Sample records for additional protocol ap

  1. U.S. Additional Protocol Outreach Program-Tabletop Exercises to Implement the AP.

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

    Langner, D. C.; Thomas, K. E.; Smith, M. K.

    2005-01-01

    The Office of International Regimes and Agreement (NA-243) is the lead office in the Department of Energy (DOE) to assist DOE and National Nuclear Security Administration (NNSA) sites in the preparation of providing declarations on relevant civilian, nuclear fuel cycle-related research and development activities to the International Atomic Energy Agency (IAEA). This is in accordance to the implementation of the ''Protocol Additional to the AGreement between the United STates and the International Atomic Energy Agency for the Applications of Safeguards in the United States. In preparation for entry-into-force, NA-243 conducted two tabletop exercises under the Additional Protocol Outreach Program. Themore » first one, held in May 2004 at Los Alamos National Laboratory, focused on the factors important to protect national security assets and intellectual property. The other, held in August 2004 at the Idaho National Laboratory explored the level of detail or granularity for reporting declarable activities. Both tabletops invited participants from the national laboratories and DOE/NNSA organizations. Discussions were based around the process to identify potential declarable activities relating to the nuclear fuel cycle-related R and D projects from the Advanced Fuel Cycle Initiative program. The two tabletop exercises provided recommendations and conclusions that would be helpful to other DOE/NNSA locations for preparing for and reporting relevant and concise information to the IAEA under the Additional Protocol. This paper provides details on the events, discussions, observations, and lessons learned from both the LANL and INL tabletop exercises.« less

  2. Developments in Assisting Countries in Implementing the IAEA Additional Protocol

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

    Killinger, Mark H.; Hansen, Linda H.; Cain, Ronald A.

    In 2008, the U.S. Department of Energy (DOE) began assisting selected non-nuclear weapon states in planning and preparing for implementation of the International Atomic Energy Agency’s Additional Protocol (AP). Since then, the AP international implementation program has contributed to the substantial progress made by Vietnam, Thailand, Iraq, and Malaysia in preparing for entry-into-force of the AP. An overall engagement plan has been developed with components designed to train government AP implementing agencies, inform policy makers, conduct outreach to industry and universities, make AP reporting software available and useful, and plan a detailed approach for implementing the declaration and complementary accessmore » provisions of the AP. DOE recently began collaborating with Indonesia, which has already entered the AP into force, requiring a second method of engagement somewhat different from that taken with countries that have not entered the AP into force. The AP international implementation program, administered by the International Nuclear Safeguards and Engagement Program, is working more closely with DOE’s International Nonproliferation Export Control Program to ensure countries are aware of and prepared to implement the export/import provisions of the AP. As the AP implementation program matures and helps move countries closer to entry-into-force or improved AP implementation, it is identifying characteristics of a country’s “end-state” that indicate that DOE assistance is no longer required. The U.S. AP Implementation Act and Senate Resolution of Ratification require the Administration to report annually to Congress on measures taken to achieve the adoption of the AP in non-nuclear weapon states. DOE’s AP international implementation program is a significant part of these measures. This paper describes recent developments to increase the scope and effectiveness of the program.« less

  3. Layered Electrical Product Application Protocol (AP). Draft: Initial Graphics Exchange Specification (IGES)

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

    Not Available

    1994-09-01

    An application protocol is an information systems engineering view of a specific product. The view represents an agreement on the generic activities needed to design and fabricate the product, the agreement on the information needed to support those activities, and the specific constructs of a product data standard for use in transfering some or all of the information required. This applications protocol describes the data for electrical and electronic products in terms of a product description standard called the Initial Graphics Exchange Specification (IGES). More specifically, the Layered Electrical Product IGES Application Protocol (AP) specifies the mechanisms for defining andmore » exchanging computer-models and their associated data for those products which have been designed in two dimensional geometry so as to be produced as a series of layers in IGES format. The AP defines the appropriateness of the data items for describing the geometry of the various parts of a product (shape and location), the connectivity, and the processing and material characteristics. Excluded is the behavioral requirements which the product was intended to satisfy, except as those requirements have been recorded as design rules or product testing requirements.« less

  4. Report on July 2015 Additional Protocol Coordinators Best Practices Workshop

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

    Gitau, Ernest T.N.; Burbank, Roberta L.; Finch, Valerie A.

    After 10 years of implementation experience, the Office of Nonproliferation and Arms Control (NPAC) within the Department of Energy/National Nuclear Security Administration (DOE/NNSA) conducted the Additional Protocol (AP) Coordinators Best Practices Workshop at Oak Ridge National Laboratory from July 29-30, 2015. The goal of this workshop was to identify implementation best practices, lessons learned, and compliance challenges from the various Additional Protocol Coordinators (APCs) at each laboratory in the DOE/NNSA complex and associated sites. The workshop provided the opportunity for participants to share their insights and establish networks that APCs can utilize to continue to discuss challenges (new and old),more » identify best practices, and enhance communication and coordination for reporting multi-lab research projects during review activities. Workshop participants included DOE/NNSA HQ, laboratory and site APCs, seasoned experts, members of the original implementation outreach team, and Field Element and site security representatives.« less

  5. Experimental Evaluation of Unicast and Multicast CoAP Group Communication

    PubMed Central

    Ishaq, Isam; Hoebeke, Jeroen; Moerman, Ingrid; Demeester, Piet

    2016-01-01

    The Internet of Things (IoT) is expanding rapidly to new domains in which embedded devices play a key role and gradually outnumber traditionally-connected devices. These devices are often constrained in their resources and are thus unable to run standard Internet protocols. The Constrained Application Protocol (CoAP) is a new alternative standard protocol that implements the same principals as the Hypertext Transfer Protocol (HTTP), but is tailored towards constrained devices. In many IoT application domains, devices need to be addressed in groups in addition to being addressable individually. Two main approaches are currently being proposed in the IoT community for CoAP-based group communication. The main difference between the two approaches lies in the underlying communication type: multicast versus unicast. In this article, we experimentally evaluate those two approaches using two wireless sensor testbeds and under different test conditions. We highlight the pros and cons of each of them and propose combining these approaches in a hybrid solution to better suit certain use case requirements. Additionally, we provide a solution for multicast-based group membership management using CoAP. PMID:27455262

  6. Department of Energy Efforts to Promote Universal Adherence to the IAEA Additional Protocol

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

    Killinger, Mark H.; Hansen, Linda H.; Kovacic, Don N.

    2009-10-06

    Entry-into-force of the U.S. Additional Protocol (AP) in January 2009 continues to demonstrate the ongoing commitment by the United States to promote universal adherence to the AP. The AP is a critical tool for improving the International Atomic Energy Agency’s (IAEA) capabilities to detect undeclared activities that indicate a clandestine nuclear weapons program. This is because States Parties are required to provide information about, and access to, nuclear fuel cycle activities beyond their traditional safeguards reporting requirements. As part of the U.S. AP Implementation Act and Senate Resolution of Ratification, the Administration is required to report annually to Congress onmore » measures taken to achieve the adoption of the AP in non-nuclear weapon states, as well as assistance to the IAEA to promote the effective implementation of APs in those states. A key U.S. effort in this area is being managed by the International Nuclear Safeguards and Engagement Program (INSEP) of the U.S. Department of Energy (DOE). Through new and existing bilateral cooperation agreements, INSEP has initiated technical assistance projects for AP implementation with selected non-weapon states. States with which INSEP is currently cooperating include Vietnam and Thailand, with Indonesia, Algeria, Morocco, and other countries as possible future collaborators in the area of AP implementation. The INSEP collaborative model begins with a joint assessment with our partners to identify specific needs they may have regarding entering the AP into force and any impediments to successful implementation. An action plan is then developed detailing and prioritizing the necessary joint activities. Such assistance may include: advice on developing legal frameworks and regulatory documents; workshops to promote understanding of AP requirements; training to determine possible declarable activities; assistance in developing a system to collect and submit declarations; performing industry

  7. Effects of aluminum and iron nanoparticle additives on composite AP/HTPB solid propellant regression rate

    NASA Astrophysics Data System (ADS)

    Styborski, Jeremy A.

    This project was started in the interest of supplementing existing data on additives to composite solid propellants. The study on the addition of iron and aluminum nanoparticles to composite AP/HTPB propellants was conducted at the Combustion and Energy Systems Laboratory at RPI in the new strand-burner experiment setup. For this study, a large literature review was conducted on history of solid propellant combustion modeling and the empirical results of tests on binders, plasticizers, AP particle size, and additives. The study focused on the addition of nano-scale aluminum and iron in small concentrations to AP/HTPB solid propellants with an average AP particle size of 200 microns. Replacing 1% of the propellant's AP with 40-60 nm aluminum particles produced no change in combustive behavior. The addition of 1% 60-80 nm iron particles produced a significant increase in burn rate, although the increase was lesser at higher pressures. These results are summarized in Table 2. The increase in the burn rate at all pressures due to the addition of iron nanoparticles warranted further study on the effect of concentration of iron. Tests conducted at 10 atm showed that the mean regression rate varied with iron concentration, peaking at 1% and 3%. Regardless of the iron concentration, the regression rate was higher than the baseline AP/HTPB propellants. These results are summarized in Table 3.

  8. A CoAP-Based Network Access Authentication Service for Low-Power Wide Area Networks: LO-CoAP-EAP.

    PubMed

    Garcia-Carrillo, Dan; Marin-Lopez, Rafael; Kandasamy, Arunprabhu; Pelov, Alexander

    2017-11-17

    The Internet-of-Things (IoT) landscape is expanding with new radio technologies. In addition to the Low-Rate Wireless Personal Area Network (LR-WPAN), the recent set of technologies conforming the so-called Low-Power Wide Area Networks (LP-WAN) offers long-range communications, allowing one to send small pieces of information at a reduced energy cost, which promotes the creation of new IoT applications and services. However, LP-WAN technologies pose new challenges since they have strong limitations in the available bandwidth. In general, a first step prior to a smart object being able to gain access to the network is the process of network access authentication. It involves authentication, authorization and key management operations. This process is of vital importance for operators to control network resources. However, proposals for managing network access authentication in LP-WAN are tailored to the specifics of each technology, which could introduce interoperability problems in the future. In this sense, little effort has been put so far into providing a wireless-independent solution for network access authentication in the area of LP-WAN. To fill this gap, we propose a service named Low-Overhead CoAP-EAP (LO-CoAP-EAP), which is based on previous work designed for LR-WPAN. LO-CoAP-EAP integrates the use of Authentication, Authorization and Accounting (AAA) infrastructures and the Extensible Authentication Protocol (EAP) protocol. For this integration, we use the Constrained Application Protocol (CoAP) to design a network authentication service independent of the type of LP-WAN technology. LO-CoAP-EAP represents a trade-off between flexibility, wireless technology independence, scalability and performance in LP-WAN.

  9. A CoAP-Based Network Access Authentication Service for Low-Power Wide Area Networks: LO-CoAP-EAP

    PubMed Central

    Garcia-Carrillo, Dan; Marin-Lopez, Rafael; Kandasamy, Arunprabhu; Pelov, Alexander

    2017-01-01

    The Internet-of-Things (IoT) landscape is expanding with new radio technologies. In addition to the Low-Rate Wireless Personal Area Network (LR-WPAN), the recent set of technologies conforming the so-called Low-Power Wide Area Networks (LP-WAN) offers long-range communications, allowing one to send small pieces of information at a reduced energy cost, which promotes the creation of new IoT applications and services. However, LP-WAN technologies pose new challenges since they have strong limitations in the available bandwidth. In general, a first step prior to a smart object being able to gain access to the network is the process of network access authentication. It involves authentication, authorization and key management operations. This process is of vital importance for operators to control network resources. However, proposals for managing network access authentication in LP-WAN are tailored to the specifics of each technology, which could introduce interoperability problems in the future. In this sense, little effort has been put so far into providing a wireless-independent solution for network access authentication in the area of LP-WAN. To fill this gap, we propose a service named Low-Overhead CoAP-EAP (LO-CoAP-EAP), which is based on previous work designed for LR-WPAN. LO-CoAP-EAP integrates the use of Authentication, Authorization and Accounting (AAA) infrastructures and the Extensible Authentication Protocol (EAP) protocol. For this integration, we use the Constrained Application Protocol (CoAP) to design a network authentication service independent of the type of LP-WAN technology. LO-CoAP-EAP represents a trade-off between flexibility, wireless technology independence, scalability and performance in LP-WAN. PMID:29149040

  10. CoAP-Based Mobility Management for the Internet of Things

    PubMed Central

    Chun, Seung-Man; Kim, Hyun-Su; Park, Jong-Tae

    2015-01-01

    Most of the current mobility management protocols such as Mobile IP and its variants standardized by the IETF may not be suitable to support mobility management for Web-based applications in an Internet of Things (IoT) environment. This is because the sensor nodes have limited power capacity, usually operating in sleep/wakeup mode in a constrained wireless network. In addition, sometimes the sensor nodes may act as the server using the CoAP protocol in an IoT environment. This makes it difficult for Web clients to properly retrieve the sensing data from the mobile sensor nodes in an IoT environment. In this article, we propose a mobility management protocol, named CoMP, which can effectively retrieve the sensing data of sensor nodes while they are moving. The salient feature of CoMP is that it makes use of the IETF CoAP protocol for mobility management, instead of using Mobile IP. Thus CoMP can eliminates the additional signaling overhead of Mobile IP, provides reliable mobility management, and prevents the packet loss. CoMP employs a separate location management server to keep track of the location of the mobile sensor nodes. In order to prevent the loss of important sensing data during movement, a holding mode of operation has been introduced. All the signaling procedures including discovery, registration, binding and holding have been designed by extending the IETF CoAP protocol. The numerical analysis and simulation have been done for performance evaluation in terms of the handover latency and packet loss. The results show that the proposed CoMP is superior to previous mobility management protocols, i.e., Mobile IPv4/v6 (MIPv4/v6), Hierarchical Mobile IPv4/v6 (HMIPv4/v6), in terms of the handover latency and packet loss. PMID:26151214

  11. Lightweight CoAP-Based Bootstrapping Service for the Internet of Things.

    PubMed

    Garcia-Carrillo, Dan; Marin-Lopez, Rafael

    2016-03-11

    The Internet of Things (IoT) is becoming increasingly important in several fields of industrial applications and personal applications, such as medical e-health, smart cities, etc. The research into protocols and security aspects related to this area is continuously advancing in making these networks more reliable and secure, taking into account these aspects by design. Bootstrapping is a procedure by which a user obtains key material and configuration information, among other parameters, to operate as an authenticated party in a security domain. Until now solutions have focused on re-using security protocols that were not developed for IoT constraints. For this reason, in this work we propose a design and implementation of a lightweight bootstrapping service for IoT networks that leverages one of the application protocols used in IoT : Constrained Application Protocol (CoAP). Additionally, in order to provide flexibility, scalability, support for large scale deployment, accountability and identity federation, our design uses technologies such as the Extensible Authentication Protocol (EAP) and Authentication Authorization and Accounting (AAA). We have named this service CoAP-EAP. First, we review the state of the art in the field of bootstrapping and specifically for IoT. Second, we detail the bootstrapping service: the architecture with entities and interfaces and the flow operation. Third, we obtain performance measurements of CoAP-EAP (bootstrapping time, memory footprint, message processing time, message length and energy consumption) and compare them with PANATIKI. The most significant and constrained representative of the bootstrapping solutions related with CoAP-EAP. As we will show, our solution provides significant improvements, mainly due to an important reduction of the message length.

