argentina); Ancarani, L U; Cappello, C Dal [Laboratoire de Physique Moleculaire et des Collisions, Universite Paul Verlaine - Metz, 57078 Metz (France); Charpentier, I [Laboratoire de Physique et Mecanique des Materiaux, UMR CNRS 7554, Ile du Saulcy, 57045 Metz (France)

    2009-11-01

    We study the double ionization of helium-like ions by impact of electrons with high incident energy. Within the isoelectronic sequence, an approximate scaling law for (e,3e) differential cross sections is proposed and confirmed by calculations. The latter are performed using 14-parameters Hylleraas-like wave functions to represent the bound electrons in the initial channel, plane waves for the fast incoming and scattered electrons, and a continuum distorted wave approach for the two ejected electrons in the final channel.

  9. Status of the Boeing Dish Engine Critical Component Project

    Energy Technology Data Exchange (ETDEWEB)

    Brau, H.W.; Diver, R.B.; Nelving, H.; Stone, K.W.

    1999-01-08

    The Boeing Company's Dish Engine Critical Component (DECC) project started in April of 1998. It is a continuation of a solar energy program started by McDonnell Douglas (now Boeing) and United Stirling of Sweden in the mid 1980s. The overall objectives, schedule, and status of this project are presented in this paper. The hardware test configuration, hardware background, operation, and test plans are also discussed. A summary is given of the test data, which includes the daily power performance, generated energy, working-gas usage, mirror reflectivity, solar insolation, on-sun track time, generating time, and system availability. The system performance based upon the present test data is compared to test data from the 1984/88 McDonnell Douglas/United Stirling AB/Southem California Edison test program. The test data shows that the present power, energy, and mirror performance is comparable to when the hardware was first manufactured 14 years ago.

  10. Searching for Environments That Could Support Life: Lessons Learned From Six Deep Sea Cruises with the Sentry and Nereus Autonomous Underwater Vehicles

    Science.gov (United States)

    Yoerger, D. R.; Kinsey, J. C.; Jakuba, M.; Camilli, R.; German, C. R.; Shank, T. M.; Bowen, A.; Nakamura, K.; Seeps 2009 Science Team; Oases 2009 Science Team; Gruvee 2010 Science Team; Enlighten 2010 Science Team; Hmmv 2010 Science Team

    2010-12-01

    In the past year, we have used our Sentry and Nereus Autonomous Underwater Vehicles (AUV) on six deep sea cruises searching for extreme environments that can support life. Two of these cruises took place on Mid-Ocean Ridge terrain (Mid Cayman Rise, Galapagos Rift), three on active methane seeps (Santa Monica/Santa Barbara Basins, Hydrate Ridge, Haakon-Mosby Mud Volcano), and one took place at the site of the Deepwater Horizon blowout. This presentation summarizes how we used the vehicles, their automatic control systems, and their sensor suites in these different environments to identify and quantify chemical fluxes emerging from the seafloor. We also took advantage of complementary data from lowered and towed platforms. Examples will include the following: * ●In the Cayman Trough and the Galapagos Rift, we used in-situ chemical sensing (conductivity, temperature, optical backscatter, and redox potential) to locate hydrothermal sources. * ●In the Galapagos Rift, we also used our 400khz multibeam sonar to locate hydrothermal sites using acoustic backscatter from plumes and by building bathymetric maps of likely hydrothermal structures. * ●In the Santa Monica and Santa Barbara Basins, we used the TETHYS in-situ mass spectrometer to locate active methane seeps and to determine the ratio of biogenic to thermogenic methane through isotopic analysis. We used this information in real-time to alter the vehicle's trajectory and, hence, improve measurements over the most interesting locations. * ●At the site of the Deepwater Horizon blowout, we used Sentry and TETHYS to map a deep hydrocarbon plume from just outside the vessel exclusion zone out to a distance of 35 km. Analysis of oxygen data from an electrode, an optode, the mass spectrometer, and from titration of samples brought to the surface supported estimates of microbial respiration rates. * ●On Hydrate Ridge, we showed that the 400khz multibeam sonar is an effective tool for locating active methane bubble

  11. Effects of Breakpoint Changes on Carbapenem Susceptibility Rates ofEnterobacteriaceae: Results from the SENTRY Antimicrobial Surveillance Program, United States, 2008 to 2012

    Directory of Open Access Journals (Sweden)

    Robert P Rennie

    2014-01-01

    Full Text Available In the absence of clinical resistance, breakpoints for many antimicrobial agents are often set high. Clinical failures following use of the agents over time requires re-evaluation of breakpoints. This is based on patient response, pharmacokinetic/pharmacodynamic information and in vitro minimal inhibitory concentration data. Data from the SENTRY Antimicrobial Surveillance Program has shown that Clinical and Laboratory Standards Institute breakpoint changes for carbapenems that occurred between 2008 and 2012 in North America have resulted in decreased levels of susceptibility for some species. In particular, reduced susceptibility to imipenem was observed for Proteus mirabilis (35% and Morganella morganii (80%. Minor decreases in susceptibility were also noted for Enterobacter species with ertapenem (5% and imipenem (4.3%, and Serratia species with imipenem (6.4%. No significant decreases in susceptibility were observed for meropenem following the breakpoint changes. There were no earlier breakpoints established for doripenem. Very few of these Enterobacteriaceae produce carbapenamase enzymes; therefore, the clinical significance of these changes has not yet been clearly determined. In conclusion, ongoing surveillance studies with in vitro minimum inhibitory concentration data are essential in predicting the need for breakpoint changes and in identifying the impact of such changes on the percent susceptibility of different species.

  12. 75 FR 21499 - Airworthiness Directives; The Boeing Company Model 737-600, -700, -700C, -800, -900, and -900ER...

    Science.gov (United States)

    2010-04-26

    ..., Airline Support, e-mail: rse.boecom@boeing.com . The report must include the inspection results including... Commercial Airplanes Group, Attention: Manager, Airline Support, e-mail: rse.boecom@boeing.com . The report...

  13. 75 FR 52242 - Airworthiness Directives; The Boeing Company Model 737-600, -700, -700C, -800, -900, and -900ER...

    Science.gov (United States)

    2010-08-25

    ...: Manager, Airline Support, e- mail: rse.boecom@boeing.com . The report must include the inspection results..., Airline Support, e-mail: rse.boecom@boeing.com . The report must include the inspection results...

  14. 75 FR 15328 - Airworthiness Directives; The Boeing Company Model 757 Airplanes

    Science.gov (United States)

    2010-03-29

    ...: Nicholas Wilson, Aerospace Engineer, Cabin Safety and Environmental Systems Branch, ANM-150S, FAA, Seattle... Boeing Service Bulletin 757-35A0015, Revision 2, dated June 15, 2000. The commenter states that this... condition. The commenter also states that, since Boeing Service Bulletin 757-35A0015, dated September...

  15. Measurement of the Radiative $K_{e3}$ Branching Ratio

    CERN Document Server

    Lai, A; Bevan, A; Dosanjh, R S; Gershon, T J; Hay, B; Kalmus, George Ernest; Lazzeroni, C; Munday, D J; Olaiya, E; Parker, M A; White, T O; Wotton, S A; Barr, G; Bocquet,; Ceccucci, A; Çuhadar-Dönszelmann, T; Cundy, Donald C; D'Agostini, G; Doble, Niels T; Falaleev, V; Gatignon, L; Gonidec, A; Gorini, B; Govi, G; Grafström, P; Kubischta, Werner; Mikulec, I; Lacourt, A; Norton, A; Palestini, S; Panzer-Steindel, B; Taureg, H; Velasco, M; Wahl, H; Cheshkov, C; Khristov, P Z; Kekelidze, Vladimir D; Litov, L; Madigozhin, D T; Molokanova, N A; Potrebenikov, Yu K; Stoynev, S; Zinchenko, A I; Knowles, I; Martin, V; Sacco, R; Walker, A; Contalbrigo, M; Dalpiaz, Pietro; Duclos, J; Frabetti, P L; Gianoli, A; Martini, M; Petrucci, F; Savrié, M; Bizzeti, A; Calvetti, M; Collazuol, G; Graziani, G; Iacopini, E; Lenti, M; Martelli, F; Veltri, M; Becker, H G; Eppard, K; Eppard, M; Fox, H; Kalter, A; Kleinknecht, K; Koch, U; Köpke, L; Lopes da Silva, P; Marouelli, P; Pellmann, I A; Peters, A; Renk, B; Schmidt, S A; Schönharting, V; Schué, Yu; Wanke, R; Winhart, A; Wittgen, M; Chollet, J C; Fayard, L; Iconomidou-Fayard, L; Ocariz, J; Unal, G; Wingerter-Seez, I; Anzivino, Giuseppina; Cenci, P; Imbergamo, E; Lubrano, P; Mestvirishvili, A; Nappi, A; Pepé, M; Piccini, M; Bertanza, L; Carosi, R; Casali, R; Cerri, C; Cirilli, M; Costantini, F; Fantechi, R; Giudici, Sergio; Mannelli, I; Pierazzini, G M; Sozzi, M; Chèze, J B; Cogan, J; De Beer, M; Debu, P; Formica, A; Granier de Cassagnac, R; Mazzucato, E; Peyaud, B; Turlay, René; Vallage, B; Holder, M; Maier, A; Ziolkowski, M; Arcidiacono, R; Biino, C; Cartiglia, N; Marchetto, F; Menichetti, E; Pastrone, N; Nassalski, J P; Rondio, Ewa; Szleper, M; Wislicki, W; Wronka, S; Dibon, Heinz; Fischer, G; Jeitler, Manfred; Markytan, Manfred; Neuhofer, G; Pernicka, M; Taurok, A; Widhalm, L

    2005-01-01

    We present a measurement of the relative branching ratio of the decay {K}^0 -> pi+-e-+ nu gamma ({K}_e3 gamma) with respect to {K}^0 -> pi+- e-+ nu (gamma) ({k}_e3 + k}_e3 gamma) decay. The result is based on observation of 19 000 {K}_e3 gamma and 5.6 . {10}^6 {K}_e3 decays. The value of branching ratio is Br({K}^0 _e3 gamma{E}^*_gamma > 30 MeV, {theta}^*_e gamma > 20 deg) / Br({K}^0_e3 = (0.964 +- {0.008}^+0.011_0.009)%. This result agrees with the theoretical predictions but is at variance with a recently published result.

  16. Regional variation in the prevalence of extended-spectrum beta-lactamase-producing clinical isolates in the Asia-Pacific region (SENTRY 1998-2002).

    Science.gov (United States)

    Hirakata, Yoichi; Matsuda, Junichi; Miyazaki, Yoshitsugu; Kamihira, Shimeru; Kawakami, Sayoko; Miyazawa, Yukihisa; Ono, Yasuo; Nakazaki, Nobuhiko; Hirata, Yasuyoshi; Inoue, Matsuhisa; Turnidge, John D; Bell, Jan M; Jones, Ronald N; Kohno, Shigeru

    2005-08-01

    We examined the prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains of Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Proteus mirabilis, Citrobacter koseri, and Salmonella spp. that were isolated as part of the SENTRY Asia-Pacific Surveillance Program between 1998 and 2002. During the study period, a total of 6,388 strains were gathered from 17 medical centers in 7 countries and examined for ESBL production and hyperproduction of K. oxytoca chromosomal K1 beta-lactamase enzyme. High rates of confirmed ESBL-producing isolates were found in K. pneumoniae strains from Singapore (35.6%), followed by those from mainland China (30.7%), South Africa (28.1%), and the Philippines (21.9%), whereas the rates were less than 10% in Japan and Australia. ESBL-producing E. coli strains were also prominent in mainland China (24.5%), Hong Kong (14.3%), and Singapore (11.3%). ESBL-producing K. oxytoca were common in the Philippines (38.5%), Singapore (33.3%), and China (30.0%). Hyperproduction of K. oxytoca chromosomal K1 beta-lactamase enzyme was common in Australia and Japan. P. mirabilis strains from Singapore produced ESBL (17.9%) despite the low prevalence (0-8.1%) in other countries. Few ESBL-producing C. koseri and Salmonella spp. strains were found in Japan, Singapore, Taiwan, and South Africa. Although there was variation among countries in substrate preference, ceftazidime was more likely to detect presumptive ESBL phenotype in K. pneumoniae and aztreonam more likely in E. coli, whereas ceftriaxone was the best substrate for the confirmation of ESBL production. ESBL-producing strains showed high levels of co-resistance to aminoglycosides, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin. Imipenem retained activity against all ESBL-producing strains. Organisms expressing ESBLs are widely distributed in the Asia-Pacific region, although prevalence rates vary significantly.

  17. E3: Economy - Energy - Environment; Supporting Manufacturing Leadership through Sustainability

    Science.gov (United States)

    The E3 initiative is designed to help you thrive in a new business era focused on sustainability and, working together, to promote sustainable manufacturing and economic growth throughout the United States. Within the E3 framework, we can: - Drive Innovation - Increase Manufacturing Productivity - Boost Local Economies - Reduce Environmental Impacts - Foster Development - Conserve Energy and Resources This website provides information and tools for E3, including fact sheets, contacts, and calculators.

  18. The BOES spectropolarimeter for Zeeman measurements of stellar magnetic fields

    CERN Document Server

    Kim, Kang-Min; Valyavin, Gennady G; Plachinda, Sergei; Jang, Jeong Gyun; Jang, Be-Ho; Seong, Hyeon Cheol; Lee, Byeong-Cheol; Kang, Dong-Il; Park, Byeong-Gon; Yoon, Tae Seog; Vogt, Steven S

    2007-01-01

    We introduce a new polarimeter installed on the high-resolution fiber-fed echelle spectrograph (called BOES) of the 1.8-m telescope at the Bohyunsan Optical Astronomy Observatory, Korea. The instrument is intended to measure stellar magnetic fields with high-resolution (R $\\sim$ 60000) spectropolarimetric observations of intrinsic polarization in spectral lines. In this paper we describe the spectropolarimeter and present test observations of the longitudinal magnetic fields in some well-studied F-B main sequence magnetic stars (m_v < 8.8^m). The results demonstrate that the instrument has a high precision ability of detecting the fields of these stars with typical accuracies ranged from about 2G to a few tens of gauss.

  19. ATM Technology Demonstration-1 Phase II Boeing Configurable Graphical Display (CGD) Software Design Description

    Science.gov (United States)

    Wilber, George F.

    2017-01-01

    This Software Description Document (SDD) captures the design for developing the Flight Interval Management (FIM) system Configurable Graphics Display (CGD) software. Specifically this SDD describes aspects of the Boeing CGD software and the surrounding context and interfaces. It does not describe the Honeywell components of the CGD system. The SDD provides the system overview, architectural design, and detailed design with all the necessary information to implement the Boeing components of the CGD software and integrate them into the CGD subsystem within the larger FIM system. Overall system and CGD system-level requirements are derived from the CGD SRS (in turn derived from the Boeing System Requirements Design Document (SRDD)). Display and look-and-feel requirements are derived from Human Machine Interface (HMI) design documents and working group recommendations. This Boeing CGD SDD is required to support the upcoming Critical Design Review (CDR).

  20. Estonian Airi Boeing sattus kaks korda hädaolukorda / Krister Kivi

    Index Scriptorium Estoniae

    Kivi, Krister, 1975-

    2011-01-01

    Estonian Airi Boeing ES-ABL sattus 2011. aasta algus kahel korral ohtlikku olukorda. Lennuamet tegi Estonian Airile ettekirjutuse, kuid seda pole ameti kodulehel avaldatud. Lennufirma kapteni ja lennuohutuse inspektori Andreas Kari, lennuameti selgitusi

  1. Estonian Airi Boeing sattus kaks korda hädaolukorda / Krister Kivi

    Index Scriptorium Estoniae

    Kivi, Krister, 1975-

    2011-01-01

    Estonian Airi Boeing ES-ABL sattus 2011. aasta algus kahel korral ohtlikku olukorda. Lennuamet tegi Estonian Airile ettekirjutuse, kuid seda pole ameti kodulehel avaldatud. Lennufirma kapteni ja lennuohutuse inspektori Andreas Kari, lennuameti selgitusi

  2. The DoD C-17 Versus the Boeing 777. A Comparison of Acquisition and Development

    Science.gov (United States)

    1999-10-01

    American Airlines, Delta Air Lines, British Airways , Japan Air Lines, All-Nippon Airways , Qantas , and Cathay Pacific. It also allowed A Lee Battershell...United and All N ipon Airways were "snooping around. -1° Summary By October 1990, Boeing had completed its market analysis, selected the 777...took to develop and produce the C-17. The 777 originated in the late 1980s during market research by the Seattle-based Boeing Company. To determine

  3. Molecular insights into RBR E3 ligase ubiquitin transfer mechanisms.

    Science.gov (United States)

    Dove, Katja K; Stieglitz, Benjamin; Duncan, Emily D; Rittinger, Katrin; Klevit, Rachel E

    2016-08-01

    RING-in-between-RING (RBR) ubiquitin (Ub) ligases are a distinct class of E3s, defined by a RING1 domain that binds E2 Ub-conjugating enzyme and a RING2 domain that contains an active site cysteine similar to HECT-type E3s. Proposed to function as RING/HECT hybrids, details regarding the Ub transfer mechanism used by RBRs have yet to be defined. When paired with RING-type E3s, E2s perform the final step of Ub ligation to a substrate. In contrast, when paired with RBR E3s, E2s must transfer Ub onto the E3 to generate a E3~Ub intermediate. We show that RBRs utilize two strategies to ensure transfer of Ub from the E2 onto the E3 active site. First, RING1 domains of HHARI and RNF144 promote open E2~Ubs. Second, we identify a Ub-binding site on HHARI RING2 important for its recruitment to RING1-bound E2~Ub. Mutations that ablate Ub binding to HHARI RING2 also decrease RBR ligase activity, consistent with RING2 recruitment being a critical step for the RBR Ub transfer mechanism. Finally, we demonstrate that the mechanism defined here is utilized by a variety of RBRs.

  4. Contemporary potencies of minocycline and tetracycline HCL tested against Gram-positive pathogens: SENTRY Program results using CLSI and EUCAST breakpoint criteria.

    Science.gov (United States)

    Jones, Ronald N; Wilson, Michael L; Weinstein, Melvin P; Stilwell, Matthew G; Mendes, Rodrigo E

    2013-04-01

    Tetracycline class agents vary widely in their activity against emerging important antimicrobial-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter spp. Also, published susceptibility breakpoints are discordant between the Clinical and Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST), and regulatory-approved documents. We have assessed the impact of these differences for tetracycline HCL and minocycline when tested against contemporary Gram-positive pathogens. The SENTRY Antimicrobial Surveillance Program (2011) compared minocycline and tetracycline HCL activity via reference methods (M07-A9) using a worldwide collection of S. aureus (SA; 4917 strains with 1955 MRSA), Streptococcus pneumoniae (SPN; 1899), S. pyogenes (GRA; 246), and S. agalactiae (GRB; 217). Regardless of applied categorical breakpoints, minocycline exhibited wider coverage (% susceptible) than tetracycline HCL of 4.5-11.8/0.5-2.6/1.4-2.3/0.4-0.4% for MRSA/SPN/GRB/GRA, respectively. Lower EUCAST susceptible breakpoints produced reduced susceptibility rates for minocycline ranging from no difference (≤0.5 μg/mL) for GRA to -8.9% (≤1 μg/mL) for MRSA (97.2% susceptible by CLSI; 88.3% by EUCAST). Use of tetracycline HCL-susceptible results to predict minocycline susceptibility was very accurate (99.0-100.0%), with absolute categorical agreement rates ranging from 92.1% to 98.4% (CLSI) to 98.4% to 99.6% (EUCAST) for streptococci; greatest predictive error was noted using the CLSI breakpoints (14.7%) compared to EUCAST criteria (only 5.0%; acceptable), both for MRSA testing dominated by false-resistant results for minocycline. In conclusion, minocycline demonstrates continued superior in vitro activity compared to tetracycline HCL when testing SA (especially MRSA) and pathogenic streptococci. When testing tetracyclines, laboratories must recognize the expanded spectrum of minocycline against

  5. E3: Economy - Energy - Environment; Supporting Manufacturing Leadership through Sustainability

    Data.gov (United States)

    U.S. Environmental Protection Agency — The E3 initiative is designed to help you thrive in a new business era focused on sustainability and, working together, to promote sustainable manufacturing and...

  6. About E3: Economy – Energy – Environment

    Science.gov (United States)

    This page explains EPA's E3 – Economy, Energy, and Environment – program, a federal and local technical assistance initiative, helping manufacturers adapt and thrive with a focus on sustainability.

  7. E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration

    Directory of Open Access Journals (Sweden)

    Arun Upadhyay

    2017-05-01

    Full Text Available Cells regularly synthesize new proteins to replace old or damaged proteins. Deposition of various aberrant proteins in specific brain regions leads to neurodegeneration and aging. The cellular protein quality control system develop various defense mechanisms against the accumulation of misfolded and aggregated proteins. The mechanisms underlying the selective recognition of specific crucial protein or misfolded proteins are majorly governed by quality control E3 ubiquitin ligases mediated through ubiquitin-proteasome system. Few known E3 ubiquitin ligases have shown prominent neurodevelopmental functions, but their interactions with different developmental proteins play critical roles in neurodevelopmental disorders. Several questions are yet to be understood properly. How E3 ubiquitin ligases determine the specificity and regulate degradation of a particular substrate involved in neuronal proliferation and differentiation is certainly the one, which needs detailed investigations. Another important question is how neurodevelopmental E3 ubiquitin ligases specifically differentiate between their versatile range of substrates and timing of their functional modulations during different phases of development. The premise of this article is to understand how few E3 ubiquitin ligases sense major molecular events, which are crucial for human brain development from its early embryonic stages to throughout adolescence period. A better understanding of these few E3 ubiquitin ligases and their interactions with other potential proteins will provide invaluable insight into disease mechanisms to approach toward therapeutic interventions.

  8. Ares I Aerodynamic Testing at the Boeing Polysonic Wind Tunnel

    Science.gov (United States)

    Pinier, Jeremy T.; Niskey, Charles J.; Hanke, Jeremy L.; Tomek, William G.

    2011-01-01

    Throughout three full design analysis cycles, the Ares I project within the Constellation program has consistently relied on the Boeing Polysonic Wind Tunnel (PSWT) for aerodynamic testing of the subsonic, transonic and supersonic portions of the atmospheric flight envelope (Mach=0.5 to 4.5). Each design cycle required the development of aerodynamic databases for the 6 degree-of-freedom (DOF) forces and moments, as well as distributed line-loads databases covering the full range of Mach number, total angle-of-attack, and aerodynamic roll angle. The high fidelity data collected in this facility has been consistent with the data collected in NASA Langley s Unitary Plan Wind Tunnel (UPWT) at the overlapping condition ofMach=1.6. Much insight into the aerodynamic behavior of the launch vehicle during all phases of flight was gained through wind tunnel testing. Important knowledge pertaining to slender launch vehicle aerodynamics in particular was accumulated. In conducting these wind tunnel tests and developing experimental aerodynamic databases, some challenges were encountered and are reported as lessons learned in this paper for the benefit of future crew launch vehicle aerodynamic developments.

  9. Integration of NOAA Ship Okeanos Explorer Seafloor Mapping, Little Hercules ROV, and Sentry AUV Data into Ocean Exploration Operations and Public Data Holdings

    Science.gov (United States)

    Lobecker, E.; Malik, M.; Skarke, A. D.; VerPlanck, N.

    2012-12-01

    Within NOAA's Office of Ocean Exploration and Research, the Okeanos Explorer Program's main tools for preliminary ocean exploration include a Kongsberg EM 302 multibeam sonar (30 kHz), Kongsberg EK 60 singlebeam sonar (18 kHz), and Knudsen subbottom profiler (3.5 kHz chirp). The program devoted multiple expeditions in the Gulf of Mexico and U.S. Atlantic Margin during its 2012 Field Season to confirm and further develop the EM 302 multibeam sonar's water column backscatter data capability to detect gaseous seeps and vents. While mapping in the seafloor and water column in the vicinity of the salt domes of the Northern Gulf of Mexico, the EM 302 detected over two hundred distinct seeps in the water column. Several seeps have been explored in more detail using high definition cameras and lighting systems of the remotely operated vehicle Little Hercules and the camera platform Seirios. This included filming bubbles escaping from the seafloor at the locations determined by the EM 302 data to ground truth EM302 observations and deduce other properties of these gas seeps e.g. gas flux, and effect of these seeps on surrounding ecosystem. These seeps are now a major research focus area by scientists at the University of New Hampshire's Center for Coastal and Ocean Mapping and other academic institutions around the U.S., and the U.S. Bureau of Ocean Energy Management. . While mapping the Blake Ridge and Cape Fear Diapirs, seven distinct seeps were detected, each rising approximately 900 meters from the seafloor in water depths ranging from 2200 to 2500 meters. Several of these seeps were further explored with Woods Hole Oceanographic Institute's Sentry autonomous underwater vehicle, utilizing itsReson 7125 high resolution multibeam, photo imagery, sidescan, subbottom, and various in-situ sensors to characterize the local environment. It is to be noted that very few of these seeps were previously known. Following the Okeanos Explorer Program's paradigm of "Always Exploring

  10. Radiative origin of solar scale and $U_{e3}$

    CERN Document Server

    Joshipura, A S

    2002-01-01

    We make a general study of possibility of generating the solar scale $\\Delta_{\\odot}$ and the CHOOZ angle $U_{e3}$ radiatively by assuming that they are zero at some high scale. The most general neutrino mass matrix leading to this result is determined in a CP conserving theory. This matrix contains four independent parameters which can be fixed in terms of physical observables. The standard weak radiative corrections then lead to non-zero $\\Delta_{\\odot}$ and $U_{e3}$ without drastically altering the other tree level results. As a consequence, both $\\Delta_{\\odot}$ and $U_{e3}$ are predicted in terms of other physically observable parameters. These predictions are insensitive to specific form of the neutrino mass matrix. The solar scale and $U_{e3}$ are strongly correlated with the effective neutrino mass $m_{ee}$ probed in neutrinoless double beta decay. In particular, the LMA solution to the solar neutrino problem arise for $m_{ee}$ close to the present experimental limit. An example of specific texture is...

  11. Summary of Model Predictions for $U_{e3}$

    CERN Document Server

    Joshipura, A S

    2004-01-01

    We present a short discussion on the expected magnitude of $|U_{e3}|$ in the context of various scenarios proposed to describe neutrino masses and mixing. Generic expectation is relatively large ($>0.05$) values for $\\ue3$ which occur in many well-motivated theoretical scenarios and models.

  12. CHANG'E-3 contingency scheme and trajectory

    Science.gov (United States)

    Liu, Lei; Cao, Jian-feng; Liu, Yong; Hu, Song-jie; Tang, Ge-shi; Xie, Jian-feng

    2015-02-01

    This paper addresses contingency trajectories of CHANG'E-3 in the case of a failure of the lunar brake, which is crucial to the CHANG'E-3 mission, i.e., the first Chinese lunar soft-landing and rover mission. Considering the flight-time and control-energy requirements placed on the contingency trajectories, the paper proposes a direct return method and a low-energy return method and develops the corresponding contingency trajectories based on the CHANG'E-3 cislunar transfer trajectory. The direct return method was studied on return style, flight time, control energy, and influence of maneuver time on energy. The low-energy return method was investigated using the method of invariant manifold calculations for a Lissajous orbit, the method of direct libration-point orbit transfer and injection, and the control strategy used for a low-energy trajectory. The results demonstrate that the control energy for direct return trajectories can be reduced using a certain flight course. When a flight time of less than half of a month is desired, a trajectory from the north celestial pole should be selected as a lunar approach trajectory for CHANG'E-3. Otherwise, a trajectory from the south celestial pole should be selected. Furthermore, these two trajectories have approximately equal velocity increments if their flight-time difference is close to half of a month. In the case of the low-energy return method, methods using approximate manifold calculations for a Lissajous orbit and the direct transfer and injection to a libration-point orbit are proposed and shown to be useful. CHANG'E-3 would return via the Sun-Earth L2 libration point and would require four maneuvers during its flight. The low-energy return method offers remarkable energy savings of up to 267 m/s compared to the direct return method. The methodology not only provides a contingency control technique for CHANG'E-3 and for future lunar missions, but it also serves as a beneficial supplement to the present studies

  13. The Boeing Company's Manufacturing Technology Student Internship. Evaluation Report (1994-95).

    Science.gov (United States)

    Wang, Changhua; Owens, Thomas R.

    An evaluation was conducted of the Boeing Company's summer internship program for students enrolled in a manufacturing technology program after grades 11, 12, and 13 (first year of community college). The evaluation included the following activities: a review of documents describing the internship structure, student selection process, and…

  14. The Boeing Company gives $50,000 to Student Design Team Endowment

    OpenAIRE

    Nystrom, Lynn A.

    2007-01-01

    Last April, Virginia Tech's Student Engineers' Council (SEC) announced the creation of an endowment to benefit student design teams at the university. With the beginning of the fall semester, The Boeing Company increased the size of this endowment with a gift of $50,000 from its Global Corporate Citizenship (GCC) disaster relief team budget.

  15. The Boeing Company's Manufacturing Technology Student Internship. Final Evaluation Report for 1996.

    Science.gov (United States)

    Owens, Tom

    A study evaluated The Boeing Company's Student Internship Program for students enrolled in a manufacturing technology program. The programs in the Seattle (Washington) and Portland (Oregon) areas provided students with three progressive internship levels offered in the summers of grades 11, 12, and 13 (the first year of community college). The…

  16. The Boeing Company Applied Academics Project Evaluation: Year Four. Evaluation Report.

    Science.gov (United States)

    Wang, Changhua; Owens, Thomas R.

    This paper describes fourth-year outcomes (1993-94) of the Boeing Company-funded Applied Academics Project. Since the 1990-91 school year, the company has provided funds to improve and expand applied academics in 60 Washington high schools. Data were collected from pre- and post-surveys of students enrolled in the project's Applied Mathematics…

  17. 75 FR 75 - Special Conditions: Boeing Model 787-8 Airplane; Overhead Crew Rest Compartment

    Science.gov (United States)

    2010-01-04

    ... Model 787-8 Airplane; Overhead Crew Rest Compartment AGENCY: Federal Aviation Administration (FAA), DOT... installation of an overhead crew rest compartment. The applicable airworthiness regulations do not contain... Design Features Crew rest compartments have been installed and certificated on several Boeing...

  18. 75 FR 8279 - Airworthiness Directives; The Boeing Company Model 747 Airplanes

    Science.gov (United States)

    2010-02-24

    .... For airplanes with previously installed repairs, before further flight, do rework (i.e., replace any... contact Boeing for repair or rework data, the data must be approved in accordance with the procedures specified in paragraph (x) of this AD and the repair or rework must be done before further flight. (i)...

  19. 世代更迭 E3争锋

    Institute of Scientific and Technical Information of China (English)

    华尔兹

    2013-01-01

    《GT赛车6》来了!不同于《GT赛车5》经历的长时间等待,已经对PS3机能了如指掌的制作组将在今年冬天为大家带来全新的《GT赛车》!“《GT》系列”每一作都伴随着惊人的进化,相信已经看过E3的《GT赛车6》预告片的玩家已经激动不已了吧,

  20. Perfil de sensibilidade a antimicrobianos de bactérias isoladas do trato respiratório baixo de pacientes com pneumonia internados em hospitais brasileiros: resultados do Programa SENTRY, 1997 e 1998

    Directory of Open Access Journals (Sweden)

    SADER HÉLIO S.

    2001-01-01

    Full Text Available Introdução: Pneumonia hospitalar é a mais fatal das infecções hospitalares, com taxas de mortalidade de 30 a 60%. Estima-se que 15% de todas as mortes associadas à hospitalização estejam diretamente relacionadas a pneumonias hospitalares. O SENTRY é um estudo de vigilância de resistência a antimicrobianos envolvendo centros médicos em todo o mundo. Objetivo: Avaliar a sensibilidade a antimicrobianos de bactérias isoladas no trato respiratório baixo de pacientes com pneumonia internados em hospitais brasileiros. Material e métodos: Foram avaliadas 525 amostras bacterianas de 11 hospitais brasileiros, como parte do programa SENTRY. Os isolados foram testados por microdiluição em caldo contra um grande número de antimicrobianos. Resultados: As cinco espécies mais freqüentes foram (n/%: Pseudomonas aeruginosa (158/30,1%, Staphylococcus aureus (103/19,6%, Acinetobacter spp. (68/13,0%, Klebsiella spp. (50/9,5%, e Enterobacter spp. (44/8,4%. Essas cinco espécies representam mais de 80% de toda a amostragem. A P. aeruginosa apresentou altas taxas de resistência à maioria dos antimicrobianos testados. As maiores taxas de sensibilidade foram apresentadas por piperacilina/tazobactam (71,5% e meropenem (69,0%. Os compostos com maior atividade in vitro contra Acinetobacter spp. foram imipenem e meropenem (80,9% de sensibilidade seguido pela tetraciclina (63,2%. A sensibilidade das amostras de Klebsiella spp. foi muito baixa. MICs > ou = 2mig/mL para ceftriaxona ou ceftazidima, indicando produção de ESBL, foram encontrados em 36,0% das amostras. Os antimicrobianos mais ativos contra Klebsiella spp. foram os carbapenens (100% de sensibilidade e as quinolonas (92,0% de sensibilidade. Ceftriaxona foi ativa contra somente 56,8% das amostras de Enterobacter spp. (MIC50, 1mig/mL, enquanto a cefepima foi ativa contra 88,6% destes isolados (MIC50, <= 0,12mig/mL. A resistência à oxacilina foi detectada em 43,7% dos isolados de S. aureus. As

  1. Ubiquitin E3 ligase FIEL1 regulates fibrotic lung injury through SUMO-E3 ligase PIAS4.

    Science.gov (United States)

    Lear, Travis; McKelvey, Alison C; Rajbhandari, Shristi; Dunn, Sarah R; Coon, Tiffany A; Connelly, William; Zhao, Joe Y; Kass, Daniel J; Zhang, Yingze; Liu, Yuan; Chen, Bill B

    2016-05-30

    The E3 small ubiquitin-like modifier (SUMO) protein ligase protein inhibitor of activated STAT 4 (PIAS4) is a pivotal protein in regulating the TGFβ pathway. In this study, we discovered a new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFβ signaling pathway through the site-specific ubiquitination of PIAS4. FIEL1 targets PIAS4 using a double locking mechanism that is facilitated by the kinases PKCζ and GSK3β. Specifically, PKCζ phosphorylation of PIAS4 and GSK3β phosphorylation of FIEL1 are both essential for the degradation of PIAS4. FIEL1 protein is highly expressed in lung tissues from patients with idiopathic pulmonary fibrosis (IPF), whereas PIAS4 protein levels are significantly reduced. FIEL1 overexpression significantly increases fibrosis in a bleomycin murine model, whereas FIEL1 knockdown attenuates fibrotic conditions. Further, we developed a first-in-class small molecule inhibitor toward FIEL1 that is highly effective in ameliorating fibrosis in mice. This study provides a basis for IPF therapeutic intervention by modulating PIAS4 protein abundance.

  2. Spectrin’s chimeric E2/E3 enzymatic activity

    Science.gov (United States)

    Goodman, Steven R; Petrofes Chapa, Rachel

    2015-01-01

    In this minireview, we cover the discovery of the human erythrocyte α spectrin E2/E3 ubiquitin conjugating/ligating enzymatic activity and the specific cysteines involved. We then discuss the consequences when this activity is partially inhibited in sickle cell disease and the possibility that the same attenuation is occurring in multiple organ dysfunction syndrome. We finish by discussing the reasons for believing that nonerythroid α spectrin isoforms (I and II) also have this activity and the importance of testing this hypothesis. If correct, this would suggest that the nonerythroid spectrin isoforms play a major role in protein ubiquitination in all cell types. This would open new fields in experimental biology focused on uncovering the impact that this enzymatic activity has upon protein–protein interactions, protein turnover, cellular signaling, and many other functions impacted by spectrin, including DNA repair. PMID:26283706

  3. Akt is negatively regulated by the MULAN E3 ligase

    Institute of Scientific and Technical Information of China (English)

    Seunghee Bae; Jongdoo Kim; Hong-Duck Um; In-Chul Park; Su-Jae Lee; Seon Young Nam; Young-Woo Jin; Jae Ho Lee; Sungkwan An; Sun-Yong Kim; Jin Hyuk Jung; Yeongmin Yoon; Hwa Jun Cha; Hyunjin Lee; Karam Kim; Jongran Kim; In-Sook An

    2012-01-01

    The serine/threonine kinase Akt functions in multiple cellular processes,including cell survival and tumor development.Studies of the mechanisms that negatively regulate Akt have focused on dephosphorylation-mediated inactivation.In this study,we identified a negative regulator of Akt,MULAN,which possesses both a RING finger domain and E3 ubiquitin ligase activity.Akt was found to directly interact with MULAN and to be ubiquitinated by MULAN in vitro and in vivo.Other molecular assays demonstrated that phosphorylated Akt is a substantive target for both interaction with MULAN and ubiquitination by MULAN.The results of the functional studies suggest that the degradation of Akt by MULAN suppresses cell proliferation and viability.These data provide insight into the Akt ubiquitination signaling network.

  4. Strategická analýza společností Airbus a Boeing

    OpenAIRE

    Engelmajer, Tomáš

    2009-01-01

    The market for large commercial aircraft is in turn dominated by the duopoly of Airbus SAS, a division of EADS, and Boeing Commercial Airplanes, a division of The Boeing Company. My Aim is to describe the current strategic and financial situation of the two largest companies in the aerospace industry with a particular focus on the divisions supplying Large Commercial Aircraft. I describe the production of civil airliners in the whole context of the current global economic situation and the fu...

  5. Plan, formulate, discuss and correlate a NASTRAN finite element vibrations model of the Boeing Model 360 helicopter airframe

    Science.gov (United States)

    Gabel, R.; Lang, P. F.; Smith, L. A.; Reed, D. A.

    1989-01-01

    Boeing Helicopter, together with other United States helicopter manufacturers, participated in a finite element applications program to emplace in the United States a superior capability to utilize finite element analysis models in support of helicopter airframe design. The activities relating to planning and creating a finite element vibrations model of the Boeing Model 36-0 composite airframe are summarized, along with the subsequent analytical correlation with ground shake test data.

  6. Market Dominance, Efficiency, Innovation, and Globalization: A Case Study of the Tanker Competition Between Boeing and Northrop Grumman/EADS

    Science.gov (United States)

    2008-04-23

    corporate practices in the post- Enron world, to more up-to- date and open government procurement practices. These trends have resulted in the coalescence of...tankers from Boeing for $23.5 billion following a Pentagon procurement scandal , in which one of the key Air Force procurement officials, Darleen Druyen...and the CFO of Boeing, Michael Sears, went to jail. The scandal was brought to light partially with the assistance of Senator McCain’s office (Wolf

  7. Data Mining of NASA Boeing 737 Flight Data: Frequency Analysis of In-Flight Recorded Data

    Science.gov (United States)

    Butterfield, Ansel J.

    2001-01-01

    Data recorded during flights of the NASA Trailblazer Boeing 737 have been analyzed to ascertain the presence of aircraft structural responses from various excitations such as the engine, aerodynamic effects, wind gusts, and control system operations. The NASA Trailblazer Boeing 737 was chosen as a focus of the study because of a large quantity of its flight data records. The goal of this study was to determine if any aircraft structural characteristics could be identified from flight data collected for measuring non-structural phenomena. A number of such data were examined for spatial and frequency correlation as a means of discovering hidden knowledge of the dynamic behavior of the aircraft. Data recorded from on-board dynamic sensors over a range of flight conditions showed consistently appearing frequencies. Those frequencies were attributed to aircraft structural vibrations.

  8. Salapärane Boeing tõi Eestisse konteinereid / Ester Vilgats

    Index Scriptorium Estoniae

    Vilgats, Ester

    2005-01-01

    Ilmunud ka: Pärnu Postimees 8. nov., lk. 3, Postimees : na russkom jazõke 10. nov. lk. 10. Pärnu lennujaama juhataja Erki Teemägi ja Kaitsepolitsei Pärnu osakonna politseidirektor Kalev Kont kinnitasid, et Pärnu lennuväljal 12. jaanuaril 2003. aastal maandunud Boeing 737 vedas kaubakonteinereid, mitte terroristidest sõjavange, nagu väitis ajaleht Washington Post. Vt. samas: Neeme Raud. Inimõiguslased ootavad euroliidu sekkumist

  9. Salapärane Boeing tõi Eestisse konteinereid / Ester Vilgats

    Index Scriptorium Estoniae

    Vilgats, Ester

    2005-01-01

    Ilmunud ka: Pärnu Postimees 8. nov., lk. 3, Postimees : na russkom jazõke 10. nov. lk. 10. Pärnu lennujaama juhataja Erki Teemägi ja Kaitsepolitsei Pärnu osakonna politseidirektor Kalev Kont kinnitasid, et Pärnu lennuväljal 12. jaanuaril 2003. aastal maandunud Boeing 737 vedas kaubakonteinereid, mitte terroristidest sõjavange, nagu väitis ajaleht Washington Post. Vt. samas: Neeme Raud. Inimõiguslased ootavad euroliidu sekkumist

  10. Management strategies in the aerospace industry. Particular case: The Boeing Company

    Directory of Open Access Journals (Sweden)

    Daniela MOCENCO

    2015-03-01

    Full Text Available The present paper aims to provide an overview of the aviation industry in the United States (US. The study focuses on Boeing Company analyzing the organizational architecture and management strategies applied throughout its evolution. The paper is structured in three parts: the first part presents the scientific references; part two focuses on the structure, management strategies and performances of the company; the last part is devoted to conclusions

  11. Management strategies in the aerospace industry. Particular case: The Boeing Company

    OpenAIRE

    Daniela MOCENCO

    2015-01-01

    The present paper aims to provide an overview of the aviation industry in the United States (US). The study focuses on Boeing Company analyzing the organizational architecture and management strategies applied throughout its evolution. The paper is structured in three parts: the first part presents the scientific references; part two focuses on the structure, management strategies and performances of the company; the last part is devoted to conclusions

  12. Advanced composite elevator for Boeing 727 aircraft. Volume 1: Technical summary

    Science.gov (United States)

    Chovil, D. V.; Harvey, S. T.; Mccarty, J. E.; Desper, O. E.; Jamison, E. S.; Syder, H.

    1981-01-01

    The design, development, analysis, and testing activities and results that were required to produce five and one-half shipsets of advanced composite elevators for Boeing 727 aircraft are summarized. During the preliminary design period, alternative concepts were developed. After selection of the best design, detail design and basic configuration improvements were evaluated. Five and one-half shipsets were manufactured. All program goals (except competitive cost demonstration) were accomplished when our design met or exceeded all requirements, criteria, and objectives.

  13. Using binary optical elements (BOEs) to generate rectangular spots for illumination in micro flow cytometer

    Science.gov (United States)

    Zhao, Jingjing; You, Zheng

    2016-01-01

    This work introduces three rectangular quasi-flat-top spots, which are provided by binary optical elements (BOEs) and utilized for the illumination in a microflow cytometer. The three spots contain, respectively, one, two, and three rectangles (R1, R2, and R3). To test the performance of this mechanism, a microflow cytometer is established by integrating the BOEs and a three-dimensional hydrodynamic focusing chip. Through the experiments of detecting fluorescence microbeads, the three spots present good fluorescence coefficients of variation in comparison with those derived from commercial instruments. Benefiting from a high spatial resolution, when using R1 spot, the micro flow cytometer can perform a throughput as high as 20 000 events per second (eps). Illuminated by R2 or R3 spot, one bead emits fluorescence twice or thrice, thus the velocity can be measured in real time. Besides, the R3 spot provides a long-time exposure, which is conducive to improving fluorescence intensity and the measurement stability. In brief, using the spots shaped and homogenized by BOEs for illumination can increase the performance and the functionality of a micro flow cytometer. PMID:27733892

  14. Nuclear targeting of an endosomal E3 ubiquitin ligase.

    Science.gov (United States)

    Bocock, Jeffrey P; Carmicle, Stephanie; Madamba, Egbert; Erickson, Ann H

    2010-06-01

    Ring finger protein 13 (RNF13) is an E3 ubiquitin ligase embedded in endosome membranes. The protein undergoes constitutive post-translational proteolysis, making its detection difficult unless cells are incubated with a proteasome inhibitor to allow biosynthetic forms to accumulate. When cells were treated with phorbol 12-myristate 13-acetate (PMA), RNF13 avoided proteolysis. A similar stabilization was seen on ionomycin treatment of cells. Drug treatment stabilized both the full-length protein and a membrane-embedded C-terminal fragment generated following ectodomain shedding. Immunofluorescence staining revealed that PMA treatment caused the protein to accumulate in recycling endosomes, where it colocalized with transferrin receptor, and on the inner nuclear membrane, where it colocalized with lamin B. Expression of dominant-negative Rab11 inhibited nuclear localization, suggesting RNF13 was targeted to the inner nuclear membrane through recycling endosomes. New protein synthesis was necessary for this targeting. Nuclear localization was confirmed by immunoelectron microscopy and by purification of the inner nuclear membrane. Stress-induced transport of an endosomal protein to the inner nuclear membrane is a novel mechanism for introduction of regulatory proteins to the DNA environment. RNF13, with its ubiquitin ligase-active RING domain, has the potential to turn over key nuclear proteins in response to signals received at the plasma membrane.

