WorldWideScience

Sample records for boeing e-3 sentry

  1. 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.

  2. 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.

  3. Canberra Alpha Sentry Installation Functional Design Criteria (FDC)

    International Nuclear Information System (INIS)

    WHITE, W.F.

    1999-01-01

    This document provides the functional design criteria for the installation of the Canberra Alpha Sentry System at selected locations within the Plutonium Finishing Plant (PFP). The equipment being installed is identified by part number in Section 3 and the locations are given in Section 5. The design, procurement and installation are assigned to Fluor Federal Services

  4. Home Sentry: servicio al cliente en la práctica

    OpenAIRE

    Mauricio Nieto Potes

    2006-01-01

    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

  5. The Sentry Autonomous Underwater Vehicle: Field Trial Results and Future Capabilities

    Science.gov (United States)

    Yoerger, D. R.; Bradley, A. M.; Martin, S. C.; Whitcomb, L. L.

    2006-12-01

    The Sentry autonomous underwater vehicle combines an efficient long range survey capability with the ability to maneuver at low speeds. These attributes will permit Sentry to perform a variety of conventional and unconventional surveys including long range sonar surveys, hydrothermal plume surveys and near-bottom photo surveys. Sentry's streamlined body and fore and aft tilting planes, each possessing an independently controlled thruster, enable efficient operation in both near-bottom and cruising operations. Sentry is capable of being configured in two modes: hover mode, which commands Sentry's control surfaces to be aligned vertically, and forward flight mode, which allows Sentry's control surfaces to actuate between plus or minus 45 degrees. Sentry is equipped for full 6-Degrees of freedom position measurement. Vehicle heading, roll, and pitch are instrumented with a TCM2 PNI heading and attitude sensor. A Systron Donner yaw rate sensor instrumented heading rate. Depth is instrumented by a Paroscientific depth sensor. A 300kHz RD Instruments Doppler Sonar provides altitude and XYZ velocity measurements. In April 2006, we conducted our first deep water field trials of Sentry in Bermuda. These trials enabled us to examine a variety of issues, including the control software, vehicle safety systems, launch and recovery procedures, operation at depth, heading and depth controllers over a range of speeds, and power consumption. Sentry employ's a control system based upon the Jason 2 control system for low-level control, which has proven effective and reliable over several hundred deep-water dives. The Jason 2 control system, developed jointly at Johns Hopkins University and Woods Hole Oceanographic Institution, was augmented to manage Sentry-specific devices (sensors, actuators, and power storage) and to employ a high-level mission controller that supported autonomous mission scripting and error detection and response. This control suite will also support the Nereus

  6. 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...

  7. 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.

  8. 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

  9. 78 FR 6200 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-01-30

    ... L/ N 3518 excluding Boeing Sky Interior (BSI).'' Boeing considered the existing language too general... contain life rafts, palletized equipment, or miscellaneous equipment. Boeing based its original [[Page...

  10. Dissection of the sentry ganglion by laparoscopic boarding in patients with cervix uterine cancer clinical stages IA2 at IIB

    International Nuclear Information System (INIS)

    Valdez U, J.J.; Pichardo M, P.A.; Cortes M, G.; Escudero de los Rios, P.

    2005-01-01

    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 99m Tc, total dose of 3 MCi) to achieve the identification of the ganglion. (Author)

  11. 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.

  12. Acoustic Emission based on sentry function to monitor the initiation of delamination in composite materials

    International Nuclear Information System (INIS)

    Bakhtiary Davijani, A.A.; Hajikhani, M.; Ahmadi, M.

    2011-01-01

    Research highlights: → Constant load does not confirm constant damage in composite materials. → Different damages have different AE events. → Sentry function is a useful tool to monitor the initiation of damage in delamination. → The less sentry function number is the more damage the material has endured. -- Abstract: Delamination is the most common failure mode in composite materials, since it will result in the reduction of stiffness and can grow throughout other layers. Delamination is consisted of two main stages including initiation and propagation. Understanding the behavior of the material in these zones is very important, hence it has been thoroughly studied by different methods such as numerical methods, Acoustic Emission (AE), and modeling. Between these two regions initiation is a more vital stage in the delamination of the material. Once initiation occurs, which normally requires greater amount of force, cracks can easily propagate through the structure with little force and cause the failure of the structure. A better knowledge of initiation can lead to better design and production of stronger materials. Additionally, more knowledge about crack initiation and its internal microevents would help improve other parameters and result in higher strength against crack initiation. AE is a suitable method for in situ monitoring of damage in composite materials. In this study, AE was applied to test different glass/epoxy specimens which were loaded under mode I delamination. A function that combines AE and mechanical information is employed to investigate the initiation of delamination. Scanning electron microscope (SEM) was used to verify the results of this function. It is shown that this method is an appropriate technique to monitor the behavior of the initiation of delamination.

  13. Schmidt Reaction of E-3-Benzylidenechromanones and E-3-Benzylidenethiochromanones

    Directory of Open Access Journals (Sweden)

    Tapas K. Mandal

    2013-01-01

    Full Text Available On treatment with NaN3/c. H2SO4-HOAc or NaN3/TFA, E-3-benzylidenechromanones are mostly converted to E-β-aminobenzylidenechromanones while E-3-benzylidenethiochromanones are converted to 3-benzoylthiochromones. A structurally new type of product has been isolated for the reaction of E-3-benzylidene-4′-methoxychromanone with NaN3/TFA. Mechanistic paths have been suggested for formation of the products.

  14. Estimating the Total Heat Flux from the ASHES Hydrothermal Vent Field Using the Sentry Autonomous Underwater Vehicle

    Science.gov (United States)

    Crone, T. J.; Kinsey, J. C.; Mittelstaedt, E. L.

    2017-12-01

    Hydrothermal venting at mid-ocean ridges influences ocean chemistry, the thermal and chemical structure of the oceanic crust, and the evolution of unique and diverse autolithotrophically-supported ecosystems. Axially-hosted hydrothermal systems are responsible for 20-25% of the total heat flux out of Earth's interior, and likely play a large role in local as well as global biogeochemical cycles. Despite the importance of these systems, only a few studies have attempted to constrain the volume and heat flux of an entire hydrothermal vent field. In July of 2014 we used the Sentry autonomous underwater vehicle (AUV) to survey the water column over the ASHES hydrothermal vent field which is located within the caldera of Axial Seamount, an active submarine volcano located on the Juan de Fuca Ridge. To estimate the total heat and mass flux from this vent field, we equipped Sentry with a Nortek acoustic Doppler velocimeter (ADV), an inertial measurement unit (IMU), two acoustic Doppler current profilers (ADCPs), and two SBE3 temperature probes, allowing us to obtain precise measurements of fluid temperature and water velocity. The survey was designed using a control volume approach in which Sentry was pre-programmed to survey a 150-m-square centered over the vent field flying a grid pattern with 5-m track line spacing followed by a survey of the perimeter. This pattern was repeated multiple times during several 10-h dives at different altitudes, including 10, 20, 40, and 60 m above the seafloor, and during one 40-h survey at an altitude of 10 m. During the 40-h survey, the pattern was repeated nine times allowing us to obtain observations over several tidal cycles. Water velocity data obtained with Sentry were corrected for platform motion and then combined with the temperature measurements to estimate heat flux. The analysis of these data will likely provide the most accurate and highest resolution heat and mass flux estimates at a seafloor hydrothermal field to date.

  15. Development of a self-navigating mobile interior robot application as a security guard/sentry

    International Nuclear Information System (INIS)

    Klarer, P.R.; Harrington, J.J.

    1986-07-01

    This paper describes a mobile robot system designed to function as part of an overall security system at a high security facility. The features of this robot system include specialized software and sensors for navigation without the need for external locator beacons or signposts, sensors for remote imaging and intruder detection, and the ability to communicate information either directly to the electronic portion of the security system or to a manned central control center. Other desirable features of the robot system include low weight, compact size, and low power consumption. The robot system can be operated either by remote manual control, or it can operate autonomously where direct human control can be limited to the global command level. The robot can act as a mobile remote sensing platform for alarm assessment or roving patrol, as a point sensor (sentry) in routine security applications, or as an exploratory device in situations potentially hazardous to humans. This robot system may also be used to ''walk-test'' intrusion detection sensors as part of a routine test and maintenance program for an interior intrusion detection system. The hardware, software, and operation of this robot system will be briefly described herein

  16. A review of acceptance testing of the Los Alamos, Canberra Alpha Sentry Continuous Air Monitor (CAM)

    International Nuclear Information System (INIS)

    Rodgers, J.C.

    1998-01-01

    Los Alamos National Laboratory (LANL) undertook the design and development of a new generation of alpha continuous air monitor (CAM) instrumentation that would incorporate advanced technologies in the design of the sampling inlet, multi-channel analyzer (MCA) electronics, solid state alpha detectors, radon background interference suppression, background interference compensation and based on spectral analysis, and microcomputer based data communication, processing, storage, and retrieval. The ANSI air monitoring instrument standards (Performance Specifications for Health Physics Instrumentation -- Occupational Airborne Radioactivity Monitoring Instrumentation, N42.17B) specify performance criteria and testing procedures for instruments and instrument systems designed to continuously sample and quantify airborne radioactivity in the workplace. Although the intent of the standard is to provide performance testing criteria for type testing, it is appropriate to evaluate the performance of a new instrument such as the Alpha Sentry against certain of these criteria for purposes of an acceptance test based on stated specifications and the Los Alamos CAM Requirements document. This report provides an overview of the results of these tests, as they pertain to instruments designed to detect alpha-emitting radionuclides in particulate form

  17. 78 FR 70211 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-11-25

    ... Replacement figures of Boeing Special Attention Service Bulletin 757- 57-0071, dated September 12, 2012. The... information identified in this AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management... Operations, M-30, West Building [[Page 70212

  18. 78 FR 72564 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-12-03

    .../ground relay in the P36 panel versus the location specified in Figure 15, Sheet 2, of Boeing Special... alternate relay locations. Figure 15, Sheet 2, of Boeing Special Attention Service Bulletin 757-24-0132... bundle routing described in Figure 1, Sheet 2, of Boeing Special Attention Service Bulletin 757-24-0132...

  19. GRP1 PH Domain, Like AKT1 PH Domain, Possesses a Sentry Glutamate Residue Essential for Specific Targeting to Plasma Membrane PI(3,4,5)P3

    Science.gov (United States)

    Pilling, Carissa; Landgraf, Kyle E.; Falke, Joseph J.

    2011-01-01

    During the appearance of the signaling lipid PI(3,4,5)P3, an important subset of pleckstrin homology (PH) domains target signaling proteins to the plasma membrane. To ensure proper pathway regulation, such PI(3,4,5)P3-specific PH domains must exclude the more prevalant, constitutive plasma membrane lipid PI(4,5)P2 and bind the rare PI(3,4,5)P3 target lipid with sufficiently high affinity. Our previous study of the E17K mutant of protein kinase B (AKT1) PH domain, together with evidence from Carpten et al (1), revealed that the native AKT1 E17 residue serves as a sentry glutamate that excludes PI(4,5)P2, thereby playing an essential role in specific PI(3,4,5)P3 targeting (2). The sentry glutamate hypothesis proposes that an analogous sentry glutamate residue is a widespread feature of PI(3,4,5)P3-specific PH domains, and that charge reversal mutation at the sentry glutamate position will yield both increased PI(4,5)P2 affinity and constitutive plasma membrane targeting. To test this hypothesis the present study investigates the E345 residue, a putative sentry glutamate, of General Receptor for Phosphoinositides 1 (GRP1) PH domain. The results show that incorporation of the E345K charge reversal mutation into GRP1 PH domain enhances PI(4,5)P2 affinity 8-fold and yields constitutive plasma membrane targeting in cells, reminiscent of the effects of the E17K mutation in AKT1 PH domain. Hydrolysis of plasma membrane PI(4,5)P2 releases E345K GRP1 PH domain into the cytoplasm and the efficiency of this release increases when target Arf6 binding is disrupted. Overall, the findings provide strong support for the sentry glutamate hypothesis and suggest that the GRP1 E345K mutation will be linked to changes in cell physiology and human pathologies, as demonstrated for AKT1 E17K (1, 3). Analysis of available PH domain structures suggests that a lone glutamate residue (or, in some cases an aspartate) is a common, perhaps ubiquitous, feature of PI(3,4,5)P3-specific binding

  20. 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

    ... DEPARTMENT OF LABOR Employment and Training Administration TA-W-82,705, the Boeing Company Boeing... Services and Yoh Services Auburn, Washington; TA-W-82,705A, the Boeing Company Boeing Commercial Aircraft...., Triad Systems International, Volt Services and Yoh Services Everett, Washington; TA-W-82,705B, The...

  1. 78 FR 49978 - Airworthiness Directives; the Boeing Company Airplanes

    Science.gov (United States)

    2013-08-16

    ... Pohl, Aerospace Engineer, Airframe Branch, ANM-120S, FAA, Seattle Aircraft Certification Office, 1601... Engineering Representative. Differences Between the Proposed AD and the Service Information Boeing Alert... structure not covered by the repair instructions in Boeing Alert Service Bulletin 737-53A1075, Revision 3...

  2. 77 FR 16147 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-03-20

    ... identified in this AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box... Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE... that note (f) of Figures 10 and 24 of Boeing Alert Service Bulletin 767-56A0010, Revision 1, dated...

  3. 77 FR 41041 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-07-12

    ... Clarify Note (d) of Figures 1 and 2 UAL noted that STEP 2, Note (d), of Boeing Special Attention Service... in this AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707... Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE...

  4. 78 FR 17285 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-03-21

    ..., contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H-65... Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590... performing Figures 7 through 10 of Boeing Service Bulletin 767-27A0224, Revision 1, dated December 16, 2011...

  5. 78 FR 11972 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-02-21

    ... corresponding figures of Boeing Special Attention Service Bulletin 737-53-1287, Revision 1, dated November 15... service information identified in this AD, contact Boeing Commercial Airplanes, Attention: Data & Services... Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE...

  6. 78 FR 9 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-01-02

    ..., Revision 1, dated March 31, 2005. (ii) At the times specified in Figure 8 of Boeing Special Attention... information identified in this AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management... Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE...

  7. 78 FR 79289 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-12-30

    ... service information identified in this AD, contact Boeing Commercial Airplanes, Attention: Data & Services... Management Facility, U.S. Department of Transportation, Docket Operations, M-30, West Building Ground Floor... that Figure 4, Sheets 2 and 3 of Boeing Alert Service Bulletin 747-25A3613, dated June 22, 2012, show...

  8. 78 FR 65166 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-10-31

    ..., contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H-65... Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590. FOR FURTHER...'' inspections, done in accordance with Part 4 and Figure 8 of Boeing Alert Service Bulletin 747-53A2371...

  9. 77 FR 2669 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-01-19

    ...'' column of Table 1 of Figure 1 of Boeing Special Attention Service Bulletin 737-53-1234, Revision 1, dated... times specified in Figure 8 of Boeing Special Attention Service Bulletin 737-53-1234, Revision 1, dated... Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE...

  10. 78 FR 33193 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-06-04

    ... modifications (such as the installation of felt on Model 767 airplanes per Figure 18 of Boeing Special Attention... information identified in this AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management... Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE...

  11. 77 FR 41931 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-07-17

    ... changes shown in Figures 2 and 7 of Boeing Special Attention Service Bulletin 737-30- 1058, Revision 3... Information Reference American stated that, in Figures 4 and 9 of Boeing Special Attention Service Bulletin... Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE...

  12. 77 FR 54798 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-09-06

    ... that Figures 18 and 23 of Boeing Special Attention Service Bulletin 747-25-3586, dated November 12.... ADDRESSES: For service information identified in this AD, contact Boeing Commercial Airplanes, Attention.... Department of Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New...

  13. 78 FR 25369 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-01

    ..., contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H-65... Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590... and corresponding figures of Boeing Service Bulletin 737-53-1310, dated October 20, 2011, are not...

  14. 78 FR 25372 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-01

    ... this AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management, P. O. Box 3707, MC... Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590... Part 5 of the Accomplishment Instructions and corresponding figures of Boeing Service Bulletin 737-53...

  15. 78 FR 47549 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-08-06

    ... Airworthiness Directives; The Boeing Company Airplanes AGENCY: Federal Aviation Administration (FAA), DOT... to certain The Boeing Company Model 737-200, -200C, -300, and -400 series airplanes. AD 2000-06-13 R1..., adds inspections and related investigative and corrective actions, revises certain inspection types...

  16. 77 FR 71723 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-12-04

    ... Airworthiness Directives; The Boeing Company Airplanes AGENCY: Federal Aviation Administration (FAA), DOT... directive (AD) that applies to certain The Boeing Company Model 737-200, -200C, - 300, and -400 series... related investigative and corrective actions, and revise certain inspection types. This proposed AD would...

  17. E3Net: a system for exploring E3-mediated regulatory networks of cellular functions.

    Science.gov (United States)

    Han, Youngwoong; Lee, Hodong; Park, Jong C; Yi, Gwan-Su

    2012-04-01

    Ubiquitin-protein ligase (E3) is a key enzyme targeting specific substrates in diverse cellular processes for ubiquitination and degradation. The existing findings of substrate specificity of E3 are, however, scattered over a number of resources, making it difficult to study them together with an integrative view. Here we present E3Net, a web-based system that provides a comprehensive collection of available E3-substrate specificities and a systematic framework for the analysis of E3-mediated regulatory networks of diverse cellular functions. Currently, E3Net contains 2201 E3s and 4896 substrates in 427 organisms and 1671 E3-substrate specific relations between 493 E3s and 1277 substrates in 42 organisms, extracted mainly from MEDLINE abstracts and UniProt comments with an automatic text mining method and additional manual inspection and partly from high throughput experiment data and public ubiquitination databases. The significant functions and pathways of the extracted E3-specific substrate groups were identified from a functional enrichment analysis with 12 functional category resources for molecular functions, protein families, protein complexes, pathways, cellular processes, cellular localization, and diseases. E3Net includes interactive analysis and navigation tools that make it possible to build an integrative view of E3-substrate networks and their correlated functions with graphical illustrations and summarized descriptions. As a result, E3Net provides a comprehensive resource of E3s, substrates, and their functional implications summarized from the regulatory network structures of E3-specific substrate groups and their correlated functions. This resource will facilitate further in-depth investigation of ubiquitination-dependent regulatory mechanisms. E3Net is freely available online at http://pnet.kaist.ac.kr/e3net.

  18. 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,...

  19. E3 Financing How-to Guide

    Science.gov (United States)

    The Financing How-to-Guide is intended to help manufacturers and their communities navigate financing and investment opportunities. While this guide provides an overview, there is no one-way to pay for E3 activities or attract investment.

  20. 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.

  1. 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.

  2. 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)

  3. 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

  4. 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.

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

    International Nuclear Information System (INIS)

    Gasaneo, G; Rodriguez, K V; Ancarani, L U; Cappello, C Dal; Charpentier, I

    2009-01-01

    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.

  6. The GRP1 PH domain, like the AKT1 PH domain, possesses a sentry glutamate residue essential for specific targeting to plasma membrane PI(3,4,5)P(3).

    Science.gov (United States)

    Pilling, Carissa; Landgraf, Kyle E; Falke, Joseph J

    2011-11-15

    During the appearance of the signaling lipid PI(3,4,5)P(3), an important subset of pleckstrin homology (PH) domains target signaling proteins to the plasma membrane. To ensure proper pathway regulation, such PI(3,4,5)P(3)-specific PH domains must exclude the more prevalant, constitutive plasma membrane lipid PI(4,5)P(2) and bind the rare PI(3,4,5)P(3) target lipid with sufficiently high affinity. Our previous study of the E17K mutant of the protein kinase B (AKT1) PH domain, together with evidence from Carpten et al. [Carpten, J. D., et al. (2007) Nature 448, 439-444], revealed that the native AKT1 E17 residue serves as a sentry glutamate that excludes PI(4,5)P(2), thereby playing an essential role in specific PI(3,4,5)P(3) targeting [Landgraf, K. E., et al. (2008) Biochemistry 47, 12260-12269]. The sentry glutamate hypothesis proposes that an analogous sentry glutamate residue is a widespread feature of PI(3,4,5)P(3)-specific PH domains, and that charge reversal mutation at the sentry glutamate position will yield both increased PI(4,5)P(2) affinity and constitutive plasma membrane targeting. To test this hypothesis, we investigated the E345 residue, a putative sentry glutamate, of the general receptor for phosphoinositides 1 (GRP1) PH domain. The results show that incorporation of the E345K charge reversal mutation into the GRP1 PH domain enhances PI(4,5)P(2) affinity 8-fold and yields constitutive plasma membrane targeting in cells, reminiscent of the effects of the E17K mutation in the AKT1 PH domain. Hydrolysis of plasma membrane PI(4,5)P(2) releases the E345K GRP1 PH domain into the cytoplasm, and the efficiency of this release increases when Arf6 binding is disrupted. Overall, the findings provide strong support for the sentry glutamate hypothesis and suggest that the GRP1 E345K mutation will be linked to changes in cell physiology and human pathologies, as demonstrated for AKT1 E17K [Carpten, J. D., et al. (2007) Nature 448, 439-444; Lindhurst, M. J., et al

  7. E3 Success Story - E3 Southwest Virginia: Economy, Energy and the Environment

    Science.gov (United States)

    E3 Southwest Virginia supports sustainable manufacturing in 17 counties in southwest Virginia. The MTC provides manufacturers with assessments of production processes to reduce their energy consumption and drive innovation.

  8. Boeing's STAR-FODB test results

    Science.gov (United States)

    Fritz, Martin E.; de la Chapelle, Michael; Van Ausdal, Arthur W.

    1995-05-01

    Boeing has successfully concluded a 2 1/2 year, two phase developmental contract for the STAR-Fiber Optic Data Bus (FODB) that is intended for future space-based applications. The first phase included system analysis, trade studies, behavior modeling, and architecture and protocal selection. During this phase we selected AS4074 Linear Token Passing Bus (LTPB) protocol operating at 200 Mbps, along with the passive, star-coupled fiber media. The second phase involved design, build, integration, and performance and environmental test of brassboard hardware. The resulting brassboard hardware successfully passed performance testing, providing 200 Mbps operation with a 32 X 32 star-coupled medium. This hardware is suitable for a spaceflight experiment to validate ground testing and analysis and to demonstrate performace in the intended environment. The fiber bus interface unit (FBIU) is a multichip module containing transceiver, protocol, and data formatting chips, buffer memory, and a station management controller. The FBIU has been designed for low power, high reliability, and radiation tolerance. Nine FBIUs were built and integrated with the fiber optic physical layer consisting of the fiber cable plant (FCP) and star coupler assembly (SCA). Performance and environmental testing, including radiation exposure, was performed on selected FBIUs and the physical layer. The integrated system was demonstrated with a full motion color video image transfer across the bus while simultaneously performing utility functions with a fiber bus control module (FBCM) over a telemetry and control (T&C) bus, in this case AS1773.

  9. Transparência: Bacen versus BoE

    Directory of Open Access Journals (Sweden)

    Eduardo de Carvalho Andrade

    2005-12-01

    Full Text Available Transparency: Bacen versus BoE. The aim of this paper is to compare the degree of transparency of the Brazilian Central Bank (Bacen with the one verified in the Bank of England (BoE. In order to accomplish this objective, an indicator of transparency is built based on the information that each central bank provides to the public about its monetary policy, its expectation about the future of the economy, its intervention in the financial market, and if there are clear limits and restrictions to the release of information to the general public. The analysis suggests that the Bacen is less transparent and has a less individualistic Monetary Policy Committee in comparison with the BoE. Moreover, it indicates some procedures that could be adopted by the Bacen in order to make its monetary policy more transparent.

  10. E3 Success Story - San Antonio E3 Case Study: UEMC “Now Hiring”

    Science.gov (United States)

    exas Manufacturing Assistance Center conducted an E3 assessment as part of the local Lean-Clean-Energy program in October of 2009. Overall, UEMC has reduced demand by approximately 30kw and reduced consumption by over 100,000 kwh/year.

  11. The Chang'e 3 Mission Overview

    Science.gov (United States)

    Li, Chunlai; Liu, Jianjun; Ren, Xin; Zuo, Wei; Tan, Xu; Wen, Weibin; Li, Han; Mu, Lingli; Su, Yan; Zhang, Hongbo; Yan, Jun; Ouyang, Ziyuan

    2015-07-01

    The Chang'e 3 (CE-3) mission was implemented as the first lander/rover mission of the Chinese Lunar Exploration Program (CLEP). After its successful launch at 01:30 local time on December 2, 2013, CE-3 was inserted into an eccentric polar lunar orbit on December 6, and landed to the east of a 430 m crater in northwestern Mare Imbrium (19.51°W, 44.12°N) at 21:11 on December 14, 2013. The Yutu rover separated from the lander at 04:35, December 15, and traversed for a total of 0.114 km. Acquisition of science data began during the descent of the lander and will continue for 12 months during the nominal mission. The CE-3 lander and rover each carry four science instruments. Instruments on the lander are: Landing Camera (LCAM), Terrain Camera (TCAM), Extreme Ultraviolet Camera (EUVC), and Moon-based Ultraviolet Telescope (MUVT). The four instruments on the rover are: Panoramic Camera (PCAM), VIS-NIR Imaging Spectrometer (VNIS), Active Particle induced X-ray Spectrometer (APXS), and Lunar Penetrating Radar (LPR). The science objectives of the CE-3 mission include: (1) investigation of the morphological features and geological structures of and near the landing area; (2) integrated in-situ analysis of mineral and chemical composition of and near the landing area; and (3) exploration of the terrestrial-lunar space environment and lunar-based astronomical observations. This paper describes the CE-3 objectives and measurements that address the science objectives outlined by the Comprehensive Demonstration Report of Phase II of CLEP. The CE-3 team has archived the initial science data, and we describe data accessibility by the science community.

  12. 77 FR 63714 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-17

    .... ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for certain The Boeing... instructions and doing the work specified in those instructions. We are issuing this AD to detect and correct..., Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590. FOR FURTHER INFORMATION CONTACT: Kelly...

  13. 78 FR 60660 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-10-02

    ... compound (CIC) Boeing Material Specification (BMS) 3-23 to the surfaces of the repaired area. As an option... fracture and failure of the skin panels of the fuselage, and consequent rapid decompression of the airplane... availability of this material at the FAA, call 425-227-1221. Examining the AD Docket You may examine the AD...

  14. 77 FR 69747 - Airworthiness Directives; The Boeing Company Model Airplanes

    Science.gov (United States)

    2012-11-21

    ... cycles after the effective date of this AD.'' The new language in paragraph (i)(1) of the NPRM states... language specified in paragraphs (l) through (n) of the NPRM from paragraph (o) of the NPRM. In the... inclusive. Boeing stated that the NPRM requirements do not differentiate for Model 737-200 series airplanes...

  15. 78 FR 31389 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-24

    ... ``New Inspections and Corrective Actions to Ensure Cross Beam Reinforcement,'' and suggested language... door. Boeing added that the current language in the NPRM and this service information leave open the...) of this AD. (i) For airplanes with line numbers 1 through 1231 inclusive: Install a cross beam repair...

  16. 77 FR 5195 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-02-02

    ...). Support for Proposed Actions United Parcel Service Co. (UPS) supports mandating the Stage 2 inspections...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service information identified in this proposed AD, contact Boeing Commercial Airplanes, Attention: Data & Services...

  17. 78 FR 14644 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-03-07

    ... support clamps installed within the left environmental control systems (ECS) bay, which could allow wiring... the installation of winglets per Supplemental Type Certificate (STC) ST00830SE ( http://rgl.faa.gov... Change the ``Parts Installation Prohibition'' Section Boeing requested the ``Parts Installation...

  18. 77 FR 38547 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-06-28

    ... (including cracking, misdrilled fastener holes, elongated fastener holes, corrosion, oil-cans, and existing..., corrosion, oil-cans, and existing repairs), or for certain discrepancies, contacting Boeing for repair... Designated Engineering Representative (DER). We have revised the date of the document specified in paragraph...

  19. 77 FR 61548 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-10

    ...-indicating and crew-alerting system (EICAS) messages ALT DISAGREE and IAS DISAGREE displayed. The flightcrew... Special Attention Service Bulletin 727-34-0245, dated June 4, 2008 (for Model airplanes); [[Page 61549... -200C series airplanes); and Boeing Special Attention Service Bulletin 747-34-2925, dated June 4, 2008...

  20. 78 FR 57053 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-09-17

    ... Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H-65, Seattle, WA... Management Facility, U.S. Department of Transportation, Docket Operations, M-30, West Building Ground Floor... frame from stringers 23 through 31 per Figure 5 or Figure 6 of the service bulletins specified in...

  1. 77 FR 54854 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-09-06

    .... Department of Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New... 5 p.m., Monday through Friday, except Federal holidays. Boeing Commercial Airplanes, Attention: Data... airplanes), except as specified in paragraphs (h)(1) and (h)(2) of this AD. (1) Steps 1 through 5 of Figure...

  2. 77 FR 49708 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-17

    .... ADDRESSES: For service information identified in this AD, contact Boeing Commercial Airplanes, Attention.... Department of Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New... Figure 24 as an accepted procedure'' for the HFEC inspection, this AD requires that the inspection be...

  3. 77 FR 52212 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-29

    ... request to revise this AD. The inspections specified in Figure 1 in both Boeing Special Attention Service... Commercial Airplanes, Attention: Data & Services Management, P. O. Box 3707, MC 2H-65, Seattle, Washington... Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590. FOR FURTHER...

  4. 78 FR 14469 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-03-06

    ...-2251. Mail: U.S. Department of Transportation, Docket Operations, M-30, West Building Ground Floor... identified in this proposed AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management, P... through 31 per Figure 5 or Figure 6 of the service bulletins specified in paragraph (g) or (h) of this AD...

  5. 78 FR 68693 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-11-15

    ... Special Attention Service Bulletin 737-53-1296, dated January 11, 2011, in Step 1, ``Move,'' of Figure 10.... ADDRESSES: For service information identified in this AD, contact Boeing Commercial Airplanes, Attention... Facility, U.S. Department of Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12...

  6. 78 FR 43839 - Airworthiness Directives; the Boeing Company

    Science.gov (United States)

    2013-07-22

    .... Department of Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New... AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management, P. O. Box 3707, MC 2H..., performed in accordance with Part 4 and Figure 8 of this service bulletin. This service information is being...

  7. 77 FR 16188 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-03-20

    ..., M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590... Airplanes, Attention: Data & Services Management, P. O. Box 3707, MC 2H-65, Seattle, Washington 98124-2207... AD would require repair using a method approved in accordance with paragraph (l). Figure 1 of Boeing...

  8. 78 FR 61161 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-10-03

    ... bolts being fabricated from bar stock with a machined head instead of from a forged blank with an upset... are issuing this AD to prevent damage to the MLG and consequent damage to airplane structure, which...'' fabrication. Boeing stated that it approved the fabrication of the bolts from bar stock with a machined head...

  9. 78 FR 73744 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-12-09

    ... paragraph (g) of this second SNPRM. Costs of Compliance We estimate that this proposed AD affects 1,147... 2,975 3,412,325 = $1,445. We have received no definitive data that would enable us to provide a cost... to be a rotable part, we note that Boeing Document D042A525, ``Compliance Document and Repair...

  10. 78 FR 66254 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-11-05

    ... AD. Costs of Compliance We estimate that this AD affects 84 airplanes of U.S. registry. We estimate... inspection cycle. We have received no definitive data that would enable us to provide a cost estimate for the... 2 of paragraph 1.E., ``Compliance,'' of Boeing Service Bulletin 747-53A2688, Revision 1, dated...

  11. 78 FR 70851 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-11-27

    ... (EICAS) message that displays ``ENG THRUST (L,R)'' (for Model 787-8 airplanes) or ``ENG (1, 2, 3, or 4... The Boeing Company Model 747-8 and 747-8F series airplanes and Model 787-8 airplanes powered by GEnx...: 202-493-2251. Mail: U.S. Department of Transportation, Docket Operations, M-30, West Building Ground...

  12. 77 FR 64711 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-23

    ... Service Bulletin 737-22A1224, dated May 18, 2012, requires installation of FCC software P/N 2274-COL-AC1..., 2010, because that service bulletin only specifies to install FCC OPS software P/N 2276-COL-AC1-05 or P...) Install software identified in table 2 of the Accomplishment Instructions of Boeing Alert Service Bulletin...

  13. 77 FR 60285 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-10-03

    ... the MLG for chicken- wire cracks, corrosion, and chrome plate distress; repetitive magnetic particle..., contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H-65... magnetic particle inspections of the outer diameter chrome on the center axles of the MLG for cracks; and...

  14. 77 FR 47267 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2012-08-08

    ... contained within those paragraphs. Request To Clarify Undefined Requirement UPS stated that the actions... modification, which is currently undefined in Boeing Service Bulletin 747 53A2559, Revision 1, dated August 4... believe it will be affected; however, UPS is concerned with the precedent of mandating undefined...

  15. 78 FR 26286 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-05-06

    ... the first post-modification high frequency eddy current (HFEC) repetitive inspection may be extended... Boeing (the original equipment manufacturer) had time to build up an adequate stock of kits and/or frames.... We have also revised paragraph (g) in this supplemental NPRM to correspond to the manufacturer's...

  16. Effect of BioSentry 904 and ethylenediaminetetraacetic acid-tris disinfecting during incubation of chicken eggs on microbial levels and productivity of poultry.

    Science.gov (United States)

    Walker, S E; Sander, J E

    2004-01-01

    Proper sanitation practices and the use of efficacious disinfectants in a hatchery have an effect on chick quality. Aerosol bacterial counts, egg moisture loss, hatchability, chick quality, and broiler productivity were evaluated when egg surfaces were contaminated by immersion of each egg into a broth medium containing a field isolate of Pseudomonas aeruginosa and incubated with exposure to one of three disinfectant treatments administered by fine spray: distilled water, BioSentry 904 (904), and a 1:1 ratio of 904 and ethylenediaminetetraacetic acid (EDTA)-Tris. The aerosol bacteria levels were statistically greater on day 21 of incubation in the group treated with distilled water than in those receiving disinfectants. Overall hatch of fertile eggs and egg moisture loss were comparable among all three treatments. At 1 day of age, the chicks incubated with 904 had a statistically lower yolk sac contamination rate than those incubated with 904+EDTA-Tris or distilled water. The 2-wk mortality rates, body weights, feed conversion ratios, yolk sac weights, and yolk sac contamination rates were all similar among the three treatments.

  17. 78 FR 22439 - Airworthiness Directives; The Boeing Company Airplanes

    Science.gov (United States)

    2013-04-16

    ..., West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590. Hand..., Attention: Data & Services Management, P. O. Box 3707, MC 2H-65, Seattle, WA 98124-2207; phone: 206-544-5000... SRM 53-30-1, Figures 20, 21, 31, or 32; and Boeing 737-300/-400/-500 SRM 53-10-01, Repair 5, 6, or 8...

  18. BOES: Building Occupancy Estimation System using sparse ambient vibration monitoring

    Science.gov (United States)

    Pan, Shijia; Bonde, Amelie; Jing, Jie; Zhang, Lin; Zhang, Pei; Noh, Hae Young

    2014-04-01

    In this paper, we present a room-level building occupancy estimation system (BOES) utilizing low-resolution vibration sensors that are sparsely distributed. Many ubiquitous computing and building maintenance systems require fine-grained occupancy knowledge to enable occupant centric services and optimize space and energy utilization. The sensing infrastructure support for current occupancy estimation systems often requires multiple intrusive sensors per room, resulting in systems that are both costly to deploy and difficult to maintain. To address these shortcomings, we developed BOES. BOES utilizes sparse vibration sensors to track occupancy levels and activities. Our system has three major components. 1) It extracts features that distinguish occupant activities from noise prone ambient vibrations and detects human footsteps. 2) Using a sequence of footsteps, the system localizes and tracks individuals by observing changes in the sequences. It uses this tracking information to identify when an occupant leaves or enters a room. 3) The entering and leaving room information are combined with detected individual location information to update the room-level occupancy state of the building. Through validation experiments in two different buildings, our system was able to achieve 99.55% accuracy for event detection, less than three feet average error for localization, and 85% accuracy in occupancy counting.

  19. Some nonunitary, indecomposable representations of the Euclidean algebra e(3)

    International Nuclear Information System (INIS)

    Douglas, Andrew; De Guise, Hubert

    2010-01-01

    The Euclidean group E(3) is the noncompact, semidirect product group E(3)≅R 3 x SO(3). It is the Lie group of orientation-preserving isometries of three-dimensional Euclidean space. The Euclidean algebra e(3) is the complexification of the Lie algebra of E(3). We construct three distinct families of finite-dimensional, nonunitary representations of e(3) and show that each representation is indecomposable. The representations of the first family are explicitly realized as subspaces of the polynomial ring F[X,Y,Z] with the action of e(3) given by differential operators. The other families are constructed via duals and tensor products of the representations within the first family. We describe subrepresentations, quotients and duals of these indecomposable representations.

  20. Antifungal susceptibilities of Candida, Cryptococcus neoformans and Aspergillus fumigatus from the Asia and Western Pacific region: data from the SENTRY antifungal surveillance program (2010-2012).

    Science.gov (United States)

    Pfaller, Michael A; Messer, Shawn A; Jones, Ronald N; Castanheira, Mariana

    2015-09-01

    The SENTRY Antifungal Surveillance Program monitors global susceptibility rates of newer and established antifungal agents. We report the in vitro activity of seven antifungal agents against 496 contemporary clinical isolates of yeasts and molds. The isolates were obtained from 20 laboratories in the Asia-Western Pacific (APAC) region during 2010 through 2012. Anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole and voriconazole were susceptibility tested using CLSI methods and species-specific interpretive criteria. Sequencing of fks hot spots was performed for echinocandin-resistant strains. Isolates included 13 species of Candida (n=460), 5 species of non-Candida yeasts (21), 5 species of Aspergillus (11) and 4 other molds. Echinocandin resistance was uncommon among eight species of Candida and was only detected in three isolates of Candida glabrata, two from Australia harboring mutations in fks1 (F625S) and fks2 (S663P). Resistance to the azoles was much more common and was observed among all species with the exception of Candida dubliniensis. Fluconazole resistance rates observed with C. glabrata (6.8%) was comparable to that seen with Candida parapsilosis (5.7%) and Candida tropicalis (3.6%). Cross resistance among the triazoles was seen with each of these three species. The mold-active azoles and the echinocandins were all active against isolates of Aspergillus fumigatus. Azole resistance was not detected among the isolates of Cryptococcus neoformans. Antifungal resistance is uncommon among isolates of fungi causing invasive fungal infections in the APAC region. As in other regions of the world, emerging resistance to the echinocandins among invasive isolates of C. glabrata bears close monitoring.

  1. 76 FR 21815 - Airworthiness Directives; The Boeing Company Model 737 Airplanes

    Science.gov (United States)

    2011-04-19

    ... proposed AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC... and pictures be added to Section 3.B.1.n.(1) of Boeing Alert Service Bulletin 737-27A1277, Revision 1... information directly to the manager of the ACO, send it to the attention of the person identified in the...

  2. 75 FR 68688 - Airworthiness Directives; The Boeing Company Model 757 Airplanes

    Science.gov (United States)

    2010-11-09

    ... the part number of a washer used in Figures 1 and 4 of Boeing Special Attention Service Bulletin 757... Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H-65, Seattle... Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE...

  3. 76 FR 2848 - Airworthiness Directives; The Boeing Company Model 757 Airplanes

    Science.gov (United States)

    2011-01-18

    ... bracket on the left wing as shown in Figure 3 of Boeing Special Attention Service Bulletin 757-24-0105... lower bracket on the left wing, in accordance with Figure 3 of Boeing Special Attention Service Bulletin.... Mail: U.S. Department of Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12...

  4. 76 FR 8615 - Airworthiness Directives; The Boeing Company Model 767 Airplanes

    Science.gov (United States)

    2011-02-15

    ... distinct checks as specified in Steps 1 and 2 of Figures 2 and 5 of Boeing Special Attention Service..., contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H-65..., Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE...

  5. STS-65 crewmembers participate in bench review at Boeing Building

    Science.gov (United States)

    1994-01-01

    Attired in clean suits, STS-65 Payload Commander (PLC) Richard J. Hieb (left) and Payload Specialist Chiaki Mukai examine the contents of a stowage locker during a bench review at Boeing's Flight Equipment Processing Facility (FEPF) near the Johnson Space Center (JSC). In the background, Commander Robert D. Cabana inspects additional equipment to be carried aboard the Space Shuttle Columbia, Orbiter Vehicle (OV) 102, for the scheduled July flight of the second International Microgravity Laboratory (IML-2) mission. Mukai represents Japan's National Space Development Agency (NASDA). Photo taken by NASA JSC contract photographer Scott A. Wickes.

  6. E3 Testing of Directed Energy Systems: A Challenging Future

    National Research Council Canada - National Science Library

    Brown, Lyndell R

    2009-01-01

    .... Compatibility testing and susceptibility to electromagnetic radiation is required. Standards, such as MIL-STD-464 and MIL-STD-237D, are being revised to include HPM levels and frequencies for E3 tests...

  7. 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...

  8. E3 Success Story - Working Together: E3 Ohio and the Ohio By-Product Synergy Network

    Science.gov (United States)

    The Mid-Ohio Regional Planning Commission (MORPC) received funding to support the integration of the national E3 sustainability initiative with the Ohio By-Product Synergy (BPS) Network to create an efficient and replicable model for reducing GHGs.

  9. 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).

  10. Photochemical Aryl Radical Cyclizations to Give (E-3-Ylideneoxindoles

    Directory of Open Access Journals (Sweden)

    Michael Gurry

    2014-09-01

    Full Text Available (E-3-Ylideneoxindoles are prepared in methanol in reasonable to good yields, as adducts of photochemical 5-exo-trig of aryl radicals, in contrast to previously reported analogous radical cyclizations initiated by tris(trimethylsilylsilane and azo-initiators that gave reduced oxindole adducts.

  11. Apolipoprotein E*3-Leiden transgenic mice mode for hypolipidaemic drugs

    NARCIS (Netherlands)

    Vlijmen, B.J.M. van; Pearce, N.J.; Bergö, M.; Staels, B.; Yates, J.W.; Gribble, A.D.; Bond, B.C.; Hofker, M.H.; Havekes, L.M.; Groot, P.H.E.

    1998-01-01

    Apolipoprotein (APO) E*3-Leiden mice with impaired chylomicron and VLDL (very low density lipoprotein) remnant metabolism display hyperlipidaemia and atherosclerosis. In the present study, these mice were used for testing the hypolipidaemic effect of two marketed agents, lovastatin (CAS 75330-75-5)

  12. Sentry Assurance: Bringing Outsiders "In."

    Science.gov (United States)

    Lease, Judy E.

    1998-01-01

    Presents a case study for use in business communication classes to help students understand and learn both the context and the strategies for communication with business and management. Deals with multiple problems caused by the rapid expansion of an insurance brokerage, including gender issues, clarification of responsibilities and roles, and…

  13. A Sentry on the Universe

    Science.gov (United States)

    Dixon, Robert

    This chapter introduces the Argus radio telescope concept, a radically new approach to radio telescope design (not to be confused with The SETI League's Project Argus, a linked global array of fairly conventional radio telescopes). It represents a complete departure from designs that have been used ever since the invention of the first telescope by Galileo in 1609. It starts over from the beginning, and in doing so overcomes the legacy of Galileo. Argus can do things that are amazing and even hard to believe, when viewed in the context of previous telescopes. Here are some examples.

  14. Lunar Penetrating Radar onboard the Chang'e-3 mission

    Science.gov (United States)

    Fang, Guang-You; Zhou, Bin; Ji, Yi-Cai; Zhang, Qun-Ying; Shen, Shao-Xiang; Li, Yu-Xi; Guan, Hong-Fei; Tang, Chuan-Jun; Gao, Yun-Ze; Lu, Wei; Ye, Sheng-Bo; Han, Hai-Dong; Zheng, Jin; Wang, Shu-Zhi

    2014-12-01

    Lunar Penetrating Radar (LPR) is one of the important scientific instruments onboard the Chang'e-3 spacecraft. Its scientific goals are the mapping of lunar regolith and detection of subsurface geologic structures. This paper describes the goals of the mission, as well as the basic principles, design, composition and achievements of the LPR. Finally, experiments on a glacier and the lunar surface are analyzed.

  15. Energy Exascale Earth System Model (E3SM) Project Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Bader, D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-09-18

    The E3SM project will assert and maintain an international scientific leadership position in the development of Earth system and climate models at the leading edge of scientific knowledge and computational capabilities. With its collaborators, it will demonstrate its leadership by using these models to achieve the goal of designing, executing, and analyzing climate and Earth system simulations that address the most critical scientific questions for the nation and DOE.

  16. Some Preliminary Scientific Results of Chang'E-3 Mission

    Science.gov (United States)

    Zou, Y.; Li, W.; Zheng, Y.; Li, H.

    2015-12-01

    Chang'E-3 mission is the main task of Phase two of China Lunar Exploration Program (CLEP), and also is Chinese first probe of landing, working and roving on the moon. Chang'E-3 craft composed of a lander and a rover, and each of them carry four scientific payloads respectively. The landing site of Chang'E-3 was located at 44.12 degrees north latitude and 19.51 degrees west longitude, where is in the northern part of Imbrium Which the distance in its west direction from the landing site of former Soviet probe Luna-17 is about 400 km, and about 780km far from the landing site of Appolo-17 in its southeast direction. Unfortunately, after a series of scientific tests and exploration on the surface of the moon, the motor controller communication of the rover emerged a breakdown on January 16, 2014, which leaded the four payloads onboard the rover can't obtain data anymore. However, we have received some interesting scientific data which have been studied by Chinese scientists. During the landing process of Chang'E-3, the Landing camera got total 4673 images with the Resolution in millimeters to meters, and the lander and rover took pictures for each other at different point with Topography camera and Panoramic camera. We can find characteristic changes in celestial brightness with time by analyzing image data from Lunar-based Ultraviolet Telescope (LUT) and an unprecedented constraint on water content in the sunlit lunar exosphere seen by LUT). The figure observed by EUV camera (EUVC) shows that there is a transient weak area of the Earth's plasma sphere; This event took place about three hours. The scientists think that it might be related to the change of the particle density of mid-latitude ionosphere. The preliminary spectral and mineralogical results from the landing site are derived according to the data of Visible and Near-infrared Imaging Spectrometer (VNIS). Seven major elements including Mg, Al, Si, K, Ca, Ti and Fe have been identified by the Active Particle

  17. E3D, 3-D Elastic Seismic Wave Propagation Code

    International Nuclear Information System (INIS)

    Larsen, S.; Harris, D.; Schultz, C.; Maddix, D.; Bakowsky, T.; Bent, L.

    2004-01-01

    1 - Description of program or function: E3D is capable of simulating seismic wave propagation in a 3D heterogeneous earth. Seismic waves are initiated by earthquake, explosive, and/or other sources. These waves propagate through a 3D geologic model, and are simulated as synthetic seismograms or other graphical output. 2 - Methods: The software simulates wave propagation by solving the elasto-dynamic formulation of the full wave equation on a staggered grid. The solution scheme is 4-order accurate in space, 2-order accurate in time

  18. Aspects of radiative K{sup +}{sub e3} decays

    Energy Technology Data Exchange (ETDEWEB)

    Kubis, B. [Universitaet Bonn, Helmholtz-Institut fuer Strahlen- und Kernphysik, Bonn (Germany); Mueller, E.H. [Universitaet Bonn, Helmholtz-Institut fuer Strahlen- und Kernphysik, Bonn (Germany); University of Edinburgh, School of Physics, Edinburgh (United Kingdom); Gasser, J.; Schmid, M. [Universitaet Bern, Institut fuer theoretische Physik, Bern (Switzerland)

    2007-04-15

    We re-investigate the radiative charged kaon decay K{sup {+-}}{yields}{pi}{sup 0}e{sup {+-}}{nu}{sub e}{gamma} [K{sub e3{gamma}}{sup {+-}}] in chiral perturbation theory, merging the chiral expansion with Low's theorem. We thoroughly analyze the precision of the predicted branching ratio relative to the non-radiative decay channel. Structure dependent terms and their impact on differential decay distributions are investigated in detail, and the possibility to see effects of the chiral anomaly in this decay channel is emphasized. (orig.)

  19. Aspects of radiative K+e3 decays

    International Nuclear Information System (INIS)

    Kubis, B.; Mueller, E.H.; Gasser, J.; Schmid, M.

    2007-01-01

    We re-investigate the radiative charged kaon decay K ± →π 0 e ± ν e γ [K e3γ ± ] in chiral perturbation theory, merging the chiral expansion with Low's theorem. We thoroughly analyze the precision of the predicted branching ratio relative to the non-radiative decay channel. Structure dependent terms and their impact on differential decay distributions are investigated in detail, and the possibility to see effects of the chiral anomaly in this decay channel is emphasized. (orig.)

  20. E3-transitions in sup(105, 107, 109, 111)Ag

    International Nuclear Information System (INIS)

    Shevelev, G.A.; Troitskaya, A.G.; Kartashov, V.M.

    1978-01-01

    Electron radiation of the isomeric transitions of the sup(105-111)Ag odd nuclei was studied using an iron magnetic πsup(√2) beta spectrometer. For most isomeric transitions, relative intensities of the K, L, M, and N lines have been measured; for sup(105-111)Ag and 111 Cd they were measured for the first time. Energy of gamma transitions, relative intensities of internal conversion electrons (ICE) compared with the theoretical ICE values for the E3 transitions are presented. The observations for all the shells are in a fairly gool agreement with the calculations. Systematics of low-lying excited states of the silver nuclei involved is proposed. It has been established that spins and parities of the first excited states of the sup(105-111)Ag odd nuclei are 7/2 + . Multipolarities of isomeric transitions from these staes are pure E3. Spin and parity 9/2 + of the second excited states may be uniquely determined unly for 109 Ag from direct measurements of the ICE transition at 45.8 keV

  1. Implication of SUMO E3 ligases in nucleotide excision repair.

    Science.gov (United States)

    Tsuge, Maasa; Kaneoka, Hidenori; Masuda, Yusuke; Ito, Hiroki; Miyake, Katsuhide; Iijima, Shinji

    2015-08-01

    Post-translational modifications alter protein function to mediate complex hierarchical regulatory processes that are crucial to eukaryotic cellular function. The small ubiquitin-like modifier (SUMO) is an important post-translational modification that affects transcriptional regulation, nuclear localization, and the maintenance of genome stability. Nucleotide excision repair (NER) is a very versatile DNA repair system that is essential for protection against ultraviolet (UV) irradiation. The deficiencies in NER function remarkably increase the risk of skin cancer. Recent studies have shown that several NER factors are SUMOylated, which influences repair efficiency. However, how SUMOylation modulates NER has not yet been elucidated. In the present study, we performed RNAi knockdown of SUMO E3 ligases and found that, in addition to PIASy, the polycomb protein Pc2 affected the repair of cyclobutane pyrimidine dimers. PIAS1 affected both the removal of 6-4 pyrimidine pyrimidone photoproducts and cyclobutane pyrimidine dimers, whereas other SUMO E3 ligases did not affect the removal of either UV lesion.

  2. Trajectory Determination for Chang 'e-3 Probe Soft-landing

    Science.gov (United States)

    Yezhi, S.; Huang, Y.

    2017-12-01

    On December 2, 2013, The Chang 'e-3 (ce-3) probe was successfully launched from a long march-3b carrier rocket at Xichang satellite launch center. After more than five days of flying, the probe was captured by the moon to 100 km by 100 km. The orbit maneuvered to 15 km by 100 km 4 days later. Finally, at 21:12 Beijing time on December 14, 2013, it landed at the junction of the Sinus Iridum and Mare Imbrium. In the ce-3 project, the combined test mode of the radio ranging measurement and very long baseline interferometry (VLBI) was used. The soft-landing was carried out in ce-3 mission for the sampling .The paper presents a new method of trajectory determination for soft landing and sampling returning for lunar probe by B spline approximation. By simulation and data processing of Chang'E-3(CE-3), it could be assumed that the accuracy of trajectory determination of soft landing is less than 100 meters in CE-3. It appears that the difference between the endpoint of trajectory and the location from image processed by NASA'S LRO is less than 50m .It confirms the method of soft landing trajectory determination provided by the paper is effective. The paper analyzes the dynamics and control characteristics of the sampling returning, provides the preliminary feasible trajectory determination method for soft landing and sampling return of Chang'E-5 (CE - 5).

  3. E3 analysis for crude and vacuum distillation system

    Energy Technology Data Exchange (ETDEWEB)

    Mittal, V; Zhang, J; Yang, X; Xu, Q [Dan F. Smith Department of Chemical Engineering, Lamar University, Beaumont, Texas (United States)

    2011-11-15

    Crude oil blending is a very common practice in petroleum refineries, where the main focus is to minimize the total purchase cost of crude oils under specified blending oil properties. Crude oil blending actually has significant impacts on energy consumption from heating furnaces during crude oil processing. Conceivably, furnace energy consumption from burning fuels such as natural gas, fuel oil, or propane causes huge amounts of CO{sub 2} emissions. In this paper, a methodology framework for crude oil blending and processing with simultaneous consideration of energy, emission, and economic profit (E3) is developed. It includes four stages of work: steady-state modeling, heating energy consumption calculation, emission model development, and economic evaluation. With Aspen HYSYS simulation, the developed methodology provides a quantitative support for refinery to identify an optimal E3 operating strategy. A case study is implemented to demonstrate the efficacy of this methodology. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  4. Performance Measurement of Advanced Stirling Convertors (ASC-E3)

    Science.gov (United States)

    Oriti, Salvatore M.

    2013-01-01

    NASA Glenn Research Center (GRC) has been supporting development of the Advanced Stirling Radioisotope Generator (ASRG) since 2006. A key element of the ASRG project is providing life, reliability, and performance testing data of the Advanced Stirling Convertor (ASC). The latest version of the ASC (ASC-E3, to represent the third cycle of engineering model test hardware) is of a design identical to the forthcoming flight convertors. For this generation of hardware, a joint Sunpower and GRC effort was initiated to improve and standardize the test support hardware. After this effort was completed, the first pair of ASC-E3 units was produced by Sunpower and then delivered to GRC in December 2012. GRC has begun operation of these units. This process included performance verification, which examined the data from various tests to validate the convertor performance to the product specification. Other tests included detailed performance mapping that encompassed the wide range of operating conditions that will exist during a mission. These convertors were then transferred to Lockheed Martin for controller checkout testing. The results of this latest convertor performance verification activity are summarized here.

  5. 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

  6. 76 FR 63163 - Airworthiness Directives; The Boeing Company Model 777-200, -200LR, -300, and -300ER Series...

    Science.gov (United States)

    2011-10-12

    ..., January 18, 2011) as follows: ``Figure 1 of the Accomplishment Instructions of Boeing Special Attention... Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H-65, Seattle... Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590...

  7. Radiative K{sub e3} decays revisited

    Energy Technology Data Exchange (ETDEWEB)

    Gasser, J. [Universitaet Bern, Institut fuer Theoretische Physik, Bern (Switzerland); Kubis, B. [Universitaet Bern, Institut fuer Theoretische Physik, Bern (Switzerland); Universitaet Bonn, Helmholtz-Institut fuer Strahlen- und Kernphysik, Bonn (Germany); Paver, N. [Universita degli Studi di Trieste, Dipartimento di Fisica Teorica, Trieste (Italy); INFN-Trieste, Trieste (Italy); Verbeni, M. [Universidad de Granada, Departamento de Fisica Teorica y del Cosmos, Granada (Spain)

    2005-03-01

    Motivated by recent experimental results and ongoing measurements, we review the chiral perturbation theory prediction for K{sub L}{yields}{pi}{sup -+}e{sup {+-}}{nu}{sub e}{gamma} decays. Special emphasis is given to the stability of the inner bremsstrahlung-dominated relative branching ratio versus the K{sub e3} form factors, and on the separation of the structure-dependent amplitude in differential distributions over the phase space. For the structure-dependent terms, an assessment of the order p{sup 6} corrections is given, in particular, a full next-to-leading order calculation of the axial component is performed. The experimental analysis of the photon energy spectrum is discussed, and other potentially useful distributions are introduced. (orig.)

  8. The EISCAT_3D Project in Norway: E3DN

    Science.gov (United States)

    La Hoz, C.; Oksavik, K.

    2013-12-01

    EISCAT_3D (E3D) is a project to build the next generation of incoherent scatter radars endowed with 3-dimensional scalar and vector capabilities that will replace the current EISCAT radars in Northern Scandinavia. One active (transmitting) site in Norway and four passive (receiving) sites in the Nordic countries will provide 3-D vector imaging capabilities by rapid scanning and multi-beam forming. The unprecedented flexibility of the solid-state transmitter with high duty-cycle, arbitrary wave-forming and polarisation and its pulsed power of 10 MW will provide unrivalled experimental capabilities to investigate the highly non-stationary and non-homogeneous state of the polar upper atmosphere. Aperture Synthesis Imaging Radar (ASIR) will to endow E3D with imaging capabilities in 3-dimensions that includes sub-beam resolution. Complemented by pulse compression, it will provide 3-dimensional images of certain types of incoherent scatter radar targets resolved to about 100 metres at 100 km range, depending on the signal-to-noise ratio. The Norwegian scientific programme is inspired by the pioneer polar scientist Kristian Birkeland (picture) and includes pressing questions on polar upper atmospheric research, among others: (Q1) How to proceed beyond the present simplistic, static, stationary and homogeneous analysis of upper atmospheric and ionospheric processes? (Q2) How does space weather affect ionospheric processes and how to support modelling and space weather services? (Q3) How to advance fundamental plasma physics by employing the ionosphere as a natural plasma physics laboratory? (Q4) How does the influx of extraterrestrial material interact with the upper atmosphere and where does the material originate from? (Q5) How does solar activity couple from geospace into the lower atmosphere and climate system, and does this energy change the wave forcing of geospace from below? Kristian Birkeland, Norwegian scientist and pioneer in polar and auroral research.

  9. Payload topography camera of Chang'e-3

    International Nuclear Information System (INIS)

    Yu, Guo-Bin; Liu, En-Hai; Zhao, Ru-Jin; Zhong, Jie; Zhou, Xiang-Dong; Zhou, Wu-Lin; Wang, Jin; Chen, Yuan-Pei; Hao, Yong-Jie

    2015-01-01

    Chang'e-3 was China's first soft-landing lunar probe that achieved a successful roving exploration on the Moon. A topography camera functioning as the lander's “eye” was one of the main scientific payloads installed on the lander. It was composed of a camera probe, an electronic component that performed image compression, and a cable assembly. Its exploration mission was to obtain optical images of the lunar topography in the landing zone for investigation and research. It also observed rover movement on the lunar surface and finished taking pictures of the lander and rover. After starting up successfully, the topography camera obtained static images and video of rover movement from different directions, 360° panoramic pictures of the lunar surface around the lander from multiple angles, and numerous pictures of the Earth. All images of the rover, lunar surface, and the Earth were clear, and those of the Chinese national flag were recorded in true color. This paper describes the exploration mission, system design, working principle, quality assessment of image compression, and color correction of the topography camera. Finally, test results from the lunar surface are provided to serve as a reference for scientific data processing and application. (paper)

  10. 75 FR 61999 - Airworthiness Directives; The Boeing Company Model 767 Airplanes

    Science.gov (United States)

    2010-10-07

    ... new rework procedures, is necessary. We also have reviewed Boeing Service Bulletins 767-57A0094 (for... Service Bulletin 767-57-0068, Revision 1, dated May 9, 2002, specifies that the compliance time to rework...,236 $6,256 255 $1,595,280. (required by AD 2001-14-19). Bonding jumper assembly rework 4 322 $662 47...