  12. Lightweight CoAP-Based Bootstrapping Service for the Internet of Things

    PubMed Central

    Garcia-Carrillo, Dan; Marin-Lopez, Rafael

    2016-01-01

    The Internet of Things (IoT) is becoming increasingly important in several fields of industrial applications and personal applications, such as medical e-health, smart cities, etc. The research into protocols and security aspects related to this area is continuously advancing in making these networks more reliable and secure, taking into account these aspects by design. Bootstrapping is a procedure by which a user obtains key material and configuration information, among other parameters, to operate as an authenticated party in a security domain. Until now solutions have focused on re-using security protocols that were not developed for IoT constraints. For this reason, in this work we propose a design and implementation of a lightweight bootstrapping service for IoT networks that leverages one of the application protocols used in IoT : Constrained Application Protocol (CoAP). Additionally, in order to provide flexibility, scalability, support for large scale deployment, accountability and identity federation, our design uses technologies such as the Extensible Authentication Protocol (EAP) and Authentication Authorization and Accounting (AAA). We have named this service CoAP-EAP. First, we review the state of the art in the field of bootstrapping and specifically for IoT. Second, we detail the bootstrapping service: the architecture with entities and interfaces and the flow operation. Third, we obtain performance measurements of CoAP-EAP (bootstrapping time, memory footprint, message processing time, message length and energy consumption) and compare them with PANATIKI. The most significant and constrained representative of the bootstrapping solutions related with CoAP-EAP. As we will show, our solution provides significant improvements, mainly due to an important reduction of the message length. PMID:26978362

  13. Effect of diadenosine tetraphosphate (AP4A) on coronary arterial microvessels in the beating canine heart.

    PubMed

    Sugimura, A; Kanatsuka, H; Tanikawa, T; Ong, B H; Shirato, K

    2000-11-01

    Diadenosine tetraphosphate (AP4A) can be released from activated platelets and the present study examined its effect on coronary arterial microvessels. The role of purinoceptors in the coronary microcirculation in vivo was also investigated. In open chest dogs, coronary arterioles were observed using a microscope with a floating objective. In Protocol 1, AP4A (1, 10, 100 and 1,000 micromol/L) was superfused onto the heart surface before and during the superfusion of 10 micromol/L of 8-phenyltheophylline (8-PT), a P1 purinoceptor blocker. In Protocol 2, AP4A (0.1, 1, 10, and 100 nmol x kg(-1) x min(-1)) was infused into the left anterior descending coronary artery before and during the superfusion of 10 micromol/L of 8-PT. In addition to 8-PT, 30 micromol/L of pyridoxalphosphate-6-azophenyl 2',4'-disulphonic acid (PPADS), a P2X purinoceptor blocker in Protocol 3, or 300 micromol/L of N(omega)-nitro-L-arginine (LNNA) in Protocol 4, was continuously superfused, and 4 doses of AP4A were cumulatively superfused as in Protocol 1. In Protocol 5, 10 micromol/L of alpha,beta-methylene ATP, an agonist of P2X purinoceptors, was superfused for 60 min. Superfused AP4A dilated arterioles in a dose-dependent manner. The magnitude of dilatation was greater in smaller arterioles (small vessel < or = 150 microm: 24.5+/-2.2% vs large vessel > 150 microm: 10.6+/-1.5% at a dose of 1,000 micromol/L, p<0.001). On the other hand, intraluminally applied AP4A also dilated arterioles, but no size dependency was shown. In the presence of 8-PT, vasodilatory responses to superfused and intraluminally applied AP4A were attenuated and the lower doses of AP4A constricted arterioles. This vasoconstrictor effect was not affected by PPADS. The vasodilatory effect of the higher doses of AP4A was almost abolished in the presence of LNNA. Alpha,beta-methylene ATP had no effect on coronary microvascular diameters. AP4A has bidirectional effects on coronary arterial microvessels: vasodilatory effects

  14. AP233: An Information Model for Systems Engineering

    NASA Technical Reports Server (NTRS)

    Siebes, Georg

    2009-01-01

    In today's world, information is abundant. We have no problems generating it. But we are challenged to find, organize, and exchange information. center dot A standardized model of information can help. Such a model nearly completed its development for Systems Engineering. It is referred to as AP233 (AP = Application Protocol).

  15. 15 CFR 781.2 - Purposes of the Additional Protocol and APR.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL... and less any information to which the U.S. Government applies the national security exclusion, is... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Purposes of the Additional Protocol...

  16. A Proxy Design to Leverage the Interconnection of CoAP Wireless Sensor Networks with Web Applications

    PubMed Central

    Ludovici, Alessandro; Calveras, Anna

    2015-01-01

    In this paper, we present the design of a Constrained Application Protocol (CoAP) proxy able to interconnect Web applications based on Hypertext Transfer Protocol (HTTP) and WebSocket with CoAP based Wireless Sensor Networks. Sensor networks are commonly used to monitor and control physical objects or environments. Smart Cities represent applications of such a nature. Wireless Sensor Networks gather data from their surroundings and send them to a remote application. This data flow may be short or long lived. The traditional HTTP long-polling used by Web applications may not be adequate in long-term communications. To overcome this problem, we include the WebSocket protocol in the design of the CoAP proxy. We evaluate the performance of the CoAP proxy in terms of latency and memory consumption. The tests consider long and short-lived communications. In both cases, we evaluate the performance obtained by the CoAP proxy according to the use of WebSocket and HTTP long-polling. PMID:25585107

  17. 48 CFR 204.470 - U.S.-International Atomic Energy Agency Additional Protocol.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false U.S.-International Atomic Energy Agency Additional Protocol. 204.470 Section 204.470 Federal Acquisition Regulations System DEFENSE... Information Within Industry 204.470 U.S.-International Atomic Energy Agency Additional Protocol. ...

  18. 48 CFR 204.470 - U.S.-International Atomic Energy Agency Additional Protocol.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false U.S.-International Atomic Energy Agency Additional Protocol. 204.470 Section 204.470 Federal Acquisition Regulations System DEFENSE... Information Within Industry 204.470 U.S.-International Atomic Energy Agency Additional Protocol. ...

  19. 48 CFR 204.470 - U.S.-International Atomic Energy Agency Additional Protocol.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false U.S.-International Atomic Energy Agency Additional Protocol. 204.470 Section 204.470 Federal Acquisition Regulations System DEFENSE... Information Within Industry 204.470 U.S.-International Atomic Energy Agency Additional Protocol. ...

  20. 48 CFR 204.470 - U.S.-International Atomic Energy Agency Additional Protocol.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false U.S.-International Atomic Energy Agency Additional Protocol. 204.470 Section 204.470 Federal Acquisition Regulations System DEFENSE... Information Within Industry 204.470 U.S.-International Atomic Energy Agency Additional Protocol. ...

  1. 48 CFR 204.470 - U.S.-International Atomic Energy Agency Additional Protocol.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false U.S.-International Atomic Energy Agency Additional Protocol. 204.470 Section 204.470 Federal Acquisition Regulations System DEFENSE... Information Within Industry 204.470 U.S.-International Atomic Energy Agency Additional Protocol. ...

  2. CREATION OF THE MODEL ADDITIONAL PROTOCOL

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

    Houck, F.; Rosenthal, M.; Wulf, N.

    In 1991, the international nuclear nonproliferation community was dismayed to discover that the implementation of safeguards by the International Atomic Energy Agency (IAEA) under its NPT INFCIRC/153 safeguards agreement with Iraq had failed to detect Iraq's nuclear weapon program. It was now clear that ensuring that states were fulfilling their obligations under the NPT would require not just detecting diversion but also the ability to detect undeclared materials and activities. To achieve this, the IAEA initiated what would turn out to be a five-year effort to reappraise the NPT safeguards system. The effort engaged the IAEA and its Member Statesmore » and led to agreement in 1997 on a new safeguards agreement, the Model Protocol Additional to the Agreement(s) between States and the International Atomic Energy Agency for the Application of Safeguards. The Model Protocol makes explicit that one IAEA goal is to provide assurance of the absence of undeclared nuclear material and activities. The Model Protocol requires an expanded declaration that identifies a State's nuclear potential, empowers the IAEA to raise questions about the correctness and completeness of the State's declaration, and, if needed, allows IAEA access to locations. The information required and the locations available for access are much broader than those provided for under INFCIRC/153. The negotiation was completed in quite a short time because it started with a relatively complete draft of an agreement prepared by the IAEA Secretariat. This paper describes how the Model Protocol was constructed and reviews key decisions that were made both during the five-year period and in the actual negotiation.« less

  3. Abbreviated MRI Protocols for Detecting Breast Cancer in Women with Dense Breasts.

    PubMed

    Chen, Shuang-Qing; Huang, Min; Shen, Yu-Ying; Liu, Chen-Lu; Xu, Chuan-Xiao

    2017-01-01

    To evaluate the validity of two abbreviated protocols (AP) of MRI in breast cancer screening of dense breast tissue. This was a retrospective study in 356 participants with dense breast tissue and negative mammography results. The study was approved by the Nanjing Medical University Ethics Committee. Patients were imaged with a full diagnostic protocol (FDP) of MRI. Two APs (AP-1 consisting of the first post-contrast subtracted [FAST] and maximum-intensity projection [MIP] images, and AP-2 consisting of AP-1 combined with diffusion-weighted imaging [DWI]) and FDP images were analyzed separately, and the sensitivities and specificities of breast cancer detection were calculated. Of the 356 women, 67 lesions were detected in 67 women (18.8%) by standard MR protocol, and histological examination revealed 14 malignant lesions and 53 benign lesions. The average interpretation time of AP-1 and AP-2 were 37 seconds and 54 seconds, respectively, while the average interpretation time of the FDP was 3 minutes and 25 seconds. The sensitivities of the AP-1, AP-2, and FDP were 92.9, 100, and 100%, respectively, and the specificities of the three MR protocols were 86.5, 95.0, and 96.8%, respectively. There was no significant difference among the three MR protocols in the diagnosis of breast cancer ( p > 0.05). However, the specificity of AP-1 was significantly lower than that of AP-2 ( p = 0.031) and FDP ( p = 0.035), while there was no difference between AP-2 and FDP ( p > 0.05). The AP may be efficient in the breast cancer screening of dense breast tissue. FAST and MIP images combined with DWI of MRI are helpful to improve the specificity of breast cancer detection.

  4. A percutaneous drainage protocol for severe and moderately severe acute pancreatitis.

    PubMed

    Sugimoto, Motokazu; Sonntag, David P; Flint, Greggory S; Boyce, Cody J; Kirkham, John C; Harris, Tyler J; Carr, Sean M; Nelson, Brent D; Barton, Joshua G; Traverso, L William

    2015-11-01

    According to the revised Atlanta classification, severe and moderately severe acute pancreatitis (AP) includes patients with pancreatic and peripancreatic collections with or without organ failure. These collections suggest the presence of pancreatic juice leakage. The aim of this study was to evaluate the efficacy of a percutaneous catheter drainage (PCD) protocol designed to control leakage and decrease disease severity. Among 663 patients with clinical AP, 122 were classified as moderately severe or severe AP (all had collections). The computed tomography severity index (CTSI) score was calculated. The indication for PCD was based on progressive clinical signs and symptoms. Drain patency, position, and need for additional drainage sites were assessed using CT scans and drain studies initially every 3 days using a proactive protocol. Drain fluid was examined for amylase concentration and microbiological culture. Clinicopathological variables for patients with and without PCD were compared. Since there was no mortality, we used prolonged drainage time to measure the success of PCD. Within the group treated with PCD, variables that resulted in prolonged drainage time were analyzed. PCD was used in 47/122 (39 %) patients of which 33/47 (70 %) had necrosis. PCD cases had a median CTSI of 8 and were classified as moderately severe AP (57 %) and severe AP (43 %). Inhospital mortality was zero. Surgical necrosectomy was not required for patients with necrosis. Independent risk factors for prolonged drainage time were persistent organ failure >48 h (P = 0.001), CTSI 8-10 (P = 0.038), prolonged duration of amylase-rich fluid in drains (P < 0.001), and polymicrobial culture fluid in drains (P = 0.015). A proactive PCD protocol persistently maintaining drain patency advanced to the site of leak controlled the prolonged amylase in drainage fluid resulting in a mortality rate of zero.