  15. $\\pi_{e3}$ form factor $f_{-}$ near mass shell

    CERN Document Server

    Krivoruchenko, M I

    2014-01-01

    Generalized Ward-Takahashi identity (gWTI) in the pion sector for broken isotopic symmetry is derived and used for the model-independent calculation of the longitudinal form factor $f_{-}$ of the $\\pi_{e3}$ vector vertex. The on-shell $f_{-}$ is found to be proportional to the mass difference of pions and the difference between vector isospin $ T = 1 $ and scalar isospin $ T = 2 $ pion radii. A numerical estimate of the form factor gives a value two times higher than the earlier estimate in the quark model. Off-shell form factors are known to be ambiguous because of the gauge dependence and the freedom in parameterization of the fields. The near-mass-shell $f_{-}$ appears to be an exception, allowing the experimental verification of the gWTI consequences. We calculate the near-mass-shell $f_{-}$ using the gWTI and dispersion techniques. The results are discussed in the context of the conservation of vector current (CVC) condition.

  16. E3 Success Story - Transforming and Promoting Sustainable Manufacturing in Alabama

    Science.gov (United States)

    Alabama E3 is expanding to other manufacturing sectors and expanding its scope. Alabama E3 now includes a workforce training and education component and is also developing a new innovation engineering green module that focuses on improving sustainability

  17. Apolipoprotein E3/E3 genotype decreases the risk of pituitary dysfunction after traumatic brain injury due to various causes: preliminary data.

    Science.gov (United States)

    Tanriverdi, Fatih; Taheri, Serpil; Ulutabanca, Halil; Caglayan, Ahmet Okay; Ozkul, Yusuf; Dundar, Munis; Selcuklu, Ahmet; Unluhizarci, Kursad; Casanueva, Felipe F; Kelestimur, Fahrettin

    2008-09-01

    Traumatic brain injury (TBI) is a devastating public health problem which may result in hypopituitarism. However, the mechanisms and the risk factors responsible for hypothalamo-pituitary dysfunction due to TBI are still unclear. Although APO E is one of the most abundant protein in hypothalamo-pituitary region, there is no study investigating the relation between APO E polymorphism and TBI-induced hypopituitarism. This study was undertaken to determine whether APO E genotypes modulate the pituitary dysfunction risk after TBI due to various causes, including traffic accident, boxing, and kickboxing. Ninety-three patients with TBI (mean age, 30.61 +/- 1.25 years) and 27 healthy controls (mean age, 29.03 +/- 1.70 years) were included in the study. Pituitary functions were evaluated, and APO E genotypes (E2/E2; E3/E3; E4/E4; E2/E3; E2/E4; E3/E4) were screened. Twenty-four of 93 subjects (25.8%) had pituitary dysfunction after TBI. The ratio of pituitary dysfunction was significantly lower in subjects with APO E3/E3 (17.7%) than the subjects without APO E3/E3 genotype (41.9%; p = 0.01), and the corresponding odds ratio was 0.29 (95% confidence interval [CI], 0.11-0.78). In conclusion, this study provides strong evidence for the first time that APO E polymorphism is associated with the development of TBI-induced pituitary dysfunction. Present data demonstrated that APO E3/E3 genotype decreases the risk of hypopituitarism after TBI. The demonstration of the association between the APO E polymorphism and TBI may provide a new point of view in this field and promote further studies.

  18. Influence of Machine-Derived Smoke Yields on Biomarker of Exposure (BOE Levels in Cigarette Smokers*

    Directory of Open Access Journals (Sweden)

    Scherer Gerhard

    2015-01-01

    Full Text Available Individual uptake of tobacco smoke constituents by smoking is highly variable in cigarette smokers and cannot be predicted by smoking behaviour variables and machine-derived smoke yields. It is well established that uptake of smoke constituents is best described by a series of bio-markers of exposure (BOEs such as metabolites of nico-tine, tobacco-specific nitrosamines (TSNAs, polycyclic aromatic hydrocarbons (PAHs, aromatic amines, benzene, 1,3-butadiene, acrolein, hydrogen cyanide, 2,5-dimethyl-furan and other smoke constituents.

  19. Parametric Evaluation of Absorption Losses and Comparison of Numerical Results to Boeing 707 Aircraft Experimental HIRF Results

    Science.gov (United States)

    Kitaygorsky, J.; Amburgey, C.; Elliott, J. R.; Fisher, R.; Perala, R. A.

    A broadband (100 MHz-1.2 GHz) plane wave electric field source was used to evaluate electric field penetration inside a simplified Boeing 707 aircraft model with a finite-difference time-domain (FDTD) method using EMA3D. The role of absorption losses inside the simplified aircraft was investigated. It was found that, in this frequency range, none of the cavities inside the Boeing 707 model are truly reverberant when frequency stirring is applied, and a purely statistical electromagnetics approach cannot be used to predict or analyze the field penetration or shielding effectiveness (SE). Thus it was our goal to attempt to understand the nature of losses in such a quasi-statistical environment by adding various numbers of absorbing objects inside the simplified aircraft and evaluating the SE, decay-time constant τ, and quality factor Q. We then compare our numerical results with experimental results obtained by D. Mark Johnson et al. on a decommissioned Boeing 707 aircraft.

  20. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Specificity of protein ubiquitylation is conferred by E3 ubiquitin (Ub ligases. We have annotated approximately 617 putative E3s and substrate-recognition subunits of E3 complexes encoded in the human genome. The limited knowledge of the function of members of the large E3 superfamily prompted us to generate genome-wide E3 cDNA and RNAi expression libraries designed for functional screening. An imaging-based screen using these libraries to identify E3s that regulate mitochondrial dynamics uncovered MULAN/FLJ12875, a RING finger protein whose ectopic expression and knockdown both interfered with mitochondrial trafficking and morphology. We found that MULAN is a mitochondrial protein - two transmembrane domains mediate its localization to the organelle's outer membrane. MULAN is oriented such that its E3-active, C-terminal RING finger is exposed to the cytosol, where it has access to other components of the Ub system. Both an intact RING finger and the correct subcellular localization were required for regulation of mitochondrial dynamics, suggesting that MULAN's downstream effectors are proteins that are either integral to, or associated with, mitochondria and that become modified with Ub. Interestingly, MULAN had previously been identified as an activator of NF-kappaB, thus providing a link between mitochondrial dynamics and mitochondria-to-nucleus signaling. These findings suggest the existence of a new, Ub-mediated mechanism responsible for integration of mitochondria into the cellular environment.

  1. Antibody to the E3 Glycoprotein Protects Mice against Lethal Venezuelan Equine Encephalitis Virus Infection▿

    Science.gov (United States)

    Parker, Michael D.; Buckley, Marilyn J.; Melanson, Vanessa R.; Glass, Pamela J.; Norwood, David; Hart, Mary Kate

    2010-01-01

    Six monoclonal antibodies were isolated that exhibited specificity for a furin cleavage site deletion mutant (V3526) of Venezuelan equine encephalitis virus (VEEV). These antibodies comprise a single competition group and bound the E3 glycoprotein of VEEV subtype I viruses but failed to bind the E3 glycoprotein of other alphaviruses. These antibodies neutralized V3526 virus infectivity but did not neutralize the parental strain of Trinidad donkey (TrD) VEEV. However, the E3-specific antibodies did inhibit the production of virus from VEEV TrD-infected cells. In addition, passive immunization of mice demonstrated that antibody to the E3 glycoprotein provided protection against lethal VEEV TrD challenge. This is the first recognition of a protective epitope in the E3 glycoprotein. Furthermore, these results indicate that E3 plays a critical role late in the morphogenesis of progeny virus after E3 appears on the surfaces of infected cells. PMID:20926570

  2. Boeing's variable geometry chevron: morphing aerospace structures for jet noise reduction

    Science.gov (United States)

    Calkins, Frederick T.; Mabe, James H.; Butler, George W.

    2006-03-01

    Boeing is applying cutting edge smart material actuators to the next generation morphing technologies for aircraft. This effort has led to the Variable Geometry Chevrons (VGC), which utilize compact, light weight, and robust shape memory alloy (SMA) actuators. These actuators morph the shape of chevrons on the trailing edge of a jet engine in order to optimize acoustic and performance objectives at multiple flight conditions. We have demonstrated a technical readiness level of 7 by successfully flight testing the VGCs on a Boeing 777-300ER with GE-115B engines. In this paper we describe the VGC design, development and performance during flight test. Autonomous operation of the VGCs, which did not require a control system or aircraft power, was demonstrated. A parametric study was conducted showing the influence of VGC configurations on shockcell generated cabin noise reduction during cruise. The VGC system provided a robust test vehicle to explore chevron configurations for community and shockcell noise reduction. Most importantly, the VGC concept demonstrated an exciting capability to optimize jet nozzle performance at multiple flight conditions.

  3. 78 FR 70848 - Special Conditions: Boeing Model 777-200, -300, and -300ER Series Airplanes; Aircraft Electronic...

    Science.gov (United States)

    2013-11-27

    .... The Boeing Model 777-200 airplanes are long-range, wide-body, twin-engine jet airplanes with a maximum... networks connected to systems that perform functions required for the safe operation of the airplane. This... allow increased connectivity to, or access by, external airplane sources, airline operations,...

  4. 78 FR 70849 - Special Conditions: Boeing Model 777-200, -300, and -300ER Series Airplanes; Aircraft Electronic...

    Science.gov (United States)

    2013-11-27

    .... The Boeing Model 777-200 airplanes are long-range, wide-body, twin-engine jet airplanes with a maximum... networks connected to systems that perform functions required for the safe operation of the airplane. This... required for safe flight and operations. 2. The applicant must establish appropriate procedures to...

  5. The Boeing Company's Tech Prep Story: A Community College Bridge to the School-to-Work Strategy.

    Science.gov (United States)

    Gayton, Carver; Parnell, Dale

    1996-01-01

    Reviews the Boeing Tech Prep Program, an associate degree program combining high school and community college vocational and academic curricula. Describes the three phases of the program's development: the provision of seed grants to schools, the development of an associate degree program, and the institution of an internship program. (MAB)

  6. 75 FR 43803 - Airworthiness Directives; The Boeing Company Model 737-100, -200, -200C, -300, -400, and -500...

    Science.gov (United States)

    2010-07-27

    ... FR 67027, December 1, 2003). (3) For service information identified in this AD, contact Boeing... spindles, and to prevent severe flap asymmetry, which could result in reduced control or loss of..., 2010. On December 4, 2003 (68 FR 67027, December 1, 2003), the Director of the Federal...

  7. The Boeing Company's Tech Prep Story: A Community College Bridge to the School-to-Work Strategy.

    Science.gov (United States)

    Gayton, Carver; Parnell, Dale

    1996-01-01

    Reviews the Boeing Tech Prep Program, an associate degree program combining high school and community college vocational and academic curricula. Describes the three phases of the program's development: the provision of seed grants to schools, the development of an associate degree program, and the institution of an internship program. (MAB)

  8. 75 FR 38014 - Airworthiness Directives; The Boeing Company Model 737-200, -300, -400, and -500 Series Airplanes

    Science.gov (United States)

    2010-07-01

    ...., Washington, DC 20590. FOR FURTHER INFORMATION CONTACT: Nicholas Wilson, Aerospace Engineer, Cabin Safety and... Boeing Special Attention Service Bulletin 737-35-1099, Revision 1, dated April 23, 2009, which refers to B/E Aerospace Service Bulletin 174080-35-01, dated February 6, 2006; Revision 1, dated May 1,...

  9. 75 FR 50859 - Airworthiness Directives; The Boeing Company Model 737-600, -700, -700C, -800, and -900 Series...

    Science.gov (United States)

    2010-08-18

    ... Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H-65, Seattle... assembly and through the housing. AirTran asserts that an arc of this significance would trip the currently... conditions identified in the NPRM. CAL contends that the use of arc fault circuit interrupters (AFCIs) is...

  10. 78 FR 76731 - Special Conditions: Boeing Model 777-200, -300, and -300ER Series Airplanes; Rechargeable Lithium...

    Science.gov (United States)

    2013-12-19

    ... Series Airplanes; Rechargeable Lithium Ion Batteries and Battery Systems AGENCY: Federal Aviation... lithium ion batteries and battery system that will be used on an International Communications Group (ICG... uses rechargeable lithium ion batteries and battery systems in the Boeing Model 777-200, -300,...

  11. (e, 3e) reactions at moderate energies visualization of average field effects in atom

    CERN Document Server

    Kuzakov, K A; Gusev, A A; Popov, Y V; Vinitsky, S I

    2002-01-01

    In the case of helium atom the theory is presented for quasi-elastic A (e, 3e) A sup + sup + and A (e, 3 -1e) A sup + sup + atomic reactions in the coplanar symmetric geometry at incident electron energy of several hundreds eV. The comparison with the recent (e, 3 - 1 e) experiment has allowed one to observe the effect of the mean atomic field as well as postcollisional effects.

  12. Mission Analysis and Conceptual Design of a Space Ambulance Utilizing the Boeing X-37B Platform

    Science.gov (United States)

    Blaesser, Nathaniel James

    This paper discusses the concept of operations and modifications for a crew return vehicle from the International Space Station based on the Boeing X-37B platform. The modifications necessary include accommodating a three person crew, adding an environmental control and life support system and modifying the propulsion system to be more conducive to a fast evacuation. Two crew seating configurations were considered and traded for vehicle mass, crew envelope and ease of loading and unloading the injured patient. Computer models were generated to determine key parameters, and the models were validated using physical mock-ups. The mission is considerably shorter than the design reference mission, meaning that there are significant reductions in propellant mass and volume. The results showed that by utilizing the space saved from smaller propellant tanks, and combining the crew's oxygen supply with the propulsion system, the vehicle can be retooled without modifying the outer mold line..

  13. Design and Test of a Blast Shield for Boeing 737 Overhead Compartment

    Directory of Open Access Journals (Sweden)

    Xinglai Dang

    2006-01-01

    Full Text Available This work demonstrates the feasibility of using a composite blast shield for hardening an overhead bin compartment of a commercial aircraft. If a small amount of explosive escapes detection and is brought onboard and stowed in an overhead bin compartment of a passenger aircraft, the current bins provide no protection against a blast inside the compartment. A blast from the overhead bin will certainly damage the fuselage and likely lead to catastrophic inflight structural failure. The feasibility of using an inner blast shield to harden the overhead bin compartment of a Boeing 737 aircraft to protect the fuselage skin in such a threat scenario has been demonstrated using field tests. The blast shield was constructed with composite material based on the unibody concept. The design was carried out using LS-DYNA finite element model simulations. Material panels were first designed to pass the FAA shock holing and fire tests. The finite element model included the full coupling of the overhead bin with the fuselage structure accounting for all the different structural connections. A large number of iterative simulations were carried out to optimize the fiber stacking sequence and shield thickness to minimize weight and achieve the design criterion. Three designs, the basic, thick, and thin shields, were field-tested using a frontal fuselage section of the Boeing 737–100 aircraft. The basic and thick shields protected the integrity of the fuselage skin with no skin crack. This work provides very encouraging results and useful data for optimization implementation of the blast shield design for hardening overhead compartments against the threat of small explosives.

  14. Intricate Crystal Structure of Dihydrolipoamide Dehydrogenase (E3) with its Binding Protein: Multiple Copies, Dynamic and Static Disorders

    Science.gov (United States)

    Makal, A.; Hong, Y. S.; Potter, R.; Vettaikkorumakankauv, A. K.; Korotchkina, L. G.; Patel, M. S.; Ciszak, E.

    2004-01-01

    Human E3 and binding protein E3BP are two components of the pyruvate dehydrogenase complex. Crystallization of E3 with 221-amino acid fragment of E3BP (E3BPdd) led to crystals that diffracted to a resolution of 2.6 Angstroms. Structure determination involved molecular replacement using a dimer of E3 homolog as a search model and de novo building of the E3BPdd peptide. Solution was achieved by inclusion of one E3 dimer at a time, followed by refinement until five E3 dimers were located. This complete content of E3 provided electron density maps suitable for tracing nine peptide chains of E3BPdd, eight of them being identified with partial occupancies. Final content of the asymmetric unit consists of five E3 dimers, each binding one E3BPdd molecule. In four of these molecular complexes, E3BPdd is in static disorder resulting in E3BPdd binding to either one or the other monomer of the E3 dimer. However, E3BPdd of the fifth E3 dimer forms specific contacts that lock it at one monomer. In addition to this static disorder, E3BPdd reveals high mobility in the limited space of the crystal lattice. Support from NIH and NASA.

  15. Procedure Redesign Methods : E3-Control: a redesign methodology for control procedures

    NARCIS (Netherlands)

    Liu, J.; Hofman, W.J.; Tan, Y.H.

    2011-01-01

    This chapter highlights the core research methodology, e3-control, that is applied throughout the ITAIDE project for the purpose of control procedure redesign. We present the key concept of the e3-control methodology and its technical guidelines. Based on the output of this chapter, domain experts

  16. Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice

    NARCIS (Netherlands)

    Leppänen, P.; Luoma, J.S.; Hofker, M.H.; Havekes, L.M.; Ylä-Herttuala, S.

    1998-01-01

    Apo E3-leiden transgenic mice express human dysfunctional apo E variant and develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet. We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic mice using immunocytochemical methods in order to examine foam

  17. Data of evolutionary structure change: 1Q95E-3GD5E [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1Q95E-3GD5E 1Q95 3GD5 E E ANPLYQKHIISINDLSRDDLNLVLATAAKLKANPQPELL...KHKVIASCFFEASTRTRLSFETSMHRLGASVVGFSDSANTSLGKKGETLADTISVISTYVDAIVMRHPQEGAARLATEFSGNVPVLNAGDGSNQHPTQTLLDLFTIQETQGRLDNLHVAMVGD...TELEEYAHYAG-IPVINALTD-HEHPCQVVADLLTIRENFGRLAGLKLAYVGDG--NNVAHSLLLGCAKVG-MSIAVATPEGFTPDPAVSARASEIAGRTGAEVQIL-...line> ILE CA 374 ALA CA 275 THR CA 238 3GD...5 E 3GD5E

  18. Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice

    NARCIS (Netherlands)

    Leppänen, P.; Luoma, J.S.; Hofker, M.H.; Havekes, L.M.; Ylä-Herttuala, S.

    1998-01-01

    Apo E3-leiden transgenic mice express human dysfunctional apo E variant and develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet. We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic mice using immunocytochemical methods in order to examine foam

  19. Procedure Redesign Methods : E3-Control: a redesign methodology for control procedures

    NARCIS (Netherlands)

    Liu, J.; Hofman, W.J.; Tan, Y.H.

    2011-01-01

    This chapter highlights the core research methodology, e3-control, that is applied throughout the ITAIDE project for the purpose of control procedure redesign. We present the key concept of the e3-control methodology and its technical guidelines. Based on the output of this chapter, domain experts m

  20. Map-Based Cloning of the Gene Associated With the Soybean Maturity Locus E3

    Science.gov (United States)

    Watanabe, Satoshi; Hideshima, Rumiko; Xia, Zhengjun; Tsubokura, Yasutaka; Sato, Shusei; Nakamoto, Yumi; Yamanaka, Naoki; Takahashi, Ryoji; Ishimoto, Masao; Anai, Toyoaki; Tabata, Satoshi; Harada, Kyuya

    2009-01-01

    Photosensitivity plays an essential role in the response of plants to their changing environments throughout their life cycle. In soybean [Glycine max (L.) Merrill], several associations between photosensitivity and maturity loci are known, but only limited information at the molecular level is available. The FT3 locus is one of the quantitative trait loci (QTL) for flowering time that corresponds to the maturity locus E3. To identify the gene responsible for this QTL, a map-based cloning strategy was undertaken. One phytochrome A gene (GmPhyA3) was considered a strong candidate for the FT3 locus. Allelism tests and gene sequence comparisons showed that alleles of Misuzudaizu (FT3/FT3; JP28856) and Harosoy (E3/E3; PI548573) were identical. The GmPhyA3 alleles of Moshidou Gong 503 (ft3/ft3; JP27603) and L62-667 (e3/e3; PI547716) showed weak or complete loss of function, respectively. High red/far-red (R/FR) long-day conditions enhanced the effects of the E3/FT3 alleles in various genetic backgrounds. Moreover, a mutant line harboring the nonfunctional GmPhyA3 flowered earlier than the original Bay (E3/E3; PI553043) under similar conditions. These results suggest that the variation in phytochrome A may contribute to the complex systems of soybean flowering response and geographic adaptation. PMID:19474204

  1. A design principle underlying the paradoxical roles of E3 ubiquitin ligases

    Science.gov (United States)

    Lee, Daewon; Kim, Minjin; Cho, Kwang-Hyun

    2014-07-01

    E3 ubiquitin ligases are important cellular components that determine the specificity of proteolysis in the ubiquitin-proteasome system. However, an increasing number of studies have indicated that E3 ubiquitin ligases also participate in transcription. Intrigued by the apparently paradoxical functions of E3 ubiquitin ligases in both proteolysis and transcriptional activation, we investigated the underlying design principles using mathematical modeling. We found that the antagonistic functions integrated in E3 ubiquitin ligases can prevent any undesirable sustained activation of downstream genes when E3 ubiquitin ligases are destabilized by unexpected perturbations. Interestingly, this design principle of the system is similar to the operational principle of a safety interlock device in engineering systems, which prevents a system from abnormal operation unless stability is guaranteed.

  2. Overview of the membrane-associated RING-CH (MARCH) E3 ligase family.

    Science.gov (United States)

    Bauer, Johannes; Bakke, Oddmund; Morth, J Preben

    2016-12-14

    E3 ligases are critical checkpoints for protein ubiquitination, a signal that often results in protein sorting and degradation but has also been linked to regulation of transcription and DNA repair. In line with their key role in cellular trafficking and cell-cycle control, malfunction of E3 ligases is often linked to human disease. Thus, they have emerged as prime drug targets. However, the molecular basis of action of membrane-bound E3 ligases is still unknown. Here, we review the current knowledge on the membrane-embedded MARCH E3 ligases (MARCH-1-6,7,8,11) with a focus on how the transmembrane regions can contribute via GxxxG-motifs to the selection and recognition of other membrane proteins as substrates for ubiquitination. Further understanding of the molecular parameters that govern target protein recognition of MARCH E3 ligases will contribute to development of strategies for therapeutic regulation of MARCH-induced ubiquitination.

  3. E3 ubiquitin ligases as drug targets and prognostic biomarkers in melanoma

    Directory of Open Access Journals (Sweden)

    Kristina Bielskienė

    2015-01-01

    E3 ligases are of interest as drug targets for their ability to regulate proteins stability and functions. Compared to the general proteasome inhibitor bortezomib, which blocks the entire protein degradation, drugs that target a particular E3 ligase are expected to have better selectivity with less associated toxicity. Components of different E3 ligases complexes (FBW7, MDM2, RBX1/ROC1, RBX2/ROC2, cullins and many others are known as oncogenes or tumor suppressors in melanomagenesis. These proteins participate in regulation of different cellular pathways and such important proteins in cancer development as p53 and Notch. In this review we summarized published data on the role of known E3 ligases in the development of melanoma and discuss the inhibitors of E3 ligases as a novel approach for the treatment of malignant melanomas.

  4. 75 FR 81427 - Airworthiness Directives; The Boeing Company Model 747-200C, -200F, -400, -400D, and -400F Series...

    Science.gov (United States)

    2010-12-28

    ... Certain Language in Paragraph (k) of the NPRM Boeing asked that we revise the language in paragraph (k) of... Information Japan Airlines (JAL) asked that we delay issuance until the manufacturer can release Revision 2...

  5. Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase.

    Directory of Open Access Journals (Sweden)

    Donald E Spratt

    Full Text Available The ubiquitin-signaling pathway utilizes E1 activating, E2 conjugating, and E3 ligase enzymes to sequentially transfer the small modifier protein ubiquitin to a substrate protein. During the last step of this cascade different types of E3 ligases either act as scaffolds to recruit an E2 enzyme and substrate (RING, or form an ubiquitin-thioester intermediate prior to transferring ubiquitin to a substrate (HECT. The RING-inBetweenRING-RING (RBR proteins constitute a unique group of E3 ubiquitin ligases that includes the Human Homologue of Drosophila Ariadne (HHARI. These E3 ligases are proposed to use a hybrid RING/HECT mechanism whereby the enzyme uses facets of both the RING and HECT enzymes to transfer ubiquitin to a substrate. We now present the solution structure of the HHARI RING2 domain, the key portion of this E3 ligase required for the RING/HECT hybrid mechanism. The structure shows the domain possesses two Zn²⁺-binding sites and a single exposed cysteine used for ubiquitin catalysis. A structural comparison of the RING2 domain with the HECT E3 ligase NEDD4 reveals a near mirror image of the cysteine and histidine residues in the catalytic site. Further, a tandem pair of aromatic residues exists near the C-terminus of the HHARI RING2 domain that is conserved in other RBR E3 ligases. One of these aromatic residues is remotely located from the catalytic site that is reminiscent of the location found in HECT E3 enzymes where it is used for ubiquitin catalysis. These observations provide an initial structural rationale for the RING/HECT hybrid mechanism for ubiquitination used by the RBR E3 ligases.

  6. Behavior as a sentry of metal toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B.

    1978-01-01

    Many of the toxic properties of metals are expressed as behavioral aberrations. Some of these arise from direct actions on the central nervous system. Others arise from primary events elsewhere, but still influence behavior. Toxicity may be expressed either as objectively measurable phenomena, such as ataxia, or as subjective complaints, such as depression. In neither instance is clinical medicine equipped to provide assessments of subtle, early indices of toxicity. Reviewers of visual disturbances, paresthesia, and mental retardation exemplify the potential contribution of psychology to the toxicology of metals. Behavior and nervous system functions act as sensitive mirrors of metal toxicity. Sensitivity is the prime aim in environmental health assessments. Early detection of adverse effects, before they progress to irreversibility, underlies the strategy for optimal health protection. Some of the toxic actions of metals originate in direct nervous system dysfunction. Others may reflect disturbances of systems less directly linked to behavior than the central nervous system. But behavior, because it expresses the integrated functioning of the organism, can indicate flaws in states and processes outside the nervous system.

  7. Application of winglets and/or wing tip extensions with active load control on the Boeing 747

    Science.gov (United States)

    Allison, R. L.; Perkin, B. R.; Schoenman, R. L.

    1978-01-01

    The application of wing tip modifications and active control technology to the Boeing 747 airplane for the purpose of improving fuel efficiency is considered. Wing tip extensions, wing tip winglets, and the use of the outboard ailerons for active wing load alleviation are described. Modest performance improvements are indicated. A costs versus benefits approach is taken to decide which, if any, of the concepts warrant further development and flight test leading to possible incorporation into production airplanes.

  8. E3 Success Story - Whirlpool Trains Staff on Lean and Green Advantage

    Science.gov (United States)

    Whirlpool Corporation invited Green Suppliers Network representatives to its Monterrey facility to provide training on the Lean and Green Advantage. The project sought to expand E3 initiatives to every part of the company's operations.

  9. E3 Success Story - Advancing Performance in Sustainability and Workforce Development

    Science.gov (United States)

    E3: North Carolina advances performance in sustainability and workforce development strategies for the state's manufacturers. The initiative helps communities and manufacturers address energy and sustainability challenges by leveraging expertise.

  10. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Boomsma, Wouter Krogh; Nielsen, Sofie Vincents; Lindorff-Larsen, Kresten

    2016-01-01

    The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2...... ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions...... of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we...

  11. Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases

    National Research Council Canada - National Science Library

    Riley, B E; Lougheed, J C; Callaway, K; Velasquez, M; Brecht, E; Nguyen, L; Shaler, T; Walker, D; Yang, Y; Regnstrom, K; Diep, L; Zhang, Z; Chiou, S; Bova, M; Artis, D R; Yao, N; Baker, J; Yednock, T; Johnston, J A

    2013-01-01

    Parkin is a RING-between-RING E3 ligase that functions in the covalent attachment of ubiquitin to specific substrates, and mutations in Parkin are linked to Parkinson's disease, cancer and mycobacterial infection...

  12. Protein microarrays for the identification of praja1 e3 ubiquitin ligase substrates.

    Science.gov (United States)

    Loch, Christian M; Eddins, Michael J; Strickler, James E

    2011-06-01

    Although they are the primary determinants of substrate specificity, few E3-substrate pairs have been positively identified, and few E3's profiled in a proteomic fashion. Praja1 is an E3 implicated in bone development and highly expressed in brain. Although it has been well studied relative to the majority of E3's, little is known concerning the repertoire of proteins it ubiquitylates. We sought to identify high confidence substrates for Praja1 from an unbiased proteomic profile of thousands of human proteins using protein microarrays. We first profiled Praja1 activity against a panel of E2's to identify its optimal partner in vitro. We then ubiquitylated multiple, identical protein arrays and detected putative substrates with reagents that vary in ubiquitin recognition according to the extent of chain formation. Gene ontology clustering identified putative substrates consistent with information previously known about Praja1 function, and provides clues into novel aspects of this enzyme's function.

  13. Experimental and Computational Sonic Boom Assessment of Boeing N+2 Low Boom Models

    Science.gov (United States)

    Durston, Donald A.; Elmiligui, Alaa; Cliff, Susan E.; Winski, Courtney S.; Carter, Melissa B.; Walker, Eric L.

    2015-01-01

    Near-field pressure signatures were measured and computational predictions made for several sonic boom models representing Boeing's Quiet Experimental Validation Concept (QEVC) supersonic transport, as well as three axisymmetric calibration models. Boeing developed the QEVC under a NASA Research Announcement (NRA) contract for Experimental Systems Validations for N+2 Supersonic Commercial Transport Aircraft, which was led by the NASA High Speed Project under the Fundamental Aeronautics Program. The concept was designed to address environmental and performance goals given in the NRA, specifically for low sonic boom loudness levels and high cruise efficiency, for an aircraft anticipated to enter service in the 2020 timeframe. Wind tunnel tests were conducted on the aircraft and calibration models during Phases I and II of the NRA contract from 2011 to 2013 in the NASA Ames 9- by 7-Foot and NASA Glenn 8- by 6-Foot Supersonic Wind Tunnels. Sonic boom pressure signatures were acquired primarily at Mach 1.6 and 1.8, and force and moment data were acquired from Mach 0.8 to 1.8. The sonic boom test data were obtained using a 2-in. flat-top pressure rail and a 14-in. round-top tapered "reflection factor 1" (RF1) pressure rail. Both rails capture an entire pressure signature in one data point, and successive signatures at varying positions along or above the rail were used to improve data quality through spatial averaging. The sonic boom data obtained by the rails were validated with high-fidelity numerical simulations of off-body pressures using the CFD codes USM3D, Cart3D, and OVERFLOW. The test results from the RF1 rail showed good agreement between the computational and experimental data when a variety of testing techniques including spatial averaging of a series of pressure signatures were employed, however, reflections off the 2-in. flat-top rail caused distortions in the signatures that did not agree with the CFD predictions. The 9 x 7 and 8 x 6 wind tunnels generally

  14. Ghosts of Milky Way's past: the globular cluster ESO 37-1 (E 3)

    CERN Document Server

    Marcos, R de la Fuente; Bidin, C Moni; Ortolani, S; Carraro, G

    2015-01-01

    Context. In the Milky Way, most globular clusters are highly conspicuous objects that were found centuries ago. However, a few dozen of them are faint, sparsely populated systems identified largely during the second half of the past century. One of the faintest is ESO 37-1 (E 3) and as such it remains poorly studied, with no spectroscopic observations published so far, although it was discovered in 1976. Aims. We investigate the globular cluster E 3 in an attempt to better constrain its fundamental parameters. Spectroscopy of stars in the field of E 3 is shown here for the first time. Methods. Deep, precise VI CCD photometry of E 3 down to V=26 mag is presented and analyzed. Low resolution, medium signal-to-noise ratio spectra of 9 candidate members are studied to derive radial velocity and metallicity. Proper motions from the UCAC4 catalogue are used to explore the kinematics of the bright members of E 3. Results. Isochrone fitting indicates that E 3 is probably very old, with an age of about 13 Gyr; its dis...

  15. Site Environmental Report for Calendar Year 2001. DOE Operations at The Boeing Company, Rocketdyne Propulsion & Power

    Energy Technology Data Exchange (ETDEWEB)

    Rutherford, Phil [The Boeing Company, Canoga Park, CA (United States); Samuels, Sandy [The Boeing Company, Canoga Park, CA (United States); Leee, Majelle [The Boeing Company, Canoga Park, CA (United States)

    2002-09-01

    This Annual Site Environmental Report (ASER) for 2001 describes the environmental conditions related to work performed for the Department of Energy (DOE) at Area IV of the Boeing Rocketdyne Santa Susana Field Laboratory (SSFL). In the past, these operations included development, fabrication, and disassembly of nuclear reactors, reactor fuel, and other radioactive materials under the former Atomics International (AI) Division. Other activities included the operation of large-scale liquid metal facilities for testing of liquid metal fast breeder components at the Energy Technology Engineering Center (ETEC), a government-owned, company-operated test facility within Area IV. All nuclear work was terminated in 1988, and subsequently, all radiological work has been directed toward decontamination and decommissioning (D&D) of the previously used nuclear facilities and associated site areas. Closure of the sodium test facilities began in 1996. Results of the radiological monitoring program for the calendar year of 2001 continue to indicate that there are no significant releases of radioactive material from Area IV of SSFL. All potential exposure pathways are sampled and/or monitored, including air, soil, surface water, groundwater, direct radiation, transfer of property (land, structures, waste), and recycling. All radioactive wastes are processed for disposal at DOE disposal sites and other sites approved by DOE and licensed for radioactive waste. Liquid radioactive wastes are not released into the environment and do not constitute an exposure pathway. No structural debris from buildings, released for unrestricted use, was transferred to municipal landfills or recycled in 2001.

  16. Site Environmental Report for Calendar Year 1999. DOE Operations at The Boeing Company, Rocketdyne

    Energy Technology Data Exchange (ETDEWEB)

    None

    2000-09-01

    OAK A271 Site Environmental Report for Calendar Year 1999. DOE Operations at The Boeing Company, Rocketdyne. This Annual Site Environmental Report (ASER) for 1999 describes the environmental conditions related to work performed for the Department of Energy (DOE) at Area IV of the Rocketdyne Santa Susana Field Laboratory (SSFL). In the past, these operations included development, fabrication, and disassembly of nuclear reactors, reactor fuel, and other radioactive materials under the former Atomics International Division. Other activities included the operation of large-scale liquid metal facilities for testing of liquid metal fast breeder components at the Energy Technology Engineering Center (ETEC), a government-owned, company-operated test facility within Area IV. All nuclear work was terminated in 1988, and subsequently, all radiological work has been directed toward decontamination and decommissioning (D&D) of the previously used nuclear facilities and associated site areas. Large-scale D&D activities of the sodium test facilities began in 1996. This Annual Site Environmental Report provides information showing that there are no indications of any potential impact on public health and safety due to the operations conducted at the SSFL. All measures and calculations of off-site conditions demonstrate compliance with applicable regulations, which provide for protection of human health and the environment.

  17. An overview of Boeing flywheel energy storage systems with high-temperature superconducting bearings

    Science.gov (United States)

    Strasik, M.; Hull, J. R.; Mittleider, J. A.; Gonder, J. F.; Johnson, P. E.; McCrary, K. E.; McIver, C. R.

    2010-03-01

    An overview summary of recent Boeing work on high-temperature superconducting (HTS) bearings is presented. A design is presented for a small flywheel energy storage system that is deployable in a field installation. The flywheel is suspended by a HTS bearing whose stator is conduction cooled by connection to a cryocooler. At full speed, the flywheel has 5 kW h of kinetic energy, and it can deliver 3 kW of three-phase 208 V power to an electrical load. The entire system, which includes a containment structure, is compatible with transportation by forklift or crane. Laboratory measurements of the bearing loss are combined with the parasitic loads to estimate the efficiency of the system. Improvements in structural composites are expected to enable the operation of flywheels with very high rim velocities. Small versions of such flywheels will be capable of very high rotational rates and will likely require the low loss inherent in HTS bearings to achieve these speeds. We present results of experiments with small-diameter rotors that use HTS bearings for levitation and rotate in vacuum at kHz rates. Bearing losses are presented as a function of rotor speed.

  18. SUPPLY CHAIN FEATURES OF THE AEROSPACE INDUSTRY PARTICULAR CASE AIRBUS AND BOEING

    Directory of Open Access Journals (Sweden)

    Daniela MOCENCO

    2015-10-01

    Full Text Available Aerospace sector is one of the most globalized industries in terms of market structure and production system. Through aircraft development programs aviation industry has introduced new solutions to develop its products. The role of the partners involved in the development programs for the new generation aircraft is becoming increasingly important. Supply chain management has become a key factor for major manufacturers in the industry. The new strategies introduced by the aircraft manufacturers have increased the complexity of the supply process, design and production from the aviation industry. This paper highlights a series of factors regarding the aircraft programs supply chain management. In the first part are described the problems encountered by the manufacturers and airlines during the development of the most recent aircraft launched A350XWB and B787 Dreamliner; the second part focuses on the organizational structure of the supply chain, suppliers role within supply chain and also there are described the effects of the new strategies adopted by Airbus and Boeing in the aircraft development; the last part focuses on the risks and challenges that aviation industry is facing.

  19. Auxiliary power unit noise of Boeing B737 and B747 aircraft

    Science.gov (United States)

    Kwan, Jimmy S. W.; Yang, S. J. Eric

    Most modern civil aircraft have an Auxiliary Power Unit (APU) which provides compressed air for engine starting and the air-conditioning system on ground and electrical power for aircraft use both on-ground and in-fligth. It is basically a gas turbine engine and it consists of a compressor section, a turbine section, and an accessory drive section. For Boeing B737 and B747 aircraft, the APU is located inside a compartment in the tail section of the aircraft and is completely enclosed by a sound-reduction fire-proof titanium shroud. APU noise is one of the major noise sources at many airports and is extremely important for a densely populated city such as Hong Kong. The noise from APU can affect many people, including ground crew aircraft maintenance staff, and people living in the vicinity of the airport. However, there is very little information available in the literature about APU noise. This paper describes the noise measurement method and presents the measurement results for APUs of one B747 and two B737 aircraft under both 'loaded' and 'no-load' conditions.

  20. Site Environmental Report for Calendar Year 2003 DOE Operations at The Boeing Company, Rocketdyne Propulsion & Power

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ning [The Boeing Company, Canoga Park, CA (US). Rocketdyne Propulsion and Power; Rutherford, Phil [The Boeing Company, Canoga Park, CA (US). Rocketdyne Propulsion and Power; Samuels, Sandy [The Boeing Company, Canoga Park, CA (US). Rocketdyne Propulsion and Power; Lee, Majelle [The Boeing Company, Canoga Park, CA (US). Rocketdyne Propulsion and Power

    2004-09-30

    This Annual Site Environmental Report (ASER) for 2003 describes the environmental conditions related to work performed for the Department of Energy (DOE) at Area IV of Boeing Rocketdyne’s Santa Susana Field Laboratory (SSFL). In the past, the Energy Technology Engineering Center (ETEC), a government-owned, company-operated test facility, was located in Area IV. The operations at ETEC included development, fabrication, and disassembly of nuclear reactors, reactor fuel, and other radioactive materials. Other activities at ETEC involved the operation of large-scale liquid metal facilities that were used for testing liquid metal fast breeder components. All nuclear work was terminated in 1988; all subsequent radiological work has been directed toward decontamination and decommissioning (D&D) of the former nuclear facilities and their associated sites. Closure of the liquid metal test facilities began in 1996. Results of the radiological monitoring program for the calendar year 2003 continue to indicate that there are no significant releases of radioactive material from Area IV of SSFL. All potential exposure pathways are sampled and/or monitored, including air, soil, surface water, groundwater, direct radiation, transfer of property (land, structures, waste), and recycling.

  1. Ditching Investigation of a 1/24-Scale Model of the Boeing B-47 Airplane

    Science.gov (United States)

    Fisher, Lloyd J.; Windham, John O.

    1950-01-01

    An investigation of a 1/24-scale dynamically similar model of the Boeing B-47 airplane was made to determine the ditching characteristics and proper ditching technique for the airplane. Various conditions of damage, landing attitude, flap setting, and speed were investigated. The behavior of the model was determined from visual observations, motion-picture records, and time-history deceleration records. The results of the investigation are presented in table form, photographs, and curves. The airplane should be ditched at the lowest speed and highest attitude consistent with adequate control; the flaps should be full down. The airplane will probably make a deep but fairly smooth run. The fuselage bottom will be damaged and partially filled with water; consequently, crew members should be assigned ditching stations near an exit in the upper or forward part of the fuselage. The nacelles may be expected to be torn away from the wing. In calm water the maximum decelerations will be about 3g and the landing run will be about 6 fuselage lengths.

  2. Ditching Investigation of a 1/20-Scale Model of the Boeing Stratocruiser Airplane (C-97)

    Science.gov (United States)

    Fisher, Lloyd J.; Windham, John O.

    1955-01-01

    An investigation of a 1/20-scale dynamically similar model of the Boeing Stratocruiser airplane (C-97) was made to determine the ditching characteristics and proper technique for ditching the airplane. Scale-strength bottoms were used to determine probable damage to the fuselage and the effect of damage on behavior. The behavior of the model was determined from visual observations, motion-picture records, and time-history deceleration records. Data are presented in a table, photographs, and curves. It was concluded that the airplane should be ditched at a medium nose-high landing attitude (near 6 deg) with landing flaps full down. The airplane will probably make a smooth run of medium depth with light spray and may even trim up slightly in the water. The fuselage will probably be damaged and the lower compartment filled with water. In calm water, the maximum longitudinal deceleration will be about 4g and the landing run will be about four fuselage lengths.

  3. An Analysis of 20 Years of Space Weathering Effects on the Boeing 376 Spacecraft

    Science.gov (United States)

    Frith, James; Anz-Meador, Phillip; Cowardin, Heather; Buckalew, Brent; Lederer, Susan

    2015-01-01

    The Boeing HS-376 spin stabilized spacecraft was a popular design that was launched continuously into geosynchronous orbit starting in 1980, with the last launch occurring in 2003. Over 50 of the HS-376 buses were produced to fulfill a variety of different communication missions for countries all over the world. The design of the bus is easily approximated as a telescoping cylinder that is covered with solar cells and an Earth-facing antenna that is despun at the top of the cylinder. The similarity in design and the number of spacecraft launched over a long period of time make the HS-376 a prime target for studying the effects of solar weathering on solar panels as a function of time. A selection of primarily non-operational HS-376 spacecraft launched over a 20-year time period were observed using the United Kingdom Infrared Telescope on Mauna Kea and multi-band, near-infrared photometry produced. Each spacecraft was observed for an entire night cycling through ZYJHK filters and time-varying colors produced to compare near-infrared color as a function of launch date. The resulting analysis shown here may help in the future to set launch date constraints on the parent object of unidentified debris objects or other unknown spacecraft.