  11. 76 FR 22828 - Airworthiness Directives; The Boeing Company Model 737-700 Series Airplanes

    Science.gov (United States)

    2011-04-25

    ... January 20, 2010. Those special attention service bulletins describe procedures for doing a general visual... General Visual Inspection of Seat Tracks (i) For airplanes identified in Boeing Special Attention Service... results from reports that the aft seat leg fittings span the station (STA) 521.45 stay-out zone. We are...

  12. Simulation model for the Boeing 720B aircraft-flight control system in continuous flight.

    Science.gov (United States)

    1971-08-01

    A mathematical model of the Boeing 720B aircraft and autopilot has been derived. The model is representative of the 720B aircraft for continuous flight within a flight envelope defined by a Mach number of .4 at 20,000 feet altitude in a cruise config...

  13. 75 FR 22514 - Airworthiness Directives; The Boeing Company Model 747-200B Series Airplanes

    Science.gov (United States)

    2010-04-29

    ... Administration (FAA), DOT. ACTION: Final rule; request for comments. SUMMARY: We are adopting a new airworthiness... cracking of the fuselage skin lap joints at stringer 6 on the left and right sides from station (STA) 340... repetitive inspections for the modified area. This AD results from reviews done by Boeing, which show that...

  14. 76 FR 39763 - Special Conditions: Boeing Model 787-8 Airplane; Interaction of Systems and Structures...

    Science.gov (United States)

    2011-07-07

    ... Conditions No. 25-354A-SC] Special Conditions: Boeing Model 787-8 Airplane; Interaction of Systems and..., electronic flight control system control surface awareness, HIRF protection, limit engine torque loads for... standards. A special condition is needed to require consideration of the effects of systems on the...

  15. Climate Change Communicators: The C3E3 Project

    Science.gov (United States)

    Sharif, H. O.; Joseph, J.

    2013-12-01

    The University of Texas at San Antonio (UTSA), San Antonio College (SAC), and the University of North Dakota (UND) have partnered with NASA to provide underrepresented undergraduates from UTSA, SAC, and other community colleges climate-related research and education experiences through the Climate Change Communication: Engineer, Environmental science, and Education (C3E3) project. The program aims to develop a robust response to climate change by providing K-16 climate change education; enhance the effectiveness of K-16 education particularly in engineering and other STEM disciplines by use of new instructional technologies; increase the enrollment in engineering programs and the number of engineering degrees awarded by showing engineering's usefulness in relation to the much-discussed contemporary issue of climate change; increase persistence in STEM degrees by providing student research opportunities; and increase the ethnic diversity of those receiving engineering degrees and help ensure an ethnically diverse response to climate change. Students participated in the second summer internship funded by the project. More than 60 students participated in guided research experiences aligned with NASA Science Plan objectives for climate and Earth system science and the educational objectives of the three institutions. The students went through training in modern media technology (webcasts), and in using this technology to communicate the information on climate change to others, especially high school students, culminating in production of webcasts on investigating the aspects of climate change using NASA data. Content developed is leveraged by NASA Earth observation data and NASA Earth system models and tools. Several departments are involved in the educational program.

  16. Full-scale testing, production and cost analysis data for the advanced composite stabilizer for Boeing 737 aircraft, volume 2

    Science.gov (United States)

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

    1982-01-01

    The development, testing, production activities, and associated costs that were required to produce five-and-one-half advanced-composite stabilizer shipsets for Boeing 737 aircraft are defined and discussed.

  17. The Orf virus E3L homologue is able to complement deletion of the vaccinia virus E3L gene in vitro but not in vivo

    International Nuclear Information System (INIS)

    Vijaysri, Sangeetha; Talasela, Latha; Mercer, Andrew A.; Mcinnes, Colin J.; Jacobs, Bertram L.; Langland, Jeffrey O.

    2003-01-01

    Orf virus (OV), the prototypic parapoxvirus, is resistant to the effects of interferon (IFN) and this function of OV has been mapped to the OV20.0L gene. The protein product of this gene shares 31% amino acid identity to the E3L-encoded protein of vaccinia virus (VV) that is required for the broad host range and IFN-resistant phenotype of VV in cells in culture and for virulence of the virus in vivo. In this study we investigated whether the distantly related OV E3L homologue could complement the deletion of E3L in VV. The recombinant VV (VV/ORF-E3L) expressing the OV E3L homologue in place of VV E3L was indistinguishable from wt VV in its cell-culture phenotype. But VV/ORF-E3L was over a 1000-fold less pathogenic than wt VV (LD 50 > 5 x 10 6 PFU, compared to LD 50 of wtVV = 4 x 10 3 PFU) following intranasal infection of mice. While wt VV spread to the lungs and brain and replicated to high titers in the brain of infected mice, VV/ORF-E3L could not be detected in the lungs or brain following intranasal infection. VV/ORF-E3L was at least 100,000-fold less pathogenic than wt VV on intracranial injection. Domain swap experiments demonstrate that the difference in pathogenesis maps to the C-terminal domain of these proteins. This domain has been shown to be required for the dsRNA binding function of the VV E3L

  18. 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.

  19. 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

    2008-01-01

    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.

  20. 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.

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

    Science.gov (United States)

    1999-10-01

    Standard Encyclopedia (New York: Unicorn Publishers, 1955), 102-103. 9. The World Book Encyclopedia (Kansas City, MO: Field Enterprises Educational...costs about $25.25 per mile to operate--including insurance, administration, and financing . The amount is similar for the MD-11 and Airbus A340-300X, 9...resources that include investments, income from operations (airplane sales), or outside financing . Although Boeing customarily receives a deposit

  2. 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

  3. Electronic and structural properties of B i2S e3:Cu

    Science.gov (United States)

    Sobczak, Kamil; Strak, Pawel; Kempisty, Pawel; Wolos, Agnieszka; Hruban, Andrzej; Materna, Andrzej; Borysiuk, Jolanta

    2018-04-01

    Electronic and structural properties of B i2S e3 and its extension to copper doped B i2S e3:Cu were studied using combined ab initio simulations and transmission electron microscopy based techniques, including electron energy loss spectroscopy, energy filtered transmission electron microscopy, and energy dispersive x-ray spectroscopy. The stability of the mixed phases was investigated for substitutional and intercalation changes of basic B i2S e3 structure. Four systems were compared: B i2S e3 , structures obtaining by Cu intercalation of the van der Waals gap, by substitution of Bi by Cu in quintuple layers, and C u2Se . The structures were identified and their electronic properties were obtained. Transmission electron microscopy measurements of B i2S e3 and the B i2S e3:Cu system identified the first structure as uniform and the second as composite, consisting of a nonuniform lower-Cu-content matrix and randomly distributed high-Cu-concentration precipitates. Critical comparison of the ab initio and experimental data identified the matrix as having a B i2S e3 dominant part with randomly distributed Cu-intercalated regions having 1Cu-B i2S e3 structure. The precipitates were determined to have 3Cu-B i2S e3 structure.

  4. 75 FR 9760 - Airworthiness Directives; The Boeing Company Model 747-100, 747-100B, 747-100B SUD, 747-200B, 747...

    Science.gov (United States)

    2010-03-04

    .... ADDRESSES: For service information identified in this AD, contact Boeing Commercial Airplanes, Attention... Management Facility, U.S. Department of Transportation, Docket Operations, M-30, West Building Ground Floor.... Figure 31, Sheet 7, of the Accomplishment Instructions of Boeing Alert Service Bulletin 747- 51A2060...

  5. (e,3e) collisions on He in the quasi-dipolar regime

    International Nuclear Information System (INIS)

    Taouil, I.; Lahmam-Bennani, A.; Duguet, A.

    1999-01-01

    We report the first measurement of the angular distributions of the two ejected electrons following electron impact double ionization of helium, using a multi-parameter (e,3e) spectrometer. The high incident energy of these experiments allows comparison with photo-double ionization results. Comparison is also made with existing (e,3e) theoretical calculations. (orig.)

  6. PXR agonism decreases plasma HDL levels in ApoE*3-Leiden.CETP mice

    NARCIS (Netherlands)

    Haan, W. de; Vries-van der Weij, J. de; Mol, I.M.; Hoekstra, M.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Princen, H.M.G.; Rensen, P.C.N.

    2009-01-01

    Pregnane X receptor (PXR) agonism has been shown to affect multiple steps in both the synthesis and catabolism of HDL, but its integrated effect on HDL metabolism in vivo remains unclear. The aim of this study was to evaluate the net effect of PXR agonism on HDL metabolism in ApoE*3-Leiden (E3L) and

  7. G2E3 is a nucleo-cytoplasmic shuttling protein with DNA damage responsive localization

    International Nuclear Information System (INIS)

    Brooks, William S.; Banerjee, Sami; Crawford, David F.

    2007-01-01

    G2E3 was originally described as a G2/M-specific gene with DNA damage responsive expression. The presence of a conserved HECT domain within the carboxy-terminus of the protein indicated that it likely functions as a ubiquitin ligase or E3. Although HECT domains are known to function in this capacity for many proteins, we demonstrate that a portion of the HECT domain from G2E3 plays an important role in the dynamic subcellular localization of the protein. We have shown that G2E3 is a nucleo-cytoplasmic shuttling protein with nuclear export mediated by a novel nuclear export domain that functions independently of CRM1. In full-length G2E3, a separate region of the HECT domain suppresses the function of the NES. Additionally, G2E3 contains a nucleolar localization signal (NoLS) in its amino terminus. Localization of G2E3 to the nucleolus is a dynamic process, and the protein delocalizes from the nucleolus rapidly after DNA damage. Cell cycle phase-specific expression and highly regulated subcellular localization of G2E3 suggest a possible role in cell cycle regulation and the cellular response to DNA damage

  8. 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

  9. 17 CFR 270.22e-3 - Exemption for liquidation of money market funds.

    Science.gov (United States)

    2010-04-01

    ... money market funds. 270.22e-3 Section 270.22e-3 Commodity and Securities Exchanges SECURITIES AND... for liquidation of money market funds. (a) Exemption. A registered open-end management investment company or series thereof (“fund”) that is regulated as a money market fund under § 270.2a-7 is exempt...

  10. 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

  11. 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.

  12. 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.

  13. A novel NR2E3 gene mutation in autosomal recessive retinitis pigmentosa with cystic maculopathy

    OpenAIRE

    Mahajan, D.; Votruba, Marcela

    2017-01-01

    NR2E3 is a gene that encodes for photoreceptor cell specific nuclear receptor, which is involved in cone proliferation. The splice site mutation 119-2A>C in NR2E3 (15q23) has been previously reported to underlie recessive enhanced cone S sensitivity syndrome, clumped pigmentary retinal degeneration, Goldman-Favre syndrome and also autosomal dominant and autosomal recessive retinitis pigmentosa (RP). However, the mutation c 571 + 2 T > C in NR2E3 has not been previously reported with retinal d...

  14. First results with the general equilibrium model GEM-E3 Switzerland

    International Nuclear Information System (INIS)

    Bahn, O.; Frei, C.

    2000-01-01

    The GEM-E3 model has been implemented and applied for Switzerland. It has been in particular used to assess an ecological tax reform in Switzerland. Results of this analysis are presented here. (author)

  15. Scaling of cross-sections for asymmetric (e,3e) process on helium ...

    Indian Academy of Sciences (India)

    , India ... (e, 3e) process; five-fold differential cross-section; scaling; helium isoelec- tronic ions. ... ration and experimental control of the target and the intensity related problems make the measurements extremely difficult. The scaling laws of ...

  16. Redefining E-3 Core Competencies for Dominant Battlespace Knowledge in Future Combat Operations

    National Research Council Canada - National Science Library

    Kirkendall, David A

    2005-01-01

    .... The study focuses on how E-3 training is driven by the maintenance of a set of battle management core competencies rooted in the basics of aircraft tactical fluid control force accountability and aerial refueling...

  17. 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.

  18. 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.

  19. A study of the profile of the E3 electron trap in GaAs

    Energy Technology Data Exchange (ETDEWEB)

    Kourkoutas, C.D. (TEI Athens (Greece). Dept. of Physics Chemistry and Material Technology); Kovacs, B.; Szentpali, B.; Somogyi, K. (Research Inst. for Technical Physics, Budapest (Hungary)); Euthymiou, P.C. (Athens Univ. (Greece)); Giakoumakis, G.E. (Ioannina Univ. (Greece). Dept. of Physics)

    1994-01-01

    Electron irradiation at room temperature introduces in GaAs a donor type electronic state Tx at 0.18 eV, which is associated with the E3 electron trap. The presence of Tx is observed at depths d > 1.5 [mu]m, which correspond to the limits of the depletion region under the highest applied reverse bias voltage, while the E3 trap concentration drops off into the same region. (author).

  20. A study of the profile of the E3 electron trap in GaAs

    International Nuclear Information System (INIS)

    Kourkoutas, C.D.; Euthymiou, P.C.; Giakoumakis, G.E.

    1994-01-01

    Electron irradiation at room temperature introduces in GaAs a donor type electronic state Tx at 0.18 eV, which is associated with the E3 electron trap. The presence of Tx is observed at depths d > 1.5 μm, which correspond to the limits of the depletion region under the highest applied reverse bias voltage, while the E3 trap concentration drops off into the same region. (author)

  1. 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.

  2. Aircraft Fire Sentry. Volume 2. Appendices

    Science.gov (United States)

    1993-01-01

    including New Mexico Engineering Research Institute (NMERI), National Institute of Standards and Technology (NIST), Wright-Patterson AFB, and AFESC at...Installation Remove the mounting bracket from the smoke alarm by depresing the release tab marked "PRESS" (see Figure 1. pg. 5). Pivot the bracket awey from and

  3. 75 FR 81508 - Airworthiness Directives; The Boeing Company Model 777-200, -200LR, -300, and -300ER Series...

    Science.gov (United States)

    2010-12-28

    ... require installing new panels in the main equipment center, making certain wiring changes, installing new..., Boeing found indications of wiring deterioration that could cause electrical faults in the main tank... center; making certain wiring changes; installing new GFI relays in the P301 and P302 panels; and...

  4. 75 FR 8554 - Airworthiness Directives; The Boeing Company Model 747-100, -200B, and -200F Series Airplanes

    Science.gov (United States)

    2010-02-25

    ...-0132; Directorate Identifier 2009-NM-096-AD] RIN 2120-AA64 Airworthiness Directives; The Boeing Company... approaching or have exceeded their design life goal. We issued that AD to prevent separation of fuselage skin...,000 flight cycles to 1,000 flight cycles. Differences Between the Proposed AD and Service Bulletin...

  5. 76 FR 60710 - Airworthiness Directives; The Boeing Company Model 737-600, -700, -700C, -800, and -900 Series...

    Science.gov (United States)

    2011-09-30

    ... universal fault interrupters (UFIs) using a certain supplemental type certificate. This new AD continues to... interrupter (GFI) feature, or installation and maintenance of universal fault interrupters (UFIs) using a... section of this AD to include this contact information. Request To Revise a Word Boeing requested a change...

  6. 78 FR 68986 - Special Conditions: Boeing Model 777-200, -300, and -300ER Series Airplanes; Aircraft Electronic...

    Science.gov (United States)

    2013-11-18

    .... SUPPLEMENTARY INFORMATION: Background On August 21, 2012, The Boeing Company applied for a change to Type... vulnerabilities from intentional or unintentional corruption of data and systems critical to the safety and maintenance of the airplane. The existing regulations and guidance material did not anticipate this type of...

  7. 78 FR 68985 - Special Conditions: Boeing Model 777-200, -300, and -300ER Series Airplanes; Aircraft Electronic...

    Science.gov (United States)

    2013-11-18

    ... Boeing Company applied for a change to Type Certificate No. T00001SE Rev. 30 dated June 6, 2012 for... integration may result in security vulnerabilities from intentional or unintentional corruption of data and... material did not anticipate this type of system architecture or electronic access to aircraft systems...

  8. 76 FR 24354 - Airworthiness Directives; The Boeing Company Model 777-200 and -300 Series Airplanes Equipped...

    Science.gov (United States)

    2011-05-02

    ... this AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC.... Department of Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New.... Required parts cost about $122,617 per product. Based on these figures, we estimate the cost of this AD to...

  9. 75 FR 5677 - Airworthiness Directives; The Boeing Company Model 767-200, -300, and -300F Series Airplanes

    Science.gov (United States)

    2010-02-04

    ... AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H... a magnetic particle inspection (MPI) in accordance with Part 4, ``Magnetic Particle Inspection of... November 5, 2009, or MPI in accordance with Part 4, ``Magnetic Particle Inspection of the Midspar Fuse Pin...

  10. 75 FR 9137 - Airworthiness Directives; The Boeing Company Model 737-100, -200, -200C, -300, -400, and -500...

    Science.gov (United States)

    2010-03-01

    ... AD, contact Boeing Commercial Airplanes, P.O. Box 3707, Seattle, Washington 98124-2207. Examining the... repetitive detailed and magnetic particle inspections to detect discrepancies (including corrosion, pitting... detailed inspection for corrosion, pitting, and cracking of the carriage spindle, the magnetic particle...

  11. 76 FR 42607 - Airworthiness Directives; The Boeing Company Model 767-200, -300, and -400ER Series Airplanes

    Science.gov (United States)

    2011-07-19

    ... CONTACT: Stephen Styskal, Aerospace Engineer, Cabin Safety and Environmental Systems Branch, ANM-150S, FAA...) 917-6439; fax: (425) 917-6590; e- mail: stephen[email protected] . SUPPLEMENTARY INFORMATION: Comments... Information (h) Actions done before the effective date of this AD in accordance with Boeing Special Attention...

  12. 75 FR 2433 - Special Conditions: Boeing Model 747-8/-8F Airplanes, Systems and Data Networks Security...

    Science.gov (United States)

    2010-01-15

    ... Conditions No. 25-401-SC] Special Conditions: Boeing Model 747-8/-8F Airplanes, Systems and Data Networks Security--Protection of Airplane Systems and Data Networks From Unauthorized External Access AGENCY... that effective electronic system security protection strategies are implemented to protect the airplane...

  13. Molecular structure and spectral properties of ethyl 3-quinolinecarboxylate (E3Q) and [Ag(E3Q)2(TCA)] complex (TCA = Trichloroacetate)

    Science.gov (United States)

    Soliman, Saied M.; Kassem, Taher S.; Badr, Ahmed M. A.; Abou Youssef, Morsy A.; Assem, Rania

    2014-09-01

    A new [Ag(E3Q)2(TCA)] complex; (E3Q = Ethyl 3-quinolinecarboxylate and TCA = Trichloroacetate) has been synthesized and characterized using elemental analysis, FTIR, NMR and mass spectroscopy. The molecular geometry and spectroscopic properties of the complex as well as the free ligand have been calculated using the hybrid B3LYP method. The calculations predicted a distorted tetrahedral arrangement around Ag(I) ion. The vibrational spectra of the studied compounds have been assigned using potential energy distribution (PED). TD-DFT method was used to predict the electronic absorption spectra. The most intense absorption band showed a bathochromic shift and lowering of intensity in case of the complex (233.7 nm, f = 0.5604) compared to E3Q (λmax = 228.0 nm, f = 0.9072). The calculated 1H NMR chemical shifts using GIAO method showed good correlations with the experimental data. The computed dipole moment, polarizability and HOMO-LUMO energy gap were used to predict the nonlinear optical (NLO) properties. It is found that Ag(I) enhances the NLO activity. The natural bond orbital (NBO) analyses were used to elucidate the intramolecular charge transfer interactions causing stabilization for the investigated systems.

  14. 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

  15. STS-65 crewmembers and backup participate in bench review at Boeing Building

    Science.gov (United States)

    1994-01-01

    STS-65 crewmembers, wearing clean suits, look over equipment to be carried aboard the Space Shuttle Columbia, Orbiter Vehicle (OV) 102, for the scheduled July flight of the second International Microgravity Laboratory (IML-2) mission. Surrounding a table full of equipment at Boeing's Flight Equipment Processing Facility near the Johnson Space Center (JSC), are (left to right) Mission Specialist (MS) Leroy Chiao, MS Donald A. Thomas, Commander Robert D. Cabana, Payload Specialist Chiaki Mukai, Payload Commander (PLC) Richard J. Hieb, and backup (alternate) payload specialist Jean-Jacques Favier. Mukai represents Japan's National Space Development Agency (NASDA) and Favier represents France's Centre National d'Etudes Spatiales. Photo taken by NASA JSC contract photographer Scott A. Wickes.

  16. 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....

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

    Directory of Open Access Journals (Sweden)

    Wouter Boomsma

    2016-02-01

    Full Text Available 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 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 of their ordered regions, and did not capture the unique disorder patterns that encode the functional mechanism of San1. However, by searching specifically for key features of the San1 sequence, such as long regions of intrinsic disorder embedded with short stretches predicted to be suitable for substrate interaction, we identified several E3 ligases with these characteristics. Our initial analysis revealed that another remarkable trait of San1 is shared with several candidate E3 ligases: long stretches of complete lysine suppression, which in San1 limits auto-ubiquitination. We encode these characteristic features into a San1 similarity-score, and present a set of proteins that are plausible candidates as San1 counterparts in humans. In conclusion, our work

  18. 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.

  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. NMR characterization of foldedness for the production of E3 RING domains

    NARCIS (Netherlands)

    Huang, A.; de Jong, R.N.; Folkers, G.E.; Boelens, R.

    2010-01-01

    We summarize the use of NMR spectroscopy in the production and the screening of stability and foldedness of protein domains, and apply it to the RING domains of E3 ubiquitin-ligases. RING domains are involved in specific interactions with E2 ubiquitin-conjugating enzymes and thus play an essential

  1. 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

  2. Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C.

    Science.gov (United States)

    Brown, Nicholas G; VanderLinden, Ryan; Watson, Edmond R; Weissmann, Florian; Ordureau, Alban; Wu, Kuen-Phon; Zhang, Wei; Yu, Shanshan; Mercredi, Peter Y; Harrison, Joseph S; Davidson, Iain F; Qiao, Renping; Lu, Ying; Dube, Prakash; Brunner, Michael R; Grace, Christy R R; Miller, Darcie J; Haselbach, David; Jarvis, Marc A; Yamaguchi, Masaya; Yanishevski, David; Petzold, Georg; Sidhu, Sachdev S; Kuhlman, Brian; Kirschner, Marc W; Harper, J Wade; Peters, Jan-Michael; Stark, Holger; Schulman, Brenda A

    2016-06-02

    Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized catalytic architectures for these two distinct forms of polyubiquitination. The APC/C RING constrains UBE2C proximal to a substrate and simultaneously binds a substrate-linked UB to drive processive multiubiquitination. Alternatively, during UB chain elongation, the RING does not bind UBE2S but rather lures an evolving substrate-linked UB to UBE2S positioned through a cullin interaction to generate a Lys11-linked chain. Our findings define mechanisms of APC/C regulation, and establish principles by which specialized E3-E2-substrate-UB architectures control different forms of polyubiquitination. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Characterizations of Space Curves According to Bishop Darboux Vector in Euclidean 3-Space E3

    OpenAIRE

    Huseyin KOCAYIGIT; Ali OZDEMIR

    2014-01-01

    In this paper, we obtained some characterizations of space curves according to Bihop frame in Euclidean 3-space E3 by using Laplacian operator and Levi-Civita connection. Furthermore, we gave the general differential equations which characterize the space curves according to the Bishop Darboux vector and the normal Bishop Darboux vector.

  4. 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

  5. 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.

  6. E3 protein of bovine coronavirus is a receptor-destroying enzyme with acetylesterase activity

    International Nuclear Information System (INIS)

    Vlasak, R.; Luytjes, W.; Leider, J.; Spaan, W.; Palese, P.

    1988-01-01

    In addition to members of the Orthomyxoviridae and Paramyxoviridae, several coronaviruses have been shown to possess receptor-destroying activities. Purified bovine coronavirus (BCV) preparations have an esterase activity which inactivates O-acetylsialic acid-containing receptors on erythrocytes. Diisopropyl fluorophosphate (DFP) completely inhibits this receptor-destroying activity of BCV, suggesting that the viral enzyme is a serine esterase. Treatment of purified BCV with [ 3 H]DFP and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the proteins revealed that the esterase/receptor-destroying activity of BCV is associated with the E3 protein was specifically phosphorylated. This finding suggests that the esterase/receptor-destroying activity of BCV is associated with the E3 protein. Furthermore, treatment of BCV with DFP dramatically reduced its infectivity in a plaque assay. It is assumed that the esterase activity of BCV is required in an early step of virus replication, possible during virus entry or uncoating

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

    Science.gov (United States)

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

    2015-09-01

    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 that were 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 analysed. Low-resolution, medium signal-to-noise ratio spectra of nine 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 distance from the Sun is nearly 10 kpc. It is also somewhat metal rich with [Fe/H] = -0.7. Regarding its kinematics, our tentative estimate for the proper motions is (μα cosδ,μδ) = (-7.0 ± 0.8, 3.5 ± 0.3) mas yr-1 (or a tangential velocity of 382 ± 79 km s-1) and for the radial velocity 45 ± 5 km s-1 in the solar rest frame. Conclusions: E 3 is one of the most intriguing globular clusters in the Galaxy. Having an old age and being metal rich is clearly a peculiar combination, only seen in a handful of objects like the far more conspicuous NGC 104 (47 Tucanae). In addition, its low luminosity and sparse population make it a unique template for the study of the final evolutionary phases in the life of a star cluster. Unfortunately, E 3 is among the most elusive and challenging known globular clusters because field contamination severely hampers spectroscopic studies. This research note is based on observations made with the ESO VLT at the

  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. E3 protein of bovine coronavirus is a receptor-destroying enzyme with acetylesterase activity

    Energy Technology Data Exchange (ETDEWEB)

    Vlasak, R.; Luytjes, W.; Leider, J.; Spaan, W.; Palese, P.

    1988-12-01

    In addition to members of the Orthomyxoviridae and Paramyxoviridae, several coronaviruses have been shown to possess receptor-destroying activities. Purified bovine coronavirus (BCV) preparations have an esterase activity which inactivates O-acetylsialic acid-containing receptors on erythrocytes. Diisopropyl fluorophosphate (DFP) completely inhibits this receptor-destroying activity of BCV, suggesting that the viral enzyme is a serine esterase. Treatment of purified BCV with (/sup 3/H)DFP and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the proteins revealed that the esterase/receptor-destroying activity of BCV is associated with the E3 protein was specifically phosphorylated. This finding suggests that the esterase/receptor-destroying activity of BCV is associated with the E3 protein. Furthermore, treatment of BCV with DFP dramatically reduced its infectivity in a plaque assay. It is assumed that the esterase activity of BCV is required in an early step of virus replication, possible during virus entry or uncoating.

  10. Establishment of a Wheat Cell-Free Synthesized Protein Array Containing 250 Human and Mouse E3 Ubiquitin Ligases to Identify Novel Interaction between E3 Ligases and Substrate Proteins.

    Directory of Open Access Journals (Sweden)

    Hirotaka Takahashi

    Full Text Available Ubiquitination is a key post-translational modification in the regulation of numerous biological processes in eukaryotes. The primary roles of ubiquitination are thought to be the triggering of protein degradation and the regulation of signal transduction. During protein ubiquitination, substrate specificity is mainly determined by E3 ubiquitin ligase (E3. Although more than 600 genes in the human genome encode E3, the E3s of many target proteins remain unidentified owing to E3 diversity and the instability of ubiquitinated proteins in cell. We demonstrate herein a novel biochemical analysis for the identification of E3s targeting specific proteins. Using wheat cell-free protein synthesis system, a protein array containing 227 human and 23 mouse recombinant E3s was synthesized. To establish the high-throughput binding assay using AlphaScreen technology, we selected MDM2 and p53 as the model combination of E3 and its target protein. The AlphaScreen assay specifically detected the binding of p53 and MDM2 in a crude translation mixture. Then, a comprehensive binding assay using the E3 protein array was performed. Eleven of the E3s showed high binding activity, including four previously reported E3s (e.g., MDM2, MDM4, and WWP1 targeting p53. This result demonstrated the reliability of the assay. Another interactors, RNF6 and DZIP3-which there have been no report to bind p53-were found to ubiquitinate p53 in vitro. Further analysis showed that RNF6 decreased the amount of p53 in H1299 cells in E3 activity-dependent manner. These results suggest the possibility that the RNF6 ubiquitinates and degrades p53 in cells. The novel in vitro screening system established herein is a powerful tool for finding novel E3s of a target protein.

  11. Lunar Penetrating Radar onboard the Chang'e-3 mission

    International Nuclear Information System (INIS)

    Fang Guang-You; Zhou Bin; Ji Yi-Cai; Zhang Qun-Ying; Shen Shao-Xiang; Li Yu-Xi; Guan Hong-Fei; Tang Chuan-Jun; Gao Yun-Ze; Lu Wei; Ye Sheng-Bo; Han Hai-Dong; Zheng Jin; Wang Shu-Zhi

    2014-01-01

    Lunar Penetrating Radar (LPR) is one of the important scientific instruments onboard the Chang'e-3 spacecraft. Its scientific goals are the mapping of lunar regolith and detection of subsurface geologic structures. This paper describes the goals of the mission, as well as the basic principles, design, composition and achievements of the LPR. Finally, experiments on a glacier and the lunar surface are analyzed

  12. ISG15 inhibits Nedd4 ubiquitin E3 activity and enhances the innate antiviral response.

    Science.gov (United States)

    Malakhova, Oxana A; Zhang, Dong-Er

    2008-04-04

    Interferons regulate diverse immune functions through the transcriptional activation of hundreds of genes involved in anti-viral responses. The interferon-inducible ubiquitin-like protein ISG15 is expressed in cells in response to a variety of stress conditions like viral or bacterial infection and is present in its free form or is conjugated to cellular proteins. In addition, protein ubiquitination plays a regulatory role in the immune system. Many viruses modulate the ubiquitin (Ub) pathway to alter cellular signaling and the antiviral response. Ubiquitination of retroviral group-specific antigen precursors and matrix proteins of the Ebola, vesicular stomatitis, and rabies viruses by Nedd4 family HECT domain E3 ligases is an important step in facilitating viral release. We found that Nedd4 is negatively regulated by ISG15. Free ISG15 specifically bound to Nedd4 and blocked its interaction with Ub-E2 molecules, thus preventing further Ub transfer from E2 to E3. Furthermore, overexpression of ISG15 diminished the ability of Nedd4 to ubiquitinate viral matrix proteins and led to a decrease in the release of Ebola VP40 virus-like particles from the cells. These results point to a mechanistically novel function of ISG15 in the enhancement of the innate anti-viral response through specific inhibition of Nedd4 Ub-E3 activity. To our knowledge, this is the first example of a Ub-like protein with the ability to interfere with Ub-E2 and E3 interaction to inhibit protein ubiquitination.

  13. Proteolytic regulation of metabolic enzymes by E3 ubiquitin ligase complexes: lessons from yeast.

    Science.gov (United States)

    Nakatsukasa, Kunio; Okumura, Fumihiko; Kamura, Takumi

    2015-01-01

    Eukaryotic organisms use diverse mechanisms to control metabolic rates in response to changes in the internal and/or external environment. Fine metabolic control is a highly responsive, energy-saving process that is mediated by allosteric inhibition/activation and/or reversible modification of preexisting metabolic enzymes. In contrast, coarse metabolic control is a relatively long-term and expensive process that involves modulating the level of metabolic enzymes. Coarse metabolic control can be achieved through the degradation of metabolic enzymes by the ubiquitin-proteasome system (UPS), in which substrates are specifically ubiquitinated by an E3 ubiquitin ligase and targeted for proteasomal degradation. Here, we review select multi-protein E3 ligase complexes that directly regulate metabolic enzymes in Saccharomyces cerevisiae. The first part of the review focuses on the endoplasmic reticulum (ER) membrane-associated Hrd1 and Doa10 E3 ligase complexes. In addition to their primary roles in the ER-associated degradation pathway that eliminates misfolded proteins, recent quantitative proteomic analyses identified native substrates of Hrd1 and Doa10 in the sterol synthesis pathway. The second part focuses on the SCF (Skp1-Cul1-F-box protein) complex, an abundant prototypical multi-protein E3 ligase complex. While the best-known roles of the SCF complex are in the regulation of the cell cycle and transcription, accumulating evidence indicates that the SCF complex also modulates carbon metabolism pathways. The increasing number of metabolic enzymes whose stability is directly regulated by the UPS underscores the importance of the proteolytic regulation of metabolic processes for the acclimation of cells to environmental changes.

  14. A bacterial E3 ubiquitin ligase targets a host protein kinase to disrupt plant immunity.

    Science.gov (United States)

    Rosebrock, Tracy R; Zeng, Lirong; Brady, Jennifer J; Abramovitch, Robert B; Xiao, Fangming; Martin, Gregory B

    2007-07-19

    Many bacterial pathogens of plants and animals use a type III secretion system to deliver diverse virulence-associated 'effector' proteins into the host cell. The mechanisms by which these effectors act are mostly unknown; however, they often promote disease by suppressing host immunity. One type III effector, AvrPtoB, expressed by the plant pathogen Pseudomonas syringae pv. tomato, has a carboxy-terminal domain that is an E3 ubiquitin ligase. Deletion of this domain allows an amino-terminal region of AvrPtoB (AvrPtoB(1-387)) to be detected by certain tomato varieties leading to immunity-associated programmed cell death. Here we show that a host kinase, Fen, physically interacts with AvrPtoB(1-387 )and is responsible for activating the plant immune response. The AvrPtoB E3 ligase specifically ubiquitinates Fen and promotes its degradation in a proteasome-dependent manner. This degradation leads to disease susceptibility in Fen-expressing tomato lines. Various wild species of tomato were found to exhibit immunity in response to AvrPtoB(1-387 )and not to full-length AvrPtoB. Thus, by acquiring an E3 ligase domain, AvrPtoB has thwarted a highly conserved host resistance mechanism.

  15. Quantum phase transition in the U(4) vibron model and the E(3) symmetry

    International Nuclear Information System (INIS)

    Zhang Yu; Hou Zhanfeng; Chen Huan; Wei Haiqing; Liu Yuxin

    2008-01-01

    We study the details of the U(3)-O(4) quantum phase transition in the U(4) vibron model. Both asymptotic analysis in the classical limit and rigorous calculations for finite boson number systems indicate that a second-order phase transition is still there even for the systems with boson number N ranging from tens to hundreds. Two kinds of effective order parameters, including E1 transition ratios B(E1:2 1 →1 1 )/B(E1:1 1 →0 1 ) and B(E1:0 2 →1 1 )/B(E1:1 1 →0 1 ), and the energy ratios E 2 1 /E 0 2 and E 3 1 /E 0 2 are proposed to identify the second-order phase transition in experiments. We also found that the critical point of phase transition can be approximately described by the E(3) symmetry, which persists even for moderate N∼10 protected by the scaling behaviors of quantities at the critical point. In addition, a possible empirical example exhibiting roughly the E(3) symmetry is discussed

  16. 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.

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

    International Nuclear Information System (INIS)

    Augusto, Silas C.; Oliveira, Mauro V.

    2011-01-01

    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 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 TM E3 Studio processes and using iLog Studio. (author)

  19. 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.

  20. Identification of Arabidopsis MYB56 as a novel substrate for CRL3BPM E3 ligases.

    Science.gov (United States)

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

    2014-10-24

    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 pointed out 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 the flowering time point in plants. © The Author 2014. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

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

    International Nuclear Information System (INIS)

    None

    2000-01-01

    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 and D) of the previously used nuclear facilities and associated site areas. Large-scale D and 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

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

    International Nuclear Information System (INIS)

    Bahn, O.; Frei, C.

    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 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 2 emissions were evaluated: a carbon tax ('tax only' strategy), and the combination of a carbon tax with the buying of CO 2 emission permits ('permits and tax' strategy). In the first strategy, Switzerland would impose the necessary carbon tax to achieve the reduction target, and use the tax

  7. Structure of the Human FANCL RING-Ube2T Complex Reveals Determinants of Cognate E3-E2 Selection

    Science.gov (United States)

    Hodson, Charlotte; Purkiss, Andrew; Miles, Jennifer Anne; Walden, Helen

    2014-01-01

    Summary The combination of an E2 ubiquitin-conjugating enzyme with an E3 ubiquitin-ligase is essential for ubiquitin modification of a substrate. Moreover, the pairing dictates both the substrate choice and the modification type. The molecular details of generic E3-E2 interactions are well established. Nevertheless, the determinants of selective, specific E3-E2 recognition are not understood. There are ∼40 E2s and ∼600 E3s giving rise to a possible ∼24,000 E3-E2 pairs. Using the Fanconi Anemia pathway exclusive E3-E2 pair, FANCL-Ube2T, we report the atomic structure of the FANCL RING-Ube2T complex, revealing a specific and extensive network of additional electrostatic and hydrophobic interactions. Furthermore, we show that these specific interactions are required for selection of Ube2T over other E2s by FANCL. PMID:24389026

  8. 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.

  9. Subsurface structures in the northern Mare Imbrium measured by Chang'E-3 and SELENE

    Science.gov (United States)

    Kumamoto, A.; Ishiyama, K.; Feng, J.

    2016-12-01

    Subsurface structures in the northern Mare Imbrium measured by Chang'E-3 and SELENE have been compared. In Chang'E-3 mission, subsurface radar sounding at (19.51W, 44.12N) was performed by Lunar Penetrating Radar (LPR) onboard the Yutu rover. The LPR was pulse radar operated at two frequencies: 60 MHz and 500 MHz. During its operation period from December 2013 to January 2014, the LPR observed subsurface echoes along the rover's track with total distance of 114 m. From the observation in 60 MHz, the subsurface echoes from buried regolith layers at depths of 35, 50, 140, 240, and 360 m were reported (Xiao et al., 2015). In SELENE mission, global subsurface radar sounding of the moon was performed by Lunar Radar Sounder (LRS) onboard the SELENE (Kaguya) spacecraft from the polar orbit with an altitude of 100 km. The LRS was chirp radar operated in a frequency range from 4-6 MHz. So the range resolution of LRS was 75 m in vacuum. During operation period from December 2007 to September 2008, subsurface echoes from all areas of the Moon was observed with a lateral resolution of 76 m. From the global observation, the subsurface echoes from the buried regolith layers in the neraside maria including Mare Imbrium at depths of several hundred meters were reported (Ono et al., 2009).In the present study, we focus on SELENE/LRS data obtained at (19.50W, 44.12N) which is the nearest to the Chang'E-3 landing site. While clear and large-scale subsurface reflectors, as found in Ono et al. (2009), are not found in it, we can identify some echo components from the depths of 140 ( 2000 ns), 240 ( 4000 ns), and 360 m ( 6000 ns). Further analyses utilizing high-resolution data from Chang'E-3/LPR and large-scale data from SELENE/LRS, we will be able to determine the thickness and large-scale structures of the buried regolith layers found by the both radars, and discuss their formation processes in volcanic history of Mare Imbrium.

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

    OpenAIRE

    Gao Yun-ze; Dong Ze-hua; Fang Guang-you; Ji Yi-cai; Zhou Bin

    2015-01-01

    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. Mo...

  11. High-spin yrast isomers in 211Rn and 212Rn with enhanced E3 decays

    International Nuclear Information System (INIS)

    Dracoulis, G.D.; Byrne, A.P.; Fabricius, B.

    1990-01-01

    New isomeric states with J π =69/2 + ,τ m = 13 (1) ns in 211 Rn and J π =33 - ,τ m = 7(1) ns in 212 Rn have been identified. They decay by enchanced E3 transitions with strengths of 33(3) and 43(6) single particle units to the known 63/2 - and 30 + isomers 211 Rn and 212 Rn, respectively. The excitation energies and transition strengths agree well with predictions of the multi-particle, octupole-vibration coupled model. 13 refs., 2 tabs., 3 figs

  12. IFT20 modulates ciliary PDGFRα signaling by regulating the stability of Cbl E3 ubiquitin ligases

    DEFF Research Database (Denmark)

    Schmid, Fabian Marc; Schou, Kenneth Bødtker; Vilhelm, Martin Juel

    2018-01-01

    ciliogenesis, and ciliary localization of the receptor is required for its appropriate ligand-mediated activation by PDGF-AA. However, the mechanisms regulating sorting of PDGFRα and feedback inhibition of PDGFRα signaling at the cilium are unknown. Here, we provide evidence that intraflagellar transport...... protein 20 (IFT20) interacts with E3 ubiquitin ligases c-Cbl and Cbl-b and is required for Cbl-mediated ubiquitination and internalization of PDGFRα for feedback inhibition of receptor signaling. In wild-type cells treated with PDGF-AA, c-Cbl becomes enriched in the cilium, and the receptor...

  13. Coplanar (e, 3e) differential cross-section of He atom

    CERN Document Server

    Choubisa, R; Sud, K K

    2003-01-01

    We present in this paper the results of our calculation of five-fold differential cross-section (FDCS) for (e, 3e) process on He atom in low momentum transfer and high electron impact energy in shake-off mechanism. The formalism has been developed in Born approximation using plane waves. Byron and Joachain as well as Le Sech and correlated BBK-type wave functions respectively for incident and scattered. bound and ejected electrons. The angular distribution of FDCS of our calculation is presented in various modes of coplanar geometry and comparison is made with the available experimental data. We observe that the present calculation is able to reproduce the trend of the experimental data. However, it differs in magnitude from the experiment. The present theory does not predict four-peak structure in summed mutual angle mode for lower excess ejected electron energies. We also discuss the importance of momentum transfer, post-collision interaction (PCI) and ion participation in the (e, 3e) process in constant th...

  14. 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).

  15. Aurora Kinase A Promotes AR Degradation via the E3 Ligase CHIP.

    Science.gov (United States)

    Sarkar, Sukumar; Brautigan, David L; Larner, James M

    2017-08-01

    Reducing the levels of the androgen receptor (AR) is one of the most viable approaches to combat castration-resistant prostate cancer. Previously, we observed that proteasomal-dependent degradation of AR in response to 2-methoxyestradiol (2-ME) depends primarily on the E3 ligase C-terminus of HSP70-interacting protein (STUB1/CHIP). Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation. Aurora A kinase is activated by 2-ME in the S-phase as well as during mitosis, and phosphorylates CHIP at S273. Prostate cancer cells expressing an S273A mutant of CHIP have attenuated AR degradation upon 2-ME treatment compared with cells expressing wild-type CHIP, supporting the idea that CHIP phosphorylation by Aurora A activates its E3 ligase activity for the AR. These results reveal a novel 2-ME→Aurora A→CHIP→AR pathway that promotes AR degradation via the proteasome that may offer novel therapeutic opportunities for prostate cancer. Mol Cancer Res; 15(8); 1063-72. ©2017 AACR . ©2017 American Association for Cancer Research.

  16. The MIEL1 E3 Ubiquitin Ligase Negatively Regulates Cuticular Wax Biosynthesis in Arabidopsis Stems.

    Science.gov (United States)

    Lee, Hong Gil; Kim, Juyoung; Suh, Mi Chung; Seo, Pil Joon

    2017-07-01

    Cuticular wax is an important hydrophobic layer that covers the plant aerial surface. Cuticular wax biosynthesis is shaped by multiple layers of regulation. In particular, a pair of R2R3-type MYB transcription factors, MYB96 and MYB30, are known to be the main participants in cuticular wax accumulation. Here, we report that the MYB30-INTERACTING E3 LIGASE 1 (MIEL1) E3 ubiquitin ligase controls the protein stability of the two MYB transcription factors and thereby wax biosynthesis in Arabidopsis. MIEL1-deficient miel1 mutants exhibit increased wax accumulation in stems, with up-regulation of wax biosynthetic genes targeted by MYB96 and MYB30. Genetic analysis reveals that wax accumulation of the miel1 mutant is compromised by myb96 or myb30 mutation, but MYB96 is mainly epistatic to MIEL1, playing a predominant role in cuticular wax deposition. These observations indicate that the MIEL1-MYB96 module is important for balanced cuticular wax biosynthesis in developing inflorescence stems. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. 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.

  18. 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.

  19. A conserved role for the ARC1 E3 ligase in Brassicaceae self-incompatibility

    Directory of Open Access Journals (Sweden)

    Daphne eGoring

    2014-05-01

    Full Text Available Ubiquitination plays essential roles in the regulation of many processes in plants including pollen rejection in self-incompatible species. In the Brassicaceae (mustard family, self-incompatibility drives the rejection of self-pollen by preventing pollen hydration following pollen contact with the stigmatic surface. Self-pollen is recognized by a ligand-receptor pair: the pollen S-locus Cysteine Rich/S-locus Protein 11 (SCR/SP11 ligand and the pistil S Receptor Kinase (SRK. Following self-pollen contact, the SCR/SP11 ligand on the pollen surface binds to SRK on the pistil surface, and the SRK-activated signaling pathway is initiated. This pathway includes the ARM Repeat Containing 1 (ARC1 protein, a member of the Plant U-box (PUB family of E3 ubiquitin ligases. ARC1 is a functional E3 ligase and is required downstream of SRK for the self-incompatibility response. This mini review highlights our recent progress in establishing ARC1’s conserved role in self-pollen rejection in Brassica and Arabidopsis species and discusses future research directions in this field.

  20. Force Tests of the Boeing XB-47 Full-Scale Empennage in the Ames 40- by 80-Foot Wind Tunnel

    Science.gov (United States)

    Hunton, Lynn W.

    1947-01-01

    A wind-tunnel investigation of the Boeing XB-47 full-scale empennage was conducted to provide, prior to flight tests, data required on the effectiveness of the elevator and rudder. The XB-47 airplane is a jet-propelled medium bomber having wing and tail surfaces swept back 35 degrees. The investigation included tests of the effectiveness of the elevator with normal straight sides, with a buldged trailing edge, and with a modified hinge-line gap and tests of the effectiveness of the rudder with a normal straight-sided tab and with a bulged tab.

  1. Differential effects of amlodipine and atorvastatin treatment and their combination on atherosclerosis in ApoE*3-Leiden transgenic mice

    NARCIS (Netherlands)

    Delsing, D.J.; Jukema, J.W.; van de Wiel, M.A.; Emeis, J.; van der Laarse, A.; Havekes, L.M.; Princen, H.M.G.

    2003-01-01

    This study was designed to investigate the potential antiatherosclerotic effects of the calcium antagonist amlodipine as compared with the HMG-CoA reductase inhibitor atorvastatin and the combination of both in ApoE*3-Leiden transgenic mice. Four groups of 15 ApoE*3-Leiden mice were put on a

  2. 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.

  3. 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

  4. Structural Analysis of Lunar Subsurface with Chang'E 3 Lunar Penetrating Radar

    Science.gov (United States)

    Xu, Yi; Lai, Jialong; Tang, Zesheng

    2015-04-01

    Geological structure of the subsurface of the Moon provides valuable information for our understanding of 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 higher horizontal and vertical resolution and less clutter impact compared to spaceborne radars such as Chandrayaan-1 and Kaguya. 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. First, filter method and amplitude recover algorithms are introduced for data processing to alleviate the adverse effects of environment and system noises and compensate the amplitude losses during signal propagation. Next, based on the processed LPR data, we present the methods to determine the interfaces between layers. A three-layered structure of the shallow surface of the Moon has been observed. The corresponding real part of relative dielectric constant is inverted with deconvolution method. The average dielectric constants of the surface, second and third layer is 2.8, 3.2 and 3.6, respectively. The phenomenon that the average dielectric constant increases with the depth is consistent with prior art. With the obtained dielectric constants, the thickness of each layer can be calculated. One possible geological picture of the observed three-layered structure is presented as follows. The top layer is lunar regolith with its thickness ranging from 0.59 m to 0.9 m. The second layer is the ejecta blanket of the nearby impact crater, and the corresponding thickness is between 3.6m to 3.9m, which is in good agreement with the model of ejecta blanket thickness (height) as a function of distance from the crater center proposed by Melosh in 1989. The third layer is regarded as early lunar regolith with 4

  5. Phylogenetic analysis of the SINA/SIAH ubiquitin E3 ligase family in Metazoa.

    Science.gov (United States)

    Pepper, Ian J; Van Sciver, Robert E; Tang, Amy H

    2017-08-07

    The RAS signaling pathway is a pivotal developmental pathway that controls many fundamental biological processes including cell proliferation, differentiation, movement and apoptosis. Drosophila Seven-IN-Absentia (SINA) is a ubiquitin E3 ligase that is the most downstream signaling "gatekeeper" whose biological activity is essential for proper RAS signal transduction. Vertebrate SINA homologs (SIAHs) share a high degree of amino acid identity with that of Drosophila SINA. SINA/SIAH is the most conserved signaling component in the canonical EGFR/RAS/RAF/MAPK signal transduction pathway. Vertebrate SIAH1, 2, and 3 are the three orthologs to invertebrate SINA protein. SINA and SIAH1 orthologs are found in all major taxa of metazoans. These proteins have four conserved functional domains, known as RING (Really Interesting New Gene), SZF (SIAH-type zinc finger), SBS (substrate binding site) and DIMER (Dimerization). In addition to the siah1 gene, most vertebrates encode two additional siah genes (siah2 and siah3) in their genomes. Vertebrate SIAH2 has a highly divergent and extended N-terminal sequence, while its RING, SZF, SBS and DIMER domains maintain high amino acid identity/similarity to that of SIAH1. But unlike vertebrate SIAH1 and SIAH2, SIAH3 lacks a functional RING domain, suggesting that SIAH3 may be an inactive E3 ligase. The SIAH3 subtree exhibits a high degree of amino acid divergence when compared to the SIAH1 and SIAH2 subtrees. We find that SIAH1 and SIAH2 are expressed in all human epithelial cell lines examined thus far, while SIAH3 is only expressed in a limited subset of cancer cell lines. Through phylogenetic analyses of metazoan SINA and SIAH E3 ligases, we identified many invariant and divergent amino acid residues, as well as the evolutionarily conserved functional motifs in this medically relevant gene family. Our phylomedicinal study of this unique metazoan SINA/SIAH protein family has provided invaluable evolution-based support towards future

  6. Global economics/energy/environmental (E3) modeling of long-term nuclear energy futures

    International Nuclear Information System (INIS)

    Krakowski, R.A.; Davidson, J.W.; Bathke, C.G.; Arthur, E.D.; Wagner, R.L. Jr.

    1997-01-01

    A global energy, economics, environment (E 3 ) model has been adopted and modified with a simplified, but comprehensive and multi-regional, nuclear energy module. Using this model, consistent nuclear energy scenarios are constructed. A spectrum of future is examined at two levels in a hierarchy of scenario attributes in which drivers are either external or internal to nuclear energy. Impacts of a range of nuclear fuel-cycle scenarios are reflected back to the higher-level scenario attributes. An emphasis is placed on nuclear materials inventories (in magnitude, location, and form) and their contribution to the long-term sustainability of nuclear energy and the future competitiveness of both conventional and advanced nuclear reactors

  7. 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.

  8. Data processing and initial results of Chang'e-3 lunar penetrating radar

    Science.gov (United States)

    Su, Yan; Fang, Guang-You; Feng, Jian-Qing; Xing, Shu-Guo; Ji, Yi-Cai; Zhou, Bin; Gao, Yun-Ze; Li, Han; Dai, Shun; Xiao, Yuan; Li, Chun-Lai

    2014-12-01

    To improve our understanding of the formation and evolution of the Moon, one of the payloads onboard the Chang'e-3 (CE-3) rover is Lunar Penetrating Radar (LPR). This investigation is the first attempt to explore the lunar subsurface structure by using ground penetrating radar with high resolution. We have probed the subsurface to a depth of several hundred meters using LPR. In-orbit testing, data processing and the preliminary results are presented. These observations have revealed the configuration of regolith where the thickness of regolith varies from about 4 m to 6 m. In addition, one layer of lunar rock, which is about 330 m deep and might have been accumulated during the depositional hiatus of mare basalts, was detected.

  9. Data processing and initial results of Chang'e-3 lunar penetrating radar

    International Nuclear Information System (INIS)

    Su Yan; Feng Jian-Qing; Xing Shu-Guo; Li Han; Dai Shun; Xiao Yuan; Li Chun-Lai; Fang Guang-You; Ji Yi-Cai; Zhou Bin; Gao Yun-Ze

    2014-01-01

    To improve our understanding of the formation and evolution of the Moon, one of the payloads onboard the Chang'e-3 (CE-3) rover is Lunar Penetrating Radar (LPR). This investigation is the first attempt to explore the lunar subsurface structure by using ground penetrating radar with high resolution. We have probed the subsurface to a depth of several hundred meters using LPR. In-orbit testing, data processing and the preliminary results are presented. These observations have revealed the configuration of regolith where the thickness of regolith varies from about 4 m to 6 m. In addition, one layer of lunar rock, which is about 330 m deep and might have been accumulated during the depositional hiatus of mare basalts, was detected

  10. A young multilayered terrane of the northern Mare Imbrium revealed by Chang’E-3 mission

    Science.gov (United States)

    Xiao, Long; Zhu, Peimin; Fang, Guangyou; Xiao, Zhiyong; Zou, Yongliao; Zhao, Jiannan; Zhao, Na; Yuan, Yuefeng; Qiao, Le; Zhang, Xiaoping; Zhang, Hao; Wang, Jiang; Huang, Jun; Huang, Qian; He, Qi; Zhou, Bin; Ji, Yicai; Zhang, Qunying; Shen, Shaoxiang; Li, Yuxi; Gao, Yunze

    2015-03-01

    China’s Chang’E-3 (CE-3) spacecraft touched down on the northern Mare Imbrium of the lunar nearside (340.49°E, 44.12°N), a region not directly sampled before. We report preliminary results with data from the CE-3 lander descent camera and from the Yutu rover’s camera and penetrating radar. After the landing at a young 450-meter crater rim, the Yutu rover drove 114 meters on the ejecta blanket and photographed the rough surface and the excavated boulders. The boulder contains a substantial amount of crystals, which are most likely plagioclase and/or other mafic silicate mineral aggregates similar to terrestrial dolerite. The Lunar Penetrating Radar detection and integrated geological interpretation have identified more than nine subsurface layers, suggesting that this region has experienced complex geological processes since the Imbrian and is compositionally distinct from the Apollo and Luna landing sites.

  11. The preliminary processing and analysis of LPR Channel-2B data from Chang'E-3

    Science.gov (United States)

    Zhao, Na; Zhu, PeiMin; Yang, KeSi; Yuan, YueFeng; Guo, ShiLi

    2014-12-01

    The Lunar Penetrating Radar (LPR) carried by Chang'E-3 has imaged the shallow subsurface of the landing site at the northern Mare Imbrium. The antenna B of the Channel-2 onboard the LPR (LPR Channel-2B) has collected more than 2000 traces of usable raw data. Because of the low resolution and noise of the raw data, only a few shallow geological structures are visible. To improve the resolution and the signal-to-noise ratio of the LPR data, we processed the LPR data including amplitude compensation, filtering, and deconvolution processes. The processing results reveal that the data processing in this study not only improves the signal-to-noise ratio of the LPR Channel-2B data but also makes the geological structures vivid. The processing results will lay the foundation for the subsequent geological interpretation and physical property inversion of lunar materials.

  12. Regolith stratigraphy at the Chang'E-3 landing site as seen by lunar penetrating radar

    Science.gov (United States)

    Fa, Wenzhe; Zhu, Meng-Hua; Liu, Tiantian; Plescia, Jeffrey B.

    2015-12-01

    The Chang'E-3 lunar penetrating radar (LPR) observations at 500 MHz reveal four major stratigraphic zones from the surface to a depth of ~20 m along the survey line: a layered reworked zone (<1 m), an ejecta layer (~2-6 m), a paleoregolith layer (~4-11 m), and the underlying mare basalts. The reworked zone has two to five distinct layers and consists of surface regolith. The paleoregolith buried by the ejecta from a 500 m crater is relatively homogenous and contains only a few rocks. Population of buried rocks increases with depth to ~2 m at first, and then decreases with depth, representing a balance between initial deposition of the ejecta and later turnover of the regolith. Combining with the surface age, the LPR observations indicate a mean accumulation rate of about 5-10 m/Gyr for the surface regolith, which is at least 4-8 times larger than previous estimation.

  13. A young multilayered terrane of the northern Mare Imbrium revealed by Chang'E-3 mission.

    Science.gov (United States)

    Xiao, Long; Zhu, Peimin; Fang, Guangyou; Xiao, Zhiyong; Zou, Yongliao; Zhao, Jiannan; Zhao, Na; Yuan, Yuefeng; Qiao, Le; Zhang, Xiaoping; Zhang, Hao; Wang, Jiang; Huang, Jun; Huang, Qian; He, Qi; Zhou, Bin; Ji, Yicai; Zhang, Qunying; Shen, Shaoxiang; Li, Yuxi; Gao, Yunze

    2015-03-13

    China's Chang'E-3 (CE-3) spacecraft touched down on the northern Mare Imbrium of the lunar nearside (340.49°E, 44.12°N), a region not directly sampled before. We report preliminary results with data from the CE-3 lander descent camera and from the Yutu rover's camera and penetrating radar. After the landing at a young 450-meter crater rim, the Yutu rover drove 114 meters on the ejecta blanket and photographed the rough surface and the excavated boulders. The boulder contains a substantial amount of crystals, which are most likely plagioclase and/or other mafic silicate mineral aggregates similar to terrestrial dolerite. The Lunar Penetrating Radar detection and integrated geological interpretation have identified more than nine subsurface layers, suggesting that this region has experienced complex geological processes since the Imbrian and is compositionally distinct from the Apollo and Luna landing sites. Copyright © 2015, American Association for the Advancement of Science.

  14. Structure and catalytic activation of the TRIM23 RING E3 ubiquitin ligase: DAWIDZIAK et al.

    Energy Technology Data Exchange (ETDEWEB)

    Dawidziak, Daria M. [Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville Virginia; Sanchez, Jacint G. [Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville Virginia; Wagner, Jonathan M. [Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville Virginia; Ganser-Pornillos, Barbie K. [Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville Virginia; Pornillos, Owen [Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville Virginia

    2017-07-24

    Tripartite motif (TRIM) proteins comprise a large family of RING-type ubiquitin E3 ligases that regulate important biological processes. An emerging general model is that TRIMs form elongated antiparallel coiled-coil dimers that prevent interaction of the two attendant RING domains. The RING domains themselves bind E2 conjugating enzymes as dimers, implying that an active TRIM ligase requires higher-order oligomerization of the basal coiled-coil dimers. Here, we report crystal structures of the TRIM23 RING domain in isolation and in complex with an E2–ubiquitin conjugate. Our results indicate that TRIM23 enzymatic activity requires RING dimerization, consistent with the general model of TRIM activation.

  15. RING E3 ligases: key regulatory elements are involved in abiotic stress responses in plants.

    Science.gov (United States)

    Cho, Seok Keun; Ryu, Moon Young; Kim, Jong Hum; Hong, Jeong Soo; Oh, Tae Rin; Kim, Woo Taek; Yang, Seong Wook

    2017-08-01

    Plants are constantly exposed to a variety of abiotic stresses, such as drought, heat, cold, flood, and salinity. To survive under such unfavorable conditions, plants have evolutionarily developed their own resistant-mechanisms. For several decades, many studies have clarified specific stress 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. [BMB Reports 2017; 50(8): 393-400].