  5. The Role of Additional Pulses in Electropermeabilization Protocols

    PubMed Central

    Suárez, Cecilia; Soba, Alejandro; Maglietti, Felipe; Olaiz, Nahuel; Marshall, Guillermo

    2014-01-01

    Electropermeabilization (EP) based protocols such as those applied in medicine, food processing or environmental management, are well established and widely used. The applied voltage, as well as tissue electric conductivity, are of utmost importance for assessing final electropermeabilized area and thus EP effectiveness. Experimental results from literature report that, under certain EP protocols, consecutive pulses increase tissue electric conductivity and even the permeabilization amount. Here we introduce a theoretical model that takes into account this effect in the application of an EP-based protocol, and its validation with experimental measurements. The theoretical model describes the electric field distribution by a nonlinear Laplace equation with a variable conductivity coefficient depending on the electric field, the temperature and the quantity of pulses, and the Penne's Bioheat equation for temperature variations. In the experiments, a vegetable tissue model (potato slice) is used for measuring electric currents and tissue electropermeabilized area in different EP protocols. Experimental measurements show that, during sequential pulses and keeping constant the applied voltage, the electric current density and the blackened (electropermeabilized) area increase. This behavior can only be attributed to a rise in the electric conductivity due to a higher number of pulses. Accordingly, we present a theoretical modeling of an EP protocol that predicts correctly the increment in the electric current density observed experimentally during the addition of pulses. The model also demonstrates that the electric current increase is due to a rise in the electric conductivity, in turn induced by temperature and pulse number, with no significant changes in the electric field distribution. The EP model introduced, based on a novel formulation of the electric conductivity, leads to a more realistic description of the EP phenomenon, hopefully providing more accurate

  6. Comparison of expression and enzymatic properties of Aspergillus oryzae lysine aminopeptidases ApsA and ApsB.

    PubMed

    Marui, Junichiro; Matsushita-Morita, Mayumi; Tada, Sawaki; Hattori, Ryota; Suzuki, Satoshi; Amano, Hitoshi; Ishida, Hiroki; Yamagata, Youhei; Takeuchi, Michio; Kusumoto, Ken-Ichi

    2012-08-01

    The apsA and apsB genes encoding family M1 aminopeptidases were identified in the industrial fungus Aspergillus oryzae. The apsB was transcriptionally up-regulated up to 2.5-fold in response to the deprivation of nitrogen or carbon sources in growth media, while up-regulation of apsA was less significant. The encoded proteins were bacterially expressed and purified to characterize their enzymatic properties. ApsA and ApsB were optimally active at pH 7.0 and 35 °C and stable at pH ranges of 6-10 and 4-10, respectively, up to 40 °C. The enzymes were inhibited by bestatin and EDTA, as has been reported for family M1 aminopeptidases that characteristically contain a zinc-binding catalytic motif. Both enzymes preferentially liberated N-terminal lysine, which is an essential amino acid and an important additive to animal feed. Enzymes that efficiently release N-terminal lysine from peptides could be useful for food and forage industries. Examination of the reactivity toward peptide substrate of varying length revealed that ApsB exhibited broader substrate specificity than ApsA although the reactivity of ApsB decreased as the length of peptide substrate decreased.

  7. Greenhouse evaluation of Bacillus subtilis AP-01 and Trichoderma harzianum AP-001 in controlling tobacco diseases.

    PubMed

    Maketon, Monchan; Apisitsantikul, Jirasak; Siriraweekul, Chatchai

    2008-04-01

    Two biological control agents, Bacillus subtilis AP-01 (Larminar(™)) and Trichoderma harzianum AP-001 (Trisan(™)) alone or/in combination were investigated in controlling three tobacco diseases, including bacterial wilt (Ralstonia solanacearum), damping-off (Pythium aphanidermatum), and frogeye leaf spot (Cercospora nicotiana). Tests were performed in greenhouse by soil sterilization prior to inoculation of the pathogens. Bacterial-wilt and damping off pathogens were drenched first and followed with the biological control agents and for comparison purposes, two chemical fungicides. But for frogeye leaf spot, which is an airborne fungus, a spraying procedure for every treatment including a chemical fungicide was applied instead of drenching. Results showed that neither B. subtilis AP-01 nor T harzianum AP-001 alone could control the bacterial wilt, but when combined, their controlling capabilities were as effective as a chemical treatment. These results were also similar for damping-off disease when used in combination. In addition, the combined B. subtilis AP-01 and T. harzianum AP-001 resulted in a good frogeye leaf spot control, which was not significantly different from the chemical treatment.

  8. Antibiotic prophylaxis audit and questionnaire study: Traffic Light Poster improves adherence to protocol in gastrointestinal surgery.

    PubMed

    Cameron, Michaella; Jones, Stacey; Adedeji, Olufunso

    2015-07-01

    To measure adherence to antibiotic prophylaxis (AP) protocol amongst surgeons and anesthetists and explore their understanding of AP prescribing in practice. A prospective audit of AP in gastrointestinal surgery and re-audit after intervention. A questionnaire survey of practice. 58 (38%- clean; 62%- clean contaminated) operations were audited and 73 (48%-clean; 51%-clean contaminated) operations were re-audited after intervention with "Traffic Light Poster" (TFP) .55 colleagues (32 consultants and 23 trainees) were recruited for questionnaire survey in three West Midlands hospitals. Audit and Re-Audits. Only 31% of procedures followed the protocol correctly in the initial audit and this increased to 73% in the re-audit. 73% of patients undergoing clean procedures received AP inappropriately in the initial audit but reduced significantly to 20% (p < 0.002) in the re-audit. In the initial audit, 62% of clean contaminated procedures did not receive the appropriate first line AP but this fell to 35% (p < 0.05) in the re-audit. Questionnaire Survey- Only 30% of respondents would not give AP in clean surgery as recommended. 45% would use appropriate AP for clean-contaminated wounds. 73% of respondents will give AP at induction, 20% 1 h pre op and 7% just before incision. There is poor compliance with AP protocols in gastrointestinal surgery in part due to general lack of awareness. An educational intervention in the form of a 'Traffic Light Poster' improved adherence to AP protocol two fold. There was improved rationalizing of AP. Clean procedures, in particular, had less inappropriate prescribing. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  9. Physico-chemical profiles of the wobble ↔ Watson-Crick G*·2AP(w) ↔ G·2AP(WC) and A·2AP(w) ↔ A*·2AP(WC) tautomerisations: a QM/QTAIM comprehensive survey.

    PubMed

    Brovarets', Ol'ha O; Voiteshenko, Ivan S; Hovorun, Dmytro M

    2017-12-20

    This study is intended to clarify in detail the tautomeric transformations of the wobble (w) G*·2AP(w) and A·2AP(w) nucleobase mispairs involving 2-aminopurine (2AP) into the Watson-Crick (WC) G·2AP(WC) and A*·2AP(WC) base mispairs (asterisks denote mutagenic tautomers of the DNA bases), respectively, by quantum-mechanical methods and Bader's Quantum Theory of Atoms in Molecules. Our previously reported methodology has been used, which allows the evolution of the physico-chemical parameters to be tracked along the entire internal reaction coordinate (IRC), not exclusively in the stationary states of these reactions. These biologically important G*·2AP(w) ↔ G·2AP(WC) and A·2AP(w) ↔ A*·2AP(WC) w ↔ WC tautomerisations, which are involved in mutagenic tautomerically-conformational pathways, determine the origin of the transitions and transversions induced by 2AP. In addition, it is established that they proceed through planar, highly stable, zwitterionic transition states and they exhibit similar physico-chemical profiles and stages of sequential intrapair proton transfer, followed by spatial rearrangement of the nucleobases relative to each other within the base pairs. These w ↔ WC tautomerisations occur non-dissociatively and are accompanied by a significant alteration in geometry (from wobble to Watson-Crick and vice versa) and redistribution of the specific intermolecular interactions, which can be divided into 10 patterns including AHB H-bonds and loosened A-H-B covalent bridges along the IRC of tautomerisation. Based on the redistribution of the geometrical and electron-topological parameters of the intrapair hydrogen bonds, exactly 9 key points have been allocated to characterize the evolution of these reactions.

  10. Diadenosine polyphosphates Ap3A and Ap4A, but not Ap5A or Ap6A, induce proliferation of vascular smooth muscle cells.

    PubMed

    Bobbert, Peter; Schlüter, Hartmut; Schultheiss, Heinz Peter; Reusch, Hans Peter

    2008-05-15

    Depending on the number of phosphate groups, diadenosine polyphosphates (ApnA, Ap3A, Ap4A, Ap5A and Ap6A) differ in properties such as proliferation, apoptosis, vasoconstriction and vasodilatation of vascular smooth muscle cells (VSMCs). Possible signaling pathways leading to effects such as proliferation are still unknown. This study examined the proliferative effects of diadenosine polyphosphates on VSMCs and their intracellular pathways. Proliferation of VSMCs was measured by the cell count and [(3)H] thymidine incorporation. Phosphorylation of the MAP kinases ERK1/2 was determined by Western blotting. Single-cell [Ca(2+)](i) measurements were done to determine the influence of [Ca(2+)](i) on intracellular signaling. Stress fiber formation was assessed by fluorescence microscopy to detect an influence of G alpha(12). Ap3A and Ap4A, but not Ap5A or Ap6A, were shown to increase proliferation of VSMCs by activating P2Y receptors, which leads to stimulation of the Ras-Raf-MEK-ERK1/2 cascade. Ap3A- and Ap4A-induced activation of the MAP kinases ERK1/2 was dependent on a signaling pathway that included the EGF receptor, PKC, PLCbeta and the increase of [Ca(2+)](i). In conclusion, Ap3A and Ap4A, but not Ap5A or Ap6A, induce proliferation of VSMCs by a signaling pathway that begins with activation of P2Y receptors and leads to stimulation of the MAP kinases ERK1/2.

  11. Assessment of three AC electroosmotic flow protocols for mixing in microfluidic channel.

    PubMed

    Chen, Jia-Kun; Weng, Chi-Neng; Yang, Ruey-Jen

    2009-05-07

    This study performs an experimental investigation into the micromixer capabilities of three different protocols of AC electroosmotic flow (AC EOF), namely capacitive charging (CC), Faradaic charging (FC) and asymmetric polarization (AP). The results reveal that the vortices generated by the FC protocol (the frequency is around 50-350 Hz) are stronger than those induced by the CC protocol (the frequency is higher than 350 Hz), and therefore provide an improved mixing effect. However, in the FC protocol, the frequency of the external AC voltage must be carefully controlled to avoid damaging electrodes as a result of Faradaic reactions. The experimental results indicate that the AP polarization effect (the applied voltage and frequency are V(1) = 1 V(pp) and V(2) = 20 V(pp)/5 kHz) induces more powerful vortices than either the CC protocol or the FC protocol, and therefore yields a better mixing performance. Two AP-based micromixers are fabricated with symmetric and asymmetric electrode configurations, respectively. The mixing indices achieved by the two devices after an elapsed time of 60 seconds are found to be 56.49 % and 71.77 %, respectively. This result shows that of the two devices, an asymmetric electrode configuration represents a more suitable choice for micromixer in microfluidic devices.

  12. Analytical Model of Large Data Transactions in CoAP Networks

    PubMed Central

    Ludovici, Alessandro; Di Marco, Piergiuseppe; Calveras, Anna; Johansson, Karl H.

    2014-01-01

    We propose a novel analytical model to study fragmentation methods in wireless sensor networks adopting the Constrained Application Protocol (CoAP) and the IEEE 802.15.4 standard for medium access control (MAC). The blockwise transfer technique proposed in CoAP and the 6LoWPAN fragmentation are included in the analysis. The two techniques are compared in terms of reliability and delay, depending on the traffic, the number of nodes and the parameters of the IEEE 802.15.4 MAC. The results are validated trough Monte Carlo simulations. To the best of our knowledge this is the first study that evaluates and compares analytically the performance of CoAP blockwise transfer and 6LoWPAN fragmentation. A major contribution is the possibility to understand the behavior of both techniques with different network conditions. Our results show that 6LoWPAN fragmentation is preferable for delay-constrained applications. For highly congested networks, the blockwise transfer slightly outperforms 6LoWPAN fragmentation in terms of reliability. PMID:25153143

  13. Apheresis and intravenous immunoglobulins used in addition to conventional therapy to treat high-risk pregnant antiphospholipid antibody syndrome patients. A prospective study.