  4. Wide field nulling imager for TPF: the Boeing-SVS hypertelescope concept

    Science.gov (United States)

    Guyon, Olivier

    2003-02-01

    The Terrestrial Planet Finder (TPF) mission is aimed at providing direct images of Earth-like planets orbiting nearby stars and characterizing their atmospheres (low resolution spectroscopy). The BOEING/SVS hypertelescope concept, NRLA (Non-Redundant Linear Array), uses a 35m baseline interferometric rotating array of six 2.3-meter telescopes operating in the infrared (7 to 12 microns) to produce wide field images of exoplanetary systems. The full (u,v) plane coverage of the array offers very good imaging capabilities, which is essential to unambiguously confirm the detection of planets, and also provides an outstanding capability for high resolution/high dynamic range imaging for general astrophysics. Thanks to a novel approach combining pupil densification, phase mask coronagraphy and pupil redilution, this concept combines wide field of view imaging and interferometric nulling of the central star. We first briefly present the techniques used by this concept (phase mask coronagraphy, pupil densification and redilution, aperture synthesis imaging) and demonstrate how they can be used to overcome the limitations commonly encountered by interferometers (low (u,v) plane coverage, small field of view, low dynamical range). A complete computer simulation of the concept has been written and is used to study the performance of the array for exoplanet imaging and spectroscopy. We show that with this concept, detection (S/N=5) of Earth-like planets at 10pc with a 5 microns spectral bandwidth can be achieved in less than an hour (for a 100% quantum efficiency).

  5. Stardust is lifted in the launch tower for mating with a Boeing Delta II rocket

    Science.gov (United States)

    1999-01-01

    Workers inside the launch tower at Pad 17-A, Cape Canaveral Air Station, watch as the third stage of a Boeing Delta II rocket is lowered for mating with the second stage below it. The Stardust spacecraft, above it out of sight, is connected to the rocket's third stage. Stardust, targeted for liftoff on Feb. 6, is destined for a close encounter with the comet Wild 2 in January 2004. Using a silicon-based substance called aerogel, Stardust will capture comet particles flying off the nucleus of the comet. The spacecraft also will bring back samples of interstellar dust. These materials consist of ancient pre-solar interstellar grains and other remnants left over from the formation of the solar system. Scientists expect their analysis to provide important insights into the evolution of the sun and planets and possibly into the origin of life itself. The collected samples will return to Earth in a sample return capsule to be jettisoned as Stardust swings by Earth in January 2006.

  6. Sensibilidade a antimicrobianos de bactérias isoladas do trato respiratório de pacientes com infecções respiratórias adquiridas na comunidade: resultados brasileiros do Programa SENTRY de Vigilância de Resistência a Antimicrobianos dos anos de 1997 e 1998 Susceptibility to respiratory tract isolated bacteria to antimicrobial agents in patients with community-acquired respiratory tract infections: 1997 and 1998 Brazilian data of the SENTRY surveillance program of resistance to antimicrobial agents

    Directory of Open Access Journals (Sweden)

    HÉLIO S. SADER

    2001-01-01

    Full Text Available O tratamento da pneumonia adquirida na comunidade (PAC é habitualmente empírico e o uso de antimicrobianos é baseado em estudos de vigilância. O programa SENTRY foi desenhado para monitorar a resistência a antimicrobianos através de uma rede internacional de laboratórios. Três centros no Brasil participaram do Programa SENTRY em 1997 e em 1998. Métodos: Um total de 344 isolados bacterianos coletados de pacientes com PAC em 1997 e 1998 foram testados contra mais de 20 agentes antimicrobianos pelo método de microdiluição em caldo. Resultados: Entre os S. pneumoniae (176 isolados, 71,6% foram sensíveis à penicilina. Alto nível de resistência à penicilina e resistência à cefotaxima foram encontrados em 2,3 e 4,0%, respectivamente. As novas quinolonas levofloxacina (MIC90, 2mig/mL e gatifloxacina (MIC90, 0,5mig/mL foram ativas contra 100% dos isolados testados. Entre os outros antimicrobianos não beta-lactâmicos testados, os mais ativos foram (% de sensibilidade: cloranfenicol (97,5% > clindamicina (94% > azitromicina (90,3% > claritromicina (89,4% > tetraciclina (76,4% > sulfametoxazol/trimetoprim (60,2%. A percentagem de Haemophilus influenzae (101 isolados resistentes à amoxicilina foi de 90,1%, enquanto entre Moraxella catarrhalis (67 isolados somente 9,0% foram sensíveis. O ácido clavulânico restaurou a atividade de amoxicilina contra H. influenzae e M. catarrhalis. Porém, H. influenzae demonstrou níveis aumentados de resistência para sulfametoxazol/trimetoprim (55,1% de sensibilidade, claritromicina (80,4% de sensibilidade e cefaclor (88,2% de sensibilidade. Todos os isolados de H. influenzae e M. catarrhalis foram sensíveis à levofloxacina (MIC90, Background: Antimicrobial treatment of community-acquired respiratory tract infections (CARTI is usually empiric and antibiotics are chosen on the basis of surveillance studies. The SENTRY Program was designed to monitor antimicrobial resistance via a worldwide

  7. Evidence of an Antimicrobial Peptide Signature Encrypted in HECT E3 Ubiquitin Ligases

    Science.gov (United States)

    Candido-Ferreira, Ivan Lavander; Kronenberger, Thales; Sayegh, Raphael Santa Rosa; Batista, Isabel de Fátima Correia; da Silva Junior, Pedro Ismael

    2017-01-01

    The ubiquitin-proteasome pathway (UPP) is a hallmark of the eukaryotic cell. In jawed vertebrates, it has been co-opted by the adaptive immune system, where proteasomal degradation produces endogenous peptides for major histocompatibility complex class I antigen presentation. However, proteolytic products are also necessary for the phylogenetically widespread innate immune system, as they often play a role as host defense peptides (HDPs), pivotal effectors against pathogens. Here, we report the identification of the arachnid HDP oligoventin, which shares homology to a core member of the UPP, E3 ubiquitin ligases. Oligoventin has broad antimicrobial activity and shows strong synergy with lysozymes. Using computational and phylogenetic approaches, we show high conservation of the oligoventin signature in HECT E3s. In silico simulation of HECT E3s self-proteolysis provides evidence that HDPs can be generated by fine-tuned 26S proteasomal degradation, and therefore are consistent with the hypothesis that oligoventin is a cryptic peptide released by the proteolytic processing of an Nedd4 E3 precursor protein. Finally, we compare the production of HDPs and endogenous antigens from orthologous HECT E3s by proteasomal degradation as a means of analyzing the UPP coupling to metazoan immunity. Our results highlight the functional plasticity of the UPP in innate and adaptive immune systems as a possibly recurrent mechanism to generate functionally diverse peptides. PMID:28119686

  8. A novel role of Drosophila cytochrome P450-4e3 in permethrin insecticide tolerance.

    Science.gov (United States)

    Terhzaz, Selim; Cabrero, Pablo; Brinzer, Robert A; Halberg, Kenneth A; Dow, Julian A T; Davies, Shireen-A

    2015-12-01

    The exposure of insects to xenobiotics, such as insecticides, triggers a complex defence response necessary for survival. This response includes the induction of genes that encode key Cytochrome P450 monooxygenase detoxification enzymes. Drosophila melanogaster Malpighian (renal) tubules are critical organs in the detoxification and elimination of these foreign compounds, so the tubule response induced by dietary exposure to the insecticide permethrin was examined. We found that expression of the gene encoding Cytochrome P450-4e3 (Cyp4e3) is significantly up-regulated by Drosophila fed on permethrin and that manipulation of Cyp4e3 levels, specifically in the principal cells of the Malpighian tubules, impacts significantly on the survival of permethrin-fed flies. Both dietary exposure to permethrin and Cyp4e3 knockdown cause a significant elevation of oxidative stress-associated markers in the tubules, including H2O2 and lipid peroxidation byproduct, HNE (4-hydroxynonenal). Thus, Cyp4e3 may play an important role in regulating H2O2 levels in the endoplasmic reticulum (ER) where it resides, and its absence triggers a JAK/STAT and NF-κB-mediated stress response, similar to that observed in cells under ER stress. This work increases our understanding of the molecular mechanisms of insecticide detoxification and provides further evidence of the oxidative stress responses induced by permethrin metabolism.

  9. A Dual E3 Mechanism for Rub1 Ligation to Cdc53

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Daniel C.; Monda, Julie K.; Grace, Christy R.R.; Duda, David M.; Kriwacki, Richard W.; Kurz, Thimo; Schulman, Brenda A. (Dundee); (SJCH)

    2010-09-16

    In ubiquitin-like protein (UBL) cascades, a thioester-linked E2 {approx} UBL complex typically interacts with an E3 enzyme for UBL transfer to the target. Here we demonstrate a variant mechanism, whereby the E2 Ubc12 functions with two E3s, Hrt1 and Dcn1, for ligation of the UBL Rub1 to Cdc53's WHB subdomain. Hrt1 functions like a conventional RING E3, with its N terminus recruiting Cdc53 and C-terminal RING activating Ubc12Rub1. Dcn1's potentiating neddylation domain (Dcn1{sup P}) acts as an additional E3, reducing nonspecific Hrt1-mediated Ubc12 {approx} Rub1 discharge and directing Ubc12's active site to Cdc53. Crystal structures of Dcn1{sup P}-Cdc53{sup WHB} and Ubc12 allow modeling of a catalytic complex, supported by mutational data. We propose that Dcn1's interactions with both Cdc53 and Ubc12 would restrict the otherwise flexible Hrt1 RING-bound Ubc12 {approx} Rub1 to a catalytically competent orientation. Our data reveal mechanisms by which two E3s function synergistically to promote UBL transfer from one E2 to a target.

  10. Electron delocalization and relaxation behavior in Cu-doped B i2S e3 films

    Science.gov (United States)

    Li, Mingze; Wang, Zhenhua; Yang, Liang; Li, Da; Yao, Q. R.; Rao, G. H.; Gao, Xuan P. A.; Zhang, Zhidong

    2017-08-01

    C uxB i2S e3 is known for superconductivity due to Cu intercalation in the van der Waals gaps between the quintuple layers of B i2S e3 at x >0.10 . Here we report the synthesis and transport properties of Cu-doped C uxB i2S e3 films prepared by the chemical-vapor-deposition (CVD) method with 0.11 ≥x ≥0 . It is found that the insulatinglike temperature-dependent resistivity of polycrystalline C uxB i2S e3 films exhibits a marked metallic downturn and an increase of carrier concentration below ˜37 K. There is also a time-dependent slow relaxation behavior in the resistance at low temperature. These effects might be related to the strong hybridization between C u+ and C u2 + conduction bands from the intercalated C u+ and substituted C u2 + sites in B i2S e3 films. The findings here have important implications for the understanding and development of doping-induced superconductivity in topological insulators.

  11. The centrosomal E3 ubiquitin ligase FBXO31-SCF regulates neuronal morphogenesis and migration.

    Directory of Open Access Journals (Sweden)

    Mayur Vadhvani

    Full Text Available Neuronal development requires proper migration, polarization and establishment of axons and dendrites. Growing evidence identifies the ubiquitin proteasome system (UPS with its numerous components as an important regulator of various aspects of neuronal development. F-box proteins are interchangeable subunits of the Cullin-1 based E3 ubiquitin ligase, but only a few family members have been studied. Here, we report that the centrosomal E3 ligase FBXO31-SCF (Skp1/Cullin-1/F-box protein regulates neuronal morphogenesis and axonal identity. In addition, we identified the polarity protein Par6c as a novel interaction partner and substrate targeted for proteasomal degradation in the control of axon but not dendrite growth. Finally, we ascribe a role for FBXO31 in dendrite growth and neuronal migration in the developing cerebellar cortex. Taken together, we uncovered the centrosomal E3 ligase FBXO31-SCF as a novel regulator of neuronal development.

  12. RBR E3 ubiquitin ligases: new structures, new insights, new questions.

    Science.gov (United States)

    Spratt, Donald E; Walden, Helen; Shaw, Gary S

    2014-03-15

    The RBR (RING-BetweenRING-RING) or TRIAD [two RING fingers and a DRIL (double RING finger linked)] E3 ubiquitin ligases comprise a group of 12 complex multidomain enzymes. This unique family of E3 ligases includes parkin, whose dysfunction is linked to the pathogenesis of early-onset Parkinson's disease, and HOIP (HOIL-1-interacting protein) and HOIL-1 (haem-oxidized IRP2 ubiquitin ligase 1), members of the LUBAC (linear ubiquitin chain assembly complex). The RBR E3 ligases share common features with both the larger RING and HECT (homologous with E6-associated protein C-terminus) E3 ligase families, directly catalysing ubiquitin transfer from an intrinsic catalytic cysteine housed in the C-terminal domain, as well as recruiting thioester-bound E2 enzymes via a RING domain. Recent three-dimensional structures and biochemical findings of the RBRs have revealed novel protein domain folds not previously envisioned and some surprising modes of regulation that have raised many questions. This has required renaming two of the domains in the RBR E3 ligases to more accurately reflect their structures and functions: the C-terminal Rcat (required-for-catalysis) domain, essential for catalytic activity, and a central BRcat (benign-catalytic) domain that adopts the same fold as the Rcat, but lacks a catalytic cysteine residue and ubiquitination activity. The present review discusses how three-dimensional structures of RBR (RING1-BRcat-Rcat) E3 ligases have provided new insights into our understanding of the biochemical mechanisms of these important enzymes in ubiquitin biology.

  13. Fluorescence study of domain structure and lipid interaction of human apolipoproteins E3 and E4.

    Science.gov (United States)

    Mizuguchi, Chiharu; Hata, Mami; Dhanasekaran, Padmaja; Nickel, Margaret; Okuhira, Keiichiro; Phillips, Michael C; Lund-Katz, Sissel; Saito, Hiroyuki

    2014-12-01

    Human apolipoprotein E (apoE) isoforms exhibit different conformational stabilities and lipid-binding properties that give rise to altered cholesterol metabolism among the isoforms. Using Trp-substituted mutations and site- directed fluorescence labeling, we made a comprehensive comparison of the conformational organization of the N- and C-terminal domains and lipid interactions between the apoE3 and apoE4 isoforms. Trp fluorescence measurements for selectively Trp-substituted variants of apoE isoforms demonstrated that apoE4 adopts less stable conformations in both the N- and C-terminal domains compared to apoE3. Consistent with this, the conformational reorganization of the N-terminal helix bundle occurs at lower guanidine hydrochloride concentration in apoE4 than in apoE3 as monitored by fluorescence resonance energy transfer (FRET) from Trp residues to acrylodan attached at the N-terminal helix. Upon binding of apoE3 and apoE4 variants to egg phosphatidylcholine small unilamellar vesicles, similar changes in Trp fluorescence or FRET efficiency were observed for the isoforms, indi- cating that the opening of the N-terminal helix bundle occurs similarly in apoE3 and apoE4. Introduction of mutations into the C-terminal domain of the apoE isoforms to prevent self-association and maintain the monomeric state resulted in great increase in the rate of binding of the C-terminal helices to a lipid surface. Overall, our results demonstrate that the different conformational organizations of the N- and C-terminal domains have a minor effect on the steady-state lipid-binding behavior of apoE3 and apoE4: rather, self-association property is a critical determinant in the kinetics of lipid binding through the C-terminal helices of apoE isoforms.

  14. Case study of the interdisciplinary integration in an IST-E3 project

    DEFF Research Database (Denmark)

    Jørgensen, Ulrik

    2002-01-01

    Case study of a specific IST-E3 project funded by the EU commissions 5th framework program. The case study highlights the difficulties in integrating different disciplinary approaches and suggests that a more openended research strategy should be applied by the commission.......Case study of a specific IST-E3 project funded by the EU commissions 5th framework program. The case study highlights the difficulties in integrating different disciplinary approaches and suggests that a more openended research strategy should be applied by the commission....

  15. Monitoring of high-risk pregnancies using E3 and HPL

    Energy Technology Data Exchange (ETDEWEB)

    Bieglmayer, Ch.; Spona, J.

    1981-01-01

    Routine determinations of HPL and E3 together with other clinical and laboratory checks offer usable information on the state of pregnancy and assist the doctor in taking decisions on the use of therapeutical measures. The anamnesis, the presence of placental insufficiency of EPH-gestosis are important indications for monitoring the pregnancy using HPL and E3. A commercial RIA apparatus (Centria 2) allowing the determination of HPL in a mere hour was compared with our established laboratory method. In 140 determinations, the correlation was r=0.75. Considering its capacity and method, the instrument seems to be more suitable for a small specialized laboratory.

  16. Folding Behaviour for Proteins BBL and E3BD with Gō-like Models

    Institute of Scientific and Technical Information of China (English)

    ZUO Guang-Hong; ZHANG Jian; WANG Jun; WANG Wei

    2005-01-01

    @@ Folding behaviour of protein BBL and its homologue domain E3BD are studied by using an off-lattice Gō-like model. It is found that the folding behaviours of these two proteins are different. Protein BBL folds in a downhill manner, which is consistent with experiments. In contrast, protein E3BD folds cooperatively and has a bimodal distribution of the Q values (the similarity to the native state). By analysing the native structures of the two proteins, it is found that the difference in folding behaviours can be attributed to the different structural features described by the number of nonlocal contacts per residue.

  17. NASA Boeing 757 HIRF test series low power on-the-ground tests

    Energy Technology Data Exchange (ETDEWEB)

    Poggio, A.J.; Pennock, S.T.; Zacharias, R.A.; Avalle, C.A.; Carney, H.L. [National Aeronautics and Space Administration, Langley AFB, VA (United States). Langley Research Center

    1996-08-01

    The data acquisition phase of a program intended to provide data for the validation of computational, analytical, and experimental techniques for the assessment of electromagnetic effects in commercial transports; for the checkout of instrumentation for following test programs; and for the support of protection engineering of airborne systems has been completed. Funded by the NASA Fly-By-Light/ Power-By-Wire Program, the initial phase involved on-the-ground electromagnetic measurements using the NASA Boeing 757 and was executed in the LESLI Facility at the USAF Phillips Laboratory. The major participants in this project were LLNL, NASA Langley Research Center, Phillips Laboratory, and UIE, Inc. The tests were performed over a five week period during September through November, 1994. Measurements were made of the fields coupled into the aircraft interior and signals induced in select structures and equipment under controlled illumination by RF fields. A characterization of the ground was also performed to permit ground effects to be included in forthcoming validation exercises. This report and the associated test plan that is included as an appendix represent a definition of the overall on-the-ground test program. They include descriptions of the test rationale, test layout, and samples of the data. In this report, a detailed description of each executed test is provided, as is the data identification (data id) relating the specific test with its relevant data files. Samples of some inferences from the data that will be useful in protection engineering and EM effects mitigation are also presented. The test plan which guided the execution of the tests, a test report by UIE Inc., and the report describing the concrete pad characterization are included as appendices.

  18. Ophthalmic epidemiology in Europe : the "European Eye Epidemiology" (E3) consortium

    NARCIS (Netherlands)

    Delcourt, Cecile; Korobelnik, Jean-Francois; Buitendijk, Gabrielle H. S.; Foster, Paul J.; Hammond, Christopher J.; Piermarocchi, Stefano; Peto, Tunde; Jansonius, Nomdo; Mirshahi, Alireza; Hogg, Ruth E.; Bretillon, Lionel; Topouzis, Fotis; Deak, Gabor; Grauslund, Jakob; Broe, Rebecca; Souied, Eric H.; Creuzot-Garcher, Catherine; Sahel, Jose; Daien, Vincent; Lehtimaki, Terho; Hense, Hans-Werner; Prokofyeva, Elena; Oexle, Konrad; Rahi, Jugnoo S.; Cumberland, Phillippa M.; Schmitz-Valckenberg, Steffen; Fauser, Sascha; Bertelsen, Geir; Hoyng, Carel; Bergen, Arthur; Silva, Rufino; Wolf, Sebastian; Lotery, Andrew; Chakravarthy, Usha; Fletcher, Astrid; Klaver, Caroline C. W.

    The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000

  19. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Boomsma, Wouter Krogh; Nielsen, Sofie Vincents; Lindorff-Larsen, Kresten;

    2016-01-01

    conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology...

  20. Total Synthesis and Tentative Structural Elucidation of Cryptomoscatone E3: Interplay of Experimental and Computational Studies.

    Science.gov (United States)

    Novaes, Luiz F T; Sarotti, Ariel M; Pilli, Ronaldo A

    2015-12-18

    A successful combination of computational chemistry and total synthesis was explored to tentatively elucidate the absolute configuration of cryptomoscatone E3, a polyketide isolated from the Brazilian tree Cryptocarya mandiocanna. Two independent synthetic approaches are discussed based on asymmetric allylation, ring closing metathesis, and aldol reactions.

  1. Yeast SREBP cleavage activation requires the Golgi Dsc E3 ligase complex.

    Science.gov (United States)

    Stewart, Emerson V; Nwosu, Christine C; Tong, Zongtian; Roguev, Assen; Cummins, Timothy D; Kim, Dong-Uk; Hayles, Jacqueline; Park, Han-Oh; Hoe, Kwang-Lae; Powell, David W; Krogan, Nevan J; Espenshade, Peter J

    2011-04-22

    Mammalian lipid homeostasis requires proteolytic activation of membrane-bound sterol regulatory element binding protein (SREBP) transcription factors through sequential action of the Golgi Site-1 and Site-2 proteases. Here we report that while SREBP function is conserved in fungi, fission yeast employs a different mechanism for SREBP cleavage. Using genetics and biochemistry, we identified four genes defective for SREBP cleavage, dsc1-4, encoding components of a transmembrane Golgi E3 ligase complex with structural homology to the Hrd1 E3 ligase complex involved in endoplasmic reticulum-associated degradation. The Dsc complex binds SREBP and cleavage requires components of the ubiquitin-proteasome pathway: the E2-conjugating enzyme Ubc4, the Dsc1 RING E3 ligase, and the proteasome. dsc mutants display conserved aggravating genetic interactions with components of the multivesicular body pathway in fission yeast and budding yeast, which lacks SREBP. Together, these data suggest that the Golgi Dsc E3 ligase complex functions in a post-ER pathway for protein degradation.

  2. Motion of Bishop Frenet Offsets of Ruled Surfaces in E3

    Directory of Open Access Journals (Sweden)

    H. N. Abd-Ellah

    2015-01-01

    Full Text Available The main goal of this paper is to study the motion of two associated ruled surfaces in Euclidean 3-space E3. In particular, the motion of Bishop Frenet offsets of ruled surfaces is investigated. Additionally, the characteristic properties for such ruled surfaces are given. Finally, an application is presented and plotted using computer aided geometric design.

  3. Selectivity of E2-E3 interactions in the human ubiquitin system

    NARCIS (Netherlands)

    van Wijk, S.J.L.

    2010-01-01

    Highly selective interactions between ubiquitin-conjugating enzymes and RING-type E3 ligases are crucial for the adequate and efficient action of ubiquitin and ubiquitin-like pathways. Within these cascades, E2 enzymes provide a connecting link between activation and the final covalent conjugation,

  4. Ophthalmic epidemiology in Europe : the "European Eye Epidemiology" (E3) consortium

    NARCIS (Netherlands)

    Delcourt, Cecile; Korobelnik, Jean-Francois; Buitendijk, Gabrielle H. S.; Foster, Paul J.; Hammond, Christopher J.; Piermarocchi, Stefano; Peto, Tunde; Jansonius, Nomdo; Mirshahi, Alireza; Hogg, Ruth E.; Bretillon, Lionel; Topouzis, Fotis; Deak, Gabor; Grauslund, Jakob; Broe, Rebecca; Souied, Eric H.; Creuzot-Garcher, Catherine; Sahel, Jose; Daien, Vincent; Lehtimaki, Terho; Hense, Hans-Werner; Prokofyeva, Elena; Oexle, Konrad; Rahi, Jugnoo S.; Cumberland, Phillippa M.; Schmitz-Valckenberg, Steffen; Fauser, Sascha; Bertelsen, Geir; Hoyng, Carel; Bergen, Arthur; Silva, Rufino; Wolf, Sebastian; Lotery, Andrew; Chakravarthy, Usha; Fletcher, Astrid; Klaver, Caroline C. W.

    2016-01-01

    The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 Europea

  5. Biochemical function of typical and variant Arabidopsis thaliana U-box E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Wiborg, Jakob; O'Shea, Charlotte; Skriver, Karen

    2008-01-01

    The variance of the U-box domain in 64 Arabidopsis thaliana (thale cress) E3s (ubiquitin-protein ligases) was used to examine the interactions between E3s and E2s (ubiquitin-conjugating enzymes). E2s and E3s are components of the ubiquitin protein degradation pathway. Seven U-box proteins were...

  6. Novel E3 ubiquitin ligases that regulate histone protein levels in the budding yeast Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar Singh

    Full Text Available Core histone proteins are essential for packaging the genomic DNA into chromatin in all eukaryotes. Since multiple genes encode these histone proteins, there is potential for generating more histones than what is required for chromatin assembly. The positively charged histones have a very high affinity for negatively charged molecules such as DNA, and any excess of histone proteins results in deleterious effects on genomic stability and cell viability. Hence, histone levels are known to be tightly regulated via transcriptional, posttranscriptional and posttranslational mechanisms. We have previously elucidated the posttranslational regulation of histone protein levels by the ubiquitin-proteasome pathway involving the E2 ubiquitin conjugating enzymes Ubc4/5 and the HECT (Homologous to E6-AP C-Terminus domain containing E3 ligase Tom1 in the budding yeast. Here we report the identification of four additional E3 ligases containing the RING (Really Interesting New Gene finger domains that are involved in the ubiquitylation and subsequent degradation of excess histones in yeast. These E3 ligases are Pep5, Snt2 as well as two previously uncharacterized Open Reading Frames (ORFs YKR017C and YDR266C that we have named Hel1 and Hel2 (for Histone E3 Ligases respectively. Mutants lacking these E3 ligases are sensitive to histone overexpression as they fail to degrade excess histones and accumulate high levels of endogenous histones on histone chaperones. Co-immunoprecipitation assays showed that these E3 ligases interact with the major E2 enzyme Ubc4 that is involved in the degradation related ubiquitylation of histones. Using mutagenesis we further demonstrate that the RING domains of Hel1, Hel2 and Snt2 are required for histone regulation. Lastly, mutants corresponding to Hel1, Hel2 and Pep5 are sensitive to replication inhibitors. Overall, our results highlight the importance of posttranslational histone regulatory mechanisms that employ multiple E3

  7. Pathfinding the Flight Advanced Stirling Convertor Design with the ASC-E3

    Science.gov (United States)

    Wong, Wayne A.; Wilson, Kyle; Smith, Eddie; Collins, Josh

    2012-01-01

    The Advanced Stirling Convertor (ASC) was initially developed by Sunpower, Inc. under contract to NASA Glenn Research Center (GRC) as a technology development project. The ASC technology fulfills NASA's need for high efficiency power convertors for future Radioisotope Power Systems (RPS). Early successful technology demonstrations between 2003 to 2005 eventually led to the expansion of the project including the decision in 2006 to use the ASC technology on the Advanced Stirling Radioisotope Generator (ASRG). Sunpower has delivered 22 ASC convertors of progressively mature designs to date to GRC. Currently, Sunpower with support from GRC, Lockheed Martin Space System Company (LMSSC), and the Department of Energy (DOE) is developing the flight ASC-F in parallel with the ASC-E3 pathfinders. Sunpower will deliver four pairs of ASC-E3 convertors to GRC which will be used for extended operation reliability assessment, independent validation and verification testing, system interaction tests, and to support LMSSC controller verification. The ASC-E3 and -F convertors are being built to the same design and processing documentation and the same product specification. The initial two pairs of ASC-E3 are built before the flight units and will validate design and processing changes prior to implementation on the ASC-F flight convertors. This paper provides a summary on development of the ASC technology and the status of the ASC-E3 build and how they serve the vital pathfinder role ahead of the flight build for ASRG. The ASRG is part of two of the three candidate missions being considered for selection for the Discovery 12 mission.

  8. Light Distribution in the E3 and E4 Scintillation Counters of the ATLAS Tile Calorimeter

    CERN Document Server

    Hsu, Catherine

    2013-01-01

    The Tile Calorimeter (TileCal) of the ATLAS experiment is an important component of the ATLAS calorimetry because they play a crucial role in the search for new particles. The E3 and E4 are crack scintillators of TileCal that extend into the gap region between the EM barrel and EM endcaps. They thus sample the energy of the EM showers produced by particles interacting with the dead material in the EM calorimeters and with the inner detector cables. This project focuses on the study of the light collection uniformity in the E3 and E4 scintillating tiles using low energy electrons as the ionising particles. It is important to have uniform light response in the tiles because it would ensure a good energy resolution for the dead region. However, many factors affect the uniform light collection within the scintillating tiles.

  9. A Bacterial Inhibitor of Host Programmed Cell Death Defenses is an E3 Ubiquitin Ligase

    Energy Technology Data Exchange (ETDEWEB)

    Janjusevic,R.; Abramovitch, R.; Martin, G.; Stebbins, C.

    2005-01-01

    The Pseudomonas syringae protein AvrPtoB is translocated into plant cells, where it inhibits immunity-associated programmed cell death (PCD). The structure of a C-terminal domain of AvrPtoB that is essential for anti-PCD activity reveals an unexpected homology to the U-box and RING-finger components of eukaryotic E3 ubiquitin ligases, and we show that AvrPtoB has ubiquitin ligase activity. Mutation of conserved residues involved in the binding of E2 ubiquitin-conjugating enzymes abolishes this activity in vitro, as well as anti-PCD activity in tomato leaves, which dramatically decreases virulence. These results show that Pseudomonas syringae uses a mimic of host E3 ubiquitin ligases to inactivate plant defenses.

  10. Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis

    Science.gov (United States)

    Plechanovová, Anna; Jaffray, Ellis; Tatham, Michael H.; Naismith, James H.; Hay, Ronald T.

    2012-01-01

    SUMMARY Ubiquitin modification is mediated by a large family of specificity determining ubiquitin E3 ligases. To facilitate ubiquitin transfer, RING E3 ligases bind both substrate and a ubiquitin E2 conjugating enzyme linked to ubiquitin via a thioester bond, but the mechanism of transfer has remained elusive. Here we report the crystal structure of the dimeric RING of RNF4 in complex with E2 (UbcH5a) linked by an isopeptide bond to ubiquitin. While the E2 contacts a single protomer of the RING, ubiquitin is folded back onto the E2 by contacts from both RING protomers. The C-terminal tail of ubiquitin is locked into an active site groove on the E2 by an intricate network of interactions, resulting in changes at the E2 active site. This arrangement is primed for catalysis as it can deprotonate the incoming substrate lysine residue and stabilise the consequent tetrahedral transition state intermediate. PMID:22842904

  11. The E3 ubiquitin ligase CTRIP controls CLOCK levels and PERIOD oscillations in Drosophila.

    Science.gov (United States)

    Lamaze, Angélique; Lamouroux, Annie; Vias, Carine; Hung, Hsiu-Cheng; Weber, Frank; Rouyer, François

    2011-06-01

    In the Drosophila circadian clock, the CLOCK/CYCLE complex activates the period and timeless genes that negatively feedback on CLOCK/CYCLE activity. The 24-h pace of this cycle depends on the stability of the clock proteins. RING-domain E3 ubiquitin ligases have been shown to destabilize PERIOD or TIMELESS. Here we identify a clock function for the circadian trip (ctrip) gene, which encodes a HECT-domain E3 ubiquitin ligase. ctrip expression in the brain is mostly restricted to clock neurons and its downregulation leads to long-period activity rhythms in constant darkness. This altered behaviour is associated with high CLOCK levels and persistence of phosphorylated PERIOD during the subjective day. The control of CLOCK protein levels does not require PERIOD. Thus, CTRIP seems to regulate the pace of the oscillator by controlling the stability of both the activator and the repressor of the feedback loop.

  12. Petrology and oxygen isotope compositions of chondrules in E3 chondrites

    Science.gov (United States)

    Weisberg, Michael K.; Ebel, Denton S.; Connolly, Harold C.; Kita, Noriko T.; Ushikubo, Takayuki

    2011-11-01

    Chondrules in E3 chondrites differ from those in other chondrite groups. Many contain near-pure endmember enstatite (Fs metal, Cr-bearing troilite, and, in some cases Mg, Mn- and Ca-sulfides. Olivine and more FeO-rich pyroxene grains are present but much less common than in ordinary or carbonaceous chondrite chondrules. In some cases, the FeO-rich grains contain dusty inclusions of metal. The oxygen three-isotope ratios (δ 18O, δ 17O) of olivine and pyroxene in chondrules from E3 chondrites, which are measured using a multi-collection SIMS, show a wide range of values. Most enstatite data plots on the terrestrial fractionation (TF) line near whole rock values and some plot near the ordinary chondrite region on the 3-isotope diagram. Pyroxene with higher FeO contents (˜2-10 wt.% FeO) generally plots on the TF line similar to enstatite, suggesting it formed locally in the EC (enstatite chondrite) region and that oxidation/reduction conditions varied within the E3 chondrite chondrule-forming region. Olivine shows a wide range of correlated δ 18O and δ 17O values and data from two olivine-bearing chondrules form a slope ˜1 mixing line, which is approximately parallel to but distinct from the CCAM (carbonaceous chondrite anhydrous mixing) line. We refer to this as the ECM (enstatite chondrite mixing) line but it also may coincide with a line defined by chondrules from Acfer 094 referred to as the PCM (Primitive Chondrite Mineral) line ( Ushikubo et al., 2011). The range of O isotope compositions and mixing behavior in E3 chondrules is similar to that in O and C chondrite groups, indicating similar chondrule-forming processes, solid-gas mixing and possibly similar 16O-rich precursors solids. However, E3 chondrules formed in a distinct oxygen reservoir. Internal oxygen isotope heterogeneity was found among minerals from some of the chondrules in E3 chondrites suggesting incomplete melting of the chondrules, survival of minerals from previous generations of

  13. Shark (Prionace glauca) elastoidin: characterization of its collagen as [alpha 1(E)]3 homotrimers.

    Science.gov (United States)

    Kimura, S; Uematsu, Y; Miyauchi, Y

    1986-01-01

    A new type of collagen was isolated from elastoidin of great blue shark by limited pepsin digestion. The collagen alpha chain of elastoidin, designated alpha 1(E), was very similar in electrophoretic and chromatographic behavior and amino acid composition to shark skin alpha 1(I) chain, but they were genetically-distinct on the basis of CNBr-peptide maps. The collagen molecule of elastoidin was shown to be an [alpha 1(E)]3 homotrimer.

  14. The substrate binding domains of human SIAH E3 ubiquitin ligases are now crystal clear

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qi; Wang, Zhongduo; Hou, Feng; Harding, Rachel; Huang, Xinyi; Dong, Aiping; Walker, John R.; Tong, Yufeng

    2017-01-01

    Seven in absentia homologs (SIAHs) comprise a family of highly conserved E3 ubiquitin ligases that play an important role in regulating signalling pathways in tumorigenesis, including the DNA damage repair and hypoxia response pathways. SIAH1 and SIAH2 have been found to function as a tumour repressor and a proto-oncogene, respectively, despite the high sequence identity of their substrate binding domains (SBDs). Ubiquitin-specific protease USP19 is a deubiquitinase that forms a complex with SIAHs and counteracts the ligase function. Much effort has been made to find selective inhibitors of the SIAHs E3 ligases. Menadione was reported to inhibit SIAH2 specifically. We used X-ray crystallography, peptide array, bioinformatic analysis, and biophysical techniques to characterize the structure and interaction of SIAHs with deubiquitinases and literature reported compounds. We solved the crystal structures of SIAH1 in complex with a USP19 peptide and of the apo form SIAH2. Phylogenetic analysis revealed the SIAH/USP19 complex is conserved in evolution. We demonstrated that menadione destabilizes both SIAH1 and SIAH2 non-specifically through covalent modification. The SBDs of SIAH E3 ligases are structurally similar with a subtle stability difference. USP19 is the only deubiquitinase that directly binds to SIAHs through the substrate binding pocket. Menadione is not a specific inhibitor for SIAH2. The crystallographic models provide structural insights into the substrate binding of the SIAH family E3 ubiquitin ligases that are critically involved in regulating cancer-related pathways. Our results suggest caution should be taken when using menadione as a specific SIAH2 inhibitor.

  15. HSV-1 ICP0: An E3 Ubiquitin Ligase That Counteracts Host Intrinsic and Innate Immunity

    Directory of Open Access Journals (Sweden)

    Mirna Perusina Lanfranca

    2014-05-01

    Full Text Available The herpes simplex virus type 1 (HSV-1 encoded E3 ubiquitin ligase, infected cell protein 0 (ICP0, is required for efficient lytic viral replication and regulates the switch between the lytic and latent states of HSV-1. As an E3 ubiquitin ligase, ICP0 directs the proteasomal degradation of several cellular targets, allowing the virus to counteract different cellular intrinsic and innate immune responses. In this review, we will focus on how ICP0’s E3 ubiquitin ligase activity inactivates the host intrinsic defenses, such as nuclear domain 10 (ND10, SUMO, and the DNA damage response to HSV-1 infection. In addition, we will examine ICP0’s capacity to impair the activation of interferon (innate regulatory mediators that include IFI16 (IFN γ-inducible protein 16, MyD88 (myeloid differentiation factor 88, and Mal (MyD88 adaptor-like protein. We will also consider how ICP0 allows HSV-1 to evade activation of the NF-κB (nuclear factor kappa B inflammatory signaling pathway. Finally, ICP0’s paradoxical relationship with USP7 (ubiquitin specific protease 7 and its roles in intrinsic and innate immune responses to HSV-1 infection will be discussed.

  16. Identification of Arabidopsis MYB56 as a novel substrate for CRL3(BPM) E3 ligases.

    Science.gov (United States)

    Chen, Liyuan; Bernhardt, Anne; Lee, JooHyun; Hellmann, Hanjo

    2015-02-01

    Controlled stability of proteins is a highly efficient mechanism to direct diverse processes in living cells. A key regulatory system for protein stability is given by the ubiquitin proteasome pathway, which uses E3 ligases to mark specific proteins for degradation. In this work, MYB56 is identified as a novel target of a CULLIN3 (CUL3)-based E3 ligase. Its stability depends on the presence of MATH-BTB/POZ (BPM) proteins, which function as substrate adaptors to the E3 ligase. Genetic studies have indicated that MYB56 is a negative regulator of flowering, while BPMs positively affect this developmental program. The interaction between BPMs and MYB56 occurs at the promoter of FLOWERING LOCUS T (FT), a key regulator in initiating flowering in Arabidopsis, and results in instability of MYB56. Overall the work establishes MYB transcription factors as substrates of BPM proteins, and provides novel information on components that participate in controlling flowering time in plants. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  17. Construction of new operation interface for the LABIHS simulator using the ELIPSE E3 studio software

    Energy Technology Data Exchange (ETDEWEB)

    Augusto, Silas C.; Oliveira, Mauro V., E-mail: silas@ien.gov.b, E-mail: mvitor@ien.gov.b [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2011-07-01

    The Human-System Interface Laboratory (LABIHS), located at the Instituto de Engenharia Nuclear (IEN), has a compact simulator that simulate the processes of a pressurized water reactor nuclear power plant of 930 MWe of power. This simulator is composed by a HP-UX workstation computer, where the simulation software runs, and a set of computer stations, that represent an advanced control room, where the simulator is operated by software control panels that represent several systems of the simulated nuclear power plant. The current HSIs for the LABIHS simulator was built using iLog software tool. The development of new human-system interfaces (HSIs) for the simulator is one of the research fields of LABIHS. This paper presents the screen components development process for a new HSI for the LABIHS simulator, using the software Elipse{sup TM} E3 Studio. These new components developed using the E3 Studio are similar to the ones used in the current simulator interface. The article shows some comparisons between the component and screen development with Elipse{sup TM} E3 Studio processes and using iLog Studio. (author)

  18. MDM2 is a novel E3 ligase for HIV-1 Vif

    Directory of Open Access Journals (Sweden)

    Tomonaga Mitsunori

    2009-01-01

    Full Text Available Abstract The human immunodeficiency virus type 1 (HIV-1 Vif plays a crucial role in the viral life cycle by antagonizing a host restriction factor APOBEC3G (A3G. Vif interacts with A3G and induces its polyubiquitination and subsequent degradation via the formation of active ubiquitin ligase (E3 complex with Cullin5-ElonginB/C. Although Vif itself is also ubiquitinated and degraded rapidly in infected cells, precise roles and mechanisms of Vif ubiquitination are largely unknown. Here we report that MDM2, known as an E3 ligase for p53, is a novel E3 ligase for Vif and induces polyubiquitination and degradation of Vif. We also show the mechanisms by which MDM2 only targets Vif, but not A3G that binds to Vif. MDM2 reduces cellular Vif levels and reversely increases A3G levels, because the interaction between MDM2 and Vif precludes A3G from binding to Vif. Furthermore, we demonstrate that MDM2 negatively regulates HIV-1 replication in non-permissive target cells through Vif degradation. These data suggest that MDM2 is a regulator of HIV-1 replication and might be a novel therapeutic target for anti-HIV-1 drug.

  19. Instanton induced Yukawa couplings from distant E3 and E(-1) instantons

    Energy Technology Data Exchange (ETDEWEB)

    Goodsell, Mark D. [Sorbonne Universités, UPMC Univ Paris 06, UMR 7589, LPTHE,F-75005, Paris (France); CNRS, UMR 7589, LPTHE,F-75005, Paris (France); Witkowski, Lukas T. [Institute for Theoretical Physics, University of Heidelberg,Philosophenweg 19, 69120 Heidelberg (Germany)

    2016-01-07

    We calculate non-perturbative contributions to Yukawa couplings on D3-branes at orbifold singularities due to E3 and fractional E(-1) instantons which do not intersect the visible sector branes. While distant E3 instantons on bulk cycles typically contribute to Yukawa couplings, we find that distant fractional E(-1) can also give rise to new Yukawa couplings. However, fractional E(-1) instantons only induce Yukawa couplings if they are located at a singularity which shares a collapsed homologous two-cycle with the singularity supporting the visible sector. The non-perturbative contributions to Yukawa couplings exhibit a different flavour structure than the tree-level Yukawa couplings and, as a result, they can be sources of flavour violation. This is particularly relevant for schemes of moduli stabilisation which rely on superpotential contributions from E3 instantons, such as KKLT or the Large Volume Scenario. As a byproduct of our analysis, we shed some new light on the properties of annulus diagrams with matter field insertions in stringy instanton calculus.

  20. Arabidopsis HIGH PLOIDY2 sumoylates and stabilizes flowering locus C through its E3 ligase activity

    Directory of Open Access Journals (Sweden)

    Jun Soo eKwak

    2016-04-01

    Full Text Available Flowering Locus C (FLC, a floral repressor, plays an important role in flowering. The mechanisms regulating FLC gene expression and protein function have been studied extensively; however, post-translational regulation of FLC remains unclear. Here, we identified Arabidopsis HIGH PLOIDY2 (HPY2 as an E3 SUMO ligase for FLC. In vitro and vivo pull-down assays showed that FLC physically interacts with HPY2. In vitro assays showed that the stimulation of FLC sumoylation by HPY2 was dependent on SUMO-activating enzyme E1 and -conjugating enzyme E2, indicating that HPY2 was an E3 SUMO ligase for FLC. In transgenic plants, inducible HPY2 overexpression increased the concentration of FLC, indicating that HPY2 stabilized FLC through direct sumoylation. Flowering time in hpy2-2 mutants was shorter than in wild-type plants under long- and short-day conditions, with a greater effect under short-day conditions, and FLC was downregulated in hpy2-2 mutants. These data indicate that HPY2 regulates FLC function and stability at both the transcriptional and post-translational levels through its E3 SUMO ligase activity.