  16. Degradation of human Lipin-1 by BTRC E3 ubiquitin ligase.

    Science.gov (United States)

    Ishimoto, Kenji; Hayase, Ayaka; Kumagai, Fumiko; Kawai, Megumi; Okuno, Hiroko; Hino, Nobumasa; Okada, Yoshiaki; Kawamura, Takeshi; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Tachibana, Keisuke; Doi, Takefumi

    2017-06-17

    Lipin-1 has dual functions in the regulation of lipid and energy metabolism according to its subcellular localization, which is tightly controlled. However, it is unclear how Lipin-1 degradation is regulated. Here, we demonstrate that Lipin-1 is degraded through its DSGXXS motif. We show that Lipin-1 interacts with either of two E3 ubiquitin ligases, BTRC or FBXW11, and that this interaction is DSGXXS-dependent and mediates the attachment of polyubiquitin chains. Further, we demonstrate that degradation of Lipin-1 is regulated by BTRC in the cytoplasm and on membranes. These novel insights into the regulation of human Lipin-1 stability will be useful in planning further studies to elucidate its metabolic processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response.

    Directory of Open Access Journals (Sweden)

    Qiang Wang

    2017-03-01

    Full Text Available The cyclic GMP-AMP synthase (cGAS, upon cytosolic DNA stimulation, catalyzes the formation of the second messenger 2'3'-cGAMP, which then binds to stimulator of interferon genes (STING and activates downstream signaling. It remains to be elucidated how the cGAS enzymatic activity is modulated dynamically. Here, we reported that the ER ubiquitin ligase RNF185 interacted with cGAS during HSV-1 infection. Ectopic-expression or knockdown of RNF185 respectively enhanced or impaired the IRF3-responsive gene expression. Mechanistically, RNF185 specifically catalyzed the K27-linked poly-ubiquitination of cGAS, which promoted its enzymatic activity. Additionally, Systemic Lupus Erythematosus (SLE patients displayed elevated expression of RNF185 mRNA. Collectively, this study uncovers RNF185 as the first E3 ubiquitin ligase of cGAS, shedding light on the regulation of cGAS activity in innate immune responses.

  18. 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.

  19. Spectroscopy of 215Ra: the shell model and enhanced E3 transitions

    International Nuclear Information System (INIS)

    Stuchbery, A.E.; Dracoulis, G.D.; Kibedi, T.; Fabricius, B.; Lane, G.J.; Poletti, A.R.; Baxter, A.M.

    1998-01-01

    Excited states in the N=127 nucleus 215 Ra have been studied using γ-ray and electron spectroscopy following reactions of 13 C on 206 Pb targets. Levels were identified up to spins of ∝61/2 ℎ and excitation energies of ∝6 MeV. Enhanced octupole transitions are a feature of the level scheme. Lifetimes and magnetic moments were measured for several isomeric levels. The level scheme, transition rates and magnetic moments are compared with empirical shell model calculations and multiparticle octupole-coupled shell model calculations. In general, the experimental data are well described, but in comparison with its success in describing enhanced E3 transitions between related states in the radon isotopes, some limitations of the multiparticle octupole-coupling approach are revealed in 215 Ra. (orig.)

  20. 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.

  1. Merkel cell polyomavirus small T antigen induces genome instability by E3 ubiquitin ligase targeting.

    Science.gov (United States)

    Kwun, H J; Wendzicki, J A; Shuda, Y; Moore, P S; Chang, Y

    2017-12-07

    The formation of a bipolar mitotic spindle is an essential process for the equal segregation of duplicated DNA into two daughter cells during mitosis. As a result of deregulated cellular signaling pathways, cancer cells often suffer a loss of genome integrity that might etiologically contribute to carcinogenesis. Merkel cell polyomavirus (MCV) small T (sT) oncoprotein induces centrosome overduplication, aneuploidy, chromosome breakage and the formation of micronuclei by targeting cellular ligases through a sT domain that also inhibits MCV large T oncoprotein turnover. These results provide important insight as to how centrosome number and chromosomal stability can be affected by the E3 ligase targeting capacity of viral oncoproteins such as MCV sT, which may contribute to Merkel cell carcinogenesis.

  2. [Near infrared distance sensing method for Chang'e-3 alpha particle X-ray spectrometer].

    Science.gov (United States)

    Liang, Xiao-Hua; Wu, Ming-Ye; Wang, Huan-Yu; Peng, Wen-Xi; Zhang, Cheng-Mo; Cui, Xing-Zhu; Wang, Jin-Zhou; Zhang, Jia-Yu; Yang, Jia-Wei; Fan, Rui-Rui; Gao, Min; Liu, Ya-Qing; Zhang, Fei; Dong, Yi-Fan; Guo, Dong-Ya

    2013-05-01

    Alpha particle X-ray spectrometer (APXS) is one of the payloads of Chang'E-3 lunar rover, the scientific objective of which is in-situ observation and off-line analysis of lunar regolith and rock. Distance measurement is one of the important functions for APXS to perform effective detection on the moon. The present paper will first give a brief introduction to APXS, and then analyze the specific requirements and constraints to realize distance measurement, at last present a new near infrared distance sensing algorithm by using the inflection point of response curve. The theoretical analysis and the experiment results verify the feasibility of this algorithm. Although the theoretical analysis shows that this method is not sensitive to the operating temperature and reflectance of the lunar surface, the solar infrared radiant intensity may make photosensor saturation. The solutions are reducing the gain of device and avoiding direct exposure to sun light.

  3. Socio-economic factors associated with a healthy diet: results from the E3N study.

    Science.gov (United States)

    Affret, Aurélie; Severi, Gianluca; Dow, Courtney; Rey, Grégoire; Delpierre, Cyrille; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Fagherazzi, Guy

    2017-06-01

    To identify individual and contextual socio-economic factors associated with a healthy diet. Dietary data from a large cohort study were used to derive two mutually exclusive dietary patterns through a latent class analysis. Associations between dietary patterns and socio-economic factors were studied with logistic regression. E3N, a French prospective cohort study composed of women recruited from a national health insurance plan covering people working in the national education system. E3N participants (n 73 031) with dietary and socio-economic data available. The 'Healthy' pattern was characterized by a large consumption of fruits and vegetables and the 'Less Healthy' pattern by a large consumption of pizza and processed meat. When all socio-economic factors were analysed together, all of the individual factors considered were associated with a healthy diet (e.g. women with three or more children were less likely to follow a healthy diet v. women with no children, OR (95 % CI): 0·70 (0·66, 0·75)) while the contextual factors associated with a healthy diet included the size of the agglomeration of residence and the area of birth and residence (e.g. women living in the West of France were less likely to follow a healthy diet v. those living in the South of France: 0·78 (0·72, 0·83)). We demonstrated that individual and contextual factors are both associated with diet. Rather than focusing only on individual factors, we recommend future studies or public health and nutritional strategies on diet to consider both types of factors.

  4. 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

  5. The interactions in K{sub μ3} and K{sub e3} decay

    Energy Technology Data Exchange (ETDEWEB)

    McDowell, S. W. [Brazilian Centre of Research in Physics, Rio de Janeiro (Brazil)

    1963-01-15

    An attractive feature common to all present theories of weak interactions is the assumption that they result from the coupling (either direct or via intermediate bosons) of vector-axial vector currents. The V-A coupling of leptonic currents and baryonic currents conserving strangeness successfully explains the characteristic properties of μ-decay, π-decay and μ-decay. On the other hand, the leptonic decay modes of K-mesons provide the best source of information on the nature of the currents carrying strangeness. From K{sub μ2} one learns that there must exist an axial-vector current carrying strangeness; further, if the leptonic weak interaction is universal, one can explain the absence of the K{sub e2} mode by excluding a pseudo-scalar interaction. From K{sub μ3} and K{sub e3} decay one can obtain information on scalar, vector and tensor coupling of strangeness non-conserving currents with leptons. In recent experiments on K{sub e3} decay a good fitting of the pion spectrum was obtained with a constant vector form factor. Although regarding this result as strong evidence of pure vector coupling, one might still argue that other possibilities, such as a mixture of vector and tensor couplings with energy-dependent form factors, are not excluded. I shall discuss here, in the first place, some properties of the transition amplitudes which are independent of the structure of form factors. They provide a test of universality and a criterion for unambiguous determination of the nature of the weak interaction involved in these processes. Secondly, I shall discuss the structure of form factors, by means of dispersion relations and introducing explicitly the effect of the K*-resonance in the Kπ-interaction.

  6. The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function.

    Science.gov (United States)

    Wan, Lixin; Chen, Ming; Cao, Juxiang; Dai, Xiangpeng; Yin, Qing; Zhang, Jinfang; Song, Su-Jung; Lu, Ying; Liu, Jing; Inuzuka, Hiroyuki; Katon, Jesse M; Berry, Kelsey; Fung, Jacqueline; Ng, Christopher; Liu, Pengda; Song, Min Sup; Xue, Lian; Bronson, Roderick T; Kirschner, Marc W; Cui, Rutao; Pandolfi, Pier Paolo; Wei, Wenyi

    2017-04-01

    BRAF drives tumorigenesis by coordinating the activation of the RAS/RAF/MEK/ERK oncogenic signaling cascade. However, upstream pathways governing BRAF kinase activity and protein stability remain undefined. Here, we report that in primary cells with active APC FZR1 , APC FZR1 earmarks BRAF for ubiquitination-mediated proteolysis, whereas in cancer cells with APC-free FZR1, FZR1 suppresses BRAF through disrupting BRAF dimerization. Moreover, we identified FZR1 as a direct target of ERK and CYCLIN D1/CDK4 kinases. Phosphorylation of FZR1 inhibits APC FZR1 , leading to elevation of a cohort of oncogenic APC FZR1 substrates to facilitate melanomagenesis. Importantly, CDK4 and/or BRAF/MEK inhibitors restore APC FZR1 E3 ligase activity, which might be critical for their clinical effects. Furthermore, FZR1 depletion cooperates with AKT hyperactivation to transform primary melanocytes, whereas genetic ablation of Fzr1 synergizes with Pten loss, leading to aberrant coactivation of BRAF/ERK and AKT signaling in mice. Our findings therefore reveal a reciprocal suppression mechanism between FZR1 and BRAF in controlling tumorigenesis. Significance: FZR1 inhibits BRAF oncogenic functions via both APC-dependent proteolysis and APC-independent disruption of BRAF dimers, whereas hyperactivated ERK and CDK4 reciprocally suppress APC FZR1 E3 ligase activity. Aberrancies in this newly defined signaling network might account for BRAF hyperactivation in human cancers, suggesting that targeting CYCLIN D1/CDK4, alone or in combination with BRAF/MEK inhibition, can be an effective anti-melanoma therapy. Cancer Discov; 7(4); 424-41. ©2017 AACR. See related commentary by Zhang and Bollag, p. 356 This article is highlighted in the In This Issue feature, p. 339 . ©2017 American Association for Cancer Research.

  7. E2-EPF UCP Possesses E3 Ubiquitin Ligase Activity via Its Cysteine 118 Residue.

    Science.gov (United States)

    Lim, Jung Hwa; Shin, Hee Won; Chung, Kyung-Sook; Kim, Nam-Soon; Kim, Ju Hee; Jung, Hong-Ryul; Im, Dong-Soo; Jung, Cho-Rok

    Here, we show that E2-EPF ubiquitin carrier protein (UCP) elongated E3-independent polyubiquitin chains on the lysine residues of von Hippel-Lindau protein (pVHL) and its own lysine residues both in vitro and in vivo. The initiation of the ubiquitin reaction depended on not only Lys11 linkage but also the Lys6, Lys48 and Lys63 residues of ubiquitin, which were involved in polyubiquitin chain formation on UCP itself. UCP self-association occurred through the UBC domain, which also contributed to the interaction with pVHL. The polyubiquitin chains appeared on the N-terminus of UCP in vivo, which indicated that the N-terminus of UCP contains target lysines for polyubiquitination. The Lys76 residue of UCP was the most critical site for auto-ubiquitination, whereas the polyubiquitin chain formation on pVHL occurred on all three of its lysines (Lys159, Lys171 and Lys196). A UCP mutant in which Cys118 was changed to alanine (UCPC118A) did not form a polyubiquitin chain but did strongly accumulate mono- and di-ubiquitin via auto-ubiquitination. Polyubiquitin chain formation required the coordination of Cys95 and Cys118 between two interacting molecules. The mechanism of the polyubiquitin chain reaction of UCP may involve the transfer of ubiquitin from Cys95 to Cys118 by trans-thiolation, with polyubiquitin chains forming at Cys118 by reversible thioester bonding. The polyubiquitin chains are then moved to the lysine residues of the substrate by irreversible isopeptide bonding. During the elongation of the ubiquitin chain, an active Cys118 residue is required in both parts of UCP, namely, the catalytic enzyme and the substrate. In conclusion, UCP possesses not only E2 ubiquitin conjugating enzyme activity but also E3 ubiquitin ligase activity, and Cys118 is critical for polyubiquitin chain formation.

  8. E2-EPF UCP Possesses E3 Ubiquitin Ligase Activity via Its Cysteine 118 Residue.

    Directory of Open Access Journals (Sweden)

    Jung Hwa Lim

    Full Text Available Here, we show that E2-EPF ubiquitin carrier protein (UCP elongated E3-independent polyubiquitin chains on the lysine residues of von Hippel-Lindau protein (pVHL and its own lysine residues both in vitro and in vivo. The initiation of the ubiquitin reaction depended on not only Lys11 linkage but also the Lys6, Lys48 and Lys63 residues of ubiquitin, which were involved in polyubiquitin chain formation on UCP itself. UCP self-association occurred through the UBC domain, which also contributed to the interaction with pVHL. The polyubiquitin chains appeared on the N-terminus of UCP in vivo, which indicated that the N-terminus of UCP contains target lysines for polyubiquitination. The Lys76 residue of UCP was the most critical site for auto-ubiquitination, whereas the polyubiquitin chain formation on pVHL occurred on all three of its lysines (Lys159, Lys171 and Lys196. A UCP mutant in which Cys118 was changed to alanine (UCPC118A did not form a polyubiquitin chain but did strongly accumulate mono- and di-ubiquitin via auto-ubiquitination. Polyubiquitin chain formation required the coordination of Cys95 and Cys118 between two interacting molecules. The mechanism of the polyubiquitin chain reaction of UCP may involve the transfer of ubiquitin from Cys95 to Cys118 by trans-thiolation, with polyubiquitin chains forming at Cys118 by reversible thioester bonding. The polyubiquitin chains are then moved to the lysine residues of the substrate by irreversible isopeptide bonding. During the elongation of the ubiquitin chain, an active Cys118 residue is required in both parts of UCP, namely, the catalytic enzyme and the substrate. In conclusion, UCP possesses not only E2 ubiquitin conjugating enzyme activity but also E3 ubiquitin ligase activity, and Cys118 is critical for polyubiquitin chain formation.

  9. Overexpression of herbaceous peony miR156e-3p improves anthocyanin accumulation in transgenic Arabidopsis thaliana lateral branches.

    Science.gov (United States)

    Zhao, Daqiu; Xia, Xing; Wei, Mengran; Sun, Jing; Meng, Jiasong; Tao, Jun

    2017-12-01

    microRNAs (miRNAs) play critical regulatory roles in plant growth and development. In the present study, the function of herbaceous peony ( Paeonia lactiflora Pall.) miR156e-3p in the regulation of color formation has been investigated. Firstly, P. lactiflora miR156e-3p precursor sequence (pre-miR156e-3p) was isolated. Subsequently, the overexpression vector of pre-miR156e-3p was constructed and transformed into Arabidopsis thaliana . Moreover, the medium screening, GUS staining, polymerase chain reaction (PCR) of the GUS region and real-time quantitative PCR (qRT-PCR) of miR156e-3p all confirmed that the purpose gene had been successfully transferred into Arabidopsis plants and expressed, which resulted in apparent purple lateral branches. And this change in color was caused by the improved anthocyanin accumulation. In addition, expression analysis had shown that the level of miR156e-3p transcript was increased, while transcription level of target gene squamosa promoter binding protein-like gene ( SPL1 ), encoding SPL transcription factor that negatively regulated anthocyanin accumulation, was repressed in miR156e-3p-overexpressing transgenic plants, and its downstream gene dihydroflavonol 4-reductase gene ( DFR ) that was directly involved in anthocyanin biosynthesis was strongly expressed, which resulted in anthocyanin accumulation of Arabidopsis lateral branches. These findings would improve the understanding of miRNAs regulation of color formation in P. lactiflora .

  10. 10 CFR 830 Major Modification Determination for the ATR Diesel Bus (E-3) and Switchgear Replacement

    International Nuclear Information System (INIS)

    Duckwitz, Noel

    2011-01-01

    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: (1) Provide commercial power as the normal source of power to the ATR loads currently supplied by diesel-electric power. (2) Provide backup power to the critical ATR loads in the event of a loss of commercial power. (3) 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 No.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 No.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

  11. 75 FR 12657 - Airworthiness Directives; The Boeing Company Model 777-200, -200LR, -300, -300ER, and 777F Series...

    Science.gov (United States)

    2010-03-17

    ..., Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. Hand Delivery: U.S. Department of... Boeing Company has also discovered during flight simulations that the climb gradient is less than optimal... bulletin describes procedures for installing new operational program software for the left, center, and...

  12. 75 FR 52907 - Airworthiness Directives; The Boeing Company Model 747-100, 747-100B, 747-100B SUD, 747-200B, 747...

    Science.gov (United States)

    2010-08-30

    ... CONTACT: Nicholas Han, Aerospace Engineer, Airframe Branch, ANM-120S, FAA, Seattle Aircraft Certification... Airlines (JAL) reports that certain structures prevented the accomplishment of the inspection specified in... time for certain inspection locations. Boeing reports that recent engineering analysis has revealed...

  13. 75 FR 10669 - Airworthiness Directives; The Boeing Company Model 747-100, 747-200B, 747-300, and 747SR Series...

    Science.gov (United States)

    2010-03-09

    ... base assembly to the moisture shroud as given in Figure 10 in Boeing Alert Service Bulletin 747- 25A3368, Revision 2, dated June 12, 2008, and to fill any unused pilot holes in the mounting base assembly... 25, 2007, and to fill any unused pilot holes in the mounting base assembly in accordance with the...

  14. 76 FR 24349 - Airworthiness Directives; The Boeing Company Model 747-200B, -300, -400, -400D, and -400F Series...

    Science.gov (United States)

    2011-05-02

    ... this AD, contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC.... Department of Transportation, Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New... to this issue. Request To Clarify Figures in Service Information UPS requested that we clarify the...

  15. 75 FR 27424 - Airworthiness Directives; The Boeing Company Model 747-100, 747-100B, 747-100B SUD, 747-200B, 747...

    Science.gov (United States)

    2010-05-17

    ... Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H-65, Seattle... Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590... reviewed the figures we have used over the past several years to calculate AD costs to operators. To...

  16. 75 FR 61337 - Airworthiness Directives; The Boeing Company Model 747-100, 747-100B, 747-100B SUD, 747-200B, 747...

    Science.gov (United States)

    2010-10-05

    ..., contact Boeing Commercial Airplanes, Attention: Data & Services Management, P.O. Box 3707, MC 2H-65..., Docket Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE...-60-15, Figure 201, Repair 5, do the inspection, including the threshold and intervals in accordance...

  17. 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.

  18. Sustainable energy development in Austria until 2020: Insights from applying the integrated model 'e3.at'

    International Nuclear Information System (INIS)

    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. - Highlights: → Together with stakeholders three renewable energy scenarios for Austria were defined. → The scenarios were simulated using an integrated environment-energy-economy model. → Increasing the share of renewables in total energy use is important but insufficient. → Efficiency and a cut of energy use are also essential for a sustainable energy system.

  19. Correlated compositional and mineralogical investigations at the Chang′e-3 landing site

    Science.gov (United States)

    Ling, Zongcheng; Jolliff, Bradley L.; Wang, Alian; Li, Chunlai; Liu, Jianzhong; Zhang, Jiang; Li, Bo; Sun, Lingzhi; Chen, Jian; Xiao, Long; Liu, Jianjun; Ren, Xin; Peng, Wenxi; Wang, Huanyu; Cui, Xingzhu; He, Zhiping; Wang, Jianyu

    2015-01-01

    The chemical compositions of relatively young mare lava flows have implications for the late volcanism on the Moon. Here we report the composition of soil along the rim of a 450-m diameter fresh crater at the Chang′e-3 (CE-3) landing site, investigated by the Yutu rover with in situ APXS (Active Particle-induced X-ray Spectrometer) and VNIS (Visible and Near-infrared Imaging Spectrometer) measurements. Results indicate that this region's composition differs from other mare sample-return sites and is a new type of mare basalt not previously sampled, but consistent with remote sensing. The CE-3 regolith derived from olivine-normative basaltic rocks with high FeO/(FeO+MgO). Deconvolution of the VNIS data indicates abundant high-Ca ferropyroxene (augite and pigeonite) plus Fe-rich olivine. We infer from the regolith composition that the basaltic source rocks formed during late-stage magma-ocean differentiation when dense ferropyroxene-ilmenite cumulates sank and mixed with deeper, relatively ferroan olivine and orthopyroxene in a hybridized mantle source. PMID:26694712

  20. Preface: The Chang'e-3 lander and rover mission to the Moon

    International Nuclear Information System (INIS)

    Ip Wing-Huen; Yan Jun; Li Chun-Lai; Ouyang Zi-Yuan

    2014-01-01

    The Chang'e-3 (CE-3) lander and rover mission to the Moon was an intermediate step in China's lunar exploration program, which will be followed by a sample return mission. The lander was equipped with a number of remote-sensing instruments including a pair of cameras (Landing Camera and Terrain Camera) for recording the landing process and surveying terrain, an extreme ultraviolet camera for monitoring activities in the Earth's plasmasphere, and a first-ever Moon-based ultraviolet telescope for astronomical observations. The Yutu rover successfully carried out close-up observations with the Panoramic Camera, mineralogical investigations with the VIS-NIR Imaging Spectrometer, study of elemental abundances with the Active Particle-induced X-ray Spectrometer, and pioneering measurements of the lunar subsurface with Lunar Penetrating Radar. This special issue provides a collection of key information on the instrumental designs, calibration methods and data processing procedures used by these experiments with a perspective of facilitating further analyses of scientific data from CE-3 in preparation for future missions

  1. Correlated compositional and mineralogical investigations at the Chang'e-3 landing site.

    Science.gov (United States)

    Ling, Zongcheng; Jolliff, Bradley L; Wang, Alian; Li, Chunlai; Liu, Jianzhong; Zhang, Jiang; Li, Bo; Sun, Lingzhi; Chen, Jian; Xiao, Long; Liu, Jianjun; Ren, Xin; Peng, Wenxi; Wang, Huanyu; Cui, Xingzhu; He, Zhiping; Wang, Jianyu

    2015-12-22

    The chemical compositions of relatively young mare lava flows have implications for the late volcanism on the Moon. Here we report the composition of soil along the rim of a 450-m diameter fresh crater at the Chang'e-3 (CE-3) landing site, investigated by the Yutu rover with in situ APXS (Active Particle-induced X-ray Spectrometer) and VNIS (Visible and Near-infrared Imaging Spectrometer) measurements. Results indicate that this region's composition differs from other mare sample-return sites and is a new type of mare basalt not previously sampled, but consistent with remote sensing. The CE-3 regolith derived from olivine-normative basaltic rocks with high FeO/(FeO+MgO). Deconvolution of the VNIS data indicates abundant high-Ca ferropyroxene (augite and pigeonite) plus Fe-rich olivine. We infer from the regolith composition that the basaltic source rocks formed during late-stage magma-ocean differentiation when dense ferropyroxene-ilmenite cumulates sank and mixed with deeper, relatively ferroan olivine and orthopyroxene in a hybridized mantle source.

  2. SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements.

    Directory of Open Access Journals (Sweden)

    Jason Liang

    2018-03-01

    Full Text Available Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO. Here we show that the mms21-CH mutation, which inactivates Mms21 ligase activity, causes increased accumulation of gross chromosomal rearrangements (GCRs selected in the dGCR assay. These dGCRs are formed by non-allelic homologous recombination between divergent DNA sequences mediated by Rad52-, Rrm3- and Pol32-dependent break-induced replication. Combining mms21-CH with sgs1Δ caused a synergistic increase in GCRs rates, indicating the distinct roles of Mms21 and Sgs1 in suppressing GCRs. The mms21-CH mutation also caused increased rates of accumulating uGCRs mediated by breakpoints in unique sequences as revealed by whole genome sequencing. Consistent with the accumulation of endogenous DNA lesions, mms21-CH mutants accumulate increased levels of spontaneous Rad52 and Ddc2 foci and had a hyper-activated DNA damage checkpoint. Together, these findings support that Mms21 prevents the accumulation of spontaneous DNA lesions that cause diverse GCRs.

  3. Preface: The Chang'e-3 lander and rover mission to the Moon

    Science.gov (United States)

    Ip, Wing-Huen; Yan, Jun; Li, Chun-Lai; Ouyang, Zi-Yuan

    2014-12-01

    The Chang'e-3 (CE-3) lander and rover mission to the Moon was an intermediate step in China's lunar exploration program, which will be followed by a sample return mission. The lander was equipped with a number of remote-sensing instruments including a pair of cameras (Landing Camera and Terrain Camera) for recording the landing process and surveying terrain, an extreme ultraviolet camera for monitoring activities in the Earth's plasmasphere, and a first-ever Moon-based ultraviolet telescope for astronomical observations. The Yutu rover successfully carried out close-up observations with the Panoramic Camera, mineralogical investigations with the VIS-NIR Imaging Spectrometer, study of elemental abundances with the Active Particle-induced X-ray Spectrometer, and pioneering measurements of the lunar subsurface with Lunar Penetrating Radar. This special issue provides a collection of key information on the instrumental designs, calibration methods and data processing procedures used by these experiments with a perspective of facilitating further analyses of scientific data from CE-3 in preparation for future missions.

  4. The Processing of Lunar Penetrating Radar Channel-2B Data from Chang'E-3

    Science.gov (United States)

    Zhu, P.; Zhao, N.; Yang, K.; Yuan, Y.; Guo, S.

    2014-12-01

    The Lunar Penetrating Radar (LPR) carried by Chang'E-3 has imaged the shallow subsurface of the landing site at the northern Mare Imbrium. The antenna B of the Channel-2 onboard the LPR (LPR Channel-2B) has collected more than 20000 traces of raw data. The raw LPR data could not be directly used for geological interpretation because of the operation mode of the LPR, noise and fast attenuation of radar wave. This study focuses data preprocessing and processing methods to obtain higher quality data. A section of usable LPR data of over 2000 traces is gained after the preprocessing of selecting, splicing, removing delay time and fine-correcting to raw data, but only a few shallow geological structures are visible. To further improve the resolution and the signal-to-noise ratio of the LPR data, we have processed the LPR data including amplitude compensation, filtering, and deconvolution processes based on electromagnetic wave theory. The processing results reveal that (1) the spherical spreading compensation and auto gain control enhance the amplitude of reflection echoes from deeper strata and make the geological structures more obvious, (2) the spiking deconvolution applied to narrow reflection events down makes it possible to identify thin layers with 30% improved resolution, and (3) the band-pass filtering removes the multiple reflections and, consequently, improves the signal-to-noise ratio of LPR data. The processing results will lay the foundation for the subsequent geological interpretation and physical property inversion of lunar materials.

  5. Deviations between experimental and theoretical results in Ar (e, 3e) double ionization

    International Nuclear Information System (INIS)

    Jia, C C; Lahmam-Bennani, A; Cappello, C Dal; Duguet, A; Avaldi, L

    2003-01-01

    The coplanar (e, 3e) relative cross sections for double ionization of argon have been measured at an electron impact energy of E 0 = 561.4 eV and under equal energy sharing among the two 'ejected' electrons, E b = E c = 9 eV. The scattering angle is fixed to θ a = 1.5 degrees, corresponding to a momentum transfer K=0.4 au to the target. The experimental results have been compared with calculations in the first Born approximation, which include only first-order processes in the target-projectile interaction. The comparison shows severe deviations between the experimental and theoretical results. These deviations are much larger than the ones previously observed in helium under comparable kinematics. To fill this gap between theory and experiment, a decisive improvement in the theory is needed. This can be achieved by improving the first-order calculations and by including higher-order processes such as the two-step mechanism, or even new mechanisms, for instance the simultaneous ejection of the pair of target electrons. (letter to the editor)

  6. The Impact of Parametric Uncertainties on Biogeochemistry in the E3SM Land Model

    Science.gov (United States)

    Ricciuto, Daniel; Sargsyan, Khachik; Thornton, Peter

    2018-02-01

    We conduct a global sensitivity analysis (GSA) of the Energy Exascale Earth System Model (E3SM), land model (ELM) to calculate the sensitivity of five key carbon cycle outputs to 68 model parameters. This GSA is conducted by first constructing a Polynomial Chaos (PC) surrogate via new Weighted Iterative Bayesian Compressive Sensing (WIBCS) algorithm for adaptive basis growth leading to a sparse, high-dimensional PC surrogate with 3,000 model evaluations. The PC surrogate allows efficient extraction of GSA information leading to further dimensionality reduction. The GSA is performed at 96 FLUXNET sites covering multiple plant functional types (PFTs) and climate conditions. About 20 of the model parameters are identified as sensitive with the rest being relatively insensitive across all outputs and PFTs. These sensitivities are dependent on PFT, and are relatively consistent among sites within the same PFT. The five model outputs have a majority of their highly sensitive parameters in common. A common subset of sensitive parameters is also shared among PFTs, but some parameters are specific to certain types (e.g., deciduous phenology). The relative importance of these parameters shifts significantly among PFTs and with climatic variables such as mean annual temperature.

  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. 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.

  9. 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. PMID:23365531

  10. Reaction (γ,2e) and (e,3e) as probe of electron correlation in atoms

    International Nuclear Information System (INIS)

    Amusia, M.Y.

    1995-01-01

    Cross sections of the (γ,2e) and (e,3e) reactions contain information about the two vacancy-energy spectrum and electron-pair correlations in initial and final states of the target atom. Physical pictures of these processes are presented for two- and many-electron atoms. The simplest mechanisms are discussed, demonstrating some features which await experimental confirmation. Attention is given to high photon energy and the relativistic energy region of these reactions. The energy distribution of outgoing relativistic electrons is qualitatively different from the nonrelativistic case. The origin and types of corrections to the simplest mechanisms, and possible means of their detection, are discussed. In addition, the role of different resonances: shape, giant, autoionizational, and Feshbach-type are considered. Results of calculations are compared with experimental data, mainly on double photoionization cross sections. Different possible objects as targets for the reactions are considered, including negative ions, excited atoms, molecules, and clusters. The modification of these reactions due to photon emission is discussed. The future of the domain is outlined

  11. Reactions (γ,2e) and (e,3e) as probes of electronic correlations in atoms

    International Nuclear Information System (INIS)

    Amusia, M.Ya.

    1993-01-01

    Cross sections of the (γ,2e) and (e,3e) reactions carry information on two vacancy energy spectrum and on electron pair correlations in initial and final states of the target atom. Physical pictures of these processes are presented for two- and many-electron atoms. Simplest mechanisms of them are discussed, demonstrating some features which are waiting for experimental confirmation. Attention is given to high photon energy and even to relativistic energy region of these reactions. The energy distribution of outgoing relativistic electrons is qualitatively different from what it is for the nonrelativistic case. Origin and types of corrections to the simplest mechanisms and possible means of their detection are discussed. Role of different resonances: shape, giant, autoionizational, and Feschbach-type are considered. Results of calculations are compared with experimental data, mainly on double photoionization cross sections. Different possible objects as targets for the reactions are mentioned, including negative ions, excited atoms, molecules and clusters. Modification of the type of these reactions due to rather probable emission of the photon is discussed. Future of the domain is outlined. (orig.)

  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. 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.

  14. An Arabidopsis SUMO E3 Ligase, SIZ1, Negatively Regulates Photomorphogenesis by Promoting COP1 Activity

    KAUST Repository

    Lin, Xiao-Li; Niu, De; Hu, Zi-Liang; Kim, Dae Heon; Jin, Yin Hua; Cai, Bin; Liu, Peng; Miura, Kenji; Yun, Dae-Jin; Kim, Woe-Yeon; Lin, Rongcheng; Jin, Jing Bo

    2016-01-01

    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.

  15. 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.

  16. Two- to one-phonon E3 transition strength in {sup 148}Gd

    Energy Technology Data Exchange (ETDEWEB)

    Piiparinen, M [Niels Bohr Institute, Tandem Accelerator Laboratory, Roskilde (Denmark); [Jyvaeskylae Univ. (Finland). Dept. of Physics; Atac, A; Nyberg, J; Ramsoy, T; Sletten, G [Niels Bohr Institute, Tandem Acceleratory Laboratory, Roskile, (Denmark); Virtanen, A; Muller, D [Jyvaeskylae Univ. (Finland). Dept. of Physics; Kleinheinz, P [Forschungszentrum Juelich GmbH (Germany). Inst. fuer Kernphysik; Blomqvist, J [Manne Siegbahn Inst. of Physics, Stockholm (Sweden)

    1992-08-01

    In a plunger experiment the mean life of the ({nu} f{sub 6}{sup 2}x3{sup -}x3{sup -})12{sup +} state at 3.981 MeV in {sub 64}{sup 148}Gd{sub 84} was measured as {tau}=83(10)ps, giving 77(11)B{sub w} for the 1286 keV 12{sup +} {yields} 9{sup -} E3 transition rate, which confirms the double-octupole character of the 12{sup +} state. The observed deviations in energy and transition rate from harmonic vibration are shown to be caused by the exclusion principle acting between nucleons in the two phonons and are related to the dominant contributions to the {sup 148}Gd octupole phonon of the low-lying {Delta}l={Delta}j=3 proton- and neutron in-shell 3{sup -} excitations which are of vital significance for the octupole mode in open-shell nuclei. (author). 17 refs., 2 figs.

  17. Enhanced E3 Excitations in 144,146Ba and the Evolution of Octupole Collectivity

    Science.gov (United States)

    Bucher, B.; Zhu, S.; ANL, LLNL, LBNL, INL, UAM, Rochester, Maryland Collaboration

    2017-09-01

    Recent Coulomb excitation studies on 144,146Ba using the GRETINA-CHICO2 detection system with post-accelerated CARIBU beams have confirmed the existence of enhanced E3 transitions in these isotopes which are centered in a region that has long been predicted to exhibit stable octupole-deformed shapes. Furthermore, the widely-varying E1 strength observed between these isotopes is well-accounted for by models having octupole-deformed potentials, and the variation has been linked to increased occupancies of specific single-particle orbitals in the reflection-asymmetric potential. This talk will summarize the most recent experimental and theoretical results. In addition, data on octupole-related properties in the surrounding isotopes will be discussed in an attempt to better understand the origin and evolution of octupole collectivity in this mass region. This work is supported by the U.S. Department of Energy, Office of Nuclear Physics, under Contract No. DE-AC02-06CH11357 (ANL), DE-AC02-05CH11231 (LBNL, GRETINA), DOE DE-AC52-07NA27344 (LLNL), DE-AC07-05ID14517 (INL), and MINECO (Spain).

  18. 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.

  19. Test Hardware Design for Flightlike Operation of Advanced Stirling Convertors (ASC-E3)

    Science.gov (United States)

    Oriti, Salvatore M.

    2012-01-01

    NASA Glenn Research Center (GRC) has been supporting development of the Advanced Stirling Radioisotope Generator (ASRG) since 2006. A key element of the ASRG project is providing life, reliability, and performance testing of the Advanced Stirling Convertor (ASC). For this purpose, the Thermal Energy Conversion branch at GRC has been conducting extended operation of a multitude of free-piston Stirling convertors. The goal of this effort is to generate long-term performance data (tens of thousands of hours) simultaneously on multiple units to build a life and reliability database. The test hardware for operation of these convertors was designed to permit in-air investigative testing, such as performance mapping over a range of environmental conditions. With this, there was no requirement to accurately emulate the flight hardware. For the upcoming ASC-E3 units, the decision has been made to assemble the convertors into a flight-like configuration. This means the convertors will be arranged in the dual-opposed configuration in a housing that represents the fit, form, and thermal function of the ASRG. The goal of this effort is to enable system level tests that could not be performed with the traditional test hardware at GRC. This offers the opportunity to perform these system-level tests much earlier in the ASRG flight development, as they would normally not be performed until fabrication of the qualification unit. This paper discusses the requirements, process, and results of this flight-like hardware design activity.

  20. Functional Characterization of the Apple RING E3 Ligase MdMIEL1 in Transgenic Arabidopsis

    Directory of Open Access Journals (Sweden)

    Jianping AN

    2017-03-01

    Full Text Available E3 ubiquitin ligases are involved in various physiological processes, and they play pivotal roles in growth and development. In this study, we identified a previously unknown gene in the apple fruit (Malus × domestica and named it MdMIEL1. The MdMIEL1 gene encoded a protein that contained a zinc-finger domain at its N-terminus and a RING-finger motif at its C-terminus. To investigate MdMIEL1 functions, we generated transgenic Arabidopsis lines expressing the MdMIEL1 gene under the control of the Cauliflower mosaic virus 35S promoter. Interestingly, ectopic expression of MdMIEL1 in Arabidopsis produced multiple phenotypes, including early germination, early flowering and a lateral root number increase relative to wild-type plants. Further analysis indicated that MdMIEL1 regulated lateral root initiation by increasing auxin accumulation in the roots. In a word, these results suggest that, MdMIEL1 as a novel RING-finger ubiquitin ligase influences plant growth and development, and highlight that MdMIEL1 regulates lateral root growth.

  1. TRIM32 ubiquitin E3 ligase, one enzyme for several pathologies: From muscular dystrophy to tumours.

    Science.gov (United States)

    Lazzari, Elisa; Meroni, Germana

    2016-10-01

    TRIM32 is a member of the TRIpartite Motif family characterised by the presence of an N-terminal three-domain-module that includes a RING domain, which confers E3 ubiquitin ligase activity, one or two B-box domains and a Coiled-Coil region that mediates oligomerisation. Several TRIM32 substrates were identified including muscular proteins and proteins involved in cell cycle regulation and cell motility. As ubiquitination is a versatile post-translational modification that can affect target turnover, sub-cellular localisation or activity, it is likely that diverse substrates may be differentially affected by TRIM32-mediated ubiquitination, reflecting its multi-faceted roles in muscle physiology, cancer and immunity. With particular relevance for muscle physiology, mutations in TRIM32 are associated with autosomal recessive Limb-Girdle Muscular Dystrophy 2H, a muscle-wasting disease with variable clinical spectrum ranging from almost asymptomatic to wheelchair-bound patients. In this review, we will focus on the ability of TRIM32 to mark specific substrates for proteasomal degradation discussing how the TRIM32-proteasome axis may (i) be important for muscle homeostasis and for the pathogenesis of muscular dystrophy; and (ii) define either an oncogenic or tumour suppressive role for TRIM32 in the context of different types of cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. E3 Ubiquitin Ligase c-cbl Inhibits Microglia Activation After Chronic Constriction Injury.

    Science.gov (United States)

    Xue, Pengfei; Liu, Xiaojuan; Shen, Yiming; Ju, Yuanyuan; Lu, Xiongsong; Zhang, Jinlong; Xu, Guanhua; Sun, Yuyu; Chen, Jiajia; Gu, Haiyan; Cui, Zhiming; Bao, Guofeng

    2018-06-22

    E3 ubiquitin ligase c-Caritas B cell lymphoma (c-cbl) is associated with negative regulation of receptor tyrosine kinases, signal transduction of antigens and cytokine receptors, and immune response. However, the expression and function of c-cbl in the regulation of neuropathic pain after chronic constriction injury (CCI) are unknown. In rat CCI model, c-cbl inhibited the activation of spinal cord microglia and the release of pro-inflammatory factors including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), which alleviated mechanical and heat pain through down-regulating extracellular signal-regulated kinase (ERK) pathway. Additionally, exogenous TNF-α inhibited c-cbl protein level vice versa. In the primary microglia transfected with c-cbl siRNA, when treated with TNF-α or TNF-α inhibitor, the corresponding secretion of IL-1β and IL-6 did not change. In summary, CCI down-regulated c-cbl expression and induced the activation of microglia, then activated microglia released inflammatory factors via ERK signaling to cause pain. Our data might supply a novel molecular target for the therapy of CCI-induced neuropathic pain.

  3. 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.

  4. Complete replication-competent adenovirus 11p vectors with E1 or E3 insertions show improved heat stability

    Energy Technology Data Exchange (ETDEWEB)

    Mei, Ya-Fang, E-mail: ya-fang.mei@umu.se [Department of Clinical Microbiology and Virology, Umeå University, SE-901 85 Umeå (Sweden); Wu, Haidong, E-mail: haidong.wu@umu.se [Department of Clinical Microbiology and Virology, Umeå University, SE-901 85 Umeå (Sweden); Hultenby, Kjell, E-mail: kjell.hultenby@ki.se [Division of Clinical Research Centre, Department of Laboratory Medicine, Karolinska Institute, SE-14186 Stockholm (Sweden); Silver, Jim, E-mail: jim.silver@umu.se [Department of Clinical Microbiology and Virology, Umeå University, SE-901 85 Umeå (Sweden)

    2016-10-15

    Conventional adenovirus vectors harboring E1 or E3 deletions followed by the insertion of an exogenous gene show considerably reduced virion stability. Here, we report strategies to generate complete replication-competent Ad11p(RCAd11p) vectors that overcome the above disadvantage. A GFP cassette was successfully introduced either upstream of E1A or in the E3A region. The resulting vectors showed high expression levels of the hexon and E1genes and also strongly induced the cytopathic effect in targeted cells. When harboring oversized genomes, the RCAd11pE1 and RCAd11pE3 vectors showed significantly improved heat stability in comparison to Ad11pwt;of the three, RCAd11pE3 was the most tolerant to heat treatment. Electron microscopy showed that RCAd11pE3, RCAd11pE1, Ad11pwt, and Ad11pE1 Delmanifested dominant, moderate, minimum, or no full virus particles after heat treatment at 47 °C for 5 h. Our results demonstrated that both genome size and the insertion site in the viral genome affect virion stability. -- Highlights: •Replicating adenovirus 11p GFP vectors at the E1 or E3 region were generated. •RCAd11pE3 and RCAd11pE1 vectors manifested significantly improved heat stability. •RCAd11pE3 and RCAd11pE1 showed more full viral particles than Ad11pwt after heating. •We demonstrated that both genome size and the insertion site affect virion stability.

  5. Complete replication-competent adenovirus 11p vectors with E1 or E3 insertions show improved heat stability

    International Nuclear Information System (INIS)

    Mei, Ya-Fang; Wu, Haidong; Hultenby, Kjell; Silver, Jim

    2016-01-01

    Conventional adenovirus vectors harboring E1 or E3 deletions followed by the insertion of an exogenous gene show considerably reduced virion stability. Here, we report strategies to generate complete replication-competent Ad11p(RCAd11p) vectors that overcome the above disadvantage. A GFP cassette was successfully introduced either upstream of E1A or in the E3A region. The resulting vectors showed high expression levels of the hexon and E1genes and also strongly induced the cytopathic effect in targeted cells. When harboring oversized genomes, the RCAd11pE1 and RCAd11pE3 vectors showed significantly improved heat stability in comparison to Ad11pwt;of the three, RCAd11pE3 was the most tolerant to heat treatment. Electron microscopy showed that RCAd11pE3, RCAd11pE1, Ad11pwt, and Ad11pE1 Delmanifested dominant, moderate, minimum, or no full virus particles after heat treatment at 47 °C for 5 h. Our results demonstrated that both genome size and the insertion site in the viral genome affect virion stability. -- Highlights: •Replicating adenovirus 11p GFP vectors at the E1 or E3 region were generated. •RCAd11pE3 and RCAd11pE1 vectors manifested significantly improved heat stability. •RCAd11pE3 and RCAd11pE1 showed more full viral particles than Ad11pwt after heating. •We demonstrated that both genome size and the insertion site affect virion stability.

  6. Analysis of the geomorphology surrounding the Chang'e-3 landing site

    International Nuclear Information System (INIS)

    Li Chun-Lai; Mu Ling-Li; Zou Xiao-Duan; Liu Jian-Jun; Ren Xin; Zeng Xing-Guo; Yang Yi-Man; Zhang Zhou-Bin; Liu Yu-Xuan; Zuo Wei; Li Han

    2014-01-01

    Chang'e-3 (CE-3) landed on the Mare Imbrium basin in the east part of Sinus Iridum (19.51°W, 44.12°N), which was China's first soft landing on the Moon and it started collecting data on the lunar surface environment. To better understand the environment of this region, this paper utilizes the available high-resolution topography data, image data and geological data to carry out a detailed analysis and research on the area surrounding the landing site (Sinus Iridum and 45 km×70 km of the landing area) as well as on the topography, landform, geology and lunar dust of the area surrounding the landing site. A general topographic analysis of the surrounding area is based on a digital elevation model and digital elevation model data acquired by Chang'e-2 that have high resolution; the geology analysis is based on lunar geological data published by USGS; the study on topographic factors and distribution of craters and rocks in the surrounding area covering 4 km×4 km or even smaller is based on images from the CE-3 landing camera and images from the topographic camera; an analysis is done of the effect of the CE-3 engine plume on the lunar surface by comparing images before and after the landing using data from the landing camera. A comprehensive analysis of the results shows that the landing site and its surrounding area are identified as typical lunar mare with flat topography. They are suitable for maneuvers by the rover, and are rich in geological phenomena and scientific targets, making it an ideal site for exploration

  7. Life course evolution of body size and breast cancer survival in the E3N cohort.

    Science.gov (United States)

    His, Mathilde; Le Guélennec, Marine; Mesrine, Sylvie; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Dossus, Laure

    2018-04-15

    Although adult obesity has been associated with poor breast cancer survival, data on adiposity at different periods in life and its lifelong evolution are scarce. Our aims were to assess the associations between breast cancer survival and body size during childhood, puberty and early adulthood and body size trajectories from childhood to adulthood. Self-assessed body size at age 8, at puberty, at age 20-25 and at age 35-40 and trajectories of body size of 4,662 breast cancer survivors from the prospective E3N cohort were studied in relation to risk of death from any cause, death from breast cancer and second invasive cancer event using multivariate Cox regression models. Four trajectories of body size were identified (T1 "moderate increase," T2 "stable/low increase," T3 "increase at puberty" and T4 "constantly high"). Compared with stable body size, an increase in body size during adult life was associated with an increased risk of death from any cause (HR T1 vs. T2 = 1.27; 95% CI = 1.01-1.60) and an increased risk of second invasive cancer event (HR T1 vs. T2 = 1.25; 95% CI = 1.06-1.47). Silhouettes at various ages were not associated with survival. Our results suggest that the evolution of body size from childhood to adulthood has a long-term influence on breast cancer survival. Although these results need to be confirmed, this work sheds light on the need to combine lifelong approaches to current BMI to better identify breast cancer survivors who are at higher risk of recurrence or second primary cancer, or of death. © 2017 UICC.

  8. Extensions of the 3-dimensional plasma transport code E3D

    International Nuclear Information System (INIS)

    Runov, A.; Schneider, R.; Kasilov, S.; Reiter, D.

    2004-01-01

    One important aspect of modern fusion research is plasma edge physics. Fluid transport codes extending beyond the standard 2-D code packages like B2-Eirene or UEDGE are under development. A 3-dimensional plasma fluid code, E3D, based upon the Multiple Coordinate System Approach and a Monte Carlo integration procedure has been developed for general magnetic configurations including ergodic regions. These local magnetic coordinates lead to a full metric tensor which accurately accounts for all transport terms in the equations. Here, we discuss new computational aspects of the realization of the algorithm. The main limitation to the Monte Carlo code efficiency comes from the restriction on the parallel jump of advancing test particles which must be small compared to the gradient length of the diffusion coefficient. In our problems, the parallel diffusion coefficient depends on both plasma and magnetic field parameters. Usually, the second dependence is much more critical. In order to allow long parallel jumps, this dependence can be eliminated in two steps: first, the longitudinal coordinate x 3 of local magnetic coordinates is modified in such a way that in the new coordinate system the metric determinant and contra-variant components of the magnetic field scale along the magnetic field with powers of the magnetic field module (like in Boozer flux coordinates). Second, specific weights of the test particles are introduced. As a result of increased parallel jump length, the efficiency of the code is about two orders of magnitude better. (copyright 2004 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  9. 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.

  10. E3 Ubiquitin Ligase RNF125 Activates Interleukin-36 Receptor Signaling and Contributes to Its Turnover.

    Science.gov (United States)

    Saha, Siddhartha S; Caviness, Gary; Yi, Guanghui; Raymond, Ernest L; Mbow, M Lamine; Kao, C Cheng

    2018-01-01

    Signaling by the interleukin-36 receptor (IL-36R) is linked to inflammatory diseases such as psoriasis. However, the regulation of IL-36R signaling is poorly understood. Activation of IL-36R signaling in cultured cells results in an increased polyubiquitination of the receptor subunit, IL-1Rrp2. Treatment with deubiquitinases shows that the receptor subunit of IL-36R, IL-1Rrp2, is primarily polyubiquitinated at the K63 position, which is associated with endocytic trafficking and signal transduction. A minor amount of ubiquitination is at the K48 position that is associated with protein degradation. A focused siRNA screen identified RNF125, an E3 ubiquitin ligase, to ubiquitinate IL-1Rrp2 upon activation of IL-36R signaling while not affecting the activated IL-1 receptor. Knockdown of RNF125 decreases signal transduction by the IL-36R. Overexpression of RNF125 in HEK293T cells activates IL-36R signaling and increases the ubiquitination of IL-1Rrp2 and its subsequent turnover. RNF125 can coimmunoprecipitate with the IL-36R, and it traffics with IL-1Rrp2 from the cell surface to lysosomes. Mutations of Lys568 and Lys569 in the C-terminal tail of IL-1Rrp2 decrease ubiquitination by RNF125 and increase the steady-state levels of IL-1Rrp2. These results demonstrate that RNF125 has multiple regulatory roles in the signaling, trafficking, and turnover of the IL-36R. © 2017 S. Karger AG, Basel.

  11. Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase

    Directory of Open Access Journals (Sweden)

    Kaitlin A. Davis

    2017-11-01

    Full Text Available Viruses manipulate cellular processes to create an environment favorable to replication. For most viruses, this includes subverting the expression of interferon (IFN, a signaling molecule that can stimulate production of a vast array of antiviral gene products. Rotavirus, a segmented double-stranded RNA virus that causes acute gastroenteritis in infants and young children, inhibits IFN expression through its nonstructural protein NSP1. This viral protein stifles IFN expression by inducing the degradation of host factors that are necessary for upregulating the activity of IFN genes. In the case of nearly all human and porcine rotavirus strains, NSP1 induces the ubiquitination-dependent proteasomal degradation of β-transducin repeat containing protein (β-TrCP, a host factor that plays an essential role in activating the IFN-transcription factor, NF-κB. Key to the process is the presence of a decoy sequence (degron at the C-terminus of NSP1 that causes β-TrCP to mistakenly bind NSP1 instead of its natural target, inhibitor-of-κB (IκB. In a recent report published by Davis et al [2017; mBio 8(4: e01213-17], we describe molecular requirements that govern NSP1 recognition of β-TrCP, including an essential degron phosphorylation event, and the step-wise incorporation of NSP1 into hijacked cullin-RING E3 ligases (CRLs that ubiquitinate and tag β-TrCP for degradation. Notably, although β-TrCP is chiefly recognized for its role as a master regulator of NF-κB signaling and IFN expression, β-TrCP also controls the stability of checkpoint proteins implicated in numerous other cellular pathways with antiviral activities, including autophagy and apoptosis. Thus, the impact of NSP1 on creating an intracellular environment favorable to virus replication may extend well beyond the IFN signaling pathway.

  12. Analysis of the geomorphology surrounding the Chang'e-3 landing site

    Science.gov (United States)

    Li, Chun-Lai; Mu, Ling-Li; Zou, Xiao-Duan; Liu, Jian-Jun; Ren, Xin; Zeng, Xing-Guo; Yang, Yi-Man; Zhang, Zhou-Bin; Liu, Yu-Xuan; Zuo, Wei; Li, Han

    2014-12-01

    Chang'e-3 (CE-3) landed on the Mare Imbrium basin in the east part of Sinus Iridum (19.51°W, 44.12°N), which was China's first soft landing on the Moon and it started collecting data on the lunar surface environment. To better understand the environment of this region, this paper utilizes the available high-resolution topography data, image data and geological data to carry out a detailed analysis and research on the area surrounding the landing site (Sinus Iridum and 45 km×70 km of the landing area) as well as on the topography, landform, geology and lunar dust of the area surrounding the landing site. A general topographic analysis of the surrounding area is based on a digital elevation model and digital elevation model data acquired by Chang'e-2 that have high resolution; the geology analysis is based on lunar geological data published by USGS; the study on topographic factors and distribution of craters and rocks in the surrounding area covering 4 km×4 km or even smaller is based on images from the CE-3 landing camera and images from the topographic camera; an analysis is done of the effect of the CE-3 engine plume on the lunar surface by comparing images before and after the landing using data from the landing camera. A comprehensive analysis of the results shows that the landing site and its surrounding area are identified as typical lunar mare with flat topography. They are suitable for maneuvers by the rover, and are rich in geological phenomena and scientific targets, making it an ideal site for exploration.

  13. TRIM37 defective in mulibrey nanism is a novel RING finger ubiquitin E3 ligase

    International Nuclear Information System (INIS)

    Kallijaervi, Jukka; Lahtinen, Ulla; Haemaelaeinen, Riikka; Lipsanen-Nyman, Marita; Palvimo, Jorma J.; Lehesjoki, Anna-Elina

    2005-01-01

    Mulibrey nanism is an autosomal recessive prenatal-onset growth disorder characterized by dysmorphic features, cardiomyopathy, and hepatomegaly. Mutations in TRIM37 encoding a tripartite motif (TRIM, RING-B-box-coiled-coil)-family protein underlie mulibrey nanism. We investigated the ubiquitin ligase activity predicted for the RING domain of TRIM37 by analyzing its autoubiquitination. Full-length TRIM37 and its TRIM domain were highly polyubiquitinated when co-expressed with ubiquitin. Polyubiquitination was decreased in a mutant protein with disrupted RING domain (Cys35Ser;Cys36Ser) and in the Leu76Pro mutant protein, a disease-associated missense mutation affecting the TRIM domain of TRIM37. Bacterially produced GST-TRIM domain fusion protein, but not its Cys35Ser;Cys36Ser or Leu76Pro mutants, were polyubiquitinated in cell-free conditions, implying RING-dependent modification. Ubiquitin was also identified as an interaction partner for TRIM37 in a yeast two-hybrid screen. Ectopically expressed TRIM37 rapidly formed aggregates that were ubiquitin-, proteasome subunit-, and chaperone-positive in immunofluorescence analysis, defining them as aggresomes. The Cys35Ser;Cys36Ser mutant and the Leu76Pro and Gly322Val patient mutant proteins were markedly less prone to aggregation, implying that aggresomal targeting reflects a physiological function of TRIM37. These findings suggest that TRIM37 acts as a TRIM domain-dependent E3 ubiquitin ligase and imply defective ubiquitin-dependent degradation of an as-yet-unidentified target protein in the pathogenesis of mulibrey nanism

  14. Evaluation of the energy-climate package with the help of Gemini-E3 Model

    International Nuclear Information System (INIS)

    Vielle, M.; Moulinier, J.M.; Bernard, A.

    2009-01-01

    This article presents an evaluation of the energy-climate package carried out at the request of the Ministry of Sustainable Development (MEEDDAT) by simulating several scenarios on the general calculable equilibrium model GEMINI-E3. The analysis was carried out during the European negotiations in very close collaboration with the services of the Ministry and has thus constituted a useful tool for deciding and defining the position of France, which, besides, chaired the Union in the course of the transition period of the second half of 2008 and was in charge of finding and gaining acceptance of a compromise between all the member countries, while taking into account the aspirations of the professionals most closely involved. As one might guess, the study shows that the easing of constraints through mechanisms of flexibility yields reductions in the cost of European policy on climate change, particularly for the achievement of the main objective, viz. the 20% reduction of greenhouse gas emissions by 2020. This cost is reasonable, although its distribution between countries is neither homogeneous, nor in conformity with concerns over equity. Many indirect effects of the policy on climate change, in particular the gains or losses caused by the modification of the terms of trade, may significantly upset the hierarchy of direct costs. This article also looks into the carbon leakage issue and suggests, in particular, favouring the net leakage concept, this being the discrepancy between the additional emissions in non-annex B countries and those which would have been incurred if production in response to demand from annex B countries relatively insensitive to the policy o climatic change, had not been relocated. Another feature of this study is an evaluation, after the event, of the extent to which the use of a modelling tool has effectively allowed identification of the issues raised in the course of the European negotiation, and to provide relevant answers. (authors)

  15. Specific IgE for Fag e 3 Predicts Oral Buckwheat Food Challenge Test Results and Anaphylaxis: A Pilot Study.

    Science.gov (United States)

    Yanagida, Noriyuki; Sato, Sakura; Maruyama, Nobuyuki; Takahashi, Kyohei; Nagakura, Ken-Ichi; Ogura, Kiyotake; Asaumi, Tomoyuki; Ebisawa, Motohiro

    2018-01-01

    Buckwheat (BW) is the source of a life-threatening allergen. Fag e 3-specific serum IgE (sIgE) is more useful than BW-sIgE for diagnosis; however, it is unknown whether Fag e 3-sIgE can predict oral food challenge (OFC) results and anaphylaxis. This study aimed to clarify the efficacy of Fag e 3-sIgE in predicting OFC results and anaphylaxis. We conducted a retrospective review of BW- and Fag e 3-sIgE data obtained using the ImmunoCAP® assay system and fluorescent enzyme-linked immunosorbent assay from children who underwent OFC using 3,072 mg of BW protein between July 2006 and March 2014 at Sagamihara National Hospital, Kanagawa, Japan. We analyzed 60 patients aged 1.9-13.4 years (median 6.0 years); 20 (33%) showed objective symptoms upon BW OFC. The patients without symptoms had significantly lower Fag e 3-sIgE than those with non-anaphylactic (p tested factor that significantly predicted positive OFC results (odds ratio 8.93, 95% confidence interval 3.10-25.73, p < 0.001) and OFC-induced anaphylaxis (2.67, 1.12-6.35, p = 0.027). We suggest that a threshold Fag e 3-sIgE level of 18.0 kUE/L has 95% probability of provoking a positive reaction to BW. Fag e 3-sIgE predicted OFC results and OFC-induced anaphylaxis. We further emphasize paying careful attention to the risk of BW OFC-induced anaphylaxis. © 2018 The Author(s) Published by S. Karger AG, Basel.

  16. Plutonium-burn high temperature gas-cooled reactor for 3E+3S

    International Nuclear Information System (INIS)

    Okamoto, Koji

    2015-01-01

    . Plutonium can not be extracted from the YSZ-PuO 2 fuel. Therefore, the fuel cannot be used for fuel cycle. However, the direct disposal fuel will be safe in view points of non-proliferation. Nobody can use the Pu spent fuel. The HTGR is superior in viewpoint of 2S, security and safeguards. The Pu-burn HTGR is the solution for Nuclear Energy under 3E+3S. (author)

  17. 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.