    PubMed

    Ruffatti, Amelia; Favaro, Maria; Hoxha, Ariela; Zambon, Alessandra; Marson, Piero; Del Ross, Teresa; Calligaro, Antonia; Tonello, Marta; Nardelli, Giovanni B

    2016-06-01

    Pregnant women with triple antibody positive antiphospholipid syndrome (APS) who have had thrombosis or a history of early, severe pregnancy complications are generally considered at high risk of pregnancy loss. The objectives of this study were to investigate the efficacy and safety of a relatively new treatment protocol used in addition to conventional therapy in high-risk pregnant patients affected with primary APS. The study's two inclusion criteria were: (1) the presence of triple antiphospholipid positivity, (2) previous thrombosis and/or a history of one or more early, severe pregnancy complications. Eighteen pregnancies occurring between 2002 and 2015 in 14 APS patients, (mean age 34.8±3.6 SD) were monitored. All 14 (100%) patients had triple antiphospholipid positivity. In addition, six of them (42.8%) had a history of thrombosis, four (28.6%) had one or more previous early and severe pregnancy complications, and four (30.8%) met both clinical study criteria. The study protocol included weekly plasmapheresis or immunoadsorption and fortnightly 1g/kg intravenous immunoglobulins. Seventeen of the pregnancies (94.4%) produced live neonates, all born between the 26th and 37th weeks of gestation (mean 33.1±3.5 SD). One female (5.5%), born prematurely at 24 weeks, died of sepsis a week after birth. There were two cases (11.1%) of severe pregnancy complications. No treatment side effects were registered. Given the high live birth rate and the safety associated to it, the study protocol described here could be taken into consideration by medical teams treating high-risk APS pregnant patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. VGLUT2 Trafficking Is Differentially Regulated by Adaptor Proteins AP-1 and AP-3

    PubMed Central

    Li, Haiyan; Santos, Magda S.; Park, Chihyung K.; Dobry, Yuriy; Voglmaier, Susan M.

    2017-01-01

    Release of the major excitatory neurotransmitter glutamate by synaptic vesicle exocytosis depends on glutamate loading into synaptic vesicles by vesicular glutamate transporters (VGLUTs). The two principal isoforms, VGLUT1 and 2, exhibit a complementary pattern of expression in adult brain that broadly distinguishes cortical (VGLUT1) and subcortical (VGLUT2) systems, and correlates with distinct physiological properties in synapses expressing these isoforms. Differential trafficking of VGLUT1 and 2 has been suggested to underlie their functional diversity. Increasing evidence suggests individual synaptic vesicle proteins use specific sorting signals to engage specialized biochemical mechanisms to regulate their recycling. We observed that VGLUT2 recycles differently in response to high frequency stimulation than VGLUT1. Here we further explore the trafficking of VGLUT2 using a pHluorin-based reporter, VGLUT2-pH. VGLUT2-pH exhibits slower rates of both exocytosis and endocytosis than VGLUT1-pH. VGLUT2-pH recycling is slower than VGLUT1-pH in both hippocampal neurons, which endogenously express mostly VGLUT1, and thalamic neurons, which endogenously express mostly VGLUT2, indicating that protein identity, not synaptic vesicle membrane or neuronal cell type, controls sorting. We characterize sorting signals in the C-terminal dileucine-like motif, which plays a crucial role in VGLUT2 trafficking. Disruption of this motif abolishes synaptic targeting of VGLUT2 and essentially eliminates endocytosis of the transporter. Mutational and biochemical analysis demonstrates that clathrin adaptor proteins (APs) interact with VGLUT2 at the dileucine-like motif. VGLUT2 interacts with AP-2, a well-studied adaptor protein for clathrin mediated endocytosis. In addition, VGLUT2 also interacts with the alternate adaptors, AP-1 and AP-3. VGLUT2 relies on distinct recycling mechanisms from VGLUT1. Abrogation of these differences by pharmacological and molecular inhibition reveals that

  15. VGLUT2 Trafficking Is Differentially Regulated by Adaptor Proteins AP-1 and AP-3.

    PubMed

    Li, Haiyan; Santos, Magda S; Park, Chihyung K; Dobry, Yuriy; Voglmaier, Susan M

    2017-01-01

    Release of the major excitatory neurotransmitter glutamate by synaptic vesicle exocytosis depends on glutamate loading into synaptic vesicles by vesicular glutamate transporters (VGLUTs). The two principal isoforms, VGLUT1 and 2, exhibit a complementary pattern of expression in adult brain that broadly distinguishes cortical (VGLUT1) and subcortical (VGLUT2) systems, and correlates with distinct physiological properties in synapses expressing these isoforms. Differential trafficking of VGLUT1 and 2 has been suggested to underlie their functional diversity. Increasing evidence suggests individual synaptic vesicle proteins use specific sorting signals to engage specialized biochemical mechanisms to regulate their recycling. We observed that VGLUT2 recycles differently in response to high frequency stimulation than VGLUT1. Here we further explore the trafficking of VGLUT2 using a pHluorin-based reporter, VGLUT2-pH. VGLUT2-pH exhibits slower rates of both exocytosis and endocytosis than VGLUT1-pH. VGLUT2-pH recycling is slower than VGLUT1-pH in both hippocampal neurons, which endogenously express mostly VGLUT1, and thalamic neurons, which endogenously express mostly VGLUT2, indicating that protein identity, not synaptic vesicle membrane or neuronal cell type, controls sorting. We characterize sorting signals in the C-terminal dileucine-like motif, which plays a crucial role in VGLUT2 trafficking. Disruption of this motif abolishes synaptic targeting of VGLUT2 and essentially eliminates endocytosis of the transporter. Mutational and biochemical analysis demonstrates that clathrin adaptor proteins (APs) interact with VGLUT2 at the dileucine-like motif. VGLUT2 interacts with AP-2, a well-studied adaptor protein for clathrin mediated endocytosis. In addition, VGLUT2 also interacts with the alternate adaptors, AP-1 and AP-3. VGLUT2 relies on distinct recycling mechanisms from VGLUT1. Abrogation of these differences by pharmacological and molecular inhibition reveals that

  16. A comparison of the additional protocols of the five nuclear weapon states and the ensuing safeguards benefits to international nonproliferation efforts

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

    Uribe, Eva C; Sandoval, M Analisa; Sandoval, Marisa N

    2009-01-01

    With the 6 January 2009 entry into force of the Additional Protocol by the United States of America, all five declared Nuclear Weapon States that are part of the Nonproliferation Treaty have signed, ratified, and put into force the Additional Protocol. This paper makes a comparison of the strengths and weaknesses of the five Additional Protocols in force by the five Nuclear Weapon States with respect to the benefits to international nonproliferation aims. This paper also documents the added safeguards burden to the five declared Nuclear Weapon States that these Additional Protocols put on the states with respect to accessmore » to their civilian nuclear programs and the hosting of complementary access activities as part of the Additional Protocol.« less

  17. Tailored Synthesis of 162-Residue S-Monoglycosylated GM2-Activator Protein (GM2AP) Analogues that Allows Facile Access to a Protein Library.

    PubMed

    Nakamura, Takahiro; Sato, Kohei; Naruse, Naoto; Kitakaze, Keisuke; Inokuma, Tsubasa; Hirokawa, Takatsugu; Shigenaga, Akira; Itoh, Kohji; Otaka, Akira

    2016-10-17

    A synthetic protocol for the preparation of 162-residue S-monoglycosylated GM2-activator protein (GM2AP) analogues bearing various amino acid substitutions for Thr69 has been developed. The facile incorporation of the replacements into the protein was achieved by means of a one-pot/N-to-C-directed sequential ligation strategy using readily accessible middle N-sulfanylethylanilide (SEAlide) peptides each consisting of seven amino acid residues. A kinetically controlled ligation protocol was successfully applied to the assembly of three peptide segments covering the GM2AP. The native chemical ligation (NCL) reactivities of the SEAlide peptides can be tuned by the presence or absence of phosphate salts. Furthermore, NCL of the alkyl thioester fragment [GM2AP (1-31)] with the N-terminal cysteinyl prolyl thioester [GM2AP (32-67)] proceeded smoothly to yield the 67-residue prolyl thioester, with the prolyl thioester moiety remaining intact. This newly developed strategy enabled the facile synthesis of GM2AP analogues. Thus, we refer to this synthetic protocol as "tailored synthesis" for the construction of a GM2AP library. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Prediction of three-dimensional femoral offset from AP pelvis radiographs in primary hip osteoarthritis.

    PubMed

    Merle, C; Waldstein, W; Pegg, E C; Streit, M R; Gotterbarm, T; Aldinger, P R; Murray, D W; Gill, H S

    2013-08-01

    In pre-operative planning for total hip arthroplasty (THA), femoral offset (FO) is frequently underestimated on AP pelvis radiographs as a result of inaccurate patient positioning, imprecise magnification, and radiographic beam divergence. The aim of the present study was to evaluate the accuracy and reliability of predicting three-dimensional (3-D) FO from standardised AP pelvis radiographs. In a retrospective cohort study, pre-operative AP pelvis radiographs, AP hip radiographs and CT scans of a consecutive series of 345 patients (345 hips, 146 males, 199 females, mean age 60 (range: 40-79) years, mean body-mass-index 27 (range: 19-57)kg/m(2)) with primary end-stage hip OA were reviewed. Patients were positioned according to a standardised protocol and all images were calibrated. Using validated custom programmes, FO was measured on corresponding radiographs and CT scans. Measurement reliability was evaluated using intra-class-correlation-coefficients. To predict 3-D FO from AP pelvis measurements and to assess the accuracy compared to CT, the entire cohort was randomly split into subgroups A and B. Gender specific regression equations were derived from group A (245 patients) and the accuracy of prediction was evaluated in group B (100 patients) using Bland-Altman plots. In the entire cohort, mean FO was 39.2mm (95%CI: 38.5-40.0mm) on AP pelvis radiographs, 44.1mm (95%CI: 43.4-44.9mm) on AP hip radiographs and 44.6mm (95%CI: 44.0-45.2mm) on CT scans. In group B, we observed no significant difference between gender specific predicted FO (males: 48.0mm, 95%CI: 47.1-48.8mm; females: 42.0mm, 95%CI: 41.1-42.8mm) and FO as measured on CT (males: 47.7mm, 95%CI: 46.1-49.4mm, p=0.689; females: 41.6mm, 95%CI: 40.3-43.0mm, p=0.607). The present study suggests that FO can be accurately and reliably predicted from AP pelvis radiographs in patients with primary end-stage hip osteoarthritis. Our findings support the surgeon in pre-operative templating on AP-pelvis radiographs

  19. Tank 241-AP-106, Grab samples, 6AP-98-1, 6AP-98-2 and 6AP-98-3 Analytical results for the final report

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

    FULLER, R.K.

    1999-02-23

    This document is the final report for tank 241-AP-106 grab samples. Three grab samples 6AP-98-1, 6AP-98-2 and 6AP-98-3 were taken from riser 1 of tank 241-AP-106 on May 28, 1998 and received by the 222-S Laboratory on May 28, 1998. Analyses were performed in accordance with the ''Compatability Grab Sampling and Analysis Plan'' (TSAP) (Sasaki, 1998) and the ''Data Quality Objectives for Tank Farms Waste Compatability Program (DQO). The analytical results are presented in the data summary report. No notification limits were exceeded. The request for sample analysis received for AP-106 indicated that the samples were polychlorinated biphenyl (PCB) suspects.more » The results of this analysis indicated that no PCBs were present at the Toxic Substance Control Act (TSCA) regulated limit of 50 ppm. The results and raw data for the PCB analysis are included in this document.« less

  20. Chromosome localization of human genes for clathrin adaptor polypeptides AP2{beta} and AP50 and the clathrin-binding protein, VCP

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

    Druck, T.; Gu, Y.; Prabhala, G.

    1995-11-01

    Clathrin-coated vesicles, involved in endocytosis and Golgi processing, have a surface lattice containing clathrin triskelia and stoichiometric amounts of additional components termed {open_quotes}assembly proteins,{close_quotes} or APs. The AP form at the plasma membrane, AP2, is composed of two large subunits of 100-115 kDa, denoted AP2{alpha} and AP2{beta}, a medium chain of 50 kDa, designated AP50, and a small chain. We have determined human chromosomal locations of genes for a large AP2{beta} (CLAPB1) and a medium (CLAPM1) AP subunit and of a novel clathrin-binding protein, VCP, that binds clathrin simultaneously with A1`s. Chromosomal in situ hybridization of a human genomic clonemore » demonstrated that the CLAPM1 gene mapped to chromosome region 3q28. The gene for the CLAPB1 large subunit was mapped to 17q11.2-q12 by PCR amplification of an AP2{beta} fragment from a panel of rodent-human hybrid DNAs. To map the human VCP sequence, a human-specific probe was made by RT-PCR of human mRNA using oligonucleotide primers from conserved regions of the porcine sequence. The amplified human fragment served as probe on Southern blots of hybrid DNAs to determine that the human VCP locus maps to chromosome region 9pter-q34. 13 refs., 2 figs.« less

  1. Methanopyrus kandleri topoisomerase V contains three distinct AP lyase active sites in addition to the topoisomerase active site

    PubMed Central

    Rajan, Rakhi; Osterman, Amy; Mondragón, Alfonso

    2016-01-01

    Topoisomerase V (Topo-V) is the only topoisomerase with both topoisomerase and DNA repair activities. The topoisomerase activity is conferred by a small alpha-helical domain, whereas the AP lyase activity is found in a region formed by 12 tandem helix-hairpin-helix ((HhH)2) domains. Although it was known that Topo-V has multiple repair sites, only one had been mapped. Here, we show that Topo-V has three AP lyase sites. The atomic structure and Small Angle X-ray Scattering studies of a 97 kDa fragment spanning the topoisomerase and 10 (HhH)2 domains reveal that the (HhH)2 domains extend away from the topoisomerase domain. A combination of biochemical and structural observations allow the mapping of the second repair site to the junction of the 9th and 10th (HhH)2 domains. The second site is structurally similar to the first one and to the sites found in other AP lyases. The 3rd AP lyase site is located in the 12th (HhH)2 domain. The results show that Topo-V is an unusual protein: it is the only known protein with more than one (HhH)2 domain, the only known topoisomerase with dual activities and is also unique by having three AP lyase repair sites in the same polypeptide. PMID:26908655

  2. Proactive AP Selection Method Considering the Radio Interference Environment

    NASA Astrophysics Data System (ADS)

    Taenaka, Yuzo; Kashihara, Shigeru; Tsukamoto, Kazuya; Yamaguchi, Suguru; Oie, Yuji

    In the near future, wireless local area networks (WLANs) will overlap to provide continuous coverage over a wide area. In such ubiquitous WLANs, a mobile node (MN) moving freely between multiple access points (APs) requires not only permanent access to the Internet but also continuous communication quality during handover. In order to satisfy these requirements, an MN needs to (1) select an AP with better performance and (2) execute a handover seamlessly. To satisfy requirement (2), we proposed a seamless handover method in a previous study. Moreover, in order to achieve (1), the Received Signal Strength Indicator (RSSI) is usually employed to measure wireless link quality in a WLAN system. However, in a real environment, especially if APs are densely situated, it is difficult to always select an AP with better performance based on only the RSSI. This is because the RSSI alone cannot detect the degradation of communication quality due to radio interference. Moreover, it is important that AP selection is completed only on an MN, because we can assume that, in ubiquitous WLANs, various organizations or operators will manage APs. Hence, we cannot modify the APs for AP selection. To overcome these difficulties, in the present paper, we propose and implement a proactive AP selection method considering wireless link condition based on the number of frame retransmissions in addition to the RSSI. In the evaluation, we show that the proposed AP selection method can appropriately select an AP with good wireless link quality, i.e., high RSSI and low radio interference.