  1. {ital E}3 transition probabilities in the platinum, mercury, and lead isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Egido, J.L.; Martin, V.; Robledo, L.M.; Sun, Y. [Departamento de Fisica Teorica C-XI, Universidad Autonoma de Madrid, E-28049 Madrid (Spain)]|[Analisis Numerico, Facultad de Informatica, Universidad Politecnica de Madrid, E-28660 Madrid (Spain)]|[Department of Physics and Atmospheric Science, Drexel University, Philadelphia, Pennsylvania 19104 (United States)]|[Joint Institute for Heavy Ion Research, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States)

    1996-06-01

    Spectroscopical properties of the platinum, mercury, and lead isotopes are studied within the Hartree-Fock plus BCS framework with the finite range density-dependent Gogny force. These properties are also studied beyond mean-field theory by combining the use of generator-coordinate-method-like wave functions with the angular momentum projection technique as to generate many-body correlated wave functions that are at the same time eigenstates of the angular momentum operator. We apply this formalism to the calculation of reduced transition probabilities {ital B}({ital E}3) from the lowest-lying octupole collective state to the ground state of several isotopes of the platinum, mercury, and lead nuclei whose experimental {ital B}({ital E}3) values present a peculiar behavior. The projected calculations show a large improvement over the unprojected ones when compared with the experimental data. The unprojected calculations are unable to predict any structure in the {ital B}({ital E}3). {copyright} {ital 1996 The American Physical Society.}

  2. Photometric characterization of the Chang'e-3 landing site using LROC NAC images

    Science.gov (United States)

    Clegg-Watkins, R. N.; Jolliff, B. L.; Boyd, A.; Robinson, M. S.; Wagner, R.; Stopar, J. D.; Plescia, J. B.; Speyerer, E. J.

    2016-07-01

    China's robotic Chang'e-3 spacecraft, carrying the Yutu rover, touched down in Mare Imbrium on the lunar surface on 14 December 2013. The Lunar Reconnaissance Orbiter (LRO) Narrow Angle Camera (NAC) imaged the site both before and after landing. Multi-temporal NAC images taken before and after the landing, phase-ratio images made from NAC images taken after the landing, and Hapke photometric techniques were used to evaluate surface changes caused by the disturbance of regolith at the landing site (blast zone) by the descent engines of the Chang'e-3 spacecraft. The reflectance of the landing site increased by 10 ± 1% (from I/F = 0.040 to 0.044 at 30° phase angle) as a result of the landing, a value similar to reflectance increases estimated for the Apollo, Luna, and Surveyor landing sites. The spatial extent of the disturbed area at the Chang'e-3 landing site, 2530 m2, also falls close to what is predicted on the basis of correlations between lander mass, thrust, and blast zone areas for the historic landed missions. A multi-temporal ratio image of the Chang'e-3 landing site reveals a main blast zone (slightly elongate in the N-S direction; ∼75 m across N-S and ∼43 m across in the E-W direction) and an extended diffuse, irregular halo that is less reflective than the main blast zone (extending ∼40-50 m in the N-S direction and ∼10-15 m in the E-W direction beyond the main blast zone). The N-S elongation of the blast zone likely resulted from maneuvering during hazard avoidance just prior to landing. The phase-ratio image reveals that the blast zone is less backscattering than surrounding undisturbed areas. The similarities in magnitude of increased reflectance between the Chang'e-3 landing site and the Surveyor, Apollo, and Luna landing sites suggest that lunar soil reflectance changes caused by interaction with rocket exhaust are not significantly altered over a period of 40-50 years. The reflectance changes are independent of regolith composition

  3. GEM-E3: A computable general equilibrium model applied for Switzerland

    Energy Technology Data Exchange (ETDEWEB)

    Bahn, O. [Paul Scherrer Inst., CH-5232 Villigen PSI (Switzerland); Frei, C. [Ecole Polytechnique Federale de Lausanne (EPFL) and Paul Scherrer Inst. (Switzerland)

    2000-01-01

    The objectives of the European Research Project GEM-E3-ELITE, funded by the European Commission and coordinated by the Centre for European Economic Research (Germany), were to further develop the general equilibrium model GEM-E3 (Capros et al., 1995, 1997) and to conduct policy analysis through case studies. GEM-E3 is an applied general equilibrium model that analyses the macro-economy and its interaction with the energy system and the environment through the balancing of energy supply and demand, atmospheric emissions and pollution control, together with the fulfillment of overall equilibrium conditions. PSI's research objectives within GEM-E3-ELITE were to implement and apply GEM-E3 for Switzerland. The first objective required in particular the development of a Swiss database for each of GEM-E3 modules (economic module and environmental module). For the second objective, strategies to reduce CO{sub 2} emissions were evaluated for Switzerland. In order to develop the economic, PSI collaborated with the Laboratory of Applied Economics (LEA) of the University of Geneva and the Laboratory of Energy Systems (LASEN) of the Federal Institute of Technology in Lausanne (EPFL). The Swiss Federal Statistical Office (SFSO) and the Institute for Business Cycle Research (KOF) of the Swiss Federal Institute of Technology (ETH Zurich) contributed also data. The Swiss environmental database consists mainly of an Energy Balance Table and of an Emission Coefficients Table. Both were designed using national and international official statistics. The Emission Coefficients Table is furthermore based on know-how of the PSI GaBE Project. Using GEM-E3 Switzerland, two strategies to reduce the Swiss CO{sub 2} emissions were evaluated: a carbon tax ('tax only' strategy), and the combination of a carbon tax with the buying of CO{sub 2} emission permits ('permits and tax' strategy). In the first strategy, Switzerland would impose the necessary carbon tax to achieve

  4. Photographer: N/A Boeing CH-47B (USA 66-19138 NASA-737) Chinook in-flight simulator with Moffet

    Science.gov (United States)

    1985-01-01

    Photographer: N/A Boeing CH-47B (USA 66-19138 NASA-737) Chinook in-flight simulator with Moffet Field Navy Hangar and Ames VMS in background. Note: Used in publication in Flight Research at Ames; 57 Years of Development and Validation of Aeronautical Technology NASA SP-1998-3300 fig. 133

  5. Full-scale testing, production and cost analysis data for the advanced composite stabilizer for Boeing 737 aircraft. Volume 1: Technical summary

    Science.gov (United States)

    Aniversario, R. B.; Harvey, S. T.; Mccarty, J. E.; Parsons, J. T.; Peterson, D. C.; Pritchett, L. D.; Wilson, D. R.; Wogulis, E. R.

    1983-01-01

    The full scale ground test, ground vibration test, and flight tests conducted to demonstrate a composite structure stabilizer for the Boeing 737 aircraft and obtain FAA certification are described. Detail tools, assembly tools, and overall production are discussed. Cost analyses aspects covered include production costs, composite material usage factors, and cost comparisons.

  6. 75 FR 38007 - Airworthiness Directives; The Boeing Company Model 747-100, 747-100B, 747-100B SUD, 747-200B, 747...

    Science.gov (United States)

    2010-07-01

    ... cost Duct assembly rework, specified 8 per duct $12,305 (average). $100,705 (average) 185 $18,630,425. in Boeing Service Bulletin 747- (average of 130 21A2421. ducts per airplane). Duct assembly rework or... the actions have already been done. ECS Duct Assembly Rework or Replacement (g) Within 72 months...

  7. Connecting the World in the Spirit of Zheng He--Boeing 777-200LR Worldliner Commemorates 600th Anniversary of Zheng He's Voyages

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

      The Boeing [NYSE:BA] 777-200LR Worldliner, the world's longest range commercial airplane, was officially named "Zheng He" at Beijing's Capital International Airport during a ceremony to commemorate the seven incredible voyages by the great Chinese navigator and explorer Zheng He.……

  8. Connecting the World in the Spirit of Zheng He--Boeing 777-200LR Worldliner Commemorates 600th Anniversary of Zheng He's Voyages

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ The Boeing [NYSE:BA] 777-200LR Worldliner, the world's longest range commercial airplane, was officially named "Zheng He" at Beijing's Capital International Airport during a ceremony to commemorate the seven incredible voyages by the great Chinese navigator and explorer Zheng He.

  9. Analysis on establishing Chang'E-3 landing site as a reflectance calibration target

    Science.gov (United States)

    Liu, Bin; Fu, Xiaohui; Zeng, Xingguo; Yao, Meijuan; Zhang, Hongbo; Su, Yan; Zhao, Shu; Xue, Xiping; Li, Chunlai; Zou, Yongliao

    2015-04-01

    Recent lunar orbital observations suggested that the surface reflectance calculated based on the Apollo 16 standard area and Apollo 16 sample laboratory measurement is significantly different from its true value [1-3], one reason is the composition and maturity differences between the 62231 sampling site and the Apollo 16 standard site existed, the other reason is the physical properties of the returned lunar sample, such as porosity, have been changed during the sampling operations. So more new standard targets on the Moon, besides the widely used Apollo 16 area, are needed for imaging spectrometers on lunar missions to improve their reflectance calibration accuracies. The Chang'E-3 VIS/NIR Imaging Spectrometer (VNIS), which is just fixed at the front of the Yutu rover [4], equipped with a white spectralon panel as reflectance calibration standard, can perform in situ multispectral observations around the Chang'E-3 landing site without altering the physical and mineralogical natures of lunar soils. Therefore, it provides an opportunity to establish a new reliable standard target for in-flight reflectance calibration. The reflectance calibration target should be compositional homogeneous, the topography of which must be flat, and the reflectance should be identical with no nearby units of other different materials. As we have known, Chang'e-3 probe landed on the Mare Imbrium basin in the east part of Sinus Iridum, the landing site is relatively flat at a spatial coverage of ~660km2, and this region belongs to Eratosthenian low-Ti/high-Ti mare basalts [5-6]. According to much higher resolution topography data, elemental data and reflectance data of Chang'E-2 and Chang'E-3[7-8], we preliminary analyse the possibility on establishing Chang'E-3 landing site as a reflectance calibration target. Firstly, the overall terrain of the 4 km×4 km area around the landing site is flat, but there are still three bigger craters existed. Secondly, the composition on Chang'E-3

  10. Endoplasmic Reticulum Exit of Golgi-resident Defective for SREBP Cleavage (Dsc) E3 Ligase Complex Requires Its Activity.

    Science.gov (United States)

    Raychaudhuri, Sumana; Espenshade, Peter J

    2015-06-01

    Layers of quality control ensure proper protein folding and complex formation prior to exit from the endoplasmic reticulum. The fission yeast Dsc E3 ligase is a Golgi-localized complex required for sterol regulatory element-binding protein (SREBP) transcription factor activation that shows architectural similarity to endoplasmic reticulum-associated degradation E3 ligases. The Dsc E3 ligase consists of five integral membrane proteins (Dsc1-Dsc5) and functionally interacts with the conserved AAA-ATPase Cdc48. Utilizing an in vitro ubiquitination assay, we demonstrated that Dsc1 has ubiquitin E3 ligase activity that requires the E2 ubiquitin-conjugating enzyme Ubc4. Mutations that specifically block Dsc1-Ubc4 interaction prevent SREBP cleavage, indicating that SREBP activation requires Dsc E3 ligase activity. Surprisingly, Golgi localization of the Dsc E3 ligase complex also requires Dsc1 E3 ligase activity. Analysis of Dsc E3 ligase complex formation, glycosylation, and localization indicated that Dsc1 E3 ligase activity is specifically required for endoplasmic reticulum exit of the complex. These results define enzyme activity-dependent sorting as an autoregulatory mechanism for protein trafficking.

  11. An integrated design of the payload for Chang'e 3 Lunar Rover

    Science.gov (United States)

    Zhouchangyi, Zhouchangyi

    Chang’e 3 detector is launched in China Xichang Satellite Launch Center on December 2, 2013. Its project task was a complete success. CE-3 detector achieved a soft landing and started its lunar exploration andinspection. It is composed of the lander and Rover (Yutu). This paper introduces an integrated designing payload of Chang’e 3 Lunar Rover. Chang’e 3 Lunar Rover is allocated with infrared imaging spectrometer,moon-measuring radar, Alpha Particle X-ray Spectrometer(APXS), panoramic camera and other payloads. The infrared spectrometer is used to analyse the infrared spectrum and take images of the patrolling areas, to analyse the mineral composition and distribution of the lunar surface, and to do a comprehensive study of the energy sources and mineral sources.The radar is used for inspecting the thickness and structure of the lunar soil on the patrolling path as well as probing the structure of the shallow lunar crust. The APXS will use the method of alpha-particle-induced X-ray fluorescence to study in detail the composition of soil in specific areas. The panoramic camera is for obtaining three-dimensional images of the lunar surface around the patrolling path, accomplishing the inspection of near landscapes and topographic analysis. Limited by the total weight, the Rover is equipped with a payload controller, through which an integrated design consisting of the power supply, data processing, electronic units, operating management and other functions of the payload is done, to realize the centralized power supply, centralized management, centralized data processing, centralized operating controlling and centralized interfaces with the integrated electronic system of the Rover.

  12. Topographic modeling and analysis of the landing site of Chang'E-3 on the Moon

    Science.gov (United States)

    Wu, Bo; Li, Fei; Ye, Lei; Qiao, Si; Huang, Jun; Wu, Xueying; Zhang, He

    2014-11-01

    The Chinese lunar probe Chang'E-3, carrying the “Jade Rabbit” lunar rover, successfully landed in the Sinus Iridum area on the Moon on December 14, 2013. This paper presents the characterization activities that were done for the selection of the landing area, including topographic modeling and analysis based on multisource lunar remote sensing data. Seven meter-resolution Chang'E-2 imagery and Lunar Orbiter Laser Altimeter data were integrated to generate a digital elevation model (DEM) with a resolution of 20 m for the entire Sinus Iridum landing area. Long baseline slopes were assessed according to this DEM for all of this area. Lunar Reconnaissance Orbiter narrow-angle camera images and 1.5 m-resolution Chang'E-2 imagery were used to derive DEMs with higher resolution (4 m) at several local regions within the Sinus Iridum landing area. Slope analyses at lander footprint scale (˜8 m) were performed in these local regions. Craters were detected from the DEMs and the derived orthophotos, and size-frequency distributions were generated. Crater morphological statistics, including the depth/diameter ratios, rim height/diameter ratios and wall slopes, were analyzed. The results showed that the Sinus Iridum landing area is relatively flat. Most of the area has slopes of less than 15°. The steeper slopes are mainly alongside craters and ridges. The crater size-frequency distribution is close to the equilibrium distribution. The crater ages, as indicated by their morphological statistics, vary from mature to relatively fresh in different regions. These topographic modeling and analysis results were used for strategic planning to identify the landing site for the Chang'E-3 and made a useful contribution to the success of the Chang'E-3 mission.

  13. Alteration of airway responsiveness mediated by receptors in ovalbumin-induced asthmatic E3 rats

    Institute of Scientific and Technical Information of China (English)

    Jing-wen LONG; Xu-dong YANG; Lei CAO; She-min LU; Yong-xiao CAO

    2009-01-01

    Aim:Airway hyperresponsiveness is a constant feature of asthma.The aim of the present study was to investigate airway hyperreactivity mediated by contractile and dilative receptors in an ovalbumin (OVA)-induced model of rat asthma.Methods:Asthmatic E3 rats were prepared by intraperitoneal injection with OVA/aluminum hydroxide and then challenged with intranasal instillation of OVA-PBS two weeks later.The myograph method was used to measure the responses of constriction and dilatation in the trachea,main bronchi and lobar bronchi.Results:In asthmatic E3 rata,β2 adrenoceptor-mediated relaxation of airway smooth muscle pre-contracted with 5-HT was inhibited,and there were no obvious difference in relaxation compared with normal E3 rats.Contraction of lobar bronchi mediated by 5-HT and sarafotoxin 6c was more potent than in the trachea or main bronchi.Airway contractions mediated by the endothelin (ET)A receptor,ETB receptor and M3 muscarinic receptor were augmented,and the augmented contraction was most obvious in lobar bronchi.The order of efficacy of contraction for lobar bronchi induced by agonists was ET-1,sarafotoxin 6c>ACh>5-HT.OX8 (an antibody against CD8+ T cells) strongly shifted and 0X35 (an antibody against CD4+ T cells) modestly shifted isoprenaline-induced concentration-relaxation curves in a nonparallel fashion to the left with an increased Rmax in asthmatic rats and sarafotoxin 6c-induced concentration-contractile curves to the right with a decreased Emax.Conclusion:The inhibition of airway relaxation and the augmentation of contraction mediated by receptors contribute to airway hyperresponsiveness and involve CD8+ and CD4+ T cells.

  14. Momentum correlation of the final-state wavefunction for (e, 3e) collisions on helium

    Institute of Scientific and Technical Information of China (English)

    Zhang Sui- Meng

    2004-01-01

    Based on our earlier paper, the momentum correlation of the four bodies in the final state is further considered for (e, 3e) processes on helium. A fivefold differential cross section (FDCS) for electron-impact double ionization of helium is calculated by use of the modified model for high incident energy (1-5.6keV). It has been found that the present results give a better description for the experimental data, as compared with the results of our earlier paper.

  15. The Processing and Analysis of Lunar Penetrating Radar Channel-1 Data from Chang'E-3

    Directory of Open Access Journals (Sweden)

    Gao Yun-ze

    2015-10-01

    Full Text Available Lunar Penetrating Radar (LPR, which is one of the most important science payloads onboard the Chang'E-3 (CE-3 rover, is used to obtain electromagnetic image less than 100 m beneath the lunar surface. This paper describes the system composition and working mechanism of the LPR and presents a detailed analysis of its data. We investigated special signal-processing methods and present the result of channel-1 data. The result shows that the effective echo occurs at depths greater than 100 m. Moreover, an unusual reflection exists at depth of 40 m, which may be the boundary of two geological units beneath the lunar surface.

  16. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide

    OpenAIRE

    Fischer, Eric S.; Böhm, Kerstin; Lydeard, John R.; Yang, Haidi; Stadler, Michael B.; Cavadini, Simone; Nagel, Jane; Serluca, Fabrizio; Acker, Vincent; Lingaraju, Gondichatnahalli M.; Tichkule, Ritesh B.; Schebesta, Michael; Forrester, William C.; Schirle, Markus; Hassiepen, Ulrich

    2015-01-01

    In the 1950s the drug thalidomide administered as a sedative to pregnant women led to the birth of thousands of children with multiple defects. Despite its teratogenicity, thalidomide and its derivatives lenalidomide and pomalidomide (together known as Immunomodulatory Drugs: IMiDs) recently emerged as effective treatments for multiple myeloma and 5q-dysplasia. IMiDs target the CUL4-RBX1-DDB1-CRBN (CRL4CRBN) E3 ubiquitin ligase and promote the ubiquitination of Ikaros/Aiolos transcription fac...

  17. CHANG'E-3 Active Particle-induced X-ray Spectrometer: ground verification test

    Science.gov (United States)

    Guo, Dongya; Peng, Wenxi; Cui, XingZhu; Wang, Huanyu

    The Active Particle-induced X-ray Spectrometer (APXS) is one of the payloads of Chang’E-3 rover Yutu, with which the major elemental composition of lunar soils and rocks can be measured on site. In order to assess the instrument performance and the accuracy of determination, ground verification test was carried out with two blind samples(basaltic rock, powder). Details of the experiments and data analysis method are discussed. The results show that the accuracy of quantitative analysis for major elements(Mg,Al,Si,K,Ca,Ti,Fe) is better than 15%.

  18. The E3 Ligase CHIP Mediates Ubiquitination and Degradation of Mixed-Lineage Kinase 3

    OpenAIRE

    Blessing, Natalya A.; Brockman, April L.; Chadee, Deborah N.

    2014-01-01

    Mixed-lineage kinase 3 (MLK3) activates mitogen-activated protein kinase (MAPK) signaling pathways and has important functions in migration, invasion, proliferation, tumorigenesis, and apoptosis. We investigated the role of the E3 ligase carboxyl terminus of Hsc70-interacting protein (CHIP) in the regulation of MLK3 protein levels. We show that CHIP interacts with MLK3 and, together with the E2 ubiquitin-conjugating enzyme UbcH5 (UbcH5a, -b, -c, or -d), ubiquitinates MLK3 in vitro. CHIP or Hs...

  19. A prediction for |U{sub e3}| from patterns in the charged lepton spectra

    Energy Technology Data Exchange (ETDEWEB)

    Ferrandis, Javier; Pakvasa, Sandip

    2004-09-22

    It is shown that empirical relations between the charged lepton spectra and the quark spectra together with a bimaximal or near bimaximal neutrino mixing matrix necessarily imply that there is a contribution to |U{sub e3}| given by {theta}{sub C}/ 3{radical}2 {approx} {radical}(m{sub e}/2m{sub {mu}}) {approx} 0.052, where {theta}{sub C}is the Cabibbo angle. This prediction could be tested in the near future reactor experiments. The charged lepton mixing also generates a less robust prediction for the angle {theta}{sub 23} and a small contribution to the phase {delta}.

  20. 八斑球腹蛛的生物学特性%The Bionomics of Theridion Octomacutatum Boes. et str.

    Institute of Scientific and Technical Information of China (English)

    刘汉才; 曾青兰

    2001-01-01

    八斑球腹蛛(Theridonn octomacutatum Boes.et str.)是节肢动物门(Arthropoda)蛛形纲(Arachnida)蜘蛛目(Arcneida)球腹蛛科(Theridum)动物.幼蛛期四龄,雌蛛一生交尾一次,多次产卵,护卵习性强.在鄂南地区八斑球腹蛛一年之内发生完整六个世代,幼蛛和成蛛均能越冬.八斑球腹蛛的生活习性介于结网和游措蜘蛛之间,是农作物害虫的重要天敌,有一定的利用价值.

  1. THE NATURE OF THE MAIN STRUCTURAL DAMAGE IN BOEING 737-400 AS IDENTIFIED DURING OVERHAUL TYPE C

    Directory of Open Access Journals (Sweden)

    Piotr GOLDA

    2016-03-01

    Full Text Available In its preliminary part, the article characterises Boeings 737-400 as due to undergo further tests as well as the basic materials used in their construction. It also defines to what extend these materials are prone to damage in the course of their regular use over the planes’ working lives. The object of the analysis is the most prevalent structural damage to the fuselage of the planes discovered during overhaul type C and the definition of the best preventive service. Further on the article categorises the discovered problems and provides their genesis. The main part of the article is devoted to the definition of the sources and reasons for the damage. Consequently, the article forms guidelines how to prevent the occurrence of such and similar damage to the uselage.

  2. The NASA/Industry Design Analysis Methods for Vibrations (DAMVIBS) Program - Boeing helicopters airframe finite element modeling

    Science.gov (United States)

    Gabel, R.; Lang, P.; Reed, D.

    1992-01-01

    Finite-element modeling of the airframe vibration of the Army/Boeing CH-47D helicopter is conducted with comparisons to experimental data in an effort to improve the design process. A NASTRAN FEM is developed that is fully representative of the test configuration and includes the support fixture, shakers, and the aircraft/shaker suspension system. The analysis is conducted with specific attention given to the prediction of reasonable forced amplitudes throughout the airframe. Reasonable correlation is noted between the FEM and experimental results, although improved correlation can be obtained by including more accurate damping values and secondary effects such as stringer shear loading. It is shown that the general stress model does not provide an adequate dynamic analysis on which to base design improvements. A more detailed model is required that emphasizes highly detailed helicopter elements and employs a finer mesh particularly in the description of the mass distribution.

  3. Blocking an N-terminal acetylation–dependent protein interaction inhibits an E3 ligase

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Daniel C.; Hammill, Jared T.; Min, Jaeki; Rhee, David Y.; Connelly, Michele; Sviderskiy, Vladislav O.; Bhasin, Deepak; Chen, Yizhe; Ong, Su-Sien; Chai, Sergio C.; Goktug, Asli N.; Huang, Guochang; Monda, Julie K.; Low, Jonathan; Kim, Ho Shin; Paulo, Joao A.; Cannon, Joe R.; Shelat, Anang A.; Chen, Taosheng; Kelsall, Ian R.; Alpi, Arno F.; Pagala, Vishwajeeth; Wang, Xusheng; Peng, Junmin; Singh , Bhuvanesh; Harper, J. Wade; Schulman, Brenda A.; Guy, R. Kip (MSKCC); (Dundee); (SJCH); (Harvard-Med); (MXPL)

    2017-06-05

    N-terminal acetylation is an abundant modification influencing protein functions. Because ~80% of mammalian cytosolic proteins are N-terminally acetylated, this modification is potentially an untapped target for chemical control of their functions. Structural studies have revealed that, like lysine acetylation, N-terminal acetylation converts a positively charged amine into a hydrophobic handle that mediates protein interactions; hence, this modification may be a druggable target. We report the development of chemical probes targeting the N-terminal acetylation–dependent interaction between an E2 conjugating enzyme (UBE2M or UBC12) and DCN1 (DCUN1D1), a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8. The inhibitors are highly selective with respect to other protein acetyl-amide–binding sites, inhibit NEDD8 ligation in vitro and in cells, and suppress anchorage-independent growth of a cell line with DCN1 amplification. Overall, our data demonstrate that N-terminal acetyl-dependent protein interactions are druggable targets and provide insights into targeting multiprotein E2–E3 ligases.

  4. Treatability study of Tank E-3-1 waste: mixed waste stream SR-W049

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C.A. [Westinghouse Savannah River Company, AIKEN, SC (United States)

    1997-08-21

    Treatability studies were conducted for tank E-3-1 waste which was previously characterized in WSRC-RP-87-0078. The waste was determined to be mixed waste because it displayed the characteristic of metal toxicity for Hg and Cr and was also contaminated with low levels of radionuclides. Two types of treatments for qualifying this waste suitable for land disposal were evaluated: ion exchange and stabilization with hydraulic materials (portland cement, slag and magnesium phosphate cement). These treatments were selected for testing because: (1) Both treatments can be carried out as in-drum processes., (2) Cement stabilization is the RCRA/LDR best developed available technology (BDAT) for Hg (less than 280 mg/L) and for Cr., and (3) Ion exchange via Mag-Sep is a promising alternative technology for in drum treatment of liquid wastes displaying metal toxicity. Cement stabilization of the E-3-1 material ( supernate and settled solids) resulted in waste forms which passed the TCLP test for both Hg and Cr. However, the ion exchange resins tested were ineffective in removing the Hg from this waste stream. Consequently, cement stabilization is recommended for a treatment of the five drums of the actual waste.

  5. The E3 Ligase CHIP Mediates p21 Degradation to Maintain Radioresistance.

    Science.gov (United States)

    Biswas, Kuntal; Sarkar, Sukumar; Du, Kangping; Brautigan, David L; Abbas, Tarek; Larner, James M

    2017-06-01

    Lung cancer resists radiotherapy, making it one of the deadliest forms of cancer. Here, we show that human lung cancer cell lines can be rendered sensitive to ionizing radiation (IR) by RNAi knockdown of C-terminus of Hsc70-interacting protein (CHIP/STUB1), a U-box-type E3 ubiquitin ligase that targets a number of stress-induced proteins. Mechanistically, ubiquitin-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor, p21 protein, is reduced by CHIP knockdown, leading to enhanced senescence of cells in response to exposure to IR. Cellular senescence and sensitivity to IR is prevented by CRISPR/Cas9-mediated deletion of the p21 gene (CDKN1A) in CHIP knockdown cells. Conversely, overexpression of CHIP potentiates p21 degradation and promotes greater radioresistance of lung cancer cells. In vitro and cell-based assays demonstrate that p21 is a novel and direct ubiquitylation substrate of CHIP that also requires the CHIP-associated chaperone HSP70. These data reveal that the inhibition of the E3 ubiquitin ligase CHIP promotes radiosensitivity, thus suggesting a novel strategy for the treatment of lung cancer.Implications: The CHIP-HSP70-p21 ubiquitylation/degradation axis identified here could be exploited to enhance the efficacy of radiotherapy in patients with non-small cell lung cancer. Mol Cancer Res; 15(6); 651-9. ©2017 AACR. ©2017 American Association for Cancer Research.

  6. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide.

    Science.gov (United States)

    Fischer, Eric S; Böhm, Kerstin; Lydeard, John R; Yang, Haidi; Stadler, Michael B; Cavadini, Simone; Nagel, Jane; Serluca, Fabrizio; Acker, Vincent; Lingaraju, Gondichatnahalli M; Tichkule, Ritesh B; Schebesta, Michael; Forrester, William C; Schirle, Markus; Hassiepen, Ulrich; Ottl, Johannes; Hild, Marc; Beckwith, Rohan E J; Harper, J Wade; Jenkins, Jeremy L; Thomä, Nicolas H

    2014-08-07

    In the 1950s, the drug thalidomide, administered as a sedative to pregnant women, led to the birth of thousands of children with multiple defects. Despite the teratogenicity of thalidomide and its derivatives lenalidomide and pomalidomide, these immunomodulatory drugs (IMiDs) recently emerged as effective treatments for multiple myeloma and 5q-deletion-associated dysplasia. IMiDs target the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4(CRBN)) and promote the ubiquitination of the IKAROS family transcription factors IKZF1 and IKZF3 by CRL4(CRBN). Here we present crystal structures of the DDB1-CRBN complex bound to thalidomide, lenalidomide and pomalidomide. The structure establishes that CRBN is a substrate receptor within CRL4(CRBN) and enantioselectively binds IMiDs. Using an unbiased screen, we identified the homeobox transcription factor MEIS2 as an endogenous substrate of CRL4(CRBN). Our studies suggest that IMiDs block endogenous substrates (MEIS2) from binding to CRL4(CRBN) while the ligase complex is recruiting IKZF1 or IKZF3 for degradation. This dual activity implies that small molecules can modulate an E3 ubiquitin ligase and thereby upregulate or downregulate the ubiquitination of proteins.

  7. Odd tensor E3 transitions and the generalized seniority in Sn-isotopes

    CERN Document Server

    Maheshwari, Bhoomika

    2016-01-01

    In our recent paper [Phys. Lett. B 753, (2016) 122], we have shown that both the odd and even tensor electric transition probabilities exhibit similar behavior within the generalized seniority scheme in a multi-j environment. This microscopic approach was used to show for the first time the occurrence of seniority isomers in the $ {13}^-$ isomers of Sn-isotopes, which decay by odd tensor $E1$ transition to the same seniority ($\\Delta v = 0$) state. In this letter, we extend our studies to odd tensor $E3$ transitions connecting different seniority states ($\\Delta v = 2$), and show for the first time that the generalized seniority scheme explains reasonably well the systematics of the $B(E3)$ values for the $(0^+ \\rightarrow 3_1^-)$ transitions in the Sn-isotopes. Additionally, we support these results by seniority guided Large Scale Shell Model (LSSM) calculations. The generalized seniority results are able to single out the most crucial valence space required in the LSSM calculations.

  8. Noninvasive visualization of adenovirus replication with a fluorescent reporter in the E3 region.

    Science.gov (United States)

    Ono, Hidetaka A; Le, Long P; Davydova, Julia G; Gavrikova, Tatyana; Yamamoto, Masato

    2005-11-15

    To overcome the inefficacy and undesirable side effects of current cancer treatment strategies, conditionally replicative adenoviruses have been developed to exploit the unique mechanism of oncolysis afforded by tumor-specific viral replication. Despite rapid translation into clinical trials and the established safety of oncolytic adenoviruses, the in vivo function of these agents is not well understood due to lack of a noninvasive detection system for adenovirus replication. To address this issue, we propose the expression of a reporter from the adenovirus E3 region as a means to monitor replication. Adenovirus replication reporter vectors were constructed with the enhanced green fluorescent protein (EGFP) gene placed in the deleted E3 region under the control of the adenoviral major late promoter while retaining expression of the adenovirus death protein to conserve the native oncolytic capability of the virus. Strong EGFP fluorescence was detected from these vectors in a replication-dependent manner, which correlated with viral DNA replication. Fluorescence imaging in vivo confirmed the ability to noninvasively detect fluorescent signal during replication, which generally corresponded with the underlying level of viral DNA replication. EGFP representation of viral replication was further confirmed by Western blot comparison with the viral DNA content in the tumors. Imaging reporter expression controlled by the adenoviral major late promoter provides a viable approach to noninvasively monitor adenovirus replication in preclinical studies and has the potential for human application with clinically relevant imaging reporters.

  9. Multiple charge density wave states at the surface of TbT e3

    Science.gov (United States)

    Fu, Ling; Kraft, Aaron M.; Sharma, Bishnu; Singh, Manoj; Walmsley, Philip; Fisher, Ian R.; Boyer, Michael C.

    2016-11-01

    We studied TbT e3 using scanning tunneling microscopy (STM) in the temperature range of 298-355 K. Our measurements detect a unidirectional charge density wave (CDW) state in the surface Te layer with a wave vector consistent with that of the bulk qCDW=0.30 ±0.01 c* . However, unlike previous STM measurements, and differing from measurements probing the bulk, we detect two perpendicular orientations for the unidirectional CDW with no directional preference for the in-plane crystal axes (a or c axis) and no noticeable difference in wave vector magnitude. In addition, we find regions in which the bidirectional CDW states coexist. We propose that observation of two unidirectional CDW states indicates a decoupling of the surface Te layer from the rare-earth block layer below, and that strain variations in the Te surface layer drive the local CDW direction to the specific unidirectional or, in rare occurrences, bidirectional CDW orders observed. This indicates that similar driving mechanisms for CDW formation in the bulk, where anisotropic lattice strain energy is important, are at play at the surface. Furthermore, the wave vectors for the bidirectional order we observe differ from those theoretically predicted for checkerboard order competing with stripe order in a Fermi-surface nesting scenario, suggesting that factors beyond Fermi-surface nesting drive CDW order in TbT e3 . Finally, our temperature-dependent measurements provide evidence for localized CDW formation above the bulk transition temperature TCDW.

  10. Diagramming Transactive Building Business Cases: Using Principles of e3 Value to Document Valuation Studies

    Energy Technology Data Exchange (ETDEWEB)

    Hammerstrom, Donald J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Makhmalbaf, Atefe [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Marinovici, Maria C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-12-30

    Energy management in buildings is becoming more transactive. Pacific Northwest National Laboratory and the U.S. Department of Energy Building Technologies Office recently defined innovative use cases wherein market-like mechanisms are used to manage energy within buildings, between buildings, and between buildings and third-party entities, such as power utilities. A next step toward defining a set of transactive use cases in the buildings domain is to carefully diagram the corresponding business cases to capture details of transactions among all stakeholders and their economic value propositions. The principles of e3-value diagramming are applied in this report toward creating business value diagrams. These principles are extended to be consistent with Universal Modeling Language use-case diagrams. Example diagrams are presented for a subset of buildings-domain use cases that were introduced in an earlier Pacific Northwest National Laboratory report. The diagrams are intended to clearly represent an understanding of the transactions through which individual entities accumulate value in their respective use cases, and the diagrams should therefore support economic valuation studies. The report reviews some of the foundational principles of e3 value and includes authors’ insights concerning the formulation of these diagrams using Universal Modeling Language as a more systematic modeling approach.

  11. No Evidence for Multiple Stellar Populations in the Low-mass Galactic Globular Cluster E 3

    Science.gov (United States)

    Salinas, Ricardo; Strader, Jay

    2015-08-01

    Multiple stellar populations are a widespread phenomenon among Galactic globular clusters. Even though the origin of the enriched material from which new generations of stars are produced remains unclear, it is likely that self-enrichment will be feasible only in clusters massive enough to retain this enriched material. We searched for multiple populations in the low mass (M˜ 1.4× {10}4 {M}⊙ ) globular cluster E3, analyzing SOAR/Goodman multi-object spectroscopy centered on the blue cyanogen (CN) absorption features of 23 red giant branch stars. We find that the CN abundance does not present the typical bimodal behavior seen in clusters hosting multistellar populations, but rather a unimodal distribution that indicates the presence of a genuine single stellar population, or a level of enrichment much lower than in clusters that show evidence for two populations from high-resolution spectroscopy. E3 would be the first bona fide Galactic old globular cluster where no sign of self-enrichment is found. Based on observations obtained at the Southern Astrophysical Research (SOAR) Telescope, which is a joint project of the Ministério da Ciência, Tecnologia, e Inovação (MCTI) da República Federativa do Brasil, the US National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU).

  12. Rock size-frequency distribution analysis at the Chang'E-3 landing site

    Science.gov (United States)

    Di, Kaichang; Xu, Bin; Peng, Man; Yue, Zongyu; Liu, Zhaoqin; Wan, Wenhui; Li, Lichun; Zhou, Jianliang

    2016-01-01

    This paper presents a comprehensive analysis of the rock size-frequency distribution at the Chang'E-3 landing site. Using 84 Navcam stereo images acquired at 7 waypoints by the Yutu rover and an interactive stereo image processing system, a total of 582 rocks larger than 0.05 m in diameter were identified and measured. The statistical results of the size-frequency distribution show that the cumulative fractional area covered by rocks versus their diameter follows a simple exponential function and has a convex-up shape on log-log graphs with the slope increasing with diameter. The cumulative number of rocks versus diameter derived by numerically integrating the cumulative fractional area also shows a good fit with the data. A diameter-height relationship was also determined from height and diameter ratios. The observed rock statistics were also compared with those from other lunar missions, including the Surveyor, Apollo, and Lunokhod missions; results suggest that the rock distribution at the Chang'E-3 landing site is similar to that found by Surveyor III.

  13. No evidence for multiple stellar populations in the low-mass Galactic globular cluster E 3

    CERN Document Server

    Salinas, Ricardo

    2015-01-01

    Multiple stellar populations are a widespread phenomenon among Galactic globular clusters. Even though the origin of the enriched material from which new generations of stars are produced remains unclear, it is likely that self-enrichment will be feasible only in clusters massive enough to retain this enriched material. We searched for multiple populations in the low mass (M~1.4 x 10^4 M_sun) globular cluster E 3, analyzing SOAR/Goodman multi-object spectroscopy centered on the blue CN absorption features of 23 red giant branch stars. We find that the CN abundance does not present the typical bimodal behavior seen in clusters hosting multi stellar populations, but rather a unimodal distribution that indicates the presence of a genuine single stellar population, or a level of enrichment much lower than in clusters that show evidence for two populations from high-resolution spectroscopy. E 3 would be the first bona fide Galactic old globular cluster where no sign of self-enrichment is found.

  14. Self-clearance mechanism of mitochondrial E3 ligase MARCH5 contributes to mitochondria quality control.

    Science.gov (United States)

    Kim, Song-Hee; Park, Yong-Yea; Yoo, Young-Suk; Cho, Hyeseong

    2016-01-01

    MARCH5, a mitochondrial E3 ubiquitin ligase, controls mitochondrial dynamics proteins and misfolded proteins, and has been proposed to play a role in mitochondria quality control. However, it remains unclear how mutant MARCH5 found in cancer tissues is removed from cells. Here, we show that mutation in the MARCH5 ligase domain increased its half-life fourfold, resulting in a drastic increase in its protein level. Abnormal accumulation of the E3 ligase-defective MARCH5 mutants MARCH5(H43W) and MARCH5(C65/68S) was diminished by overexpression of active MARCH5(WT) ; the mutant proteins were degraded through the ubiquitin-proteasome pathway. Coimmunoprecipitation revealed that MARCH5 forms homodimers, and that substitution of Gly to Leu at the first putative GxxxG dimerization motif, but not the second, resulted in a loss of dimeric interaction. Moreover, overexpression of the dimerization-defective mutant MARCH5(4GL) could not decrease the level of accumulated MARCH5(H43W) , suggesting that dimerization of MARCH5 is necessary for self-clearance. Abnormal accumulation of MARCH5(H43W) and mitochondrial hyperfusion led to NF-ĸB activation, which was suppressed by overexpression of MARCH5(WT) . Together, the data reveal a self-protective mechanism involving MARCH5, which can target its own dysfunctional mutant for degradation in order to maintain mitochondrial homeostasis.

  15. Mutations in the DNA-binding domain of NR2E3 affect in vivo dimerization and interaction with CRX.

    Directory of Open Access Journals (Sweden)

    Raphael Roduit

    Full Text Available BACKGROUND: NR2E3 (PNR is an orphan nuclear receptor essential for proper photoreceptor determination and differentiation. In humans, mutations in NR2E3 have been associated with the recessively inherited enhanced short wavelength sensitive (S- cone syndrome (ESCS and, more recently, with autosomal dominant retinitis pigmentosa (adRP. NR2E3 acts as a suppressor of the cone generation program in late mitotic retinal progenitor cells. In adult rod photoreceptors, NR2E3 represses cone-specific gene expression and acts in concert with the transcription factors CRX and NRL to activate rod-specific genes. NR2E3 and CRX have been shown to physically interact in vitro through their respective DNA-binding domains (DBD. The DBD also contributes to homo- and heterodimerization of nuclear receptors. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed NR2E3 homodimerization and NR2E3/CRX complex formation in an in vivo situation by Bioluminescence Resonance Energy Transfer (BRET(2. NR2E3 wild-type protein formed homodimers in transiently transfected HEK293T cells. NR2E3 homodimerization was impaired in presence of disease-causing mutations in the DBD, except for the p.R76Q and p.R104W mutant proteins. Strikingly, the adRP-linked p.G56R mutant protein interacted with CRX with a similar efficiency to that of NR2E3 wild-type and p.R311Q proteins. In contrast, all other NR2E3 DBD-mutant proteins did not interact with CRX. The p.G56R mutant protein was also more effective in abolishing the potentiation of rhodospin gene transactivation by the NR2E3 wild-type protein. In addition, the p.G56R mutant enhanced the transrepression of the M- and S-opsin promoter, while all other NR2E3 DBD-mutants did not. CONCLUSIONS/SIGNIFICANCE: These results suggest different disease mechanisms in adRP- and ESCS-patients carrying NR2E3 mutations. Titration of CRX by the p.G56R mutant protein acting as a repressor in trans may account for the severe clinical phenotype in adRP patients.

  16. Biophysical analysis of apolipoprotein E3 variants linked with development of type III hyperlipoproteinemia.

    Directory of Open Access Journals (Sweden)

    Dimitra Georgiadou

    Full Text Available BACKGROUND: Apolipoprotein E (apoE is a major protein of the lipoprotein transport system that plays important roles in lipid homeostasis and protection from atherosclerosis. ApoE is characterized by structural plasticity and thermodynamic instability and can undergo significant structural rearrangements as part of its biological function. Mutations in the 136-150 region of the N-terminal domain of apoE, reduce its low density lipoprotein (LDL receptor binding capacity and have been linked with lipoprotein disorders, such as type III hyperlipoproteinemia (HLP in humans. However, the LDL-receptor binding defects for these apoE variants do not correlate well with the severity of dyslipidemia, indicating that these variants may carry additional properties that contribute to their pathogenic potential. METHODOLOGY/PRINCIPAL FINDINGS: In this study we examined whether three type III HLP predisposing apoE3 variants, namely R136S, R145C and K146E affect the biophysical properties of the protein. Circular dichroism (CD spectroscopy revealed that these mutations do not significantly alter the secondary structure of the protein. Thermal and chemical unfolding analysis revealed small thermodynamic alterations in each variant compared to wild-type apoE3, as well as effects in the reversibility of the unfolding transition. All variants were able to remodel multillamelar 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC vesicles, but R136S and R145C had reduced kinetics. Dynamic light scattering analysis indicated that the variant R136S exists in a higher-order oligomerization state in solution. Finally, 1-anilinonaphthalene-8-sulfonic acid (ANS binding suggested that the variant R145C exposes a larger amount of hydrophobic surface to the solvent. CONCLUSIONS/SIGNIFICANCE: Overall, our findings suggest that single amino acid changes in the functionally important region 136-150 of apoE3 can affect the molecule's stability and conformation in solution and may

  17. Structural analysis of lunar subsurface with Chang'E-3 lunar penetrating radar

    Science.gov (United States)

    Lai, Jialong; Xu, Yi; Zhang, Xiaoping; Tang, Zesheng

    2016-01-01

    Geological structure of the subsurface of the Moon provides valuable information on lunar evolution. Recently, Chang'E-3 has utilized lunar penetrating radar (LPR), which is equipped on the lunar rover named as Yutu, to detect the lunar geological structure in Northern Imbrium (44.1260N, 19.5014W) for the first time. As an in situ detector, Chang'E-3 LPR has relative higher horizontal and vertical resolution and less clutter impact compared to spaceborne radars and earth-based radars. In this work, we analyze the LPR data at 500 MHz transmission frequency to obtain the shallow subsurface structure of the landing area of Chang'E-3 in Mare Imbrium. Filter method and amplitude recovery algorithms are utilized to alleviate the adverse effects of environment and system noises and compensate the amplitude losses during signal propagation. Based on the processed radar image, we observe numerous diffraction hyperbolae, which may be caused by discrete reflectors beneath the lunar surface. Hyperbolae fitting method is utilized to reverse the average dielectric constant to certain depth (ε bar). Overall, the estimated ε bar increases with the depth and ε bar could be classified into three categories. Average ε bar of each category is 2.47, 3.40 and 6.16, respectively. Because of the large gap between the values of ε bar of neighboring categories, we speculate a three-layered structure of the shallow surface of LPR exploration region. One possible geological picture of the speculated three-layered structure is presented as follows. The top layer is weathered layer of ejecta blanket with its average thickness and bound on error is 0.95±0.02 m. The second layer is the ejecta blanket of the nearby impact crater, and the corresponding average thickness is about 2.30±0.07 m, which is in good agreement with the two primary models of ejecta blanket thickness as a function of distance from the crater center. The third layer is regarded as a mixture of stones and soil. The

  18. Novel roles of Skp2 E3 ligase in cellular senescence, cancer progression, and metastasis

    Institute of Scientific and Technical Information of China (English)

    Guocan Wang; Chia-Hsin Chan; Yuan Gao; Hui-Kuan Lin

    2012-01-01

    S-phase kinase-associated protein 2 (Skp2) belongs to the F-box protein family.It is a component of the SCF E3 ubiquitin ligase complex.Skp2 has been shown to regulate cellular proliferation by targeting several cell cycle-regulated proteins for ubiquitination and degradation,including cyclin-dependent kinase inhibitor p27.Skp2 has also been demonstrated to display an oncogenic function since its overexpression has been observed in many human cancers.This review discusses the recent discoveries on the novel roles of Skp2 in regulating cellular senescence,cancer progression,and metastasis,as well as the therapeutic potential of targeting Skp2 for human cancer treatment.