  18. Global Energy-Economy-Environment (E3) Scenarios to 2050 and Beyond

    International Nuclear Information System (INIS)

    Schrattenholzer, L.

    2005-01-01

    The Environmentally Compatible Energy Strategies (ECS) Program at the International Institute for Applied Systems Analysis (IIASA) develops policy-relevant global and world-regional energy perspectives. The basic premise of the ECS's research program is a global trend of d ecarbonization . Firstly, decarbonization includes a trend toward ever-greater efficiency, or ever less waste, in society's use of energy resources. Secondly, it includes a trend towards less carbon-intensive fossil fuels (e.g., from coal toward natural gas) and, further, to non-fossil fuels, especially renewable energy carriers. Technological change is generally regarded as one of the key drivers of sustained economic growth. Long-term energy scenarios developed at IIASA and elsewhere show that, depending on key assumptions on drivers such as population, economic growth and technological development, global energy development can be environmentally unsustainable. First, energy development might not lead to stabilizing greenhouse concentrations and might thus have significant negative impacts on the global climate. In addition, some, especially coal-intensive, scenarios might lead to levels of acid deposition at which significant damage to sensitive ecosystems is expected to occur in Europe and, even more so, in Asia. A continuation of the observed historical long-term trends of decarbonization, dematerialization, and energy efficiency improvements might therefore not be sufficient to achieve sustainable growth. Targeted technological development aiming at accelerating decarbonization, dematerialization, and/or efficiency improvement may be one of the most effective means for reconciling economic growth with global environmental objectives. This might require a step-up in investments in R and D and in the demonstration of technologies so as to stimulate both learning-by-searching and learning-by-doing. In this presentation, global E3 scenarios will be summarized in the following three groups: Non

  19. 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)

  20. X-Ray and optical study of low core density globular clusters NGC6144 and E3

    NARCIS (Netherlands)

    Lan, S.-H.; Kong, A.K.H.; Verbunt, F.W.M.; Lewin, W.H.G.; Bassa, C.G.; Anderson, S.F.; Pooley, D.

    2010-01-01

    We report on the Chandra X-ray Observatory and Hubble Space Telescope (HST) observations of two low coredensity globular clusters, NGC6144 and E3. By comparing the number of X-ray sources inside the half-mass radius to those outside, we found six X-ray sources within the half-mass radius of NGC6144,

  1. 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

    Purified protein synthesis initiation factors IF-E2 and IF-E3 from rabbit reticulocytes were phosphorylated in vitro with protein kinases isolated from the same source. The highest levels of phosphorylation resulted from incubation of the factors with a cyclic nucleotide-independent protein kinase...

  2. A role for non-covalent SUMO interaction motifs in Pc2/CBX4 E3 activity.

    Directory of Open Access Journals (Sweden)

    Jacqueline C Merrill

    2010-01-01

    Full Text Available Modification of proteins by the small ubiquitin like modifier (SUMO is an essential process in mammalian cells. SUMO is covalently attached to lysines in target proteins via an enzymatic cascade which consists of E1 and E2, SUMO activating and conjugating enzymes. There is also a variable requirement for non-enzymatic E3 adapter like proteins, which can increase the efficiency and specificity of the sumoylation process. In addition to covalent attachment of SUMO to target proteins, specific non-covalent SUMO interaction motifs (SIMs that are generally short hydrophobic peptide motifs have been identified.Intriguingly, consensus SIMs are present in most SUMO E3s, including the polycomb protein, Pc2/Cbx4. However, a role for SIMs in SUMO E3 activity remains to be shown. We show that Pc2 contains two functional SIMs, both of which contribute to full E3 activity in mammalian cells, and are also required for sumoylation of Pc2 itself. Pc2 forms distinct sub-nuclear foci, termed polycomb bodies, and can recruit partner proteins, such as the corepressor CtBP. We demonstrate that mutation of the SIMs in Pc2 prevents Pc2-dependent CtBP sumoylation, and decreases enrichment of SUMO1 and SUMO2 at polycomb foci. Furthermore, mutational analysis of both SUMO1 and SUMO2 reveals that the SIM-interacting residues of both SUMO isoforms are required for Pc2-mediated sumoylation and localization to polycomb foci.This work provides the first clear evidence for a role for SIMs in SUMO E3 activity.

  3. RavN is a member of a previously unrecognized group of Legionella pneumophila E3 ubiquitin ligases

    Science.gov (United States)

    Lin, Yi-Han; Evans, Timothy R.; Doms, Alexandra G.; Beauchene, Nicole A.; Hierro, Aitor

    2018-01-01

    The eukaryotic ubiquitylation machinery catalyzes the covalent attachment of the small protein modifier ubiquitin to cellular target proteins in order to alter their fate. Microbial pathogens exploit this post-translational modification process by encoding molecular mimics of E3 ubiquitin ligases, eukaryotic enzymes that catalyze the final step in the ubiquitylation cascade. Here, we show that the Legionella pneumophila effector protein RavN belongs to a growing class of bacterial proteins that mimic host cell E3 ligases to exploit the ubiquitylation pathway. The E3 ligase activity of RavN was located within its N-terminal region and was dependent upon interaction with a defined subset of E2 ubiquitin-conjugating enzymes. The crystal structure of the N-terminal region of RavN revealed a U-box-like motif that was only remotely similar to other U-box domains, indicating that RavN is an E3 ligase relic that has undergone significant evolutionary alteration. Substitution of residues within the predicted E2 binding interface rendered RavN inactive, indicating that, despite significant structural changes, the mode of E2 recognition has remained conserved. Using hidden Markov model-based secondary structure analyses, we identified and experimentally validated four additional L. pneumophila effectors that were not previously recognized to possess E3 ligase activity, including Lpg2452/SdcB, a new paralog of SidC. Our study provides strong evidence that L. pneumophila is dedicating a considerable fraction of its effector arsenal to the manipulation of the host ubiquitylation pathway. PMID:29415051

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

    Science.gov (United States)

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

    2008-08-01

    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 analysed for their ability to ubiquitinate proteins in vitro in co-operation with different E2s. All U-box domains exhibited ubiquitination activity and interacted productively with UBC4/5-type E2s. Three and four of the U-box domains mediated ubiquitin addition in the presence of UBC13 and UBC7 E2s respectively, but no productive interaction was observed with the UBC15 E2 tested. The activity of AtPUB54 [Arabidopsis thaliana (thale cress) plant U-box 54 protein] was dependent on Trp(266) in the E2-binding cleft, and the E2 selectivity was changed by substitution of this position. The function of the distant U-box protein, AtPUB49, representing a large family of eukaryotic proteins containing a U-box linked to a cyclophilin-like peptidyl-prolyl cis-trans isomerase domain, was characterized biochemically. AtPUB49 functioned both as a prolyl isomerase and a chaperone by catalysing cis-trans isomerization of peptidyl-prolyl bonds and dissolving protein aggregates. In conclusion, both typical and atypical Arabidopsis U-box proteins were active E3s. The overlap in the E3/E2 selectivity suggests that in vivo specificity is not determined only by the E3-E2 interactions, but also by other parameters, e.g. co-existence or interactions with additional domains. The biochemical functions of AtPUB49 suggest that the protein can be involved in folding or degradation of protein substrates. Similar functions can also be retained within a protein complex with separate chaperone and U-box proteins.

  5. 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.

  6. 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.

  7. 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.

  8. The E-3 Test Facility at Stennis Space Center: Research and Development Testing for Cryogenic and Storable Propellant Combustion Systems

    Science.gov (United States)

    Pazos, John T.; Chandler, Craig A.; Raines, Nickey G.

    2009-01-01

    This paper will provide the reader a broad overview of the current upgraded capabilities of NASA's John C. Stennis Space Center E-3 Test Facility to perform testing for rocket engine combustion systems and components using liquid and gaseous oxygen, gaseous and liquid methane, gaseous hydrogen, hydrocarbon based fuels, hydrogen peroxide, high pressure water and various inert fluids. Details of propellant system capabilities will be highlighted as well as their application to recent test programs and accomplishments. Data acquisition and control, test monitoring, systems engineering and test processes will be discussed as part of the total capability of E-3 to provide affordable alternatives for subscale to full scale testing for many different requirements in the propulsion community.

  9. Magnetic moments, E3 transitions and the structure of high spin core excited states in 211Rn

    International Nuclear Information System (INIS)

    Poletti, A.R.; Dracoulis, G.D.; Byrne, A.P.; Stuchbery, A.E.; Poletti, S.J.; Gerl, J.; Lewis, P.M.

    1985-03-01

    The results of g-factor measurements of high spin states in 211 Rn are: Esub(x)=8856+Δsup(') keV (Jsup(π)=63/2 - ), g=0.626(7); 6101+Δsup(') keV (49/2 + ), 0.766(8); 5247+Δsup(') keV (43/2 - ), 0.74(2); 3927+Δsup(') keV (35/2 + ), 1/017(12); 1578+Δsup(') keV (17/2 - ), 0.912(9). These results together with measured E3 transition strengths and shell model calculations are used to assign configurations to the core excited states in 211 Rn. Mixed configurations are required to explain the g-factors and enhanced E3 strengths simultaneously

  10. Magnetic moments, E3 transitions and the structure of high-spin core excited states in 211Rn

    International Nuclear Information System (INIS)

    Poletti, A.R.; Dracoulis, G.D.; Byrne, A.P.; Stuchbery, A.E.; Poletti, S.J.; Gerl, J.; Lewis, P.M.

    1985-01-01

    The results of g-factor measurements of high-spin states in 211 Rn are: Esub(x)=8856+Δ' keV (Jsup(π)=63/2 - ), g=0.626(7); 6101+Δ' keV (49/2 + ), 0.766(8); 5347+Δ' keV (43/2 - ), 0.74(2); 3927+Δ keV (35/2 + ), 1.017(12); 1578+Δ keV (17/2 - ), 0.912(9). These results together with measured E3 transition strengths and shell model calculations are used to assign configurations to the core excited states in 211 Rn. Mixed configurations are required to explain the g-factors and enhanced E3 strengths simultaneously. (orig.)

  11. Plasma and liver lipidomics response to an intervention of rimonabant in ApoE*3Leiden.CETP transgenic mice.

    Directory of Open Access Journals (Sweden)

    Chunxiu Hu

    Full Text Available Lipids are known to play crucial roles in the development of life-style related risk factors such as obesity, dyslipoproteinemia, hypertension and diabetes. The first selective cannabinoid-1 receptor blocker rimonabant, an anorectic anti-obesity drug, was frequently used in conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m(2 with associated risk factors such as type II diabetes and dyslipidaemia in the past. Less is known about the impact of this drug on the regulation of lipid metabolism in plasma and liver in the early stage of obesity.We designed a four-week parallel controlled intervention on apolipoprotein E3 Leiden cholesteryl ester transfer protein (ApoE*3Leiden.CETP transgenic mice with mild overweight and hypercholesterolemia. A liquid chromatography-linear ion trap-Fourier transform ion cyclotron resonance-mass spectrometric approach was employed to investigate plasma and liver lipid responses to the rimonabant intervention. Rimonabant was found to induce a significant body weight loss (9.4%, p<0.05 and a significant plasma total cholesterol reduction (24%, p<0.05. Six plasma and three liver lipids in ApoE*3Leiden.CETP transgenic mice were detected to most significantly respond to rimonabant treatment. Distinct lipid patterns between the mice were observed for both plasma and liver samples in rimonabant treatment vs. non-treated controls. This study successfully applied, for the first time, systems biology based lipidomics approaches to evaluate treatment effects of rimonabant in the early stage of obesity.The effects of rimonabant on lipid metabolism and body weight reduction in the early stage obesity were shown to be moderate in ApoE*3Leiden.CETP mice on high-fat diet.

  12. Regolith thickness at the Chang'E-3 landing site from the Lunar Penetrating Radar and impact craters

    Science.gov (United States)

    Fa, W.; Zhu, M.-H.; Liu, T.

    2015-10-01

    The Chang'E-3 lunar penetrating radar (LPR) observations reveal a newly formed regolith layer (<1 m), an ejecta layer (~2-6 m), and a palaeoregolith layer (~4-9 m) from the surface to a depth of ~ 20 m. The thicknesses of the newly formed regolith layer and the palaeoregolith layer are consistent with the estimations based on the excavation depth and morphology of small fresh craters.

  13. Smurf2 E3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a CNKSR2 dependent manner

    OpenAIRE

    David, Diana; Jagadeeshan, Sankar; Hariharan, Ramkumar; Nair, Asha Sivakumari; Pillai, Radhakrishna Madhavan

    2014-01-01

    Background Smurf2 is a member of the HECT family of E3 ubiquitin ligases that play important roles in determining the competence of cells to respond to TGF- β/BMP signaling pathway. However, besides TGF-β/BMP pathway, Smurf2 regulates a repertoire of other signaling pathways ranging from planar cell polarity during embryonic development to cell proliferation, migration, differentiation and senescence. Expression of Smurf2 is found to be dysregulated in many cancers including breast cancer. Th...

  14. Enhanced E3 transitions and mixed configurations for core excited isomers in 210At and 211At

    International Nuclear Information System (INIS)

    Dracoulis, G.D.; Steed, C.A.; Byrne, A.P.; Poletti, S.J.; Stuchbery, A.E.; Bark, R.A.

    1986-09-01

    The lifetime and branching ratio of the 19 + isomer in 210 At have been measured. Its enhanced E3 decay and g-factor, and those of the related 39/2 - isomer in 211 At are compared with the results of a semi-empirical shell model calculation which includes couplings to the 3 - octupole vibration, resulting in mixed configurations. Lifetimes were also obtained for the 15 - isomer in 210 At, and he 29/2 + isomer in 209 At

  15. 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.

  16. (E-3-Methyl-6-(3-oxo-3-(thiophen-2-yl-1-propenyl-2(3H-benzothiazolone

    Directory of Open Access Journals (Sweden)

    Yordanka Ivanova

    2016-04-01

    Full Text Available The title compound, (E-3-methyl-6-(3-oxo-3-(thiophen-2-yl-1-propenyl-2(3H-benzothiazolone, was synthesized by Claisen-Schmidt condensation of 3-methyl-2(3H-benzothiazolone-6-carbaldehyde with 2-acetylthiophene in 94% yield. The structure of the target compound was confirmed using 1H-NMR, 13C-NMR, IR, MS, and elemental analysis.

  17. Functional characterization of DnSIZ1, a SIZ/PIAS-type SUMO E3 ligase from Dendrobium.

    Science.gov (United States)

    Liu, Feng; Wang, Xiao; Su, Mengying; Yu, Mengyuan; Zhang, Shengchun; Lai, Jianbin; Yang, Chengwei; Wang, Yaqin

    2015-09-17

    SUMOylation is an important post-translational modification of eukaryotic proteins that involves the reversible conjugation of a small ubiquitin-related modifier (SUMO) polypeptide to its specific protein substrates, thereby regulating numerous complex cellular processes. The PIAS (protein inhibitor of activated signal transducers and activators of transcription [STAT]) and SIZ (scaffold attachment factor A/B/acinus/PIAS [SAP] and MIZ) proteins are SUMO E3 ligases that modulate SUMO conjugation. The characteristic features and SUMOylation mechanisms of SIZ1 protein in monocotyledon are poorly understood. Here, we examined the functions of a homolog of Arabidopsis SIZ1, a functional SIZ/PIAS-type SUMO E3 ligase from Dendrobium. In Dendrobium, the predicted DnSIZ1 protein has domains that are highly conserved among SIZ/PIAS-type proteins. DnSIZ1 is widely expressed in Dendrobium organs and has a up-regulated trend by treatment with cold, high temperature and wounding. The DnSIZ1 protein localizes to the nucleus and shows SUMO E3 ligase activity when expressed in an Escherichia coli reconstitution system. Moreover, ectopic expression of DnSIZ1 in the Arabidopsis siz1-2 mutant partially complements several phenotypes and results in enhanced levels of SUMO conjugates in plants exposed to heat shock conditions. We observed that DnSIZ1 acts as a negative regulator of flowering transition which may be via a vernalization-induced pathway. In addition, ABA-hypersensitivity of siz1-2 seed germination can be partially suppressed by DnSIZ1. Our results suggest that DnSIZ1 is a functional homolog of the Arabidopsis SIZ1 with SUMO E3 ligase activity and may play an important role in the regulation of Dendrobium stress responses, flowering and development.

  18. Modulated magnetic structure of F e3P O7 as seen by 57Fe Mössbauer spectroscopy

    Science.gov (United States)

    Sobolev, A. V.; Akulenko, A. A.; Glazkova, I. S.; Pankratov, D. A.; Presniakov, I. A.

    2018-03-01

    The paper reports results of the 57Fe Mössbauer measurements on an F e3P O4O3 powder sample recorded at various temperatures, including the point of magnetic phase transition TN≈163 K . The spectra measured above TN consist of a quadrupole doublet with high quadrupole splitting of Δ300 K≈1.10 mm /s , emphasizing that F e3 + ions are located in crystal positions with a strong electric-field gradient (EFG). To predict the sign and orientation of the main components of the EFG tensor, we calculated the EFG using the density-functional-theory approach. In the temperature range T spiral spin structure results from easy-axis anisotropy in the plane of the iron spin rotation. The temperature evolution of the hyperfine field Hhf(T ) was described by the Bean-Rodbell model, which takes into account that the exchange magnetic interactions are a strong function of the lattice spacing. The obtained Mössbauer data are in qualitative agreement with previous neutron-diffraction data for a modulated helical magnetic structure in strongly frustrated F e3P O4O3 .

  19. 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

    of the distant U-box protein, AtPUB49, representing a large family of eukaryotic proteins containing a U-box linked to a cyclophilin-like peptidyl-prolyl cis-trans isomerase domain, was characterized biochemically. AtPUB49 functioned both as a prolyl isomerase and a chaperone by catalysing cis......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...... analysed for their ability to ubiquitinate proteins in vitro in co-operation with different E2s. All U-box domains exhibited ubiquitination activity and interacted productively with UBC4/5-type E2s. Three and four of the U-box domains mediated ubiquitin addition in the presence of UBC13 and UBC7 E2s...

  20. E3N, a French cohort study on cancer risk factors. E3N Group. Etude Epidémiologique auprès de femmes de l'Education Nationale.

    Science.gov (United States)

    Clavel-Chapelon, F; van Liere, M J; Giubout, C; Niravong, M Y; Goulard, H; Le Corre, C; Hoang, L A; Amoyel, J; Auquier, A; Duquesnel, E

    1997-10-01

    This paper describes the design of E3N, a prospective cohort study conducted in France on risk factors for female cancers. The cohort comprises 100,000 women, aged 40-65 years at baseline in 1990. Participants were asked to complete questionnaires every 18 months. The main hypotheses studied concern the relationship between diet and cancer and between hormonal treatments and cancer. All cancers diagnosed are registered, together with other diseases (cardiovascular diseases, diabetes, osteoporosis). The study population and the follow-up procedure are described.

  1. Glider communications and controls for the sea sentry mission.

    Energy Technology Data Exchange (ETDEWEB)

    Feddema, John Todd; Dohner, Jeffrey Lynn

    2005-03-01

    This report describes a system level study on the use of a swarm of sea gliders to detect, confirm and kill littoral submarine threats. The report begins with a description of the problem and derives the probability of detecting a constant speed threat without networking. It was concluded that glider motion does little to improve this probability unless the speed of a glider is greater than the speed of the threat. Therefore, before detection, the optimal character for a swarm of gliders is simply to lie in wait for the detection of a threat. The report proceeds by describing the effect of noise on the localization of a threat once initial detection is achieved. This noise is estimated as a function of threat location relative to the glider and is temporally reduced through the use of an information or Kalman filtering. In the next section, the swarm probability of confirming and killing a threat is formulated. Results are compared to a collection of stationary sensors. These results show that once a glider has the ability to move faster than the threat, the performance of the swarm is equal to the performance of a stationary swarm of gliders with confirmation and kill ranges equal to detection range. Moreover, at glider speeds greater than the speed of the threat, swarm performance becomes a weak function of speed. At these speeds swarm performance is dominated by detection range. Therefore, to future enhance swarm performance or to reduce the number of gliders required for a given performance, detection range must be increased. Communications latency is also examined. It was found that relatively large communication delays did little to change swarm performance. Thus gliders may come to the surface and use SATCOMS to effectively communicate in this application.

  2. New truncation mutation of the NR2E3 gene in a Japanese patient with enhanced S-cone syndrome.

    Science.gov (United States)

    Kuniyoshi, Kazuki; Hayashi, Takaaki; Sakuramoto, Hiroyuki; Mishima, Hiroshi; Tsuneoka, Hiroshi; Tsunoda, Kazushige; Iwata, Takeshi; Shimomura, Yoshikazu

    2016-11-01

    The enhanced S-cone syndrome (ESCS) is a rare hereditary retinal degeneration that has enhanced short wavelength-sensitive cone (S-cone) functions. The longitudinal clinical course of this disease has been rarely reported, and the genetic aspects of ESCS have not been well investigated in the Japanese population. In this report, we present our clinical and genetic findings for 2 patients with ESCS. The patients were 2 unrelated Japanese men. Standard ophthalmic examinations and mutation screening for the NR2E3 gene were performed. Patient 1 was a 36-year-old man, and his clinical findings were typical of ESCS. His decimal best-corrected visual acuity (BCVA) was 1.0 OD and 0.5 OS after removal of cataracts. Genetic investigations revealed a homozygous truncation frameshift, the p.I307LfsX33 mutation. Patient 2 was an 11-year-old boy when he was first examined by us. His clinical findings were typical of ESCS except for uveitis in the left eye. His decimal BCVA at the age of 39 years was maintained at 1.5 in each eye, although the retinal degeneration and visual field impairments had progressed during the follow-up period. The genetic investigations revealed homozygous mutations of p.R104Q in the NR2E3 gene. The frameshift mutation, p.I307LfsX33, in the NR2E3 gene is a new causative mutation for ESCS. The clinical observations for patient 2 are the longest ever reported. The retinal degeneration caused by this mutation is slowly progressive, and these patients maintained good vision with maintenance of the foveal structure until their late thirties.

  3. COP1 Controls Abiotic Stress Responses by Modulating AtSIZ1 Function Through its E3 Ubiquitin Ligase Activity

    Directory of Open Access Journals (Sweden)

    Joo Yong Kim

    2016-08-01

    Full Text Available Ubiquitination and sumoylation are essential post-translational modifications that regulate growth and development processes in plants, including control of hormone signaling mechanisms and responses to stress. This study showed that COP1 (Constitutive photomorphogenic 1 regulated the activity of Arabidopsis E3 SUMO (Small ubiquitin-related modifier ligase AtSIZ1 through its E3 ubiquitin ligase activity. Yeast two hybrid analysis demonstrated that COP1 and AtSIZ1 directly interacted with one another, and subcellular localization assays indicated that COP1 and AtSIZ1 co-localized in nuclear bodies. Analysis of ubiquitination showed that AtSIZ1 was polyubiquitinated by COP1. The AtSIZ1 level was higher in cop1-4 mutants than in wild-type seedlings under light or dark conditions, and overexpression of a dominant-negative (DN-COP1 mutant led to a substantial increase in AtSIZ1 accumulation. In addition, under drought, cold, and high salt conditions, SUMO-conjugate levels were elevated in DN-COP1-overexpressing plants and cop1-4 mutant plants compared to wild-type plants. Taken together, our results indicate that COP1 controls responses to abiotic stress by modulation of AtSIZ1 levels and activity.

  4. 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.

  5. Human cytomegalovirus IE1 downregulates Hes1 in neural progenitor cells as a potential E3 ubiquitin ligase.

    Directory of Open Access Journals (Sweden)

    Xi-Juan Liu

    2017-07-01

    Full Text Available Congenital human cytomegalovirus (HCMV infection is the leading cause of neurological disabilities in children worldwide, but the mechanisms underlying these disorders are far from well-defined. HCMV infection has been shown to dysregulate the Notch signaling pathway in human neural progenitor cells (NPCs. As an important downstream effector of Notch signaling, the transcriptional regulator Hairy and Enhancer of Split 1 (Hes1 is essential for governing NPC fate and fetal brain development. In the present study, we report that HCMV infection downregulates Hes1 protein levels in infected NPCs. The HCMV 72-kDa immediate-early 1 protein (IE1 is involved in Hes1 degradation by assembling a ubiquitination complex and promoting Hes1 ubiquitination as a potential E3 ubiquitin ligase, followed by proteasomal degradation of Hes1. Sp100A, an important component of PML nuclear bodies, is identified to be another target of IE1-mediated ubiquitination. A C-terminal acidic region in IE1, spanning amino acids 451 to 475, is required for IE1/Hes1 physical interaction and IE1-mediated Hes1 ubiquitination, but is dispensable for IE1/Sp100A interaction and ubiquitination. Our study suggests a novel mechanism linking downregulation of Hes1 protein to neurodevelopmental disorders caused by HCMV infection. Our findings also complement the current knowledge of herpesviruses by identifying IE1 as the first potential HCMV-encoded E3 ubiquitin ligase.

  6. The Replisome-Coupled E3 Ubiquitin Ligase Rtt101Mms22 Counteracts Mrc1 Function to Tolerate Genotoxic Stress.

    Directory of Open Access Journals (Sweden)

    Raymond Buser

    2016-02-01

    Full Text Available Faithful DNA replication and repair requires the activity of cullin 4-based E3 ubiquitin ligases (CRL4, but the underlying mechanisms remain poorly understood. The budding yeast Cul4 homologue, Rtt101, in complex with the linker Mms1 and the putative substrate adaptor Mms22 promotes progression of replication forks through damaged DNA. Here we characterized the interactome of Mms22 and found that the Rtt101(Mms22 ligase associates with the replisome progression complex during S-phase via the amino-terminal WD40 domain of Ctf4. Moreover, genetic screening for suppressors of the genotoxic sensitivity of rtt101Δ cells identified a cluster of replication proteins, among them a component of the fork protection complex, Mrc1. In contrast to rtt101Δ and mms22Δ cells, mrc1Δ rtt101Δ and mrc1Δ mms22Δ double mutants complete DNA replication upon replication stress by facilitating the repair/restart of stalled replication forks using a Rad52-dependent mechanism. Our results suggest that the Rtt101(Mms22 E3 ligase does not induce Mrc1 degradation, but specifically counteracts Mrc1's replicative function, possibly by modulating its interaction with the CMG (Cdc45-MCM-GINS complex at stalled forks.

  7. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells.

    Science.gov (United States)

    Paolino, Magdalena; Choidas, Axel; Wallner, Stephanie; Pranjic, Blanka; Uribesalgo, Iris; Loeser, Stefanie; Jamieson, Amanda M; Langdon, Wallace Y; Ikeda, Fumiyo; Fededa, Juan Pablo; Cronin, Shane J; Nitsch, Roberto; Schultz-Fademrecht, Carsten; Eickhoff, Jan; Menninger, Sascha; Unger, Anke; Torka, Robert; Gruber, Thomas; Hinterleitner, Reinhard; Baier, Gottfried; Wolf, Dominik; Ullrich, Axel; Klebl, Bert M; Penninger, Josef M

    2014-03-27

    Tumour metastasis is the primary cause of mortality in cancer patients and remains the key challenge for cancer therapy. New therapeutic approaches to block inhibitory pathways of the immune system have renewed hopes for the utility of such therapies. Here we show that genetic deletion of the E3 ubiquitin ligase Cbl-b (casitas B-lineage lymphoma-b) or targeted inactivation of its E3 ligase activity licenses natural killer (NK) cells to spontaneously reject metastatic tumours. The TAM tyrosine kinase receptors Tyro3, Axl and Mer (also known as Mertk) were identified as ubiquitylation substrates for Cbl-b. Treatment of wild-type NK cells with a newly developed small molecule TAM kinase inhibitor conferred therapeutic potential, efficiently enhancing anti-metastatic NK cell activity in vivo. Oral or intraperitoneal administration using this TAM inhibitor markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells. We further report that the anticoagulant warfarin exerts anti-metastatic activity in mice via Cbl-b/TAM receptors in NK cells, providing a molecular explanation for a 50-year-old puzzle in cancer biology. This novel TAM/Cbl-b inhibitory pathway shows that it might be possible to develop a 'pill' that awakens the innate immune system to kill cancer metastases.

  8. Pathways to a low-carbon economy for the UK with the macro-econometric E3MG model

    International Nuclear Information System (INIS)

    Dagoumas, A.S.; Barker, T.S.

    2010-01-01

    This paper examines different carbon pathways for achieving deep CO 2 reduction targets for the UK using a macro-econometric hybrid model E3MG, which stands for Energy-Economy-Environment Model at the Global level. The E3MG, with the UK as one of its regions, combines a top-down approach for modeling the global economy and for estimating the aggregate and disaggregate energy demand and a bottom-up approach (Energy Technology subModel, ETM) for simulating the power sector, which then provides feedback to the energy demand equations and the whole economy. The ETM submodel uses a probabilistic approach and historical data for estimating the penetration levels of the different technologies, considering their economic, technical and environmental characteristics. Three pathway scenarios (CFH, CLC and CAM) simulate the CO 2 reduction by 40%, 60% and 80% by 2050 compared to 1990 levels respectively and are compared with a reference scenario (REF), with no reduction target. The targets are modeled as the UK contribution to an international mitigation effort, such as achieving the G8 reduction targets, which is a more realistic political framework for the UK to move towards deep reductions rather than moving alone. This paper aims to provide modeling evidence that deep reduction targets can be met through different carbon pathways while also assessing the macroeconomic effects of the pathways on GDP and investment.

  9. Plasma lipoproteins in familial dysbetalipoproteinemia associated with apolipoproteins E2 (Arg158 -->Cys), E3-Leiden, and E2 (Lys146-->Gln), and effects of treatment with simvastatin

    NARCIS (Netherlands)

    Zhao, S.P.; Smelt, A.H.; Maagdenberg, A.M. van den; Tol, A. van; Vroom T.F.; Gevers Leuven, J.A.; Frants, R.R.; Havekes, L.M.; Laarse, A. van der; Hooft, F.M. van 't

    1994-01-01

    Using a density-gradient ultracentrifugation technique, we analyzed in detail the plasma lipoprotein profiles of 18 patients with familial dysbetalipoproteinemia (FD) who had apolipoprotein (apo) E2(Arg158-->Cys) homozygosity (the E2-158 variant, n = 6), apoE3-Leiden heterozygosity (the E3-Leiden

  10. Distinct functional domains contribute to degradation of the low density lipoprotein receptor (LDLR) by the E3 ubiquitin ligase inducible Degrader of the LDLR (IDOL)

    NARCIS (Netherlands)

    Sorrentino, Vincenzo; Scheer, Lilith; Santos, Ana; Reits, Eric; Bleijlevens, Boris; Zelcer, Noam

    2011-01-01

    We recently identified the liver X receptor-regulated E3 ubiquitin ligase inducible degrader of the LDL receptor (IDOL) as a modulator of lipoprotein metabolism. Acting as an E3 ubiquitin ligase, IDOL triggers ubiquitination and subsequent degradation of the low density lipoprotein receptor (LDLR).

  11. Reversal of hypercholesterolemia in apolipoprotein E2 and apolipoprotein E3-Leiden transgenic mice by adenovirus-mediated gene transfer of the VLDL receptor

    NARCIS (Netherlands)

    Dijk, K.W. van; Vlijmen, B.J.M. van; Zee, A. van der; Hof, B. van 't; Boom, H. van der; Kobayashi, K.; Chan, L.; Havekes, L.M.; Hofker, M.H.

    1998-01-01

    We have investigated the interaction of apolipoprotein E2(Arg158- Cys) (apoE2) and apolipoprotein E3Leiden (apoE3-Leiden) with the very low density lipoprotein (VLDL) receptor in vivo and in vitro to define the possible role of this receptor in lipoprotein metabolism and atherosclerosis. The in vivo

  12. 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

  13. The 3-D geological model around Chang'E-3 landing site based on lunar penetrating radar Channel 1 data

    Science.gov (United States)

    Yuan, Yuefeng; Zhu, Peimin; Zhao, Na; Xiao, Long; Garnero, Edward; Xiao, Zhiyong; Zhao, Jiannan; Qiao, Le

    2017-07-01

    High-frequency lunar penetrating radar (LPR) data from an instrument on the lunar rover Yutu, from the Chang'E-3 (CE-3) robotic lander, were used to build a three-dimensional (3-D) geological model of the lunar subsurface structure. The CE-3 landing site is in the northern Mare Imbrium. More than five significant reflection horizons are evident in the LPR profile, which we interpret as different period lava flow sequences deposited on the lunar surface. The most probable directions of these flows were inferred from layer depths, thicknesses, and other geological information. Moreover, the apparent Imbrian paleoregolith homogeneity in the profile supports the suggestion of a quiescent period of lunar surface evolution. Similar subsurface structures are found at the NASA Apollo landing sites, indicating that the cause and time of formation of the imaged phenomena may be similar between the two distant regions.

  14. H2B ubiquitination: Conserved molecular mechanism, diverse physiologic functions of the E3 ligase during meiosis.

    Science.gov (United States)

    Wang, Liying; Cao, Chunwei; Wang, Fang; Zhao, Jianguo; Li, Wei

    2017-09-03

    RNF20/Bre1 mediated H2B ubiquitination (H2Bub) has various physiologic functions. Recently, we found that H2Bub participates in meiotic recombination by promoting chromatin relaxation during meiosis. We then analyzed the phylogenetic relationships among the E3 ligase for H2Bub, its E2 Rad6 and their partner WW domain-containing adaptor with a coiled-coil (WAC) or Lge1, and found that the molecular mechanism underlying H2Bub is evolutionarily conserved from yeast to mammals. However, RNF20 has diverse physiologic functions in different organisms, which might be caused by the evolutionary divergency of their domain/motif architectures. In the current extra view, we not only elucidate the evolutionarily conserved molecular mechanism underlying H2Bub, but also discuss the diverse physiologic functions of RNF20 during meiosis.

  15. 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.

  16. The β-catenin E3 ubiquitin ligase SIAH-1 is regulated by CSN5/JAB1 in CRC cells.

    Science.gov (United States)

    Jumpertz, Sandra; Hennes, Thomas; Asare, Yaw; Vervoorts, Jörg; Bernhagen, Jürgen; Schütz, Anke K

    2014-09-01

    COP9 signalosome subunit 5 (CSN5) plays a decisive role in cellular processes such as cell cycle regulation and apoptosis via promoting protein degradation, gene transcription, and nuclear export. CSN5 regulates cullin-RING-E3 ligase (CRL) activity through its deNEDDylase function. It is overexpressed in several tumor entities, but its role in colorectal cancer (CRC) is poorly understood. Wnt/β-catenin signaling is aberrant in most CRC cells, resulting in increased levels of oncogenic β-catenin and thus tumor progression. Under physiological conditions, β-catenin levels are tightly regulated by continuous proteasomal degradation. We recently showed that knockdown of CSN5 in model and CRC cells results in decreased (phospho)-β-catenin levels. Reduced β-catenin levels were associated with an attenuated proliferation rate of different CRC cell types after CSN5 knockdown. The canonical Wnt pathway involves degradation of β-catenin by a β-TrCP1-containing E3 ligase, but is mostly non-functional in CRC cells. We thus hypothesized that alternative β-catenin degradation mediated by SIAH-1 (seven in absentia homolog-1), is responsible for the effect of CSN5 on β-catenin signaling in CRC cells. We found that SIAH-1 plays an essential role in β-catenin degradation in HCT116 CRC cells and that CSN5 affects β-catenin target gene expression in these cells. Of note, CSN5 affected SIAH-1 mRNA and SIAH-1 protein levels. Moreover, β-catenin and SIAH-1 form protein complexes with CSN5 in HCT116 cells. Lastly, we demonstrate that CSN5 promotes SIAH-1 degradation in HCT116 and SW480 cells and that this is associated with its deNEDDylase activity. In conclusion, we have identified a CSN5/β-catenin/SIAH-1 interaction network that might control β-catenin degradation in CRC cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Functional characterization of Anaphase Promoting Complex/Cyclosome (APC/C) E3 ubiquitin ligases in tumorigenesis

    Science.gov (United States)

    Zhang, Jinfang; Wan, Lixin; Dai, Xiangpeng; Sun, Yi; Wei, Wenyi

    2014-01-01

    The Anaphase Promoting Complex/Cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that primarily governs cell cycle progression. APC/C is composed of at least 14 core subunits and recruits its substrates for ubiquitination via one of the two adaptor proteins, Cdc20 or Cdh1, in M or M/early G1 phase, respectively. Furthermore, recent studies have shed light on crucial functions for APC/C in maintaining genomic integrity, neuronal differentiation, cellular metabolism and tumorigenesis. To gain better insight into the in vivo physiological functions of APC/C in regulating various cellular processes, particularly development and tumorigenesis, a number of mouse models of APC/C core subunits, coactivators or inhibitors have been established and characterized. However, due to their essential role in cell cycle regulation, most of the germline knockout mice targeting the APC/C pathway are embryonic lethal, indicating the need for generating conditional knockout mouse models to assess the role in tumorigenesis for each APC/C signaling component in specific tissues. In this review, we will first provide a brief introduction of the ubiquitin-proteasome system (UPS) and the biochemical activities and cellular functions of the APC/C E3 ligase. We will then focus primarily on characterizing genetic mouse models used to understand the physiological roles of each APC/C signaling component in embryogenesis, cell proliferation, development and carcinogenesis. Finally, we discuss future research directions to further elucidate the physiological contributions of APC/C components during tumorigenesis and validate their potentials as a novel class of anti-cancer targets. PMID:24569229

  18. Global Kinetic Analysis of Mammalian E3 Reveals pH-dependent NAD+/NADH Regulation, Physiological Kinetic Reversibility, and Catalytic Optimum*

    Science.gov (United States)

    Moxley, Michael A.; Beard, Daniel A.; Bazil, Jason N.

    2016-01-01

    Mammalian E3 is an essential mitochondrial enzyme responsible for catalyzing the terminal reaction in the oxidative catabolism of several metabolites. E3 is a key regulator of metabolic fuel selection as a component of the pyruvate dehydrogenase complex (PDHc). E3 regulates PDHc activity by altering the affinity of pyruvate dehydrogenase kinase, an inhibitor of the enzyme complex, through changes in reduction and acetylation state of lipoamide moieties set by the NAD+/NADH ratio. Thus, an accurate kinetic model of E3 is needed to predict overall mammalian PDHc activity. Here, we have combined numerous literature data sets and new equilibrium spectroscopic experiments with a multitude of independently collected forward and reverse steady-state kinetic assays using pig heart E3. The latter kinetic assays demonstrate a pH-dependent transition of NAD+ activation to inhibition, shown here, to our knowledge, for the first time in a single consistent data set. Experimental data were analyzed to yield a thermodynamically constrained four-redox-state model of E3 that simulates pH-dependent activation/inhibition and active site redox states for various conditions. The developed model was used to determine substrate/product conditions that give maximal E3 rates and show that, due to non-Michaelis-Menten behavior, the maximal flux is different compared with the classically defined kcat. PMID:26644471

  19. E3B1, a human homologue of the mouse gene product Abi-1, sensitizes activation of Rap1 in response to epidermal growth factor

    International Nuclear Information System (INIS)

    Jenei, Veronika; Andersson, Tommy; Jakus, Judit; Dib, Karim

    2005-01-01

    E3B1, a human homologue of the mouse gene product Abi-1, has been implicated in growth-factor-mediated regulation of the small GTPases p21 Ras and Rac. E3b1 is a regulator of Rac because it can form a complex with Sos-1 and eps8, and such a Sos-1-e3B1-eps8 complex serves as a guanine nucleotide exchange factor for Rac. In the present study, we found that overexpression of e3B1 in NIH3T3/EGFR cells sensitized EGF-induced activation of Rac1, whereas it had no impact on EGF-induced activation of p21 Ras . Remarkably, we found that EGF-induced activation of the p21 Ras -related GTPase Rap1 was also sensitized in NIH3T3/EGFR-e3B1 cells. Thus, in NIH3T3/EGFR-e3B1 cells, maximal EGF-induced activation of Rap1 occurs with a dose of EGF much lower than in NIH3T3/EGFR cells. We also report that overexpression of e3B1 in NIH3T3/EGFR cells renders EGF-induced activation of Rap1 completely dependent on Src tyrosine kinases but not on c-Abl. However, EGF-induced tyrosine phosphorylation of the Rap GEF C3G occurred regardless of whether e3B1 was overexpressed or not, and this did not involve Src tyrosine kinases. Accordingly, we propose that overexpression of e3B1 in NIH3T3/EGFR cells leads to mobilization of Src tyrosine kinases that participate in EGF-induced activation of Rap1 and inhibition of cell proliferation

  20. Decay of the isoscalar 1(h/2π)ω giant E3 resonance in 92Mo

    International Nuclear Information System (INIS)

    Klein, R.A.

    1984-01-01

    By means of the Heidelberg tandem-post accelerator combination the decay of the isoscalar 1 (h/2π)ω giant E3 resonance (LEOR) in 92 Mo was studied by (α, α', γ) coincidence measurements. At an incident energy of 50.4 MeV of the α particles the scattered helium nuclei were spectroscoped by eight semiconductor detectors in a maximum of the L=3 angular distribution. The γ quanta emitted coincidently by the excited target nuclei were detected in three high-resolution Ge diodes. Because of the good resolution both in the alpha and in the gamma branch for about 30 states in the excitation energy range of 1-7 MeV branching ratios for the gamma decay could be measured. For 16 of these levels lifetimes were determined by the Doppler-shift attenuation method. Starting from the determined branching ratios and typical lifetimes (40-90 fs) for 3 - states in the excitation-energy range of the LEOR (5-10 MeV) an earlier reported strong ground-state decay (8%) of the LEOR can be excluded. Rather the LEOR decays so as it is expected by the model of the statistical decay namely dominantly to low-lying 3 - , 4 - , and above all 5 - levels. A likewise reported strong E1-decay of the LEOR to the 2 + 1 state in 90 Zr which is implicated in the framework of a collective model in connection with the E3 ground-state transitions can in 92 Mo also not be confirmed. In spite of the strongly collective nature of the first 2 + state in 92 Mo an increased LEOR decay to this level was not observed. Against that in the LEOR region ground-state transitions of 1 - states with isoscalar nature were spectroscoped. The observation of these levels is also reproduced by performed RPA calculations. A parallel measurement on 90 Zr confirms the results of this thesis. (orig./HSI) [de

  1. Human Adenovirus Infection Causes Cellular E3 Ubiquitin Ligase MKRN1 Degradation Involving the Viral Core Protein pVII.

    Science.gov (United States)

    Inturi, Raviteja; Mun, Kwangchol; Singethan, Katrin; Schreiner, Sabrina; Punga, Tanel

    2018-02-01

    Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein, VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. Here we report the identification of several cellular proteins interacting with the precursor pVII protein. We show that the cellular E3 ubiquitin ligase MKRN1 is a novel precursor pVII-interacting protein in HAdV-C5-infected cells. Surprisingly, the endogenous MKRN1 protein underwent proteasomal degradation during the late phase of HAdV-C5 infection in various human cell lines. MKRN1 protein degradation occurred independently of the HAdV E1B55K and E4orf6 proteins. We provide experimental evidence that the precursor pVII protein binding enhances MKRN1 self-ubiquitination, whereas the processed mature VII protein is deficient in this function. Based on these data, we propose that the pVII protein binding promotes MKRN1 self-ubiquitination, followed by proteasomal degradation of the MKRN1 protein, in HAdV-C5-infected cells. In addition, we show that measles virus and vesicular stomatitis virus infections reduce the MKRN1 protein accumulation in the recipient cells. Taken together, our results expand the functional repertoire of the HAdV-C5 precursor pVII protein in lytic virus infection and highlight MKRN1 as a potential common target during different virus infections. IMPORTANCE Human adenoviruses (HAdVs) are common pathogens causing a wide range of diseases. To achieve pathogenicity, HAdVs have to counteract a variety of host cell antiviral defense systems, which would otherwise hamper virus replication. In this study, we show that the HAdV-C5 histone-like core protein pVII binds to and promotes self-ubiquitination of a cellular E3 ubiquitin ligase named MKRN1. This mutual interaction between the pVII and

  2. The Host E3-Ubiquitin Ligase TRIM6 Ubiquitinates the Ebola Virus VP35 Protein and Promotes Virus Replication.

    Science.gov (United States)

    Bharaj, Preeti; Atkins, Colm; Luthra, Priya; Giraldo, Maria Isabel; Dawes, Brian E; Miorin, Lisa; Johnson, Jeffrey R; Krogan, Nevan J; Basler, Christopher F; Freiberg, Alexander N; Rajsbaum, Ricardo

    2017-09-15

    Ebola virus (EBOV), a member of the Filoviridae family, is a highly pathogenic virus that causes severe hemorrhagic fever in humans and is responsible for epidemics throughout sub-Saharan, central, and West Africa. The EBOV genome encodes VP35, an important viral protein involved in virus replication by acting as an essential cofactor of the viral polymerase as well as a potent antagonist of the host antiviral type I interferon (IFN-I) system. By using mass spectrometry analysis and coimmunoprecipitation assays, we show here that VP35 is ubiquitinated on lysine 309 (K309), a residue located on its IFN antagonist domain. We also found that VP35 interacts with TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family. We recently reported that TRIM6 promotes the synthesis of unanchored K48-linked polyubiquitin chains, which are not covalently attached to any protein, to induce efficient antiviral IFN-I-mediated responses. Consistent with this notion, VP35 also associated noncovalently with polyubiquitin chains and inhibited TRIM6-mediated IFN-I induction. Intriguingly, we also found that TRIM6 enhances EBOV polymerase activity in a minigenome assay and TRIM6 knockout cells have reduced replication of infectious EBOV, suggesting that VP35 hijacks TRIM6 to promote EBOV replication through ubiquitination. Our work provides evidence that TRIM6 is an important host cellular factor that promotes EBOV replication, and future studies will focus on whether TRIM6 could be targeted for therapeutic intervention against EBOV infection. IMPORTANCE EBOV belongs to a family of highly pathogenic viruses that cause severe hemorrhagic fever in humans and other mammals with high mortality rates (40 to 90%). Because of its high pathogenicity and lack of licensed antivirals and vaccines, EBOV is listed as a tier 1 select-agent risk group 4 pathogen. An important mechanism for the severity of EBOV infection is its suppression of innate immune responses. The EBOV VP35

  3. Boes Skov 1 Udgravningsberetning

    DEFF Research Database (Denmark)

    Løvschal, Mette; Søndergaard, Louise; Vinter, Michael

    2018-01-01

    . Aktivitetsområdet rummer flere keramikrige gruber, ildsteder samt en kogestensgrube. På baggrund af keramikken kan oldtidsagrene og grubekomplekset dateres til omtrent den samme periode: yngre bronzealder-førromersk jernalder med en koncentration i førromersk jernalder periode 1. Aktivitetsområdet er tegnet i 1......:10 til 1:50, oversigtskortene er 1:75 til 1:250 og enkelte øvrige anlæg er tegnet i 1:20....

  4. RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for Interstrand Crosslink Repair and Human Health.

    Science.gov (United States)

    Feeney, Laura; Muñoz, Ivan M; Lachaud, Christophe; Toth, Rachel; Appleton, Paul L; Schindler, Detlev; Rouse, John

    2017-06-01

    Defects in the repair of DNA interstrand crosslinks (ICLs) are associated with the genome instability syndrome Fanconi anemia (FA). Here we report that cells with mutations in RFWD3, an E3 ubiquitin ligase that interacts with and ubiquitylates replication protein A (RPA), show profound defects in ICL repair. An amino acid substitution in the WD40 repeats of RFWD3 (I639K) found in a new FA subtype abolishes interaction of RFWD3 with RPA, thereby preventing RFWD3 recruitment to sites of ICL-induced replication fork stalling. Moreover, single point mutations in the RPA32 subunit of RPA that abolish interaction with RFWD3 also inhibit ICL repair, demonstrating that RPA-mediated RFWD3 recruitment to stalled replication forks is important for ICL repair. We also report that unloading of RPA from sites of ICL induction is perturbed in RFWD3-deficient cells. These data reveal important roles for RFWD3 localization in protecting genome stability and preserving human health. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. A new lunar absolute control point: established by images from the landing camera on Chang'e-3

    International Nuclear Information System (INIS)

    Wang Fen-Fei; Liu Jian-Jun; Li Chun-Lai; Ren Xin; Mu Ling-Li; Yan Wei; Wang Wen-Rui; Xiao Jing-Tao; Tan Xu; Zhang Xiao-Xia; Zou Xiao-Duan; Gao Xing-Ye

    2014-01-01

    The establishment of a lunar control network is one of the core tasks in selenodesy, in which defining an absolute control point on the Moon is the most important step. However, up to now, the number of absolute control points has been very sparse. These absolute control points have mainly been lunar laser ranging retroreflectors, whose geographical location can be observed by observations on Earth and also identified in high resolution lunar satellite images. The Chang'e-3 (CE-3) probe successfully landed on the Moon, and its geographical location has been monitored by an observing station on Earth. Since its positional accuracy is expected to reach the meter level, the CE-3 landing site can become a new high precision absolute control point. We use a sequence of images taken from the landing camera, as well as satellite images taken by CE-1 and CE-2, to identify the location of the CE-3 lander. With its geographical location known, the CE-3 landing site can be established as a new absolute control point, which will effectively expand the current area of the lunar absolute control network by 22%, and can greatly facilitate future research in the field of lunar surveying and mapping, as well as selenodesy

  6. FUSION OF MULTI-SCALE DEMS FROM DESCENT AND NAVCM IMAGES OF CHANG’E-3 USING COMPRESSED SENSING METHOD

    Directory of Open Access Journals (Sweden)

    M. Peng

    2017-07-01

    Full Text Available The multi-source DEMs generated using the images acquired in the descent and landing phase and after landing contain supplementary information, and this makes it possible and beneficial to produce a higher-quality DEM through fusing the multi-scale DEMs. The proposed fusion method consists of three steps. First, source DEMs are split into small DEM patches, then the DEM patches are classified into a few groups by local density peaks clustering. Next, the grouped DEM patches are used for sub-dictionary learning by stochastic coordinate coding. The trained sub-dictionaries are combined into a dictionary for sparse representation. Finally, the simultaneous orthogonal matching pursuit (SOMP algorithm is used to achieve sparse representation. We use the real DEMs generated from Chang’e-3 descent images and navigation camera (Navcam stereo images to validate the proposed method. Through the experiments, we have reconstructed a seamless DEM with the highest resolution and the largest spatial coverage among the input data. The experimental results demonstrated the feasibility of the proposed method.

  7. Loss of Ubr2, an E3 ubiquitin ligase, leads to chromosome fragility and impaired homologous recombinational repair

    International Nuclear Information System (INIS)

    Ouyang, Yan; Kwon, Yong Tae; An, Jee Young; Eller, Danny; Tsai, S.-C.; Diaz-Perez, Silvia; Troke, Joshua J.; Teitell, Michael A.; Marahrens, York

    2006-01-01

    The N-end rule pathway of protein degradation targets proteins with destabilizing N-terminal residues. Ubr2 is one of the E3 ubiquitin ligases of the mouse N-end rule pathway. We have previously shown that Ubr2 -/- male mice are infertile, owing to the arrest of spermatocytes between the leptotene/zygotene and pachytene of meiosis I, the failure of chromosome pairing, and subsequent apoptosis. Here, we report that mouse fibroblast cells derived from Ubr2 -/- embryos display genome instability. The frequency of chromosomal bridges and micronuclei were much higher in Ubr2 -/- fibroblasts than in +/+ controls. Metaphase chromosome spreads from Ubr2 -/- cells revealed a high incidence of spontaneous chromosomal gaps, indicating chromosomal fragility. These fragile sites were generally replicated late in S phase. Ubr2 -/- cells were hypersensitive to mitomycin C, a DNA cross-linking agent, but displayed normal sensitivity to gamma-irradiation. A reporter assay showed that Ubr2 -/- cells are significantly impaired in the homologous recombination repair of a double strand break. In contrast, Ubr2 -/- cells appeared normal in an assay for non-homologous end joining. Our results therefore unveil the role of the ubiquitin ligase Ubr2 in maintaining genome integrity and in homologous recombination repair

  8. Loss of Ubr2, an E3 ubiquitin ligase, leads to chromosome fragility and impaired homologous recombinational repair

    Energy Technology Data Exchange (ETDEWEB)

    Ouyang, Yan [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Kwon, Yong Tae [Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261 (United States); An, Jee Young [Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Eller, Danny [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Tsai, S.-C. [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Diaz-Perez, Silvia [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Troke, Joshua J. [Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Teitell, Michael A. [Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Marahrens, York [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States)]. E-mail: ymarahrens@mednet.ucla.edu

    2006-04-11

    The N-end rule pathway of protein degradation targets proteins with destabilizing N-terminal residues. Ubr2 is one of the E3 ubiquitin ligases of the mouse N-end rule pathway. We have previously shown that Ubr2{sup -/-} male mice are infertile, owing to the arrest of spermatocytes between the leptotene/zygotene and pachytene of meiosis I, the failure of chromosome pairing, and subsequent apoptosis. Here, we report that mouse fibroblast cells derived from Ubr2{sup -/-} embryos display genome instability. The frequency of chromosomal bridges and micronuclei were much higher in Ubr2{sup -/-} fibroblasts than in +/+ controls. Metaphase chromosome spreads from Ubr2{sup -/-} cells revealed a high incidence of spontaneous chromosomal gaps, indicating chromosomal fragility. These fragile sites were generally replicated late in S phase. Ubr2{sup -/-} cells were hypersensitive to mitomycin C, a DNA cross-linking agent, but displayed normal sensitivity to gamma-irradiation. A reporter assay showed that Ubr2{sup -/-} cells are significantly impaired in the homologous recombination repair of a double strand break. In contrast, Ubr2{sup -/-} cells appeared normal in an assay for non-homologous end joining. Our results therefore unveil the role of the ubiquitin ligase Ubr2 in maintaining genome integrity and in homologous recombination repair.

  9. A method and results of color calibration for the Chang'e-3 terrain camera and panoramic camera

    International Nuclear Information System (INIS)

    Ren Xin; Li Chun-Lai; Liu Jian-Jun; Wang Fen-Fei; Yang Jian-Feng; Xue Bin; Liu En-Hai; Zhao Ru-Jin

    2014-01-01

    The terrain camera (TCAM) and panoramic camera (PCAM) are two of the major scientific payloads installed on the lander and rover of the Chang'e 3 mission respectively. They both use a Bayer color filter array covering CMOS sensor to capture color images of the Moon's surface. RGB values of the original images are related to these two kinds of cameras. There is an obvious color difference compared with human visual perception. This paper follows standards published by the International Commission on Illumination to establish a color correction model, designs the ground calibration experiment and obtains the color correction coefficient. The image quality has been significantly improved and there is no obvious color difference in the corrected images. Ground experimental results show that: (1) Compared with uncorrected images, the average color difference of TCAM is 4.30, which has been reduced by 62.1%. (2) The average color differences of the left and right cameras in PCAM are 4.14 and 4.16, which have been reduced by 68.3% and 67.6% respectively

  10. Parameters and structure of lunar regolith in Chang'E-3 landing area from lunar penetrating radar (LPR) data

    Science.gov (United States)

    Dong, Zehua; Fang, Guangyou; Ji, Yicai; Gao, Yunze; Wu, Chao; Zhang, Xiaojuan

    2017-01-01

    Chang'E-3 (CE-3) landed in the northwest Mare Imbrium, a region that has not been explored before. Yutu rover that released by CE-3 lander carried the first lunar surface penetrating radar (LPR) for exploring lunar regolith thickness and subsurface shallow geological structures. In this paper, based on the LPR data and the Panoramic Camera (PC) data, we first calculate the lunar surface regolith parameters in CE-3 landing area including its permittivity, density, conductivity and FeO + TiO2 content. LPR data provides a higher spatial resolution and more accuracy for the lunar regolith parameters comparing to other remote sensing techniques, such as orbit radar sounder and microwave sensing or earth-based powerful radar. We also derived the regolith thickness and its weathered rate with much better accuracy in the landing area. The results indicate that the regolith growth rate is much faster than previous estimation, the regolith parameters are not uniform even in such a small study area and the thickness and growth rate of lunar regolith here are different from other areas in Mare Imbrium. We infer that the main reason should be geological deformation that caused by multiple impacts of meteorites in different sizes.

  11. Dielectric constant and low-frequency infrared spectra for liquid water and ice Ih within the E3B model

    Energy Technology Data Exchange (ETDEWEB)

    Shi, L.; Ni, Y.; Drews, S. E. P.; Skinner, J. L. [Theoretical Chemistry Institute and Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706 (United States)

    2014-08-28

    Two intrinsic difficulties in modeling condensed-phase water with conventional rigid non-polarizable water models are: reproducing the static dielectric constants for liquid water and ice Ih, and generating the peak at about 200 cm{sup −1} in the low-frequency infrared spectrum for liquid water. The primary physical reason for these failures is believed to be the missing polarization effect in these models, and consequently various sophisticated polarizable water models have been developed. However, in this work we pursue a different strategy and propose a simple empirical scheme to include the polarization effect only on the dipole surface (without modifying a model's intermolecular interaction potential). We implement this strategy for our explicit three-body (E3B) model. Our calculated static dielectric constants and low-frequency infrared spectra are in good agreement with experiment for both liquid water and ice Ih over wide temperature ranges, albeit with one fitting parameter for each phase. The success of our modeling also suggests that thermal fluctuations about local minima and the energy differences between different proton-disordered configurations play minor roles in the static dielectric constant of ice Ih. Our analysis shows that the polarization effect is important in resolving the two difficulties mentioned above and sheds some light on the origin of several features in the low-frequency infrared spectra for liquid water and ice Ih.

  12. E3 Ligase Subunit Fbxo15 and PINK1 Kinase Regulate Cardiolipin Synthase 1 Stability and Mitochondrial Function in Pneumonia

    Directory of Open Access Journals (Sweden)

    Bill B. Chen

    2014-04-01

    Full Text Available Acute lung injury (ALI is linked to mitochondrial injury, resulting in impaired cellular oxygen utilization; however, it is unknown how these events are linked on the molecular level. Cardiolipin, a mitochondrial-specific lipid, is generated by cardiolipin synthase (CLS1. Here, we show that S. aureus activates a ubiquitin E3 ligase component, Fbxo15, that is sufficient to mediate proteasomal degradation of CLS1 in epithelia, resulting in decreased cardiolipin availability and disrupted mitochondrial function. CLS1 is destabilized by the phosphatase and tensin homolog (PTEN-induced putative kinase 1 (PINK1, which binds CLS1 to phosphorylate and regulates CLS1 disposal. Like Fbxo15, PINK1 interacts with and regulates levels of CLS1 through a mechanism dependent upon Thr219. S. aureus infection upregulates this Fbxo15-PINK1 pathway to impair mitochondrial integrity, and Pink1 knockout mice are less prone to S. aureus-induced ALI. Thus, ALI-associated disruption of cellular bioenergetics involves bioeffectors that utilize a phosphodegron to elicit ubiquitin-mediated disposal of a key mitochondrial enzyme.

  13. Structure of the Siz/PIAS SUMO E3 ligase Siz1 and determinants required for SUMO modification of PCNA

    Science.gov (United States)

    Yunus, Ali A.; Lima, Christopher D.