  3. Using ProHits to store, annotate and analyze affinity purification - mass spectrometry (AP-MS) data

    PubMed Central

    Liu, Guomin; Zhang, Jianping; Choi, Hyungwon; Lambert, Jean-Philippe; Srikumar, Tharan; Larsen, Brett; Nesvizhskii, Alexey I.; Raught, Brian; Tyers, Mike; Gingras, Anne-Claude

    2012-01-01

    Affinity purification coupled with mass spectrometry (AP-MS) is a robust technique used to identify protein-protein interactions. With recent improvements in sample preparation, and dramatic advances in MS instrumentation speed and sensitivity, this technique is becoming more widely used throughout the scientific community. To meet the needs of research groups both large and small, we have developed software solutions for tracking, scoring and analyzing AP-MS data. Here, we provide details for the installation and utilization of ProHits, a Laboratory Information Management System designed specifically for AP-MS interaction proteomics. This protocol explains: (i) how to install the complete ProHits system, including modules for the management of mass spectrometry files and the analysis of interaction data, and (ii) alternative options for the use of pre-existing search results in simpler versions of ProHits, including a virtual machine implementation of our ProHits Lite software. We also describe how to use the main features of the software to analyze AP-MS data. PMID:22948730

  4. Coaching Strategies for AP: Building a Successful AP European History Program

    ERIC Educational Resources Information Center

    Fornaciari, Jim

    2014-01-01

    The October 2013 special issue of "Social Education" dealt with almost all AP social studies subjects, but omitted AP European History. This is one of the most fascinating AP subjects for students and teachers alike. In this article, the author shares his experiences since hewas given the responsibility of building his school's Advanced…

  5. Identification and embryonic expression of a new AP-2 transcription factor, AP-2 epsilon.

    PubMed

    Wang, Hao-Ven; Vaupel, Kristina; Buettner, Reinhard; Bosserhoff, Anja-Katrin; Moser, Markus

    2004-09-01

    AP-2 proteins comprise a family of highly related transcription factors, which are expressed during mouse embryogenesis in a variety of ectodermal, neuroectodermal, and mesenchymal tissues. AP-2 transcription factors were shown to be involved in morphogenesis of craniofacial, urogenital, neural crest-derived, and placental tissues. By means of a partial cDNA fragment identified during an expressed sequence tag search for AP-2 genes, we identified a fifth, previously unknown AP-2-related gene, AP-2 epsilon. AP-2 epsilon encodes an open reading frame of 434 amino acids, which reveals the typical modular structure of AP-2 transcription factors with highly conserved C-terminal DNA binding and dimerization domains. Although the N-terminally localized activation domain is less homologous, position and identity of amino acids essential for transcriptional transactivation are conserved. Reverse transcriptase-polymerase chain reaction analyses of murine embryos revealed AP-2 epsilon expression from gestational stage embryonic day 7.5 throughout all later embryonic stages until birth. Whole-mount in situ hybridization using a specific AP-2 epsilon cDNA fragment demonstrated that during embryogenesis, expression of AP-2 epsilon is mainly restricted to neural tissue, especially the midbrain, hindbrain, and olfactory bulb. This expression pattern was confirmed by immunohistochemistry with an AP-2 epsilon-specific antiserum. By using this antiserum, we could further localize AP-2 epsilon expression in a hypothalamic nucleus and the neuroepithelium of the vomeronasal organ, suggesting an important function of AP-2 epsilon for the development of the olfactory system.

  6. Diadenosine tetraphosphate (Ap4A) and triphosphate (Ap3A) signaling of human sperm motility.

    PubMed

    Chan, P J; Su, B C; Tredway, D R

    1991-01-01

    The ubiquitous dinucleotide polyphosphate, diadenosine tetraphosphate (Ap4A), has been shown to be a signal molecule for DNA replication in mammalian cells. In this study, Ap4A and a related compound, diadenosine triphosphate (Ap3A), were tested for possible signaling functions in human spermatozoa. A computerized automated semen analyzer was used to detect changes in spermatozoa motility parameters. Cryopreserved-thawed donor spermatozoa were washed and incubated in 0.1 mM Ap4A, 0.1 mM Ap3A, or control medium. The data indicated that both Ap4A and Ap3A decreased the percentage of motile spermatozoa after 4 or more hours of incubation in vitro. The two dinucleotide polyphosphates caused an increase in the amplitude of lateral spermatozoa head displacement parameter only at the start of incubation. The other spermatozoa kinematic parameters were unaffected. No opposing ying-yang dual actions of Ap4A to Ap3A were seen. From the results, Ap4A and Ap3A were observed to be potential inhibitory signals of spermatozoa motility after prolonged exposure.

  7. APS Science 2006.

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

    Gibson, J. M.; Fenner, R. B.; Long, G.

    2007-05-24

    In my five years as the Director of the Advanced Photon Source (APS), I have been fortunate to see major growth in the scientific impact from the APS. This year I am particularly enthusiastic about prospects for our longer-term future. Every scientific instrument must remain at the cutting edge to flourish. Our plans for the next generation of APS--an APS upgrade--got seriously in gear this year with strong encouragement from our users and sponsors. The most promising avenue that has emerged is the energy-recovery linac (ERL) (see article on page xx), for which we are beginning serious R&D. The ERL{at}APSmore » would offer revolutionary performance, especially for x-ray imaging and ultrafast science, while not seriously disrupting the existing user base. I am very proud of our accelerator physics and engineering staff, who not only keep the current APS at the forefront, but were able to greatly impress our international Machine Advisory Committee with the quality of their work on the possible upgrade option (see page xx). As we prepare for long-term major upgrades, our plans to develop and optimize all the sectors at APS in the near future are advancing. Several new beamlines saw first light this year, including a dedicated powder diffraction beamline (11-BM), two instruments for inelastic x-ray scattering at sector 30, and the Center for Nanoscale Materials (CNM) Nanoprobe beamline at sector 26. Our partnership in the first x-ray free-electron laser (LCLS) to be built at Stanford contributes to revolutionary growth in ultrafast science (see page xx), and we are developing a pulse chirping scheme to get ps pulses at sector 7 of the APS within a year or so. In this report, you will find selected highlights of scientific research at the APS from calendar year 2006. The highlighted work covers diverse disciplines, from fundamental to applied science. In the article on page xx you can see the direct impact of APS research on technology. Several new products have

  8. Got AP?

    ERIC Educational Resources Information Center

    Digby, Joan

    2016-01-01

    Families, especially those considering sending their children to a private four-year university, need all the help they can get in funding college. Annmarie Guzy's essay "AP, Dual Enrollment, and the Survival of Honors Education" in this issue powerfully spells out the financial benefits that accrue from using AP courses to satisfy…

  9. APS Science 2009.

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

    Gibson, J. M; Mills, D. M.; Gerig, R.

    It is my pleasure to introduce the 2009 annual report of the Advanced Photon Source. This was a very good year for us. We operated with high reliability and availability, despite growing problems with obsolete systems, and our users produced a record output of publications. The number of user experiments increased by 14% from 2008 to more than 3600. We congratulate the recipients of the 2009 Nobel Prize in Chemistry-Venkatraman Ramakrishnan (Cambridge Institute for Medical Research), Thomas Steitz (Yale University), and Ada Yonath (Weizmann Institute) - who did a substantial amount of this work at APS beamlines. Thanks to themore » efforts of our users and staff, and the ongoing counsel of the APS Scientific Advisory Committee, we made major progress in advancing our planning for the upgrade of the APS (APS-U), producing a proposal that was positively reviewed. We hope to get formal approval in 2010 to begin the upgrade. With advocacy from our users and the support of our sponsor, the Office of Basic Energy Sciences in the Department of Energy (DOE) Office of Science, our operating budgets have grown to the level needed to more adequately staff our beamlines. We were also extremely fortunate to have received $7.9 M in American Recovery and Reinvestment Act ('stimulus') funding to acquire new detectors and improve several of our beamlines. The success of the new Linac Coherent Light Source at Stanford, the world's first x-ray free-electron laser, made us particularly proud since the undulators were designed and built by the APS. Among other highlights, we note that more than one-quarter of the 46 Energy Frontier Research Centers, funded competitively across the U.S. in 2009 by the DOE, included the Advanced Photon Source in their proposed work, which shows that synchrotron radiation, and the APS in particular, are central to energy research. While APS research covers everything from fundamental to applied science (reflected by the highlights in this report), the

  10. Flexible Unicast-Based Group Communication for CoAP-Enabled Devices †

    PubMed Central

    Ishaq, Isam; Hoebeke, Jeroen; Van den Abeele, Floris; Rossey, Jen; Moerman, Ingrid; Demeester, Piet

    2014-01-01

    Smart embedded objects will become an important part of what is called the Internet of Things. Applications often require concurrent interactions with several of these objects and their resources. Existing solutions have several limitations in terms of reliability, flexibility and manageability of such groups of objects. To overcome these limitations we propose an intermediately level of intelligence to easily manipulate a group of resources across multiple smart objects, building upon the Constrained Application Protocol (CoAP). We describe the design of our solution to create and manipulate a group of CoAP resources using a single client request. Furthermore we introduce the concept of profiles for the created groups. The use of profiles allows the client to specify in more detail how the group should behave. We have implemented our solution and demonstrate that it covers the complete group life-cycle, i.e., creation, validation, flexible usage and deletion. Finally, we quantitatively analyze the performance of our solution and compare it against multicast-based CoAP group communication. The results show that our solution improves reliability and flexibility with a trade-off in increased communication overhead. PMID:24901978

  11. AP-Gate

    ERIC Educational Resources Information Center

    Whitman, Glenn

    2003-01-01

    In May 2001, students in the author's Advanced Placement (AP) United States History class were embroiled in a controversy surrounding the AP exam, in particular, having access to the exam's Document Based Question (DBQ) and free response portion prior to the test's administration. Prior to the exam, the College Board had provided a fifty-year time…

  12. 15 CFR 781.1 - Definitions of terms used in the Additional Protocol Regulations (APR).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... United States of America and the International Atomic Energy Agency for the Application of Safeguards in... Additional Protocol. Agreement State. Any State of the United States with which the U.S. Nuclear Regulatory Commission (NRC) has entered into an effective agreement under Subsection 274b of the Atomic Energy Act of...

  13. 15 CFR 781.1 - Definitions of terms used in the Additional Protocol Regulations (APR).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... United States of America and the International Atomic Energy Agency for the Application of Safeguards in... Additional Protocol. Agreement State. Any State of the United States with which the U.S. Nuclear Regulatory Commission (NRC) has entered into an effective agreement under Subsection 274b of the Atomic Energy Act of...

  14. 15 CFR 781.1 - Definitions of terms used in the Additional Protocol Regulations (APR).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... United States of America and the International Atomic Energy Agency for the Application of Safeguards in... Additional Protocol. Agreement State. Any State of the United States with which the U.S. Nuclear Regulatory Commission (NRC) has entered into an effective agreement under Subsection 274b of the Atomic Energy Act of...

  15. 15 CFR 781.1 - Definitions of terms used in the Additional Protocol Regulations (APR).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... United States of America and the International Atomic Energy Agency for the Application of Safeguards in... Additional Protocol. Agreement State. Any State of the United States with which the U.S. Nuclear Regulatory Commission (NRC) has entered into an effective agreement under Subsection 274b of the Atomic Energy Act of...

  16. 15 CFR 781.1 - Definitions of terms used in the Additional Protocol Regulations (APR).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... United States of America and the International Atomic Energy Agency for the Application of Safeguards in... Additional Protocol. Agreement State. Any State of the United States with which the U.S. Nuclear Regulatory Commission (NRC) has entered into an effective agreement under Subsection 274b of the Atomic Energy Act of...