  19. RING finger palmitoylation of the endoplasmic reticulum Gp78 E3 ubiquitin ligase.

    Science.gov (United States)

    Fairbank, Maria; Huang, Kun; El-Husseini, Alaa; Nabi, Ivan R

    2012-07-30

    Gp78 is an E3 ubiquitin ligase within the endoplasmic reticulum-associated degradation pathway. We show that Flag-tagged gp78 undergoes sulfhydryl cysteine palmitoylation (S-palmitoylation) within the RING finger motif, responsible for its ubiquitin ligase activity. Screening of 19 palmitoyl acyl transferases (PATs) identified five that increased gp78 RING finger palmitoylation. Endoplasmic reticulum (ER)-localized Myc-DHHC6 overexpression promoted the peripheral ER distribution of Flag-gp78 while RING finger mutation and the palmitoylation inhibitor 2-bromopalmitate restricted gp78 to the central ER. Palmitoylation of RING finger cysteines therefore regulates gp78 distribution to the peripheral ER. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  20. K-shell (e, 3e) double ionization of beryllium by relativistic electrons

    Energy Technology Data Exchange (ETDEWEB)

    Becher, M; Joulakian, B [Universite Paul Verlaine-Metz, Laboratoire de Physique Moleculaire et des Collisions, Member FR CNRS 2843 Jean Barriol 1 Bd Arago, 57078 Metz Cedex 3 (France)

    2009-03-28

    The (e, 3e) process, producing hollow metastable Be{sup 2+}(2s{sup 2}) by very energetic electrons (>100 keV), is studied by using a relativistic procedure based on the application of the first term of the Born series for the determination of the corresponding fully differential cross section. The very fast projectile electron, impinging on the K shell of the neutral beryllium, is described by Dirac plane-wave solutions with the appropriate wave vectors. All atomic electrons and the two final-state-bound electrons are taken into account by non-relativistic Jastrow-type correlated functions. The two slow ejected electrons in the continuum are described by the fully correlated three-Coulomb (3C) function. The comparison of the results with those obtained by our recent non-relativistic approach shows the necessity of the introduction of the relativistic treatment.

  1. Analysis of observational data from Extreme Ultra-Violet Camera onboard Chang'E-3 mission

    Science.gov (United States)

    Yan, Yan; Wang, Hua-Ning; He, Han; He, Fei; Chen, Bo; Feng, Jian-Qing; Ping, Jin-Song; Shen, Chao; Xu, Rong-Lan; Zhang, Xiao-Xin

    2016-02-01

    The Extreme Ultra-Violet Camera (hereafter EUVC) is a scientific payload onboard the lander of the Chang'E-3 (hereafter CE-3) mission launched on December 1st, 2013. Centering on a spectral band around 30.4 nm, EUVC provides the global images of the Earth's plasmasphere from the meridian view, with a spatial resolution of 0.1 R_{oplus} in 150 × 150 pixels and a cadence of 10 minutes. Along with the data being publicly released online, some unsettled issues in the early stage have been clarified, including the geometrical preparations, the refined approach on the coefficient K for the background, and the alignment among the images. A demo of data after all the above processes is therefore presented as a guidance for users who are studying the structure and dynamics of the plasmasphere.

  2. TRIM E3 ligases interfere with early and late stages of the retroviral life cycle.

    Directory of Open Access Journals (Sweden)

    Pradeep D Uchil

    2008-02-01

    Full Text Available Members of the TRIpartite interaction Motif (TRIM family of E3 ligases have been shown to exhibit antiviral activities. Here we report a near comprehensive screen for antiretroviral activities of 55 TRIM proteins (36 human, 19 mouse. We identified approximately 20 TRIM proteins that, when transiently expressed in HEK293 cells, affect the entry or release of human immunodeficiency virus 1 (HIV, murine leukemia virus (MLV, or avian leukosis virus (ALV. While TRIM11 and 31 inhibited HIV entry, TRIM11 enhanced N-MLV entry by interfering with Ref1 restriction. Strikingly, many TRIM proteins affected late stages of the viral life cycle. Gene silencing of endogenously expressed TRIM 25, 31, and 62 inhibited viral release indicating that they play an important role at late stages of the viral life cycle. In contrast, downregulation of TRIM11 and 15 enhanced virus release suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells.

  3. [Suppression of E3 ubiquitin ligase Cbl-b in interleukin-1 signaling].

    Science.gov (United States)

    Yu, Jiang-Tian; Bu, Xin; Zhao, Hu; Su, Jin

    2015-08-25

    The present study aims to investigate the effect of Cbl-b, a member of E3 ubiquitin ligase family, on interleukin-1 (IL-1) pathway in synoviocytes. The protein expression levels of Cbl-b and IL-1-induced matrix metalloproteinase 13 (MMP-13) in synoviocytes were analyzed by Western blot. Collagen substrates were incubated with the conditioned medium collected from synoviocytes cultures and then subjected to SDS-PAGE for analysis of collagen degradation. The results showed that compared with wild-type cells, Cbl-b-deficient cells expressed more MMP-13 protein and had enhanced ability to degrade collagens under IL-1 stimulation. These data suggest that Cbl-b may negatively regulate IL-1-triggered degradation of collagen matrix in synoviocytes.

  4. Structure and aggregation proclivity of C12E3 in aqueous solution

    Science.gov (United States)

    Zahariev, Ts.; Ivanova, A.; Velinova, M.; Tadjer, A.

    2013-01-01

    Olygo(ethylene glycol) alkyl ethers - CxEy are well known for their high surface activity and rich phase behavior. These substances exhibit some unusual aggregation characteristics in aqueous solution even at concentrations well below CMC attributed to the formation of pre-aggregates of small size, e.g., dimers. To verify this, a series of C12E3 dimers with initial geometries taken from coarse-grained molecular dynamics simulations is subject to geometry optimization with two quantum chemical methods: DFT and ONIOM in implicit water solvent. The resulting structures are classified into groups based on structural parameters. Their stability is assessed by relative and binding energy and rationalized in terms of molecular characteristics. All studied dimers are stable and various mutual alignments of the surfactants therein are feasible. The loss of surface area is outlined as the predominant stabilizing factor. Substantial number of the structures is suitable for further aggregation.

  5. Design and Environmental Verification of Chang'E-3 Moon-night Survival Device for APXS

    Science.gov (United States)

    Chen, D. Y.; Wu, J.; Hu, Y. M.; Chang, J.; Gong, Y. Z.; Cai, M. S.; Wang, H. Y.; Zhang, J. Y.; Cui, X. Z.; Wang, J. Y.

    2015-09-01

    The Active Particle X-ray Spectrum (APXS) is one of the 4 scientific payloads of Chang'E-3 (CE-3) Lunar Rover, of which the scientific object is to identify the elements of lunar soil and rock samples. In this paper, the moon-night temperature of the moon surface will be described, and due to the cold environment the APXS will undergo after its landing. Thus, a specialized instrument which is named the moon-night survival device using the Radioisotope Heat Unit (RHU) as its heater source is designed to ensure APXS storage temperature requirements with limited sources on the satellite. In the end, a series of environmental tests are performed, and the installation of RHU on the launch tower as well as the status of the APXS working on orbit is presented since its launching in 2013.

  6. Design and Experimental Verification of Chang'E-3 Moon-night Survival Device for APXS

    Science.gov (United States)

    Deng-yi, Chen; Jian, Wu; Yi-ming, Hu; Jin, Chang; Yi-zhong, Gong; Ming-sheng, Cai; Huan-yu, Wang; Jia-yu, Zhang; Xing-zhu, Cui; Jin-zhou, Wang

    2016-07-01

    The Active Particle X-ray Spectrometer (APXS) is one of the 4 scientific payloads of Chang'E-3 (CE-3) Lunar Rover, of which the scientific object is to identify the elements of lunar soil and rock samples by a carried radioactive source to trigger and detect the characteristic X-ray from them. According to the extreme temperature environment of the APXS and under the restriction of limited resources, this paper presents the design and analysis of the moon-night survival device RHU (radioisotope heating unit) for the APXS, and describes the corresponding environmental tests on its structure dynamics and moon-night survival. Finally, its reinstallation on the launch tower and the preliminary result of its on-orbit operation are introduced.

  7. Lunar soil strength estimation based on Chang'E-3 images

    Science.gov (United States)

    Gao, Yang; Spiteri, Conrad; Li, Chun-Lai; Zheng, Yong-Chun

    2016-11-01

    Chang'E-3 (CE-3) was the third mission by China to explore the Moon which had landed two spacecraft, the CE-3 lander and Yutu rover on the lunar surface in late 2013. The paper presents analytical results of high-resolution terrain data taken by CE-3's onboard cameras. The image data processing aims to extract sinkage profiles of the wheel tracks during the rover traverse. Further analysis leads to derivation or estimation of lunar soil physical properties (in terms of strength and stiffness) based on the wheel sinkage, despite the fact Yutu does not possess in situ soil measurement instruments. Our findings indicate that the lunar soil at the CE-3 landing site has similar stiffness to what is measured at the Luna 17 landing site but has much less strength compared to the Apollo 15 landing site.

  8. Speed Measurement and Motion Analysis of Chang'E-3 Rover Based on Differential Phase Delay

    Science.gov (United States)

    Chao, Pan; Qing-hui, Liu; Xin, Zheng; Qing-bao, He; Ya-jun, Wu

    2016-04-01

    On 14th December 2013, the Chang'E-3 made a successful soft landing on the lunar surface, and then carried out the tasks of separating the lander and the rover, and taking pictures of each other. With the same beam VLBI (Very Long Baseline Interferometry) technique to observe the signals transmitted by the lander and the rover simultaneously, the differential phase delay between them is calculated, which can reflect the minor changes of the rover's position on a scale of a few centimeters. Based on the high sensitivity of differential phase delay, the rover's speeds during 5 movements are obtained with an average of 0.056 m/s. The relationship between the rover's shake in the moving process and the lunar terrain is analyzed by using the spectrum of the residual of the differential phase delay after the first-order polynomial fitting.

  9. Cullin4B/E3-ubiquitin ligase negatively regulates -catenin

    Indian Academy of Sciences (India)

    Rachana Tripathi; Satya Keerthi Kota; Usha K Srinivas

    2007-09-01

    -catenin is the key transducer of Wingless-type MMTV integration site family member (Wnt) signalling, upregulation of which is the cause of cancer of the colon and other tissues. In the absence of Wnt signals, -catenin is targeted to ubiquitin–proteasome-mediated degradation. Here we present the functional characterization of E3-ubiquitin ligase encoded by cul4B. RNAi-mediated knock-down of Cul4B in a mouse cell line C3H T10 (1/2) results in an increase in -catenin levels. Loss-of-function mutation in Drosophila cul4 also shows increased -catenin/Armadillo levels in developing embryos and displays a characteristic naked-cuticle phenotype. Immunoprecipitation experiments suggest that Cul4B and -catenin are part of a signal complex in Drosophila, mouse and human. These preliminary results suggest a conserved role for Cul4B in the regulation of -catenin levels.

  10. Ret Finger Protein: An E3 Ubiquitin Ligase Juxtaposed to the XY Body in Meiosis

    Directory of Open Access Journals (Sweden)

    Isabelle Gillot

    2009-01-01

    Full Text Available During prophase I of male meiosis, the sex chromosomes form a compact structure called XY body that associates with the nuclear membrane of pachytene spermatocytes. Ret Finger Protein is a transcriptional repressor, able to interact with both nuclear matrix-associated proteins and double-stranded DNA. We report the precise and unique localization of Ret Finger Protein in pachytene spermatocytes, in which Ret Finger Protein takes place of lamin B1, between the XY body and the inner nuclear membrane. This localization of Ret Finger Protein does not seem to be associated with O-glycosylation or sumoylation. In addition, we demonstrate that Ret Finger Protein contains an E3 ubiquitin ligase activity. These observations lead to an attractive hypothesis in which Ret Finger Protein would be involved in the positioning and the attachment of XY body to the nuclear lamina of pachytene spermatocytes.

  11. Chang'e 3 and Jade Rabbit's: observations and the landing zone

    Science.gov (United States)

    Ping, Jinsong

    Chang’E-3 was launched and landed on the near side of the Moon in December 2013. It is realizing the 2nd phase of Chinese lunar scientific exploration projects. Together with the various in-situ optical observations around the landing sites, the mission carried 4 kinds of radio science experiments, cover the various lunar scientific disciplines as well as lunar surface radio astronomy studies. The key payloads onboard the lander and rover include the near ultraviolet telescope, extreme ultraviolet cameras, ground penetrating radar, very low frequency radio spectrum analyzer, which have not been used in earlier lunar landing missions. Optical spectrometer, Alpha Paticle X-ray spectrometer and Gama Ray spectrometer is also used. The mission is using extreme ultraviolet camera to observe the sun activity and geomagnetic disturbances on geo-space plasma layer of extreme ultraviolet radiation, studying space weather in the plasma layer role in the process; the mission also carries the first time lunar base optical astronomical observations. Most importantly, the topography, landforms and geological structure has been explored in detail. Additionally, the very precise Earth-Moon radio phase ranging technique was firstly tested and realized in this mission. It may increase the study of lunar dyanmics together with LLR technique. Similar to Luna-Glob landers, together with the VLBI radio beacons, the radio transponders are also set on the Chang’E-3. Transponder will receive the uplink X band radio wave transmitted from the two newly constructed Chinese deep space stations, where the high quality hydrogen maser atomic clocks have been used as local time and frequency standard. Radio science receivers have been developed by updating the multi-channel open loop Doppler receiver developed for VLBI and Doppler tracking in Yinghuo-1 and Phobos-Glob Martian missions. This experiment will improve the study of lunar dynamics, by means of measuring the lunar physical liberations

  12. Immersive Virtual Moon Scene System Based on Panoramic Camera Data of Chang'E-3

    Science.gov (United States)

    Gao, X.; Liu, J.; Mu, L.; Yan, W.; Zeng, X.; Zhang, X.; Li, C.

    2014-12-01

    The system "Immersive Virtual Moon Scene" is used to show the virtual environment of Moon surface in immersive environment. Utilizing stereo 360-degree imagery from panoramic camera of Yutu rover, the system enables the operator to visualize the terrain and the celestial background from the rover's point of view in 3D. To avoid image distortion, stereo 360-degree panorama stitched by 112 images is projected onto inside surface of sphere according to panorama orientation coordinates and camera parameters to build the virtual scene. Stars can be seen from the Moon at any time. So we render the sun, planets and stars according to time and rover's location based on Hipparcos catalogue as the background on the sphere. Immersing in the stereo virtual environment created by this imaged-based rendering technique, the operator can zoom, pan to interact with the virtual Moon scene and mark interesting objects. Hardware of the immersive virtual Moon system is made up of four high lumen projectors and a huge curve screen which is 31 meters long and 5.5 meters high. This system which take all panoramic camera data available and use it to create an immersive environment, enable operator to interact with the environment and mark interesting objects contributed heavily to establishment of science mission goals in Chang'E-3 mission. After Chang'E-3 mission, the lab with this system will be open to public. Besides this application, Moon terrain stereo animations based on Chang'E-1 and Chang'E-2 data will be showed to public on the huge screen in the lab. Based on the data of lunar exploration,we will made more immersive virtual moon scenes and animations to help the public understand more about the Moon in the future.

  13. Chaperone-dependent E3 ligase CHIP ubiquitinates and mediates proteasomal degradation of soluble guanylyl cyclase.

    Science.gov (United States)

    Xia, Tian; Dimitropoulou, Christiana; Zeng, Jingmin; Antonova, Galina N; Snead, Connie; Venema, Richard C; Fulton, David; Qian, Shuibing; Patterson, Cam; Papapetropoulos, Andreas; Catravas, John D

    2007-11-01

    The nitric oxide receptor soluble guanylyl cyclase (sGC) exists in multimeric protein complexes, including heat shock protein (HSP) 90 and endothelial nitric oxide synthase. Inhibition of HSP90 by geldanamycin causes proteasomal degradation of sGC protein. In this study, we have investigated whether COOH terminus of heat shock protein 70-interacting protein (CHIP), a co-chaperone molecule that is involved in protein folding but is also a chaperone-dependent ubiquitin E3 ligase, could play a role in the process of degradation of sGC. Transient overexpression of CHIP in COS-7 cells degraded heterologous sGC in a concentration-related manner; this downregulation of sGC was abrogated by the proteasome inhibitor MG-132. Transfection of tetratricopeptide repeats and U-box domain CHIP mutants attenuated sGC degradation, suggesting that both domains are indispensable for CHIP function. Results from immunoprecipitation and indirect immunofluorescent microscopy experiments demonstrated that CHIP is associated with sGC, HSP90, and HSP70 in COS-7 cells. Furthermore, CHIP increased the association of HSP70 with sGC. In in vitro ubiquitination assays using purified proteins and ubiquitin enzymes, E3 ligase CHIP directly ubiquitinated sGC; this ubiquitination was potentiated by geldanamycin in COS-7 cells, followed by proteasomal degradation. In rat aortic smooth muscle cells, endogenous sGC was also degraded by adenovirus-infected wild-type CHIP but not by the chaperone interaction-deficient K30A CHIP, whereas CHIP, but not K30A, attenuated sGC expression in, and nitric oxide donor-induced relaxation of, rat aortic rings, suggesting that CHIP plays a regulatory role under physiological conditions. This study reveals a new mechanism for the regulation of sGC, an important mediator of cellular and vascular function.

  14. Lenalidomide Stabilizes the Erythropoietin Receptor by Inhibiting the E3 Ubiquitin Ligase RNF41.

    Science.gov (United States)

    Basiorka, Ashley A; McGraw, Kathy L; De Ceuninck, Leentje; Griner, Lori N; Zhang, Ling; Clark, Justine A; Caceres, Gisela; Sokol, Lubomir; Komrokji, Rami S; Reuther, Gary W; Wei, Sheng; Tavernier, Jan; List, Alan F

    2016-06-15

    In a subset of patients with non-del(5q) myelodysplastic syndrome (MDS), lenalidomide promotes erythroid lineage competence and effective erythropoiesis. To determine the mechanism by which lenalidomide promotes erythropoiesis, we investigated its action on erythropoietin receptor (EpoR) cellular dynamics. Lenalidomide upregulated expression and stability of JAK2-associated EpoR in UT7 erythroid cells and primary CD71+ erythroid progenitors. The effects of lenalidomide on receptor turnover were Type I cytokine receptor specific, as evidenced by coregulation of the IL3-Rα receptor but not c-Kit. To elucidate this mechanism, we investigated the effects of lenalidomide on the E3 ubiquitin ligase RNF41. Lenalidomide promoted EpoR/RNF41 association and inhibited RNF41 auto-ubiquitination, accompanied by a reduction in EpoR ubiquitination. To confirm that RNF41 is the principal target responsible for EpoR stabilization, HEK293T cells were transfected with EpoR and/or RNF41 gene expression vectors. Steady-state EpoR expression was reduced in EpoR/RNF41 cells, whereas EpoR upregulation by lenalidomide was abrogated, indicating that cellular RNF41 is a critical determinant of drug-induced receptor modulation. Notably, shRNA suppression of CRBN gene expression failed to alter EpoR upregulation, indicating that drug-induced receptor modulation is independent of cereblon. Immunohistochemical staining showed that RNF41 expression decreased in primary erythroid cells of lenalidomide-responding patients, suggesting that cellular RNF41 expression merits investigation as a biomarker for lenalidomide response. Our findings indicate that lenalidomide has E3 ubiquitin ligase inhibitory effects that extend to RNF41 and that inhibition of RNF41 auto-ubiquitination promotes membrane accumulation of signaling competent JAK2/EpoR complexes that augment Epo responsiveness. Cancer Res; 76(12); 3531-40. ©2016 AACR.

  15. Chang'E-3 data pre-processing system based on scientific workflow

    Science.gov (United States)

    tan, xu; liu, jianjun; wang, yuanyuan; yan, wei; zhang, xiaoxia; li, chunlai

    2016-04-01

    The Chang'E-3(CE3) mission have obtained a huge amount of lunar scientific data. Data pre-processing is an important segment of CE3 ground research and application system. With a dramatic increase in the demand of data research and application, Chang'E-3 data pre-processing system(CEDPS) based on scientific workflow is proposed for the purpose of making scientists more flexible and productive by automating data-driven. The system should allow the planning, conduct and control of the data processing procedure with the following possibilities: • describe a data processing task, include:1)define input data/output data, 2)define the data relationship, 3)define the sequence of tasks,4)define the communication between tasks,5)define mathematical formula, 6)define the relationship between task and data. • automatic processing of tasks. Accordingly, Describing a task is the key point whether the system is flexible. We design a workflow designer which is a visual environment for capturing processes as workflows, the three-level model for the workflow designer is discussed:1) The data relationship is established through product tree.2)The process model is constructed based on directed acyclic graph(DAG). Especially, a set of process workflow constructs, including Sequence, Loop, Merge, Fork are compositional one with another.3)To reduce the modeling complexity of the mathematical formulas using DAG, semantic modeling based on MathML is approached. On top of that, we will present how processed the CE3 data with CEDPS.

  16. Role of SKP1-CUL1-F-Box-Protein (SCF) E3 Ubiquitin Ligases in Skin Cancer

    Institute of Scientific and Technical Information of China (English)

    Chuan-Ming Xie; Wenyi Wei; Yi Sun

    2013-01-01

    Many biological processes such as cell proliferation,differentiation,and cell death depend precisely on the timely synthesis and degradation of key regulatory proteins.While protein synthesis can be regulated at multiple levels,protein degradation is mainly controlled by the ubiquitin-proteasome system (UPS),which consists of two distinct steps:(1) ubiquitylation of targeted protein by E1 ubiquitin-activating enzyme,E2 ubiquitin-conjugating enzyme and E3 ubiquitin ligase,and (2) subsequent degradation by the 26S proteasome.Among all E3 ubiquitin ligases,the SCF (SKP1-CUL1-F-box protein) E3 ligases are the largest family and are responsible for the turnover of many key regulatory proteins.Aberrant regulation of SCF E3 ligases is associated with various human diseases,such as cancers,including skin cancer.In this review,we provide a comprehensive overview of all currently published data to define a promoting role of SCF E3 ligases in the development of skin cancer.The future directions in this area of research are also discussed with an ultimate goal to develop small molecule inhibitors of SCF E3 ligases as a novel approach for the treatment of human skin cancer.Furthermore,altered components or substrates of SCF E3 ligases may also be developed as the biomarkers for early diagnosis or predicting prognosis.

  17. A hybrid toxin from bacteriophage f1 attachment protein and colicin E3 has altered cell receptor specificity.

    OpenAIRE

    Jakes, K S; Davis, N G; Zinder, N D

    1988-01-01

    A hybrid protein was constructed in vitro which consists of the first 372 amino acids of the attachment (gene III) protein of filamentous bacteriophage f1 fused, in frame, to the carboxy-terminal catalytic domain of colicin E3. The hybrid toxin killed cells that had the F-pilus receptor for phage f1 but not F- cells. The activity of the hybrid protein was not dependent upon the presence of the colicin E3 receptor, BtuB protein. The killing activity was colicin E3 specific, since F+ cells expr...

  18. 10 CFR 830 Major Modification Determination for the ATR Diesel Bus (E-3) and Switchgear Replacement

    Energy Technology Data Exchange (ETDEWEB)

    Noel Duckwtiz

    2011-05-01

    Near term replacement of aging and obsolescent original ATR equipment has become important to ensure ATR capability in support of NE’s long term national missions. To that end, a mission needs statement has been prepared for a non-major system acquisition which is comprised of three interdependent subprojects. The first project, subject of this determination, will replace the existent diesel-electrical bus (E-3) and associated switchgear. More specifically, INL proposes transitioning ATR to 100% commercial power with appropriate emergency backup to include: • Provide commercial power as the normal source of power to the ATR loads currently supplied by diesel-electric power. • Provide backup power to the critical ATR loads in the event of a loss of commercial power. • Replace obsolescent critical ATR power distribution equipment, e.g., switchgear, transformers, motor control centers, distribution panels. Completion of this and two other age-related projects (primary coolant pump and motor replacement and emergency firewater injection system replacement) will resolve major age related operational issues plus make a significant contribution in sustaining the ATR safety and reliability profile. The major modification criteria evaluation of the project pre-conceptual design identified several issues make the project a major modification: 1. Evaluation Criteria #2 (Footprint change). The addition of a new PC-4 structure to the ATR Facility to house safety-related SSCs requires careful attention to maintaining adherence to applicable engineering and nuclear safety design criteria (e.g., structural qualification, fire suppression) to ensure no adverse impacts to the safety-related functions of the housed equipment. 2. Evaluation Criteria #3 (Change of existing process). The change to the strategy for providing continuous reliable power to the safety-related emergency coolant pumps requires careful attention and analysis to ensure it meets a project primary object

  19. Cassini Plasma Spectrometer Ion Observations Close to Enceladus: E3, E5 and E7

    Science.gov (United States)

    Tokar, R. L.; Johnson, R. E.; Thomsen, M. F.; Wilson, R. J.; Crary, F. J.; Young, D. T.; Goldstein, R.; Reisenfeld, D. B.; Sittler, E. C.; Coates, A. J.; Paty, C. S.; Jia, Y.; Omidi, N.; Russell, C.

    2009-12-01

    The Cassini Plasma Spectrometer (CAPS) detected freshly-produced water-group ions (O+, OH+, H2O+, H3O+) and heavier water dimer ions (HxO2)+ very close to Enceladus where the plasma begins to emerge from the south polar plume (1). The data were obtained during two close (52 and 25 km) flybys of Enceladus in 2008 (E3 and E5) and are consistent with measurements from the Cassini Ion Neutral Mass Spectrometer (INMS). The ions are observed in CAPS detectors looking in the Cassini ram direction close to the ram kinetic energy, indicative of a nearly stagnant plasma flow in the plume. North of Enceladus the plasma slowing commences about 4 to 6 Enceladus radii away, while south of Enceladus signatures of the plasma interaction with the plume are detected 22 Enceladus radii away. Here we review and contrast these observations including the E7 flyby (anticipated Nov. 2, 2009). E7 is planned for a closest approach ~103 km south of Enceladus and CAPS should detect ions at rest with respect to Enceladus and over a broad range of gyrophase angles. Plasma fluid parameters both upstream and downstream of these encounters are extracted from the CAPS data. In addition, we compare the CAPS ion measurements with both fluid and 3D hybrid simulations. The MHD simulations (BATSRUS) are tuned to agree with Cassini Magnetometer (MAG) observations during the encounters then compared with CAPS observations. For example, for the E3 encounter the CAPS/BATSRUS comparison is striking, with features reproduced such as: the overall spatial scale of the interaction, the slowing of the ion flow within the dust plume to less than 5 km/s with respect to Enceladus, the temperature, flow and density signature of the geometric wake, and the flow perturbation along the magnetic field due to wake expansion. For E5, BATSRUS tuned against MAG suggests a 15 km/s bulk plasma flow toward Saturn during the encounter. We search for signatures of this flow in the CAPS ion data. 1.) Tokar,R.L. et al. Geophys. Res

  20. 76 FR 39251 - Airworthiness Directives; The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD...

    Science.gov (United States)

    2011-07-06

    ... Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes AGENCY... Jersey Avenue, SE., Washington, DC 20590. FOR FURTHER INFORMATION CONTACT: Roger Durbin, Aerospace.... Applicability (c) This AD applies to all The Boeing Company Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83...

  1. 76 FR 53346 - Airworthiness Directives; The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD...

    Science.gov (United States)

    2011-08-26

    ... Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes AGENCY... Jersey Avenue, SE., Washington, DC 20590. Hand Delivery: Deliver to Mail address above between 9 a.m. and...) This AD applies to The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD-83),...

  2. 76 FR 1993 - Airworthiness Directives; The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD...

    Science.gov (United States)

    2011-01-12

    ... Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes AGENCY... Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. FOR FURTHER INFORMATION.... Applicability (c) This AD applies to The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83...

  3. 76 FR 41651 - Airworthiness Directives; The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD...

    Science.gov (United States)

    2011-07-15

    ... Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes AGENCY... Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. FOR FURTHER INFORMATION...) This AD applies to The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD-83),...

  4. 76 FR 31462 - Airworthiness Directives; The Boeing Company Model DC-10-10, DC-10-10F, DC-10-15, DC-10-30, DC-10...

    Science.gov (United States)

    2011-06-01

    ... Model DC-10-10, DC- 10-10F, DC-10-15, DC-10-30, DC-10-30F (KC-10A and KDC-10), DC-10-40, DC-10-40F... Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590.... Applicability (c) This AD applies to all The Boeing Company Model DC-10-10, DC-10-10F, DC-10-15,......

  5. 76 FR 52225 - Airworthiness Directives; The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD...

    Science.gov (United States)

    2011-08-22

    ... Model DC-9-81 (MD- 81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes AGENCY... Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. FOR FURTHER INFORMATION... ADs (b) None. Applicability (c) This AD applies to The Boeing Company Model DC-9-81 (MD-81),...

  6. Active Flow Control (AFC) and Insect Accretion and Mitigation (IAM) System Design and Integration on the Boeing 757 ecoDemonstrator

    Science.gov (United States)

    Alexander, Michael G.; Harris, F. Keith; Spoor, Marc A.; Boyland, Susannah R.; Farrell, Thomas E.; Raines, David M.

    2016-01-01

    This paper presents a systems overview of how the Boeing and NASA team designed, analyzed, fabricated, and integrated the Active Flow Control (AFC) technology and Insect Accretion Mitigation (IAM) systems on the Boeing 757 ecoDemonstrator. The NASA Environmentally Responsible Aviation (ERA) project partnered with Boeing to demonstrate these two technology systems on a specially outfitted Boeing 757 ecoDemonstrator during the spring of 2015. The AFC system demonstrated attenuation of flow separation on a highly deflected rudder and increased the side force generated. This AFC system may enable a smaller vertical tail to provide the control authority needed in the event of an engine failure during takeoff while still operating in a conventional manner over the rest of the flight envelope. The AFC system consisted of ducting to obtain air from the Auxiliary Power Unit (APU), a control valve to modulate the system mass flow, a heat exchanger to lower the APU air temperature, and additional ducting to deliver the air to the AFC actuators located on the vertical tail. The IAM system demonstrated how to mitigate insect residue adhesion on a wing's leading edge. Something as small as insect residue on a leading edge can cause turbulent wedges that interrupt laminar flow, resulting in an increase in drag and fuel use. The IAM system consisted of NASA developed Engineered Surfaces (ES) which were thin aluminum sheet substrate panels with coatings applied to the exterior. These ES were installed on slats 8 and 9 on the right wing of the 757 ecoDemonstrator. They were designed to support panel removal and installation in one crew shift. Each slat accommodated 4 panels. Both the AFC and IAM flight test were the culmination of several years of development and produced valuable data for the advancement of modern aircraft designs.

  7. Initial clinical evaluation of radiolabeled MX-DTPA humanized BrE-3 antibody in patients with advanced breast cancer.

    Science.gov (United States)

    Kramer, E L; Liebes, L; Wasserheit, C; Noz, M E; Blank, E W; Zabalegui, A; Melamed, J; Furmanski, P; Peterson, J A; Ceriani, R L

    1998-07-01

    To evaluate radiometal-labeled humanized BrE-3 (huBrE-3) monoclonal antibody as a radioimmunolocalization and therapeutic agent in breast cancer patients, tumor localization, pharmacokinetics, radiation dosimetry, and immunogenicity of (111)In-labeled combined 1-p-isothiocyanatobenzyl 3-methyl- and 1-p-isothiocyanatobenzyl 4-methyldiethylenetriamine pentaacetic acid (MX-DTPA) huBrE-3 were studied. Seven women with BrE-3 antigen-positive, metastatic breast carcinoma underwent (111)In huBrE-3 infusion (5 mCi; 50 mg), followed by serial gamma camera imaging and plasma sampling. Region of interest analysis of images was used to make radiation absorbed dose estimates for (111)In huBrE-3. Data were extrapolated to 90Y huBrE-3. Human anti-human antibody (HAHA) response was measured in serum samples obtained up to 3 months after infusion. Patients tolerated infusions well. Seventy-six percent of 105 known sites of disease were identified on planar and single-photon emission computed tomography scans. For six of seven patients, a biexponential model fit the plasma time-activity curve best with an average T1/2alpha=10.6+/-8.5 (SD) h and average T1/2beta=114.2+/-39.2 h. Radiation absorbed dose estimates for (111)In huBrE-3 for whole body averaged 0.53+/-.08 rads/mCi. Dose estimates for 90Y huBrE-3 for marrow averaged 8.4+/-11.9 rads/mCi, and for tumors, 70+/-31.5 rads/mCi. Liver radioactivity uptake averaged 19.7+/-8.8% injected dose at 24 h after infusion, translating into an average radiation absorbed dose 21.1+/-12 rads/90Y mCi administered. Only one of seven patients demonstrated a low level of HAHA response. Although the plasma half-lives are longer and marrow dose higher for radiolabeled huBrE-3 compared with the murine construct, the excellent tumor localization, good tumor dosimetry, and low immunogenicity support the use of 90Y-huBrE-3 antibody for radioimmunotherapy of breast cancer.

  8. A Co-Dominant Marker BoE332 Applied to Marker-Assisted Selection of Homozygous Male-Sterile Plants in Cabbage (Brassica oleracea var. capitata L.)

    Institute of Scientific and Technical Information of China (English)

    CHEN Chen; ZHUANG Mu; FANG Zhi-yuan; WANG Qing-biao; ZHANG Yang-yong; LIU Yu-mei; YANG Li-mei; CHENG Fei

    2013-01-01

    The dominant genic male sterility (DGMS) gene CDMs399-3 derived from a spontaneous mutation in the line 79-399-3 of spring cabbage (Brassica oleracea var. capitata L.), has been successfully applied in hybrid seed production of several cabbage cultivars in China. During the development of dominant male sterility lines in cabbage, the conventional identification of homozygous male-sterile plants (CDMs399-3/CDMs399-3) is a laborious and time-consuming process. For marker-assisted selection (MAS) of the gene CDMs399-3 transferred into key spring cabbage line 397, expressed sequence tag-simple sequence repeats (EST-SSR) and SSR technology were used to identify markers that were linked to CDMs399-3 based on method of bulked segregant analysis (BSA). By screening a set of 978 EST-SSRs and 395 SSRs, a marker BoE332 linked to the CDMs399-3 at a distance of 3.6 cM in the genetic background of cabbage line 397 were identified. 7 homozygous male-sterile plants in population P1170 with 20 plants were obtained finally via MAS of BoE332. Thus, BoE332 will greatly facilitate the transferring of the gene CDMs399-3 into the key spring cabbage line 397 and improve the application of DGMS in cabbage hybrid breeding.

  9. The Arabidopsis MIEL1 E3 ligase negatively regulates ABA signalling by promoting protein turnover of MYB96

    OpenAIRE

    Lee, Hong Gil; Seo, Pil Joon

    2016-01-01

    The phytohormone abscisic acid (ABA) regulates plant responses to various environmental challenges. Controlled protein turnover is an important component of ABA signalling. Here we show that the RING-type E3 ligase MYB30-INTERACTING E3 LIGASE 1 (MIEL1) regulates ABA sensitivity by promoting MYB96 turnover in Arabidopsis. Germination of MIEL1-deficient mutant seeds is hypersensitive to ABA, whereas MIEL1-overexpressing transgenic seeds are less sensitive. MIEL1 can interact with MYB96, a regul...

  10. Ophthalmic epidemiology in Europe: the "European Eye Epidemiology" (E3) consortium.

    Science.gov (United States)

    Delcourt, Cécile; Korobelnik, Jean-François; Buitendijk, Gabriëlle H S; Foster, Paul J; Hammond, Christopher J; Piermarocchi, Stefano; Peto, Tunde; Jansonius, Nomdo; Mirshahi, Alireza; Hogg, Ruth E; Bretillon, Lionel; Topouzis, Fotis; Deak, Gabor; Grauslund, Jakob; Broe, Rebecca; Souied, Eric H; Creuzot-Garcher, Catherine; Sahel, José; Daien, Vincent; Lehtimäki, Terho; Hense, Hans-Werner; Prokofyeva, Elena; Oexle, Konrad; Rahi, Jugnoo S; Cumberland, Phillippa M; Schmitz-Valckenberg, Steffen; Fauser, Sascha; Bertelsen, Geir; Hoyng, Carel; Bergen, Arthur; Silva, Rufino; Wolf, Sebastian; Lotery, Andrew; Chakravarthy, Usha; Fletcher, Astrid; Klaver, Caroline C W

    2016-02-01

    The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.

  11. Interaction between Mnk2 and CBCVHL ubiquitin ligase E3 complex

    Institute of Scientific and Technical Information of China (English)

    WANG Pingzhang; WANG Xin; WANG Feng; CAI Tianjing; LUO Ying

    2006-01-01

    MAP kinase-interacting kinase-2 (Mnk2) is one of the downstream kinases activated by MAP kinases. It phosphorylates the eukaryotic initiation factor 4E (eIF4E), although the role of eIF4E phosphorylation and the role of Mnk2 in the process of protein translation are not well understood. Except for eIF4E, other physiological substrates of Mnk2 are still unidentified. To look for these unidentified substrates and to reveal the physiological function of Mnk2, we performed a yeast two-hybrid screening with Mnk2 as the bait. The results demonstrated Mnk2 could interact with VHL (von Hippel-Lindau tumor suppressor), Rbx1 (ring-box 1) and Cul2 (Cullin2) proteins in yeast cells. Furthermore, we validated the interaction between Mnk2 and VHL proteins in mammalian cells by co-immunoprecipitation analysis. Because the three proteins VHL, Rbx1 and Cul2 are all components of the CBCVHL ubiquitin ligase E3 complex, it has been shown that Mnk2 can interact with CBCVHL complex, and is probably one of the new substrates of the CBCVHL complex. Furthermore, during the interaction of Mnk2 with von Hippel-Lindau (VHL) tumor suppressor- binding protein 1 (VBP1), it appears that Mnk2 also joins to modulate cell shape as VBP1 plays an important role in the process of the maturation of the cytoskeleton and in the process of morphogenesis.

  12. High Precision Topographic Mapping at Chang'E-3 Landing Site with Multi-Source Data

    Science.gov (United States)

    Liu, Y.; Liu, B.; Xu, B.; Liu, Z.; Di, K.; Zhou, J.

    2014-04-01

    Chang'e-3 (CE-3) is the first lander and rover of China following the success of Chang'e-1 and Chang'e-2 (CE-2) orbiters. High precision topographic mapping can provide detailed terrain information to ensure the safety of the rover as well as to support scientific investigations. In this research, multi-source data are co-registered into a uniform geographic framework for high precision topographic mapping at the CE-3 landing site. CE-2 CCD images with 7 m- and 1.5 m- resolutions are registered using selfcalibration bundle adjustment method with ground control points (GCPs) selected from LRO WAC mosaic map and LOLA DTM. The trajectory of CE-3 descent images are recovered using self-calibration free net bundle adjustment, and then the topographic data is rectified by absolute orientation with GCPs selected from the adjusted CE-2 DEM and DOM. Finally, these topographic data are integrated into the same geographic framework for unified, multi-scale, high precision mapping of the CE-3 landing site. Key technologies and the mapping products of this research have been used to support the surface operations of CE-3 mission.

  13. The E3 ubiquitin ligase activity of Trip12 is essential for mouse embryogenesis.

    Directory of Open Access Journals (Sweden)

    Masashi Kajiro

    Full Text Available Protein ubiquitination is a post-translational protein modification that regulates many biological conditions. Trip12 is a HECT-type E3 ubiquitin ligase that ubiquitinates ARF and APP-BP1. However, the significance of Trip12 in vivo is largely unknown. Here we show that the ubiquitin ligase activity of Trip12 is indispensable for mouse embryogenesis. A homozygous mutation in Trip12 (Trip12(mt/mt that disrupts the ubiquitin ligase activity resulted in embryonic lethality in the middle stage of development. Trip12(mt/mt embryos exhibited growth arrest and increased expression of the negative cell cycle regulator p16. In contrast, Trip12(mt/mt ES cells were viable. They had decreased proliferation, but maintained both the undifferentiated state and the ability to differentiate. Trip12(mt/mt ES cells had increased levels of the BAF57 protein (a component of the SWI/SNF chromatin remodeling complex and altered gene expression patterns. These data suggest that Trip12 is involved in global gene expression and plays an important role in mouse development.

  14. Disorder-driven topological phase transition in B i2S e3 films

    Science.gov (United States)

    Brahlek, Matthew; Koirala, Nikesh; Salehi, Maryam; Moon, Jisoo; Zhang, Wenhan; Li, Haoxiang; Zhou, Xiaoqing; Han, Myung-Geun; Wu, Liang; Emge, Thomas; Lee, Hang-Dong; Xu, Can; Rhee, Seuk Joo; Gustafsson, Torgny; Armitage, N. Peter; Zhu, Yimei; Dessau, Daniel S.; Wu, Weida; Oh, Seongshik

    2016-10-01

    Topological insulators (TI) are a phase of matter that host unusual metallic surface states. Unlike the states that exist on the surface of conventional materials, these so-called topological surfaces states (TSS) are protected against disorder-related localization effects by time reversal symmetry through strong spin-orbit coupling. By combining transport measurements, angle-resolved photoemission spectroscopy, and scanning tunneling microscopy, we show that there exists a critical level of disorder beyond which the TI B i2S e3 loses its ability to protect the metallic TSS and transitions to a fully insulating state. The absence of the metallic surface channels dictates that there is a change in the material's topological character, implying that disorder can lead to a topological phase transition even without breaking the time reversal symmetry. This observation challenges the conventional notion of topologically protected surface states and should prompt new studies as to the fundamental nature of topological phase of matter in the presence of disorder.

  15. The evolutionarily conserved E3 ubiquitin ligase AtCHIP contributes to plant immunity

    Directory of Open Access Journals (Sweden)

    Xin eLi

    2016-03-01

    Full Text Available Plants possess a sophisticated immune system to recognize and respond to microbial threats in their environment. The level of immune signaling must be tightly regulated so that immune responses can be quickly activated in the presence of pathogens, while avoiding autoimmunity. HSP90s, along with their diverse array of co-chaperones, forms chaperone complexes that have been shown to play both positive and negative roles in regulating the accumulation of immune receptors and regulators. In this study, we examined the role of AtCHIP, an evolutionarily conserved E3 ligase that was known to interact with chaperones including HSP90s in multicellular organisms including fruit fly, C. elegans, plants and human. Atchip knockout mutants display enhanced disease susceptibility to a virulent oomycete pathogen, and overexpression of AtCHIP causes enhanced disease resistance at low temperature. Although CHIP was reported to target HSP90 for ubiquitination and degradation, accumulation of HSP90.3 was not affected in Atchip plants. In addition, protein accumulation of nucleotide-binding, leucine-rich repeat domain immune receptor (NLR SNC1 is not altered in Atchip mutant. Thus, while AtCHIP plays a role in immunity, it does not seem to regulate the turnover of HSP90 or SNC1. Further investigation is needed in order to determine the exact mechanism behind AtCHIP’s role in regulating plant immune responses.