    2009-01-01

    Summary 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 E2~SUMO thioester while the PINIT domain is essential for redirecting SUMO conjugation to the proliferating cell nuclear antigen (PCNA) at lysine 164, a non-consensus 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. PMID:19748360

  14. LOSS OF JAK2 REGULATION VIA VHL-SOCS1 E3 UBIQUITIN HETEROCOMPLEX UNDERLIES CHUVASH POLYCYTHEMIA

    Science.gov (United States)

    Russell, Ryan C.; Sufan, Roxana I.; Zhou, Bing; Heir, Pardeep; Bunda, Severa; Sybingco, Stephanie S.; Greer, Samantha N.; Roche, Olga; Heathcote, Samuel A.; Chow, Vinca W.K.; Boba, Lukasz M.; Richmond, Terri D.; Hickey, Michele M.; Barber, Dwayne L.; Cheresh, David A.; Simon, M. Celeste; Irwin, Meredith S.; Kim, William Y.; Ohh, Michael

    2011-01-01

    SUMMARY Chuvash polycythemia (CP) is a rare congenital form of polycythemia caused by homozygous R200W and H191D mutations in the von Hippel-Lindau (VHL) gene whose gene product is the principal negative regulator of hypoxia-inducible factor. However, the molecular mechanisms underlying some of the hallmark features of CP such as hypersensitivity to erythropoietin are unclear. Here, we show that VHL directly binds suppressor of cytokine signalling 1 (SOCS1) to form a heterodimeric E3 ligase that targets phosphorylated (p)JAK2 for ubiquitin-mediated destruction. In contrast, CP-associated VHL mutants have altered affinity for SOCS1 and fail to engage and degrade pJAK2. Systemic administration of a highly selective JAK2 inhibitor, TG101209, reverses the disease phenotype in vhlR200W/R200W knock-in mice, a model that faithfully recapitulates human CP. These results reveal VHL as a SOCS1-cooperative negative regulator of JAK2 and provide compelling biochemical and preclinical evidence for JAK2- targeted therapy in CP patients. PMID:21685897

  15. The Arabidopsis E3 Ubiquitin Ligase HOS1 Negatively Regulates CONSTANS Abundance in the Photoperiodic Control of Flowering[W

    Science.gov (United States)

    Lazaro, Ana; Valverde, Federico; Piñeiro, Manuel; Jarillo, Jose A.

    2012-01-01

    The Arabidopsis thaliana early in short days6 (esd6) mutant was isolated in a screen for mutations that accelerate flowering time. Among other developmental alterations, esd6 displays early flowering in both long- and short-day conditions. Fine mapping of the mutation showed that the esd6 phenotype is caused by a lesion in the HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 (HOS1) locus, which encodes a RING finger–containing E3 ubiquitin ligase. The esd6/hos1 mutation causes decreased FLOWERING LOCUS C expression and requires CONSTANS (CO) protein for its early flowering phenotype under long days. Moreover, CO and HOS1 physically interact in vitro and in planta, and HOS1 regulates CO abundance, particularly during the daylight period. Accordingly, hos1 causes a shift in the regular long-day pattern of expression of FLOWERING LOCUS T (FT) transcript, starting to rise 4 h after dawn in the mutant. In addition, HOS1 interacts synergistically with CONSTITUTIVE PHOTOMORPHOGENIC1, another regulator of CO protein stability, in the regulation of flowering time. Taken together, these results indicate that HOS1 is involved in the control of CO abundance, ensuring that CO activation of FT occurs only when the light period reaches a certain length and preventing precocious flowering in Arabidopsis. PMID:22408073

  16. A method and results of color calibration for the Chang'e-3 terrain camera and panoramic camera

    Science.gov (United States)

    Ren, Xin; Li, Chun-Lai; Liu, Jian-Jun; Wang, Fen-Fei; Yang, Jian-Feng; Liu, En-Hai; Xue, Bin; Zhao, Ru-Jin

    2014-12-01

    The terrain camera (TCAM) and panoramic camera (PCAM) are two of the major scientific payloads installed on the lander and rover of the Chang'e 3 mission respectively. They both use a Bayer color filter array covering CMOS sensor to capture color images of the Moon's surface. RGB values of the original images are related to these two kinds of cameras. There is an obvious color difference compared with human visual perception. This paper follows standards published by the International Commission on Illumination to establish a color correction model, designs the ground calibration experiment and obtains the color correction coefficient. The image quality has been significantly improved and there is no obvious color difference in the corrected images. Ground experimental results show that: (1) Compared with uncorrected images, the average color difference of TCAM is 4.30, which has been reduced by 62.1%. (2) The average color differences of the left and right cameras in PCAM are 4.14 and 4.16, which have been reduced by 68.3% and 67.6% respectively.

  17. Two distinct E3 ubiquitin ligases have complementary functions in the regulation of delta and serrate signaling in Drosophila.

    Directory of Open Access Journals (Sweden)

    Roland Le Borgne

    2005-04-01

    Full Text Available Signaling by the Notch ligands Delta (Dl and Serrate (Ser regulates a wide variety of essential cell-fate decisions during animal development. Two distinct E3 ubiquitin ligases, Neuralized (Neur and Mind bomb (Mib, have been shown to regulate Dl signaling in Drosophila melanogaster and Danio rerio, respectively. While the neur and mib genes are evolutionarily conserved, their respective roles in the context of a single organism have not yet been examined. We show here that the Drosophila mind bomb (D-mib gene regulates a subset of Notch signaling events, including wing margin specification, leg segmentation, and vein determination, that are distinct from those events requiring neur activity. D-mib also modulates lateral inhibition, a neur- and Dl-dependent signaling event, suggesting that D-mib regulates Dl signaling. During wing development, expression of D-mib in dorsal cells appears to be necessary and sufficient for wing margin specification, indicating that D-mib also regulates Ser signaling. Moreover, the activity of the D-mib gene is required for the endocytosis of Ser in wing imaginal disc cells. Finally, ectopic expression of neur in D-mib mutant larvae rescues the wing D-mib phenotype, indicating that Neur can compensate for the lack of D-mib activity. We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila.

  18. The E3 Ubiquitin Ligase MIB-1 Is Necessary To Form the Nuclear Halo in Caenorhabditis elegans Sperm.

    Science.gov (United States)

    Herrera, Leslie A; Starr, Daniel A

    2018-05-18

    Unlike the classical nuclear envelope with two membranes found in other eukaryotic cells, most nematode sperm nuclei are not encapsulated by membranes. Instead, they are surrounded by a nuclear halo of unknown composition. How the halo is formed and regulated is unknown. We used forward genetics to identify molecular lesions behind three classical fer (fertilization defective) mutations that disrupt the ultrastructure of the Caenorhabditis elegans sperm nuclear halo. We found fer-2 and fer-4 alleles to be nonsense mutations in mib-1. fer-3 was caused by a nonsense mutation in eri-3 GFP::MIB-1 was expressed in the germline during early spermatogenesis, but not in mature sperm. mib-1 encodes a conserved E3 ubiquitin ligase homologous to vertebrate Mib1 and Mib2, which function in Notch signaling. Here, we show that mib-1 is important for male sterility and is involved in the regulation or formation of the nuclear halo during nematode spermatogenesis. Copyright © 2018, G3: Genes, Genomes, Genetics.

  19. 29 CFR 550.1 - “Talent fees” as used in section 7(e)(3)(c) of the Fair Labor Standards Act, as amended.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false âTalent feesâ as used in section 7(e)(3)(c) of the Fair...) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS DEFINING AND DELIMITING THE TERM âTALENT FEESâ § 550.1 “Talent fees” as used in section 7(e)(3)(c) of the Fair Labor Standards Act, as amended. The...

  20. NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP).

    Science.gov (United States)

    Schorderet, Daniel F; Escher, Pascal

    2009-11-01

    NR2E3, also called photoreceptor-specific nuclear receptor (PNR), is a transcription factor of the nuclear hormone receptor superfamily whose expression is uniquely restricted to photoreceptors. There, its physiological activity is essential for proper rod and cone photoreceptor development and maintenance. Thirty-two different mutations in NR2E3 have been identified in either homozygous or compound heterozygous state in the recessively inherited enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), and clumped pigmentary retinal degeneration (CPRD). The clinical phenotype common to all these patients is night blindness, rudimental or absent rod function, and hyperfunction of the "blue" S-cones. A single p.G56R mutation is inherited in a dominant manner and causes retinitis pigmentosa (RP). We have established a new locus-specific database for NR2E3 (www.LOVD.nl/eye), containing all reported mutations, polymorphisms, and unclassified sequence variants, including novel ones. A high proportion of mutations are located in the evolutionarily-conserved DNA-binding domains (DBDs) and ligand-binding domains (LBDs) of NR2E3. Based on homology modeling of these NR2E3 domains, we propose a structural localization of mutated residues. The high variability of clinical phenotypes observed in patients affected by NR2E3-linked retinal degenerations may be caused by different disease mechanisms, including absence of DNA-binding, altered interactions with transcriptional coregulators, and differential activity of modifier genes.

  1. Reduced electric-octupole transition probabilities, B(E3;O1+ → 31-), for even-even nuclides throughout the periodic table

    International Nuclear Information System (INIS)

    Spear, R.H.

    1988-11-01

    Adopted values for the excitation energy, E x( 3 1 - ), of the first 3 - state of the even-even nuclei are tabulated. Values of the reduced electric-octupole transition probability, B(E3;O 1 + → 3 1 - ), from the ground state to this state, as determined from Coulomb excitation, lifetime measurements, inelastic electron scattering, deformation parameters β 3 obtained from angular distributions of inelastically scattered nucleons and light ions, and other miscellaneous procedures are listed in separate Tables. Adopted values for B(E3; O 1 + → 3 1 - ) are presented in Table VII, together with the E3 transition strengths, in Weisskopf units, and the product E x( 3 1 - ) x B(E3; O 1 + → 3 1 - - ) expressed as a percentage of the energy-weighted E3 sum-rule strength. An evaluation is made of the reliability of B(E3; O 1 + → 3 1 - ) values deduced from deformation parameters β 3 . The literature has been covered to March 1988

  2. 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.

  3. Urban e-Mobility - Challenges and potential solutions using the example of the "E3W" concept vehicle

    Science.gov (United States)

    Perterer, M.; Martin, P.; Lochner, H.

    2014-05-01

    Due to the increasing number of people in urban areas, there is a need for affordable individual transportation. Limited space in cities together with the need for a significant reduction of pollution will lead to new mobility concepts in the near future. The aim of these concepts is not replacing the car itself, but to supply an additional personal transportation solution with local zero emission. Therefore, electrical powered vehicle concepts may be used. Due to the limited energy density and high cost of current Li-ion batteries, a significant weight reduction of the vehicle could lead to acceptable range and cost. In order to develop an affordable urban concept, the requirements for this kind of vehicle also have to be adjusted in comparison to conventional cars. This concept, the so called "E3W", combines the advantages of a two-wheeler with those of a four-wheeler, resulting in a lightweight and compact vehicle. This concept accommodates space for two persons with luggage and guarantees a high level of safety including wind and weather protection. The overall measures of this vehicle are smaller than current compact cars and allow therefore better use in cities. In order to fulfill technical and commercial requirements, a load carrying, short fiber reinforced thermoplastic body structure is chosen, combining good weight specific mechanical properties and low production costs. This highly integrated body structure also provides the body cover all in one. Pultruded glass fiber reinforced plastic (GFRP) beams are used as the backbone for the vehicle by carrying the main loads, the front crash structure and the rear swingarm. Finally, two prototypes are built to investigate the driving behavior, proof the concept and the suitability for daily use.

  4. Phosphorylation by PINK1 releases the UBL domain and initializes the conformational opening of the E3 ubiquitin ligase Parkin.

    Directory of Open Access Journals (Sweden)

    Thomas R Caulfield

    2014-11-01

    Full Text Available Loss-of-function mutations in PINK1 or PARKIN are the most common causes of autosomal recessive Parkinson's disease. Both gene products, the Ser/Thr kinase PINK1 and the E3 Ubiquitin ligase Parkin, functionally cooperate in a mitochondrial quality control pathway. Upon stress, PINK1 activates Parkin and enables its translocation to and ubiquitination of damaged mitochondria to facilitate their clearance from the cell. Though PINK1-dependent phosphorylation of Ser65 is an important initial step, the molecular mechanisms underlying the activation of Parkin's enzymatic functions remain unclear. Using molecular modeling, we generated a complete structural model of human Parkin at all atom resolution. At steady state, the Ub ligase is maintained inactive in a closed, auto-inhibited conformation that results from intra-molecular interactions. Evidently, Parkin has to undergo major structural rearrangements in order to unleash its catalytic activity. As a spark, we have modeled PINK1-dependent Ser65 phosphorylation in silico and provide the first molecular dynamics simulation of Parkin conformations along a sequential unfolding pathway that could release its intertwined domains and enable its catalytic activity. We combined free (unbiased molecular dynamics simulation, Monte Carlo algorithms, and minimal-biasing methods with cell-based high content imaging and biochemical assays. Phosphorylation of Ser65 results in widening of a newly defined cleft and dissociation of the regulatory N-terminal UBL domain. This motion propagates through further opening conformations that allow binding of an Ub-loaded E2 co-enzyme. Subsequent spatial reorientation of the catalytic centers of both enzymes might facilitate the transfer of the Ub moiety to charge Parkin. Our structure-function study provides the basis to elucidate regulatory mechanisms and activity of the neuroprotective Parkin. This may open up new avenues for the development of small molecule Parkin

  5. Scientific data products and the data pre-processing subsystem of the Chang'e-3 mission

    International Nuclear Information System (INIS)

    Tan Xu; Liu Jian-Jun; Li Chun-Lai; Feng Jian-Qing; Ren Xin; Wang Fen-Fei; Yan Wei; Zuo Wei; Wang Xiao-Qian; Zhang Zhou-Bin

    2014-01-01

    The Chang'e-3 (CE-3) mission is China's first exploration mission on the surface of the Moon that uses a lander and a rover. Eight instruments that form the scientific payloads have the following objectives: (1) investigate the morphological features and geological structures at the landing site; (2) integrated in-situ analysis of minerals and chemical compositions; (3) integrated exploration of the structure of the lunar interior; (4) exploration of the lunar-terrestrial space environment, lunar surface environment and acquire Moon-based ultraviolet astronomical observations. The Ground Research and Application System (GRAS) is in charge of data acquisition and pre-processing, management of the payload in orbit, and managing the data products and their applications. The Data Pre-processing Subsystem (DPS) is a part of GRAS. The task of DPS is the pre-processing of raw data from the eight instruments that are part of CE-3, including channel processing, unpacking, package sorting, calibration and correction, identification of geographical location, calculation of probe azimuth angle, probe zenith angle, solar azimuth angle, and solar zenith angle and so on, and conducting quality checks. These processes produce Level 0, Level 1 and Level 2 data. The computing platform of this subsystem is comprised of a high-performance computing cluster, including a real-time subsystem used for processing Level 0 data and a post-time subsystem for generating Level 1 and Level 2 data. This paper describes the CE-3 data pre-processing method, the data pre-processing subsystem, data classification, data validity and data products that are used for scientific studies

  6. Dietary antioxidant capacity and risk of type 2 diabetes in the large prospective E3N-EPIC cohort.

    Science.gov (United States)

    Mancini, Francesca Romana; Affret, Aurélie; Dow, Courtney; Balkau, Beverley; Bonnet, Fabrice; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy

    2018-02-01

    Recent evidence suggests that oxidative stress may contribute to the pathogenesis of type 2 diabetes. The diet, and especially fruit and vegetables, contains a variety of compounds with antioxidant activity, which may have cumulative/synergistic antioxidant effects. The total antioxidant capacity, an index derived from dietary intake, is a single estimate of antioxidant capacity from all dietary antioxidants. The main aim of this study was to investigate the relationship between total antioxidant capacity and risk of type 2 diabetes. Among 64,223 women (mean age 52 ± 7 years) from the French E3N-European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 1751 women had validated type 2 diabetes during 15 years of follow-up. The total antioxidant capacity was estimated with the ferric ion-reducing antioxidant power (FRAP) method. Adjusted Cox proportional hazards regression models were used to calculate HRs and 95% CIs for the associations between total antioxidant capacity and type 2 diabetes risk, adjusted for potential confounders. In multivariable models, higher levels of total antioxidant capacity were associated with a lower risk of type 2 diabetes. Compared with women in the lowest quintile, women in the third, fourth and fifth quintiles for total antioxidant capacity had HRs of 0.74 (95% CI 0.63, 0.86), 0.70 (95% CI 0.59, 0.83) and 0.73 (95% CI 0.60, 0.89), respectively. The inverse association between total antioxidant capacity and risk of type 2 diabetes was linear up to values of 15 mmol/day, after which the effect reached a plateau. Our findings suggest that the total antioxidant capacity may play an important role in reducing the risk of type 2 diabetes in middle-aged women. More studies are warranted to better understand the biological mechanisms underlying this inverse association.

  7. Tumor characteristics and family history in relation to mammographic density and breast cancer: The French E3N cohort.

    Science.gov (United States)

    Maskarinec, Gertraud; Dartois, Laureen; Delaloge, Suzette; Hopper, John; Clavel-Chapelon, Françoise; Baglietto, Laura

    2017-08-01

    Mammographic density is a known heritable risk factor for breast cancer, but reports how tumor characteristics and family history may modify this association are inconsistent. Dense and total breast areas were assessed using Cumulus™ from pre-diagnostic mammograms for 820 invasive breast cancer cases and 820 matched controls nested within the French E3N cohort study. To allow comparisons across models, percent mammographic density (PMD) was standardized to the distribution of the controls. Odds ratios (OR) and 95% confidence intervals (CI) of breast cancer risk for mammographic density were estimated by conditional logistic regression while adjusting for age and body mass index. Heterogeneity according to tumor characteristic and family history was assessed using stratified analyses. Overall, the OR per 1 SD for PMD was 1.50 (95% CI, 1.33-1.69). No evidence for significant heterogeneity by tumor size, lymph node status, grade, and hormone receptor status (estrogen, progesterone, and HER2) was detected. However, the association of PMD was stronger for women reporting a family history of breast cancer (OR 1SD =2.25; 95% CI, 1.67-3.04) than in women reporting none (OR 1SD =1.41; 95% CI, 1.24-1.60; p heterogeneity =0.002). Similarly, effect modification by FHBC was observed using categories of PMD (p heterogeneity =0.02) with respective ORs of 15.16 (95% CI, 4.23-54.28) vs. 3.14 (95% CI, 1.89-5.22) for ≥50% vs. breast cancer risk with a family history supports the hypothesis of shared genetic factors responsible for familial aggregation of breast cancer and the heritable component of mammographic density. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Inhibition of xanthine oxidase by allopurinol prevents skeletal muscle atrophy: role of p38 MAPKinase and E3 ubiquitin ligases.

    Directory of Open Access Journals (Sweden)

    Frederic Derbre

    Full Text Available Alterations in muscle play an important role in common diseases and conditions. Reactive oxygen species (ROS are generated during hindlimb unloading due, at least in part, to the activation of xanthine oxidase (XO. The major aim of this study was to determine the mechanism by which XO activation causes unloading-induced muscle atrophy in rats, and its possible prevention by allopurinol, a well-known inhibitor of this enzyme. For this purpose we studied one of the main redox sensitive signalling cascades involved in skeletal muscle atrophy i.e. p38 MAPKinase, and the expression of two well known muscle specific E3 ubiquitin ligases involved in proteolysis, the Muscle atrophy F-Box (MAFbx; also known as atrogin-1 and Muscle RING (Really Interesting New Gene Finger-1 (MuRF-1. We found that hindlimb unloading induced a significant increase in XO activity and in the protein expression of the antioxidant enzymes CuZnSOD and Catalase in skeletal muscle. The most relevant new fact reported in this paper is that inhibition of XO with allopurinol, a drug widely used in clinical practice, prevents soleus muscle atrophy by ~20% after hindlimb unloading. This was associated with the inhibition of the p38 MAPK-MAFbx pathway. Our data suggest that XO was involved in the loss of muscle mass via the activation of the p38MAPK-MAFbx pathway in unloaded muscle atrophy. Thus, allopurinol may have clinical benefits to combat skeletal muscle atrophy in bedridden, astronauts, sarcopenic, and cachexic patients.

  9. 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

  10. 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

    2016-07-01

    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.

  11. Swapping the N- and C-terminal domains of human apolipoprotein E3 and AI reveals insights into their structure/activity relationship.

    Directory of Open Access Journals (Sweden)

    Mark T Lek

    Full Text Available Apolipoprotein (apo E3 and apoAI are exchangeable apolipoproteins that play a dominant role in regulating plasma lipoprotein metabolism. ApoE3 (299 residues is composed of an N-terminal (NT domain bearing a 4-helix bundle and a C-terminal (CT domain bearing a series of amphipathic α-helices. ApoAI (243 residues also comprises a highly helical NT domain and a less structured CT tail. The objective of this study was to understand their structural and functional role by generating domain swapped chimeras: apoE3-NT/apoAI-CT and apoAI-NT/apoE-CT. The bacterially overexpressed chimeras were purified by affinity chromatography and their identity confirmed by immunoblotting and mass spectrometry. Their α-helical content was comparable to that of the parent proteins. ApoE3-NT/apoAI-CT retained the denaturation profile of apoE3 NT domain, with apoAI CT tail eliciting a relatively unstructured state; its lipid binding ability improved dramatically compared to apoE3 indicative of a significant role of apoAI CT tail in lipid binding interaction. The LDL receptor interaction and ability to promote ABCA1-mediated cholesterol efflux of apoE3-NT/apoAI-CT was comparable to that of apoE3. In contrast, apoAI-NT/apoE-CT elicited an unfolding pattern and lipid binding ability that were similar to that of apoAI. As expected, DMPC/apoAI-NT/apoE-CT discoidal particles did not elicit LDLr binding ability, and promoted SR-B1 mediated cellular uptake of lipids to a limited extent. However, apoAI-NT/apoE-CT displayed an enhanced ability to promote cholesterol efflux compared to apoAI, indicative of a significant role for apoE CT domain in mediating this function. Together, these results indicate that the functional attributes of apoAI and apoE3 can be conferred on each other and that NT-CT domain interactions significantly modulate their structure and function.

  12. Systemic and Ocular Determinants of Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in the European Eye Epidemiology (E3) Population.

    Science.gov (United States)

    Mauschitz, Matthias M; Bonnemaijer, Pieter W M; Diers, Kersten; Rauscher, Franziska G; Elze, Tobias; Engel, Christoph; Loeffler, Markus; Colijn, Johanna Maria; Ikram, M Arfan; Vingerling, Johannes R; Williams, Katie M; Hammond, Christopher J; Creuzot-Garcher, Catherine; Bron, Alain M; Silva, Rufino; Nunes, Sandrina; Delcourt, Cécile; Cougnard-Grégoire, Audrey; Holz, Frank G; Klaver, Caroline C W; Breteler, Monique M B; Finger, Robert P

    2018-04-28

    To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population. Cross-sectional meta-analysis. A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9±12.3-82.1±4.2 years) of the European Eye Epidemiology (E3) consortium. We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis. Determinants of pRNFLT. Mean pRNFLT ranged from 86.8±21.4 μm in the Rotterdam Study I to 104.7±12.5 μm in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (β = -0.38 μm/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (IOP) (β = -0.36 μm/mmHg; 95% CI, -0.56 to -0.15), visual impairment (β = -5.50 μm; 95% CI, -9.37 to -1.64), and history of systemic hypertension (β = -0.54 μm; 95% CI, -1.01 to -0.07) and stroke (β = -1.94 μm; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (β = -3.11 μm; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (β = 1.39 μm/diopter; 95% CI, 1.19-1.59) and smoking (β = 1.53 μm; 95% CI, 1.00-2.06 for current smokers compared with never-smokers). In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  13. The properties of the lunar regolith at Chang'e-3 landing site: A study based on LPR data

    Science.gov (United States)

    Feng, J.; Su, Y.; Xing, S.; Ding, C.; Li, C.

    2015-12-01

    In situ sampling from surface is difficult in the exploration of planets and sometimes radar sensing is a better choice. The properties of the surface material such as permittivity, density and depth can be obtained by a surface penetrating radar. The Chang'e-3 (CE-3) landed in the northern Mare Imbrium and a Lunar Penetrating Radar (LPR) is carried on the Yutu rover to detect the shallow structure of the lunar crust and the properties of the lunar regolith, which will give us a close look at the lunar subsurface. We process the radar data in a way which consist two steps: the regular preprocessing step and migration step. The preprocessing part includes zero time correction, de-wow, gain compensation, DC removal, geometric positioning. Then we combine all radar data obtained at the time the rover was moving, and use FIR filter to reduce the noise in the radar image with a pass band frequency range 200MHz-600MHz. A normal radar image is obtained after the preprocessing step. Using a nonlinear least squares fitting method, we fit the most hyperbolas in the radar image which are caused by the buried objects or rocks in the regolith and estimate the EM wave propagation velocity and the permittivity of the regolith. For there is a fixed mathematical relationship between dielectric constant and density, the density profile of the lunar regolith is also calculated. It seems that the permittivity and density at the landing site is larger than we thought before. Finally with a model of variable velocities, we apply the Kirchhoff migration method widely used in the seismology to transform the the unfocused space-time LPR image to a focused one showing the object's (most are stones) true location and size. From the migrated image, we find that the regolith depth in the landing site is smaller than previous study and the stone content rises rapidly with depth. Our study suggests that the landing site is a young region and the reworked history of the surface is short, which is

  14. Smurf2 E3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a CNKSR2 dependent manner.

    Science.gov (United States)

    David, Diana; Jagadeeshan, Sankar; Hariharan, Ramkumar; Nair, Asha Sivakumari; Pillai, Radhakrishna Madhavan

    2014-01-01

    Smurf2 is a member of the HECT family of E3 ubiquitin ligases that play important roles in determining the competence of cells to respond to TGF- β/BMP signaling pathway. However, besides TGF-β/BMP pathway, Smurf2 regulates a repertoire of other signaling pathways ranging from planar cell polarity during embryonic development to cell proliferation, migration, differentiation and senescence. Expression of Smurf2 is found to be dysregulated in many cancers including breast cancer. The purpose of the present study is to examine the effect of Smurf2 knockdown on the tumorigenic potential of human breast cancer cells emphasizing more on proliferative signaling pathway. siRNAs targeting different regions of the Smurf2 mRNA were employed to knockdown the expression of Smurf2. The biological effects of synthetic siRNAs on human breast cancer cells were investigated by examining the cell proliferation, migration, invasion, focus formation, anchorage-independent growth, cell cycle arrest, and cell cycle and cell proliferation related protein expressions upon Smurf2 silencing. Smurf2 silencing in human breast cancer cells resulted in a decreased focus formation potential and clonogenicity as well as in vitro cell migration/invasion capabilities. Moreover, knockdown of Smurf2 suppressed cell proliferation. Cell cycle analysis showed that the anti-proliferative effect of Smurf2 siRNA was mediated by arresting cells in the G0/G1 phase, which was caused by decreased expression of cyclin D1and cdk4, followed by upregulation p21 and p27. Furthermore, we demonstrated that silencing of Smurf2 downregulated the proliferation of breast cancer cells by modulating the PI3K- PTEN-AKT-FoxO3a pathway via the scaffold protein CNKSR2 which is involved in RAS-dependent signaling pathways. The present study provides the first evidence that silencing Smurf2 using synthetic siRNAs can regulate the tumorigenic properties of human breast cancer cells in a CNKSR2 dependent manner. Our results

  15. The E3 ubiquitin ligase NEDD4 mediates cell migration signaling of EGFR in lung cancer cells.

    Science.gov (United States)

    Shao, Genbao; Wang, Ranran; Sun, Aiqin; Wei, Jing; Peng, Ke; Dai, Qian; Yang, Wannian; Lin, Qiong

    2018-02-19

    EGFR-dependent cell migration plays an important role in lung cancer progression. Our previous study observed that the HECT E3 ubiquitin ligase NEDD4 is significantly correlated with tumor metastasis and required for migration and invasion signaling of EGFR in gastric cancer cells. However, how NEDD4 promotes the EGFR-dependent lung cancer cell migration is unknown. This study is to elucidate the mechanism by which NEDD4 mediates the EGFR lung cancer migration signaling. Lentiviral vector-loaded NEDD4 shRNA was used to deplete endogenous NEDD4 in lung cancer cell lines. Effects of the NEDD4 knockdown on the EGFR-dependent or independent lung cancer cell migration were determined using the wound-healing and transwell assays. Association of NEDD4 with activated EGFR was assayed by co-immunoprecipitation. Co-expression of NEDD4 with EGFR or PTEN was determined by immunohistochemical (IHC) staining in 63 lung adenocarcinoma tissue samples. Effects of NEDD4 ectopic expression or knockdown on PTEN ubiquitination and down-regulation, AKT activation and lysosomal secretion were examined using the GST-Uba pulldown assay, immunoblotting, immunofluorescent staining and a human cathepsin B ELISA assay respectively. The specific cathepsin B inhibitor CA-074Me was used for assessing the role of cathepsin B in lung cancer cell migration. Knockdown of NEDD4 significantly reduced EGF-stimulated cell migration in non-small cell lung carcinoma (NSCLC) cells. Co-immunoprecipitation assay found that NEDD4 is associated with EGFR complex upon EGF stimulation, and IHC staining indicates that NEDD4 is co-expressed with EGFR in lung adenocarcinoma tumor tissues, suggesting that NEDD4 might mediate lung cancer cell migration by interaction with the EGFR signaling complex. Interestingly, NEDD4 promotes the EGF-induced cathepsin B secretion, possibly through lysosomal exocytosis, as overexpression of the ligase-dead mutant of NEDD4 impedes lysosomal secretion, and knockdown of NEDD4

  16. Inhibiting sperm pyruvate dehydrogenase complex and its E3 subunit, dihydrolipoamide dehydrogenase affects fertilization in Syrian hamsters.

    Directory of Open Access Journals (Sweden)

    Archana B Siva

    Full Text Available BACKGROUND/AIMS: The importance of sperm capacitation for mammalian fertilization has been confirmed in the present study via sperm metabolism. Involvement of the metabolic enzymes pyruvate dehydrogenase complex (PDHc and its E3 subunit, dihydrolipoamide dehydrogenase (DLD in hamster in vitro fertilization (IVF via in vitro sperm capacitation is being proposed through regulation of sperm intracellular lactate, pH and calcium. METHODOLOGY AND PRINCIPAL FINDINGS: Capacitated hamster spermatozoa were allowed to fertilize hamster oocytes in vitro which were then assessed for fertilization, microscopically. PDHc/DLD was inhibited by the use of the specific DLD-inhibitor, MICA (5-methoxyindole-2-carboxylic acid. Oocytes fertilized with MICA-treated (MT [and thus PDHc/DLD-inhibited] spermatozoa showed defective fertilization where 2nd polar body release and pronuclei formation were not observed. Defective fertilization was attributable to capacitation failure owing to high lactate and low intracellular pH and calcium in MT-spermatozoa during capacitation. Moreover, this defect could be overcome by alkalinizing spermatozoa, before fertilization. Increasing intracellular calcium in spermatozoa pre-IVF and in defectively-fertilized oocytes, post-fertilization rescued the arrest seen, suggesting the role of intracellular calcium from either of the gametes in fertilization. Parallel experiments carried out with control spermatozoa capacitated in medium with low extracellular pH or high lactate substantiated the necessity of optimal sperm intracellular lactate levels, intracellular pH and calcium during sperm capacitation, for proper fertilization. CONCLUSIONS: This study confirms the importance of pyruvate/lactate metabolism in capacitating spermatozoa for successful fertilization, besides revealing for the first time the importance of sperm PDHc/ DLD in fertilization, via the modulation of sperm intracellular lactate, pH and calcium during capacitation. In

  17. The E3 ligase UBR5 regulates gastric cancer cell growth by destabilizing the tumor suppressor GKN1

    International Nuclear Information System (INIS)

    Yang, Min; Jiang, Nan; Cao, Qi-wei; Ma, Mao-qiang; Sun, Qing

    2016-01-01

    Gastric cancer is the most common digestive malignant tumor worldwide and the underlying mechanisms are not fully understood. The E3 ligase UBR5 (also known as EDD1) is essentially involved in diverse types of cancer. Here we aimed to study the functions of UBR5 in human gastric cancer. We first analyzed the mRNA and protein levels of UBR5 in human gastric cancer tissues and the results showed that UBR5 was markedly increased in gastric cancer tissues compared with normal gastric mucosa or matched non-cancer gastric tissues. The relationship between UBR5 and survival of gastric cancer patients was analyzed and we found that high UBR5 expression was associated with poor overall and disease-free survival. We further tried to investigate the effects of UBR5 on gastric cancer cell growth in vitro and in vivo. Therefore, we knocked down UBR5 with lentivirus-mediated shRNA and found that UBR5 knockdown repressed in vitro proliferation and colony formation of gastric cancer cells AGS, MG803 and MNK1. In vivo xenograft experiment also demonstrated that UBR5 knockdown inhibited AGS growth. Finally, we explored the mechanism by which UBR5 contributed to the growth of gastric cancer cells. We found that UBR5 bound the tumor suppressor gastrokine 1 (GKN1) and increased its ubiquitination to reduce the protein stability of GKN1. GKN1 knockdown with lentivirus-mediated shRNA increased the in vitro colony formation and in vivo growth of AGS cells, and UBR5 knockdown was unable to affect the colony formation and in vivo growth of AGS cells when GKN1 was knocked down, indicating that GKN1 contributed to the effects of UBR5 in human gastric cancer cells. Taken together, UBR5 plays an essential role in gastric cancer and may be a potential diagnosis and treatment target for gastric cancer. - Highlights: • UBR5 expression is up-regulated in human gastric cancer. • UBR5 overexpression predicts poor survival. • UBR5 regulates gastric cancer growth in vitro and in vivo.

  18. High frequencies of Y chromosome lineages characterized by E3b1, DYS19-11, DYS392-12 in Somali males

    DEFF Research Database (Denmark)

    Sanchez Sanchez, Juan Jose; Hallenberg, Charlotte; Børsting, Claus

    2005-01-01

    We genotyped 45 biallelic markers and 11 STR systems on the Y chromosome in 201 male Somalis. In addition, 65 sub-Saharan Western Africans, 59 Turks and 64 Iraqis were typed for the biallelic Y chromosome markers. In Somalis, 14 Y chromosome haplogroups were identified including E3b1 (77.6%) and K2...... (10.4%). The haplogroup E3b1 with the rare DYS19-11 allele (also called the E3b1 cluster gamma) was found in 75.1% of male Somalis, and 70.6% of Somali Y chromosomes were E3b1, DYS19-11, DYS392-12, DYS437-14, DYS438-11 and DYS393-13. The haplotype diversity of eight Y-STRs ('minimal haplotype') was 0......f2) (27.1%), R1b3*(xR1b3d, R1b3f) (20.3%), E3b3 and R1a1*(xR1a1b) (both 11.9%). In Iraqis, 12 haplogroups were identified including J2*(xJ2f2) (29.7%) and J*(xJ2) (26.6%). The data suggest that the male Somali population is a branch of the East African population - closely related to the Oromos...

  19. Sub-populations within the major European and African derived haplogroups R1b3 and E3a are differentiated by previously phylogenetically undefined Y-SNPs.

    Science.gov (United States)

    Sims, Lynn M; Garvey, Dennis; Ballantyne, Jack

    2007-01-01

    Single nucleotide polymorphisms on the Y chromosome (Y-SNPs) have been widely used in the study of human migration patterns and evolution. Potential forensic applications of Y-SNPs include their use in predicting the ethnogeographic origin of the donor of a crime scene sample, or exclusion of suspects of sexual assaults (the evidence of which often comprises male/female mixtures and may involve multiple perpetrators), paternity testing, and identification of non- and half-siblings. In this study, we used a population of 118 African- and 125 European-Americans to evaluate 12 previously phylogenetically undefined Y-SNPs for their ability to further differentiate individuals who belong to the major African (E3a)- and European (R1b3, I)-derived haplogroups. Ten of these markers define seven new sub-clades (equivalent to E3a7a, E3a8, E3a8a, E3a8a1, R1b3h, R1b3i, and R1b3i1 using the Y Chromosome Consortium nomenclature) within haplogroups E and R. Interestingly, during the course of this study we evaluated M222, a sub-R1b3 marker rarely used, and found that this sub-haplogroup in effect defines the Y-STR Irish Modal Haplotype (IMH). The new bi-allelic markers described here are expected to find application in human evolutionary studies and forensic genetics. (c) 2006 Wiley-Liss, Inc.

  20. PUB22 and PUB23 U-BOX E3 ligases directly ubiquitinate RPN6, a 26S proteasome lid subunit, for subsequent degradation in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Cho, Seok Keun; Bae, Hansol; Ryu, Moonyoung

    2015-01-01

    and PUB23, two U-box E3 ligase homologs, tether ubiquitins to 19S proteasome regulatory particle (RP) subunit RPN6, leading to its degradation. RPN6 was identified as an interacting substrate of PUB22 by yeast two-hybrid screening, and in vitro pull-down assay confirmed that RPN6 interacts not only......Drought stress strongly affects plant growth and development, directly connected with crop yields, accordingly. However, related to the function of U-BOX E3 ligases, the underlying molecular mechanisms of desiccation stress response in plants are still largely unknown. Here we report that PUB22...

  1. E3L and F1L Gene Functions Modulate the Protective Capacity of Modified Vaccinia Virus Ankara Immunization in Murine Model of Human Smallpox

    Directory of Open Access Journals (Sweden)

    Asisa Volz

    2018-01-01

    Full Text Available The highly attenuated Modified Vaccinia virus Ankara (MVA lacks most of the known vaccinia virus (VACV virulence and immune evasion genes. Today MVA can serve as a safety-tested next-generation smallpox vaccine. Yet, we still need to learn about regulatory gene functions preserved in the MVA genome, such as the apoptosis inhibitor genes F1L and E3L. Here, we tested MVA vaccine preparations on the basis of the deletion mutant viruses MVA-ΔF1L and MVA-ΔE3L for efficacy against ectromelia virus (ECTV challenge infections in mice. In non-permissive human tissue culture the MVA deletion mutant viruses produced reduced levels of the VACV envelope antigen B5. Upon mousepox challenge at three weeks after vaccination, MVA-ΔF1L and MVA-ΔE3L exhibited reduced protective capacity in comparison to wildtype MVA. Surprisingly, however, all vaccines proved equally protective against a lethal ECTV infection at two days after vaccination. Accordingly, the deletion mutant MVA vaccines induced high levels of virus-specific CD8+ T cells previously shown to be essential for rapidly protective MVA vaccination. These results suggest that inactivation of the anti-apoptotic genes F1L or E3L modulates the protective capacity of MVA vaccination most likely through the induction of distinct orthopoxvirus specific immunity in the absence of these viral regulatory proteins.

  2. The E3 Ubiquitin Ligase IDOL Induces the Degradation of the Low Density Lipoprotein Receptor Family Members VLDLR and ApoER2

    NARCIS (Netherlands)

    Hong, Cynthia; Duit, Sarah; Jalonen, Pilvi; Out, Ruud; Scheer, Lilith; Sorrentino, Vincenzo; Boyadjian, Rima; Rodenburg, Kees C. W.; Foley, Edan; Korhonen, Laura; Lindholm, Dan; Nimpf, Johannes; van Berkel, Theo J. C.; Tontonoz, Peter; Zelcer, Noam

    2010-01-01

    We have previously identified the E3-ubiquitin ligase Inducible Degrader of the LDLR (Idol)1 as a post-translational modulator of LDLR levels. Idol is a direct target for regulation by Liver X Receptors (LXRs) and its expression is responsive to cellular sterol status independent of the

  3. 20 CFR 655.700 - What statutory provisions govern the employment of H-1B, H-1B1, and E-3 nonimmigrants and how do...

    Science.gov (United States)

    2010-04-01

    ... Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in... occupations or certain fashion models from any country, the INA, as amended, provides as follows: (1... work in a “specialty occupation” or as a fashion model of distinguished merit and ability in the United...

  4. In the absence of endogenous mouse apolipoprotein E, apolipoprotein E*2(Arg-158 → Cys) transgenic mice develop more severe hyperlipoproteinemia than apolipoprotein E*3-Leiden transgenic mice

    NARCIS (Netherlands)

    Vlijmen, B.J.M. van; Dijk, K.W. van; Hof, H.B. van 't; Gorp, P.J.J. van; Zee, A. van der; Boom, H. van der; Breuer, M.L.; Hofker, M.H.; Havekesf, L.M.

    1996-01-01

    Apolipoprotein E*2(Arg-155 → Cys) (APOE*2) transgenic mice were generated and compared to the previously generated apolipoprotein E*3- Leiden (APOE*3-Leiden) transgenic mice to study the variable expression of hyperlipoproteinemia associated with these two APOE variants. In the presence of the

  5. TMEM129 is a Derlin-1 associated ERAD E3 ligase essential for virus-induced degradation of MHC-I.

    Science.gov (United States)

    van den Boomen, Dick J H; Timms, Richard T; Grice, Guinevere L; Stagg, Helen R; Skødt, Karsten; Dougan, Gordon; Nathan, James A; Lehner, Paul J

    2014-08-05

    The US11 gene product of human cytomegalovirus promotes viral immune evasion by hijacking the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. US11 initiates dislocation of newly translocated MHC I from the ER to the cytosol for proteasome-mediated degradation. Despite the critical role for ubiquitin in this degradation pathway, the responsible E3 ligase is unknown. In a forward genetic screen for host ERAD components hijacked by US11 in near-haploid KBM7 cells, we identified TMEM129, an uncharacterized polytopic membrane protein. TMEM129 is essential and rate-limiting for US11-mediated MHC-I degradation and acts as a novel ER resident E3 ubiquitin ligase. TMEM129 contains an unusual cysteine-only RING with intrinsic E3 ligase activity and is recruited to US11 via Derlin-1. Together with its E2 conjugase Ube2J2, TMEM129 is responsible for the ubiquitination, dislocation, and subsequent degradation of US11-associated MHC-I. US11 engages two degradation pathways: a Derlin-1/TMEM129-dependent pathway required for MHC-I degradation and a SEL1L/HRD1-dependent pathway required for "free" US11 degradation. Our data show that TMEM129 is a novel ERAD E3 ligase and the central component of a novel mammalian ERAD complex.

  6. The putative E3 ubiquitin ligase ECERIFERUM9 regulates abscisic acid biosynthesis and response during seed germination and postgermination growth in arabidopsis

    KAUST Repository

    Zhao, Huayan; Zhang, Huoming; Cui, Peng; Ding, Feng; Wang, Guangchao; Li, Rongjun; Jenks, Matthew A.; Lü , Shiyou; Xiong, Liming

    2014-01-01

    The ECERIFERUM9 (CER9) gene encodes a putative E3 ubiquitin ligase that functions in cuticle biosynthesis and the maintenance of plant water status. Here, we found that CER9 is also involved in abscisic acid (ABA) signaling in seeds and young

  7. Developing the Clarity and Openness in Reporting: E3-based (CORE) Reference user manual for creation of clinical study reports in the era of clinical trial transparency.

    Science.gov (United States)

    Hamilton, Samina; Bernstein, Aaron B; Blakey, Graham; Fagan, Vivien; Farrow, Tracy; Jordan, Debbie; Seiler, Walther; Shannon, Anna; Gertel, Art

    2016-01-01

    Interventional clinical studies conducted in the regulated drug research environment are reported using International Council for Harmonisation (ICH) regulatory guidance documents: ICH E3 on the structure and content of clinical study reports (CSRs) published in 1995 and ICH E3 supplementary Questions & Answers (Q & A) published in 2012.Since the ICH guidance documents were published, there has been heightened awareness of the importance of disclosure of clinical study results. The use of the CSR as a key source document to fulfil emerging obligations has resulted in a re-examination of how ICH guidelines are applied in CSR preparation. The dynamic regulatory and modern drug development environments create emerging reporting challenges. Regulatory medical writing and statistical professionals developed Clarity and Openness in Reporting: E3-based (CORE) Reference over a 2-year period. Stakeholders contributing expertise included a global industry association, regulatory agency, patient advocate, academic and Principal Investigator representatives. CORE Reference should help authors navigate relevant guidelines as they create CSR content relevant for today's studies. It offers practical suggestions for developing CSRs that will require minimum redaction and modification prior to public disclosure.CORE Reference comprises a Preface, followed by the actual resource. The Preface clarifies intended use and underlying principles that inform resource utility. The Preface lists references contributing to development of the resource, which broadly fall into 'regulatory' and 'public disclosure' categories. The resource includes ICH E3 guidance text, ICH E3 Q & A 2012-derived guidance text and CORE Reference text, distinguished from one another through the use of shading. Rationale comments are used throughout for clarification purposes.A separate mapping tool comparing ICH E3 sectional structure and CORE Reference sectional structure is also provided.Together, CORE Reference

  8. Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for cullin 4 E3 ubiquitin ligase to enable macrophage infection.

    Directory of Open Access Journals (Sweden)

    Smita Srivastava

    2008-05-01

    Full Text Available Vpx is a small virion-associated adaptor protein encoded by viruses of the HIV-2/SIVsm lineage of primate lentiviruses that enables these viruses to transduce monocyte-derived cells. This probably reflects the ability of Vpx to overcome an as yet uncharacterized block to an early event in the virus life cycle in these cells, but the underlying mechanism has remained elusive. Using biochemical and proteomic approaches, we have found that Vpx protein of the pathogenic SIVmac 239 strain associates with a ternary protein complex comprising DDB1 and VprBP subunits of Cullin 4-based E3 ubiquitin ligase, and DDA1, which has been implicated in the regulation of E3 catalytic activity, and that Vpx participates in the Cullin 4 E3 complex comprising VprBP. We further demonstrate that the ability of SIVmac as well as HIV-2 Vpx to interact with VprBP and its associated Cullin 4 complex is required for efficient reverse transcription of SIVmac RNA genome in primary macrophages. Strikingly, macrophages in which VprBP levels are depleted by RNA interference resist SIVmac infection. Thus, our observations reveal that Vpx interacts with both catalytic and regulatory components of the ubiquitin proteasome system and demonstrate that these interactions are critical for Vpx ability to enable efficient SIVmac replication in primary macrophages. Furthermore, they identify VprBP/DCAF1 substrate receptor for Cullin 4 E3 ubiquitin ligase and its associated protein complex as immediate downstream effector of Vpx for this function. Together, our findings suggest a model in which Vpx usurps VprBP-associated Cullin 4 ubiquitin ligase to enable efficient reverse transcription and thereby overcome a block to lentivirus replication in monocyte-derived cells, and thus provide novel insights into the underlying molecular mechanism.

  9. Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease

    OpenAIRE

    Bogdanik, Laurent P.; Sleigh, James N.; Tian, Cong; Samuels, Mark E.; Bedard, Karen; Seburn, Kevin L.; Burgess, Robert W.

    2013-01-01

    SUMMARY Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have rece...

  10. E3 ubiquitin ligase gene CMPG1-V from Haynaldia villosa L. contributes to powdery mildew resistance in common wheat (Triticum aestivum L.).

    Science.gov (United States)

    Zhu, Yanfei; Li, Yingbo; Fei, Fei; Wang, Zongkuan; Wang, Wei; Cao, Aizhong; Liu, Yuan; Han, Shuang; Xing, Liping; Wang, Haiyan; Chen, Wei; Tang, Sanyuan; Huang, Xiahe; Shen, Qianhua; Xie, Qi; Wang, Xiue

    2015-10-01

    Powdery mildew is one of the most devastating wheat fungal diseases. A diploid wheat relative, Haynaldia villosa L., is highly resistant to powdery mildew, and its genetic resource of resistances, such as the Pm21 locus, is now widely used in wheat breeding. Here we report the cloning of a resistance gene from H. villosa, designated CMPG1-V, that encodes a U-box E3 ubiquitin ligase. Expression of the CMPG1-V gene was induced in the leaf and stem of H. villosa upon inoculation with Blumeria graminis f. sp. tritici (Bgt) fungus, and the presence of Pm21 is essential for its rapid induction of expression. CMPG1-V has conserved key residues for E3 ligase, and possesses E3 ligase activity in vitro and in vivo. CMPG1-V is localized in the nucleus, endoplasmic reticulum, plasma membrane and partially in trans-Golgi network/early endosome vesicles. Transgenic wheat over-expressing CMPG1-V showed improved broad-spectrum powdery mildew resistance at seedling and adult stages, associated with an increase in expression of salicylic acid-responsive genes, H2 O2 accumulation, and cell-wall protein cross-linking at the Bgt infection sites, and the expression of CMPG1-V in H. villosa was increased when treated with salicylic acid, abscisic acid and H2 O2 . These results indicate the involvement of E3 ligase in defense responses to Bgt fungus in wheat, particularly in broad-spectrum disease resistance, and suggest association of reactive oxidative species and the phytohormone pathway with CMPG1-V-mediated powdery mildew resistance. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  11. (E-3-Methyl-6-(3-oxo-3-(3,4,5-trimethoxyphenylprop-1-en-1-yl-2(3H-benzothiazolone

    Directory of Open Access Journals (Sweden)

    Yordanka Ivanova

    2016-09-01

    Full Text Available The title compound, (E-3-methyl-6-(3-oxo-3-(3,4,5-trimethoxyphenylprop-1-en-1-yl-2(3H-benzothiazolone, was synthesized by both an acid- and base-catalyzed aldol condensation of 3-methyl-6-acetyl-2(3H-benzothiazolone and 3,4,5-trimethoxyacetophenone. The structure of the target compound was confirmed using 1H-NMR, 13C-NMR, IR, MS, and elemental analysis.

  12. Co-cultivation of mutant Penicillium oxalicum SAU(E)-3.510 and Pleurotus ostreatus for simultaneous biosynthesis of xylanase and laccase under solid-state fermentation.

    Science.gov (United States)

    Dwivedi, Pallavi; Vivekanand, V; Pareek, Nidhi; Sharma, Amit; Singh, Rajesh P

    2011-10-01

    Co-cultivation of mutant Penicillium oxalicum SAU(E)-3.510 and Pleurotus ostreatus MTCC 1804 was evaluated for the production of xylanase-laccase mixture under solid-state fermentation (SSF) condition. Growth compatibility between mutant P. oxalicum SAU(E)-3.510 and white rot fungi (P. ostreatus MTCC 1804, Trametes hirsuta MTCC 136 and Pycnoporus sp. MTCC 137) was analyzed by growing them on potato dextrose agar plate. Extracellular enzyme activities were determined spectrophotometrically. Under derived conditions, paired culturing of mutant P. oxalicum SAU(E)-3.510 and P. ostreatus MTCC 1804 resulted in 58% and 33% higher levels of xylanase and laccase production, respectively. A combination of sugarcane bagasse and black gram husk in a ratio of 3:1 was found to be the most ideal solid substrate and support for fungal colonization and enzyme production during co-cultivation. Maximum levels of xylanase (8205.31 ± 168.31 IU g(-1)) and laccase (375.53 ± 34.17 IU g(-1)) during SSF were obtained by using 4 g of solid support with 80% of moisture content. Furthermore, expressions of both xylanase and laccase were characterized during mixed culture by zymogram analysis. Improved levels of xylanase and laccase biosynthesis were achieved by co-culturing the mutant P. oxalicum SAU(E)-3.510 and P. ostreatus MTCC 1804. This may be because of efficient substrate utilization as compared to their respective monocultures in the presence of lignin degradation compounds because of synergistic action of xylanase and laccase. Understanding and developing the process of co-cultivation appears productive for the development of mixed enzyme preparation with tremendous potential for biobleaching. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. The E3 Ligase APC/C-Cdh1 Is Required for Associative Fear Memory and Long-Term Potentiation in the Amygdala of Adult Mice

    Science.gov (United States)

    Pick, Joseph E.; Malumbres, Marcos; Klann, Eric

    2013-01-01

    The anaphase promoting complex/cyclosome (APC/C) is an E3 ligase regulated by Cdh1. Beyond its role in controlling cell cycle progression, APC/C-Cdh1 has been detected in neurons and plays a role in long-lasting synaptic plasticity and long-term memory. Herein, we further examined the role of Cdh1 in synaptic plasticity and memory by generating…

  14. A large complement of the predicted Arabidopsis ARM repeat proteins are members of the U-box E3 ubiquitin ligase family.

    Science.gov (United States)

    Mudgil, Yashwanti; Shiu, Shin-Han; Stone, Sophia L; Salt, Jennifer N; Goring, Daphne R

    2004-01-01

    The Arabidopsis genome was searched to identify predicted proteins containing armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in a number of different animal proteins. Using domain database predictions and models generated in this study, 108 Arabidopsis proteins were identified that contained a minimum of two ARM repeats with the majority of proteins containing four to eight ARM repeats. Clustering analysis showed that the 108 predicted Arabidopsis ARM repeat proteins could be divided into multiple groups with wide differences in their domain compositions and organizations. Interestingly, 41 of the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a family of E3 ligases, and these proteins represented the largest class of Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there was also a novel conserved domain identified in the N-terminal region. Based on the phylogenetic tree, representative U-box/ARM repeat proteins were selected for further study. RNA-blot analyses revealed that these U-box/ARM proteins are expressed in a variety of tissues in Arabidopsis. In addition, the selected U-box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U-box/ARM proteins represent a new family of E3 ligases in Arabidopsis.

  15. A Large Complement of the Predicted Arabidopsis ARM Repeat Proteins Are Members of the U-Box E3 Ubiquitin Ligase Family1[w

    Science.gov (United States)

    Mudgil, Yashwanti; Shiu, Shin-Han; Stone, Sophia L.; Salt, Jennifer N.; Goring, Daphne R.

    2004-01-01

    The Arabidopsis genome was searched to identify predicted proteins containing armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in a number of different animal proteins. Using domain database predictions and models generated in this study, 108 Arabidopsis proteins were identified that contained a minimum of two ARM repeats with the majority of proteins containing four to eight ARM repeats. Clustering analysis showed that the 108 predicted Arabidopsis ARM repeat proteins could be divided into multiple groups with wide differences in their domain compositions and organizations. Interestingly, 41 of the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a family of E3 ligases, and these proteins represented the largest class of Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there was also a novel conserved domain identified in the N-terminal region. Based on the phylogenetic tree, representative U-box/ARM repeat proteins were selected for further study. RNA-blot analyses revealed that these U-box/ARM proteins are expressed in a variety of tissues in Arabidopsis. In addition, the selected U-box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U-box/ARM proteins represent a new family of E3 ligases in Arabidopsis. PMID:14657406

  16. Structure of a Glomulin-RBX1-CUL1 complex: inhibition of a RING E3 ligase through masking of its E2-binding surface

    Science.gov (United States)

    Duda, David M.; Olszewski, Jennifer L.; Tron, Adriana E.; Hammel, Michal; Lambert, Lester J.; Waddell, M. Brett; Mittag, Tanja; DeCaprio, James A.; Schulman, Brenda A.

    2012-01-01

    Summary The ~300 human Cullin-RING ligases (CRLs) are multisubunit E3s in which a RING protein, either RBX1 or RBX2, recruits an E2 to catalyze ubiquitination. RBX1-containing CRLs also can bind Glomulin (GLMN), which binds RBX1’s RING domain, regulates the RBX1-CUL1-containing SCFFBW7 complex, and is disrupted in the disease Glomuvenous Malformation. Here we report the crystal structure of a complex between GLMN, RBX1, and a fragment of CUL1. Structural and biochemical analyses reveal that GLMN adopts a HEAT-like repeat fold that tightly binds the E2-interacting surface of RBX1, inhibiting CRL-mediated chain formation by the E2 CDC34. The structure explains the basis for GLMN’s selectivity toward RBX1 over RBX2, and how disease-associated mutations disrupt GLMN-RBX1 interactions. Our study reveals a mechanism for RING E3 ligase regulation whereby an inhibitor blocks E2 access, and raises the possibility that other E3s are likewise controlled by cellular proteins that mask E2-binding surfaces to mediate inhibition. PMID:22748924

  17. PARAQUAT TOLERANCE3 Is an E3 Ligase That Switches off Activated Oxidative Response by Targeting Histone-Modifying PROTEIN METHYLTRANSFERASE4b.

    Directory of Open Access Journals (Sweden)

    Chao Luo

    2016-09-01

    Full Text Available Oxidative stress is unavoidable for aerobic organisms. When abiotic and biotic stresses are encountered, oxidative damage could occur in cells. To avoid this damage, defense mechanisms must be timely and efficiently modulated. While the response to oxidative stress has been extensively studied in plants, little is known about how the activated response is switched off when oxidative stress is diminished. By studying Arabidopsis mutant paraquat tolerance3, we identified the genetic locus PARAQUAT TOLERANCE3 (PQT3 as a major negative regulator of oxidative stress tolerance. PQT3, encoding an E3 ubiquitin ligase, is rapidly down-regulated by oxidative stress. PQT3 has E3 ubiquitin ligase activity in ubiquitination assay. Subsequently, we identified PRMT4b as a PQT3-interacting protein. By histone methylation, PRMT4b upregulates the expression of APX1 and GPX1, encoding two key enzymes against oxidative stress. On the other hand, PRMT4b is recognized by PQT3 for targeted degradation via 26S proteasome. Therefore, we have identified PQT3 as an E3 ligase that acts as a negative regulator of activated response to oxidative stress and found that histone modification by PRMT4b at APX1 and GPX1 loci plays an important role in oxidative stress tolerance.

  18. Experimental oral immunization of ferret badgers (Melogale moschata) with a recombinant canine adenovirus vaccine CAV-2-E3Δ-RGP and an attenuated rabies virus SRV9.

    Science.gov (United States)

    Zhao, Jinghui; Liu, Ye; Zhang, Shoufeng; Fang, Lijun; Zhang, Fei; Hu, Rongliang

    2014-04-01

    Ferret badgers (Melogale moschata) are a major reservoir of rabies virus in southeastern China. Oral immunization has been shown to be a practical method for wildlife rabies management in Europe and North America. Two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Δ-RGP, or an experimental attenuated rabies virus vaccine, SRV9. At 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging from 0.1 to 4.5 IU/mL. Titers were >0.50 IU/mL (an acceptable level) in 17/20 and 16/20 animals receiving CAV-2-E3Δ-RGP or SRV9, respectively. The serologic results indicate that the recombinant CAV-2-E3Δ-RGP is at least as effective as the attenuated rabies virus vaccine. Both may be considered for additional research as oral rabies vaccine candidates for ferret badgers.

  19. A Program for Electronic Medical Education in Colombia: Educación Electrónica Estructurada (E3 A Succesful Experience

    Directory of Open Access Journals (Sweden)

    Rafael E Riveros

    2004-02-01

    Full Text Available Medical education in Colombia remains, almost completely, with the physical presence of the lecturer in the classroom. In recent years, new alternatives in higher education have been explored, on a balanced basis. Our faculty traditionally remains teaching with conservative methods; therefore, strategies for incorporating informatics, virtual education and in general, electronics are vital in our academic environment. Our electronic medical education group, E3, is constituted by faculty, undergraduate and graduate students. E3 was designed to provide the urgent need to develop an appropriate scenario for a group of faculty and students who will provide the school with clear cut policies and strategies, to establish a permanent and dynamic program of ICT locally, institutionally and regionally. The project, enveloped in the objectives of E3 includes: Electronic Academic Contents (EAC, Virtual Education Project (VEP and Electronic Clinical Record (ECR. We will improve and increase, by the end of 2003, electronic medical education at our School and radiate to the University and the academic community.