  17. Performance Analysis of Modified Accelerative Preallocation MAC Protocol for Passive Star-Coupled WDMA Networks

    NASA Astrophysics Data System (ADS)

    Yun, Changho; Kim, Kiseon

    2006-04-01

    For the passive star-coupled wavelength-division multiple-access (WDMA) network, a modified accelerative preallocation WDMA (MAP-WDMA) media access control (MAC) protocol is proposed, which is based on AP-WDMA. To show the advantages of MAP-WDMA as an adequate MAC protocol for the network over AP-WDMA, the channel utilization, the channel-access delay, and the latency of MAP-WDMA are investigated and compared with those of AP-WDMA under various data traffic patterns, including uniform, quasi-uniform type, disconnected type, mesh type, and ring type data traffics, as well as the assumption that a given number of network stations is equal to that of channels, in other words, without channel sharing. As a result, the channel utilization of MAP-WDMA can be competitive with respect to that of AP-WDMA at the expense of insignificantly higher latency. Namely, if the number of network stations is small, MAP-WDMA provides better channel utilization for uniform, quasi-uniform-type, and disconnected-type data traffics at all data traffic loads, as well as for mesh and ring-type data traffics at low data traffic loads. Otherwise, MAP-WDMA only outperforms AP-WDMA for the first three data traffics at higher data traffic loads. In the aspect of channel-access delay, MAP-WDMA gives better performance than AP-WDMA, regardless of data traffic patterns and the number of network stations.

  18. APS SCIENCE 2016

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

    Fenner, Richard B.

    The Advanced Photon Source (APS) occupies an 80-acre site on the Argonne national laboratory campus, about 25 miles from downtown chicago, illinois. it shares the site with the center for nanoscale materials and the Advanced Protein characterization facility. for directions to Argonne, see http://www.anl.gov/directions-and-visitor-information. The APS, a national synchrotron radiation research facility operated by Argonne for the u.S. department of energy (doe) office of Science, provides this nation’s brightest high-energy x-ray beams for science. research by APS users extends from the center of the earth to outer space, from new information on combustion engines and microcircuits to new drugs andmore » nanotechnologies whose scale is measured in billionths of a meter. The APS helps researchers illuminate answers to the challenges of our high-tech world, from developing new forms of energy, to sustaining our nation’s technological and economic competitiveness, to pushing back against the ravages of disease. research at the APS promises to have far-reaching« less

  19. A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells.

    PubMed

    Gunhanlar, N; Shpak, G; van der Kroeg, M; Gouty-Colomer, L A; Munshi, S T; Lendemeijer, B; Ghazvini, M; Dupont, C; Hoogendijk, W J G; Gribnau, J; de Vrij, F M S; Kushner, S A

    2018-05-01

    Progress in elucidating the molecular and cellular pathophysiology of neuropsychiatric disorders has been hindered by the limited availability of living human brain tissue. The emergence of induced pluripotent stem cells (iPSCs) has offered a unique alternative strategy using patient-derived functional neuronal networks. However, methods for reliably generating iPSC-derived neurons with mature electrophysiological characteristics have been difficult to develop. Here, we report a simplified differentiation protocol that yields electrophysiologically mature iPSC-derived cortical lineage neuronal networks without the need for astrocyte co-culture or specialized media. This protocol generates a consistent 60:40 ratio of neurons and astrocytes that arise from a common forebrain neural progenitor. Whole-cell patch-clamp recordings of 114 neurons derived from three independent iPSC lines confirmed their electrophysiological maturity, including resting membrane potential (-58.2±1.0 mV), capacitance (49.1±2.9 pF), action potential (AP) threshold (-50.9±0.5 mV) and AP amplitude (66.5±1.3 mV). Nearly 100% of neurons were capable of firing APs, of which 79% had sustained trains of mature APs with minimal accommodation (peak AP frequency: 11.9±0.5 Hz) and 74% exhibited spontaneous synaptic activity (amplitude, 16.03±0.82 pA; frequency, 1.09±0.17 Hz). We expect this protocol to be of broad applicability for implementing iPSC-based neuronal network models of neuropsychiatric disorders.

  20. A New Photometric Study of Ap and Am Stars in the Infrared

    NASA Astrophysics Data System (ADS)

    Chen, P. S.; Liu, J. Y.; Shan, H. G.

    2017-05-01

    In this paper, 426 well known confirmed Ap and Am stars are photometrically studied in the infrared. The 2MASS, Wide-field Infrared Survey Explorer (WISE), and IRAS data are employed to make analyses. The results in this paper have shown that in the 1-3 μm region over 90% Ap and Am stars have no or little infrared excesses, and infrared radiations in the near-infrared from these stars are probably dominated by the free-free emissions. It is also shown that in the 3-12 μm region, the majority of Ap stars and Am stars have very similar behavior, I.e., in the W1-W2 (3.4-4.6 μm) region, over half of Ap and Am stars have clear infrared excesses, which are possibly due to the binarity, the multiplicity, and/or the debris disk, but in the W2-W3 (4.6-12 μm) region they have no or little infrared excess. In addition, in the 12-22 μm region, some of Ap stars and Am stars show the infrared excesses and infrared radiations for these Ap and Am stars are probably due to the free-free emissions. In addition, it is seen that the probability of being the binarity, the multiplicity and/or the debris disk for Am stars is much higher than that for Ap stars. Furthermore, it can be seen that, in general, no relations can be found between infrared colors and spectral types either for Ap stars or for Am stars.

  1. AP Music Theory Applied

    ERIC Educational Resources Information Center

    Spieker, Matthew H.

    2016-01-01

    Some American high schools include Advanced Placement (AP) Music Theory within their course offerings. Students who pass the AP exam can receive college credit either as a music or humanities credit. An AP class, however, offers music students more than future college credit; it ultimately improves musicianship skills and promotes deeper…

  2. A New Photometric Study of Ap and Am Stars in the Infrared

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

    Chen, P. S.; Liu, J. Y.; Shan, H. G., E-mail: chenps@ynao.ac.cn

    In this paper, 426 well known confirmed Ap and Am stars are photometrically studied in the infrared. The 2MASS, Wide-field Infrared Survey Explorer ( WISE ), and IRAS data are employed to make analyses. The results in this paper have shown that in the 1–3 μ m region over 90% Ap and Am stars have no or little infrared excesses, and infrared radiations in the near-infrared from these stars are probably dominated by the free–free emissions. It is also shown that in the 3–12 μ m region, the majority of Ap stars and Am stars have very similar behavior, i.e.,more » in the W 1– W 2 (3.4–4.6 μ m) region, over half of Ap and Am stars have clear infrared excesses, which are possibly due to the binarity, the multiplicity, and/or the debris disk, but in the W 2– W 3 (4.6–12 μ m) region they have no or little infrared excess. In addition, in the 12–22 μ m region, some of Ap stars and Am stars show the infrared excesses and infrared radiations for these Ap and Am stars are probably due to the free–free emissions. In addition, it is seen that the probability of being the binarity, the multiplicity and/or the debris disk for Am stars is much higher than that for Ap stars. Furthermore, it can be seen that, in general, no relations can be found between infrared colors and spectral types either for Ap stars or for Am stars.« less

  3. LaAP2L1, a heterosis-associated AP2/EREBP transcription factor of Larix, increases organ size and final biomass by affecting cell proliferation in Arabidopsis.

    PubMed

    Li, Ai; Zhou, Yanan; Jin, Chuan; Song, Wenqin; Chen, Chengbin; Wang, Chunguo

    2013-11-01

    In Larix and in some crops, heterosis is prevalent and has been widely used in breeding to produce excellent varieties. However, the molecular basis of heterosis in Larix remains ambiguous. LaAP2L1, a member of the AP2/EREBP transcription factor family, has been suggested to be involved in heterosis in Larix hybrids. Here, the function and regulation of LaAP2L1 were further explored. Overexpression of LaAP2L1 led to markedly enlarged organs and heterosis-like traits in Arabidopsis. Fresh weight of leaves was almost twice as great as in vector controls. Likewise, seed yield of 35S::LaAP2L1 individual plants was >200% greater than that of control plants. The enlarged organs and heterosis-like traits displayed by 35S::LaAP2L1 plants were mainly due to enhanced cell proliferation and prolonged growth duration. At the molecular level, LaAP2L1 upregulated the expression of ANT, EBP1, and CycD3;1 and inhibited the expression of ARGOS in 35S::LaAP2L1 plants, suggesting an important molecular role of LaAP2L1 in regulating plant organ development. These findings provide new insights into the formation of heterosis in woody plants and suggest that LaAP2L1 has potential applications in breeding high-yielding crops and energy plants. In addition, 50 AP2/EREBP transcription factors, including LaAP2L1, in Larix were identified by transcriptome sequencing, and phylogenetic analysis was conducted. This provided information that will be important in further revealing the functions of these transcription factors.

  4. Peculiar Traits of Coarse AP (Briefing Charts)

    DTIC Science & Technology

    2014-12-01

    coarse AP Bircumshaw, Newman Active centers are sources of AP decomposition gases AP low temperature decomposition (LTD) Most unstable AP particles ...delay before coarse AP ejection *Coarse AP particle flame retardancy 19 Air Force Research Laboratory Distribution A: Approved for public release...distribution unlimited. PA clearance #. Combustion bomb trials 2 AP phase change may enable coarse particle breakage Fractured coarse AP ejection agrees

  5. The duality of LysU, a catalyst for both Ap4A and Ap3A formation.

    PubMed

    Wright, Michael; Boonyalai, Nonlawat; Tanner, Julian A; Hindley, Alison D; Miller, Andrew D

    2006-08-01

    Heat shock inducible lysyl-tRNA synthetase of Escherichia coli (LysU) is known to be a highly efficient diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) synthase. However, we use an ion-exchange HPLC technique to demonstrate that active LysU mixtures actually have a dual catalytic activity, initially producing Ap4A from ATP, before converting that tetraphosphate to a triphosphate. LysU appears to be an effective diadenosine 5',5'''-P1,P3-triphosphate (Ap3A) synthase. Mechanistic investigations reveal that Ap3A formation requires: (a) that the second step of Ap4A formation is slightly reversible, thereby leading to a modest reappearance of adenylate intermediate; and (b) that phosphate is present to trap the intermediate (either as inorganic phosphate, as added ADP, or as ADP generated in situ from inorganic phosphate). Ap3A forms readily from Ap4A in the presence of such phosphate-based adenylate traps (via a 'reverse-trap' mechanism). LysU is also clearly demonstrated to exist in a phosphorylated state that is more physically robust as a catalyst of Ap4A formation than the nonphosphorylated state. However, phosphorylated LysU shows only marginally improved catalytic efficiency. We note that Ap3A effects have barely been studied in prokaryotic organisms. By contrast, there is a body of literature that describes Ap3A and Ap4A having substantially different functions in eukaryotic cells. Our data suggest that Ap3A and Ap4A biosynthesis could be linked together through a single prokaryotic dual 'synthase' enzyme. Therefore, in our view there is a need for new research into the effects and impact of Ap3A alone and the intracellular [Ap3A]/[Ap4A] ratio on prokaryotic organisms.

  6. Theoretical studies on the electronic and optoelectronic properties of [A.2AP(w)/A*.2AP(WC)/C.2AP(w)/C*.2AP(WC)/C.A(w)/C*.A(WC)]-Au8 mismatch nucleobase complexes

    NASA Astrophysics Data System (ADS)

    Srivastava, Ruby

    2018-01-01

    The electronic and optoelectronic properties of [A.2AP(w)/A*.2AP(WC)/C.2AP(w)/C*.2AP(WC)/C.A(w)/ C*.A(WC)]-Au8 metal-mismatch nucleobase complexes are investigated by means of density functional theory and time-dependent methods. We selected these mispairs as 2-aminopurine (2AP) produces incorporation errors when binding with cytosine (C) into the wobble (w) C.2AP(w) mispair, and is tautomerised into Watson-Crick (WC)-like base mispair C*.2AP(WC) and less effectively produces A.2AP(w)/A*.2AP(WC) mispairs. The vertical ionisation potential, vertical electron affinity, hardness and electrophilicity index of these complexes have also been discussed. The modifications of energy levels and charge density distributions of the frontier orbitals are also analysed. The absorption spectra of these complexes lie in the visible region, which suggests their application in fluorescent-bio imaging. The mechanism of cooperativity effect is studied by molecular orbital potential (MEP), atoms-in-molecules (AIM) and natural bond orbital analyses. Most metalated pairs have smaller HOMO-LUMO band gaps than the isolated mismatch nucleobases which suggest interesting consequences for electron transfer through DNA duplexes.

  7. Application of Abbreviated Protocol of Magnetic Resonance Imaging for Breast Cancer Screening in Dense Breast Tissue.

    PubMed

    Chen, Shuang-Qing; Huang, Min; Shen, Yu-Ying; Liu, Chen-Lu; Xu, Chuan-Xiao

    2017-03-01

    The study aimed to evaluate the usefulness of an abbreviated protocol (AP) of magnetic resonance imaging (MRI) in comparison to a full diagnostic protocol (FDP) of MRI in the breast cancer screening with dense breast tissue. There are 478 female participants with dense breast tissue and negative mammography results, who were imaged with MRI using AP and FDP. The AP and FDP images were analyzed separately, and the sensitivity and specificity of breast cancer detection were calculated. The chi-square test and receiver operating characteristics curves were used to assess the breast cancer diagnostic capabilities of the two protocols. Sixteen cases of breast cancer from 478 patients with dense breasts were detected using the FDP method, with pathologic confirmation of nine cases of ductal carcinoma in situ, six cases of invasive ductal carcinoma, and one case of mucinous carcinoma. Fifteen cases of breast cancer were successfully screened using the AP method. The sensitivity showed no obvious significant difference between AP and FDP (χ 2  = 0.592, P = 0.623), but the specificity showed a statistically significant difference (χ 2  = 4.619, P = 0.036). The receiver operating characteristics curves showed high efficacy of both methods in the detection of breast cancer in dense breast tissue (the areas under the curve were 0.931 ± 0.025 and 0.947 ± 0.024, respectively), and the ability to diagnose breast cancer was not statistically significantly different between the two methods. The AP of MRI may improve the detection rate of breast cancer in dense breast tissue, and it may be useful in efficient breast cancer screening. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  8. How Understanding the Role of an Additive Can Lead to an Improved Synthetic Protocol without an Additive: Organocatalytic Synthesis of Chiral Diarylmethyl Alkynes.