  16. BICP0 and its RING finger domain act as ubiquitin E3 ligases in vitro

    Institute of Scientific and Technical Information of China (English)

    DIAO Lirong; QIAO Wentao; CHEN Qimin; WANG Chen; GENG Yunqi

    2005-01-01

    Bovine infected-cell protein 0 (BICP0) encoded by bovine herpes virus 1 (BHV-1) immediate early gene is necessary for efficient productive infection, in a large part because it activates all 3 classes of BHV-1 genes. It also has the ability to efficiently transactivate promoters that are not derived from BHV-1. To investigate the mechanism by which BICP0 achieves these effects, we expressed and purified BICP0 and its different mutants in E. coli. In vitro assays showed that both full-length BICP0 and its isolated RING finger domain induce the accumulation of polyubiquitin chains. Mutations within the RING finger region that abolish the in vitro ubiquitination activity also cause severe reductions in BICP0 activity in other assays. Based on these, we conclude that BICP0 has the potential to act as an E3 ubiquitin ligase during viral infection and its RING finger domain is necessary for this function. These strongly support the hypothesis that BICP0 might influence virus infection through its ability to interact with the ubiquitin-proteasome pathway.

  17. CRL4A(CRBN) E3 ubiquitin ligase restricts BK channel activity and prevents epileptogenesis.

    Science.gov (United States)

    Liu, Jiye; Ye, Jia; Zou, Xiaolong; Xu, Zhenghao; Feng, Yan; Zou, Xianxian; Chen, Zhong; Li, Yuezhou; Cang, Yong

    2014-05-21

    Ion channels regulate membrane excitation, and mutations of ion channels often cause serious neurological disorders including epilepsy. Compared with extensive analyses of channel protein structure and function, much less is known about the fine tuning of channel activity by post-translational modification. Here we report that the large conductance, Ca(2+)- and voltage-activated K(+) (BK) channels are targeted by the E3 ubiquitin ligase CRL4A(CRBN) for polyubiquitination and retained in the endoplasmic reticulum (ER). Inactivation of CRL4A(CRBN) releases deubiquitinated BK channels from the ER to the plasma membrane, leading to markedly enhanced channel activity. Mice with CRL4A(CRBN) mutation in the brain or treated with a CRL4A(CRBN) inhibitor are very sensitive to seizure induction, which can be attenuated by blocking BK channels. Finally, the mutant mice develop spontaneous epilepsy when aged. Therefore, ubiquitination of BK channels before their cell surface expression is an important step to prevent systemic neuronal excitability and epileptogenesis.

  18. Natural polymorphisms in C. elegans HECW-1 E3 ligase affect pathogen avoidance behaviour.

    Science.gov (United States)

    Chang, Howard C; Paek, Jennifer; Kim, Dennis H

    2011-11-16

    Heritable variation in behavioural traits generally has a complex genetic basis, and thus naturally occurring polymorphisms that influence behaviour have been defined only in rare instances. The isolation of wild strains of Caenorhabditis elegans has facilitated the study of natural genetic variation in this species and provided insights into its diverse microbial ecology. C. elegans responds to bacterial infection with conserved innate immune responses and, although lacking the immunological memory of vertebrate adaptive immunity, shows an aversive learning response to pathogenic bacteria. Here, we report the molecular characterization of naturally occurring coding polymorphisms in a C. elegans gene encoding a conserved HECT domain-containing E3 ubiquitin ligase, HECW-1. We show that two distinct polymorphisms in neighbouring residues of HECW-1 each affect C. elegans behavioural avoidance of a lawn of Pseudomonas aeruginosa. Neuron-specific rescue and ablation experiments and genetic interaction analysis indicate that HECW-1 functions in a pair of sensory neurons to inhibit P. aeruginosa lawn avoidance behaviour through inhibition of the neuropeptide receptor NPR-1 (ref. 10), which we have previously shown promotes P. aeruginosa lawn avoidance behaviour. Our data establish a molecular basis for natural variation in a C. elegans behaviour that may undergo adaptive changes in response to microbial pathogens.

  19. An Assessment of Japanese Carbon Tax Reform Using the E3MG Econometric Model

    Directory of Open Access Journals (Sweden)

    Soocheol Lee

    2012-01-01

    Full Text Available This paper analyses the potential economic and environmental effects of carbon taxation in Japan using the E3MG model, a global macroeconometric model constructed by the University of Cambridge and Cambridge Econometrics. The paper approaches the issues by considering first the impacts of the carbon tax in Japan introduced in 2012 and then the measures necessary to reduce Japan’s emissions in line with its Copenhagen pledge of −25% compared to 1990 levels. The results from the model suggest that FY2012 Tax Reform has only a small impact on emission levels and no significant impact on GDP and employment. The potential costs of reducing emissions to meet the 25% reduction target for 2020 are quite modest, but noticeable. GDP falls by around 1.2% compared to the baseline and employment by 0.4% compared to the baseline. But this could be offset, with some potential economic benefits, if revenues are recycled efficiently. This paper considers two revenue recycling scenarios. The most positive outcome is if revenues are used both to reduce income tax rates and to increase investment in energy efficiency. This paper shows there could be double dividend effects, if Carbon Tax Reform is properly designed.

  20. The E3 Ubiquitin Ligase TMEM129 Is a Tri-Spanning Transmembrane Protein

    Directory of Open Access Journals (Sweden)

    Michael L. van de Weijer

    2016-11-01

    Full Text Available Misfolded proteins from the endoplasmic reticulum (ER are transported back into the cytosol for degradation via the ubiquitin-proteasome system. The human cytomegalovirus protein US11 hijacks this ER-associated protein degradation (ERAD pathway to downregulate human leukocyte antigen (HLA class I molecules in virus-infected cells, thereby evading elimination by cytotoxic T-lymphocytes. Recently, we identified the E3 ubiquitin ligase transmembrane protein 129 (TMEM129 as a key player in this process, where interference with TMEM129 activity in human cells completely abrogates US11-mediated class I degradation. Here, we set out to further characterize TMEM129. We show that TMEM129 is a non-glycosylated protein containing a non-cleaved signal anchor sequence. By glycosylation scanning mutagenesis, we show that TMEM129 is a tri-spanning ER-membrane protein that adopts an Nexo–Ccyto orientation. This insertion in the ER membrane positions the C-terminal really interesting new gene (RING domain of TMEM129 in the cytosol, making it available to catalyze ubiquitination reactions that are required for cytosolic degradation of secretory proteins.

  1. Natural variation and dosage of the HEI10 meiotic E3 ligase control Arabidopsis crossover recombination

    Science.gov (United States)

    Ziolkowski, Piotr A.; Underwood, Charles J.; Lambing, Christophe; Martinez-Garcia, Marina; Lawrence, Emma J.; Ziolkowska, Liliana; Griffin, Catherine; Choi, Kyuha; Franklin, F. Chris H.; Martienssen, Robert A.; Henderson, Ian R.

    2017-01-01

    During meiosis, homologous chromosomes undergo crossover recombination, which creates genetic diversity and balances homolog segregation. Despite these critical functions, crossover frequency varies extensively within and between species. Although natural crossover recombination modifier loci have been detected in plants, causal genes have remained elusive. Using natural Arabidopsis thaliana accessions, we identified two major recombination quantitative trait loci (rQTLs) that explain 56.9% of crossover variation in Col×Ler F2 populations. We mapped rQTL1 to semidominant polymorphisms in HEI10, which encodes a conserved ubiquitin E3 ligase that regulates crossovers. Null hei10 mutants are haploinsufficient, and, using genome-wide mapping and immunocytology, we show that transformation of additional HEI10 copies is sufficient to more than double euchromatic crossovers. However, heterochromatic centromeres remained recombination-suppressed. The strongest HEI10-mediated crossover increases occur in subtelomeric euchromatin, which is reminiscent of sex differences in Arabidopsis recombination. Our work reveals that HEI10 naturally limits Arabidopsis crossovers and has the potential to influence the response to selection. PMID:28223312

  2. The HECTD3 E3 ubiquitin ligase suppresses cisplatin-induced apoptosis via stabilizing MALT1.

    Science.gov (United States)

    Li, Yi; Chen, Xi; Wang, Zehua; Zhao, Dong; Chen, Hui; Chen, Wenlin; Zhou, Zhongmei; Zhang, Junran; Zhang, Jing; Li, Hongmin; Chen, Ceshi

    2013-01-01

    Homologous to the E6-associated protein carboxyl terminus domain containing 3 (HECTD3) is an E3 ubiquitin ligase with unknown functions. Here, we show that HECTD3 confers cancer cell resistance to cisplatin. To understand the molecular mechanisms, we performed a yeast two-hybrid analysis and identified mucosa-associated lymphoid tissue 1 (MALT1) as an HECTD3-interacting protein. HECTD3 promotes MALT1 ubiquitination with nondegradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it. HECTD3 depletion dramatically decreases the levels of MALT1 in MCF7 and HeLa cells treated with cisplatin, which is correlated to an increase in apoptosis. Knockdown of MALT1 likewise increases cisplatin-induced apoptosis in these cancer cells. However, HECTD3 over-expression leads to a decreased cisplatin-induced apoptosis, whereas overexpression of MALT1 partially rescues HECTD3 depletion-induced apoptosis. These findings suggest that HECTD3 promotes cell survival through stabilizing MALT1. Our data have important implications in cancer therapy by providing novel molecular targets.

  3. The HECTD3 E3 Ubiquitin Ligase Suppresses Cisplatin-Induced Apoptosis via Stabilizing MALT1

    Directory of Open Access Journals (Sweden)

    Yi Li

    2013-01-01

    Full Text Available Homologous to the E6-associated protein carboxyl terminus domain containing 3 (HECTD3 is an E3 ubiquitin ligase with unknown functions. Here, we show that HECTD3 confers cancer cell resistance to cisplatin. To understand the molecular mechanisms, we performed a yeast two-hybrid analysis and identified mucosa-associated lymphoid tissue 1 (MALT1 as an HECTD3-interacting protein. HECTD3 promotes MALT1 ubiquitination with non-degradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it. HECTD3 depletion dramatically decreases the levels of MALT1 in MCF7 and HeLa cells treated with cisplatin, which is correlated to an increase in apoptosis. Knockdown of MALT1 likewise increases cisplatin-induced apoptosis in these cancer cells. However, HECTD3 overexpression leads to a decreased cisplatin-induced apoptosis, whereas overexpression of MALT1 partially rescues HECTD3 depletion–induced apoptosis. These findings suggest that HECTD3 promotes cell survival through stabilizing MALT1. Our data have important implications in cancer therapy by providing novel molecular targets.

  4. An Arabidopsis SUMO E3 Ligase, SIZ1, Negatively Regulates Photomorphogenesis by Promoting COP1 Activity

    KAUST Repository

    Lin, Xiao-Li

    2016-04-29

    COP1 (CONSTITUTIVE PHOTOMORPHOGENIC 1), a ubiquitin E3 ligase, is a central negative regulator of photomorphogenesis. However, how COP1 activity is regulated by post-translational modifications remains largely unknown. Here we show that SUMO (small ubiquitin-like modifier) modification enhances COP1 activity. Loss-of-function siz1 mutant seedlings exhibit a weak constitutive photomorphogenic phenotype. SIZ1 physically interacts with COP1 and mediates the sumoylation of COP1. A K193R substitution in COP1 blocks its SUMO modification and reduces COP1 activity in vitro and in planta. Consistently, COP1 activity is reduced in siz1 and the level of HY5, a COP1 target protein, is increased in siz1. Sumoylated COP1 may exhibits higher transubiquitination activity than does non-sumoylated COP1, but SIZ1-mediated SUMO modification does not affect COP1 dimerization, COP1-HY5 interaction, and nuclear accumulation of COP1. Interestingly, prolonged light exposure reduces the sumoylation level of COP1, and COP1 mediates the ubiquitination and degradation of SIZ1. These regulatory mechanisms may maintain the homeostasis of COP1 activity, ensuing proper photomorphogenic development in changing light environment. Our genetic and biochemical studies identify a function for SIZ1 in photomorphogenesis and reveal a novel SUMO-regulated ubiquitin ligase, COP1, in plants.

  5. Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells

    Science.gov (United States)

    Choi, Seung H.; Wright, Jason B.; Gerber, Scott A.; Cole, Michael D.

    2010-01-01

    Rapid Myc protein turnover is critical for maintaining basal levels of Myc activity in normal cells and a prompt response to changing growth signals. We characterize a new Myc-interacting factor, TRPC4AP (transient receptor potential cation channel, subfamily C, member 4-associated protein)/TRUSS (tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein), which is the receptor for a DDB1 (damage-specific DNA-binding protein 1)–CUL4 (Cullin 4) E3 ligase complex for selective Myc degradation through the proteasome. TRPC4AP/TRUSS binds specifically to the Myc C terminus and promotes its ubiquitination and destruction through the recognition of evolutionarily conserved domains in the Myc N terminus. TRPC4AP/TRUSS suppresses Myc-mediated transactivation and transformation in a dose-dependent manner. Finally, we found that TRPC4AP/TRUSS expression is strongly down-regulated in most cancer cell lines, leading to Myc protein stabilization. These studies identify a novel pathway targeting Myc degradation that is suppressed in cancer cells. PMID:20551172

  6. ATLs and BTLs, plant-specific and general eukaryotic structurally-related E3 ubiquitin ligases.

    Science.gov (United States)

    Guzmán, Plinio

    2014-02-01

    Major components of the ubiquitin proteasome system are the enzymes that operate on the transfer of ubiquitin to selected target substrate, known as ubiquitin ligases. The RING finger is a domain that is present in key classes of ubiquitin ligases. This domain coordinates the interaction with a suitable E2 conjugase and the transfer of ubiquitin from the E2 to protein targets. Additional domains coupled to the same polypeptide are important for modulating the function of these ubiquitin ligases. Plants contain several types of E3 ubiquitin ligases that in many cases have expanded as multigene families. Some families are specific to the plant lineage, whereas others may have a common ancestor among plants and other eukaryotic lineages. Arabidopsis Tóxicos en Levadura (ATLs) and BCA2 zinc finger ATLs (BTLs) are two families of ubiquitin ligases that share some common structural features. These are intronless genes that encode a highly related RING finger domain, and yet during evolutionary history, their mode of gene expansion and function is rather different. In each of these two families, the co-occurrence of transmembrane helices or C2/C2 (BZF finger) domains with a selected variation on the RING finger has been subjected to strong selection pressure in order to preserve their unique domain architectures during evolution.

  7. An assessment of Japanese carbon tax reform using the E3MG econometric model.

    Science.gov (United States)

    Lee, Soocheol; Pollitt, Hector; Ueta, Kazuhiro

    2012-01-01

    This paper analyses the potential economic and environmental effects of carbon taxation in Japan using the E3MG model, a global macroeconometric model constructed by the University of Cambridge and Cambridge Econometrics. The paper approaches the issues by considering first the impacts of the carbon tax in Japan introduced in 2012 and then the measures necessary to reduce Japan's emissions in line with its Copenhagen pledge of -25% compared to 1990 levels. The results from the model suggest that FY2012 Tax Reform has only a small impact on emission levels and no significant impact on GDP and employment. The potential costs of reducing emissions to meet the 25% reduction target for 2020 are quite modest, but noticeable. GDP falls by around 1.2% compared to the baseline and employment by 0.4% compared to the baseline. But this could be offset, with some potential economic benefits, if revenues are recycled efficiently. This paper considers two revenue recycling scenarios. The most positive outcome is if revenues are used both to reduce income tax rates and to increase investment in energy efficiency. This paper shows there could be double dividend effects, if Carbon Tax Reform is properly designed.

  8. Termination of single-crystal B i2S e3 surfaces prepared by various methods

    Science.gov (United States)

    Zhou, Weimin; Zhu, Haoshan; Yarmoff, Jory A.

    2016-11-01

    Bismuth Selenide (B i2S e3) is a topological insulator with a two-dimensional layered structure that enables clean and well-ordered surfaces to be prepared by cleaving. Although some studies have demonstrated that the cleaved surface is terminated with Se, as expected from the bulk crystal structure, other reports have indicated either a Bi- or mixed-termination. Low-energy ion scattering (LEIS), low energy electron diffraction (LEED) and x-ray photoelectron spectroscopy (XPS) are used here to compare surfaces prepared by ex situ cleaving, in situ cleaving, and ion bombardment and annealing (IBA) in ultrahigh vacuum (UHV). Surfaces prepared by in situ cleaving and IBA are well ordered and Se-terminated. Ex situ cleaved samples could be either Se-terminated or Bi-rich, are less well ordered and have adsorbed contaminants. This suggests that a chemical reaction involving atmospheric contaminants, which may preferentially adsorb at surface defects, could contribute to the nonreproducibility of the termination.

  9. Response of plasmaspheric configuration to substorms revealed by Chang’e 3

    Science.gov (United States)

    He, Han; Shen, Chao; Wang, Huaning; Zhang, Xiaoxin; Chen, Bo; Yan, Jun; Zou, Yongliao; Jorgensen, Anders M.; He, Fei; Yan, Yan; Zhu, Xiaoshuai; Huang, Ya; Xu, Ronglan

    2016-08-01

    The Moon-based Extreme Ultraviolet Camera (EUVC) of the Chang’e 3 mission provides a global and instantaneous meridian view (side view) of the Earth’s plasmasphere. The plasmasphere is one inner component of the whole magnetosphere, and the configuration of the plasmasphere is sensitive to magnetospheric activity (storms and substorms). However, the response of the plasmaspheric configuration to substorms is only partially understood, and the EUVC observations provide a good opportunity to investigate this issue. By reconstructing the global plasmaspheric configuration based on the EUVC images observed during 20–22 April 2014, we show that in the observing period, the plasmasphere had three bulges which were located at different geomagnetic longitudes. The inferred midnight transit times of the three bulges, using the rotation rate of the Earth, coincide with the expansion phase of three substorms, which implies a causal relationship between the substorms and the formation of the three bulges on the plasmasphere. Instead of leading to plasmaspheric erosion as geomagnetic storms do, substorms initiated on the nightside of the Earth cause local inflation of the plasmasphere in the midnight region.

  10. RING finger E3 ligase PPP1R11 regulates TLR2 signaling and innate immunity

    Science.gov (United States)

    McKelvey, Alison C; Lear, Travis B; Dunn, Sarah R; Evankovich, John; Londino, James D; Bednash, Joseph S; Zhang, Yingze; McVerry, Bryan J; Liu, Yuan; Chen, Bill B

    2016-01-01

    Toll-like receptor 2 (TLR2) is a pattern recognition receptor that recognizes many types of PAMPs that originate from gram-positive bacteria. Here we describe a novel mechanism regulating TLR2 protein expression and subsequent cytokine release through the ubiquitination and degradation of the receptor in response to ligand stimulation. We show a new mechanism in which an uncharacterized RING finger E3 ligase, PPP1R11, directly ubiquitinates TLR2 both in vitro and in vivo, which leads to TLR2 degradation and disruption of the signaling cascade. Lentiviral gene transfer or knockdown of PPP1R11 in mouse lungs significantly affects lung inflammation and the clearance of Staphylococcus aureus. There is a negative correlation between PPP1R11 and TLR2 levels in white blood cell samples isolated from patients with Staphylococcus aureus infections. These results suggest that PPP1R11 plays an important role in regulating innate immunity and gram-positive bacterial clearance by functioning, in part, through the ubiquitination and degradation of TLR2. DOI: http://dx.doi.org/10.7554/eLife.18496.001 PMID:27805901

  11. Modulation of immune cell functions by the E3 ligase CBL-b

    Directory of Open Access Journals (Sweden)

    Christina eLutz-Nicoladoni

    2015-03-01

    Full Text Available Maintenance of immunological tolerance is a critical hallmark of the immune system. Several signaling checkpoints necessary to balance activating and inhibitory input to immune cells have been described so far, among which the E3 ligase Cbl-b appears to be a central player. Cbl-b is expressed in all leukocyte subsets and regulates several signaling pathways in T cells, NK cells, B cells and different types of myeloid cells. In most cases Cbl-b negatively regulates activation signals through antigen or pattern recognition receptors and co-stimulatory molecules. In line with this function, cblb-deficient immune cells display lower activation thresholds and cblb knockout mice spontaneously develop autoimmunity and are highly susceptible to experimental autoimmunity. Interestingly, genetic association studies link cblb-polymorphisms with autoimmunity also in humans. Vice versa, the increased activation potential of cblb-deficient cells renders them more potent to fight against malignancies or infections. Accordingly, several reports have shown that cblb knockout mice reject tumors, which mainly depends on cytotoxic T and NK cells. Thus targeting Cbl-b may be an interesting strategy to enhance anti-cancer immunity. In this review we summarize the findings on the molecular function of Cbl-b in different cell types and illustrate the potential of Cbl-b as target for immunomodulatory therapies.

  12. Mutation in SUMO E3 ligase, SIZ1, disrupts the mature female gametophyte in Arabidopsis

    KAUST Repository

    Ling, Yu

    2012-01-09

    Female gametophyte is the multicellular haploid structure that can produce embryo and endosperm after fertilization, which has become an attractive model system for investigating molecular mechanisms in nuclei migration, cell specification, cell-to-cell communication and many other processes. Previous reports found that the small ubiquitin-like modifier (SUMO) E3 ligase, SIZ1, participated in many processes depending on particular target substrates and suppression of salicylic acid (SA) accumulation. Here, we report that SIZ1 mediates the reproductive process. SIZ1 showed enhanced expression in female organs, but was not detected in the anther or pollen. A defect in the siz1-2 maternal source resulted in reduced seed-set regardless of high SA concentration within the plant. Moreover, aniline blue staining and scanning electron microscopy revealed that funicular and micropylar pollen tube guidance was arrested in siz1-2 plants. Some of the embryo sacs of ovules in siz1-2 were also disrupted quickly after stage FG7. There was no significant affects of the siz1-2 mutation on expression of genes involved in female gametophyte development- or pollen tube guidance in ovaries. Together, our results suggest that SIZ1 sustains the stability and normal function of the mature female gametophyte which is necessary for pollen tube guidance. © 2012 Ling et al.

  13. E3 ubiquitin ligases Pellinos as regulators of pattern recognition receptor signaling and immune responses.

    Science.gov (United States)

    Medvedev, Andrei E; Murphy, Michael; Zhou, Hao; Li, Xiaoxia

    2015-07-01

    Pellinos are a family of E3 ubiquitin ligases discovered for their role in catalyzing K63-linked polyubiquitination of Pelle, an interleukin-1 (IL-1) receptor-associated kinase homolog in the Drosophila Toll pathway. Subsequent studies have revealed the central and non-redundant roles of mammalian Pellino-1, Pellino-2, and Pelino-3 in signaling pathways emanating from IL-1 receptors, Toll-like receptors, NOD-like receptors, T- and B-cell receptors. While Pellinos ability to interact with many signaling intermediates suggested their scaffolding roles, recent findings in mice expressing ligase-inactive Pellinos demonstrated the importance of Pellino ubiquitin ligase activity. Cell-specific functions of Pellinos have emerged, e.g. Pellino-1 being a negative regulator in T lymphocytes and a positive regulator in myeloid cells, and details of molecular regulation of receptor signaling by various members of the Pellino family have been revealed. In this review, we summarize current information about Pellino-mediated regulation of signaling by pattern recognition receptors, T-cell and B-cell receptors and tumor necrosis factor receptors, and discuss Pellinos roles in sepsis and infectious diseases, as well as in autoimmune, inflammatory, and allergic disorders. We also provide our perspective on the potential of targeting Pellinos with peptide- or small molecule-based drug compounds as a new therapeutic approach for septic shock and autoimmune pathologies.

  14. MDM2 E3 ubiquitin ligase mediates UT-A1 urea transporter ubiquitination and degradation.

    Science.gov (United States)

    Chen, Guangping; Huang, Haidong; Fröhlich, Otto; Yang, Yuan; Klein, Janet D; Price, S Russ; Sands, Jeff M

    2008-11-01

    UT-A1 is the primary urea transporter in the apical plasma membrane responsible for urea reabsorption in the inner medullary collecting duct. Although the physiological function of UT-A1 has been well established, the molecular mechanisms that regulate its activity are less well understood. Analysis of the UT-A1 amino acid sequence revealed a potential MDM2 E3 ubiquitin ligase-binding motif in the large intracellular loop of UT-A1, suggesting that UT-A1 urea transporter protein may be regulated by the ubiquitin-proteasome pathway. Here, we report that UT-A1 is ubiquitinated and degraded by the proteasome but not the lysosome proteolytic pathway. Inhibition of proteasome activity causes UT-A1 cell surface accumulation and concomitantly increases urea transport activity. UT-A1 interacts directly with MDM2; the binding site is located in the NH2-terminal p53-binding region of MDM2. MDM2 mediates UT-A1 ubiquitination both in vivo and in vitro. Overexpression of MDM2 promotes UT-A1 degradation. The mechanism is likely to be physiologically important as UT-A1 ubiquitination was identified in kidney inner medullary tissue. The ubiquitin-proteasome degradation pathway provides an important novel mechanism for UT-A1 regulation.

  15. E3 ubiquitin ligase UBR5 drives the growth and metastasis of triple negative breast cancer.

    Science.gov (United States)

    Liao, Liqiu; Song, Mei; Li, Xin; Tang, Lili; Zhang, Tuo; Zhang, Lixing; Pan, Yihang; Chouchane, Lotfi; Ma, Xiaojing

    2017-03-22

    Patients with triple negative breast cancers (TNBC) are at high risk for recurrence and metastasis at an early time despite standard treatment, underscoring the need for novel therapeutic modalities. Here we report for the first time a distinctive and profound role of the E3 ubiquitin ligase UBR5 in the growth and metastasis of TNBC. An analysis of primary TNBC specimen by whole exon sequencing revealed strong gene amplifications of UBR5 associated with the disease. UBR5 overexpression in TNBC tissues was confirmed at mRNA and protein levels. CRISPR/Cas9-mediated deletion of ubr5 in an experimental murine mammary carcinoma model of TNBC dramatically abrogated tumor growth and metastasis in vivo, which could be reversed completely via reconstitution with wild type UBR5 but not a catalytically inactive mutant. Loss of UBR5 caused an impairment in angiogenesis within the tumor, associated with increased apoptosis, necrosis, and growth arrest. Absence of UBR5 in the tumor triggered aberrant epithelial to mesenchymal transition (EMT), principally via abrogated expression of E-cadherin, which resulted in severely reduced tumor metastasis to secondary organs. Use of NOD/SCID mice revealed that tumor-derived UBR5 facilitated tumor growth in a manner completely dependent upon immune cells in the microenvironment, whereas it promoted metastasis in a tumor cell-autonomous fashion. Our findings unveil UBR5 as a novel and critical regulator of tumor growth, metastasis, and immune response, and highlight the potential for UBR5 as an effective therapeutic target for the treatment of highly aggressive breast and ovarian cancers that fail conventional therapy.

  16. SUMO E3 Ligase AtMMS21 Regulates Drought Tolerance in Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    Shengchun Zhang; Yanli Qi; Ming Liu; ChengweiYang

    2013-01-01

    Post-translational modifications of proteins by small ubiquitin-like modifiers (SUMOs) play crucial roles in plant growth and development,and in stress responses.The MMS21 is a newly-identified Arabidopsis thaliana L.SUMO E3 ligase gene aside from the SIZ1,and its function requires further elucidation.Here,we show that MMS21 deficient plants display improved drought tolerance,and constitutive expression of MMS21 reduces drought tolerance.The expression of MMS21 was reduced by abscisic acid (ABA),polyethylene glycol (PEG) or drought stress.Under drought conditions,mms21 mutants showed the highest survival rate and the slowest water loss,and accumulated a higher level of free proline compared to wild-type (WT) and MMS21 over-expression plants.Stomatal aperture,seed germination and cotyledon greening analysis indicated that mms21 was hypersensitive to ABA.Molecular genetic analysis revealed that MMS21 deficiency led to elevated expression of a series of ABA-mediated stress-responsive genes,including COR15A,RD22,and P5CS1 The ABA and drought-induced stress-responsive genes,including RAB18,RD29A and RD29B,were inhibited by constitutive expression of MMS21.Moreover,ABA-induced accumulation of SUMO-protein conjugates was blocked in the mms21 mutant.We thus conclude that MMS21 plays a role in the drought stress response,likely through regulation of gene expression in an ABA-dependent pathway.

  17. CHK2 stability is regulated by the E3 ubiquitin ligase SIAH2.

    Science.gov (United States)

    García-Limones, C; Lara-Chica, M; Jiménez-Jiménez, C; Pérez, M; Moreno, P; Muñoz, E; Calzado, M A

    2016-08-18

    The serine threonine checkpoint kinase 2 (CHK2) is a critical protein involved in the DNA damage-response pathway, which is activated by phosphorylation inducing cellular response such as DNA repair, cell-cycle regulation or apoptosis. Although CHK2 activation mechanisms have been amply described, very little is known about degradation control processes. In the present study, we identify the ubiquitin E3 ligase SIAH2 as an interaction partner of CHK2, which mediates its ubiquitination and proteasomal degradation. CHK2 degradation is independent of both its activation and its kinase activity, but also of the phosphorylation in S456. We show that SIAH2-deficient cells present CHK2 accumulation together with lower ubiquitination levels. Accordingly, SIAH2 depletion by siRNA increases CHK2 levels. In response to DNA damage induced by etoposide, interaction between both proteins is disrupted, thus avoiding CHK2 degradation and promoting its stabilization. We also found that CHK2 phosphorylates SIAH2 at three residues (Thr26, Ser28 and Thr119), modifying its ability to regulate certain substrates. Cellular arrest in the G2/M phase induced by DNA damage is reverted by SIAH2 expression through the control of CHK2 levels. We observed that hypoxia decreases CHK2 levels in parallel to SIAH2 induction. Similarly, we provide evidence suggesting that resistance to apoptosis induced by genotoxic agents in cells subjected to hypoxia could be partly explained by the mutual regulation between both proteins. These results indicate that SIAH2 regulates CHK2 basal turnover, with important consequences on cell-cycle control and on the ability of hypoxia to alter the DNA damage-response pathway in cancer cells.

  18. The role of the e3 ligase cbl-B in murine dendritic cells.

    Directory of Open Access Journals (Sweden)

    Stephanie Wallner

    Full Text Available Dendritic cells (DCs are potent antigen-presenting cells with a promising potential in cancer immunotherapy. Cbl proteins are E3 ubiquitin ligases and have been implicated in regulating the functional activity of various immune cells. As an example, c-Cbl negatively affects DC activation. We here describe that another member of the Cbl-protein family (i.e. Cbl-b is highly expressed in murine bone-marrow-derived DCs (BMDCs. Differentiation of cblb-/- bone marrow mononuclear cells into classical BMDCs is unaltered, except enhanced induction of DEC-205 (CD205 expression. When tested in mixed-lymphocyte reaction (MLR, cblb-/- BMDCs exhibit increased allo-stimulatory capacity in vitro. BMDCs were next in vitro stimulated by various toll like receptor (TLR-agonists (LPS, Poly(I:C, CpG and exposed to FITC-labeled dextran. Upon TLR-stimulation, cblb-/- BMDCs produce higher levels of proinflammatory cytokines (IL-1α, IL-6 and TNF-α and exhibit a slightly higher level of FITC-dextran uptake. To further characterize the functional significance of cblb-/- BMDCs we tested them in antigen-specific T cell responses against ovalbumin (OVA protein and peptides, activating either CD8(+ OT-I or CD4(+ OT-II transgenic T cells. However, cblb-/- BMDCs are equally effective in inducing antigen-specific T cell responses when compared to wildtype BMDCs both in vitro and in vivo. The migratory capacity into lymph nodes during inflammation was similarly not affected by the absence of Cbl-b. In line with these observations, cblb-/- peptide-pulsed BMDCs are equally effective vaccines against OVA-expressing B16 tumors in vivo when compared to wildtype BMDCs. We conclude that in contrast to c-Cbl, Cbl-b plays only a limited role in the induction of Ag-specific T cell responses by murine BMDCs in vitro and in vivo.

  19. Aβ-Induced Synaptic Alterations Require the E3 Ubiquitin Ligase Nedd4-1.

    Science.gov (United States)

    Rodrigues, Elizabeth M; Scudder, Samantha L; Goo, Marisa S; Patrick, Gentry N

    2016-02-03

    Alzheimer's disease (AD) is a neurodegenerative disease in which patients experience progressive cognitive decline. A wealth of evidence suggests that this cognitive impairment results from synaptic dysfunction in affected brain regions caused by cleavage of amyloid precursor protein into the pathogenic peptide amyloid-β (Aβ). Specifically, it has been shown that Aβ decreases surface AMPARs, dendritic spine density, and synaptic strength, and also alters synaptic plasticity. The precise molecular mechanisms by which this occurs remain unclear. Here we demonstrate a role for ubiquitination in Aβ-induced synaptic dysfunction in cultured rat neurons. We find that Aβ promotes the ubiquitination of AMPARs, as well as the redistribution and recruitment of Nedd4-1, a HECT E3 ubiquitin ligase we previously demonstrated to target AMPARs for ubiquitination and degradation. Strikingly, we show that Nedd4-1 is required for Aβ-induced reductions in surface AMPARs, synaptic strength, and dendritic spine density. Our findings, therefore, indicate an important role for Nedd4-1 and ubiquitin in the synaptic alterations induced by Aβ. Synaptic changes in Alzheimer's disease (AD) include surface AMPAR loss, which can weaken synapses. In a cell culture model of AD, we found that AMPAR loss correlates with increased AMPAR ubiquitination. In addition, the ubiquitin ligase Nedd4-1, known to ubiquitinate AMPARs, is recruited to synapses in response to Aβ. Strikingly, reducing Nedd4-1 levels in this model prevented surface AMPAR loss and synaptic weakening. These findings suggest that, in AD, Nedd4-1 may ubiquitinate AMPARs to promote their internalization and weaken synaptic strength, similar to what occurs in Nedd4-1's established role in homeostatic synaptic scaling. This is the first demonstration of Aβ-mediated control of a ubiquitin ligase to regulate surface AMPAR expression. Copyright © 2016 the authors 0270-6474/16/361590-06$15.00/0.

  20. Flight test investigation of the vortex wake characteristics behind a Boeing 727 during two-segment and normal ILS approaches

    Science.gov (United States)

    Garodz, L. J.

    1975-01-01

    A series of flight tests were performed to evaluate the vortex wake characteristics of a Boeing 727 (B727-200) aircraft during conventional and two-segment ILS approaches. Flights of the B727, equipped with smoke generators for vortex marking, were flown wherein its vortex wake was intentionally encountered by a Lear Jet model 23 (LR-23) or a Piper Twin Comanche (Pa-30); and its vortex location during landing approach was measured using a system of photo-theodolites. The tests showed that at a given separation distance there were no differences in the upsets resulting from deliberate vortex encounters during the two types of approaches. Timed mappings of the position of the landing configuration vortices showed that they tended to descend approximately 91 meters (300 feet) below the flight path of the B727. The flaps of the B727 have a dominant effect on the character of the trailed wake vortex. The clean wing produces a strong, concentrated vortex. As the flaps are lowered, the vortex system becomes more diffuse. Pilot opinion and roll acceleration data indicate that 4.5 nautical miles would be a minimum separation distance at which roll control could be maintained during parallel encounters of the B727's landing configuration wake by small aircraft.

  1. Site environmental report for calendar year 2002. DOE operations at the Boeing Company, Rocketdyne Propulsion and Power

    Energy Technology Data Exchange (ETDEWEB)

    None

    2003-09-30

    This Annual Site Environmental Report (ASER) for 2002 describes the environmental conditions related to work performed for the Department of Energy (DOE) at Area IV of Boeing' s Santa Susana Field Laboratory (SSFL)). In the past, the Energy Technology Engineering Center (ETEC), a government-owned, company-operated test facility, was located in Area IV. The operations at ETEC included development, fabrication, and disassembly of nuclear reactors, reactor fuel, and other radioactive materials. Other activities at ETEC involved the operation of large-scale liquid metal facilities that were used for testing liquid metal fast breeder components. All nuclear work was terminated in 1988, and, subsequently, all radiological work has been directed toward decontamination and decommissioning (D&D) of the former nuclear facilities and their associated sites. Closure of the liquid metal test facilities began in 1996. Results of the radiological monitoring program for the calendar year 2002 continue to indicate that there are no significant releases of radioactive material from Area IV of SSFL. All potential exposure pathways are sampled and/or monitored, including air, soil, surface water, groundwater, direct radiation, transfer of property ( land, structures, waste), and recycling. All radioactive w astes are processed for disposal at DOE disposal sites and/or other licensed sites approved by DOE for radioactive waste disposal. No liquid radioactive wastes are released into the environment, and no structural debris from buildings w as transferred to municipal landfills or recycled in 2002.

  2. NIR Color vs Launch Date: A 20-Year Analysis of Space Weathering Effects on the Boeing 376 Spacecraft

    Science.gov (United States)

    Frith, James; Anz-Meador, Philip; Lederer, Sue; Cowardin, Heather; Buckalew, Brent

    2015-01-01

    The Boeing HS-376 spin stabilized spacecraft was a popular design that was launched continuously into geosynchronous orbit starting in 1980 with the last launch occurring in 2002. Over 50 of the HS-376 buses were produced to fulfill a variety of different communication missions for countries all over the world. The design of the bus is easily approximated as a telescoping cylinder that is covered with solar cells and an Earth facing antenna that is despun at the top of the cylinder. The similarity in design and the number of spacecraft launched over a long period of time make the HS-376 a prime target for studying the effects of solar weathering on solar panels as a function of time. A selection of primarily non-operational HS-376 spacecraft launched over a 20 year time period were observed using the United Kingdom Infrared Telescope on Mauna Kea and multi-band near-infrared photometry produced. Each spacecraft was observed for an entire night cycling through ZYJHK filters and time-varying colors produced to compare near-infrared color as a function of launch date. The resulting analysis shown here may help in the future to set launch date constraints on the parent object of unidentified debris objects or other unknown spacecraft.

  3. NIR Color vs Launch Date: A 20-year Analysis of Space Weathering Effects on the Boeing 376 Spacecraft

    Science.gov (United States)

    Frith, J.; Anz-Meador, P.; Lederer, S.; Cowardin, H.; Buckalew, B.

    The Boeing HS-376 spin stabilized spacecraft was a popular design that was launched continuously into geosynchronous orbit starting in 1980 with the last launch occurring in 2002. Over 50 of the HS-376 buses were produced to fulfill a variety of different communication missions for countries all over the world. The design of the bus is easily approximated as a telescoping cylinder that is covered with solar cells and an Earth facing antenna that is despun at the top of the cylinder. The similarity in design and the number of spacecraft launched over a long period of time make the HS-376 a prime target for studying the effects of solar weathering on solar panels as a function of time. A selection of primarily non-operational HS-376 spacecraft launched over a 20 year time period were observed using the United Kingdom Infrared Telescope on Mauna Kea and multi-band near-infrared photometry produced. Each spacecraft was observed for an entire night cycling through ZYJHK filters and time-varying colors produced to compare near-infrared color as a function of launch date. The resulting analysis shown here may help in the future to set launch date constraints on the parent object of unidentified debris objects or other unknown spacecraft.

  4. The NASA/industry Design Analysis Methods for Vibrations (DAMVIBS) program: Boeing Helicopters airframe finite element modeling

    Science.gov (United States)

    Gabel, R.; Lang, P.; Reed, D.

    1993-01-01

    Mathematical models based on the finite element method of structural analysis, as embodied in the NASTRAN computer code, are routinely used by the helicopter industry to calculate airframe static internal loads used for sizing structural members. Historically, less reliance has been placed on the vibration predictions based on these models. Beginning in the early 1980's NASA's Langley Research Center initiated an industry wide program with the objective of engendering the needed trust in vibration predictions using these models and establishing a body of modeling guides which would enable confident future prediction of airframe vibration as part of the regular design process. Emphasis in this paper is placed on the successful modeling of the Army/Boeing CH-47D which showed reasonable correlation with test data. A principal finding indicates that improved dynamic analysis requires greater attention to detail and perhaps a finer mesh, especially the mass distribution, than the usual stress model. Post program modeling efforts show improved correlation placing key modal frequencies in the b/rev range with 4 percent of the test frequencies.

  5. Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage

    Science.gov (United States)

    Kang, Ho Chul; Lee, Yun-Il; Shin, Joo-Ho; Andrabi, Shaida A.; Chi, Zhikai; Gagné, Jean-Philippe; Lee, Yunjong; Ko, Han Seok; Lee, Byoung Dae; Poirier, Guy G.; Dawson, Valina L.; Dawson, Ted M.

    2011-01-01

    Ubiquitin mediated protein degradation is crucial for regulation of cell signaling and protein quality control. Poly(ADP-ribose) (PAR) is a cell-signaling molecule that mediates changes in protein function through binding at PAR binding sites. Here we characterize the PAR binding protein, Iduna, and show that it is a PAR-dependent ubiquitin E3 ligase. Iduna’s E3 ligase activity requires PAR binding because point mutations at Y156A and R157A eliminate Iduna’s PAR binding and Iduna’s E3 ligase activity. Iduna’s E3 ligase activity also requires an intact really interesting new gene (RING) domain because Iduna possessing point mutations at either H54A or C60A is devoid of ubiquitination activity. Tandem affinity purification reveals that Iduna binds to a number of proteins that are either PARsylated or bind PAR including PAR polymerase-1, 2 (PARP1, 2), nucleolin, DNA ligase III, KU70, KU86, XRCC1, and histones. PAR binding to Iduna activates its E3 ligase function, and PAR binding is required for Iduna ubiquitination of PARP1, XRCC1, DNA ligase III, and KU70. Iduna’s PAR-dependent ubiquitination of PARP1 targets it for proteasomal degradation. Via PAR binding and ubiquitin E3 ligase activity, Iduna protects against cell death induced by the DNA damaging agent N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest and promotes cell survival after γ-irradiation. Moreover, Iduna facilitates DNA repair by reducing apurinic/apyrimidinic (AP) sites after MNNG exposure and facilitates DNA repair following γ-irradiation as assessed by the comet assay. These results define Iduna as a PAR-dependent E3 ligase that regulates cell survival and DNA repair. PMID:21825151

  6. Association of NR2E3 but not NRL mutations with retinitis pigmentosa in the Chinese population.

    Science.gov (United States)

    Yang, Yaping; Zhang, Xin; Chen, Li Jia; Chiang, Sylvia W Y; Tam, Pancy O S; Lai, Timothy Y Y; Chan, Carmen K M; Wang, Ningli; Lam, Dennis S C; Pang, Chi Pui

    2010-04-01

    Purpose. Mutations in the NR2E3 and NRL genes have been implicated in both autosomal dominant and autosomal recessive retinitis pigmentosa (RP). In this study, the mutation profiles of these two genes were investigated in Chinese RP patients. Methods. In 172 RP patients and 360 normal control subjects (180 from Hong Kong and 180 from Beijing), the coding exons and the exon-intron boundaries of NR2E3 and NRL were screened by direct DNA sequencing after PCR. Association analysis was performed for common single-nucleotide polymorphisms (SNPs), whereas in silico programs were used for analysis of rare missense variants. Results. In NR2E3, 14 novel sequence changes have been identified. Two missense variants, p.G56R and p.V118M, were exclusively found in RP patients with frequencies at 1.2% (2/172) and 1.7% (3/172), respectively. All five patients were found to be heterozygous for these two mutations. Computational analysis suggested functional defects on the NR2E3 protein, indicating disease-causing roles. The p.E121K variant of NR2E3, which reportedly caused enhanced S-cone syndrome (ESCS) in Caucasians, was found concurrently in RP patients (13.4%) and control subjects from Hong Kong (10.5%) and Beijing (12.8%). In NRL, six novel sequence changes were identified, none of them associated with RP. Conclusions. In this study, NR2E3 mutations (p.G56R, p.V118M) were found to be responsible for approximately 2.9% of overall RP in Chinese patients, comparable to the contributions of RHO and RP1 mutations. The p.E121K in NR2E3 is a common SNP in the Chinese, suggesting another genetic or environmental factor is involved in its causative role in ESCS in Caucasians.

  7. Characterization of the Arabidopsis thaliana E3 ubiquitin-ligase AtSINAL7 and identification of the ubiquitination sites.