  20. Surveillance of occupational exposure to ionizing radiation in the French air force: an example with a workplace study concerning the flight personnel on the E-3F; Surveillance de l'exposition professionnelle aux rayonnements ionisants dans l'armee de l'air. Exemple d'une etude de poste concernant les personnels navigants sur E-3F

    Energy Technology Data Exchange (ETDEWEB)

    Amabile, J.C.; Castagne, X.; Carbonnieres, H. de; Laroche, P. [Hopital des Armees du Val-de-Grace, 75 - Paris (France)

    2006-12-15

    This workplace study was first based on measurements of the ambient dose rates on board the E-3F (2000 to 2001). These results have been complemented by a series of measurements of individual exposure using passive and active gamma and neutrons dosimeters (2004 to 2005). We show that, from level 300 and after more than 200 flying hours per year, the air-crews of the French Air Force flying on board the E-3F are likely to annually receive an effective dose higher than 1 mSv. It is therefore necessary to organize a specific radiological and medical survey in favour of the air-crews of the E-3F and other aircraft with the same flight criteria. (authors)

  1. Aeroacoustic Study of a 26%-Scale Semispan Model of a Boeing 777 Wing in the NASA Ames 40- by 80-Foot Wind Tunnel

    Science.gov (United States)

    Horne, W. Clifton; Burnside, Nathan J.; Soderman, Paul T.; Jaeger, Stephen M.; Reinero, Bryan R.; James, Kevin D.; Arledge, Thomas K.

    2004-01-01

    An acoustic and aerodynamic study was made of a 26%-scale unpowered Boeing 777 aircraft semispan model in the NASA Ames 40- by 80-Foot Wind Tunnel for the purpose of identifying and attenuating airframe noise sources. Simulated approach and landing configurations were evaluated at Mach numbers between 0.12 and 0.24. Cruise configurations were evaluated at Mach numbers between 0.24 and 0.33. The research team used two Ames phased-microphone arrays, a large fixed array and a small traversing array, mounted under the wing to locate and compare various noise sources in the wing high-lift system and landing gear. Numerous model modifications and noise alleviation devices were evaluated. Simultaneous with acoustic measurements, aerodynamic forces were recorded to document aircraft conditions and any performance changes caused by the geometric modifications. Numerous airframe noise sources were identified that might be important factors in the approach and landing noise of the full-scale aircraft. Several noise-control devices were applied to each noise source. The devices were chosen to manipulate and control, if possible, the flow around the various tips and through the various gaps of the high-lift system so as to minimize the noise generation. Fences, fairings, tip extensions, cove fillers, vortex generators, hole coverings, and boundary-layer trips were tested. In many cases, the noise-control devices eliminated noise from some sources at specific frequencies. When scaled to full-scale third-octave bands, typical noise reductions ranged from 1 to 10 dB without significant aerodynamic performance loss.

  2. Crew Configuration, Ingress/Egress Procedures, and In-Flight Caregiving Capacity in a Space Ambulance Based on the Boeing X-37B

    Science.gov (United States)

    Halberg, Ephriam Etan

    This study proposes that a Boeing X-37B space plane, its dimensions and performance characteristics estimated from publicly available documents, diagrams, and photographs, could be internally redesigned as a medical evacuation (ambulance) vehicle for the International Space Station. As of 2017, there is currently no spacecraft designed to accommodate a contingency medical evacuation wherein a crew member aboard the ISS is injured or ailing and must be returned to Earth for immediate medical attention. The X-37B is an unmanned vehicle with a history of success in both sub-orbital testing and all four of its long-duration orbital missions to date. Research conducted at UC Davis suggests that it is possible to retain the outer mold line of the X-37B while expanding the internal payload compartment to a volume sufficient for a crew of three--pilot, crew medical officer, and injured crew member--throughout ISS un-dock and atmospheric entry, descent, and landing. In addition to crew life support systems, this re-purposed X-37B, hereafter referred to as the X-37SA (Space Ambulance), includes medical equipment for stabilization of a patient in-transit. This study suggests an optimal, ergonomic crew configuration and berthing port location, procedures for microgravity ingress and 1G egress, a minimum medical equipment list and location within the crew cabin for the medical care and monitoring equipment. Conceptual crew configuration, ingress/egress procedures, and patient/equipment access are validated via physical simulation in a full-scale mockup of the proposed X-37SA crew cabin.

  3. Top-down/bottom-up description of electricity sector for Switzerland using the GEM-E3 computable general equilibrium model

    International Nuclear Information System (INIS)

    Krakowski, R. A.

    2006-06-01

    Participation of the Paul Scherrer Institute (PSI) in the advancement and extension of the multi-region, Computable General Equilibrium (CGE) model GEM-E3 (CES/KUL, 2002) focused primarily on two top-level facets: a) extension of the model database and model calibration, particularly as related to the second component of this study, which is; b) advancement of the dynamics of innovation and investment, primarily through the incorporation of Exogenous Technical Learning (ETL) into he Bottom-Up (BU, technology-based) part of the dynamic upgrade; this latter activity also included the completion of the dynamic coupling of the BU description of the electricity sector with the 'Top-Down' (TD, econometric) description of the economy inherent to the GEM-E3 CGE model. The results of this two- component study are described in two parts that have been combined in this single summary report: Part I describes the methodology and gives illustrative results from the BUTD integration, as well as describing the approach to and giving preliminary results from incorporating an ETL description into the BU component of the overall model; Part II reports on the calibration component of task in terms of: a) formulating a BU technology database for Switzerland based on previous work; incorporation of that database into the GEM-E3 model; and calibrating the BU database with the TD database embodied in the (Swiss) Social Accounting Matrix (SAM). The BUTD coupling along with the ETL incorporation described in Part I represent the major effort embodied in this investigation, but this effort could not be completed without the calibration preamble reported herein as Part II. A brief summary of the scope of each of these key study components is given. (author)

  4. Top-down/bottom-up description of electricity sector for Switzerland using the GEM-E3 computable general equilibrium model

    Energy Technology Data Exchange (ETDEWEB)

    Krakowski, R. A

    2006-06-15

    Participation of the Paul Scherrer Institute (PSI) in the advancement and extension of the multi-region, Computable General Equilibrium (CGE) model GEM-E3 (CES/KUL, 2002) focused primarily on two top-level facets: a) extension of the model database and model calibration, particularly as related to the second component of this study, which is; b) advancement of the dynamics of innovation and investment, primarily through the incorporation of Exogenous Technical Learning (ETL) into he Bottom-Up (BU, technology-based) part of the dynamic upgrade; this latter activity also included the completion of the dynamic coupling of the BU description of the electricity sector with the 'Top-Down' (TD, econometric) description of the economy inherent to the GEM-E3 CGE model. The results of this two- component study are described in two parts that have been combined in this single summary report: Part I describes the methodology and gives illustrative results from the BUTD integration, as well as describing the approach to and giving preliminary results from incorporating an ETL description into the BU component of the overall model; Part II reports on the calibration component of task in terms of: a) formulating a BU technology database for Switzerland based on previous work; incorporation of that database into the GEM-E3 model; and calibrating the BU database with the TD database embodied in the (Swiss) Social Accounting Matrix (SAM). The BUTD coupling along with the ETL incorporation described in Part I represent the major effort embodied in this investigation, but this effort could not be completed without the calibration preamble reported herein as Part II. A brief summary of the scope of each of these key study components is given. (author)

  5. BTB-BACK Domain Protein POB1 Suppresses Immune Cell Death by Targeting Ubiquitin E3 ligase PUB17 for Degradation.

    Directory of Open Access Journals (Sweden)

    Beatriz Orosa

    2017-01-01

    Full Text Available Hypersensitive response programmed cell death (HR-PCD is a critical feature in plant immunity required for pathogen restriction and prevention of disease development. The precise control of this process is paramount to cell survival and an effective immune response. The discovery of new components that function to suppress HR-PCD will be instrumental in understanding the regulation of this fundamental mechanism. Here we report the identification and characterisation of a BTB domain E3 ligase protein, POB1, that functions to suppress HR-PCD triggered by evolutionarily diverse pathogens. Nicotiana benthamiana and tobacco plants with reduced POB1 activity show accelerated HR-PCD whilst those with increased POB1 levels show attenuated HR-PCD. We demonstrate that POB1 dimerization and nuclear localization are vital for its function in HR-PCD suppression. Using protein-protein interaction assays, we identify the Plant U-Box E3 ligase PUB17, a well established positive regulator of plant innate immunity, as a target for POB1-mediated proteasomal degradation. Using confocal imaging and in planta immunoprecipitation assays we show that POB1 interacts with PUB17 in the nucleus and stimulates its degradation. Mutated versions of POB1 that show reduced interaction with PUB17 fail to suppress HR-PCD, indicating that POB1-mediated degradation of PUB17 U-box E3 ligase is an important step for negative regulation of specific immune pathways in plants. Our data reveals a new mechanism for BTB domain proteins in suppressing HR-PCD in plant innate immune responses.

  6. Functional analysis of NopM, a novel E3 ubiquitin ligase (NEL domain effector of Rhizobium sp. strain NGR234.

    Directory of Open Access Journals (Sweden)

    Da-Wei Xin

    Full Text Available Type 3 effector proteins secreted via the bacterial type 3 secretion system (T3SS are not only virulence factors of pathogenic bacteria, but also influence symbiotic interactions between nitrogen-fixing nodule bacteria (rhizobia and leguminous host plants. In this study, we characterized NopM (nodulation outer protein M of Rhizobium sp. strain NGR234, which shows sequence similarities with novel E3 ubiquitin ligase (NEL domain effectors from the human pathogens Shigella flexneri and Salomonella enterica. NopM expressed in Escherichia coli, but not the non-functional mutant protein NopM-C338A, showed E3 ubiquitin ligase activity in vitro. In vivo, NopM, but not inactive NopM-C338A, promoted nodulation of the host plant Lablab purpureus by NGR234. When NopM was expressed in yeast, it inhibited mating pheromone signaling, a mitogen-activated protein (MAP kinase pathway. When expressed in the plant Nicotiana benthamiana, NopM inhibited one part of the plant's defense response, as shown by a reduced production of reactive oxygen species (ROS in response to the flagellin peptide flg22, whereas it stimulated another part, namely the induction of defense genes. In summary, our data indicate the potential for NopM as a functional NEL domain E3 ubiquitin ligase. Our findings that NopM dampened the flg22-induced ROS burst in N. benthamiana but promoted defense gene induction are consistent with the concept that pattern-triggered immunity is split in two separate signaling branches, one leading to ROS production and the other to defense gene induction.

  7. Time-of-day- and light-dependent expression of ubiquitin protein ligase E3 component N-recognin 4 (UBR4 in the suprachiasmatic nucleus circadian clock.

    Directory of Open Access Journals (Sweden)

    Harrod H Ling

    Full Text Available Circadian rhythms of behavior and physiology are driven by the biological clock that operates endogenously but can also be entrained to the light-dark cycle of the environment. In mammals, the master circadian pacemaker is located in the suprachiasmatic nucleus (SCN, which is composed of individual cellular oscillators that are driven by a set of core clock genes interacting in transcriptional/translational feedback loops. Light signals can trigger molecular events in the SCN that ultimately impact on the phase of expression of core clock genes to reset the master pacemaker. While transcriptional regulation has received much attention in the field of circadian biology in the past, other mechanisms including targeted protein degradation likely contribute to the clock timing and entrainment process. In the present study, proteome-wide screens of the murine SCN led to the identification of ubiquitin protein ligase E3 component N-recognin 4 (UBR4, a novel E3 ubiquitin ligase component of the N-end rule pathway, as a time-of-day-dependent and light-inducible protein. The spatial and temporal expression pattern of UBR4 in the SCN was subsequently characterized by immunofluorescence microscopy. UBR4 is expressed across the entire rostrocaudal extent of the SCN in a time-of-day-dependent fashion. UBR4 is localized exclusively to arginine vasopressin (AVP-expressing neurons of the SCN shell. Upon photic stimulation in the early subjective night, the number of UBR4-expressing cells within the SCN increases. This study is the first to identify a novel E3 ubiquitin ligase component, UBR4, in the murine SCN and to implicate the N-end rule degradation pathway as a potential player in regulating core clock mechanisms and photic entrainment.

  8. SAG/ROC-SCFβ-TrCP E3 Ubiquitin Ligase Promotes Pro-Caspase-3 Degradation as a Mechanism of Apoptosis Protection

    Directory of Open Access Journals (Sweden)

    Mingjia Tan

    2006-12-01

    Full Text Available Skp1-cullin-F-box protein (SCF is a multicomponent E3 ubiquitin (Ub ligase that ubiquitinates a number of important biologic molecules such as p27, β-catenin, and lκB for proteasomal degradation, thus regulating cell proliferation and survival. One SCF component, SAG/ROC2/Rbx2/Hrt2, a RING finger protein, was first identified as a redox-inducible protein, which, when overexpressed, inhibited apoptosis both in vitro and in vivo. We report here that sensitive to apoptosis gene (SAG, as well as its family member ROC1/Rbxi, bound to the proinactive form of caspase-3 (pro-caspase-3. Binding was likely mediated through F-box protein, β-transducin repeat-containing protein (β-TrCP, which binds to the first 38 amino acids of pro-caspase-3. Importantly, β-TrCP1 expression significantly shortened the protein half-life of pro-caspase-3, whereas expression of a dominant-negative β-TrCP1 mutant with the F-box domain deleted extended it. An in vitro ubiquitination assay showed that SAG/ROC-SCF -Trcp promoted ubiquitination of pro-caspase-3. Furthermore, endogenous levels of pro-caspase-3 were decreased by overexpression of SAG/ROC-SCFβ-TrCP E3 Ub ligases, but increased on siRNA silencing of SAG, regulator of cullin-1 (ROC1, or β-TrCPs, leading to increased apoptosis by etoposide and TNF-related apoptosis-inducing ligand through increased activation of caspase-3. Thus, pro-caspase-3 appears to be a substrate of SAG/ROC-SCFβ-TrCP E3 Ub ligase, which protects cells from apoptosis through increased apoptosis threshold by reducing the basal level of pro-caspase-3.

  9. Synthesis, Characterization and Biological Activities of Novel (E)-3-(1-(Alkyloxyamino)ethylidene)-1-alkylpyrrolidine-2,4-dione Derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Zhao Yong; Shi, Qing Ming; Han, Bao Feng; Wang, Xian Feng; Qiang, Sheng; Yang, Chun Long [Nanjing Agricultural University, Nanjing (China)

    2010-09-15

    Twenty novel tetramic acid derivatives (E)-3-(1-(alkyloxyamino)ethylidene)-1-alkylpyrrolidine-2,4-diones were synthesized by the reaction of 3-(1-hydroxyethylidene)pyrrolidine-2,4-diones with O-alkyl hydroxylamines. The title compounds were confirmed by IR, {sup 1}H NMR, MS and elemental analysis. The structure of compound 6r was further verified by X-ray diffraction crystallography. The bioassays showed that most of the title compounds exhibited noticeable herbicidal and fungicidal activities.

  10. What can we learn from the endogeneization of the technical progress in GEM - E3? The case of the Kyoto protocol

    International Nuclear Information System (INIS)

    Fougeyrollas, A.; Le Mouel, P.; Zagame, P.

    2007-01-01

    This project aims to study how the evaluation of the policies of fight against the greenhouse effect gases emission studied at an european scale, in the framework of the Kyoto agreements, is modified when the applied model, of general equilibrium takes into account the behavior of endogenous growth described by the new theories. More specially, the authors calibrated a production module with endogenous growth properties in the model GEM-E3. The new developed module show the costs reduction of policies of greenhouse effect gases emission limitation for France and Europe. (A.L.B.)

  11. (2E-3-(3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl-1-(2,5-dimethyl-3-thienylprop-2-en-1-one

    Directory of Open Access Journals (Sweden)

    Salman A. Khan

    2010-04-01

    Full Text Available The title compound, (2E-3-(3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl-1-(2,5-dimethyl-3-thienylprop-2-en-1-one (3 was synthesized in high yield by aldol condensation of 3-acetyl-2,5-dimethylthiophene and 3,5-dimethyl-1-phenylpyrazole-4-carboxaldehyde in ethanolic NaOH at room temperature. Its structure was fully characterized by elemental analysis, IR, 1H NMR, 13C NMR and EI-MS spectral analysis.

  12. SYVN1, an ERAD E3 Ubiquitin Ligase, Is Involved in GABAAα1 Degradation Associated with Methamphetamine-Induced Conditioned Place Preference

    Directory of Open Access Journals (Sweden)

    Dong-Liang Jiao

    2017-10-01

    Full Text Available Abuse of methamphetamine (METH, a powerful addictive amphetamine-type stimulants (ATS, is becoming a global public health problem. The gamma-aminobutyric acid (GABAergic system plays a critical role in METH use disorders. By using rat METH conditioned place preference (CPP model, we previously demonstrated that METH-associated rewarding memory formation was associated with the reduction of GABAAα1 expression in the dorsal straitum (Dstr, however, the underlying mechanism was unclear. In the present study, we found that METH-induced CPP formation was accompanied by a significant increase in the expression of Synovial apoptosis inhibitor 1 (SYVN1, an endoplasmic reticulum (ER-associated degradation (ERAD E3 ubiquitin ligase, in the Dstr. The siRNA knockdown of SYVN1 significantly increased GABAAα1 protein levels in both primary cultured neurons and rodent Dstr. Inhibition of proteasomal activity by MG132 and Lactacystin significantly increased GABAAα1 protein levels. We further found that SYVN1 knockdown increased GABAAα1 in the intra-ER, but not in the extra-ER. Accordingly, endoplasmic reticulum stress (ERS-associated Glucose-regulated protein 78 (GRP78 and C/EBP homologous protein (CHOP increased. Thus, this study revealed that SYVN1, as the ERAD E3 ubiquitin ligase, was associated with Dstr GABAAα1 degradation induced by METH conditioned pairing.

  13. Identification of factors required for m6 A mRNA methylation in Arabidopsis reveals a role for the conserved E3 ubiquitin ligase HAKAI.

    Science.gov (United States)

    Růžička, Kamil; Zhang, Mi; Campilho, Ana; Bodi, Zsuzsanna; Kashif, Muhammad; Saleh, Mária; Eeckhout, Dominique; El-Showk, Sedeer; Li, Hongying; Zhong, Silin; De Jaeger, Geert; Mongan, Nigel P; Hejátko, Jan; Helariutta, Ykä; Fray, Rupert G

    2017-07-01

    N6-adenosine methylation (m 6 A) of mRNA is an essential process in most eukaryotes, but its role and the status of factors accompanying this modification are still poorly understood. Using combined methods of genetics, proteomics and RNA biochemistry, we identified a core set of mRNA m 6 A writer proteins in Arabidopsis thaliana. The components required for m 6 A in Arabidopsis included MTA, MTB, FIP37, VIRILIZER and the E3 ubiquitin ligase HAKAI. Downregulation of these proteins led to reduced relative m 6 A levels and shared pleiotropic phenotypes, which included aberrant vascular formation in the root, indicating that correct m 6 A methylation plays a role in developmental decisions during pattern formation. The conservation of these proteins amongst eukaryotes and the demonstration of a role in writing m 6 A for the E3 ubiquitin ligase HAKAI is likely to be of considerable relevance beyond the plant sciences. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  14. Identification of a Cullin5-ElonginB-ElonginC E3 complex in degradation of feline immunodeficiency virus Vif-mediated feline APOBEC3 proteins.

    Science.gov (United States)

    Wang, Jiawen; Zhang, Wenyan; Lv, Mingyu; Zuo, Tao; Kong, Wei; Yu, Xianghui

    2011-12-01

    Various feline APOBEC3 (fA3) proteins exhibit broad antiviral activities against a wide range of viruses, such as feline immunodeficiency virus (FIV), feline foamy virus (FFV), and feline leukemia virus (FeLV), as well as those of other species. This activity can be counteracted by the FIV Vif protein, but the mechanism by which FIV Vif suppresses fA3s is unknown. In the present study, we demonstrated that FIV Vif could act via a proteasome-dependent pathway to overcome fA3s. FIV Vif interacted with feline cellular proteins Cullin5 (Cul5), ElonginB, and ElonginC to form an E3 complex to induce degradation of fA3s. Both the dominant-negative Cul5 mutant and a C-terminal hydrophilic replacement ElonginC mutant potently disrupted the FIV Vif activity against fA3s. Furthermore, we identified a BC-box motif in FIV Vif that was essential for the recruitment of E3 ubiquitin ligase and also required for FIV Vif-mediated degradation of fA3s. Moreover, despite the lack of either a Cul5-box or a HCCH zinc-binding motif, FIV Vif specifically selected Cul5. Therefore, FIV Vif may interact with Cul5 via a novel mechanism. These finding imply that SOCS proteins may possess distinct mechanisms to bind Cul5 during formation of the Elongin-Cullin-SOCS box complex.

  15. Synthesis and Fungicidal Activities of (Z/E-3,7-Dimethyl-2,6-octadienamide and Its 6,7-Epoxy Analogues

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    Mingyan Yang

    2015-11-01

    Full Text Available In order to find new lead compounds with high fungicidal activity, (Z/E-3,7-dimethyl-2,6-octadienoic acids were synthesized via selective two-step oxidation using the commercially available geraniol/nerol as raw materials. Twenty-eight different (Z/E-3,7-dimethyl-2,6-octadienamide derivatives were prepared by reactions of (Z/E-carboxylic acid with various aromatic and aliphatic amines, followed by oxidation of peroxyacetic acid to afford their 6,7-epoxy analogues. All of the compounds were characterized by HR-ESI-MS and 1H-NMR spectral data. The preliminary bioassays showed that some of these compounds exhibited good fungicidal activities against Rhizoctonia solani (R. solani at a concentration of 50 µg/mL. For example, 5C, 5I and 6b had 94.0%, 93.4% and 91.5% inhibition rates against R. solani, respectively. Compound 5f displayed EC50 values of 4.3 and 9.7 µM against Fusahum graminearum and R. Solani, respectively.

  16. March1 E3 Ubiquitin Ligase Modulates Features of Allergic Asthma in an Ovalbumin-Induced Mouse Model of Lung Inflammation

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    Osama A. Kishta

    2018-01-01

    Full Text Available Membrane-associated RING-CH-1 (March1 is a member of the March family of E3 ubiquitin ligases. March1 downregulates cell surface expression of MHC II and CD86 by targeting them to lysosomal degradation. Given the key roles of MHC class II and CD86 in T cell activation and to get further insights into the development of allergic inflammation, we asked whether March1 deficiency exacerbates or attenuates features of allergic asthma in mice. Herein, we used an acute model of allergy to compare the asthmatic phenotype of March1-deficient and -sufficient mice immunized with ovalbumin (OVA and later challenged by intranasal instillation of OVA in the lungs. We found that eosinophilic inflammation in airways and lung tissue was similar between WT and March1−/− allergic mice, whereas neutrophilic inflammation was significant only in March1−/− mice. Airway hyperresponsiveness as well as levels of IFN-γ, IL-13, IL-6, and IL-10 was lower in the lungs of asthmatic March1−/− mice compared to WT, whereas lung levels of TNF-α, IL-4, and IL-5 were not significantly different. Interestingly, in the serum, levels of total and ova-specific IgE were reduced in March1-deficient mice as compared to WT mice. Taken together, our results demonstrate a role of March1 E3 ubiquitin ligase in modulating allergic responses.

  17. Overexpression of E3 Ubiquitin Ligase Gene AdBiL Contributes to Resistance against Chilling Stress and Leaf Mold Disease in Tomato

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    Shuangchen Chen

    2017-06-01

    Full Text Available Ubiquitination is a common regulatory mechanism, playing a critical role in diverse cellular and developmental processes in eukaryotes. However, a few reports on the functional correlation between E3 ubiquitin ligases and reactive oxygen species (ROS or reactive nitrogen species (RNS metabolism in response to stress are currently available in plants. In the present study, the E3 ubiquitin ligase gene AdBiL (Adi3 Binding E3 Ligase was introduced into tomato line Ailsa Craig via Agrobacterium-mediated method. Transgenic lines were confirmed for integration into the tomato genome using PCR. Transcription of AdBiL in various transgenic lines was determined using real-time PCR. Evaluation of stress tolerance showed that T1 generation of transgenic tomato lines showed only mild symptoms of chilling injury as evident by higher biomass accumulation and chlorophyll content than those of non-transformed plants. Compared with wild-type plants, the contents of AsA, AsA/DHA, GSH and the activity of GaILDH, γ-GCS and GSNOR were increased, while H2O2, O2.−, MDA, NO, SNOs, and GSNO accumulations were significantly decreased in AdBiL overexpressing plants in response to chilling stress. Furthermore, transgenic tomato plants overexpressing AdBiL showed higher activities of enzymes such as G6PDH, 6PGDH, NADP-ICDH, and NADP-ME involved in pentose phosphate pathway (PPP. The transgenic tomato plants also exhibited an enhanced tolerance against the necrotrophic fungus Cladosporium fulvum. Tyrosine nitration protein was activated in the plants infected with leaf mold disease, while the inhibition could be recovered in AdBiL gene overexpressing lines. Taken together, our results revealed a possible physiological role of AdBiL in the activation of the key enzymes of AsA–GSH cycle, PPP and down-regulation of GSNO reductase, thereby reducing oxidative and nitrosative stress in plants. This study demonstrates an optimized transgenic strategy using AdBiL gene for crop

  18. The E3 ubiquitin ligase RNF146 promotes colorectal cancer by activating the Wnt/β-catenin pathway via ubiquitination of Axin1.

    Science.gov (United States)

    Shen, Jiangli; Yu, Zhaohui; Li, Na

    2018-06-20

    The E3 ubiquitin ligase ring finger protein 146 (RNF146) has been implicated in tumor development. However, the role and clinical significance of RNF146 in colorectal cancer (CRC) remain unknown. In this study, we reported for the first time that RNF146 was upregulated in CRC tissues as well as in cell lines. Further, RNF146 expression was independent prognostic factor for poor outcome of CRC patients. RNF146 knockdown in cell lines inhibited cell growth, promoted cell apoptosis in vitro and suppressed colorectal tumor growth in vivo. Mechanistic investigations revealed that RNF146 exerted oncogenic role through ubiquitination of Axin1 to activate β-catenin signalling. In addition, RNF146 expression was positively correlated with β-catenin expression in CRC tissues. Collectively, our data suggest that RNF146 might function as a oncogene in human CRC, and represent a promising prognostic factor and a valuable therapeutic target for CRC. Copyright © 2018. Published by Elsevier Inc.

  19. ACCURATE LABORATORY WAVELENGTHS OF THE e 3 Σ-(ν' = 5) - X 1 Σ+(ν'' = 0) BAND OF 12C16O

    International Nuclear Information System (INIS)

    Dickenson, G. D.; Nortje, A. C.; Steenkamp, C. M.; Rohwer, E. G.; Du Plessis, A.

    2010-01-01

    The forbidden singlet-triplet transitions of carbon monoxide (CO) are important in the interpretation of vacuum ultraviolet interstellar absorption spectra and in particular for the measurement of large CO column densities. Twenty rovibronic lines of the e 3 Σ - (ν' = 5) - X 1 Σ + (ν'' = 0) band of 12 C 16 O for which laboratory wavelengths were previously unavailable were identified in laser-induced fluorescence excitation spectra. Wavelengths were assigned to five rovibronic transitions to an average accuracy of 0.0028 A. A further 15 lines could not be fully resolved and average wavelengths were measured for these groups of closely spaced lines. A wavelength difference of 0.011 ± 0.0028 A between the measured wavelengths and the calculated wavelengths in the atlas of Eidelsberg and Rostas demonstrates the need for more experimental data on CO.

  20. Accurate Laboratory Wavelengths of the e 3 Σ-(ν' = 5) - X 1 Σ+(ν'' = 0) Band of 12C16O

    Science.gov (United States)

    Dickenson, G. D.; Nortje, A. C.; Steenkamp, C. M.; Rohwer, E. G.; Du Plessis, A.

    2010-05-01

    The forbidden singlet-triplet transitions of carbon monoxide (CO) are important in the interpretation of vacuum ultraviolet interstellar absorption spectra and in particular for the measurement of large CO column densities. Twenty rovibronic lines of the e 3Σ-(ν' = 5) - X 1Σ+(ν'' = 0) band of 12 C 16O for which laboratory wavelengths were previously unavailable were identified in laser-induced fluorescence excitation spectra. Wavelengths were assigned to five rovibronic transitions to an average accuracy of 0.0028 Å. A further 15 lines could not be fully resolved and average wavelengths were measured for these groups of closely spaced lines. A wavelength difference of 0.011 ± 0.0028 Å between the measured wavelengths and the calculated wavelengths in the atlas of Eidelsberg & Rostas demonstrates the need for more experimental data on CO.

  1. Shigella IpaH0722 E3 Ubiquitin Ligase Effector Targets TRAF2 to Inhibit PKC–NF-κB Activity in Invaded Epithelial Cells

    Science.gov (United States)

    Ashida, Hiroshi; Nakano, Hiroyasu; Sasakawa, Chihiro

    2013-01-01

    NF-κB plays a central role in modulating innate immune responses to bacterial infections. Therefore, many bacterial pathogens deploy multiple mechanisms to counteract NF-κB activation. The invasion of and subsequent replication of Shigella within epithelial cells is recognized by various pathogen recognition receptors as pathogen-associated molecular patterns. These receptors trigger innate defense mechanisms via the activation of the NF-κB signaling pathway. Here, we show the inhibition of the NF-κB activation by the delivery of the IpaH E3 ubiquitin ligase family member IpaH0722 using Shigella's type III secretion system. IpaH0722 dampens the acute inflammatory response by preferentially inhibiting the PKC-mediated activation of NF-κB by ubiquitinating TRAF2, a molecule downstream of PKC, and by promoting its proteasome-dependent degradation. PMID:23754945

  2. Lithium Suppresses Hedgehog Signaling via Promoting ITCH E3 Ligase Activity and Gli1–SUFU Interaction in PDA Cells

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    Xinshuo Wang

    2017-11-01

    Full Text Available Dysregulation of Hedgehog (Hh signaling pathway is one of the hallmarks of pancreatic ductal adenocarcinoma (PDA. Lithium, a clinical mood stabilizer for the treatment of mental disorders, is known to suppress tumorigenic potential of PDA cells by targeting the Hh/Gli signaling pathway. In this study, we investigated the molecular mechanism of lithium induced down-regulation of Hh/Gli1. Our data show that lithium promotes the poly-ubiquitination and proteasome-mediated degradation of Gli1 through activating E3 ligase ITCH. Additionally, lithium enhances interaction between Gli1 and SUFU via suppressing GSK3β, which phosphorylates SUFU and destabilizes the SUFU-Gli1 inhibitory complex. Our studies illustrate a novel mechanism by which lithium suppresses Hh signaling via simultaneously promoting ITCH-dependent Gli1 ubiquitination/degradation and SUFU-mediated Gli1 inhibition.

  3. Interactions between the S-Domain Receptor Kinases and AtPUB-ARM E3 Ubiquitin Ligases Suggest a Conserved Signaling Pathway in Arabidopsis1[W][OA

    Science.gov (United States)

    Samuel, Marcus A.; Mudgil, Yashwanti; Salt, Jennifer N.; Delmas, Frédéric; Ramachandran, Shaliny; Chilelli, Andrea; Goring, Daphne R.

    2008-01-01

    The Arabidopsis (Arabidopsis thaliana) genome encompasses multiple receptor kinase families with highly variable extracellular domains. Despite their large numbers, the various ligands and the downstream interacting partners for these kinases have been deciphered only for a few members. One such member, the S-receptor kinase, is known to mediate the self-incompatibility (SI) response in Brassica. S-receptor kinase has been shown to interact and phosphorylate a U-box/ARM-repeat-containing E3 ligase, ARC1, which, in turn, acts as a positive regulator of the SI response. In an effort to identify conserved signaling pathways in Arabidopsis, we performed yeast two-hybrid analyses of various S-domain receptor kinase family members with representative Arabidopsis plant U-box/ARM-repeat (AtPUB-ARM) E3 ligases. The kinase domains from S-domain receptor kinases were found to interact with ARM-repeat domains from AtPUB-ARM proteins. These kinase domains, along with M-locus protein kinase, a positive regulator of SI response, were also able to phosphorylate the ARM-repeat domains in in vitro phosphorylation assays. Subcellular localization patterns were investigated using transient expression assays in tobacco (Nicotiana tabacum) BY-2 cells and changes were detected in the presence of interacting kinases. Finally, potential links to the involvement of these interacting modules to the hormone abscisic acid (ABA) were investigated. Interestingly, AtPUB9 displayed redistribution to the plasma membrane of BY-2 cells when either treated with ABA or coexpressed with the active kinase domain of ARK1. As well, T-DNA insertion mutants for ARK1 and AtPUB9 lines were altered in their ABA sensitivity during germination and acted at or upstream of ABI3, indicating potential involvement of these proteins in ABA responses. PMID:18552232

  4. Interactions between the S-domain receptor kinases and AtPUB-ARM E3 ubiquitin ligases suggest a conserved signaling pathway in Arabidopsis.

    Science.gov (United States)

    Samuel, Marcus A; Mudgil, Yashwanti; Salt, Jennifer N; Delmas, Frédéric; Ramachandran, Shaliny; Chilelli, Andrea; Goring, Daphne R

    2008-08-01

    The Arabidopsis (Arabidopsis thaliana) genome encompasses multiple receptor kinase families with highly variable extracellular domains. Despite their large numbers, the various ligands and the downstream interacting partners for these kinases have been deciphered only for a few members. One such member, the S-receptor kinase, is known to mediate the self-incompatibility (SI) response in Brassica. S-receptor kinase has been shown to interact and phosphorylate a U-box/ARM-repeat-containing E3 ligase, ARC1, which, in turn, acts as a positive regulator of the SI response. In an effort to identify conserved signaling pathways in Arabidopsis, we performed yeast two-hybrid analyses of various S-domain receptor kinase family members with representative Arabidopsis plant U-box/ARM-repeat (AtPUB-ARM) E3 ligases. The kinase domains from S-domain receptor kinases were found to interact with ARM-repeat domains from AtPUB-ARM proteins. These kinase domains, along with M-locus protein kinase, a positive regulator of SI response, were also able to phosphorylate the ARM-repeat domains in in vitro phosphorylation assays. Subcellular localization patterns were investigated using transient expression assays in tobacco (Nicotiana tabacum) BY-2 cells and changes were detected in the presence of interacting kinases. Finally, potential links to the involvement of these interacting modules to the hormone abscisic acid (ABA) were investigated. Interestingly, AtPUB9 displayed redistribution to the plasma membrane of BY-2 cells when either treated with ABA or coexpressed with the active kinase domain of ARK1. As well, T-DNA insertion mutants for ARK1 and AtPUB9 lines were altered in their ABA sensitivity during germination and acted at or upstream of ABI3, indicating potential involvement of these proteins in ABA responses.

  5. Reflectance conversion methods for the VIS/NIR imaging spectrometer aboard the Chang'E-3 lunar rover: based on ground validation experiment data

    International Nuclear Information System (INIS)

    Liu Bin; Liu Jian-Zhong; Zhang Guang-Liang; Zou Yong-Liao; Ling Zong-Cheng; Zhang Jiang; He Zhi-Ping; Yang Ben-Yong

    2013-01-01

    The second phase of the Chang'E Program (also named Chang'E-3) has the goal to land and perform in-situ detection on the lunar surface. A VIS/NIR imaging spectrometer (VNIS) will be carried on the Chang'E-3 lunar rover to detect the distribution of lunar minerals and resources. VNIS is the first mission in history to perform in-situ spectral measurement on the surface of the Moon, the reflectance data of which are fundamental for interpretation of lunar composition, whose quality would greatly affect the accuracy of lunar element and mineral determination. Until now, in-situ detection by imaging spectrometers was only performed by rovers on Mars. We firstly review reflectance conversion methods for rovers on Mars (Viking landers, Pathfinder and Mars Exploration rovers, etc). Secondly, we discuss whether these conversion methods used on Mars can be applied to lunar in-situ detection. We also applied data from a laboratory bidirectional reflectance distribution function (BRDF) using simulated lunar soil to test the availability of this method. Finally, we modify reflectance conversion methods used on Mars by considering differences between environments on the Moon and Mars and apply the methods to experimental data obtained from the ground validation of VNIS. These results were obtained by comparing reflectance data from the VNIS measured in the laboratory with those from a standard spectrometer obtained at the same time and under the same observing conditions. The shape and amplitude of the spectrum fits well, and the spectral uncertainty parameters for most samples are within 8%, except for the ilmenite sample which has a low albedo. In conclusion, our reflectance conversion method is suitable for lunar in-situ detection.

  6. Arabidopsis C3HC4-RING finger E3 ubiquitin ligase AtAIRP4 positively regulates stress-responsive abscisic acid signaling.

    Science.gov (United States)

    Yang, Liang; Liu, Qiaohong; Liu, Zhibin; Yang, Hao; Wang, Jianmei; Li, Xufeng; Yang, Yi

    2016-01-01

    Degradation of proteins via the ubiquitin system is an important step in many stress signaling pathways in plants. E3 ligases recognize ligand proteins and dictate the high specificity of protein degradation, and thus, play a pivotal role in ubiquitination. Here, we identified a gene, named Arabidopsis thaliana abscisic acid (ABA)-insensitive RING protein 4 (AtAIRP4), which is induced by ABA and other stress treatments. AtAIRP4 encodes a cellular protein with a C3HC4-RING finger domain in its C-terminal side, which has in vitro E3 ligase activity. Loss of AtAIRP4 leads to a decrease in sensitivity of root elongation and stomatal closure to ABA, whereas overexpression of this gene in the T-DNA insertion mutant atairp4 effectively recovered the ABA-associated phenotypes. AtAIRP4 overexpression plants were hypersensitive to salt and osmotic stresses during seed germination, and showed drought avoidance compared with the wild-type and atairp4 mutant plants. In addition, the expression levels of ABA- and drought-induced marker genes in AtAIRP4 overexpression plants were markedly higher than those in the wild-type and atairp4 mutant plants. Hence, these results indicate that AtAIRP4 may act as a positive regulator of ABA-mediated drought avoidance and a negative regulator of salt tolerance in Arabidopsis. © 2015 The Authors. Journal of Integrative Plant Biology published by Wiley Publishing Asia Pty Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.

  7. HECT E3 Ubiquitin Ligase Itch Functions as a Novel Negative Regulator of Gli-Similar 3 (Glis3 Transcriptional Activity.

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    Gary T ZeRuth

    Full Text Available The transcription factor Gli-similar 3 (Glis3 plays a critical role in the generation of pancreatic ß cells and the regulation insulin gene transcription and has been implicated in the development of several pathologies, including type 1 and 2 diabetes and polycystic kidney disease. However, little is known about the proteins and posttranslational modifications that regulate or mediate Glis3 transcriptional activity. In this study, we identify by mass-spectrometry and yeast 2-hybrid analyses several proteins that interact with the N-terminal region of Glis3. These include the WW-domain-containing HECT E3 ubiquitin ligases, Itch, Smurf2, and Nedd4. The interaction between Glis3 and the HECT E3 ubiquitin ligases was verified by co-immunoprecipitation assays and mutation analysis. All three proteins interact through their WW-domains with a PPxY motif located in the Glis3 N-terminus. However, only Itch significantly contributed to Glis3 polyubiquitination and reduced Glis3 stability by enhancing its proteasomal degradation. Itch-mediated degradation of Glis3 required the PPxY motif-dependent interaction between Glis3 and the WW-domains of Itch as well as the presence of the Glis3 zinc finger domains. Transcription analyses demonstrated that Itch dramatically inhibited Glis3-mediated transactivation and endogenous Ins2 expression by increasing Glis3 protein turnover. Taken together, our study identifies Itch as a critical negative regulator of Glis3-mediated transcriptional activity. This regulation provides a novel mechanism to modulate Glis3-driven gene expression and suggests that it may play a role in a number of physiological processes controlled by Glis3, such as insulin transcription, as well as in Glis3-associated diseases.

  8. The Type II Hsp40 Sis1 cooperates with Hsp70 and the E3 ligase Ubr1 to promote degradation of terminally misfolded cytosolic protein.

    Directory of Open Access Journals (Sweden)

    Daniel W Summers

    Full Text Available Mechanisms for cooperation between the cytosolic Hsp70 system and the ubiquitin proteasome system during protein triage are not clear. Herein, we identify new mechanisms for selection of misfolded cytosolic proteins for degradation via defining functional interactions between specific cytosolic Hsp70/Hsp40 pairs and quality control ubiquitin ligases. These studies revolved around the use of S. cerevisiae to elucidate the degradation pathway of a terminally misfolded reporter protein, short-lived GFP (slGFP. The Type I Hsp40 Ydj1 acts with Hsp70 to suppress slGFP aggregation. In contrast, the Type II Hsp40 Sis1 is required for proteasomal degradation of slGFP. Sis1 and Hsp70 operate sequentially with the quality control E3 ubiquitin ligase Ubr1 to target slGFP for degradation. Compromise of Sis1 or Ubr1 function leads slGFP to accumulate in a Triton X-100-soluble state with slGFP degradation intermediates being concentrated into perinuclear and peripheral puncta. Interestingly, when Sis1 activity is low the slGFP that is concentrated into puncta can be liberated from puncta and subsequently degraded. Conversely, in the absence of Ubr1, slGFP and the puncta that contain slGFP are relatively stable. Ubr1 mediates proteasomal degradation of slGFP that is released from cytosolic protein handling centers. Pathways for proteasomal degradation of misfolded cytosolic proteins involve functional interplay between Type II Hsp40/Hsp70 chaperone pairs, PQC E3 ligases, and storage depots for misfolded proteins.

  9. The Tomato U-Box Type E3 Ligase PUB13 Acts With Group III Ubiquitin E2 Enzymes to Modulate FLS2-Mediated Immune Signaling

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    Bangjun Zhou

    2018-05-01

    Full Text Available In Arabidopsis and rice, the ubiquitin ligase PUB13-mediated protein degradation plays a significant role in plant pattern-triggered immunity (PTI and flowering time control. The Arabidopsis PUB13 has been shown to attenuate the pattern recognition receptor FLS2-mediated immune signaling by ubiquitinating FLS2 and consequently promoting its degradation by the 26S proteasome. Nevertheless, the cognate ubiquitin-conjugating enzymes (E2 with which PUB13 acts to modulate FLS2-mediated PTI are unknown. To address this question, we investigate here the tomato (Solanum lycopersicum homolog of PUB13, SlPUB13 by utilizing the recently characterized complete set of tomato E2s. Of the 13 groups of tomato E2s, only members in group III are found to interact and act with SlPUB13. Knocking-down of the group III E2 genes enhances callose deposition and induction of the RbohB gene in the immunity-associated, early oxidative burst after flg22 treatment. The group III E2s are also found to work with SlPUB13 to ubiquitinate FLS2 in vitro and are required for PUB13-mediated degradation of FLS2 in vivo upon flg22 treatment, suggesting an essential role for group III E2s in the modulation of FLS2-mediated immune signaling by PUB13. Additionally, another immunity-associated E3, NtCMPG1 is shown to also work specifically with members of group III E2 in the in vitro ubiquitination assay, which implies the group III E2 enzymes may cooperate with many E3 ligases to regulate different aspects of PTI. Taken together, these data corroborate the notion that group III E2 enzymes play an important role in PTI and build a foundation for further functional and mechanistic characterization of tomato PUB13.

  10. Effects of chocolate supplementation on metabolic and cardiovascular parameters in ApoE3L mice fed a high-cholesterol atherogenic diet.

    Science.gov (United States)

    Yakala, Gopala K; Wielinga, Peter Y; Suarez, Manuel; Bunschoten, Annelies; van Golde, Jolanda M; Arola, Lluis; Keijer, Jaap; Kleemann, Robert; Kooistra, Teake; Heeringa, Peter

    2013-11-01

    Dietary intake of cocoa and/or chocolate has been suggested to exhibit protective cardiovascular effects although this is still controversial. The aim of this study was to investigate the effects of chocolate supplementation on metabolic and cardiovascular parameters. Four groups of ApoE*3Leiden mice were exposed to the following diet regimens. Group 1: cholesterol-free control diet (CO). Group 2: high-dose (1.0% w/w) control cholesterol (CC). Group 3: CC supplemented chocolate A (CCA) and Group 4: CC supplemented chocolate B (CCB). Both chocolates differed in polyphenol and fiber content, CCA had a relatively high-polyphenol and low-fiber content compared to CCB. Mice fed a high-cholesterol diet showed increased plasma-cholesterol and developed atherosclerosis. Both chocolate treatments, particularly CCA, further increased plasma-cholesterol and increased atherosclerotic plaque formation. Moreover, compared to mice fed a high-cholesterol diet, both chocolate-treated groups displayed increased liver injury. Mice on high-cholesterol diet had elevated plasma levels of sVCAM-1, sE-selectin and SAA, which was further increased in the CCB group. Similar effects were observed for renal inflammation markers. The two chocolate preparations showed unfavorable, but different effects on cardiometabolic health in E3L mice, which dissimilarities may be related to differences in chocolate composition. We conclude that discrepancies reported on the effects of chocolate on cardiometabolic health may at least partly be due to differences in chocolate composition. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Haploinsufficiency of the E3 ubiquitin ligase C-terminus of heat shock cognate 70 interacting protein (CHIP produces specific behavioral impairments.

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    Bethann McLaughlin

    Full Text Available The multifunctional E3 ubiquitin ligase CHIP is an essential interacting partner of HSP70, which together promote the proteasomal degradation of client proteins. Acute CHIP overexpression provides neuroprotection against neurotoxic mitochondrial stress, glucocorticoids, and accumulation of toxic amyloid fragments, as well as genetic mutations in other E3 ligases, which have been shown to result in familial Parkinson's disease. These studies have created a great deal of interest in understanding CHIP activity, expression and modulation. While CHIP knockout mice have the potential to provide essential insights into the molecular control of cell fate and survival, the animals have been difficult to characterize in vivo due to severe phenotypic and behavioral dysfunction, which have thus far been poorly characterized. Therefore, in the present study we conducted a battery of neurobehavioral and physiological assays of adult CHIP heterozygotic (HET mutant mice to provide a better understanding of the functional consequence of CHIP deficiency. We found that CHIP HET mice had normal body and brain weight, body temperature, muscle tone and breathing patterns, but do have a significant elevation in baseline heart rate. Meanwhile basic behavioral screens of sensory, motor, emotional and cognitive functions were normative. We observed no alterations in performance in the elevated plus maze, light-dark preference and tail suspension assays, or two simple cognitive tasks: novel object recognition and spontaneous alternation in a Y maze. Significant deficits were found, however, when CHIP HET mice performed wire hang, inverted screen, wire maneuver, and open field tasks. Taken together, our data indicate a clear subset of behaviors that are altered at baseline in CHIP deficient animals, which will further guide whole animal studies of the effects of CHIP dysregulation on cardiac function, brain circuitry and function, and responsiveness to environmental and

  12. BPM-CUL3 E3 ligase modulates thermotolerance by facilitating negative regulatory domain-mediated degradation of DREB2A in Arabidopsis.

    Science.gov (United States)

    Morimoto, Kyoko; Ohama, Naohiko; Kidokoro, Satoshi; Mizoi, Junya; Takahashi, Fuminori; Todaka, Daisuke; Mogami, Junro; Sato, Hikaru; Qin, Feng; Kim, June-Sik; Fukao, Yoichiro; Fujiwara, Masayuki; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2017-10-03

    DEHYDRATION-RESPONSIVE ELEMENT BINDING PROTEIN 2A (DREB2A) acts as a key transcription factor in both drought and heat stress tolerance in Arabidopsis and induces the expression of many drought- and heat stress-inducible genes. Although DREB2A expression itself is induced by stress, the posttranslational regulation of DREB2A, including protein stabilization, is required for its transcriptional activity. The deletion of a 30-aa central region of DREB2A known as the negative regulatory domain (NRD) transforms DREB2A into a stable and constitutively active form referred to as DREB2A CA. However, the molecular basis of this stabilization and activation has remained unknown for a decade. Here we identified BTB/POZ AND MATH DOMAIN proteins (BPMs), substrate adaptors of the Cullin3 (CUL3)-based E3 ligase, as DREB2A-interacting proteins. We observed that DREB2A and BPMs interact in the nuclei, and that the NRD of DREB2A is sufficient for its interaction with BPMs. BPM -knockdown plants exhibited increased DREB2A accumulation and induction of DREB2A target genes under heat and drought stress conditions. Genetic analysis indicated that the depletion of BPM expression conferred enhanced thermotolerance via DREB2A stabilization. Thus, the BPM-CUL3 E3 ligase is likely the long-sought factor responsible for NRD-dependent DREB2A degradation. Through the negative regulation of DREB2A stability, BPMs modulate the heat stress response and prevent an adverse effect of excess DREB2A on plant growth. Furthermore, we found the BPM recognition motif in various transcription factors, implying a general contribution of BPM-mediated proteolysis to divergent cellular responses via an accelerated turnover of transcription factors.

  13. 21-O-Angeloyltheasapogenol E3, a Novel Triterpenoid Saponin from the Seeds of Tea Plants, Inhibits Macrophage-Mediated Inflammatory Responses in a NF-κB-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Woo Seok Yang

    2014-01-01

    Full Text Available 21-O-Angeloyltheasapogenol E3 (ATS-E3 is a triterpenoid saponin recently isolated from the seeds of the tea tree Camellia sinensis (L. O. Kuntze. ATS-E3 has several beneficial properties including anti-inflammatory, antidiabetic, antiatherosclerotic, and anticancer effects. Unlike other phenolic compounds isolated from tea plants, there are no studies reporting the pharmacological action of ATS-E3. In this study, we therefore aimed to explore the cellular and molecular inhibitory activities of ATS-E3 in macrophage-mediated inflammatory responses. ATS-E3 remarkably diminished cellular responses of macrophages such as FITC-dextran-induced phagocytic uptake, sodium nitroprusside- (SNP- induced radical generation, and LPS-induced nitric oxide (NO production. Analysis of its molecular activity showed that this compound significantly suppressed the expression of inducible NO synthase (iNOS, nuclear translocation of nuclear factor- (NF- κB subunits (p50 and p65, phosphorylation of inhibitor of κB kinase (IKK, and the enzyme activity of AKT1. Taken together, the novel triterpenoid saponin compound ATS-E3 contributes to the beneficial effects of tea plants by exerting anti-inflammatory and antioxidative activities in an AKT/IKK/NF-κB-dependent manner.

  14. Human Systems Integration Requirements

    Science.gov (United States)

    2009-09-01

    52 Stratofortress, C/ KC -135 Stratotanker, E-3 Sentry and contractor logistics support aircraft; as well as a substantial jet engine inventory...www.hqda.army.mil/ teo /Sutability%20Terms%20MOA%20Oct%2005.pdf q. ISO 9241-11, Ergonomic requirements for office work with visual display terminals (VDTs

  15. Data processing for the Active Particle-induced X-ray Spectrometer and initial scientific results from Chang'e-3 mission

    Science.gov (United States)

    Fu, Xiao-Hui; Li, Chun-Lai; Zhang, Guang-Liang; Zou, Yong-Liao; Liu, Jian-Jun; Ren, Xin; Tan, Xu; Zhang, Xiao-Xia; Zuo, Wei; Wen, Wei-Bin; Peng, Wen-Xi; Cui, Xing-Zhu; Zhang, Cheng-Mo; Wang, Huan-Yu

    2014-12-01

    The Active Particle-induced X-ray Spectrometer (APXS) is an important payload mounted on the Yutu rover, which is part of the Chang'e-3 mission. The scientific objective of APXS is to perform in-situ analysis of the chemical composition of lunar soil and rock samples. The radioactive sources, 55Fe and 109Cd, decay and produce α-particles and X-rays. When X-rays and α-particles interact with atoms in the surface material, they knock electrons out of their orbits, which release energy by emitting X-rays that can be measured by a silicon drift detector (SDD). The elements and their concentrations can be determined by analyzing their peak energies and intensities. APXS has analyzed both the calibration target and lunar soil once during the first lunar day and again during the second lunar day. The total detection time lasted about 266 min and more than 2000 frames of data records have been acquired. APXS has three operating modes: calibration mode, distance sensing mode and detection mode. In detection mode, work distance can be calculated from the X-ray counting rate collected by SDD. Correction for the effect of temperature has been performed to convert the channel number for each spectrum to X-ray energy. Dead time correction is used to eliminate the systematic error in quantifying the activity of an X-ray pulse in a sample and derive the real count rate. We report APXS data and initial results during the first and second lunar days for the Yutu rover. In this study, we analyze the data from the calibration target and lunar soil on the first lunar day. Seven major elements, including Mg, Al, Si, K, Ca, Ti and Fe, have been identified. Comparing the peak areas and ratios of calibration basalt and lunar soil the landing site was found to be depleted in K, and have lower Mg and Al but higher Ca, Ti, and Fe. In the future, we will obtain the elemental concentrations of lunar soil at the Chang'e-3 landing site using APXS data.

  16. Innate immune response of human plasmacytoid dendritic cells to poxvirus infection is subverted by vaccinia E3 via its Z-DNA/RNA binding domain.

    Directory of Open Access Journals (Sweden)

    Hua Cao

    Full Text Available Plasmacytoid dendritic cells (pDCs play important roles in antiviral innate immunity by producing type I interferon (IFN. In this study, we assess the immune responses of primary human pDCs to two poxviruses, vaccinia and myxoma virus. Vaccinia, an orthopoxvirus, was used for immunization against smallpox, a contagious human disease with high mortality. Myxoma virus, a Leporipoxvirus, causes lethal disease in rabbits, but is non-pathogenic in humans. We report that myxoma virus infection of human pDCs induces IFN-α and TNF production, whereas vaccinia infection does not. Co-infection of pDCs with myxoma virus plus vaccinia blocks myxoma induction effects. We find that heat-inactivated vaccinia (Heat-VAC; by incubating the virus at 55°C for 1 h gains the ability to induce IFN-α and TNF in primary human pDCs. Induction of IFN-α in pDCs by myxoma virus or Heat-VAC is blocked by chloroquine, which inhibits endosomal acidification required for TLR7/9 signaling, and by inhibitors of cellular kinases PI3K and Akt. Using purified pDCs from genetic knockout mice, we demonstrate that Heat-VAC-induced type I IFN production in pDCs requires the endosomal RNA sensor TLR7 and its adaptor MyD88, transcription factor IRF7 and the type I IFN feedback loop mediated by IFNAR1. These results indicate that (i vaccinia virus, but not myxoma virus, expresses inhibitor(s of the poxvirus sensing pathway(s in pDCs; and (ii Heat-VAC infection fails to produce inhibitor(s but rather produces novel activator(s, likely viral RNA transcripts that are sensed by the TLR7/MyD88 pathway. Using vaccinia gene deletion mutants, we show that the Z-DNA/RNA binding domain at the N-terminus of the vaccinia immunomodulatory E3 protein is an antagonist of the innate immune response of human pDCs to poxvirus infection and TLR agonists. The myxoma virus ortholog of vaccinia E3 (M029 lacks the N-terminal Z-DNA/RNA binding domain, which might contribute to the immunostimulating

  17. Innate Immune Response of Human Plasmacytoid Dendritic Cells to Poxvirus Infection Is Subverted by Vaccinia E3 via Its Z-DNA/RNA Binding Domain

    Science.gov (United States)

    Dai, Peihong; Wang, Weiyi; Li, Hao; Yuan, Jianda; Wang, Fangjin; Fang, Chee-Mun; Pitha, Paula M; Liu, Jia; Condit, Richard C; McFadden, Grant; Merghoub, Taha; Houghton, Alan N; Young, James W; Shuman, Stewart; Deng, Liang

    2012-01-01

    Plasmacytoid dendritic cells (pDCs) play important roles in antiviral innate immunity by producing type I interferon (IFN). In this study, we assess the immune responses of primary human pDCs to two poxviruses, vaccinia and myxoma virus. Vaccinia, an orthopoxvirus, was used for immunization against smallpox, a contagious human disease with high mortality. Myxoma virus, a Leporipoxvirus, causes lethal disease in rabbits, but is non-pathogenic in humans. We report that myxoma virus infection of human pDCs induces IFN-α and TNF production, whereas vaccinia infection does not. Co-infection of pDCs with myxoma virus plus vaccinia blocks myxoma induction effects. We find that heat-inactivated vaccinia (Heat-VAC; by incubating the virus at 55°C for 1 h) gains the ability to induce IFN-α and TNF in primary human pDCs. Induction of IFN-α in pDCs by myxoma virus or Heat-VAC is blocked by chloroquine, which inhibits endosomal acidification required for TLR7/9 signaling, and by inhibitors of cellular kinases PI3K and Akt. Using purified pDCs from genetic knockout mice, we demonstrate that Heat-VAC-induced type I IFN production in pDCs requires the endosomal RNA sensor TLR7 and its adaptor MyD88, transcription factor IRF7 and the type I IFN feedback loop mediated by IFNAR1. These results indicate that (i) vaccinia virus, but not myxoma virus, expresses inhibitor(s) of the poxvirus sensing pathway(s) in pDCs; and (ii) Heat-VAC infection fails to produce inhibitor(s) but rather produces novel activator(s), likely viral RNA transcripts that are sensed by the TLR7/MyD88 pathway. Using vaccinia gene deletion mutants, we show that the Z-DNA/RNA binding domain at the N-terminus of the vaccinia immunomodulatory E3 protein is an antagonist of the innate immune response of human pDCs to poxvirus infection and TLR agonists. The myxoma virus ortholog of vaccinia E3 (M029) lacks the N-terminal Z-DNA/RNA binding domain, which might contribute to the immunostimulating properties of

  18. The autoantigen Ro52 is an E3 ligase resident in the cytoplasm but enters the nucleus upon cellular exposure to nitric oxide

    International Nuclear Information System (INIS)

    Espinosa, Alexander; Oke, Vilija; Elfving, Ase; Nyberg, Filippa; Covacu, Ruxandra; Wahren-Herlenius, Marie

    2008-01-01

    Patients with the systemic autoimmune diseases Sjoegrens's syndrome and systemic lupus erythematosus often have autoantibodies against the intracellular protein Ro52. Ro52 is an E3 ligase dependent on the ubiquitin conjugation enzymes UBE2D1 and UBE2E1. While Ro52 and UBE2D1 are cytoplasmic proteins, UBE2E1 is localized to the nucleus. Here, we investigate how domains of human Ro52 regulate its intracellular localization. By expressing fluorescently labeled Ro52 and Ro52 mutants in HeLa cells, an intact coiled-coil domain was found to be necessary for the cytoplasmic localization of Ro52. The amino acids 381-470 of the B30.2 region were essential for translocation into the nucleus. Furthermore, after exposure of HeLa cells to the inflammatory mediator nitric oxide (NO), Ro52 translocated to the nucleus. A nuclear localization of Ro52 in inflamed tissue expressing inducible NO synthetase (iNOS) from cutaneous lupus patients was observed by immunohistochemistry and verified in NO-treated cultures of patient-derived primary keratinocytes. Our results show that the localization of Ro52 is regulated by endogenous sequences, and that nuclear translocation is induced by an inflammatory mediator. This suggests that Ro52 has both cytoplasmic and nuclear substrates, and that Ro52 mediates ubiquitination through UBE2D1 in the cytoplasm and through UBE2E1 in the nucleus

  19. The U-box E3 ubiquitin ligase TUD1 functions with a heterotrimeric G α subunit to regulate Brassinosteroid-mediated growth in rice.