    PubMed

    Chen, Min; Sun, Jianwei

    2017-09-18

    The use of additives for organic synthesis has become a common tactic to improve the outcome of organic reactions. Herein, by using an organocatalytic process for the synthesis of chiral diarylmethyl alkynes as a platform, we describe how an additive is involved in the improvement of the process. The evolution of an excellent synthetic protocol has been achieved in three stages, from 1) initially no catalyst turnover, to 2) good conversion and enantioselectivity with a superior additive, and eventually 3) even better efficiency and selectivity without an additive. This study is an important and rare demonstration that understanding the role of additive can be so beneficial as to obviate the need for the additive. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Functions of Adaptor Protein (AP)-3 and AP-1 in Tyrosinase Sorting from Endosomes to MelanosomesD⃞

    PubMed Central

    Theos, Alexander C.; Tenza, Danièle; Martina, José A.; Hurbain, Ilse; Peden, Andrew A.; Sviderskaya, Elena V.; Stewart, Abigail; Robinson, Margaret S.; Bennett, Dorothy C.; Cutler, Daniel F.; Bonifacino, Juan S.; Marks, Michael S.; Raposo, Graça

    2005-01-01

    Specialized cells exploit adaptor protein complexes for unique post-Golgi sorting events, providing a unique model system to specify adaptor function. Here, we show that AP-3 and AP-1 function independently in sorting of the melanocyte-specific protein tyrosinase from endosomes to the melanosome, a specialized lysosome-related organelle distinguishable from lysosomes. AP-3 and AP-1 localize in melanocytes primarily to clathrin-coated buds on tubular early endosomes near melanosomes. Both adaptors recognize the tyrosinase dileucine-based melanosome sorting signal, and tyrosinase largely colocalizes with each adaptor on endosomes. In AP-3-deficient melanocytes, tyrosinase accumulates inappropriately in vacuolar and multivesicular endosomes. Nevertheless, a substantial fraction still accumulates on melanosomes, concomitant with increased association with endosomal AP-1. Our data indicate that AP-3 and AP-1 function in partially redundant pathways to transfer tyrosinase from distinct endosomal subdomains to melanosomes and that the AP-3 pathway ensures that tyrosinase averts entrapment on internal membranes of forming multivesicular bodies. PMID:16162817

  10. Application Protocol, Initial Graphics Exchange Specification (IGES), Layered Electrical Product

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

    O`Connell, L.J.

    1994-12-01

    An application protocol is an information systems engineering view of a specific product The view represents an agreement on the generic activities needed to design and fabricate the product the agreement on the information needed to support those activities, and the specific constructs of a product data standard for use in transferring some or all of the information required. This application protocol describes the data for electrical and electronic products in terms of a product description standard called the Initial Graphics Exchange Specification (IGES). More specifically, the Layered Electrical Product IGES Application Protocol (AP) specifies the mechanisms for defining andmore » exchanging computer-models and their associated data for those products which have been designed in two dimensional geometry so as to be produced as a series of layers in IGES format The AP defines the appropriateness of the data items for describing the geometry of the various parts of a product (shape and location), the connectivity, and the processing and material characteristics. Excluded is the behavioral requirements which the product was intended to satisfy, except as those requirements have been recorded as design rules or product testing requirements.« less

  11. Artificial pancreas (AP) clinical trial participants' acceptance of future AP technology.

    PubMed

    Bevier, Wendy C; Fuller, Serena M; Fuller, Ryan P; Rubin, Richard R; Dassau, Eyal; Doyle, Francis J; Jovanovič, Lois; Zisser, Howard C

    2014-09-01

    Artificial pancreas (AP) systems are currently an active field of diabetes research. This pilot study examined the attitudes of AP clinical trial participants toward future acceptance of the technology, having gained firsthand experience. After possible influencers of AP technology adoption were considered, a 34-question questionnaire was developed. The survey assessed current treatment satisfaction, dimensions of clinical trial participant motivation, and variables of the technology acceptance model (TAM). Forty-seven subjects were contacted to complete the survey. The reliability of the survey scales was tested using Cronbach's α. The relationship of the factors to the likelihood of AP technology adoption was explored using regression analysis. Thirty-six subjects (76.6%) completed the survey. Of the respondents, 86.1% were either highly likely or likely to adopt the technology once available. Reliability analysis of the survey dimensions revealed good internal consistency, with scores of >0.7 for current treatment satisfaction, convenience (motivation), personal health benefit (motivation), perceived ease of use (TAM), and perceived usefulness (TAM). Linear modeling showed that future acceptance of the AP was significantly associated with TAM and the motivation variables of convenience plus the individual item benefit to others (R(2)=0.26, P=0.05). When insulin pump and continuous glucose monitor use were added, the model significance improved (R(2)=0.37, P=0.02). This pilot study demonstrated that individuals with direct AP technology experience expressed high likelihood of future acceptance. Results support the factors of personal benefit, convenience, perceived usefulness, and perceived ease of use as reliable scales that suggest system adoption in this highly motivated patient population.

  12. A Mechanism for Reliable Mobility Management for Internet of Things Using CoAP

    PubMed Central

    Chun, Seung-Man; Park, Jong-Tae

    2017-01-01

    Under unreliable constrained wireless networks for Internet of Things (IoT) environments, the loss of the signaling message may frequently occur. Mobile Internet Protocol version 6 (MIPv6) and its variants do not consider this situation. Consequently, as a constrained device moves around different wireless networks, its Internet Protocol (IP) connectivity may be frequently disrupted and power can be drained rapidly. This can result in the loss of important sensing data or a large delay for time-critical IoT services such as healthcare monitoring and disaster management. This paper presents a reliable mobility management mechanism in Internet of Things environments with lossy low-power constrained device and network characteristics. The idea is to use the Internet Engineering Task Force (IETF) Constrained Application Protocol (CoAP) retransmission mechanism to achieve both reliability and simplicity for reliable IoT mobility management. Detailed architecture, algorithms, and message extensions for reliable mobility management are presented. Finally, performance is evaluated using both mathematical analysis and simulation. PMID:28085109

  13. A Mechanism for Reliable Mobility Management for Internet of Things Using CoAP.

    PubMed

    Chun, Seung-Man; Park, Jong-Tae

    2017-01-12

    Under unreliable constrained wireless networks for Internet of Things (IoT) environments, the loss of the signaling message may frequently occur. Mobile Internet Protocol version 6 (MIPv6) and its variants do not consider this situation. Consequently, as a constrained device moves around different wireless networks, its Internet Protocol (IP) connectivity may be frequently disrupted and power can be drained rapidly. This can result in the loss of important sensing data or a large delay for time-critical IoT services such as healthcare monitoring and disaster management. This paper presents a reliable mobility management mechanism in Internet of Things environments with lossy low-power constrained device and network characteristics. The idea is to use the Internet Engineering Task Force (IETF) Constrained Application Protocol (CoAP) retransmission mechanism to achieve both reliability and simplicity for reliable IoT mobility management. Detailed architecture, algorithms, and message extensions for reliable mobility management are presented. Finally, performance is evaluated using both mathematical analysis and simulation.

  14. In silico simulations of experimental protocols for cardiac modeling.

    PubMed

    Carro, Jesus; Rodriguez, Jose Felix; Pueyo, Esther

    2014-01-01

    A mathematical model of the AP involves the sum of different transmembrane ionic currents and the balance of intracellular ionic concentrations. To each ionic current corresponds an equation involving several effects. There are a number of model parameters that must be identified using specific experimental protocols in which the effects are considered as independent. However, when the model complexity grows, the interaction between effects becomes increasingly important. Therefore, model parameters identified considering the different effects as independent might be misleading. In this work, a novel methodology consisting in performing in silico simulations of the experimental protocol and then comparing experimental and simulated outcomes is proposed for parameter model identification and validation. The potential of the methodology is demonstrated by validating voltage-dependent L-type calcium current (ICaL) inactivation in recently proposed human ventricular AP models with different formulations. Our results show large differences between ICaL inactivation as calculated from the model equation and ICaL inactivation from the in silico simulations due to the interaction between effects and/or to the experimental protocol. Our results suggest that, when proposing any new model formulation, consistency between such formulation and the corresponding experimental data that is aimed at being reproduced needs to be first verified considering all involved factors.

  15. Recommended Protocol for Round Robin Studies in Additive Manufacturing

    PubMed Central

    Moylan, Shawn; Brown, Christopher U.; Slotwinski, John

    2016-01-01

    One way to improve confidence and encourage proliferation of additive manufacturing (AM) technologies and parts is by generating more high quality data describing the performance of AM processes and parts. Many in the AM community see round robin studies as a way to generate large data sets while distributing the cost among the participants, thereby reducing the cost to individual users. The National Institute of Standards and Technology (NIST) has conducted and participated in several of these AM round robin studies. While the results of these studies are interesting and informative, many of the lessons learned in conducting these studies concern the logistics and methods of the study and unique issues presented by AM. Existing standards for conducting interlaboratory studies of measurement methods, along with NIST’s experience, form the basis for recommended protocols for conducting AM round robin studies. The role of round robin studies in AM qualification, some of the limitations of round robin studies, and the potential benefit of less formal collaborative experiments where multiple factors, AM machine being only one, are varied simultaneously are also discussed. PMID:27274602

  16. Recommended Protocol for Round Robin Studies in Additive Manufacturing.

    PubMed

    Moylan, Shawn; Brown, Christopher U; Slotwinski, John

    2016-03-01

    One way to improve confidence and encourage proliferation of additive manufacturing (AM) technologies and parts is by generating more high quality data describing the performance of AM processes and parts. Many in the AM community see round robin studies as a way to generate large data sets while distributing the cost among the participants, thereby reducing the cost to individual users. The National Institute of Standards and Technology (NIST) has conducted and participated in several of these AM round robin studies. While the results of these studies are interesting and informative, many of the lessons learned in conducting these studies concern the logistics and methods of the study and unique issues presented by AM. Existing standards for conducting interlaboratory studies of measurement methods, along with NIST's experience, form the basis for recommended protocols for conducting AM round robin studies. The role of round robin studies in AM qualification, some of the limitations of round robin studies, and the potential benefit of less formal collaborative experiments where multiple factors, AM machine being only one, are varied simultaneously are also discussed.

  17. Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes

    PubMed Central

    Sitaram, Anand; Dennis, Megan K.; Chaudhuri, Rittik; De Jesus-Rojas, Wilfredo; Tenza, Danièle; Setty, Subba Rao Gangi; Wood, Christopher S.; Sviderskaya, Elena V.; Bennett, Dorothy C.; Raposo, Graça; Bonifacino, Juan S.; Marks, Michael S.

    2012-01-01

    Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric adaptor AP-1 or AP-3. Some cargoes bind both adaptors, but the relative contribution of each adaptor to cargo recognition and their functional interactions with other effectors during transport to melanosomes are not clear. Here we exploit targeted mutagenesis of the acidic dileucine–based sorting signal in the pigment cell–specific protein OCA2 to dissect the relative roles of AP-1 and AP-3 in transport to melanosomes. We show that binding to AP-1 or AP-3 depends on the primary sequence of the signal and not its position within the cytoplasmic domain. Mutants that preferentially bound either AP-1 or AP-3 each trafficked toward melanosomes and functionally complemented OCA2 deficiency, but AP-3 binding was necessary for steady-state melanosome localization. Unlike tyrosinase, which also engages AP-3 for optimal melanosomal delivery, both AP-1– and AP-3–favoring OCA2 variants required BLOC-1 for melanosomal transport. These data provide evidence for distinct roles of AP-1 and AP-3 in OCA2 transport to melanosomes and indicate that BLOC-1 can cooperate with either adaptor during cargo sorting to LROs. PMID:22718909

  18. CLEARING MAGNET DESIGN FOR APS-U

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

    Abliz, M.; Grimmer, J.; Jaski, Y.

    2017-06-25

    The Advanced Photon Source is in the process of developing an upgrade (APS-U) of the storage ring. The upgrade will be converting the current double bend achromat (DBA) lattice to a multi-bend achromat (MBA) lattice. In addition, the storage ring will be operated at 6 GeV and 200 mA with regular swap-out injection to keep the stored beam current constant [1]. The swap-out injection will take place with beamline shutters open. For radiation safety to ensure that no electrons can exit the storage ring, a passive method of protecting the beamline and containing the electrons inside the storage ring ismore » proposed. A clearing magnet will be located in all beamline front ends inside the storage ring tunnel. This article will discuss the features and design of the clearing magnet scheme for APS-U.« less

  19. Coexistence of WiFi and WiMAX systems based on PS-request protocols.

    PubMed

    Kim, Jongwoo; Park, Suwon; Rhee, Seung Hyong; Choi, Yong-Hoon; Chung, Young-uk; Hwang, Ho Young

    2011-01-01

    We introduce both the coexistence zone within the WiMAX frame structure and a PS-Request protocol for the coexistence of WiFi and WiMAX systems sharing a frequency band. Because we know that the PS-Request protocol has drawbacks, we propose a revised PS-Request protocol to improve the performance. Two PS-Request protocols are based on the time division operation (TDO) of WiFi system and WiMAX system to avoid the mutual interference, and use the vestigial power management (PwrMgt) bit within the Frame Control field of the frames transmitted by a WiFi AP. The performance of the revised PS-Request protocol is evaluated by computer simulation, and compared to those of the cases without a coexistence protocol and to the original PS-Request protocol.