    Directory of Open Access Journals (Sweden)

    Diego A Peralta

    Full Text Available Protein ubiquitination leading to degradation by the proteasome is an important mechanism in regulating key cellular functions. Protein ubiquitination is carried out by a three step process involving ubiquitin (Ub activation by a E1 enzyme, the transfer of Ub to a protein E2, finally an ubiquitin ligase E3 catalyzes the transfer of the Ub peptide to an acceptor protein. The E3 component is responsible for the specific recognition of the target, making the unveiling of E3 components essential to understand the mechanisms regulating fundamental cell processes through the protein degradation pathways. The Arabidopsis thaliana seven in absentia-like 7 (AtSINAL7 gene encodes for a protein with characteristics from a C3HC4-type E3 ubiquitin ligase. We demonstrate here that AtSINAL7 protein is indeed an E3 protein ligase based on the self-ubiquitination in vitro assay. This activity is dependent of the presence of a Lys residue in position 124. We also found that higher AtSINAL7 transcript levels are present in tissues undergoing active cell division during floral development. An interesting observation is the circadian expression pattern of AtSINAL7 mRNA in floral buds. Furthermore, UV-B irradiation induces the expression of this transcript indicating that AtSINAL7 may be involved in a wide range of different cell processes.

  8. E3B1/ABI-1 Isoforms Are Down-Regulated in Cancers of Human Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Rafia A. Baba

    2012-01-01

    Full Text Available The expression of E3B1/ABI-1 protein and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors. In this study, we examined the expression pattern of E3B1/ABI-1 protein in histologically confirmed cases of esophageal (squamous cell carcinoma and adenocarcinoma, gastro-esophageal junction, colorectal cancers and corresponding normal tissues freshly resected from a cohort of 135 patients, by Western Blotting and Immunofluorescence Staining. The protein is present in its phosphorylated form in cells and tissues. Depending on the extent of phosphorylation it is either present in hyper-phosphorylated (M. Wt. 72 kDa form or in hypo-phosphorylated form (M. Wt. 68 kDa and 65 kDa. A thorough analysis revealed that expression of E3B1/ABI-1 protein is significantly decreased in esophageal, gastro-esophageal junction and colorectal carcinomas irrespective of age, gender, dietary and smoking habits of the patients. The decrease in expression of E3B1/ABI-1 was consistently observed for all the three isoforms. However, the decrease in the expression of isoforms varied with different forms of cancers. Down-regulation of E3B1/ABI-1 expression in human carcinomas may play a critical role in tumor progression and in determining disease prognosis.

  9. A preliminary investigating the geomorphological characteristics of surrounding Chang'E-3 landing site

    Science.gov (United States)

    Li, C.; Mu, L.; Zuo, W.; Li, H.; Feng, J.

    2015-12-01

    On 2013 December 14, at 13:11:13(UTC), China's first lunar probe to make a soft landing, Chang'E-3(CE-3), touched down on the east edge of Mare Imbrium beside a crater with a diameter of 430m in the east part of Sinus Iridum. To better understand the environment of this region, We utilizes the available lunar topography, image and geology data with high resolution(in meters), as well as image data captured by the landing camera and topography camera on CE-3(in centimeters) to analyze the topography, landforms, geology and lunar dust from perspectives ranging from large spatial areas(hundreds of kilometers like Sinus Iridum and North Mare Imbrium, 45×75 km) to a smaller scale of kilometers near the landing site(4×4 km) and finally to the immediate area around the landing site in meters. We can find that:1)The probe landed on a flat lunar mare with an elevation of -2615m. The landing site is high titanium basalt stratum, and its geological age is young Eratoshenian. 10km to the north of the landing site is the older Mare Imbrium stratum, and the location of the landing site is in the area that is the intersection of these two strata; 2)The landing site lies on the edge of a plateau in a flat plain with a declining trend from west to east, and the topographic slope and waviness of the area are low, which is typical for terrain in lunar mare; 3)The adjacent area of the landing point is flat terrain, with landforms such as craters, domes, strata and rocks with different albedos, which are good targets for scientific exploration; 4)By comparing images captured before and after landing, we find that during the landing process of CE-3, lots of lunar dust was blown away by the engine plume, and the scope of influence is about 60m from east to west and 135m from south to north. Thus, this leads to a redistribution of lunar dust and changes in space weathering on the lunar surface.

  10. Association between melanocytic nevi and risk of breast diseases: The French E3N prospective cohort.

    Directory of Open Access Journals (Sweden)

    Marina Kvaskoff

    2014-06-01

    Full Text Available BACKGROUND: While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk. METHODS AND FINDINGS: We prospectively analyzed data from E3N, a cohort of French women aged 40-65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs for breast cancer and 95% confidence intervals (CIs were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990-15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with "very many" nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01-1.27 versus "none"; ptrend = 0.04, although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674-4,649 per 100,000 women with "very many" nevi. The association was restricted to premenopausal women (HR = 1.40, ptrend = 0.01, even after full adjustment (HR = 1.34, ptrend = 0.03; phomogeneity = 0.04, but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose-response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; ptrend<0.0001 and family history of breast cancer in first-degree relatives (n = 7,472; ptrend = 0.0003. The main limitations of our study

  11. A Very Fast Pulsed Electron Gun for (e, 2e) and (e, 3e) Studies

    Institute of Scientific and Technical Information of China (English)

    CaoShiping; MaXinwen; ShaShan; ZhuXiaolong; LiuHuipin

    2003-01-01

    Reaction microscope is a powerful tool for studying ion-atom/molecule dynamics, it can also be employed to investigate electron impact ionization processes. Traditionally these processes are studied by using the (e, 2e) or (e, 3e) techniques, most data are collected for single ionization and for very small scattering angles, i.e. (e, 2e), experimental data of double ionization (e, 3e)[1] and multiple ionization are scarce, because in most cases the efficiencies (mainly determined by solid angles) are extremely small for (e, 3e) processes, about 10-7~10-9. On the other hand, the new technique-reaction microscope can detect mutli-fragments in one collision with very

  12. Computed and Experimental Flutter/LCO Onset for the Boeing Truss-Braced Wing Wind-Tunnel Model

    Science.gov (United States)

    Bartels, Robert E.; Scott, Robert C.; Funk, Christie J.; Allen, Timothy J.; Sexton, Bradley W.

    2014-01-01

    This paper presents high fidelity Navier-Stokes simulations of the Boeing Subsonic Ultra Green Aircraft Research truss-braced wing wind-tunnel model and compares the results to linear MSC. Nastran flutter analysis and preliminary data from a recent wind-tunnel test of that model at the NASA Langley Research Center Transonic Dynamics Tunnel. The simulated conditions under consideration are zero angle of attack, so that structural nonlinearity can be neglected. It is found that, for Mach number greater than 0.78, the linear flutter analysis predicts flutter onset dynamic pressure below the wind-tunnel test and that predicted by the Navier-Stokes analysis. Furthermore, the wind-tunnel test revealed that the majority of the high structural dynamics cases were wing limit cycle oscillation (LCO) rather than flutter. Most Navier-Stokes simulated cases were also LCO rather than hard flutter. There is dip in the wind-tunnel test flutter/LCO onset in the Mach 0.76-0.80 range. Conditions tested above that Mach number exhibited no aeroelastic instability at the dynamic pressures reached in the tunnel. The linear flutter analyses do not show a flutter/LCO dip. The Navier-Stokes simulations also do not reveal a dip; however, the flutter/LCO onset is at a significantly higher dynamic pressure at Mach 0.90 than at lower Mach numbers. The Navier-Stokes simulations indicate a mild LCO onset at Mach 0.82, then a more rapidly growing instability at Mach 0.86 and 0.90. Finally, the modeling issues and their solution related to the use of a beam and pod finite element model to generate the Navier-Stokes structure mode shapes are discussed.

  13. The effect of whole grain wheat sourdough bread consumption on serum lipids in healthy normoglycemic/normoinsulinemic and hyperglycemic/hyperinsulinemic adults depends on presence of the APOE E3/E3 genotype: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Bakovic Marica

    2010-05-01

    Full Text Available Abstract Background Epidemiological studies associate consumption of whole grain foods, including breads, with reduced cardiovascular disease (CVD risk; however, few studies have compared wheat whole grains with wheat refined grains. Methods This study investigated effects of 6-week consumption of whole grain wheat sourdough bread in comparison to white bread on fasting serum lipids in normoglycemic/normoinsulinemic (NGI; n = 14 and hyperglycemic/hyperinsulinemic (HGI; n = 14 adults. The influence of single-nucleotide polymorphisms, 3 within the APOE gene (E2, E3, E4 and 2 within the hepatic lipase gene promoter (LIPC -514C>T, LIPC -250G>A were considered. Results At baseline, HGI participants had significantly higher body weight, waist circumference, body fat, and fasted glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR, glucagon, triacylglycerols (TAG and TAG:HDL-cholesterol, compared to NGI participants; however, none of these in addition to none of the other serum lipids, differed between bread treatments, within either participant group. For participants with the APOE E3/E3 genotype, LDL-cholesterol (P = 0.02 increased in the NGI group (n = 7, and TAG (P = 0.03 and TAG:HDL-cholesterol (P = 0.04 increased in the HGI group (n = 10, following consumption of whole grain wheat sourdough compared to white bread. Conclusions In summary, 6-week consumption of whole grain wheat sourdough bread did not significantly modulate serum lipids in NGI or HGI adults; however, it significantly increased LDL-cholesterol, TAG and TAG:HDL-cholesterol in participants with the APOE E3/E3 genotype. These data add to limited literature comparing wheat whole grains to wheat refined grains on CVD risk and highlight the need to consider genetic variation in relation to lipoprotein lipid content and CVD risk.

  14. Aerodynamic results of a separation test (CA20) conducted at the Boeing transonic wind tunnel using 0.030-scale models of the configuration 140A/B (modified) SSV orbiter (model no. 45-0) and the Boeing 747 carrier (model no. AX 1319 I-1), volume 1. [wind tunnel tests

    Science.gov (United States)

    Dziubala, T.; Esparza, V.; Gillins, R. L.; Petrozzi, M.

    1975-01-01

    A Rockwell built 0.030-scale 45-0 modified Space Shuttle Orbiter Configuration 14?A/B model and a Boeing built 0.030-scale 747 carrier model were tested to provide six component force and moment data for each vehicle in proximity to the other at a matrix of relative positions, attitudes and test conditions (angles of attack and sideslip were varied). Orbiter model support system tare effects were determined for corrections to obtain support-free aerodynamics. In addition to the balance force data, pressures were measured. Pressure orifices were located at the base of the Orbiter, on either side of the vertical blade strut, and at the mid-root chord on either side of the vertical tail. Strain gages were installed on the Boeing 747 vertical tail to indicate buffet onset. Photographs of aerodynamic configurations tested are shown.

  15. Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice

    NARCIS (Netherlands)

    Vlijmen, B.J.M. van; Mensink, R.P.; Hof, H.B. van 't; Offermans, R.F.G.; Hofker, M.H.; Havekes, L.M.

    1998-01-01

    Studying the effects of dietary fish oil on VLDL metabolism in humans is subject to both large intra- and interindividual variability. In the present study we therefore used hyperlipidentic apolipoprotein (APO) E*3-Leiden mice, which have impaired chylomicron and very low density lipoprotein (VDL) r

  16. Phosphorylation in vitro of eukaryotic initiation factors IF-E2 and IF-E3 by protein kinases

    DEFF Research Database (Denmark)

    Issinger, O G; Benne, R; Hershey, J W;

    1976-01-01

    is composed of 9 to 11 nonidentical polypeptides; only 2 of these, with molecular weights of 120,000 and 70,000, were phosphorylated. A lower level of phosphorylation of initiation factor IF-E3 was found with the cyclic AMP-dependent protein kinase; the polypeptide of molecular weight 140,000 was the major...

  17. Nr2e3 and Nrl can reprogram retinal precursors to the rod fate in Xenopus retina.

    Science.gov (United States)

    McIlvain, Vera A; Knox, Barry E

    2007-07-01

    Transformation of undifferentiated progenitors into specific cell types is largely dependent on temporal and spatial expression of a complex network of transcription factors. Here, we examined whether neural retina leucine zipper (Nrl) and photoreceptor-specific nuclear receptor Nr2e3 transcription factors contribute to cell fate determination. We cloned the Xenopus Nr2e3 gene and showed that its temporal and spatial expression is similar to its mammalian ortholog. We tested its in vivo function by misexpressing these transcription factors in Xenopus eye primordia, demonstrating that either human Nr2e3 or Nrl directed photoreceptor precursors to become rods at the expense of cones. Furthermore, overexpression of Xenopus Nrl dramatically increased the number of lens fibers, whereas human Nrl did not, suggesting evolutionary divergence of function of the Nrl gene family. Misexpression of Nrl and Nr2e3 together were more effective than either transcription factor alone in directing precursors to the rod fate. Copyright 2007 Wiley-Liss, Inc.

  18. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors

    NARCIS (Netherlands)

    Koo, B.K.; Spit, M.; Jordens, I.; Low, T.Y.; Stange, D.E.; van de Wetering, M.; van Es, J.H.; Mohammed, S.; Heck, A.J.R.; Maurice, M.M.; Clevers, H.

    2012-01-01

    LGR5+ stem cells reside at crypt bottoms, intermingled with Paneth cells that provide Wnt, Notch and epidermal growth factor signals. Here we find that the related RNF43 and ZNRF3 transmembrane E3 ubiquitin ligases are uniquely expressed in LGR5+ stem cells. Simultaneous deletion of the two genes en

  19. Rosuvastatin reduces plasma lipids by inhibiting VLDL production and enhancing hepatobiliary lipid excretion in ApoE*3-Leiden mice

    NARCIS (Netherlands)

    Delsing, DJM; Post, SM; Groenendijk, M; Solaas, K; van der Boom, H; van Duyvenvoorde, W; de Wit, ECM; Bloks, VW; Kuipers, F; Havekes, LM; Princen, HMG

    The present study was designed to investigate the lipid-lowering properties and mechanisms of action of a new HMG-CoA reductase inhibitor, rosuvastatin, in female ApoE*3-Leiden transgenic mice. Mice received a high fat/cholesterol (HFC) diet containing either rosuvastatin (0 [control], 0.00125%,

  20. X-ray and Optical Study of Low Core Density Globular Clusters NGC6144 and E3

    CERN Document Server

    Lan, Shih Hao; Verbunt, Frank; Lewin, Walter H G; Bassa, Cees; Anderson, Scott F; Pooley, David

    2009-01-01

    We report on the Chandra X-ray Observatory and Hubble Space Telescope observation of two low core density globular clusters, NGC6144 and E3. By comparing the number of X-ray sources inside the half-mass radius to those outside, we found 6 X-ray sources within the half-mass radius of NGC6144, among which 4 are expected to be background sources; 3 X-ray sources are also found within the half-mass radius of E3, of which 3 is expected to be background source. Therefore, we cannot exclude that all our sources are background sources. However, combining the results from X-ray and optical observations, we found that 1-2 sources in NGC6144 and 1 source in E3 are likely to be cataclysmic variables and that 1 source in NGC6144 is an active binary, based on the X-ray and optical properties. The number of faint X-ray sources in NGC6144 and E3 found with Chandra and HST is higher than a prediction based on collision frequency, but is closer to that based on mass. Our observations strongly suggest that the compact binary sy...

  1. K48-linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression

    DEFF Research Database (Denmark)

    Hao, Zhenyue; Sheng, Yi; Duncan, Gordon S.

    2017-01-01

    T-cell proliferation is regulated by ubiquitination but the underlying molecular mechanism remains obscure. Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase. Mule is elevated in T cells upon TCR...

  2. Flight test investigation of the vortex wake characteristics behind a Boeing 727 during two-segment and normal ILS approaches (A joint NASA/FAA report)

    Science.gov (United States)

    Barber, M. R.; Kurkowski, R. L.; Garodz, L. J.; Robinson, G. H.; Smith, H. J.; Jacobsen, R. A.; Stinnett, G. W., Jr.; Mcmurtry, T. C.; Tymczyszyn, J. J.; Devereaux, R. L.

    1975-01-01

    Flight tests were performed to evaluate the vortex wake characteristics of a Boeing 727 aircraft during conventional and two-segment instrument landing approaches. Smoke generators were used for vortex marking. The vortex was intentionally intercepted by a Lear Jet and a Piper Comanche aircraft. The vortex location during landing approach was measured using a system of phototheodolites. The tests showed that at a given separation distance there are no readily apparent differences in the upsets resulting from deliberate vortex encounters during the two types of approaches. The effect of the aircraft configuration on the extent and severity of the vortices is discussed.

  3. 波音737机务维护专家系统的设计与实现%Research and Realization of Boeing 737 Maintenance Expert System

    Institute of Scientific and Technical Information of China (English)

    韩凌飞; 杨国庆

    2001-01-01

    Combining with an example,we study the architeture and the organization of the object oriented diagnosis knowledge base of Boeing 737 maintenance expert system.Its reasoning mechanism is also discussed in this paper.And we have got a good result in practice.%结合实例研究了波音737机务维护专家系统的系统结构,面向对象的诊断知识库的组织模型和推理机制,在实际运行中获得了良好的效果。

  4. 韩国LCD设备、材料业者将大举进驻BOE-HYDIS北京LCD园区

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    根据韩国媒体3月25日的报导,BOE—HYDIS目前正于北京兴建大型LCD园区,该园区规模达120万m。,其中的一半面积将供LCD相关材料与设备业者进驻。同时,BOE-HYDIS已在最近选定将进驻该园区的10余家韩国原物料

  5. The design, development, and flight test results of the Boeing 737 aircraft antennas for the ICAO demonstration of the TRSB microwave landing system

    Science.gov (United States)

    Campbell, T. G.; White, W. E.; Gilreath, M. C.

    1976-01-01

    The Research Support Flight System, a modified Boeing 737, was used to evaluate the performance of several aircraft antennas and locations for the Time Reference Scanning Beam (TRSB) Microwave Landing System (MLS). These tests were conducted at the National Aviation Facilities Experimental Center (NAFEC), Atlantic City, New Jersey on December 18, 1975. The flight tests measured the signal strength and all pertinent MLS data during a straight-in approach, a racetrack approach, and ICAO approach profiles using the independent antenna-receiver combinations simultaneously on the aircraft. Signal drop-outs were experienced during the various approaches but only a small percentage could be attributed to antenna pattern effects.

  6. Binding and repressive activities of apolipoprotein E3 and E4 isoforms on the human ApoD promoter.

    Science.gov (United States)

    Levros, Louis-Charles; Labrie, Marilyne; Charfi, Cyndia; Rassart, Eric

    2013-12-01

    Apolipoprotein D (ApoD) gene expression is increased in several neurological disorders such as Alzheimer's disease (AD) and multiple sclerosis. We previously showed that transgenic mice that overexpress human ApoD show a better resistance against paraquat or OC43 coronavirus-induced neurodegeneration. Here, we identified several nuclear factors from the cortex of control and OC43-infected mice which bind a fragment of the proximal ApoD promoter in vitro. Of interest, we detected apolipoprotein E (ApoE). Human ApoE consists of three isoforms (E2, E3, and E4) with the E4 and E2 alleles representing a greater and a lower risk for developping AD, respectively. Our results show that ApoE is located in the nucleus and on the ApoD promoter in human hepatic and glioblastoma cells lines. Furthermore, overexpression of ApoE3 and ApoE4 isoforms but not ApoE2 significantly inhibited the ApoD promoter activity in U87 cells (E3/E3 genotype) cultured under normal or different stress conditions while ApoE knock-down by siRNA had a converse effect. Consistent with these results, we also demonstrated by ChIP assay that E3 and E4 isoforms, but not E2, bind the ApoD promoter. Moreover, using the Allen Brain Atlas in situ hybridization database, we observed an inverse correlation between ApoD and ApoE mRNA expression during development and in several regions of the mouse brain, notably in the cortex, hippocampus, plexus choroid, and cerebellum. This negative correlation was also observed for cortex layers IV-VI based on a new Transcriptomic Atlas of the Mouse Neocortical Layers. These findings reveal a new function for ApoE by regulating ApoD gene expression.

  7. Cloning and Expression of Apolipoprotein E3 and Its Variant apoE2 and apoE4

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to obtain three isoforms of apolipoprotein E (apoE), the cDNA encoding apoE3 was obtained by RT-PCR from normal human liver tissue. Site-directed mutagenesis was used to obtain the cDNAs encoding apoE2 and apoE4 isoforms. The 3 cDNAs were subcloned into vector pGEM-3Z and verified by DNA sequencing. The expression recombinant which can express the target protein as a (His) 6-tagged fusion was constructed by subcloning apoE cDNA into vector pT7-PL. The purified proteins were gained by Ni-NTA column. The SDS-PAGE results revealed the 6 His fusion proteins (apoE2, apoE3 and apoE4) were correctly expressed and purified successfully.

  8. The activities of the E3 ubiquitin ligase COP1/SPA, a key repressor in light signaling.

    Science.gov (United States)

    Hoecker, Ute

    2017-06-01

    Light is a critical signal to integrate plant growth and development with the environment. Downstream of photoreceptors, the E3 ubiquitin ligase COP1/SPA is a key repressor of photomorphogenesis which targets many positive regulators of light signaling, mainly transcription factors, for degradation in darkness. In light-grown plants COP1/SPA activity is repressed, allowing light responses to occur. This review provides an overview on our current knowledge on COP1/SPA repressor function, focusing in particular on the roles of the respective protein domains and the mechanisms of light-induced inactivation of COP1/SPA. Moreover, we summarize how COP1 activity is regulated by other interacting proteins, such as a SUMO E3 ligase and Phytochrome-Interacting Factors (PIFs), as well as by hormones. At last, several novel functions of COP1 that were recently revealed are included. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Preliminary Report on Oak Ridge National Laboratory Testing of Drake/ACSS/MA2/E3X

    Energy Technology Data Exchange (ETDEWEB)

    Irminger, Philip [ORNL; Davis, Cody [General Cable Corporation; Temple, Bill [General Cable Corporation; Baker, Gord [General Cable Corporation; Starke, Michael R [ORNL

    2016-01-01

    A key to industry acceptance of a new technology is extensive validation in field trials. The Powerline Conductor Accelerated Test facility (PCAT) at Oak Ridge National Laboratory (ORNL) is specifically designed to evaluate the performance and reliability of a new conductor technology under real world conditions. The facility is set up to capture large amounts of data during testing. General Cable used the ORNL PCAT facility to validate the performance of TransPowr with E3X Technology a standard overhead conductor with an inorganic high emissivity, low absorptivity surface coating. Extensive testing has demonstrated a significant improvement in conductor performance across a wide range of operating temperatures, indicating that E3X Technology can provide a reduction in temperature, a reduction in sag, and an increase in ampacity when applied to the surface of any overhead conductor. This report provides initial results of that testing.

  10. Cyclin F: A component of an E3 ubiquitin ligase complex with roles in neurodegeneration and cancer.

    Science.gov (United States)

    Galper, Jasmin; Rayner, Stephanie L; Hogan, Alison L; Fifita, Jennifer A; Lee, Albert; Chung, Roger S; Blair, Ian P; Yang, Shu

    2017-08-01

    Cyclin F, encoded by CCNF, is the substrate recognition component of the Skp1-Cul1-F-box E3 ubiquitin ligase complex, SCF(cyclin F). E3 ubiquitin ligases play a key role in ubiquitin-proteasome mediated protein degradation, an essential component of protein homeostatic mechanisms within the cell. By recognising and regulating the availability of several protein substrates, SCF(cyclin F) plays a role in regulating various cellular processes including replication and repair of DNA and cell cycle checkpoint control. Cyclin F dysfunction has been implicated in various forms of cancer and CCNF mutations were recently linked to familial and sporadic amyotrophic lateral sclerosis and frontotemporal dementia, offering a new lead to understanding the pathogenic mechanisms underlying neurodegeneration. In this review, we evaluate the current literature on the function of cyclin F with an emphasis on its roles in cancer and neurodegeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Estimated dietary dioxin exposure and breast cancer risk among women from the French E3N prospective cohort.

    Science.gov (United States)

    Danjou, Aurélie M N; Fervers, Béatrice; Boutron-Ruault, Marie-Christine; Philip, Thierry; Clavel-Chapelon, Françoise; Dossus, Laure

    2015-03-17

    Dioxins are environmental and persistent pollutants mostly emitted from combustion facilities (e.g. waste incinerators, metal and cement industries). Known to be endocrine disrupting chemicals, dioxins are suspected to increase breast cancer (BC) risk. Although diet is considered the primary source of dioxin exposure, no previous study has been published on dietary dioxin exposure in relation to BC risk. We aimed to assess dietary dioxin exposure among women from the E3N cohort and estimate BC risk associated with this exposure. The study included 63,830 women from the E3N cohort who completed a diet history questionnaire (DHQ) in 1993 and were followed until 2008. Dietary dioxin exposure was estimated by combining consumption data from the E3N DHQ and food dioxin contamination data from a French national monitoring program. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox models adjusted for BC risk factors. Mean dietary dioxin exposure was estimated at 1.3 ± 0.4 pg/kg body weight (BW)/day. A 0.4 pg/kg BW/d increase in dioxin intake was not associated with overall BC risk (HR = 1.00; 95% CI: 0.96, 1.05). A significant decrease in risk of estrogen receptor negative (ER-)/progesterone receptor negative (PR-) tumors was observed among post-menopausal women in the upper quartile of estimated dioxin intake (HR for Q4 vs. Q1: 0.65; 95% CI: 0.45, 0.96; P for trend across quartiles = 0.0463). Overall, no association between estimated dietary dioxin exposure and BC risk was found among E3N women. Further studies should include both dietary and environmental exposures to determine whether low-dose dioxin exposure is associated with BC risk.

  12. Small, N-terminal tags activate Parkin E3 ubiquitin ligase activity by disrupting its autoinhibited conformation.

    Directory of Open Access Journals (Sweden)

    Lynn Burchell

    Full Text Available Parkin is an E3 ubiquitin ligase, mutations in which cause Autosomal Recessive Parkinson's Disease. Many studies aimed at understanding Parkin function, regulation and dysfunction are performed using N-terminal epitope tags. We report here that the use of small tags such as FLAG, cMyc and HA, influence the physical stability and activity of Parkin in and out of cells, perturbing the autoinhibited native state of Parkin, resulting in an active-for-autoubiquitination species.

  13. Inactivation of Sag/Rbx2/Roc2 E3 Ubiquitin Ligase Triggers Senescence and Inhibits Kras-Induced Immortalization

    Directory of Open Access Journals (Sweden)

    Mingjia Tan

    2015-01-01

    Full Text Available Our recent study showed that SAG/RBX2 E3 ubiquitin ligase regulates apoptosis and vasculogenesis by promoting degradation of NOXA and NF1, and co-operates with Kras to promote lung tumorigenesis by activating NFκB and mTOR pathways via targeted degradation of tumor suppressive substrates including IκB, DEPTOR, p21 and p27. Here we investigated the role of Sag/Rbx2 E3 ligase in cellular senescence and immortalization of mouse embryonic fibroblasts (MEFs and report that Sag is required for proper cell proliferation and KrasG12D-induced immortalization. Sag inactivation by genetic deletion remarkably suppresses cell proliferation by inducing senescence, which is associated with accumulation of p16, but not p53. Mechanistically, Sag deletion caused accumulation of Jun-B, a substrate of Sag-Fbxw7 E3 ligase and a transcription factor that drives p16 transcription. Importantly, senescence triggered by Sag deletion can be largely rescued by simultaneous deletion of Cdkn2a, the p16 encoding gene, indicating its causal role. Furthermore, KrasG12D-induced immortalization can also be abrogated by Sag deletion via senescence induction, which is again rescued by simultaneous deletion of Cdkn2a. Finally, we found that Sag deletion inactivates KrasG12D activity and block the MAPK signaling pathway, together with accumulated p16, to induce senescence. Taken together, our results demonstrated that Sag is a KrasG12D-cooperating oncogene required for KrasG12D-induced immortalization and transformation, and targeting SAG-SCF E3 ligase may, therefore, have therapeutic value for senescence-based cancer treatment.

  14. Non-vanishing $U_{e3}$ and $\\cos{2 \\theta_{23}}$ from a broken $Z_2$ symmetry

    CERN Document Server

    Grimus, Walter; Kaneko, S; Lavoura, L; Sawanaka, H; Tanimoto, M; Grimus, Walter; Joshipura, Anjan S.; Kaneko, Satoru; Lavoura, Lu\\'{i}s; Sawanaka, Hideyuki; Tanimoto, Morimitsu

    2004-01-01

    It is shown that the neutrino mass matrices in the flavour basis yielding a vanishing $U_{e3}$ are characterized by invariance under a class of effective $Z_2$ symmetries. A specific $Z_2$ in this class also leads to a maximal atmospheric mixing angle $\\theta_{23}$. The breaking of that $Z_2$ can be parameterized by two dimensionless quantities, $\\e$ and $\\e'$; the effects of $\\e, \\e' \

  15. Dietary factors, metabolic syndrome and risks of breast cancer and type II diabetes in the E3N cohort

    OpenAIRE

    Fagherazzi, Guy

    2011-01-01

    Breast cancer and type II diabetes are two of the main chronic diseases in women and are suspected to share common risk factors. But their etiologies are still partially unknown, in particular concerning some dietary factors and some parameters of the metabolic syndrome. If evidence is convincing that themetabolic syndrome is associated with an increased type II diabetes risk, questions remain unanswered regarding cholesterol level, anthropometric factors and breast cancer risk. The French E3...

  16. A family of Salmonella virulence factors functions as a distinct class of autoregulated E3 ubiquitin ligases

    Science.gov (United States)

    Quezada, Cindy M.; Hicks, Stuart W.; Galán, Jorge E.; Stebbins, C. Erec

    2009-01-01

    Processes as diverse as receptor binding and signaling, cytoskeletal dynamics, and programmed cell death are manipulated by mimics of host proteins encoded by pathogenic bacteria. We show here that the Salmonella virulence factor SspH2 belongs to a growing class of bacterial effector proteins that harness and subvert the eukaryotic ubiquitination pathway. This virulence protein possesses ubiquitination activity that depends on a conserved cysteine residue. A crystal structure of SspH2 reveals a canonical leucine-rich repeat (LRR) domain that interacts with a unique E3 ligase [which we have termed NEL for Novel E3 Ligase] C-terminal fold unrelated to previously observed HECT or RING-finger E3 ligases. Moreover, the LRR domain sequesters the catalytic cysteine residue contained in the NEL domain, and we suggest a mechanism for activation of the ligase requiring a substantial conformational change to release the catalytic domain for function. We also show that the N-terminal domain targets SspH2 to the apical plasma membrane of polarized epithelial cells and propose a model whereby binding of the LRR to proteins at the target site releases the ligase domain for site-specific function. PMID:19273841

  17. Allosteric Interactions by p53 mRNA Govern HDM2 E3 Ubiquitin Ligase Specificity under Different Conditions.

    Science.gov (United States)

    Medina-Medina, Ixaura; García-Beltrán, Paola; de la Mora-de la Mora, Ignacio; Oria-Hernández, Jesús; Millot, Guy; Fahraeus, Robin; Reyes-Vivas, Horacio; Sampedro, José G; Olivares-Illana, Vanesa

    2016-08-15

    HDM2 and HDMX are key negative regulatory factors of the p53 tumor suppressor under normal conditions by promoting its degradation or preventing its trans activity, respectively. It has more recently been shown that both proteins can also act as positive regulators of p53 after DNA damage. This involves phosphorylation by ATM on serine residues HDM2(S395) and HDMX(S403), promoting their respective interaction with the p53 mRNA. However, the underlying molecular mechanisms of how these phosphorylation events switch HDM2 and HDMX from negative to positive regulators of p53 is not known. Our results show that these phosphorylation events reside within intrinsically disordered domains and change the conformation of the proteins. The modifications promote the exposition of N-terminal interfaces that support the formation of a new HDMX-HDM2 heterodimer independent of the C-terminal RING-RING interaction. The E3 ubiquitin ligase activity of this complex toward p53 is prevented by the p53 mRNA ligand but, interestingly, does not affect the capacity to ubiquitinate HDMX and HDM2. These results show how ATM-mediated modifications of HDMX and HDM2 switch HDM2 E3 ubiquitin ligase activity away from p53 but toward HDMX and itself and illustrate how the substrate specificity of HDM2 E3 ligase activity is regulated.

  18. Lafora disease E3-ubiquitin ligase malin is related to TRIM32 at both the phylogenetic and functional level

    Directory of Open Access Journals (Sweden)

    Gentry Matthew S

    2011-07-01

    Full Text Available Abstract Background Malin is an E3-ubiquitin ligase that is mutated in Lafora disease, a fatal form of progressive myoclonus epilepsy. In order to perform its function, malin forms a functional complex with laforin, a glucan phosphatase that facilitates targeting of malin to its corresponding substrates. While laforin phylogeny has been studied, there are no data on the evolutionary lineage of malin. Results After an extensive search for malin orthologs, we found that malin is present in all vertebrate species and a cephalochordate, in contrast with the broader species distribution previously reported for laforin. These data suggest that in addition to forming a functional complex, laforin and perhaps malin may also have independent functions. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32, which belongs to the tripartite-motif containing family of proteins. We present experimental evidence that both malin and TRIM32 share some substrates for ubiquitination, although they produce ubiquitin chains with different topologies. However, TRIM32-specific substrates were not reciprocally ubiquitinated by the laforin-malin complex. Conclusions We found that malin and laforin are not conserved in the same genomes. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32. The latter result suggests a common origin for malin and TRIM32 and provides insights into possible functional relationships between both proteins.

  19. FERM-dependent E3 ligase recognition is a conserved mechanism for targeted degradation of lipoprotein receptors.

    Science.gov (United States)

    Calkin, Anna C; Goult, Benjamin T; Zhang, Li; Fairall, Louise; Hong, Cynthia; Schwabe, John W R; Tontonoz, Peter

    2011-12-13

    The E3 ubiquitin ligase IDOL (inducible degrader of the LDL receptor) regulates LDL receptor (LDLR)-dependent cholesterol uptake, but its mechanism of action, including the molecular basis for its stringent specificity, is poorly understood. Here we show that IDOL uses a singular strategy among E3 ligases for target recognition. The IDOL FERM domain binds directly to a recognition sequence in the cytoplasmic tails of lipoprotein receptors. This physical interaction is independent of IDOL's really interesting new gene (RING) domain E3 ligase activity and its capacity for autoubiquitination. Furthermore, IDOL controls its own stability through autoubiquitination of a unique FERM subdomain fold not present in other FERM proteins. Key residues defining the IDOL-LDLR interaction and IDOL autoubiquitination are functionally conserved in their insect homologs. Finally, we demonstrate that target recognition by IDOL involves a tripartite interaction between the FERM domain, membrane phospholipids, and the lipoprotein receptor tail. Our data identify the IDOL-LDLR interaction as an evolutionarily conserved mechanism for the regulation of lipid uptake and suggest that this interaction could potentially be exploited for the pharmacologic modulation of lipid metabolism.

  20. Association of APOE (E2, E3 and E4) gene variants and lipid levels in ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian population.

    Science.gov (United States)

    Das, Satrupa; Kaul, Subhash; Jyothy, Akka; Munshi, Anjana

    2016-08-15

    In the present study we evaluated the association of APOE (E2/E3/E4) polymorphism with ischemic stroke (n=620), its subtypes and hemorrhagic stroke (n=250) in a South Indian population from Telangana. The genotypes were determined using PCR-RFLP while lipid levels were measured using commercially available kits. We found significant difference in the genotypic distribution between hemorrhagic stroke patients and controls for certain genetic models [E2/E2 vs. E2/E4; E3/E3 vs. E2/E3; E3/E3 vs. E2/E4; E4/E4 vs. E2/E3; E4/E4 vs.E2/E4 and E3 vs. E4]. However, no significant difference was observed in genotypic distribution between ischemic stroke patients and controls. On analysing the genotypic distribution between ischemic and hemorrhagic stroke patients, statistically significant difference was observed in specific genetic models [E2/E2 vs. E2/E4; E3/E3 vs. E2/E3; E3/E3 vs. E2/E4; E4/E4 vs. E2/E3 and E4/E4 vs. E2/E4]. In ischemic stroke subtypes analysing for alleles E3 vs. E2 and E3 vs. E4, we found significant association with intracranial large artery (p=0.01), cardioembolic stroke (p=0.001 and p=0.0004) and lacunar stroke (p=0.02). Analysing the association of various genotypes with different lipid levels significant association was observed for VLDL (P=0.000) and for triglyceride (P=0.000) levels with E2/E4 and E3/E4 genotypes in ischemic stroke but not in hemorrhagic stroke. In conclusion, our results suggest that APOE polymorphism does seem to play a role in hemorrhagic stroke and also in the development of specific subtypes of ischemic stroke. Further, in ischemic stroke VLDL and triglycerides levels were found to be significantly associated with E2/E4 and E3/E4 genotypes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Roles of the TRAF6 and Pellino E3 ligases in MyD88 and RANKL signaling.

    Science.gov (United States)

    Strickson, Sam; Emmerich, Christoph H; Goh, Eddy T H; Zhang, Jiazhen; Kelsall, Ian R; Macartney, Thomas; Hastie, C James; Knebel, Axel; Peggie, Mark; Marchesi, Francesco; Arthur, J Simon C; Cohen, Philip

    2017-04-25

    It is widely accepted that the essential role of TRAF6 in vivo is to generate the Lys63-linked ubiquitin (K63-Ub) chains needed to activate the "master" protein kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is not essential for the IL-1-dependent formation of K63-Ub chains, TAK1 activation, or IL-8 production in human cells, because Pellino1 and Pellino2 generate the K63-Ub chains required for signaling in cells expressing E3 ligase-inactive TRAF6 mutants. The IL-1-induced formation of K63-Ub chains and ubiquitylation of IRAK1, IRAK4, and MyD88 was abolished in TRAF6/Pellino1/Pellino2 triple-knockout (KO) cells, but not in TRAF6 KO or Pellino1/2 double-KO cells. The reexpression of E3 ligase-inactive TRAF6 mutants partially restored IL-1 signaling in TRAF6 KO cells, but not in TRAF6/Pellino1/Pellino2 triple-KO cells. Pellino1-generated K63-Ub chains activated the TAK1 complex in vitro with similar efficiently to TRAF6-generated K63-Ub chains. The early phase of TLR signaling and the TLR-dependent secretion of IL-10 (controlled by IRAKs 1 and 2) was only reduced modestly in primary macrophages from knockin mice expressing the E3 ligase-inactive TRAF6[L74H] mutant, but the late-phase production of IL-6, IL-12, and TNFα (controlled only by the pseudokinase IRAK2) was abolished. RANKL-induced signaling in macrophages and the differentiation of bone marrow to osteoclasts was similar in TRAF6[L74H] and wild-type cells, explaining why the bone structure and teeth of the TRAF6[L74H] mice was normal, unlike TRAF6 KO mice. We identify two essential roles of TRAF6 that are independent of its E3 ligase activity.

  2. Cyber Sentries: Preparing Defenders to Win in a Contested Domain

    Science.gov (United States)

    2012-02-07

    the deliberate shortcuts and unintentional errors that adversely impact Department networks. The workforce must develop a conviction to fight through...Brown, and Rodney R. Cocking , eds. with additional material from the Committee on Learning Research and Educational Practice and the Commission on

  3. 天然产物(E)-3,5-二甲氧基二苯乙烯的合成%Synthesis of Natural Product (E) - 3, 5 - Dimethoxystilbene

    Institute of Scientific and Technical Information of China (English)

    杨金会; 刘海军

    2007-01-01

    以价廉易得的3,5-二羟基苯甲酸为原料,通过甲基化、还原、溴代、Arbuzor重排、Wittig-Horner缩合5步反应完成了目标化合物(E)-3,5-二甲氧基二苯乙烯的合成,总收率高达59.8%,各步反应所合成化合物结构均通过1H NMR及熔点进行了结构确证.

  4. 76 FR 13926 - Airworthiness Directives; The Boeing Company Model DC-8-11, DC-8-12, DC-8-21, DC-8-31, DC-8-32...

    Science.gov (United States)

    2011-03-15

    ... center spar lower cap, which could compromise the structural integrity of the wing structure. DATES: We... report summarizing each substantive verbal contact we receive about this proposed AD. Discussion We... structural integrity of the wing structure. Relevant Service Information We have reviewed Boeing...

  5. Inactivation of SAG E3 ubiquitin ligase blocks embryonic stem cell differentiation and sensitizes leukemia cells to retinoid acid.

    Directory of Open Access Journals (Sweden)

    Mingjia Tan

    Full Text Available Sensitive to Apoptosis Gene (SAG, also known as RBX2 (RING box protein-2, is the RING component of SCF (SKP1, Cullin, and F-box protein E3 ubiquitin ligase. Our previous studies have demonstrated that SAG is an anti-apoptotic protein and an attractive anti-cancer target. We also found recently that Sag knockout sensitized mouse embryonic stem cells (mES to radiation and blocked mES cells to undergo endothelial differentiation. Here, we reported that compared to wild-type mES cells, the Sag(-/- mES cells were much more sensitive to all-trans retinoic acid (RA-induced suppression of cell proliferation and survival. While wild-type mES cells underwent differentiation upon exposure to RA, Sag(-/- mES cells were induced to death via apoptosis instead. The cell fate change, reflected by cellular stiffness, can be detected as early as 12 hrs post RA exposure by AFM (Atomic Force Microscopy. We then extended this novel finding to RA differentiation therapy of leukemia, in which the resistance often develops, by testing our hypothesis that SAG inhibition would sensitize leukemia to RA. Indeed, we found a direct correlation between SAG overexpression and RA resistance in multiple leukemia lines. By using MLN4924, a small molecule inhibitor of NEDD8-Activating Enzyme (NAE, that inactivates SAG-SCF E3 ligase by blocking cullin neddylation, we were able to sensitize two otherwise resistant leukemia cell lines, HL-60 and KG-1 to RA. Mechanistically, RA sensitization by MLN4924 was mediated via enhanced apoptosis, likely through accumulation of pro-apoptotic proteins NOXA and c-JUN, two well-known substrates of SAG-SCF E3 ligase. Taken together, our study provides the proof-of-concept evidence for effective treatment of leukemia patients by RA-MLN4924 combination.

  6. The Nedd4-like ubiquitin E3 ligases target angiomotin/p130 to ubiquitin-dependent degradation.

    Science.gov (United States)

    Wang, Chenji; An, Jian; Zhang, Pingzhao; Xu, Chen; Gao, Kun; Wu, Di; Wang, Dejie; Yu, Hongxiu; Liu, Jun O; Yu, Long

    2012-06-01

    AMOT (angiomotin) is a membrane-associated protein that is expressed in ECs (endothelial cells) and controls migration, TJ (tight junction) formation, cell polarity and angiogenesis. Recent studies have revealed that AMOT and two AMOT-like proteins, AMOTL1 and AMOTL2, play critical roles in the Hippo pathway by regulating the subcellular localization of the co-activators YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif). However, it has been unclear how AMOT is regulated. In the present study, we report that AMOT undergoes proteasomal degradation. We identify three members of Nedd4 (neural-precursor-cell-expressed developmentally down-regulated)-like ubiquitin E3 ligases, Nedd4, Nedd4-2 and Itch, as the ubiquitin E3 ligases for the long isoform of AMOT, AMOT/p130. We demonstrate that Nedd4, Nedd4-2 and Itch mediate poly-ubiquitination of AMOT/p130 in vivo. Overexpression of Nedd4, Nedd4-2 or Itch leads to AMOT/p130 proteasomal degradation. Knockdown of Nedd4, Nedd4-2 and Itch causes an accumulation of steady-state level of AMOT/p130. We also show that three L/P-PXY motifs of AMOT/p130 and the WW domains of Nedd4 mediate their interaction. Furthermore, Nedd4-like ubiquitin E3 ligases might compete with YAP for the binding to AMOT/p130, and subsequently targeting AMOT/p130 for ubiquitin-dependent degradation. Together, these observations reveal a novel post-translational regulatory mechanism of AMOT/p130.

  7. The Blue Light-Dependent Polyubiquitination and Degradation of Arabidopsis Cryptochrome2 Requires Multiple E3 Ubiquitin Ligases.