    Directory of Open Access Journals (Sweden)

    Xingming Hu

    Full Text Available Heterotrimeric G proteins are an important group of signaling molecules found in eukaryotes. They function with G-protein-coupled-receptors (GPCRs to transduce various signals such as steroid hormones in animals. Nevertheless, their functions in plants are not well-defined. Previous studies suggested that the heterotrimeric G protein α subunit known as D1/RGA1 in rice is involved in a phytohormone gibberellin-mediated signaling pathway. Evidence also implicates D1 in the action of a second phytohormone Brassinosteroid (BR and its pathway. However, it is unclear how D1 functions in this pathway, because so far no partner has been identified to act with D1. In this study, we report a D1 genetic interactor Taihu Dwarf1 (TUD1 that encodes a functional U-box E3 ubiquitin ligase. Genetic, phenotypic, and physiological analyses have shown that tud1 is epistatic to d1 and is less sensitive to BR treatment. Histological observations showed that the dwarf phenotype of tud1 is mainly due to decreased cell proliferation and disorganized cell files in aerial organs. Furthermore, we found that D1 directly interacts with TUD1. Taken together, these results demonstrate that D1 and TUD1 act together to mediate a BR-signaling pathway. This supports the idea that a D1-mediated BR signaling pathway occurs in rice to affect plant growth and development.

  20. The U-Box E3 Ubiquitin Ligase TUD1 Functions with a Heterotrimeric G α Subunit to Regulate Brassinosteroid-Mediated Growth in Rice

    Science.gov (United States)

    Hu, Xingming; Qian, Qian; Xu, Ting; Zhang, Yu'e; Dong, Guojun; Gao, Ting; Xie, Qi; Xue, Yongbiao

    2013-01-01

    Heterotrimeric G proteins are an important group of signaling molecules found in eukaryotes. They function with G-protein-coupled-receptors (GPCRs) to transduce various signals such as steroid hormones in animals. Nevertheless, their functions in plants are not well-defined. Previous studies suggested that the heterotrimeric G protein α subunit known as D1/RGA1 in rice is involved in a phytohormone gibberellin-mediated signaling pathway. Evidence also implicates D1 in the action of a second phytohormone Brassinosteroid (BR) and its pathway. However, it is unclear how D1 functions in this pathway, because so far no partner has been identified to act with D1. In this study, we report a D1 genetic interactor Taihu Dwarf1 (TUD1) that encodes a functional U-box E3 ubiquitin ligase. Genetic, phenotypic, and physiological analyses have shown that tud1 is epistatic to d1 and is less sensitive to BR treatment. Histological observations showed that the dwarf phenotype of tud1 is mainly due to decreased cell proliferation and disorganized cell files in aerial organs. Furthermore, we found that D1 directly interacts with TUD1. Taken together, these results demonstrate that D1 and TUD1 act together to mediate a BR-signaling pathway. This supports the idea that a D1-mediated BR signaling pathway occurs in rice to affect plant growth and development. PMID:23526892

  1. MINERAL ABUNDANCE AND PARTICLE SIZE DISTRIBUTION DERIVED FROM IN-SITU SPECTRA MEASUREMENTS OF YUTU ROVER OF CHANG’E-3

    Directory of Open Access Journals (Sweden)

    H. Lin

    2017-07-01

    Full Text Available From geologic perspective, understanding the types, abundance, and size distributions of minerals allows us to address what geologic processes have been active on the lunar and planetary surface. The imaging spectrometer which was carried by the Yutu Rover of Chinese Chang’E-3 mission collected the reflectance at four different sites at the height of ~ 1 m, providing a new insight to understand the lunar surface. The mineral composition and Particle Size Distribution (PSD of these four sites were derived in this study using a Radiative Transfer Model (RTM and Sparse Unmixing (SU algorithm. The endmembers used were clinopyroxene, orthopyroxene, olivine, plagioclase and agglutinate collected from the lunar sample spectral dataset in RELAB. The results show that the agglutinate, clinopyroxene and olivine are the dominant minerals around the landing site. In location Node E, the abundance of agglutinate can reach up to 70 %, and the abundances of clinopyroxene and olivine are around 10 %. The mean particle sizes and the deviations of these endmembers were retrieved. PSDs of all these endmembers are close to normal distribution, and differences exist in the mean particle sizes, indicating the difference of space weathering rate of these endmembers.

  2. The E3 ubiquitin ligase ZNRF2 is a substrate of mTORC1 and regulates its activation by amino acids

    Science.gov (United States)

    Hoxhaj, Gerta; Caddye, Edward; Najafov, Ayaz; Houde, Vanessa P; Johnson, Catherine; Dissanayake, Kumara; Toth, Rachel; Campbell, David G; Prescott, Alan R; MacKintosh, Carol

    2016-01-01

    The mechanistic Target of Rapamycin complex 1 (mTORC1) senses intracellular amino acid levels through an intricate machinery, which includes the Rag GTPases, Ragulator and vacuolar ATPase (V-ATPase). The membrane-associated E3 ubiquitin ligase ZNRF2 is released into the cytosol upon its phosphorylation by Akt. In this study, we show that ZNRF2 interacts with mTOR on membranes, promoting the amino acid-stimulated translocation of mTORC1 to lysosomes and its activation in human cells. ZNRF2 also interacts with the V-ATPase and preserves lysosomal acidity. Moreover, knockdown of ZNRF2 decreases cell size and cell proliferation. Upon growth factor and amino acid stimulation, mTORC1 phosphorylates ZNRF2 on Ser145, and this phosphosite is dephosphorylated by protein phosphatase 6. Ser145 phosphorylation stimulates vesicle-to-cytosol translocation of ZNRF2 and forms a novel negative feedback on mTORC1. Our findings uncover ZNRF2 as a component of the amino acid sensing machinery that acts upstream of Rag-GTPases and the V-ATPase to activate mTORC1. DOI: http://dx.doi.org/10.7554/eLife.12278.001 PMID:27244671

  3. Numerical Simulations of the Lunar Penetrating Radar and Investigations of the Geological Structures of the Lunar Regolith Layer at the Chang’E 3 Landing Site

    Directory of Open Access Journals (Sweden)

    Chunyu Ding

    2017-01-01

    Full Text Available In the process of lunar exploration, and specifically when studying lunar surface structure and thickness, the established lunar regolith model is usually a uniform and ideal structural model, which is not well-suited to describe the real structure of the lunar regolith layer. The present study aims to explain the geological structural information contained in the channel 2 LPR (lunar penetrating radar data. In this paper, the random medium theory and Apollo drilling core data are used to construct a modeling method based on discrete heterogeneous random media, and the simulation data are processed and collected by the electromagnetic numerical method FDTD (finite-difference time domain. When comparing the LPR data with the simulated data, the heterogeneous random medium model is more consistent with the actual distribution of the media in the lunar regolith layer. It is indicated that the interior structure of the lunar regolith layer at the landing site is not a pure lunar regolith medium but rather a regolith-rock mixture, with rocks of different sizes and shapes. Finally, several reasons are given to explain the formation of the geological structures of the lunar regolith layer at the Chang’E 3 landing site, as well as the possible geological stratification structure.

  4. The Shallow Subsurface Geological Structures at the Chang'E-3 Landing Site Based on Lunar Penetrating Radar Channel-2B Data

    Science.gov (United States)

    Zhao, N.; Zhu, P.; Yuan, Y.; Yang, K.; Xiao, L.; Xiao, Z.

    2014-12-01

    The Lunar Penetrating Radar (LPR) carried by the Yutu rover of the Chinese Chang'E-3 mission has detected the shallow subsurface structures for the landing site at the northern Mare Imbrium. The antenna B of the LPR Channel-2 has collected more than 2000 traces of usable raw data. We performed calibration on the LPR data including amplitude compensation, filtering, and deconvolution. The processed results reveal that the shallow subsurface of the landing site can be divided into three major layers whose thicknesses are ~1, ~3, and 2-7 m, respectively. Variations occur on the thickness of each layer at different locations. Considering the geological background of the landing site, we interpret that the first layer is the regolith layer accumulated over ~80 Ma since the formation of the 450 m diameter Chang'E A crater. This regolith layer was formed on the basis of the ejecta deposits of Chang'E A. The second layer is the remnant continuous ejecta deposits from the Chang'E A crater, which is thicker closer to the crater rim and thinning outwardly. The Chang'E A crater formed on a paleo-regolith layer over the Eratosthenian basalts, which represents the third layer detected by the Channel 2B of the LPR.

  5. HTLV-1 Tax Functions as a Ubiquitin E3 Ligase for Direct IKK Activation via Synthesis of Mixed-Linkage Polyubiquitin Chains.

    Science.gov (United States)

    Wang, Chong; Long, Wenying; Peng, Chao; Hu, Lin; Zhang, Qiong; Wu, Ailing; Zhang, Xiaoqing; Duan, Xiaotao; Wong, Catherine C L; Tanaka, Yuetsu; Xia, Zongping

    2016-04-01

    The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events. We reconstituted Tax-stimulated IKK activation in a cell-free system to dissect the essential cellular components for primary IKK activation by Tax and studied the underlying biochemical mechanism. We found that Tax is a putative E3 ubiquitin ligase, which, together with UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of free mixed-linkage polyubiquitin chains. These free mixed-linkage polyubiquitin chains are then responsible for direct IKK activation by binding to the NEMO subunit of IKK. Our studies revealed the biochemical function of Tax in the process of IKK activation, which utilizes the minimal cellular ubiquitination components for NF-κB activation.

  6. The E3 Ubiquitin Ligase TRIM40 Attenuates Antiviral Immune Responses by Targeting MDA5 and RIG-I

    Directory of Open Access Journals (Sweden)

    Chunyuan Zhao

    2017-11-01

    Full Text Available Retinoic acid-inducible gene-I (RIG-I-like receptors (RLRs, including melanoma differentiation-associated gene 5 (MDA5 and RIG-I, are crucial for host recognition of non-self RNAs, especially viral RNA. Thus, the expression and activation of RLRs play fundamental roles in eliminating the invading RNA viruses and maintaining immune homeostasis. However, how RLR expression is tightly regulated remains to be further investigated. In this study, we identified a major histocompatibility complex (MHC-encoded gene, tripartite interaction motif 40 (TRIM40, as a suppressor of RLR signaling by directly targeting MDA5 and RIG-I. TRIM40 binds to MDA5 and RIG-I and promotes their K27- and K48-linked polyubiquitination via its E3 ligase activity, leading to their proteasomal degradation. TRIM40 deficiency enhances RLR-triggered signaling. Consequently, TRIM40 deficiency greatly enhances antiviral immune responses and decreases viral replication in vivo. Thus, we demonstrate that TRIM40 limits RLR-triggered innate activation, suggesting TRIM40 as a potential therapeutic target for the control of viral infection.

  7. Laboratory verification of the Active Particle-induced X-ray Spectrometer (APXS) on the Chang'e-3 mission

    International Nuclear Information System (INIS)

    Zhang, Guang-Liang; Li, Chun-Lai; Fu, Xiao-Hui; Zhang, Li-Yan; Ban, Cao; Li, Han; Zou, Yong-Liao; Peng, Wen-Xi; Cui, Xing-Zhu; Zhang, Cheng-Mo; Wang, Huan-Yu

    2015-01-01

    In the Chang'e-3 mission, the Active Particle-induced X-ray Spectrometer (APXS) on the Yutu rover is used to analyze the chemical composition of lunar soil and rock samples. APXS data are only valid are only if the sensor head gets close to the target and integration time lasts long enough. Therefore, working distance and integration time are the dominant factors that affect APXS results. This study confirms the ability of APXS to detect elements and investigates the effects of distance and time on the measurements. We make use of a backup APXS instrument to determine the chemical composition of both powder and bulk samples under the conditions of different working distances and integration times. The results indicate that APXS can detect seven major elements, including Mg, Al, Si, K, Ca, Ti and Fe under the condition that the working distance is less than 30 mm and having an integration time of 30 min. The statistical deviation is smaller than 15%. This demonstrates the instrument's ability to detect major elements in the sample. Our measurements also indicate the increase of integration time could reduce the measurement error of peak area, which is useful for detecting the elements Mg, Al and Si. However, an increase in working distance can result in larger errors in measurement, which significantly affects the detection of the element Mg. (paper)

  8. Interaction of the deubiquitinating enzyme Ubp2 and the e3 ligase Rsp5 is required for transporter/receptor sorting in the multivesicular body pathway.

    Directory of Open Access Journals (Sweden)

    Mandy H Y Lam

    Full Text Available Protein ubiquitination is essential for many events linked to intracellular protein trafficking. We sought to elucidate the possible involvement of the S. cerevisiae deubiquitinating enzyme Ubp2 in transporter and receptor trafficking after we (this study and others established that affinity purified Ubp2 interacts stably with the E3 ubiquitin ligase Rsp5 and the (ubiquitin associated UBA domain containing protein Rup1. UBP2 interacts genetically with RSP5, while Rup1 facilitates the tethering of Ubp2 to Rsp5 via a PPPSY motif. Using the uracil permease Fur4 as a model reporter system, we establish a role for Ubp2 in membrane protein turnover. Similar to hypomorphic rsp5 alleles, cells deleted for UBP2 exhibited a temporal stabilization of Fur4 at the plasma membrane, indicative of perturbed protein trafficking. This defect was ubiquitin dependent, as a Fur4 N-terminal ubiquitin fusion construct bypassed the block and restored sorting in the mutant. Moreover, the defect was absent in conditions where recycling was absent, implicating Ubp2 in sorting at the multivesicular body. Taken together, our data suggest a previously overlooked role for Ubp2 as a positive regulator of Rsp5-mediated membrane protein trafficking subsequent to endocytosis.

  9. The constitutive activation of the CEF-4/9E3 chemokine gene depends on C/EBPbeta in v-src transformed chicken embryo fibroblasts

    DEFF Research Database (Denmark)

    Gagliardi, M; Maynard, S; Bojovic, B

    2001-01-01

    The CEF-4/9E3 chemokine gene is expressed constitutively in chicken embryo fibroblasts (CEF) transformed by the Rous sarcoma virus (RSV). This aberrant induction is controlled at the transcriptional and post-transcriptional levels. Transcriptional activation depends on multiple elements of the CEF....../EBPbeta binds to a second element located in proximity of the TRE. A mutation of this distal CAAT box impaired the activation of the CEF-4 promoter by pp60(v-src) indicating that this element is also part of the SRU. Using the RCASBP retroviral vector, we expressed a dominant negative mutant of C....../EBPbeta (designated Delta184-C/EBPbeta) in RSV-transformed CEF. Delta184-C/EBPbeta decreased the accumulation of the CEF-4 mRNA and activation of the CEF-4 promoter by pp60(v-src). The induction of the Cox-2 gene (CEF-147) was also reduced by Delta184-C/EBPbeta. The effect of the dominant negative mutant was observed...

  10. HTLV-1 Tax Functions as a Ubiquitin E3 Ligase for Direct IKK Activation via Synthesis of Mixed-Linkage Polyubiquitin Chains.

    Directory of Open Access Journals (Sweden)

    Chong Wang

    2016-04-01

    Full Text Available The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events. We reconstituted Tax-stimulated IKK activation in a cell-free system to dissect the essential cellular components for primary IKK activation by Tax and studied the underlying biochemical mechanism. We found that Tax is a putative E3 ubiquitin ligase, which, together with UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of free mixed-linkage polyubiquitin chains. These free mixed-linkage polyubiquitin chains are then responsible for direct IKK activation by binding to the NEMO subunit of IKK. Our studies revealed the biochemical function of Tax in the process of IKK activation, which utilizes the minimal cellular ubiquitination components for NF-κB activation.

  11. Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin.

    Science.gov (United States)

    Lazarou, Michael; Jin, Seok Min; Kane, Lesley A; Youle, Richard J

    2012-02-14

    Mutations in the mitochondrial kinase PINK1 and the cytosolic E3 ligase Parkin can cause Parkinson's disease. Damaged mitochondria accumulate PINK1 on the outer membrane where, dependent on kinase activity, it recruits and activates Parkin to induce mitophagy, potentially maintaining organelle fidelity. How PINK1 recruits Parkin is unknown. We show that endogenous PINK1 forms a 700 kDa complex with the translocase of the outer membrane (TOM) selectively on depolarized mitochondria whereas PINK1 ectopically targeted to the outer membrane retains association with TOM on polarized mitochondria. Inducibly targeting PINK1 to peroxisomes or lysosomes, which lack a TOM complex, recruits Parkin and activates ubiquitin ligase activity on the respective organelles. Once there, Parkin induces organelle selective autophagy of peroxisomes but not lysosomes. We propose that the association of PINK1 with the TOM complex allows rapid reimport of PINK1 to rescue repolarized mitochondria from mitophagy, and discount mitochondrial-specific factors for Parkin translocation and activation. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Overexpression of the human ubiquitin E3 ligase CUL4A alleviates hypoxia–reoxygenation injury in pheochromocytoma (PC12) cells

    International Nuclear Information System (INIS)

    Tan, Can; Zhang, Li-Yang; Chen, Hong; Xiao, Ling; Liu, Xian-Peng; Zhang, Jian-Xiang

    2011-01-01

    Highlights: ► Overexpression of human CUL4A (hCUL4A) in PC12 cells. ► The effects of hCUL4A on hypoxia–reoxygenation injury were investigated. ► hCUL4A suppresses apoptosis and DNA damage and thus promotes cell survival. ► hCUL4A regulates apoptosis-related proteins and cell cycle regulators. -- Abstract: The ubiquitin E3 ligase CUL4A plays important roles in diverse cellular processes including carcinogenesis and proliferation. It has been reported that the expression of CUL4A can be induced by hypoxic-ischemic injury. However, the effect of elevated expression of CUL4A on hypoxia–reoxygenation injury is currently unclear. In this study, human CUL4A (hCUL4A) was expressed in rat pheochromocytoma (PC12) cells using adenoviral vector-mediated gene transfer, and the effects of hCUL4A expression on hypoxia–reoxygenation injury were investigated. In PC12 cells subjected to hypoxia and reoxygenation, we found that hCUL4A suppresses apoptosis and DNA damage by regulating apoptosis-related proteins and cell cycle regulators (Bcl-2, caspase-3, p53 and p27); consequently, hCUL4A promotes cell survival. Taken together, our results reveal the beneficial effects of hCUL4A in PC12 cells upon hypoxia–reoxygenation injury.

  13. Parthenium sp. as a plant biomass for the production of alkalitolerant xylanase from mutant Penicillium oxalicum SAU{sub E}-3.510 in submerged fermentation

    Energy Technology Data Exchange (ETDEWEB)

    Dwivedi, Pallavi; Vivekanand, V.; Ganguly, Ruma; Singh, Rajesh P. [Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667 (India)

    2009-04-15

    The use of congress grass (Parthenium sp.) and water hyacinth (Eichhornia crassipes) as low cost raw materials for xylanase production from mutant Penicillium oxalicum SAU{sub E}-3.510 in submerged fermentation was investigated. For development of mutant from wild type P. oxalicum SA-8 ITCC 6024, a strategy of mixed mutagenesis was followed using UV-irradiation and ethidium bromide, which had resulted into 1.87 fold increases in the activity of the enzyme. For enzyme production, the fungus was cultivated in mineral medium containing congress grass as carbon source. Considerably higher levels of production (475.2 {+-} 6.0 IU ml{sup -1}) were achieved in media containing congress grass, although it was slightly less than that was obtained (488.5 {+-} 6.5 IU ml{sup -1}) in presence of commercial oat spelt xylan. This fact confirms the feasibility of using this low cost non-food resource as an alternative carbon source to save costs of the enzyme production process. Maximum xylanase activity was reported at 55 C with its stability at 80 C for 2 h. The highest activity of xylanase at pH 9.0 and its stability at similar pH for 24 h denote the alkalitolerant nature of enzyme. (author)

  14. The SUD1 gene encodes a putative E3 ubiquitin ligase and is a positive regulator of 3-hydroxy-3-methylglutaryl coenzyme a reductase activity in Arabidopsis.

    Science.gov (United States)

    Doblas, Verónica G; Amorim-Silva, Vítor; Posé, David; Rosado, Abel; Esteban, Alicia; Arró, Montserrat; Azevedo, Herlander; Bombarely, Aureliano; Borsani, Omar; Valpuesta, Victoriano; Ferrer, Albert; Tavares, Rui M; Botella, Miguel A

    2013-02-01

    The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme catalyzes the major rate-limiting step of the mevalonic acid (MVA) pathway from which sterols and other isoprenoids are synthesized. In contrast with our extensive knowledge of the regulation of HMGR in yeast and animals, little is known about this process in plants. To identify regulatory components of the MVA pathway in plants, we performed a genetic screen for second-site suppressor mutations of the Arabidopsis thaliana highly drought-sensitive drought hypersensitive2 (dry2) mutant that shows decreased squalene epoxidase activity. We show that mutations in SUPPRESSOR OF DRY2 DEFECTS1 (SUD1) gene recover most developmental defects in dry2 through changes in HMGR activity. SUD1 encodes a putative E3 ubiquitin ligase that shows sequence and structural similarity to yeast Degradation of α factor (Doα10) and human TEB4, components of the endoplasmic reticulum-associated degradation C (ERAD-C) pathway. While in yeast and animals, the alternative ERAD-L/ERAD-M pathway regulates HMGR activity by controlling protein stability, SUD1 regulates HMGR activity without apparent changes in protein content. These results highlight similarities, as well as important mechanistic differences, among the components involved in HMGR regulation in plants, yeast, and animals.

  15. An Arabidopsis E3 Ligase, SHOOT GRAVITROPISM9, Modulates the Interaction between Statoliths and F-Actin in Gravity Sensing[W][OA

    Science.gov (United States)

    Nakamura, Moritaka; Toyota, Masatsugu; Tasaka, Masao; Morita, Miyo Terao

    2011-01-01

    Higher plants use the sedimentation of amyloplasts in statocytes as statolith to sense the direction of gravity during gravitropism. In Arabidopsis thaliana inflorescence stem statocyte, amyloplasts are in complex movement; some show jumping-like saltatory movement and some tend to sediment toward the gravity direction. Here, we report that a RING-type E3 ligase SHOOT GRAVITROPISM9 (SGR9) localized to amyloplasts modulates amyloplast dynamics. In the sgr9 mutant, which exhibits reduced gravitropism, amyloplasts did not sediment but exhibited increased saltatory movement. Amyloplasts sometimes formed a cluster that is abnormally entangled with actin filaments (AFs) in sgr9. By contrast, in the fiz1 mutant, an ACT8 semidominant mutant that induces fragmentation of AFs, amyloplasts, lost saltatory movement and sedimented with nearly statically. Both treatment with Latrunculin B, an inhibitor of AF polymerization, and the fiz1 mutation rescued the gravitropic defect of sgr9. In addition, fiz1 decreased saltatory movement and induced amyloplast sedimentation even in sgr9. Our results suggest that amyloplasts are in equilibrium between sedimentation and saltatory movement in wild-type endodermal cells. Furthermore, this equilibrium is the result of the interaction between amyloplasts and AFs modulated by the SGR9. SGR9 may promote detachment of amyloplasts from AFs, allowing the amyloplasts to sediment in the AFs-dependent equilibrium of amyloplast dynamics. PMID:21602290

  16. Tipe Dry Cell dan Wet Cell berdimensi 80 x 80 mm dengan Penambahan PWM E-3 FF (1 kHz

    Directory of Open Access Journals (Sweden)

    Yanur Arzaqa Ghiffari

    2013-09-01

    Full Text Available Ketersediaan bahan bakar minyak semakin terbatas dan hasil pembakarannya berdampak pada pencemaran lingkungan, salah satu solusinya dengan memanfaatkan gas HHO pada kendaraan bermotor. Penelitian dengan sistem direct connection, temperatur mencapai lebih dari 90oC menyebabkan  generator HHO menjadi rusak dan meleleh, maka penelitian ini menambahan alat untuk mengkontrol besarnya arus, frekuensi, dan duty cycle. Pengembangan generator HHO menggunakan tipe kering (dry cell dan tipe basah (wet cell dengan penambahan PWM (Pulse Width Modulation E-3 Fixed Frequency 1 kHz divariasikan berupa duty cycle: 20%, 40%, 60%, 80%  dan direct connection. Pengujian dilakukan di Laboratorium Teknik Pembakaran dan Bahan Bakar - Teknik Mesin ITS.  Dari hasil penelitian didapatkan karakteristik unjuk kerja terbaik pada kedua tipe generator HHO dengan penambahan PWM. Nilai arus dan tegangan lebih stabil dibandingkan dengan tanpa penambahan PWM (direct connection, namun arus cenderung meningkat seiring dengan kenaikan temperatur mencapai 70oC. Efisiensi terbaik pada generator tipe wet dengan duty cycle 80%,  yaitu 27,7 %.

  17. Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease

    Directory of Open Access Journals (Sweden)

    Laurent P. Bogdanik

    2013-05-01

    Charcot-Marie-Tooth disease (CMT is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have recently been shown to cause CMT. We have generated mouse mutations in Lrsam1 to create an animal model of this form of CMT (CMT2P. Mouse Lrsam1 is abundantly expressed in the motor and sensory neurons of the peripheral nervous system. Both homozygous and heterozygous mice have largely normal neuromuscular performance and only a very mild neuropathy phenotype with age. However, Lrsam1 mutant mice are more sensitive to challenge with acrylamide, a neurotoxic agent that causes axon degeneration, indicating that the axons in the mutant mice are indeed compromised. In transfected cells, LRSAM1 primarily localizes in a perinuclear compartment immediately beyond the Golgi and shows little colocalization with components of the endosome to lysosome trafficking pathway, suggesting that other cellular mechanisms also merit consideration.

  18. Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Bogdanik, Laurent P; Sleigh, James N; Tian, Cong; Samuels, Mark E; Bedard, Karen; Seburn, Kevin L; Burgess, Robert W

    2013-05-01

    Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have recently been shown to cause CMT. We have generated mouse mutations in Lrsam1 to create an animal model of this form of CMT (CMT2P). Mouse Lrsam1 is abundantly expressed in the motor and sensory neurons of the peripheral nervous system. Both homozygous and heterozygous mice have largely normal neuromuscular performance and only a very mild neuropathy phenotype with age. However, Lrsam1 mutant mice are more sensitive to challenge with acrylamide, a neurotoxic agent that causes axon degeneration, indicating that the axons in the mutant mice are indeed compromised. In transfected cells, LRSAM1 primarily localizes in a perinuclear compartment immediately beyond the Golgi and shows little colocalization with components of the endosome to lysosome trafficking pathway, suggesting that other cellular mechanisms also merit consideration.

  19. An economic and environmental assessment of future electricity generation mixes in Japan – an assessment using the E3MG macro-econometric model

    International Nuclear Information System (INIS)

    Pollitt, Hector; Park, Seung-Joon; Lee, Soocheol; Ueta, Kazuhiro

    2014-01-01

    In this paper we consider future options for Japanese energy and climate policy. We assess the economic and environmental impacts of changing the share of electricity generated by nuclear power and varying the mid-term GHG targets. The quantitative approach we use is based on the global macro-econometric E3MG model. Our analysis reveals that the cost of denuclearisation to Japanese GDP is close to zero, and for employment the impact is slightly positive. Our results also show a double-dividend effect if (revenue-neutral) carbon taxes are levied in order to meet the GHG reduction targets, and this double-dividend effect is largest in the scenarios without nuclear power. However, our analysis suggests that a very high carbon tax rate would have to be imposed in order to achieve a 25% reduction in GHG emissions in 2020 (compared to 1990 levels) while simultaneously phasing out nuclear power. - Highlights: • We modelled 12 scenarios for Japan with different shares for nuclear power and different emission targets. • The results showed that phasing out nuclear power would have at most a very small reduction in GDP. • If a carbon tax with revenue recycling is applied, there could be an increase in GDP. • But the carbon price required to meet Japan's 25% emission reduction target is very high if the share of nuclear power is reduced

  20. Haploid genetic screens identify an essential role for PLP2 in the downregulation of novel plasma membrane targets by viral E3 ubiquitin ligases.

    Directory of Open Access Journals (Sweden)

    Richard T Timms

    Full Text Available The Kaposi's sarcoma-associated herpesvirus gene products K3 and K5 are viral ubiquitin E3 ligases which downregulate MHC-I and additional cell surface immunoreceptors. To identify novel cellular genes required for K5 function we performed a forward genetic screen in near-haploid human KBM7 cells. The screen identified proteolipid protein 2 (PLP2, a MARVEL domain protein of unknown function, as essential for K5 activity. Genetic loss of PLP2 traps the viral ligase in the endoplasmic reticulum, where it is unable to ubiquitinate and degrade its substrates. Subsequent analysis of the plasma membrane proteome of K5-expressing KBM7 cells in the presence and absence of PLP2 revealed a wide range of novel K5 targets, all of which required PLP2 for their K5-mediated downregulation. This work ascribes a critical function to PLP2 for viral ligase activity and underlines the power of non-lethal haploid genetic screens in human cells to identify the genes involved in pathogen manipulation of the host immune system.

  1. The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals.

    Science.gov (United States)

    Li, Tongchao; Giagtzoglou, Nikolaos; Eberl, Daniel F; Jaiswal, Sonal Nagarkar; Cai, Tiantian; Godt, Dorothea; Groves, Andrew K; Bellen, Hugo J

    2016-06-22

    Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the mono-ubiquitination of non-muscle Myosin II, a protein associated with hearing loss in humans. The mono-ubiquitination of Myosin II promotes its physical interaction with Myosin VIIa, a protein responsible for Usher syndrome type IB. We show that ubr3 mutants phenocopy pathogenic variants of Myosin II and that Ubr3 interacts genetically and physically with three Usher syndrome proteins. The interactions between Myosin VIIa and Myosin IIa are conserved in the mammalian cochlea and in human retinal pigment epithelium cells. Our work reveals a novel mechanism that regulates protein complexes affected in two forms of syndromic deafness and suggests a molecular function for Myosin IIa in auditory organs.

  2. Overexpression of the human ubiquitin E3 ligase CUL4A alleviates hypoxia-reoxygenation injury in pheochromocytoma (PC12) cells

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Can [Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, 172 Tong Zipo Road, Changsha 410013 (China); Zhang, Li-Yang [Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, 110 Xiang Ya Road, Changsha 410078 (China); Chen, Hong [Department of Developmental Biology, School of Biological Science and Technology, Central South University, 172 Tong Zipo Road, Changsha 410013 (China); Xiao, Ling [Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, 172 Tong Zipo Road, Changsha 410013 (China); Liu, Xian-Peng, E-mail: xliu@lsuhsc.edu [Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932 (United States); Zhang, Jian-Xiang, E-mail: jianxiangzhang@yahoo.cn [Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, 172 Tong Zipo Road, Changsha 410013 (China); Department of Developmental Biology, School of Biological Science and Technology, Central South University, 172 Tong Zipo Road, Changsha 410013 (China)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Overexpression of human CUL4A (hCUL4A) in PC12 cells. Black-Right-Pointing-Pointer The effects of hCUL4A on hypoxia-reoxygenation injury were investigated. Black-Right-Pointing-Pointer hCUL4A suppresses apoptosis and DNA damage and thus promotes cell survival. Black-Right-Pointing-Pointer hCUL4A regulates apoptosis-related proteins and cell cycle regulators. -- Abstract: The ubiquitin E3 ligase CUL4A plays important roles in diverse cellular processes including carcinogenesis and proliferation. It has been reported that the expression of CUL4A can be induced by hypoxic-ischemic injury. However, the effect of elevated expression of CUL4A on hypoxia-reoxygenation injury is currently unclear. In this study, human CUL4A (hCUL4A) was expressed in rat pheochromocytoma (PC12) cells using adenoviral vector-mediated gene transfer, and the effects of hCUL4A expression on hypoxia-reoxygenation injury were investigated. In PC12 cells subjected to hypoxia and reoxygenation, we found that hCUL4A suppresses apoptosis and DNA damage by regulating apoptosis-related proteins and cell cycle regulators (Bcl-2, caspase-3, p53 and p27); consequently, hCUL4A promotes cell survival. Taken together, our results reveal the beneficial effects of hCUL4A in PC12 cells upon hypoxia-reoxygenation injury.

  3. The carboxyl terminus of FANCE recruits FANCD2 to the Fanconi Anemia (FA) E3 ligase complex to promote the FA DNA repair pathway.

    Science.gov (United States)

    Polito, David; Cukras, Scott; Wang, Xiaozhe; Spence, Paige; Moreau, Lisa; D'Andrea, Alan D; Kee, Younghoon

    2014-03-07

    Fanconi anemia (FA) is a genome instability syndrome characterized by bone marrow failure and cellular hypersensitivity to DNA cross-linking agents. In response to DNA damage, the FA pathway is activated through the cooperation of 16 FA proteins. A central player in the pathway is a multisubunit E3 ubiquitin ligase complex or the FA core complex, which monoubiquitinates its substrates FANCD2 and FANCI. FANCE, a subunit of the FA core complex, plays an essential role by promoting the integrity of the complex and by directly recognizing FANCD2. To delineate its role in substrate ubiquitination from the core complex assembly, we analyzed a series of mutations within FANCE. We report that a phenylalanine located at the highly conserved extreme C terminus, referred to as Phe-522, is a critical residue for mediating the monoubiquitination of the FANCD2-FANCI complex. Using the FANCE mutant that specifically disrupts the FANCE-FANCD2 interaction as a tool, we found that the interaction-deficient mutant conferred cellular sensitivity in reconstituted FANCE-deficient cells to a similar degree as FANCE null cells, suggesting the significance of the FANCE-FANCD2 interaction in promoting cisplatin resistance. Intriguingly, ectopic expression of the FANCE C terminus fragment alone in FA normal cells disrupts DNA repair, consolidating the importance of the FANCE-FANCD2 interaction in the DNA cross-link repair.

  4. The Carboxyl Terminus of FANCE Recruits FANCD2 to the Fanconi Anemia (FA) E3 Ligase Complex to Promote the FA DNA Repair Pathway*

    Science.gov (United States)

    Polito, David; Cukras, Scott; Wang, Xiaozhe; Spence, Paige; Moreau, Lisa; D'Andrea, Alan D.; Kee, Younghoon

    2014-01-01

    Fanconi anemia (FA) is a genome instability syndrome characterized by bone marrow failure and cellular hypersensitivity to DNA cross-linking agents. In response to DNA damage, the FA pathway is activated through the cooperation of 16 FA proteins. A central player in the pathway is a multisubunit E3 ubiquitin ligase complex or the FA core complex, which monoubiquitinates its substrates FANCD2 and FANCI. FANCE, a subunit of the FA core complex, plays an essential role by promoting the integrity of the complex and by directly recognizing FANCD2. To delineate its role in substrate ubiquitination from the core complex assembly, we analyzed a series of mutations within FANCE. We report that a phenylalanine located at the highly conserved extreme C terminus, referred to as Phe-522, is a critical residue for mediating the monoubiquitination of the FANCD2-FANCI complex. Using the FANCE mutant that specifically disrupts the FANCE-FANCD2 interaction as a tool, we found that the interaction-deficient mutant conferred cellular sensitivity in reconstituted FANCE-deficient cells to a similar degree as FANCE null cells, suggesting the significance of the FANCE-FANCD2 interaction in promoting cisplatin resistance. Intriguingly, ectopic expression of the FANCE C terminus fragment alone in FA normal cells disrupts DNA repair, consolidating the importance of the FANCE-FANCD2 interaction in the DNA cross-link repair. PMID:24451376

  5. E3 Ligase cIAP2 Mediates Downregulation of MRE11 and Radiosensitization in Response to HDAC Inhibition in Bladder Cancer.

    Science.gov (United States)

    Nicholson, Judith; Jevons, Sarah J; Groselj, Blaz; Ellermann, Sophie; Konietzny, Rebecca; Kerr, Martin; Kessler, Benedikt M; Kiltie, Anne E

    2017-06-01

    The MRE11/RAD50/NBS1 (MRN) complex mediates DNA repair pathways, including double-strand breaks induced by radiotherapy. Meiotic recombination 11 homolog (MRE11) is downregulated by histone deacetylase inhibition (HDACi), resulting in reduced levels of DNA repair in bladder cancer cells and radiosensitization. In this study, we show that the mechanism of this downregulation is posttranslational and identify a C-terminally truncated MRE11, which is formed after HDAC inhibition as full-length MRE11 is downregulated. Truncated MRE11 was stabilized by proteasome inhibition, exhibited a decreased half-life after treatment with panobinostat, and therefore represents a newly identified intermediate induced and degraded in response to HDAC inhibition. The E3 ligase cellular inhibitor of apoptosis protein 2 (cIAP2) was upregulated in response to HDAC inhibition and was validated as a new MRE11 binding partner whose upregulation had similar effects to HDAC inhibition. cIAP2 overexpression resulted in downregulation and altered ubiquitination patterns of MRE11 and mediated radiosensitization in response to HDAC inhibition. These results highlight cIAP2 as a player in the DNA damage response as a posttranscriptional regulator of MRE11 and identify cIAP2 as a potential target for biomarker discovery or chemoradiation strategies in bladder cancer. Cancer Res; 77(11); 3027-39. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. SCFJFK is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer

    Science.gov (United States)

    Yan, Ruorong; He, Lin; Li, Zhongwu; Han, Xiao; Liang, Jing; Si, Wenzhe; Chen, Zhe; Li, Lei; Xie, Guojia; Li, Wanjin; Wang, Peiyan; Lei, Liandi; Zhang, Hongquan; Pei, Fei; Cao, Dengfeng

    2015-01-01

    Loss of function/dysregulation of inhibitor of growth 4 (ING4) and hyperactivation of NF-κB are frequent events in many types of human malignancies. However, the molecular mechanisms underlying these remarkable aberrations are not understood. Here, we report that ING4 is physically associated with JFK. We demonstrated that JFK targets ING4 for ubiquitination and degradation through assembly of an Skp1–Cul1–F-box (SCF) complex. We showed that JFK-mediated ING4 destabilization leads to the hyperactivation of the canonical NF-κB pathway and promotes angiogenesis and metastasis of breast cancer. Significantly, the expression of JFK is markedly up-regulated in breast cancer, and the level of JFK is negatively correlated with that of ING4 and positively correlated with an aggressive clinical behavior of breast carcinomas. Our study identified SCFJFK as a bona fide E3 ligase for ING4 and unraveled the JFK–ING4–NF-κB axis as an important player in the development and progression of breast cancer, supporting the pursuit of JFK as a potential target for breast cancer intervention. PMID:25792601

  7. SCF(JFK) is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer.

    Science.gov (United States)

    Yan, Ruorong; He, Lin; Li, Zhongwu; Han, Xiao; Liang, Jing; Si, Wenzhe; Chen, Zhe; Li, Lei; Xie, Guojia; Li, Wanjin; Wang, Peiyan; Lei, Liandi; Zhang, Hongquan; Pei, Fei; Cao, Dengfeng; Sun, Luyang; Shang, Yongfeng

    2015-03-15

    Loss of function/dysregulation of inhibitor of growth 4 (ING4) and hyperactivation of NF-κB are frequent events in many types of human malignancies. However, the molecular mechanisms underlying these remarkable aberrations are not understood. Here, we report that ING4 is physically associated with JFK. We demonstrated that JFK targets ING4 for ubiquitination and degradation through assembly of an Skp1-Cul1-F-box (SCF) complex. We showed that JFK-mediated ING4 destabilization leads to the hyperactivation of the canonical NF-κB pathway and promotes angiogenesis and metastasis of breast cancer. Significantly, the expression of JFK is markedly up-regulated in breast cancer, and the level of JFK is negatively correlated with that of ING4 and positively correlated with an aggressive clinical behavior of breast carcinomas. Our study identified SCF(JFK) as a bona fide E3 ligase for ING4 and unraveled the JFK-ING4-NF-κB axis as an important player in the development and progression of breast cancer, supporting the pursuit of JFK as a potential target for breast cancer intervention. © 2015 Yan et al.; Published by Cold Spring Harbor Laboratory Press.

  8. The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals

    Science.gov (United States)

    Li, Tongchao; Giagtzoglou, Nikolaos; Eberl, Daniel F; Jaiswal, Sonal Nagarkar; Cai, Tiantian; Godt, Dorothea; Groves, Andrew K; Bellen, Hugo J

    2016-01-01

    Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the mono-ubiquitination of non-muscle Myosin II, a protein associated with hearing loss in humans. The mono-ubiquitination of Myosin II promotes its physical interaction with Myosin VIIa, a protein responsible for Usher syndrome type IB. We show that ubr3 mutants phenocopy pathogenic variants of Myosin II and that Ubr3 interacts genetically and physically with three Usher syndrome proteins. The interactions between Myosin VIIa and Myosin IIa are conserved in the mammalian cochlea and in human retinal pigment epithelium cells. Our work reveals a novel mechanism that regulates protein complexes affected in two forms of syndromic deafness and suggests a molecular function for Myosin IIa in auditory organs. DOI: http://dx.doi.org/10.7554/eLife.15258.001 PMID:27331610

  9. What can we learn from the endogeneization of the technical progress in GEM - E3? The case of the Kyoto protocol; Que pouvons nous apprendre de l'endogeneisation du progres technique dans GEM - E3? le cas du protocole de Kyoto

    Energy Technology Data Exchange (ETDEWEB)

    Fougeyrollas, A.; Le Mouel, P.; Zagame, P

    2007-07-01

    This project aims to study how the evaluation of the policies of fight against the greenhouse effect gases emission studied at an european scale, in the framework of the Kyoto agreements, is modified when the applied model, of general equilibrium takes into account the behavior of endogenous growth described by the new theories. More specially, the authors calibrated a production module with endogenous growth properties in the model GEM-E3. The new developed module show the costs reduction of policies of greenhouse effect gases emission limitation for France and Europe. (A.L.B.)

  10. Synthesis, spectroscopic characterization, theoretical study and anti-hepatic cancer activity study of 4-(1E,3Z,6E)-3-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,6-trien-1-yl)-2-methoxyphenyl 4-nitrobenzoate, a novel curcumin congener

    Science.gov (United States)

    Srivastava, Sangeeta; Gupta, Preeti; Singh, Ranvijay Pratap; Jafri, Asif; Arshad, M.; Banerjee, Monisha

    2017-08-01

    In the present work 4-(1E,3Z,6E)-3-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,6-trien-1-yl)-2-methoxyphenyl 4-nitrobenzoate (2), a novel curcumin ester was synthesized. The molecular structure and spectroscopic analysis were performed using experimental techniques like FT-IR, 1H,13C NMR, mass and UV-visible as well as theoretical calculations. The theoretical calculations were done by DFT level of theory using B3LYP/6-31G (d,p) basis set. The vibrational wavenumbers were calculated using DFT method and assigned with the help of potential energy distribution (PED). The electronic properties such as frontier orbitals and band gap energies have been calculated using time dependent density functional theory (TD-DFT). The strength and nature of weak intramolecular interactions have been studied by AIM approach. Global and local reactivity descriptors have been computed to predict reactivity and reactive sites in the molecule. First hyperpolarizability values have been calculated to describe the nonlinear optical (NLO) property of the synthesized compounds. Molecular electrostatic potential (MEP) analysis has also been carried out. The anti-hepatic cancer activity of compound 2 was also carried out.

  11. High expression of liver histone deacetylase 3 contributes to high-fat-diet-induced metabolic syndrome by suppressing the PPAR-γ and LXR-α-pathways in E3 rats.

    Science.gov (United States)

    Li, Dongmin; Wang, Xuan; Ren, Wuchao; Ren, Juan; Lan, Xi; Wang, Feimiao; Li, Hongmin; Zhang, Fujun; Han, Yan; Song, Tianbao; Holmdahl, Rikard; Lu, Shemin

    2011-09-15

    In the previous experiment, we found that there was a different response between E3 rats and DA.1U rats to high-fat-diet-induced metabolic syndrome (HFD-MetS). The aim of this study was to explore the cause and molecular mechanism of the genetic difference in susceptibility to metabolic syndrome in E3 rats as compared with DA.1U rats. Firstly, a 12-week HFD-MetS model in E3 and DA.1U rats was carried out and assessed. Then, the expression of key insulin signaling molecules, metabolic nuclear receptors, metabolic key enzymes and histone deacetylases (Hdacs) was determined by different methods. Finally, the effects of overexpression and disruption of Hdac3 on metabolic nuclear receptors were analyzed in CBRH-7919 cells and primarily-hepatic cells from DA.1U and E3 rats. We found that E3 rats were susceptible, while DA.1U rats were resisted to HFD-MetS. The expression of liver X receptor α,β (LXR-α,β), farnesoid X receptor (FXR), peroxisome proliferator activated receptor γ (PPAR-γ) and cholesterol 7α-hydroxylase (CYP7A1) increased markedly in DA.1U rat liver, whereas they decreased significantly in E3 rats. The expression of Hdac3 increased by HFD treatment in both E3 and DA.1U rat livers, but the constitutive Hdac3 expression was lower in DA.IU rat liver than in E3 rat liver. Importantly, overexpression of Hdac3 could downregulate the expression of LXR-α, PPAR-γ and CYP7A1 in both CBRH-7919 cells and primarily cultured hepatic cells from DA.IU rats. On the contrary, disruption of Hdac3 by shRNA upregulated the expression of LXR-α, PPAR-γ and CYP7A1 in both CBRH-7919 cells and primarily cultured hepatic cells from E3 rats. The results suggested that a high constitutive expression of Hdac3 inhibiting the expression of PPAR-γ, LXR-α and CYP7A1 in liver contributes to HFD-MetS in E3 rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Cardiac-specific ablation of the E3 ubiquitin ligase Mdm2 leads to oxidative stress, broad mitochondrial deficiency and early death.

    Directory of Open Access Journals (Sweden)

    Ludger Hauck

    Full Text Available The maintenance of normal heart function requires proper control of protein turnover. The ubiquitin-proteasome system is a principal regulator of protein degradation. Mdm2 is the main E3 ubiquitin ligase for p53 in mitotic cells thereby regulating cellular growth, DNA repair, oxidative stress and apoptosis. However, which of these Mdm2-related activities are preserved in differentiated cardiomyocytes has yet to be determined. We sought to elucidate the role of Mdm2 in the control of normal heart function. We observed markedly reduced Mdm2 mRNA levels accompanied by highly elevated p53 protein expression in the hearts of wild type mice subjected to myocardial infarction or trans-aortic banding. Accordingly, we generated conditional cardiac-specific Mdm2 gene knockout (Mdm2f/f;mcm mice. In adulthood, Mdm2f/f;mcm mice developed spontaneous cardiac hypertrophy, left ventricular dysfunction with early mortality post-tamoxifen. A decreased polyubiquitination of myocardial p53 was observed, leading to its stabilization and activation, in the absence of acute stress. In addition, transcriptomic analysis of Mdm2-deficient hearts revealed that there is an induction of E2f1 and c-Myc mRNA levels with reduced expression of the Pgc-1a/Ppara/Esrrb/g axis and Pink1. This was associated with a significant degree of cardiomyocyte apoptosis, and an inhibition of redox homeostasis and mitochondrial bioenergetics. All these processes are early, Mdm2-associated events and contribute to the development of pathological hypertrophy. Our genetic and biochemical data support a role for Mdm2 in cardiac growth control through the regulation of p53, the Pgc-1 family of transcriptional coactivators and the pivotal antioxidant Pink1.

  13. Functional characterization of the SIZ/PIAS-type SUMO E3 ligases, OsSIZ1 and OsSIZ2 in rice

    KAUST Repository

    Park, Hyeongcheol; Kim, Hun; Koo, Sungcheol; Park, Heejin; Cheong, Misun; Hong, Hyewon; Baek, Dongwon; Chung, Woosik; Kim, Dohhoon; Bressan, Ray Anthony; Lee, Sangyeol; Bohnert, Hans Jü rgen; Yun, Daejin

    2010-01-01

    Sumoylation is a post-translational regulatory process in diverse cellular processes in eukaryotes, involving conjugation/deconjugation of small ubiquitin-like modifier (SUMO) proteins to other proteins thus modifying their function. The PIAS [protein inhibitor of activated signal transducers and activators of transcription (STAT)] and SAP (scaffold attachment factor A/B/acinus/PIAS)/MIZ (SIZ) proteins exhibit SUMO E3-ligase activity that facilitates the conjugation of SUMO proteins to target substrates. Here, we report the isolation and molecular characterization of Oryza sativa SIZ1 (OsSIZ1) and SIZ2 (OsSIZ2), rice homologs of Arabidopsis SIZ1. The rice SIZ proteins are localized to the nucleus and showed sumoylation activities in a tobacco system. Our analysis showed increased amounts of SUMO conjugates associated with environmental stresses such as high and low temperature, NaCl and abscisic acid (ABA) in rice plants. The expression of OsSIZ1 and OsSIZ2 in siz1-2 Arabidopsis plants partially complemented the morphological mutant phenotype and enhanced levels of SUMO conjugates under heat shock conditions. In addition, ABA-hypersensitivity of siz1-2 seed germination was partially suppressed by OsSIZ1 and OsSIZ2. The results suggest that rice SIZ1 and SIZ2 are able to functionally complement Arabidopsis SIZ1 in the SUMO conjugation pathway. Their effects on the Arabidopsis mutant suggest a function for these genes related to stress responses and stress adaptation. © 2010 Blackwell Publishing Ltd.

  14. The putative E3 ubiquitin ligase ECERIFERUM9 regulates abscisic acid biosynthesis and response during seed germination and postgermination growth in arabidopsis

    KAUST Repository

    Zhao, Huayan

    2014-05-08

    The ECERIFERUM9 (CER9) gene encodes a putative E3 ubiquitin ligase that functions in cuticle biosynthesis and the maintenance of plant water status. Here, we found that CER9 is also involved in abscisic acid (ABA) signaling in seeds and young seedlings of Arabidopsis (Arabidopsis thaliana). The germinated embryos of the mutants exhibited enhanced sensitivity to ABA during the transition from reversible dormancy to determinate seedling growth. Expression of the CER9 gene is closely related to ABA levels and displays a similar pattern to that of ABSCISIC ACID-INSENSITIVE5 (ABI5), which encodes a positive regulator of ABA responses in seeds. cer9 mutant seeds exhibited delayed germination that is independent of seed coat permeability. Quantitative proteomic analyses showed that cer9 seeds had a protein profile similar to that of the wild type treated with ABA. Transcriptomics analyses revealed that genes involved in ABA biosynthesis or signaling pathways were differentially regulated in cer9 seeds. Consistent with this, high levels of ABA were detected in dry seeds of cer9. Blocking ABA biosynthesis by fluridone treatment or by combining an ABA-deficient mutation with cer9 attenuated the phenotypes of cer9. Whereas introduction of the abi1-1, abi3-1, or abi4-103 mutation could completely eliminate the ABA hypersensitivity of cer9, introduction of abi5 resulted only in partial suppression. These results indicate that CER9 is a novel negative regulator of ABA biosynthesis and the ABA signaling pathway during seed germination. © 2014 American Society of Plant Biologists. All Rights Reserved.

  15. ATL9, a RING zinc finger protein with E3 ubiquitin ligase activity implicated in chitin- and NADPH oxidase-mediated defense responses.

    Directory of Open Access Journals (Sweden)

    Marta Berrocal-Lobo

    2010-12-01

    Full Text Available Pathogen associated molecular patterns (PAMPs are signals detected by plants that activate basal defenses. One of these PAMPs is chitin, a carbohydrate present in the cell walls of fungi and in insect exoskeletons. Previous work has shown that chitin treatment of Arabidopsis thaliana induced defense-related genes in the absence of a pathogen and that the response was independent of the salicylic acid (SA, jasmonic acid (JA and ethylene (ET signaling pathways. One of these genes is ATL9 ( = ATL2G, which encodes a RING zinc-finger like protein. In the current work we demonstrate that ATL9 has E3 ubiquitin ligase activity and is localized to the endoplasmic reticulum. The expression pattern of ATL9 is positively correlated with basal defense responses against Golovinomyces cichoracearum, a biotrophic fungal pathogen. The basal levels of expression and the induction of ATL9 by chitin, in wild type plants, depends on the activity of NADPH oxidases suggesting that chitin-mediated defense response is NADPH oxidase dependent. Although ATL9 expression is not induced by treatment with known defense hormones (SA, JA or ET, full expression in response to chitin is compromised slightly in mutants where ET- or SA-dependent signaling is suppressed. Microarray analysis of the atl9 mutant revealed candidate genes that appear to act downstream of ATL9 in chitin-mediated defenses. These results hint at the complexity of chitin-mediated signaling and the potential interplay between elicitor-mediated signaling, signaling via known defense pathways and the oxidative burst.

  16. The Putative E3 Ubiquitin Ligase ECERIFERUM9 Regulates Abscisic Acid Biosynthesis and Response during Seed Germination and Postgermination Growth in Arabidopsis.

    Science.gov (United States)

    Zhao, Huayan; Zhang, Huoming; Cui, Peng; Ding, Feng; Wang, Guangchao; Li, Rongjun; Jenks, Matthew A; Lü, Shiyou; Xiong, Liming

    2014-07-01

    The ECERIFERUM9 (CER9) gene encodes a putative E3 ubiquitin ligase that functions in cuticle biosynthesis and the maintenance of plant water status. Here, we found that CER9 is also involved in abscisic acid (ABA) signaling in seeds and young seedlings of Arabidopsis (Arabidopsis thaliana). The germinated embryos of the mutants exhibited enhanced sensitivity to ABA during the transition from reversible dormancy to determinate seedling growth. Expression of the CER9 gene is closely related to ABA levels and displays a similar pattern to that of ABSCISIC ACID-INSENSITIVE5 (ABI5), which encodes a positive regulator of ABA responses in seeds. cer9 mutant seeds exhibited delayed germination that is independent of seed coat permeability. Quantitative proteomic analyses showed that cer9 seeds had a protein profile similar to that of the wild type treated with ABA. Transcriptomics analyses revealed that genes involved in ABA biosynthesis or signaling pathways were differentially regulated in cer9 seeds. Consistent with this, high levels of ABA were detected in dry seeds of cer9. Blocking ABA biosynthesis by fluridone treatment or by combining an ABA-deficient mutation with cer9 attenuated the phenotypes of cer9. Whereas introduction of the abi1-1, abi3-1, or abi4-103 mutation could completely eliminate the ABA hypersensitivity of cer9, introduction of abi5 resulted only in partial suppression. These results indicate that CER9 is a novel negative regulator of ABA biosynthesis and the ABA signaling pathway during seed germination. © 2014 American Society of Plant Biologists. All Rights Reserved.

  17. The Putative E3 Ubiquitin Ligase ECERIFERUM9 Regulates Abscisic Acid Biosynthesis and Response during Seed Germination and Postgermination Growth in Arabidopsis1[W][OPEN

    Science.gov (United States)

    Zhao, Huayan; Zhang, Huoming; Cui, Peng; Ding, Feng; Wang, Guangchao; Li, Rongjun; Jenks, Matthew A.; Lü, Shiyou; Xiong, Liming

    2014-01-01

    The ECERIFERUM9 (CER9) gene encodes a putative E3 ubiquitin ligase that functions in cuticle biosynthesis and the maintenance of plant water status. Here, we found that CER9 is also involved in abscisic acid (ABA) signaling in seeds and young seedlings of Arabidopsis (Arabidopsis thaliana). The germinated embryos of the mutants exhibited enhanced sensitivity to ABA during the transition from reversible dormancy to determinate seedling growth. Expression of the CER9 gene is closely related to ABA levels and displays a similar pattern to that of ABSCISIC ACID-INSENSITIVE5 (ABI5), which encodes a positive regulator of ABA responses in seeds. cer9 mutant seeds exhibited delayed germination that is independent of seed coat permeability. Quantitative proteomic analyses showed that cer9 seeds had a protein profile similar to that of the wild type treated with ABA. Transcriptomics analyses revealed that genes involved in ABA biosynthesis or signaling pathways were differentially regulated in cer9 seeds. Consistent with this, high levels of ABA were detected in dry seeds of cer9. Blocking ABA biosynthesis by fluridone treatment or by combining an ABA-deficient mutation with cer9 attenuated the phenotypes of cer9. Whereas introduction of the abi1-1, abi3-1, or abi4-103 mutation could completely eliminate the ABA hypersensitivity of cer9, introduction of abi5 resulted only in partial suppression. These results indicate that CER9 is a novel negative regulator of ABA biosynthesis and the ABA signaling pathway during seed germination. PMID:24812105

  18. MDM2 regulates hypoxic hypoxia-inducible factor 1α stability in an E3 ligase, proteasome, and PTEN-phosphatidylinositol 3-kinase-AKT-dependent manner.

    Science.gov (United States)

    Joshi, Shweta; Singh, Alok R; Durden, Donald L

    2014-08-15

    Hypoxia-inducible factor 1 (HIF1) is a heterodimeric transcription factor containing an inducibly expressed HIF1α subunit and a constitutively expressed HIF1β subunit. Under hypoxic conditions, the HIF1α subunit accumulates because of a decrease in the rate of proteolytic degradation, and the resulting HIF1α-HIF1β heterodimers undergo post-translational modifications that promote transactivation. Previous reports suggest that amplified signaling through PI3K enhances HIF1-dependent gene expression; however, its role is controversial, and the mechanism is unclear. Using genetically engineered PTEN-deficient cell lines, we demonstrate that PTEN specifically inhibited the accumulation of HIF1α in response to hypoxia. Furthermore, we report that in glioblastoma cell lines, inhibition of PI3K pathway, using pan as well as isoform-specific PI3K inhibitors SF1126, PF4691502, BEZ-235, GDC0941, and TGX221 blocked the induction of HIF1α protein and its targets vascular endothelial growth factor, HK1, and GLUT1 mRNA in response to hypoxia. Herein, we describe the first evidence that HIF1α can be degraded under hypoxic conditions via the 26 S proteasome and that MDM2 is the E3 ligase that induces the hypoxic degradation of HIF1α. Moreover, the action of MDM2 on HIF1α under hypoxia occurs in the cytoplasm and is controlled by the PTEN-PI3K-AKT signaling axis. These data strongly suggest a new role for PTEN in the regulation of HIF1α and importantly that PI3K-AKT activation is required for the hypoxic stabilization of HIF1α and that hypoxia alone is not sufficient to render HIF1α resistant to proteasomal cleavage and degradation. Moreover, these findings suggest new therapeutic considerations for PI3K and/or AKT inhibitors for cancer therapeutics. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. MDM2 Regulates Hypoxic Hypoxia-inducible Factor 1α Stability in an E3 Ligase, Proteasome, and PTEN-Phosphatidylinositol 3-Kinase-AKT-dependent Manner*

    Science.gov (United States)

    Joshi, Shweta; Singh, Alok R.; Durden, Donald L.

    2014-01-01

    Hypoxia-inducible factor 1 (HIF1) is a heterodimeric transcription factor containing an inducibly expressed HIF1α subunit and a constitutively expressed HIF1β subunit. Under hypoxic conditions, the HIF1α subunit accumulates because of a decrease in the rate of proteolytic degradation, and the resulting HIF1α–HIF1β heterodimers undergo post-translational modifications that promote transactivation. Previous reports suggest that amplified signaling through PI3K enhances HIF1-dependent gene expression; however, its role is controversial, and the mechanism is unclear. Using genetically engineered PTEN-deficient cell lines, we demonstrate that PTEN specifically inhibited the accumulation of HIF1α in response to hypoxia. Furthermore, we report that in glioblastoma cell lines, inhibition of PI3K pathway, using pan as well as isoform-specific PI3K inhibitors SF1126, PF4691502, BEZ-235, GDC0941, and TGX221 blocked the induction of HIF1α protein and its targets vascular endothelial growth factor, HK1, and GLUT1 mRNA in response to hypoxia. Herein, we describe the first evidence that HIF1α can be degraded under hypoxic conditions via the 26 S proteasome and that MDM2 is the E3 ligase that induces the hypoxic degradation of HIF1α. Moreover, the action of MDM2 on HIF1α under hypoxia occurs in the cytoplasm and is controlled by the PTEN-PI3K-AKT signaling axis. These data strongly suggest a new role for PTEN in the regulation of HIF1α and importantly that PI3K-AKT activation is required for the hypoxic stabilization of HIF1α and that hypoxia alone is not sufficient to render HIF1α resistant to proteasomal cleavage and degradation. Moreover, these findings suggest new therapeutic considerations for PI3K and/or AKT inhibitors for cancer therapeutics. PMID:24982421

  20. Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushing's syndrome.

    Science.gov (United States)

    Kang, Seol-Hee; Lee, Hae-Ahm; Kim, Mina; Lee, Eunjo; Sohn, Uy Dong; Kim, Inkyeom

    2017-06-01

    Cushing's syndrome is caused by overproduction of the adrenocorticotropic hormone (ACTH), which stimulates the adrenal grand to make cortisol. Skeletal muscle wasting occurs in pathophysiological response to Cushing's syndrome. The forkhead box (FOX) protein family has been implicated as a key regulator of muscle loss under conditions such as diabetes and sepsis. However, the mechanistic role of the FOXO family in ACTH-induced muscle atrophy is not understood. We hypothesized that FOXO3a plays a role in muscle atrophy through expression of the E3 ubiquitin ligases, muscle RING finger protein-1 (MuRF-1), and atrogin-1 in Cushing's syndrome. For establishment of a Cushing's syndrome animal model, Sprague-Dawley rats were implanted with osmotic minipumps containing ACTH (40 ng·kg -1 ·day -1 ). ACTH infusion significantly reduced muscle weight. In ACTH-infused rats, MuRF-1, atrogin-1, and FOXO3a were upregulated and the FOXO3a promoter was targeted by the glucocorticoid receptor (GR). Transcriptional activity and expression of FOXO3a were significantly decreased by the GR antagonist RU486. Treatment with RU486 reduced MuRF-1 and atrogin-1 expression in accordance with reduced enrichment of FOXO3a and Pol II on the promoters. Knockdown of FOXO3a prevented dexamethasone-induced MuRF-1 and atrogin-1 expression. These results indicate that FOXO3a plays a role in muscle atrophy through expression of MuRF-1 and atrogin-1 in Cushing's syndrome. Copyright © 2017 the American Physiological Society.

  1. Functional characterization of the SIZ/PIAS-type SUMO E3 ligases, OsSIZ1 and OsSIZ2 in rice

    KAUST Repository

    Park, Hyeongcheol

    2010-06-18

    Sumoylation is a post-translational regulatory process in diverse cellular processes in eukaryotes, involving conjugation/deconjugation of small ubiquitin-like modifier (SUMO) proteins to other proteins thus modifying their function. The PIAS [protein inhibitor of activated signal transducers and activators of transcription (STAT)] and SAP (scaffold attachment factor A/B/acinus/PIAS)/MIZ (SIZ) proteins exhibit SUMO E3-ligase activity that facilitates the conjugation of SUMO proteins to target substrates. Here, we report the isolation and molecular characterization of Oryza sativa SIZ1 (OsSIZ1) and SIZ2 (OsSIZ2), rice homologs of Arabidopsis SIZ1. The rice SIZ proteins are localized to the nucleus and showed sumoylation activities in a tobacco system. Our analysis showed increased amounts of SUMO conjugates associated with environmental stresses such as high and low temperature, NaCl and abscisic acid (ABA) in rice plants. The expression of OsSIZ1 and OsSIZ2 in siz1-2 Arabidopsis plants partially complemented the morphological mutant phenotype and enhanced levels of SUMO conjugates under heat shock conditions. In addition, ABA-hypersensitivity of siz1-2 seed germination was partially suppressed by OsSIZ1 and OsSIZ2. The results suggest that rice SIZ1 and SIZ2 are able to functionally complement Arabidopsis SIZ1 in the SUMO conjugation pathway. Their effects on the Arabidopsis mutant suggest a function for these genes related to stress responses and stress adaptation. © 2010 Blackwell Publishing Ltd.

  2. HTLV-1 Tax Stimulates Ubiquitin E3 Ligase, Ring Finger Protein 8, to Assemble Lysine 63-Linked Polyubiquitin Chains for TAK1 and IKK Activation.

    Science.gov (United States)

    Ho, Yik-Khuan; Zhi, Huijun; Bowlin, Tara; Dorjbal, Batsukh; Philip, Subha; Zahoor, Muhammad Atif; Shih, Hsiu-Ming; Semmes, Oliver John; Schaefer, Brian; Glover, J N Mark; Giam, Chou-Zen

    2015-08-01

    Human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, impacts a multitude of cellular processes, including I-κB kinase (IKK)/NF-κB signaling, DNA damage repair, and mitosis. These activities of Tax have been implicated in the development of adult T-cell leukemia (ATL) in HTLV-1-infected individuals, but the underlying mechanisms remain obscure. IKK and its upstream kinase, TGFβ-activated kinase 1 (TAK1), contain ubiquitin-binding subunits, NEMO and TAB2/3 respectively, which interact with K63-linked polyubiquitin (K63-pUb) chains. Recruitment to K63-pUb allows cross auto-phosphorylation and activation of TAK1 to occur, followed by TAK1-catalyzed IKK phosphorylation and activation. Using cytosolic extracts of HeLa and Jurkat T cells supplemented with purified proteins we have identified ubiquitin E3 ligase, ring finger protein 8 (RNF8), and E2 conjugating enzymes, Ubc13:Uev1A and Ubc13:Uev2, to be the cellular factors utilized by Tax for TAK1 and IKK activation. In vitro, the combination of Tax and RNF8 greatly stimulated TAK1, IKK, IκBα and JNK phosphorylation. In vivo, RNF8 over-expression augmented while RNF8 ablation drastically reduced canonical NF-κB activation by Tax. Activation of the non-canonical NF-κB pathway by Tax, however, is unaffected by the loss of RNF8. Using purified components, we further demonstrated biochemically that Tax greatly stimulated RNF8 and Ubc13:Uev1A/Uev2 to assemble long K63-pUb chains. Finally, co-transfection of Tax with increasing amounts of RNF8 greatly induced K63-pUb assembly in a dose-dependent manner. Thus, Tax targets RNF8 and Ubc13:Uev1A/Uev2 to promote the assembly of K63-pUb chains, which signal the activation of TAK1 and multiple downstream kinases including IKK and JNK. Because of the roles RNF8 and K63-pUb chains play in DNA damage repair and cytokinesis, this mechanism may also explain the genomic instability of HTLV-1-transformed T cells and ATL cells.

  3. Regulation of CNKSR2 protein stability by the HECT E3 ubiquitin ligase Smurf2, and its role in breast cancer progression.

    Science.gov (United States)

    David, Diana; Surendran, Arun; Thulaseedharan, Jissa V; Nair, Asha S

    2018-03-13

    Smurf2 E3 ubiquitin ligase physically associates with and regulate the stability of distinct cellular protein substrates. The multi-functional scaffold protein Connector enhancer of kinase suppressor of ras 2 (CNKSR2) plays a key role in regulating cell proliferation, and differentiation through multiple receptor tyrosine kinase pathways. The aim of this study was to investigate whether the interaction between Smurf2 and CNKSR2 has any significant role in the post transcriptional regulation of CNKSR2 expression in breast cancer. Here we demonstrate a novel interaction of CNKSR2 with Smurf2 by co-immunoprecipitation, indirect immunofluorescence studies, and surface plasmon resonance (SPR) analysis, which can ubiquitinate, but stabilize CNKSR2 by protecting it from proteasome mediated degradation. CNKSR2 protein levels were significantly increased upon forced overexpression of Smurf2, indicating the role of Smurf2 in regulating the stability of CNKSR2. Conversely, Smurf2 knockdown resulted in a marked decrease in the protein level expression of CNKSR2 by facilitating enhanced polyubiquitination and proteasomal degradation and reduced the proliferation and clonogenic survival of MDA-MB-231 breast cancer cell lines. Tissue microarray data from 84 patients with various stages of mammary carcinoma, including (in order of increasing malignant potential) normal, usual hyperplasia, fibrocystic changes, fibroadenoma, carcinoma-in-situ, and invasive ductal carcinoma showed a statistically significant association between Smurf2 and CNKSR2 expression, which is also well correlated with the ER, PR, and HER2 status of the tissue samples. A comparatively high expression of Smurf2 and CNKSR2 was observed when the expression of ER and PR was low, and HER2 was high. Consistently, both Smurf2 and CNKSR2 showed an integrated expression in MCF10 breast progression model cell lines. Altogether, our findings reveal that Smurf2 is a novel positive regulator of CNKSR2 and suggest that Smurf

  4. p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1

    Science.gov (United States)

    Ma-Lauer, Yue; Carbajo-Lozoya, Javier; Müller, Marcel A.; Deng, Wen; Lei, Jian; Meyer, Benjamin; Kusov, Yuri; von Brunn, Brigitte; Bairad, Dev Raj; Hünten, Sabine; Drosten, Christian; Hermeking, Heiko; Leonhardt, Heinrich; Mann, Matthias; Hilgenfeld, Rolf; von Brunn, Albrecht

    2016-01-01

    Highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) has developed strategies to inhibit host immune recognition. We identify cellular E3 ubiquitin ligase ring-finger and CHY zinc-finger domain-containing 1 (RCHY1) as an interacting partner of the viral SARS-unique domain (SUD) and papain-like protease (PLpro), and, as a consequence, the involvement of cellular p53 as antagonist of coronaviral replication. Residues 95–144 of RCHY1 and 389–652 of SUD (SUD-NM) subdomains are crucial for interaction. Association with SUD increases the stability of RCHY1 and augments RCHY1-mediated ubiquitination as well as degradation of p53. The calcium/calmodulin-dependent protein kinase II delta (CAMK2D), which normally influences RCHY1 stability by phosphorylation, also binds to SUD. In vivo phosphorylation shows that SUD does not regulate phosphorylation of RCHY1 via CAMK2D. Similarly to SUD, the PLpros from SARS-CoV, MERS-CoV, and HCoV-NL63 physically interact with and stabilize RCHY1, and thus trigger degradation of endogenous p53. The SARS-CoV papain-like protease is encoded next to SUD within nonstructural protein 3. A SUD–PLpro fusion interacts with RCHY1 more intensively and causes stronger p53 degradation than SARS-CoV PLpro alone. We show that p53 inhibits replication of infectious SARS-CoV as well as of replicons and human coronavirus NL63. Hence, human coronaviruses antagonize the viral inhibitor p53 via stabilizing RCHY1 and promoting RCHY1-mediated p53 degradation. SUD functions as an enhancer to strengthen interaction between RCHY1 and nonstructural protein 3, leading to a further increase in in p53 degradation. The significance of these findings is that down-regulation of p53 as a major player in antiviral innate immunity provides a long-sought explanation for delayed activities of respective genes. PMID:27519799

  5. Efeito do Exercício com 1 e 3 Minutos de Intervalo de Descanso Entre as Séries na Atividade Sérica das Transaminases

    Directory of Open Access Journals (Sweden)

    Ramon Martins Alves

    2011-12-01

    Full Text Available O treinamento de força (TF intenso ocasiona danos na estrutura muscular, que podem ser detectados por meio de marcadores indiretos. OBJETIVO. Verificar se há alterações na atividade da creatina quinase (CK, da aspartato transaminase (AST e alanina transaminase (ALT com o TF em diferentes intervalos entre séries e exercícios. MÉTODOS. Treze voluntários (± 21,8 anos; ±173,6 cm; ±68,3 kg realizaram o teste de uma repetição máxima (1RM nos exercícios: supino reto, puxada (pulley, desenvolvimento sentado, tríceps (pulley e rosca bíceps. Após sete dias, todos foram submetidos a uma coleta de sangue (PRE e realizaram 4 séries máximas até a falha concêntrica com intensidade de 85% de 1RM e intervalos de 1 ou 3 minutos entre as séries e exercícios. Todos retornaram ao mesmo local 24, 48 e 72 horas após a sessão para mais uma coleta de sangue. Repetindo os procedimentos após uma semana, porém os voluntários que realizaram o teste com intervalo de 1 minuto na semana seguinte manteriam intervalos de 3 minutos e vice-versa. Realizou-se ANOVA mantendo como significância p<0,05. RESULTADOS. Houve redução significativa do número de repetições a cada série de todos os exercícios com 1 e 3 minutos de intervalo. Observou-se um aumento significativo da atividade sérica de CK e de AST 24, 48 e 72 horas utilizando ambos os intervalos. ALT não se alterou. CONCLUSÃO. O TF causou aumento na atividade de CK e AST, mas sem apresentar diferenças com os intervalos utilizados. Porém, pequenos intervalos reduzem o volume total de repetições.

  6. Bis{(E-3-[2-(hydroxyiminopropanamido]-2,2-dimethylpropan-1-aminium} bis[μ-(E-N-(3-amino-2,2-dimethylpropyl-2-(hydroxyiminopropanamido(2−]bis{[(E-N-(3-amino-2,2-dimethylpropyl-2-(hydroxyiminopropanamide]copper(II} bis((E-{3-[2-(hydroxyiminopropanamido]-2,2-dimethylpropyl}carbamate acetonitrile disolvate

    Directory of Open Access Journals (Sweden)

    Andrii I. Buvailo

    2012-12-01

    Full Text Available The reaction between copper(II nitrate and (E-N-(3-amino-2,2-dimethylpropyl-2-(hydroxyiminopropanamide led to the formation of the dinuclear centrosymmetric copper(II title complex, (C8H18N3O22[Cu2(C8H15N3O22(C8H17N3O22](C9H16N3O42·2CH3CN, in which an inversion center is located at the midpoint of the Cu2 unit in the center of the neutral [Cu2(C8H15N3O22(C8H17N3O22] complex fragment. The Cu2+ ions are connected by two N—O bridging groups [Cu...Cu separation = 4.0608 (5 Å] while the CuII ions are five-coordinated in a square-pyramidal N4O coordination environment. The complex molecule co-crystallizes with two molecules of acetonitrile, two molecules of the protonated ligand (E-3-[2-(hydroxyiminopropanamido]-2,2-dimethylpropan-1-aminium and two negatively charged (E-{3-[2-(hydroxyiminopropanamido]-2,2-dimethylpropyl}carbamate anions, which were probably formed as a result of condensation between (E-N-(3-amino-2,2-dimethylpropyl-2-(hydroxyiminopropanamide and hydrogencarbonate anions. In the crystal, the complex fragment [Cu2(C8H15N3O22(C8H17N3O22] and the ion pair C8H18N3O2+.C9H16N3O4− are connected via an extended system of hydrogen bonds.

  7. When Sentry Goes Stealing: An Information Systems Security Case Study in Behavioural Context

    OpenAIRE

    Syed Irfan Nabi; Zaheeruddin Asif; Abdulrahman A Mirza

    2014-01-01

    In this paper we describe a case where the top management of a small holding company is involved in a love-hate relationship with its own IT department. The top management firmly believes that IT staff is involved in leaking out company’s secrets. However, having no expertise in IT and even lesser grasp on the complexity of IT architecture resulting from recent mergers and acquisition, the top management finds itself crucially dependent on its IT systems, yet unable to trust them fully. The ...

  8. Strategies to enhance venous thromboprophylaxis in hospitalized medical patients (SENTRY: a pilot cluster randomized trial

    Directory of Open Access Journals (Sweden)

    Pai Menaka

    2013-01-01

    Full Text Available Abstract Background Venous thromboembolism (VTE is a common preventable cause of mortality in hospitalized medical patients. Despite rigorous randomized trials generating strong recommendations for anticoagulant use to prevent VTE, nearly 40% of medical patients receive inappropriate thromboprophylaxis. Knowledge-translation strategies are needed to bridge this gap. Methods We conducted a 16-week pilot cluster randomized controlled trial (RCT to determine the proportion of medical patients that were appropriately managed for thromboprophylaxis (according to the American College of Chest Physician guidelines within 24 hours of admission, through the use of a multicomponent knowledge-translation intervention. Our primary goal was to determine the feasibility of conducting this study on a larger scale. The intervention comprised clinician education, a paper-based VTE risk assessment algorithm, printed physicians’ orders, and audit and feedback sessions. Medical wards at six hospitals (representing clusters in Ontario, Canada were included; three were randomized to the multicomponent intervention and three to usual care (i.e., no active strategies for thromboprophylaxis in place. Blinding was not used. Results A total of 2,611 patients (1,154 in the intervention and 1,457 in the control group were eligible and included in the analysis. This multicomponent intervention did not lead to a significant difference in appropriate VTE prophylaxis rates between intervention and control hospitals (appropriate management rate odds ratio = 0.80; 95% confidence interval: 0.50, 1.28; p = 0.36; intra-class correlation coefficient: 0.022, and thus was not considered feasible. Major barriers to effective knowledge translation were poor attendance by clinical staff at education and feedback sessions, difficulty locating preprinted orders, and lack of involvement by clinical and administrative leaders. We identified several factors that may increase uptake of a VTE prophylaxis strategy, including local champions, support from clinical and administrative leaders, mandatory use, and a simple, clinically relevant risk assessment tool. Conclusions Hospitals allocated to our multicomponent intervention did not have a higher rate of medical inpatients appropriately managed for thromboprophylaxis than did hospitals that were not allocated to this strategy.

  9. 75 FR 82202 - Utilization of Global Entry Kiosks by NEXUS and SENTRI Participants

    Science.gov (United States)

    2010-12-29

    ... terrorist databases, a 10- fingerprint law enforcement check and a personal interview with a CBP officer. An... databases, a 10-fingerprint law enforcement check and a personal interview with a CBP officer. Any one of... be posted without change to http://www.regulations.gov , including any personal information provided...

  10. When Sentry Goes Stealing: An Information Systems Security Case Study in Behavioural Context

    Directory of Open Access Journals (Sweden)

    Syed Irfan Nabi

    2014-12-01

    Full Text Available In this paper we describe a case where the top management of a small holding company is involved in a love-hate relationship with its own IT department. The top management firmly believes that IT staff is involved in leaking out company’s secrets. However, having no expertise in IT and even lesser grasp on the complexity of IT architecture resulting from recent mergers and acquisition, the top management finds itself crucially dependent on its IT systems, yet unable to trust them fully. The theories of deterrence and reasoned action are used to explain the otherwise objectionable behaviour of the perpetrator.

  11. Arachidonic acid/docosahexaenoic acid-supplemented diet in early life reduces body weight gain, plasma lipids, and adiposity in later life in ApoE*3 Leiden mice

    NARCIS (Netherlands)

    Wielinga, P.Y.; Harthoorn, L.F.; Verschuren, L.; Schoemaker, M.H.; Jouni, Z.E.; Tol, E.A.F. van; Kleemann, R.; Kooistra, T.

    2012-01-01

    Scope: This study addresses whether early life arachidonic acid (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism, and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic

  12. Properties of 15/2- states in 215Ra and 217Th; evaluation of the 15/2- to 9/2+ E3 strength in N=127 isotones

    International Nuclear Information System (INIS)

    Dracoulis, G.D.; Riess, R.; Stuchbery, A.E.; Bark, R.A.; Gupta, S.L.; Baxter, A.M.; Kruse, M.

    1988-01-01

    The lifetime of the yrast 15/2 - state in 215 Ra was measured using pulsed beams and γ-ray and electron techniques. Transition multipolarities were established from measured conversion coefficients. The B(E3) of the 15/2 - → 9/2 + transition is found to be considerably larger than previously reported. A candidate for the corresponding transition in 217 Th was also observed. The E3 strength of the 15/2 - → 9/2 + transition in the N=127 isotones is evaluated in the light of these and other recent results. Interpretation in the framework of particle-octupole vibration coupling requires a systematic lowering of the core 3 - vibration as proton pairs are added to 208 Pb

  13. Molecular docking studies of (1E,3E,5E)-1,6-Bis(substituted phenyl)hexa-1,3,5-triene and 1,4-Bis(substituted trans-styryl)benzene analogs as novel tyrosinase inhibitors.

    Science.gov (United States)

    Ha, Young Mi; Lee, Hye Jin; Park, Daeui; Jeong, Hyoung Oh; Park, Ji Young; Park, Yun Jung; Lee, Kyung Jin; Lee, Ji Yeon; Moon, Hyung Ryong; Chung, Hae Young

    2013-01-01

    We simulated the docking of the tertiary structure of mushroom tyrosinase with our compounds. From the structure-tyrosinase inhibitory activity relationship, it is notable that compounds 4, 8 and 11 showed similar or better activity rates than kojic acid which was used as a positive control. Compounds 17, 21, and 23 among benzene analogs that possess the same substituent showed significantly lower tyrosinase inhibitory effects. Therefore, we have confirmed that among the compounds showing better tyrosinase inhibitory effects than kojic acid, the compounds with triene analogs have better tyrosinase inhibitory effect than the compounds with benzene analogs. Docking simulation suggested the mechanism of compounds by several key residues which had possible hydrogen bonding interactions. The pharmacophore model underlined the features of active compounds, 4,4'-((1E,3E,5E)-hexa-1,3,5-triene-1,6-diyl)diphenol, 5,5'-((1E,3E,5E)-hexa-1,3,5-triene-1,6-diyl)bis(2-methoxy-phenol), and 5,5'-((1E,3E,5E)-hexa-1,3,5-triene-1,6-diyl)dibenzene-1,3-diol among triene derivatives which had several hydrogen bond groups on both terminal rings. The soundness of the docking results and the agreement with the pharmacophores suggest that it can be conveniently exploited to design inhibitors with an improved affinity for tyrosinase.

  14. Bag1 Co-chaperone Promotes TRC8 E3 Ligase-dependent Degradation of Misfolded Human Ether a Go-Go-related Gene (hERG) Potassium Channels.

    Science.gov (United States)

    Hantouche, Christine; Williamson, Brittany; Valinsky, William C; Solomon, Joshua; Shrier, Alvin; Young, Jason C

    2017-02-10

    Cardiac long QT syndrome type 2 is caused by mutations in the human ether a go-go-related gene (hERG) potassium channel, many of which cause misfolding and degradation at the endoplasmic reticulum instead of normal trafficking to the cell surface. The Hsc70/Hsp70 chaperones assist the folding of the hERG cytosolic domains. Here, we demonstrate that the Hsp70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at the endoplasmic reticulum to regulate hERG levels and channel activity. Dissociation of hERG complexes containing Hsp70 and the E3 ubiquitin ligase CHIP requires the interaction of Bag1 with Hsp70, but this does not involve the Bag1 ubiquitin-like domain. The interaction with Bag1 then shifts hERG degradation to the membrane-anchored E3 ligase TRC8 and its E2-conjugating enzyme Ube2g2, as determined by siRNA screening. TRC8 interacts through the transmembrane region with hERG and decreases hERG functional expression. TRC8 also mediates degradation of the misfolded hERG-G601S disease mutant, but pharmacological stabilization of the mutant structure prevents degradation. Our results identify TRC8 as a previously unknown Hsp70-independent quality control E3 ligase for hERG. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Three closely related (2E,2′E-3,3′-(1,4-phenylenebis[1-(methoxyphenylprop-2-en-1-ones]: supramolecular assemblies in one dimension mediated by hydrogen bonding and C—H...π interactions

    Directory of Open Access Journals (Sweden)

    Aijia Sim

    2017-06-01

    Full Text Available In the title compounds, (2E,2′E-3,3′-(1,4-phenylenebis[1-(2-methoxyphenylprop-2-en-1-one], C26H22O4 (I, (2E,2′E-3,3′-(1,4-phenylenebis[1-(3-methoxyphenylprop-2-en-1-one], C26H22O4 (II and (2E,2′E-3,3′-(1,4-phenylenebis[1-(3,4-dimethoxyphenylprop-2-en-1-one], C28H26O6 (III, the asymmetric unit consists of a half-molecule, completed by crystallographic inversion symmetry. The dihedral angles between the central and terminal benzene rings are 56.98 (8, 7.74 (7 and 7.73 (7° for (I, (II and (III, respectively. In the crystal of (I, molecules are linked by pairs of C—H...π interactions into chains running parallel to [101]. The packing for (II and (III, features inversion dimers linked by pairs of C—H...O hydrogen bonds, forming R22(16 and R22(14 ring motifs, respectively, as parts of [201] and [101] chains, respectively.

  16. Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase.

    Science.gov (United States)

    Mudhasani, Rajini; Tran, Julie P; Retterer, Cary; Kota, Krishna P; Whitehouse, Chris A; Bavari, Sina

    2016-02-01

    Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)(FBXW11) E3 ligase. NSs binds to the F-box protein, FBXW11, via the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through an alternate binding site to the SCF(FBXW11) E3 ligase. We further show that disrupting the assembly of the SCF(FBXW11-NSs) E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCF(FBXW11-NSs) E3 ligase is sufficient to inhibit RVFV infection. Furthermore, FBXW11 and BTRC are the two homologues of the βTrCP (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of βTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCF(FBXW11) complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection.

  17. Evaluation of a second trimester triple marker screening test for fetal status using alpha-fetoprotein (aFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3)

    International Nuclear Information System (INIS)

    Mi, Seong Young; Kim, Jong Ho; Choi, Seung Hun

    1997-01-01

    Our purpose was to assess the utility of maternal serum triple-marker screening test using alpha-fetoprotein (aFP), human Chorionic Gonadotropin (hCG) and unconjugated Estriol (uE 3 ) for fetal chromosomal abnormalities. 1,767 venous blood samples (4ml) between 15 and 20 week's gestation for maternal serum screening from January to October 1996, were tested with Kodak Amerix-M triple marker radioimmunoassay kits. Risk analysis was achieved with interpretive software such as Alpha (LMS, Kodak Clinical Diagnostics). Marker levels are transformed into multiples of median (MOM), which represent an interpretation of (weight regressed) patient marker levels relative to regressed median levels for stated gestation. By multivariate anaysis, the three MOM values are combined to generate a liklihood ratio. Calculation of a patient, risk is the product of liklihood ratio and age-related risk. Risk assessment is weight for maternal age. The median values of aFP, hCG and uE 3 were well correlated with gestational age, respectively (r=0.94, p=0.003; r=-0.97, p=0.029; r=0.99, p 3 weren't (r=-0.17, p=0.22; r=0.36, p=0.09, respectively). The values of aFP, CG and uE 3 between pregnancy younger than 35 years-old (n=87) and older than that (n=1640) were 51.67±27.44, vs 54.65±126.36, 46.45±30.08 vs 51.33±38.50 and 8.01±11.01 vs 6.68±7.23, respectively but all of them failed to show significant differences. A second-trimester risk for trisomy 21 > or = 1:270 was considered screen positive. Patients were screen positive for trisomy 21 if aFP or 2.1 MOM and E 3 2.5 MOM. The initial screen-positive rate for both Down' syndrome and neural tube defect were 1.46% (26/1767); 0.73% (13/1767) with each other. Among screen positive 26 patients, three and nine were normal karyotype and normal phenotype, respectively and five patients had still births. Reamining 9 patients underwent terminations. In conclusion, compared with the other group's data even in Koreans (Whang et al, and Song et al

  18. Policies and Predictions for a Low-Carbon Transition by 2050 in Passenger Vehicles in East Asia: Based on an Analysis Using the E3ME-FTT Model

    Directory of Open Access Journals (Sweden)

    Aileen Lam

    2018-05-01

    Full Text Available In this paper we apply a model of technological diffusion, Future Technology Transformations in the Transport Sector (FTT: Transport, linked to the E3ME macroeconomic model, to study possible future technological transitions in personal passenger transport in four East Asian countries. We assess how targeted policies could impact on these transitions by defining four scenarios based on policies that aim to reduce emissions from transport. For each country we find that an integrated approach of tax incentives, subsidies, regulations (fuel economy efficiency, kick-start programs and biofuel programs yield the most significant emission reductions because, when combined, they accelerate effectively the diffusion of electric vehicles in the region.

  19. Synthesis and structure of bis[(2E)-3-(2-furyl)prop-2-enoato]triphenylantimony Ph{sub 3}Sb[O{sub 2}CCH=CH(C{sub 4}H{sub 3}O)]{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Kalistratova, O. S., E-mail: Olga.Kalistratova@yandex.ru; Andreev, P. V.; Gushchin, A. V.; Somov, N. V.; Chuprunov, E. V. [Lobachevsky State University of Nizhny Novgorod (Russian Federation)

    2016-05-15

    Bis[(2E)-3-(2-furyl)prop-2-enoato]triphenylantimony Ph{sub 3}Sb[O{sub 2}CCH=CH(C{sub 4}H{sub 3}O)]{sub 2} is obtained for the first time by the reaction of triphenylantimony, hydrogen peroxide, and 2-furylpropene acid. The X-ray diffraction data show that the central atom of antimony is coordinated in the shape of a distorted trigonal bipyramid. The base of the bipyramid is formed by carbon atoms of phenyl ligands, and the apical vertices are occupied by acid residues. The IR and NMR spectra agree with the composition and structure of the compound.

  20. E3value to BPMN model transformation

    NARCIS (Netherlands)

    Fatemi, Hassan; van Sinderen, Marten J.; Wieringa, Roelf J.; Wieringa, P.A.; Camarinha-Matos, Luis M.; Pereira Klen, Alexandra; Afsarmanesh, Hamidesh

    2011-01-01

    Business value and coordination process perspectives need to be taken into consideration while modeling business collaborations. The need for these two models stems from the importance of separating the how from the what concerns. A business value model shows what is offered by whom to whom while a

  1. N′-[(E-3-Pyridylmethylidene]benzohydrazide

    Directory of Open Access Journals (Sweden)

    Liyuan Wen

    2009-11-01

    Full Text Available The title compound, C13H11N3O, was prepared by the reaction of benzohydrazide and nicotinaldehyde. The dihedral angle between the planes of the two aromatic rings is 47.78 (9°. The crystal structure is stabilized by intermolecular N—H...N hydrogen-bonding interactions.

  2. Experimental and computational approaches to the analysis of the molecular structure of (E)-3-(3-(4-nitrophenyl)triaz-1-en-1-yl)-1H-pyrazole-4-carbonitrile

    Science.gov (United States)

    Al-Azmi, Amal; Shalaby, Mona Abbas

    2018-03-01

    A green, fast and straightforward procedure for the synthesis of (E)-3-(3-(4-nitrophenyl)triaz-1-en-1-yl)-1H-pyrazole-4-carbonitrile is described in this paper. The method uses a coupling reaction between 4- nitrophenyl diazonium chloride and 5-aminopyrazole-4-carbonitrile. The structure is confirmed by different spectroscopic studies such as IR, NMR, HRMS and UV-vis spectroscopy in addition to X-ray single-crystal determination. The molecular geometry, vibrational frequencies and gauge-invariant atomic orbital (GIAO) 1H and 13C NMR chemical shift values of (E)-3-(3-(4-nitrophenyl)triaz-1-en-1-yl)-1H-pyrazole-4-carbonitrile are calculated in the ground state using the Hartree-Fock (HF) method and density functional theory (DFT) with the 6-31G(d) basis set, and are compared with the experimental data. The natural bond orbital (NBO) analysis is performed so as to discuss the stability of the molecule that arises from hyper conjugative interactions and charge delocalization. The electronic properties, such as HOMO and LUMO energies, were calculated using time dependent density functional theory (TD-DFT) approach.

  3. Dsc E3 ligase localization to the Golgi requires the ATPase Cdc48 and cofactor Ufd1 for activation of sterol regulatory element-binding protein in fission yeast.

    Science.gov (United States)

    Burr, Risa; Ribbens, Diedre; Raychaudhuri, Sumana; Stewart, Emerson V; Ho, Jason; Espenshade, Peter J

    2017-09-29

    Sterol regulatory element-binding proteins (SREBPs) in the fission yeast Schizosaccharomyces pombe regulate lipid homeostasis and the hypoxic response under conditions of low sterol or oxygen availability. SREBPs are cleaved in the Golgi through the combined action of the Dsc E3 ligase complex, the rhomboid protease Rbd2, and the essential ATPases associated with diverse cellular activities (AAA + ) ATPase Cdc48. The soluble SREBP N-terminal transcription factor domain is then released into the cytosol to enter the nucleus and regulate gene expression. Previously, we reported that Cdc48 binding to Rbd2 is required for Rbd2-mediated SREBP cleavage. Here, using affinity chromatography and mass spectrometry experiments, we identified Cdc48-binding proteins in S. pombe , generating a list of many previously unknown potential Cdc48-binding partners. We show that the established Cdc48 cofactor Ufd1 is required for SREBP cleavage but does not interact with the Cdc48-Rbd2 complex. Cdc48-Ufd1 is instead required at a step prior to Rbd2 function, during Golgi localization of the Dsc E3 ligase complex. Together, these findings demonstrate that two distinct Cdc48 complexes, Cdc48-Ufd1 and Cdc48-Rbd2, are required for SREBP activation and low-oxygen adaptation in S. pombe . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. The E3 ubiquitin ligases β-TrCP and FBXW7 cooperatively mediates GSK3-dependent Mcl-1 degradation induced by the Akt inhibitor API-1, resulting in apoptosis.

    Science.gov (United States)

    Ren, Hui; Koo, Junghui; Guan, Baoxiang; Yue, Ping; Deng, Xingming; Chen, Mingwei; Khuri, Fadlo R; Sun, Shi-Yong

    2013-11-22

    The novel Akt inhibitor, API-1, induces apoptosis through undefined mechanisms. The current study focuses on revealing the mechanisms by which API-1 induces apoptosis. API-1 rapidly and potently reduced the levels of Mcl-1 primarily in API-1-senstive lung cancer cell lines. Ectopic expression of Mcl-1 protected cells from induction of apoptosis by API-1. API-1 treatment decreased the half-life of Mcl-1, whereas inhibition of the proteasome with MG132 rescued Mcl-1 reduction induced by API-1. API-1 decreased Mcl-1 levels accompanied with a rapid increase in Mcl-1 phosphorylation (S159/T163). Moreover, inhibition of GSK3 inhibited Mcl-1 phosphorylation and reduction induced by API-1 and antagonized the effect of API-1 on induction of apoptosis. Knockdown of either FBXW7 or β-TrCP alone, both of which are E3 ubiquitin ligases involved in Mcl-1 degradation, only partially rescued Mcl-1 reduction induced by API-1. However, double knockdown of both E3 ubiquitin ligases enhanced the rescue of API-1-induced Mcl-1 reduction. API-1 induces GSK3-dependent, β-TrCP- and FBXW7-mediated Mcl-1 degradation, resulting in induction of apoptosis.

  5. Mechanistic aspects of the reaction between Br2 and chalcogenone donors (LE; E=S, Se): competitive formation of 10-E-3, T-shaped 1:1 molecular adducts, charge-transfer adducts, and [ (LE)2]2+ dications.

    Science.gov (United States)

    Aragoni, M C; Arca, M; Demartin, F; Devillanova, F A; Garau, A; Isaia, F; Lelj, F; Lippolis, V; Verani, G

    2001-07-16

    The synthesis and spectroscopic characterisation of the products obtained by treatment of N,N'-dimethylimidazolidine-2-thione (1), N,N'-dimethylimidazolidine-2-selone (2), N,N'-dimethylbenzoimidazole-2-thione (3) and N,N'-dimethylbenzoimidazole-2-selone (4) with Br2 in MeCN are reported, together with the crystal structures of the 10-E-3, T-shaped adducts 2 . Br2 (12), 3 . Br2 (13) and 4 . Br2 (14). A conductometric and spectrophotometric investigation into the reaction between 1-4 and Br2, carried out in MeCN, allows the equilibria involved in the formation of the isolated 10-E-3 (E = S, Se) hypervalent compounds to be hypothesised. In order to understand the reasons why S and Se donors can give different product types on treatment with Br2 and I2, DFT calculations have been carried out on 1-8, 19 and 20, and on their corresponding hypothetical [LEX]+ cations (L = organic framework; E = S, Se; X = Br, I), which are considered to be key intermediates in the formation of the different products. The results obtained in terms of NBO charge distribution on [LEX]+ species explain the different behaviour of 1-8, 19 and 20 in their reactions with Br2 and I2 fairly well. X-ray diffraction studies show 12-14 to have a T-shaped (10-E-3; E = S, Se) hypervalent chalcogen nature. They contain an almost linear Br-E-Br (E = S, Se) system roughly perpendicular to the average plane of the organic molecules. In 12, the Se atom of each adduct molecule has a short interaction with the Br(1) atom of an adjacent unit, such that the Se atom displays a roughly square planar coordination. The Se-Br distances are asymmetric [2.529(1) vs. 2.608(1) A], the shorter distance being that with the Br(1) atom involved in the short intermolecular contact. In contrast, in the molecular adducts 13 and 14, which lie on a two-fold crystallographic axis, the Br-E-Br system is symmetric and no short intermolecular interactions involving chalcogen and bromine atoms are observed. The adducts are arranged in

  6. Synthesis of (19E)-3 beta,7 alpha-dihydroxy-17-oxoandrost-5-en-19-al 19-(O-carboxymethyl)oxime, a new hapten for 7 alpha-hydroxydehydroepiandrosterone (3 beta,7 alpha-dihydroxyandrost-5-en-17-one).

    Science.gov (United States)

    Pouzar, V; Slavíková, T; Cerńy, I

    1998-09-01

    The title compound was prepared in 11 steps from 17,17-ethylenedioxy-19-hydroxyandrost-5-en-3 beta-yl acetate. After tert-butyldimethylsilyl protection of the 19-hydroxyl group, a 7-oxo group was introduced by oxidation with 3,5-dimethylpyrazole-chromium trioxide complex, and then selectively reduced with L-Selectride to give a 7 alpha-hydroxy derivative. This partially protected triol was acetylated and desilylated to 3,7-diacetate. Subsequent oxidation with pyridine-chromium trioxide complex gave 19-aldehyde, which was transformed into the corresponding protected 19-(O-carboxymethyl)oxime. Successive ketal cleavage, deacetylation, and methyl ester splitting gave the final (19E)-3 beta,7 alpha-dihydroxy-17-oxoandrost-5-en-19-al 19-(O-carboxymethyl)oxime, designed as a hapten for 7 alpha-hydroxydehydroepiandrosterone immunoassays.

  7. Molecular docking of (5E)-3-(2-aminoethyl)-5-(2- thienylmethylene)-1, 3-thiazolidine-2, 4-dione on HIV-1 reverse transcriptase: novel drug acting on enzyme.

    Science.gov (United States)

    Seniya, Chandrabhan; Yadav, Ajay; Uchadia, Kuldeep; Kumar, Sanjay; Sagar, Nitin; Shrivastava, Priyanka; Shrivastava, Shilpi; Wadhwa, Gulshan

    2012-01-01

    The study of Human immunodeficiency virus (HIV) in humans and animal models in last 31 years suggested that it is a causative agent of AIDS. This causes serious pandemic public health concern globally. It was reported that the HIV-1 reverse transcriptase (RT) played a critical role in the life cycle of HIV. Therefore, inhibition of HIV-1RT enzyme is one of the major and potential targets in the treatment of AIDS. The enzyme (HIV-1RT) was successfully targeted by non nucleotide reverse transcriptase inhibitors (NNRTIs). But frequent application of NNRTIs led drug resistance mutation on HIV infections. Therefore, there is a need to search new NNRTIs with appropriate pharmacophores. For the purpose, a virtually screened 3D model of unliganded HIV-1RT (1DLO) was explored. The unliganded HIV-1RT (1DLO) was docked with 4-thiazolidinone and its derivatives (ChemBank Database) by using AutoDock4. The best seven docking solutions complex were selected and analyzed by Ligplot. The analysis showed that derivative (5E)-3-(2- aminoethyl)-5-(2- thienylmethylene)-1, 3-thiazolidine-2, 4-dione (CID 3087795) has maximum potential against unliganded HIV-1RT (1DLO). The analysis was done on the basis of scoring and binding ability. The derivative (5E)-3-(2- aminoethyl)-5-(2- thienylmethylene)-1, 3-thiazolidine-2, 4-dione (CID 3087795) indicated minimum energy score and highest number of interactions with active site residue and could be a promising inhibitor for HIV-1 RT as Drug target.

  8. ANÁLISE QUALITATIVA DE SÓLIDOS ELASTOPLÁSTICOS SOB DEFORMAÇÃO FINITA UTILIZANDO ELEMENTOS DE BARRA BI-ARTICULADOS 2D E 3D

    Directory of Open Access Journals (Sweden)

    William Taylor Matias Silva

    2016-09-01

    Full Text Available RESUMO: Neste trabalho apresenta-se uma descrição Lagrangeana Total para retratar sólidos elastoplásticos sob deformação finita. Discretiza-se estes sólidos com elementos de treliça 2D e 3D com o intuito de obter analiticamente o vetor de forças internas e a matriz de rigidez tangente. Assume-se um modelo constitutivo hiperelástico para o estado uniaxial de tensão-deformação, utilizando a tensão de Kirchhoff e a deformação logarítmica, que formam um par energeticamente conjugado. Para descrever as deformações plásticas finitas utiliza-se a hipótese da decomposição multiplicativa do estiramento uniaxial do elemento de treliça. Por fim, apresentam-se algumas simulações numéricas de sólidos 3D discretizados com elementos de treliça 2D e 3D. ABSTRACT: This paper presents a Lagrangian Total description to describe elastoplastic solids under finite deformation. These solids are discretized with truss elements 2D and 3D aiming to obtain analytically internal force vector and the tangent stiffness matrix. Are assumed a hyperelastic constitutive model for the state of uniaxial stress-strain using the Kirchhoff's stress and logarithmic strain, to form a conjugate pair energetically. To describe the finite plastic deformation using the hypothesis of the multiplicative decomposition of uniaxial stretching of the truss element. Finally, we present some numerical simulations of solid 3D discretized with 2D and 3D truss elements.

  9. Micronutrient dietary patterns associated with type 2 diabetes mellitus among women of the E3N-EPIC (Etude Epidémiologique auprès de femmes de l'Education Nationale) cohort study.

    Science.gov (United States)

    Mancini, Francesca Romana; Dow, Courtney; Affret, Aurélie; Rajaobelina, Kalina; Dartois, Laureen; Balkau, Beverley; Bonnet, Fabrice; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy

    2018-02-19

    Micronutrients play a key role in type 2 diabetes mellitus (T2DM), but methodological difficulties arise from their collinearity and interdependencies with foods. The aim of the present study was to identify micronutrient dietary patterns in the E3N-EPIC (Etude Epidémiologique auprès de femmes de l'Education Nationale) cohort and to investigate their association with risk of T2DM. Principal component analysis was used to identify micronutrient patterns among 71 270 women from the E3N-EPIC cohort. Associations between micronutrient patterns and risk of T2DM were quantified by hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazards regression models, adjusted for potential confounders. Six micronutrient patterns were identified explaining 78% of the total variance in micronutrient intake. A positive association was found between T2DM and a pattern highly correlated with intake of vitamins B 2 and B 5 (HR 1.34; 95% CI 1.16-1.56). Similarly, a positive association was found with a pattern characterized by high intakes of vitamin B 12 and retinol, and a low intake of vitamin C (HR 1.30; 95% CI 1.15-1.48). An inverse association was observed between T2DM and another two patterns: one correlated with magnesium and vitamin B 3 (HR 0.75; 95% CI 0.66-0.86), and the other correlated with manganese intake (HR 0.82; 95% CI 0.72-0.94). The findings of the present study identify micronutrients that have an effect on the risk of T2DM, and enable better understanding of the complexity of the diet when investigating the association between micronutrients and T2DM. © 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  10. A proposed visible FEL Facility at Boeing

    Energy Technology Data Exchange (ETDEWEB)

    Dowell, D.H.; Adamski, J.L.; Hayward, T.D. [Boeing Defense & Space Group, Seattle, WA (United States)] [and others

    1995-12-31

    A 1-kW average power, visible wavelength FEL is described, based on a 120-MeV, 0.1. A macropulse average current linac operating at a duty factor of 0. 6% and having average beam power of 70 kW. The accelerator will employ a demonstrated photoinjector, 18-MeV, 433-MHz linac as an injector, followed by a 1300-MHz longitudinal phase space {open_quotes} linearizer,{close_quotes} a magnetic buncher chicane, and seven 1300-MHz, pulsed traveling wave linac sections. The magnets used to transport the beam from the linac to the FEL centerline, the 5-m THUNDER wiggler, and the optical resonator will be reclaimed from previous FEL demonstration experiments. We expect to attain pulse lengths of 7 ps for 3.5 nC, with minimal distortion of the pulse profile and normalized rms emittance of 7.5 {+-} 2.5 {pi} mm-mr. FELEX projects a laser conversion efficiency of 4.3 %, yielding average output of 3 kW.

  11. AEMS implementation cost study for Boeing 727

    Science.gov (United States)

    Allison, R. L.

    1977-01-01

    Costs for airline operational implementation of a NASA-developed approach energy management system (AEMS) concept, as applied to the 727 airplane, were determined. Estimated costs are provided for airplane retrofit and for installation of the required DME ground stations. Operational costs and fuel cost savings are presented in a cost-of-ownership study. The potential return on the equipment investment is evaluated using a net present value method. Scheduled 727 traffic and existing VASI, ILS, and collocated DME ground station facilities are summarized for domestic airports used by 727 operators.

  12. Perfil comunicativo de crianças entre 1 e 3 anos com desenvolvimento normal de linguagem Communicative profile of children between 1 and 3-years old with normal language development

    Directory of Open Access Journals (Sweden)

    Mirtes Adiles Sandri

    2009-03-01

    Full Text Available OBJETIVO: traçar o perfil comunicativo (habilidades comunicativas e interacionais, compreensão verbal e aspectos do desenvolvimento cognitivo de crianças entre 1 e 3 anos com desenvolvimento normal da linguagem, correlacionando com as variáveis faixa etária e gênero. MÉTODOS: participaram do estudo 24 crianças (12 meninos e 12 meninas, divididas em dois grupos: Grupo 1 (G1 - crianças de 1 e 2 anos e Grupo 2 (G2 - crianças de 2 e 3 anos. O instrumento de avaliação utilizado foi o Protocolo de Observação Comportamental (PROC (Zorzi e Hage, 2004. RESULTADOS: na análise dos dados quantitativos houve diferença estatisticamente significante quando comparados os grupos por faixa etária (PPURPOSE: to trace the communicative profile (communicative and interactive abilities, verbal comprehension and cognitive development aspects of children with normal linguistic development between 1 and 3-year old, correlating with the variables of age groups and gender. METHODS: twenty-four children (12 boys and 12 girls took part in the study, divided in two groups: Group 1 (G1 - children between 1 and 2-year old, and Group 2 (G2 -children between 2 and 3-year old. The used protocol was Behavioral Observation Protocol ("Protocolo de Observação Comportamental - PROC" (Zorzi and Hage, 2004. RESULTS: there was a statistically significant difference in the quantitative data when the groups where compared by their age (P<0.05. When comparing qualitative data by their age group, children of the G2 were better (P<0.05, except in the item with regards to the oral language understanding, which resulted being equivalent between the groups (P=0.217. There was no significant statistical difference related to gender, however, we observed superiority in female gender. CONCLUSION: the used test was sensitive for identifying the differences in performance between the two age groups, with regards to the communicative profile of the studied children.

  13. The small ubiquitin-like modifier E3 ligase MdSIZ1 promotes anthocyanin accumulation by sumoylating MdMYB1 under low-temperature conditions in apple.

    Science.gov (United States)

    Zhou, Li-Jie; Li, Yuan-Yuan; Zhang, Rui-Fen; Zhang, Chun-Ling; Xie, Xing-Bin; Zhao, Cheng; Hao, Yu-Jin

    2017-10-01

    MdMYB1 acts as a crucial component of the MYB-bHLH-WD40 complex to regulate anthocyanin biosynthesis in red-skinned apples (Malus domestica), but little is known about its post-translational regulation. Here, a small ubiquitin-like modifier E3 ligase MdSIZ1 was screened out as an MdMYB1-interacting protein with a yeast two-hybridization approach. The interaction between MdSIZ1 and MdMYB1 was further verified with pull-down and CoIP assays. Furthermore, it was found that MdSIZ1 directly sumoylated MdMYB1 proteins in vivo and in vitro, especially under moderately low temperature (17 °C) conditions, and that this sumoylation was required for MdMYB1 protein stability. Moreover, the transcription level of MdSIZ1 gene was remarkably induced by low temperature and phosphorus deficiency, and MdSIZ1 overexpression exerted a large positive influence on anthocyanin accumulation and red fruit coloration, suggesting its important role in the regulation of anthocyanin biosynthesis under stress conditions. Our findings reveal an important role for a small ubiquitin-like modifier modification of MYB transcription factors in regulation of anthocyanin biosynthesis in plants. © 2017 John Wiley & Sons Ltd.

  14. Synthesis, structural studies and antimicrobial activity of N'-((2Z, 3E)-3-(hydroxyimino)butan-2-ylidene)-2-phenylacetohydrazide and its Co(II), Ni(II) complexes

    Science.gov (United States)

    Karadeniz, Şeyma; Ataol, Cigdem Yuksektepe; Şahin, Onur; İdil, Önder; Bati, Hümeyra

    2018-06-01

    A new aroylhydrazoneoxime, N'-((2Z, 3E)-3-(hydroxyimino)butan-2-ylidene)-2-phenylacetohydrazide ligand (LH2) and its Ni(II) and Co(II) complexes, have been synthesized and characterized by elemental and thermal analyses, IR and UV-vis spectroscopy, magnetic moment and X-ray diffraction. The antimicrobial activities of these compounds were tested by using minimal inhibitory concentration method (MIC). The ligand-containing aroylhydrazone and oxime groups and its Ni complex crystallize in the triclinic system and P 1 - space group, while its Co complex crystallizes in the monoclinic system and the C 2/c space group. X-ray results show that the ligand in the keto form is transformed into enolic form when it forms coordination. From elemental analysis data, the stoichiometry of Co(II) complex was found to be 1:2 (metal/ligand), but 1:1 for Ni(II). IR spectra indicate that the ligand acts as monoanionic NNO- tridentate and coordination takes place form through the oxime nitrogen, imine nitrogen, and enolate oxygen atoms.

  15. Effects of probiotic Lactobacillus rhamnosus GG and Propionibacterium freudenreichii ssp. shermanii JS supplementation on intestinal and systemic markers of inflammation in ApoE*3Leiden mice consuming a high-fat diet.

    Science.gov (United States)

    Oksaharju, Anna; Kooistra, Teake; Kleemann, Robert; van Duyvenvoorde, Wim; Miettinen, Minja; Lappalainen, Jani; Lindstedt, Ken A; Kovanen, Petri T; Korpela, Riitta; Kekkonen, Riina A

    2013-07-14

    A high-fat diet disturbs the composition and function of the gut microbiota and generates local gut-associated and also systemic responses. Intestinal mast cells, for their part, secrete mediators which play a role in the orchestration of physiological and immunological functions of the intestine. Probiotic bacteria, again, help to maintain the homeostasis of the gut microbiota by protecting the gut epithelium and regulating the local immune system. In the present study, we explored the effects of two probiotic bacteria, Lactobacillus rhamnosus GG (GG) and Propionibacterium freudenreichii spp. shermanii JS (PJS), on high fat-fed ApoE*3Leiden mice by estimating the mast cell numbers and the immunoreactivity of TNF-α and IL-10 in the intestine, as well as plasma levels of several markers of inflammation and parameters of lipid metabolism. We found that mice that received GG and PJS exhibited significantly lower numbers of intestinal mast cells compared with control mice. PJS lowered intestinal immunoreactivity of TNF-α, while GG increased intestinal IL-10. PJS was also observed to lower the plasma levels of markers of inflammation including vascular cell adhesion molecule 1, and also the amount of gonadal adipose tissue. GG lowered alanine aminotransferase, a marker of hepatocellular activation. Collectively, these data demonstrate that probiotic GG and PJS tend to down-regulate both intestinal and systemic pro-inflammatory changes induced by a high-fat diet in this humanised mouse model.

  16. Change in the conversion rate for the E3-isomer sup(235m)U (76,8 eV; 1/2+ → 7/2-) at variation of configurations of the valence band of the atomic shell

    International Nuclear Information System (INIS)

    Grechukhin, D.P.; Soldatov, A.A.

    1983-01-01

    In the framework of the relativistic Hartree-Fock-Slater method, a change of the conversion rate lambda for the E3 isomer (at the transition energy of h/2πω=77 eV) with respect to the rate lambda for the normal configuration of uranium atom, (7ssup(1/2)sup(2)(6dsup(3/2))sup(1)(5fsup(5/2))sup(3), is calcUlated for 14 configurations of the valence band of the atomic shell, including considerable variations of the occupation numbers in 6d, 7s, and 5f orbits. A very strong change Δlambda/lambda 1 is found to be due to variation of the occupation number for the 5f orbit (ΔN(5f) not equal to 0); the change amounts to about 8% per ΔN(5f)=+-1, that is an order of magnitude higher than Δlambda/lambda 1 due to variations of the occupation numbers for other orbits in the cases where N(5f)=const. Though the direct contribution from the 5f electrons to the conversion is very small ( 1 for ΔN(5f) not equal to 0. A rigid correlation between the partial conversion rate and the r. m. s. radius of the orbit is obtained for 6p orbits

  17. Synthesis and structural study on (1E,2E,1'E,2'E)-3,3'-bis[(4-bromophenyl)-3,3'-(4-methy-1,2-phenylene diimine)] acetaldehyde dioxime: A combined experimental and theoretical study

    Science.gov (United States)

    Topal, T.; Kart, H. H.; Tunay Taşlı, P.; Karapınar, E.

    2015-06-01

    Tetradentate (1E,2E,1'E,2'E)-3,3'-bis[(4-bromophenyl)-3,3'-(4-methy-1,2-phenylene diimine)] acetaldehyde dioxime which possess N4 donor sets derived from the condensation of isonitroso- p-bromoacetophenone and 3,4-diaminotoluene are synthesized and characterized. The characterization of tetradentate Schiff base ligand has been deduced from LC-MS, FTIR, 13C and 1H NMR spectra and elemental analysis. Furthermore, the molecular geometry, infrared and NMR spectra of the title molecule in the ground state have been calculated by using the quantum chemical computational methods such as density functional theory (DFT) and ab initio Hartree-Fock (HF) methods with the 6-31G(d) and 6-311G(d) basis sets. The computed bond lengths and bond angles by using the both methods show the good agreement with each other. Moreover, the vibrational frequencies have been calculated and the scaled values have been compared with the experimental FTIR spectroscopic data. Assignments of the vibrational modes are made on the basis of potential energy distribution (PED) calculated from by using VEDA program. The correlations between the observed and calculated frequencies are in good agreement with each other as well as the correlation of the NMR data.

  18. Dependence of stratocumulus-topped boundary-layer entrainment on cloud-water sedimentation: Impact on global aerosol indirect effect in GISS ModelE3 single column model and global simulations

    Science.gov (United States)

    Ackerman, A. S.; Kelley, M.; Cheng, Y.; Fridlind, A. M.; Del Genio, A. D.; Bauer, S.

    2017-12-01

    Reduction in cloud-water sedimentation induced by increasing droplet concentrations has been shown in large-eddy simulations (LES) and direct numerical simulation (DNS) to enhance boundary-layer entrainment, thereby reducing cloud liquid water path and offsetting the Twomey effect when the overlying air is sufficiently dry, which is typical. Among recent upgrades to ModelE3, the latest version of the NASA Goddard Institute for Space Studies (GISS) general circulation model (GCM), are a two-moment stratiform cloud microphysics treatment with prognostic precipitation and a moist turbulence scheme that includes an option in its entrainment closure of a simple parameterization for the effect of cloud-water sedimentation. Single column model (SCM) simulations are compared to LES results for a stratocumulus case study and show that invoking the sedimentation-entrainment parameterization option indeed reduces the dependence of cloud liquid water path on increasing aerosol concentrations. Impacts of variations of the SCM configuration and the sedimentation-entrainment parameterization will be explored. Its impact on global aerosol indirect forcing in the framework of idealized atmospheric GCM simulations will also be assessed.

  19. Novel (1E,3E,5E-1,6-bis(Substituted phenylhexa-1,3,5-triene Analogs Inhibit Melanogenesis in B16F10 Cells and Zebrafish

    Directory of Open Access Journals (Sweden)

    Jisun Oh

    2018-04-01

    Full Text Available The present study aimed to evaluate the anti-melanogenic activity of 1,6-diphenyl-1,3,5-hexatriene and its derivatives in B16F10 murine melanoma cells and zebrafish embryos. Twenty five (1E,3E,5E-1,6-bis(substituted phenylhexa-1,3,5-triene analogs were synthesized and their non-cytotoxic effects were predictively analyzed using three-dimensional quantitative structure-activity relationship approach. Inhibitory activities of these synthetic compounds against melanin synthesis were determined by evaluating melanin content and melanogenic regulatory enzyme expression in B16F10 cells. The anti-melanogenic activity was verified by observing body pigmentation in zebrafishes treated with these compounds. Compound #2, #4, and #6 effectively decreased melanogenesis induced by α-melanocyte-stimulating hormone. In particular, compound #2 remarkably lowered the mRNA and protein expression levels of microphthalmia-associated transcription factor (MITF, tyrosinase (TYR, tyrosinase-related protein 1 (TYRP1, and TYRP2 in B16F10 cells and substantially reduced skin pigmentation in the developed larvae of zebrafish. These findings suggest that compound #2 may be used as an anti-melanogenic agent for cosmetic purpose.

  20. In vitro anti-Candida activity and single crystal X-ray structure of ({(1E-[3-(1H-imidazol-1-yl-1-phenylpropylidene]amino}oxy(4-nitrophenylmethanone

    Directory of Open Access Journals (Sweden)

    Mohamed I. Attia

    2014-03-01

    Full Text Available Synthesis, characterization, and anti-Candida activity of ({(E-[3-(1H-imidazol-1-yl-1-phenylpropylidene]amino}oxy(4-nitrophenylmethanone (4 are repor-ted. Compound 4 showed anti-Candida albicans activity (MIC = 0.6862 µmol/mL being nearly 5-fold more potent than the gold standard antifungal drug, fluconazole (MIC ˃ 3.265 µmol/mL, on the clinical isolates of Candida albicans. Single crystal X-ray structure of the title compound 4 confirmed its assigned (E-configuration. The compound crystallizes in the triclinic, P-1 (no. 2, a = 6.4633 (1 Å, b = 11.1063 (2 Å, c = 12.9872 (2 Å, α = 67.650 (1°, β = 86.415 (1°, γ = 86.776 (1°, V = 860.01 (3Å3, Z = 2, R(F = 0.046, wR(F2 = 0.139, T = 296 K. The crystal structure is stabilized by weak intermolecular C—H•••O hydrogen interactions.