    Science.gov (United States)

    Liu, Qing; Wang, Qin; Liu, Bin; Wang, Wei; Wang, Xu; Park, Joon; Yang, Zhenming; Du, Xinglin; Bian, Mingdi; Lin, Chentao

    2016-10-01

    Cryptochromes are blue light receptors regulated by light-dependent ubiquitination and degradation in both plant and animal lineages. The Arabidopsis genome encodes two cryptochromes, CRY1 and CRY2, of which CRY2 undergoes blue light-dependent ubiquitination and 26S proteasome-dependent degradation. The molecular mechanism regulating blue light-dependent proteolysis of CRY2 is still not fully understood. We found that the F-box proteins ZEITLUPE (ZTL) and Lov Kelch Protein2 (LKP2), which mediate blue light suppression of degradation of the CRY2 signaling partner CIB1, are not required for the blue light-dependent CRY2 degradation. We further showed that the previously reported function of the COP1-SPA1 protein complex in blue light-dependent CRY2 degradation is more likely to be attributable to its cullin 4 (CUL4)-based E3 ubiquitin ligase activity than its activity as the cryptochrome signaling partner. However, the blue light-dependent CRY2 degradation is only partially impaired in the cul4 mutant, the cop1-5 null mutant and the spa1234 quadruple mutant, suggesting a possible involvement of additional E3 ubiquitin ligases in the regulation of CRY2. Consistent with this hypothesis, we demonstrated that the blue light-dependent CRY2 degradation is significantly impaired in the temperature-sensitive cul1 mutant allele (axr6-3), especially under the non-permissive temperature. Based on these and other results presented, we propose that photoexcited CRY2 undergoes Lys48-linked polyubiquitination catalyzed by the CUL4- and CUL1-based E3 ubiquitin ligases.

  8. A Sporadic Parkinson Disease Model via Silencing of the Ubiquitin-Proteasome/E3 Ligase Component SKP1A*

    OpenAIRE

    Fishman-Jacob, Tali; Reznichenko, Lydia; Youdim, Moussa B H; Mandel, Silvia A.

    2009-01-01

    The aim of this study was to develop a new model of sporadic Parkinson disease (PD) based on silencing of the SKP1A gene, a component of the ubiquitin-proteasome/E3 ligase complex, Skp1, Cullin 1, F-box protein, which was found to be highly decreased in the substantia nigra of sporadic PD patients. Initially, an embryonic mouse substantia nigra-derived cell line (SN4741 cells) was infected with short hairpin RNA lentiviruses encoding the murine transcript of the SKP1A gene or with scrambled v...

  9. Shigella IpaH7.8 E3 ubiquitin ligase targets glomulin and activates inflammasomes to demolish macrophages

    Science.gov (United States)

    Suzuki, Shiho; Mimuro, Hitomi; Kim, Minsoo; Ogawa, Michinaga; Ashida, Hiroshi; Toyotome, Takahito; Franchi, Luigi; Suzuki, Masato; Sanada, Takahito; Suzuki, Toshihiko; Tsutsui, Hiroko; Núñez, Gabriel; Sasakawa, Chihiro

    2014-01-01

    When nucleotide-binding oligomerization domain–like receptors (NLRs) sense cytosolic-invading bacteria, they induce the formation of inflammasomes and initiate an innate immune response. In quiescent cells, inflammasome activity is tightly regulated to prevent excess inflammation and cell death. Many bacterial pathogens provoke inflammasome activity and induce inflammatory responses, including cell death, by delivering type III secreted effectors, the rod component flagellin, and toxins. Recent studies indicated that Shigella deploy multiple mechanisms to stimulate NLR inflammasomes through type III secretion during infection. Here, we show that Shigella induces rapid macrophage cell death by delivering the invasion plasmid antigen H7.8 (IpaH7.8) enzyme 3 (E3) ubiquitin ligase effector via the type III secretion system, thereby activating the NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing 4 (NLRC4) inflammasomes and caspase-1 and leading to macrophage cell death in an IpaH7.8 E3 ligase-dependent manner. Mice infected with Shigella possessing IpaH7.8, but not with Shigella possessing an IpaH7.8 E3 ligase-null mutant, exhibited enhanced bacterial multiplication. We defined glomulin/flagellar-associated protein 68 (GLMN) as an IpaH7.8 target involved in IpaH7.8 E3 ligase-dependent inflammasome activation. This protein originally was identified through its association with glomuvenous malformations and more recently was described as a member of a Cullin ring ligase inhibitor. Modifying GLMN levels through overexpression or knockdown led to reduced or augmented inflammasome activation, respectively. Macrophages stimulated with lipopolysaccharide/ATP induced GLMN puncta that localized with the active form of caspase-1. Macrophages from GLMN+/− mice were more responsive to inflammasome activation than those from GLMN+/+ mice. Together, these results highlight a unique bacterial adaptation that hijacks inflammasome activation via

  10. Overexpression of denticleless E3 ubiquitin protein ligase homolog (DTL) is related to poor outcome in gastric carcinoma

    OpenAIRE

    Kobayashi, Hiroki; Komatsu, Shuhei; Ichikawa, Daisuke; Kawaguchi, Tsutomu; Hirajima, Shoji; Miyamae, Mahito; Okajima, Wataru; Ohashi, Takuma; Kosuga, Toshiyuki; Konishi, Hirotaka; Shiozaki, Atsushi; FUJIWARA, Hitoshi; Okamoto, Kazuma; Tsuda, Hitoshi; Otsuji, Eigo

    2015-01-01

    Background Denticleless E3 ubiquitin protein ligase homolog (DTL) has been identified in amplified region (1q32) of several cancers and has an oncogenic function. In this study, we tested whether DTL acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). Methods We analyzed 7 GC cell lines and 100 primary tumors that were curatively resected in our hospital between 2001 and 2003. Results Overexpression of the DTL protein was detected in GC cell lines (4/...

  11. RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex

    Science.gov (United States)

    Brown, Nicholas G.; VanderLinden, Ryan; Watson, Edmond R.; Qiao, Renping; Grace, Christy R. R.; Yamaguchi, Masaya; Weissmann, Florian; Frye, Jeremiah J.; Dube, Prakash; Ei Cho, Shein; Actis, Marcelo L.; Rodrigues, Patrick; Fujii, Naoaki; Peters, Jan-Michael; Stark, Holger; Schulman, Brenda A.

    2015-01-01

    For many E3 ligases, a mobile RING (Really Interesting New Gene) domain stimulates ubiquitin (Ub) transfer from a thioester-linked E2∼Ub intermediate to a lysine on a remotely bound disordered substrate. One such E3 is the gigantic, multisubunit 1.2-MDa anaphase-promoting complex/cyclosome (APC), which controls cell division by ubiquitinating cell cycle regulators to drive their timely degradation. Intrinsically disordered substrates are typically recruited via their KEN-box, D-box, and/or other motifs binding to APC and a coactivator such as CDH1. On the opposite side of the APC, the dynamic catalytic core contains the cullin-like subunit APC2 and its RING partner APC11, which collaborates with the E2 UBCH10 (UBE2C) to ubiquitinate substrates. However, how dynamic RING–E2∼Ub catalytic modules such as APC11–UBCH10∼Ub collide with distally tethered disordered substrates remains poorly understood. We report structural mechanisms of UBCH10 recruitment to APCCDH1 and substrate ubiquitination. Unexpectedly, in addition to binding APC11’s RING, UBCH10 is corecruited via interactions with APC2, which we visualized in a trapped complex representing an APCCDH1–UBCH10∼Ub–substrate intermediate by cryo-electron microscopy, and in isolation by X-ray crystallography. To our knowledge, this is the first structural view of APC, or any cullin–RING E3, with E2 and substrate juxtaposed, and it reveals how tripartite cullin–RING–E2 interactions establish APC’s specificity for UBCH10 and harness a flexible catalytic module to drive ubiquitination of lysines within an accessible zone. We propose that multisite interactions reduce the degrees of freedom available to dynamic RING E3–E2∼Ub catalytic modules, condense the search radius for target lysines, increase the chance of active-site collision with conformationally fluctuating substrates, and enable regulation. PMID:25825779

  12. E3 Charter Template

    Science.gov (United States)

    This is a charter template which includes decisions made during the project planning phase, as well as local project goals, a communication strategy, an outreach strategy, distribution of responsibilities and a schedule.

  13. Real-space characterization of reactivity towards water at the B i2T e3 (111) surface

    Science.gov (United States)

    Zhang, Kai-Wen; Ding, Ding; Yang, Chao-Long; Gan, Yuan; Li, Shichao; Huang, Wen-Kai; Song, Ye-Heng; Jia, Zhen-Yu; Li, Xiang-Bing; Zhu, Zihua; Wen, Jinsheng; Chen, Mingshu; Li, Shao-Chun

    2016-06-01

    Surface reactivity is important in modifying the physical and chemical properties of surface-sensitive materials, such as the topological insulators. Even though many studies addressing the reactivity of topological insulators towards external gases have been reported, it is still under heavy debate whether and how the topological insulators react with H2O . Here, we employ scanning tunneling microscopy to directly probe the surface reaction of B i2T e3 towards H2O . Surprisingly, it is found that only the top quintuple layer is reactive to H2O , resulting in a hydrated Bi bilayer as well as some Bi islands, which passivate the surface and prevent subsequent reaction. A reaction mechanism is proposed with H2Te and hydrated Bi as the products. Unexpectedly, our study indicates that the reaction with water is intrinsic and not dependent on any surface defects. Since water inevitably exists, these findings provide key information when considering the reactions of B i2T e3 with residual gases or atmosphere.

  14. Sequence analysis of the E3 region and fiber gene of human adenovirus genome type 7h.

    Science.gov (United States)

    Kajon, A E; Wadell, G

    1996-01-15

    Adenovirus type 7h is currently the predominant virulent genome type of serotype 7 isolated in Argentina, Chile, and Uruguay in association with severe infantile pneumonia. In order to characterize possible molecular determinants of pathogenicity, the nucleotide sequence of a 5904-bp fragment (76 to 93 mu) containing the entire E3 region and the fiber gene of Ad7h was established. The organization of the ORFs within the E3 region was similar to that reported for the prototype strains of Ad7 and Ad3. A comparison of the nucleotide and amino acid sequences of all ORFs revealed a higher homology between Ad7h and Ad7p than between Ad7h and Ad3 for 12.0K and 16.1K, whereas the 15.3K ORF and the adjacent fiber gene were strikingly more homologous to those of Ad3 (99.5 vs 81.1% and 98.2 vs 66.6%, respectively). The equivalent to ORF 7.7K in Ad7p was missing in Ad7h due to a deletion and a mutation affecting the start codon (ATG-->ATT). Although the hemagglutinin of the Ad7h fiber could not be characterized due to its lack of activity on monkey erythrocytes, our results indicate that Ad7h is an intermediate strain 7-3.

  15. Iron-binding E3 ligase mediates iron response in plants by targeting basic helix-loop-helix transcription factors.

    Science.gov (United States)

    Selote, Devarshi; Samira, Rozalynne; Matthiadis, Anna; Gillikin, Jeffrey W; Long, Terri A

    2015-01-01

    Iron uptake and metabolism are tightly regulated in both plants and animals. In Arabidopsis (Arabidopsis thaliana), BRUTUS (BTS), which contains three hemerythrin (HHE) domains and a Really Interesting New Gene (RING) domain, interacts with basic helix-loop-helix transcription factors that are capable of forming heterodimers with POPEYE (PYE), a positive regulator of the iron deficiency response. BTS has been shown to have E3 ligase capacity and to play a role in root growth, rhizosphere acidification, and iron reductase activity in response to iron deprivation. To further characterize the function of this protein, we examined the expression pattern of recombinant ProBTS::β-GLUCURONIDASE and found that it is expressed in developing embryos and other reproductive tissues, corresponding with its apparent role in reproductive growth and development. Our findings also indicate that the interactions between BTS and PYE-like (PYEL) basic helix-loop-helix transcription factors occur within the nucleus and are dependent on the presence of the RING domain. We provide evidence that BTS facilitates 26S proteasome-mediated degradation of PYEL proteins in the absence of iron. We also determined that, upon binding iron at the HHE domains, BTS is destabilized and that this destabilization relies on specific residues within the HHE domains. This study reveals an important and unique mechanism for plant iron homeostasis whereby an E3 ubiquitin ligase may posttranslationally control components of the transcriptional regulatory network involved in the iron deficiency response.

  16. Ezrin ubiquitylation by the E3 ubiquitin ligase, WWP1, and consequent regulation of hepatocyte growth factor receptor activity.

    Directory of Open Access Journals (Sweden)

    Rania F Zaarour

    Full Text Available The membrane cytoskeleton linker ezrin participates in several functions downstream of the receptor Met in response to Hepatocyte Growth Factor (HGF stimulation. Here we report a novel interaction of ezrin with a HECT E3 ubiquitin ligase, WWP1/Aip5/Tiul1, a potential oncogene that undergoes genomic amplification and overexpression in human breast and prostate cancers. We show that ezrin binds to the WW domains of WWP1 via the consensus motif PPVY(477 present in ezrin's C-terminus. This association results in the ubiquitylation of ezrin, a process that requires an intact PPVY(477 motif. Interestingly ezrin ubiquitylation does not target the protein for degradation by the proteasome. We find that ezrin ubiquitylation by WWP1 in epithelial cells leads to the upregulation of Met level in absence of HGF stimulation and increases the response of Met to HGF stimulation as measured by the ability of the cells to heal a wound. Interestingly this effect requires ubiquitylated ezrin since it can be rescued, after depletion of endogenous ezrin, by wild type ezrin but not by a mutant of ezrin that cannot be ubiquitylated. Taken together our data reveal a new role for ezrin in Met receptor stability and activity through its association with the E3 ubiquitin ligase WWP1. Given the role of Met in cell proliferation and tumorigenesis, our results may provide a mechanistic basis for understanding the role of ezrin in tumor progression.

  17. The E3 Ubiquitin Ligase SCF(Cyclin F) Transmits AKT Signaling to the Cell-Cycle Machinery.

    Science.gov (United States)

    Choudhury, Rajarshi; Bonacci, Thomas; Wang, Xianxi; Truong, Andrew; Arceci, Anthony; Zhang, Yanqiong; Mills, Christine A; Kernan, Jennifer L; Liu, Pengda; Emanuele, Michael J

    2017-09-26

    The oncogenic AKT kinase is a key regulator of apoptosis, cell growth, and cell-cycle progression. Despite its important role in proliferation, it remains largely unknown how AKT is mechanistically linked to the cell cycle. We show here that cyclin F, a substrate receptor F-box protein for the SCF (Skp1/Cul1/F-box) family of E3 ubiquitin ligases, is a bona fide AKT substrate. Cyclin F expression oscillates throughout the cell cycle, a rare feature among the 69 human F-box proteins, and all of its known substrates are involved in proliferation. AKT phosphorylation of cyclin F enhances its stability and promotes assembly into productive E3 ligase complexes. Importantly, expression of mutant versions of cyclin F that cannot be phosphorylated by AKT impair cell-cycle entry. Our data suggest that cyclin F transmits mitogen signaling through AKT to the core cell-cycle machinery. This discovery has potential implications for proliferative control in malignancies where AKT is activated. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. The U-Box/ARM E3 ligase PUB13 regulates cell death, defense, and flowering time in Arabidopsis.

    Science.gov (United States)

    Li, Wei; Ahn, Il-Pyung; Ning, Yuese; Park, Chan-Ho; Zeng, Lirong; Whitehill, Justin G A; Lu, Haibin; Zhao, Qingzhen; Ding, Bo; Xie, Qi; Zhou, Jian-Min; Dai, Liangying; Wang, Guo-Liang

    2012-05-01

    The components in plant signal transduction pathways are intertwined and affect each other to coordinate plant growth, development, and defenses to stresses. The role of ubiquitination in connecting these pathways, particularly plant innate immunity and flowering, is largely unknown. Here, we report the dual roles for the Arabidopsis (Arabidopsis thaliana) Plant U-box protein13 (PUB13) in defense and flowering time control. In vitro ubiquitination assays indicated that PUB13 is an active E3 ubiquitin ligase and that the intact U-box domain is required for the E3 ligase activity. Disruption of the PUB13 gene by T-DNA insertion results in spontaneous cell death, the accumulation of hydrogen peroxide and salicylic acid (SA), and elevated resistance to biotrophic pathogens but increased susceptibility to necrotrophic pathogens. The cell death, hydrogen peroxide accumulation, and resistance to necrotrophic pathogens in pub13 are enhanced when plants are pretreated with high humidity. Importantly, pub13 also shows early flowering under middle- and long-day conditions, in which the expression of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 and FLOWERING LOCUS T is induced while FLOWERING LOCUS C expression is suppressed. Finally, we found that two components involved in the SA-mediated signaling pathway, SID2 and PAD4, are required for the defense and flowering-time phenotypes caused by the loss of function of PUB13. Taken together, our data demonstrate that PUB13 acts as an important node connecting SA-dependent defense signaling and flowering time regulation in Arabidopsis.

  19. The Salmonella Effector Protein SopA Modulates Innate Immune Responses by Targeting TRIM E3 Ligase Family Members.

    Directory of Open Access Journals (Sweden)

    Jana Kamanova

    2016-04-01

    Full Text Available Salmonella Typhimurium stimulates inflammatory responses in the intestinal epithelium, which are essential for its ability to replicate within the intestinal tract. Stimulation of these responses is strictly dependent on the activity of a type III secretion system encoded within its pathogenicity island 1, which through the delivery of effector proteins, triggers signaling pathways leading to inflammation. One of these effectors is SopA, a HECT-type E3 ligase, which is required for the efficient stimulation of inflammation in an animal model of Salmonella Typhimurium infection. We show here that SopA contributes to the stimulation of innate immune responses by targeting two host E3 ubiquitin ligases, TRIM56 and TRIM65. We also found that TRIM65 interacts with the innate immune receptor MDA5 enhancing its ability to stimulate interferon-β signaling. Therefore, by targeting TRIM56 and TRIM65, SopA can stimulate signaling through two innate immune receptors, RIG-I and MDA5. These findings describe a Salmonella mechanism to modulate inflammatory responses by directly targeting innate immune signaling mechanisms.

  20. Analysis on ATC Problems of Boeing 737NG Airplane%波音737NG飞机ATC FAIL故障浅析

    Institute of Scientific and Technical Information of China (English)

    罗康

    2015-01-01

    The occurrence frequency of ATC problems of Boeing 737NG Airplane is high in the running, as it cooperated with TCAS, it has great obstacles of the airplane’s normal operation and flight delay. This paper will analyze the fail of ACT.%波音737NG飞机在运行中经常会出现ATC FAIL故障,由于该系统牵涉到飞机的防撞系统,对飞机的正常运行产生很大的影响,引起航班延误,本文对该故障现象进行浅析。

  1. Status and test report on the LANL-Boeing APLE/HPO flying-wire beam-profile monitor. Status report

    Energy Technology Data Exchange (ETDEWEB)

    Wilke, M.; Barlow, D.; Fortgang, C.; Gilpatrick, J.; Meyer, R.; Rendon, A.; Warren, D. [Los Alamos National Lab., NM (United States); Greegor, R. [Boeing Co., Seattle, WA (United States)

    1994-07-01

    The High-Power Oscillator (HPO) demonstration of the Average Power Laser Experiment (APLE) is a collaboration by Los Alamos National Laboratory and Boeing to demonstrate a 10 kW average power, 10 {mu}m free electron laser (FEL). As part of the collaboration, Los Alamos National Laboratory (LANL) is responsible for many of the electron beam diagnostics in the linac, transport, and laser sections. Because of the high duty factor and power of the electron beam, special diagnostics are required. This report describes the flying wire diagnostic required to monitor the beam profile during high-power, high-duty operation. The authors describe the diagnostic and prototype tests on the Los Alamos APLE Prototype Experiment (APEX) FEL. They also describe the current status of the flying wires being built for APLE.

  2. Reductions in biomarkers of exposure (BoE) to harmful or potentially harmful constituents (HPHCs) following partial or complete substitution of cigarettes with electronic cigarettes in adult smokers

    Science.gov (United States)

    O’Connell, Grant; Graff, Donald W.; D’Ruiz, Carl D.

    2016-01-01

    Abstract Changes in fifteen urine, blood and exhaled breath BoEs of HPHCs representing classes of compounds reported by FDA to be significant contributors to smoking-associated disease risks were measured in 105 clinical-confined subjects following randomization and a five-day forced-switch from usual brand conventional combustible cigarettes to: (i) exclusive commercial e-cigarette use; (ii) dual-use of commercial e-cigarettes and the subject’s usual cigarette brand; or (iii) discontinued use of all tobacco or nicotine products. Levels of urinary biomarkers in subjects that completely substituted their usual cigarette with e-cigarettes were significantly lower (29–95%) after 5 days. Percent reductions in eight of nine urinary BoEs were indistinguishable to smokers who had quit smoking, except for nicotine equivalents, which declined by 25–40%. Dual users who halved self-reported daily cigarette consumption with e-cigarettes exhibited reductions (7–38%) in eight of nine urinary biomarkers, but had increase (1–20%) in nicotine equivalents. Reductions were broadly proportional to the reduced numbers of cigarettes smoked. Dual user urinary nicotine equivalents were slightly higher, but not statistically significant. After 5 days, blood nicotine biomarker levels were lower in the cessation (75–96%) and exclusive use groups (11–83%); with dual users experiencing no significant reductions. All subjects experienced significant decreases in exhaled CO. Decreases in the cessation and exclusive groups ranged from 88–89% and 27–32% in dual users. Exhaled NO increased in the cessation and exclusive groups (46–63% respectively), whereas the dual users experienced minimal changes. Overall, smokers who completely or partially substituted conventional cigarettes with e-cigarettes over five days, experienced reductions in HPHCs. PMID:27401591

  3. 基于E^3-Value的服务供应链运作管理流程和方法%E^3-value based operation management process and method for service supply chain

    Institute of Scientific and Technical Information of China (English)

    何霆; 徐晓飞; 金铮

    2011-01-01

    目前尽管存在较多以产品为中心的供应链运作管理流程和方法,但在服务供应链领域,由于服务不同于产品的诸多特性局限了其进一步的应用。因此,采用结构化分析思想和方法,提出了基于E3-value的服务供应链运作管理逻辑流程和方法,该方法以价值为导向,不但可以解决现有供应链运作管理模式的一些适应性问题,而且能够解决"供应链运作管理模式为什么是这样,潜在盈利性如何量化"问题。%There were extensive product-centered supply chain operation management processes and methods at present.In Service Supply Chain(SSC) domain,these methods and processes did not have further application due to the differences between service and product.For above reasons,by using analytic technique of structuring,E3-value based operation management logistic process and method for SSC were proposed.This value oriented method could not only resolve the problems of applicability and effectiveness of the existing supply chain management models and methods,but answer the questions of "why the management model is like this?" and "how to quantify the potential profitability of the supply chains?"

  4. [Physiological and biochemical properties of the bacterial association of Klebsiella terrigena E6 and Bacillus firmus E3].

    Science.gov (United States)

    Zlotnikov, A K; Kazakov, M L; Zlotnikov, K M; Kazakov, A V; Umarov, M M

    2007-01-01

    Physiological and biochemical properties of the natural rhizospheric association of Klebsiella terrigena E6 and Bacillusfirmus E3 were studied. It was demonstrated that this association fixed actively molecular nitrogen at a rate of 110 nmol ethylene per 1 mg protein per h. The dynamics of bacterial population in the association and in pure cultures were studied. The properties of this association depended on the ratio of its components; the maximal nitrogen fixation was recorded at a content of B. firmus E310 amounting to 15% of the total cell number. It was demonstrated that the stability basis of this association was the specific interactions via its components via metabolites--phenol and para-hydroxybenzoic acid--as well as via nitrogen fixation, respiration, and pH of the medium. A scheme of the interactions between the components of association is shown.

  5. Crystal structure of the substrate-recognition domain of the Shigella E3 ligase IpaH9.8.

    Science.gov (United States)

    Takagi, Kenji; Kim, Minsoo; Sasakawa, Chihiro; Mizushima, Tsunehiro

    2016-04-01

    Infectious diseases caused by bacteria have significant impacts on global public health. During infection, pathogenic bacteria deliver a variety of virulence factors, called effectors, into host cells. The Shigella effector IpaH9.8 functions as an ubiquitin ligase, ubiquitinating the NF-κB essential modulator (NEMO)/IKK-γ to inhibit host inflammatory responses. IpaH9.8 contains leucine-rich repeats (LRRs) involved in substrate recognition and an E3 ligase domain. To elucidate the structural basis of the function of IpaH9.8, the crystal structure of the LRR domain of Shigella IpaH9.8 was determined and this structure was compared with the known structures of other IpaH family members. This model provides insights into the structural features involved in substrate specificity.

  6. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1.

    Science.gov (United States)

    Bodine, Sue C; Baehr, Leslie M

    2014-09-15

    Muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1 were identified more than 10 years ago as two muscle-specific E3 ubiquitin ligases that are increased transcriptionally in skeletal muscle under atrophy-inducing conditions, making them excellent markers of muscle atrophy. In the past 10 years much has been published about MuRF1 and MAFbx with respect to their mRNA expression patterns under atrophy-inducing conditions, their transcriptional regulation, and their putative substrates. However, much remains to be learned about the physiological role of both genes in the regulation of mass and other cellular functions in striated muscle. Although both MuRF1 and MAFbx are enriched in skeletal, cardiac, and smooth muscle, this review will focus on the current understanding of MuRF1 and MAFbx in skeletal muscle, highlighting the critical questions that remain to be answered.

  7. Structure of the Siz/PIAS SUMO E3 Ligase Siz1 and Determinants Required for SUMO Modification of PCNA

    Energy Technology Data Exchange (ETDEWEB)

    Yunus, Ali A.; Lima, Christopher D.; (SKI)

    2010-01-12

    Siz1 is a founding member of the Siz/PIAS RING family of SUMO E3 ligases. The X-ray structure of an active Siz1 ligase revealed an elongated tripartite architecture comprised of an N-terminal PINIT domain, a central zinc-containing RING-like SP-RING domain, and a C-terminal domain we term the SP-CTD. Structure-based mutational analysis and biochemical studies show that the SP-RING and SP-CTD are required for activation of the E2SUMO thioester, while the PINIT domain is essential for redirecting SUMO conjugation to the proliferating cell nuclear antigen (PCNA) at lysine 164, a nonconsensus lysine residue that is not modified by the SUMO E2 in the absence of Siz1. Mutational analysis of Siz1 and PCNA revealed surfaces on both proteins that are required for efficient SUMO modification of PCNA in vitro and in vivo.

  8. Search for heavy top quark partners with charge 5e/3 in the single lepton final state

    Science.gov (United States)

    Sagir, Sinan; CMS Collaboration

    2016-03-01

    A search is presented for a very heavy fermionic partner of the top quark with charge 5e/3 (X5 / 3), which is expected to decay into a top quark and a W boson. Events consistent with pair production of X5 / 3, where one of the four W bosons from the decays of X5 / 3 and top quarks decays leptonically, and all the other W bosons decay hadronically, are analyzed. The results from this semi-leptonic final state are then combined with same-sign dileptons signature to enhance the sensitivity. No excess of data above SM expectations is observed and 95 % CL upper limits on the X5 / 3 production cross section are set using the data corresponding to an integrated luminosity of 2.2 fb-1 collected by the CMS detector at center-of-mass energy of 13 TeV.

  9. Ubiquitylation of FACT by the cullin-E3 ligase Rtt101 connects FACT to DNA replication.

    Science.gov (United States)

    Han, Junhong; Li, Qing; McCullough, Laura; Kettelkamp, Charisse; Formosa, Tim; Zhang, Zhiguo

    2010-07-15

    FACT plays important roles in both gene transcription and DNA replication. However, how this protein complex is targeted to these two distinct cellular processes remains largely unknown. Here we show that ubiquitylation of the Spt16 subunit of FACT by Rtt101, the cullin subunit of an E3 ubiquitin ligase in Saccharomyces cerevisiae, links FACT to DNA replication. We find Rtt101 interacts with and ubiquitylates Spt16 in vitro and in vivo. Deletion of RTT101 leads to reduced association of both FACT and the replicative helicase MCM with replication origins. Loss of Rtt101 also reduces binding of FACT to MCM, but not the association of FACT with Leo1 and Spt5, two proteins involved in transcription. Origin function is compromised in cells lacking Rtt101 or with an Spt16 mutation. These findings identify Spt16 as an Rtt101 substrate, and suggest that Spt16 ubiquitylation is important for FACT to function during DNA replication.

  10. Sustainable energy development in Austria until 2020: Insights from applying the integrated model “e3.at”

    Science.gov (United States)

    Stocker, Andrea; Großmann, Anett; Madlener, Reinhard; Wolter, Marc Ingo

    2011-01-01

    This paper reports on the Austrian research project “Renewable energy in Austria: Modeling possible development trends until 2020”. The project investigated possible economic and ecological effects of a substantially increased use of renewable energy sources in Austria. Together with stakeholders and experts, three different scenarios were defined, specifying possible development trends for renewable energy in Austria. The scenarios were simulated for the period 2006–2020, using the integrated environment–energy–economy model “e3.at”. The modeling results indicate that increasing the share of renewable energy sources in total energy use is an important but insufficient step towards achieving a sustainable energy system in Austria. A substantial increase in energy efficiency and a reduction of residential energy consumption also form important cornerstones of a sustainable energy policy. PMID:21976785

  11. (E-3,4,5-Trimethoxy-N′-[(4-oxo-4H-chromen-3-ylmethylidene]benzohydrazide

    Directory of Open Access Journals (Sweden)

    Yoshinobu Ishikawa

    2014-04-01

    Full Text Available In the title chromone-tethered benzohydrazide derivative, C20H18N2O6, the atoms of the E-3-(hydrazonomethyl-4H-chromen-4-one segment are essentially coplanar, the largest deviation being 0.065 (6 Å. The dihedral angle between this segment and the benzene ring of the trimethoxybenzene unit is 40.18 (10 Å. In the crystal, the molecule is linked to its inverse-symmetry equivalent by pairs of N—H...O hydrogen bonds and C—H...π interactions. The –CH=N—NH– segment is stacked on the benzene ring of the chromone unit of a translation-related equivalent molecule [centroid–centroid distance = 3.413 (6 Å].

  12. Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one.

    Science.gov (United States)

    Bouley, Renee; Kumarasiri, Malika; Peng, Zhihong; Otero, Lisandro H; Song, Wei; Suckow, Mark A; Schroeder, Valerie A; Wolter, William R; Lastochkin, Elena; Antunes, Nuno T; Pi, Hualiang; Vakulenko, Sergei; Hermoso, Juan A; Chang, Mayland; Mobashery, Shahriar

    2015-02-11

    In the face of the clinical challenge posed by resistant bacteria, the present needs for novel classes of antibiotics are genuine. In silico docking and screening, followed by chemical synthesis of a library of quinazolinones, led to the discovery of (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one (compound 2) as an antibiotic effective in vivo against methicillin-resistant Staphylococcus aureus (MRSA). This antibiotic impairs cell-wall biosynthesis as documented by functional assays, showing binding of 2 to penicillin-binding protein (PBP) 2a. We document that the antibiotic also inhibits PBP1 of S. aureus, indicating a broad targeting of structurally similar PBPs by this antibiotic. This class of antibiotics holds promise in fighting MRSA infections.

  13. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1

    Science.gov (United States)

    Baehr, Leslie M.

    2014-01-01

    Muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1 were identified more than 10 years ago as two muscle-specific E3 ubiquitin ligases that are increased transcriptionally in skeletal muscle under atrophy-inducing conditions, making them excellent markers of muscle atrophy. In the past 10 years much has been published about MuRF1 and MAFbx with respect to their mRNA expression patterns under atrophy-inducing conditions, their transcriptional regulation, and their putative substrates. However, much remains to be learned about the physiological role of both genes in the regulation of mass and other cellular functions in striated muscle. Although both MuRF1 and MAFbx are enriched in skeletal, cardiac, and smooth muscle, this review will focus on the current understanding of MuRF1 and MAFbx in skeletal muscle, highlighting the critical questions that remain to be answered. PMID:25096180

  14. PUB13, a U-box/ARM E3 ligase, regulates plant defense, cell death, and flowering time.

    Science.gov (United States)

    Li, Wei; Dai, Liangying; Wang, Guo-Liang

    2012-08-01

    The ubiquitination pathway is involved in a variety of cellular processes in plant growth, development, and immune responses. However, the function of this pathway in connecting plant development and innate immunity is still largely unknown. Recently, we characterized the U-box/ARM E3 ubiquitin ligase PUB13, which regulates both immune responses and flowering time in Arabidopsis. Here, we show that the rice Spl11 gene can complement the cell death and flowering functions of PUB13 in the pub13 mutant. In addition, HFR1, which functions mainly in photomorphogenesis, was identified as one of the PUB13-interacting proteins through yeast two-hybrid screening and pull-down assays. Because the flowering phenotype of pub13 depends on photoperiod, we propose that PUB13 may regulate HFR1 to fine-tune photomorphogenesis and flowering time in Arabidopsis.

  15. A sporadic Parkinson disease model via silencing of the ubiquitin-proteasome/E3 ligase component SKP1A.

    Science.gov (United States)

    Fishman-Jacob, Tali; Reznichenko, Lydia; Youdim, Moussa B H; Mandel, Silvia A

    2009-11-20

    The aim of this study was to develop a new model of sporadic Parkinson disease (PD) based on silencing of the SKP1A gene, a component of the ubiquitin-proteasome/E3 ligase complex, Skp1, Cullin 1, F-box protein, which was found to be highly decreased in the substantia nigra of sporadic PD patients. Initially, an embryonic mouse substantia nigra-derived cell line (SN4741 cells) was infected with short hairpin RNA lentiviruses encoding the murine transcript of the SKP1A gene or with scrambled vector. SKP1A silencing resulted in increased susceptibility to neuronal damages induced by the parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium ion and serum starvation, in parallel with a decline in the expression of the dopaminergic markers, dopamine transporter and vesicular monoamine transporter-2. SKP1A-deficient cells presented a delay in completion of the cell cycle and the inability to arrest at the G(0)/G(1) phase when induced to differentiate. Instead, the cells progressed through S phase, developing rounded aggregates with characteristics of aggresomes including immunoreactivity for gamma-tubulin, alpha-synuclein, ubiquitin, tyrosine hydroxylase, Hsc-70 (70-kDa heat shock cognate protein), and proteasome subunit, and culminating in a lethal phenotype. Conversely, stably enforced expression of wild type SKP1A duplicated the survival index of naïve SN4741 cells under proteasomal inhibition injury, suggesting a new structural role of SKP1 in dopaminergic neuronal function, besides its E3 ligase activity. These results link, for the first time, SKP1 to dopamine neuronal function and survival, suggesting an essential role in sporadic PD. In summary, this new model has reproduced to a significant extent the molecular alterations described in sporadic PD at the cellular level, implicating Skp1 as a potential modifier in sporadic PD neurodegeneration.

  16. A Sporadic Parkinson Disease Model via Silencing of the Ubiquitin-Proteasome/E3 Ligase Component SKP1A*

    Science.gov (United States)

    Fishman-Jacob, Tali; Reznichenko, Lydia; Youdim, Moussa B. H.; Mandel, Silvia A.

    2009-01-01

    The aim of this study was to develop a new model of sporadic Parkinson disease (PD) based on silencing of the SKP1A gene, a component of the ubiquitin-proteasome/E3 ligase complex, Skp1, Cullin 1, F-box protein, which was found to be highly decreased in the substantia nigra of sporadic PD patients. Initially, an embryonic mouse substantia nigra-derived cell line (SN4741 cells) was infected with short hairpin RNA lentiviruses encoding the murine transcript of the SKP1A gene or with scrambled vector. SKP1A silencing resulted in increased susceptibility to neuronal damages induced by the parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium ion and serum starvation, in parallel with a decline in the expression of the dopaminergic markers, dopamine transporter and vesicular monoamine transporter-2. SKP1A-deficient cells presented a delay in completion of the cell cycle and the inability to arrest at the G0/G1 phase when induced to differentiate. Instead, the cells progressed through S phase, developing rounded aggregates with characteristics of aggresomes including immunoreactivity for γ-tubulin, α-synuclein, ubiquitin, tyrosine hydroxylase, Hsc-70 (70-kDa heat shock cognate protein), and proteasome subunit, and culminating in a lethal phenotype. Conversely, stably enforced expression of wild type SKP1A duplicated the survival index of naïve SN4741 cells under proteasomal inhibition injury, suggesting a new structural role of SKP1 in dopaminergic neuronal function, besides its E3 ligase activity. These results link, for the first time, SKP1 to dopamine neuronal function and survival, suggesting an essential role in sporadic PD. In summary, this new model has reproduced to a significant extent the molecular alterations described in sporadic PD at the cellular level, implicating Skp1 as a potential modifier in sporadic PD neurodegeneration. PMID:19748892

  17. HDAC7 Ubiquitination by the E3 Ligase CBX4 Is Involved in Contextual Fear Conditioning Memory Formation.

    Science.gov (United States)

    Jing, Xu; Sui, Wen-Hai; Wang, Shuai; Xu, Xu-Feng; Yuan, Rong-Rong; Chen, Xiao-Rong; Ma, Hui-Xian; Zhu, Ying-Xiao; Sun, Jin-Kai; Yi, Fan; Chen, Zhe-Yu; Wang, Yue

    2017-04-05

    Histone acetylation, an epigenetic modification, plays an important role in long-term memory formation. Recently, histone deacetylase (HDAC) inhibitors were demonstrated to promote memory formation, which raises the intriguing possibility that they may be used to rescue memory deficits. However, additional research is necessary to clarify the roles of individual HDACs in memory. In this study, we demonstrated that HDAC7, within the dorsal hippocampus of C57BL6J mice, had a late and persistent decrease after contextual fear conditioning (CFC) training (4-24 h), which was involved in long-term CFC memory formation. We also showed that HDAC7 decreased via ubiquitin-dependent degradation. CBX4 was one of the HDAC7 E3 ligases involved in this process. Nur77, as one of the target genes of HDAC7, increased 6-24 h after CFC training and, accordingly, modulated the formation of CFC memory. Finally, HDAC7 was involved in the formation of other hippocampal-dependent memories, including the Morris water maze and object location test. The current findings facilitate an understanding of the molecular and cellular mechanisms of HDAC7 in the regulation of hippocampal-dependent memory.SIGNIFICANCE STATEMENT The current findings demonstrated the effects of histone deacetylase 7 (HDAC7) on hippocampal-dependent memories. Moreover, we determined the mechanism of decreased HDAC7 in contextual fear conditioning (CFC) through ubiquitin-dependent protein degradation. We also verified that CBX4 was one of the HDAC7 E3 ligases. Finally, we demonstrated that Nur77, as one of the important targets for HDAC7, was involved in CFC memory formation. All of these proteins, including HDAC7, CBX4, and Nur77, could be potential therapeutic targets for preventing memory deficits in aging and neurological diseases. Copyright © 2017 the authors 0270-6474/17/373848-16$15.00/0.

  18. UBR-5, a Conserved HECT-Type E3 Ubiquitin Ligase, Negatively Regulates Notch-Type Signaling in Caenorhabditis elegans

    Science.gov (United States)

    Safdar, Komal; Gu, Anniya; Xu, Xia; Au, Vinci; Taylor, Jon; Flibotte, Stephane; Moerman, Donald G.; Maine, Eleanor M.

    2016-01-01

    Notch-type signaling mediates cell−cell interactions important for animal development. In humans, reduced or inappropriate Notch signaling activity is associated with various developmental defects and disease states, including cancers. Caenorhabditis elegans expresses two Notch-type receptors, GLP-1 and LIN-12. GLP-1 mediates several cell-signaling events in the embryo and promotes germline proliferation in the developing and adult gonad. LIN-12 acts redundantly with GLP-1 in certain inductive events in the embryo and mediates several cell−cell interactions during larval development. Recovery of genetic suppressors and enhancers of glp-1 or lin-12 loss- or gain-of-function mutations has identified numerous regulators of GLP-1 and LIN-12 signaling activity. Here, we report the molecular identification of sog-1, a gene identified in screens for recessive suppressors of conditional glp-1 loss-of-function mutations. The sog-1 gene encodes UBR-5, the sole C. elegans member of the UBR5/Hyd family of HECT-type E3 ubiquitin ligases. Molecular and genetic analyses indicate that the loss of ubr-5 function suppresses defects caused by reduced signaling via GLP-1 or LIN-12. In contrast, ubr-5 mutations do not suppress embryonic or larval lethality associated with mutations in a downstream transcription factor, LAG-1. In the gonad, ubr-5 acts in the receiving cells (germ cells) to limit GLP-1 signaling activity. SEL-10 is the F-box component of SCFSEL-10 E3 ubiquitin–ligase complex that promotes turnover of Notch intracellular domain. UBR-5 acts redundantly with SEL-10 to limit Notch signaling in certain tissues. We hypothesize that UBR-5 activity limits Notch-type signaling by promoting turnover of receptor or limiting its interaction with pathway components. PMID:27185398

  19. UBR-5, a Conserved HECT-Type E3 Ubiquitin Ligase, Negatively Regulates Notch-Type Signaling in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Komal Safdar

    2016-07-01

    Full Text Available Notch-type signaling mediates cell−cell interactions important for animal development. In humans, reduced or inappropriate Notch signaling activity is associated with various developmental defects and disease states, including cancers. Caenorhabditis elegans expresses two Notch-type receptors, GLP-1 and LIN-12. GLP-1 mediates several cell-signaling events in the embryo and promotes germline proliferation in the developing and adult gonad. LIN-12 acts redundantly with GLP-1 in certain inductive events in the embryo and mediates several cell−cell interactions during larval development. Recovery of genetic suppressors and enhancers of glp-1 or lin-12 loss- or gain-of-function mutations has identified numerous regulators of GLP-1 and LIN-12 signaling activity. Here, we report the molecular identification of sog-1, a gene identified in screens for recessive suppressors of conditional glp-1 loss-of-function mutations. The sog-1 gene encodes UBR-5, the sole C. elegans member of the UBR5/Hyd family of HECT-type E3 ubiquitin ligases. Molecular and genetic analyses indicate that the loss of ubr-5 function suppresses defects caused by reduced signaling via GLP-1 or LIN-12. In contrast, ubr-5 mutations do not suppress embryonic or larval lethality associated with mutations in a downstream transcription factor, LAG-1. In the gonad, ubr-5 acts in the receiving cells (germ cells to limit GLP-1 signaling activity. SEL-10 is the F-box component of SCFSEL-10 E3 ubiquitin–ligase complex that promotes turnover of Notch intracellular domain. UBR-5 acts redundantly with SEL-10 to limit Notch signaling in certain tissues. We hypothesize that UBR-5 activity limits Notch-type signaling by promoting turnover of receptor or limiting its interaction with pathway components.

  20. HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4AVPRBP E3 ubiquitin ligase.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Belzile

    2007-07-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 viral protein R (Vpr has been shown to cause G2 cell cycle arrest in human cells by inducing ATR-mediated inactivation of p34cdc2, but factors directly engaged in this process remain unknown. We used tandem affinity purification to isolate native Vpr complexes. We found that damaged DNA binding protein 1 (DDB1, viral protein R binding protein (VPRBP, and cullin 4A (CUL4A--components of a CUL4A E3 ubiquitin ligase complex, DDB1-CUL4A(VPRBP--were able to associate with Vpr. Depletion of VPRBP by small interfering RNA impaired Vpr-mediated induction of G2 arrest. Importantly, VPRBP knockdown alone did not affect normal cell cycle progression or activation of ATR checkpoints, suggesting that the involvement of VPRBP in G2 arrest was specific to Vpr. Moreover, leucine/isoleucine-rich domain Vpr mutants impaired in their ability to interact with VPRBP and DDB1 also produced strongly attenuated G2 arrest. In contrast, G2 arrest-defective C-terminal Vpr mutants were found to maintain their ability to associate with these proteins, suggesting that the interaction of Vpr with the DDB1-VPRBP complex is necessary but not sufficient to block cell cycle progression. Overall, these results point toward a model in which Vpr could act as a connector between the DDB1-CUL4A(VPRBP E3 ubiquitin ligase complex and an unknown cellular factor whose proteolysis or modulation of activity through ubiquitination would activate ATR-mediated checkpoint signaling and induce G2 arrest.