  20. SnAP reagents for the one-step synthesis of medium-ring saturated N-heterocycles from aldehydes

    NASA Astrophysics Data System (ADS)

    Vo, Cam-Van T.; Luescher, Michael U.; Bode, Jeffrey W.

    2014-04-01

    Interest in saturated N-heterocycles as scaffolds for the synthesis of bioactive molecules is increasing. Reliable and predictable synthetic methods for the preparation of these compounds, especially medium-sized rings, are limited. We describe the development of SnAP (Sn amino protocol) reagents for the transformation of aldehydes into seven-, eight- and nine-membered saturated N-heterocycles. This process occurs under mild, room-temperature conditions and offers exceptional substrate scope and functional-group tolerance. Air- and moisture-stable SnAP reagents are prepared on a multigram scale from inexpensive starting materials by simple reaction sequences. These new reagents and processes allow widely available aryl, heteroaryl and aliphatic aldehydes to be converted into diverse N-heterocycles, including diazepanes, oxazepanes, diazocanes, oxazocanes and hexahydrobenzoxazonines, by a single synthetic operation.

  1. A comparison of the use of bony anatomy and internal markers for offline verification and an evaluation of the potential benefit of online and offline verification protocols for prostate radiotherapy.

    PubMed

    McNair, Helen A; Hansen, Vibeke N; Parker, Christopher C; Evans, Phil M; Norman, Andrew; Miles, Elizabeth; Harris, Emma J; Del-Acroix, Louise; Smith, Elizabeth; Keane, Richard; Khoo, Vincent S; Thompson, Alan C; Dearnaley, David P

    2008-05-01

    To evaluate the utility of intraprostatic markers in the treatment verification of prostate cancer radiotherapy. Specific aims were: to compare the effectiveness of offline correction protocols, either using gold markers or bony anatomy; to estimate the potential benefit of online correction protocol's using gold markers; to determine the presence and effect of intrafraction motion. Thirty patients with three gold markers inserted had pretreatment and posttreatment images acquired and were treated using an offline correction protocol and gold markers. Retrospectively, an offline protocol was applied using bony anatomy and an online protocol using gold markers. The systematic errors were reduced from 1.3, 1.9, and 2.5 mm to 1.1, 1.1, and 1.5 mm in the right-left (RL), superoinferior (SI), and anteroposterior (AP) directions, respectively, using the offline correction protocol and gold markers instead of bony anatomy. The subsequent decrease in margins was 1.7, 3.3, and 4 mm in the RL, SI, and AP directions, respectively. An offline correction protocol combined with an online correction protocol in the first four fractions reduced random errors further to 0.9, 1.1, and 1.0 mm in the RL, SI, and AP directions, respectively. A daily online protocol reduced all errors to <1 mm. Intrafraction motion had greater impact on the effectiveness of the online protocol than the offline protocols. An offline protocol using gold markers is effective in reducing the systematic error. The value of online protocols is reduced by intrafraction motion.

  2. Metallized solid rocket propellants based on AN/AP and PSAN/AP for access to space

    NASA Astrophysics Data System (ADS)

    Levi, S.; Signoriello, D.; Gabardi, A.; Molinari, M.; Galfetti, L.; Deluca, L. T.; Cianfanelli, S.; Klyakin, G. F.

    2009-09-01

    Solid rocket propellants based on dual mixes of inorganic crystalline oxidizers (ammonium nitrate (AN) and ammonium perchlorate (AP)) with binder and a mixture of micrometric-nanometric aluminum were investigated. Ammonium nitrate is a low-cost oxidizer, producing environment friendly combustion products but with lower specific impulse compared to AP. The better performance obtained with AP and the low quantity of toxic emissions obtained by using AN have suggested an interesting compromise based on a dual mixture of the two oxidizers. To improve the thermal response of raw AN, different types of phase stabilized AN (PSAN) and AN/AP co-crystals were investigated.

  3. Additionality and permanence standards in California's Forest Offset Protocol: A review of project and program level implications.

    PubMed

    Ruseva, T; Marland, E; Szymanski, C; Hoyle, J; Marland, G; Kowalczyk, T

    2017-08-01

    A key component of California's cap-and-trade program is the use of carbon offsets as compliance instruments for reducing statewide GHG emissions. Under this program, offsets are tradable credits representing real, verifiable, quantifiable, enforceable, permanent, and additional reductions or removals of GHG emissions. This paper focuses on the permanence and additionality standards for offset credits as defined and operationalized in California's Compliance Offset Protocol for U.S. Forest Projects. Drawing on a review of the protocol, interviews, current offset projects, and existing literature, we discuss how additionality and permanence standards relate to project participation and overall program effectiveness. Specifically, we provide an overview of offset credits as compliance instruments in California's cap-and-trade program, the timeline for a forest offset project, and the factors shaping participation in offset projects. We then discuss the implications of permanence and additionality at both the project and program levels. Largely consistent with previous work, we find that stringent standards for permanent and additional project activities can present barriers to participation, but also, that there may be a trade-off between project quality and quantity (i.e. levels of participation) when considering overall program effectiveness. We summarize what this implies for California's forest offset program and provide suggestions for improvements in light of potential program diffusion and policy learning. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. AP reclamation and reuse in RSRM propellant

    NASA Technical Reports Server (NTRS)

    Miks, Kathryn F.; Harris, Stacey A.

    1995-01-01

    A solid propellant ingredient reclamation pilot plant has been evaluated at the Strategic Operations of Thiokol Corporation, located in Brigham City, Utah. The plant produces AP wet cake (95 percent AP, 5 percent water) for recycling at AP vendors. AP has been obtained from two standard propellant binder systems (PBAN and HTPB). Analytical work conducted at Thiokol indicates that the vendor-recrystallized AP meets Space Shuttle propellant specification requirements. Thiokol has processed 1-, 5-, and 600-gallon propellant mixes with the recrystallized AP. Processing, cast, cure, ballistic, mechanical, and safety properties have been evaluated. Phillips Laboratory static-test-fired 70-pound and 800-pound BATES motors. The data indicate that propellant processed with reclaimed AP has nominal properties.

  5. Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1.

    PubMed

    Eriksson, Daniel; Dalin, Frida; Eriksson, Gabriel Nordling; Landegren, Nils; Bianchi, Matteo; Hallgren, Åsa; Dahlqvist, Per; Wahlberg, Jeanette; Ekwall, Olov; Winqvist, Ola; Catrina, Sergiu-Bogdan; Rönnelid, Johan; Hulting, Anna-Lena; Lindblad-Toh, Kerstin; Alimohammadi, Mohammad; Husebye, Eystein S; Knappskog, Per Morten; Rosengren Pielberg, Gerli; Bensing, Sophie; Kämpe, Olle

    2018-01-01

    Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1. To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease. We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE. In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure. We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications. Copyright © 2017 Endocrine Society

  6. Molecular and biochemical characterisation of two aspartic proteinases TcAP1 and TcAP2 from Theobroma cacao seeds.

    PubMed

    Laloi, Maryse; McCarthy, James; Morandi, Olivia; Gysler, Christof; Bucheli, Peter

    2002-09-01

    Aspartic proteinase (EC 3.4.23) activity plays a pivotal role in the degradation of Theobroma cacao L. seed proteins during the fermentation step of cacao bean processing. Therefore, this enzyme is believed to be critical for the formation of the peptide and amino acid cocoa flavor precursors that occurs during fermentation. Using cDNA cloning and northern blot analysis, we show here that there are at least two distinct aspartic proteinase genes ( TcAP1 and TcAP2) expressed during cacao seed development. Both genes are expressed early during seed development and their mRNA levels decrease towards the end of seed maturation. TcAP2 is expressed at a much higher level than TcAP1, although the expression of TcAP1 increases slightly during germination. The proteins encoded by TcAP1 and TcAP2 are relatively different from each other (73% identity). This, and the fact that the two corresponding genes have different expression patterns, suggests that the TcAP1 and TcAP2 proteins may have different functions in the maturing seeds and during germination. Because the TcAP2 gene is expressed at a much higher level during seed development than TcAP1, it is likely that the TcAP2 protein is primarily responsible for the majority of the industrially important protein hydrolysis that occurs during cacao bean fermentation. Finally, TcAP2 has been functionally expressed in the yeast Yarrowia lipolytica. The secreted recombinant protein is able to hydrolyse bovine haemoglobin at acidic pH and is sensitive to pepstatin A, confirming that TcAP2 encodes an aspartic proteinase, and strongly suggests that this gene encodes the well-characterized aspartic proteinase of mature cacao seeds.

  7. The adipocyte fatty acid–binding protein aP2 is required in allergic airway inflammation

    PubMed Central

    Shum, Bennett O.V.; Mackay, Charles R.; Gorgun, Cem Z.; Frost, Melinda J.; Kumar, Rakesh K.; Hotamisligil, Gökhan S.; Rolph, Michael S.

    2006-01-01

    The adipocyte fatty acid–binding protein aP2 regulates systemic glucose and lipid metabolism. We report that aP2, in addition to being abundantly expressed by adipocytes, is also expressed by human airway epithelial cells and shows a striking upregulation following stimulation of epithelial cells with the Th2 cytokines IL-4 and IL-13. Regulation of aP2 mRNA expression by Th2 cytokines was highly dependent on STAT6, a transcription factor with a major regulatory role in allergic inflammation. We examined aP2-deficient mice in a model of allergic airway inflammation and found that infiltration of leukocytes, especially eosinophils, into the airways was highly dependent on aP2 function. T cell priming was unaffected by aP2 deficiency, suggesting that aP2 was acting locally within the lung, and analysis of bone marrow chimeras implicated non-hematopoietic cells, most likely bronchial epithelial cells, as the site of action of aP2 in allergic airway inflammation. Thus, aP2 regulates allergic airway inflammation and may provide a link between fatty acid metabolism and asthma. PMID:16841093

  8. REVIEW OF THE NEGOTIATION OF THE MODEL PROTOCOL ADDITIONAL TO THE AGREEMENT(S) BETWEEN STATE(S) AND THE INTERNATIONAL ATOMIC ENERGY AGENCY FOR THE APPLICATION OF SAFEGUARDS, INFCIRC/540 (Corrected) VOLUME II/III IAEA COMMITTEE 24, Major Issues Underlying the Model Additional Protocol (1996-1997).

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

    Rosenthal, M.D.; Saum-Manning, L.; Houck, F.

    Volume I of this Review traces the origins of the Model Additional Protocol. It covers the period from 1991, when events in Iraq triggered an intensive review of the safeguards system, until 1996, when the IAEA Board of Governors established Committee 24 to negotiate a new protocol to safeguards agreement. The period from 1991-1996 set the stage for this negotiation and shaped its outcome in important ways. During this 5-year period, many proposals for strengthening safeguards were suggested and reviewed. Some proposals were dropped, for example, the suggestion by the IAEA Secretariat to verify certain imports, and others were refined.more » A rough consensus was established about the directions in which the international community wanted to go, and this was reflected in the draft of an additional protocol that was submitted to the IAEA Board of Governors on May 6, 1996 in document GOV/2863, Strengthening the Effectiveness and Improving the Efficiency of the Safeguards System - Proposals For Implementation Under Complementary Legal Authority, A Report by the Director General. This document ended with a recommendation that, 'the Board, through an appropriate mechanism, finalize the required legal instrument taking as a basis the draft protocol proposed by the Secretariat and the explanation of the measures contained in this document.'« less

  9. A Comparison of the Use of Bony Anatomy and Internal Markers for Offline Verification and an Evaluation of the Potential Benefit of Online and Offline Verification Protocols for Prostate Radiotherapy

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

    McNair, Helen A.; Hansen, Vibeke N.; Parker, Christopher

    2008-05-01

    Purpose: To evaluate the utility of intraprostatic markers in the treatment verification of prostate cancer radiotherapy. Specific aims were: to compare the effectiveness of offline correction protocols, either using gold markers or bony anatomy; to estimate the potential benefit of online correction protocol's using gold markers; to determine the presence and effect of intrafraction motion. Methods and Materials: Thirty patients with three gold markers inserted had pretreatment and posttreatment images acquired and were treated using an offline correction protocol and gold markers. Retrospectively, an offline protocol was applied using bony anatomy and an online protocol using gold markers. Results: Themore » systematic errors were reduced from 1.3, 1.9, and 2.5 mm to 1.1, 1.1, and 1.5 mm in the right-left (RL), superoinferior (SI), and anteroposterior (AP) directions, respectively, using the offline correction protocol and gold markers instead of bony anatomy. The subsequent decrease in margins was 1.7, 3.3, and 4 mm in the RL, SI, and AP directions, respectively. An offline correction protocol combined with an online correction protocol in the first four fractions reduced random errors further to 0.9, 1.1, and 1.0 mm in the RL, SI, and AP directions, respectively. A daily online protocol reduced all errors to <1 mm. Intrafraction motion had greater impact on the effectiveness of the online protocol than the offline protocols. Conclusions: An offline protocol using gold markers is effective in reducing the systematic error. The value of online protocols is reduced by intrafraction motion.« less

  10. Project W-211, initial tank retrieval systems, description of operations for 241-AP-102 and 241-AP-104

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

    RIECK, C.A.

    1999-02-25

    The primary purpose of the Initial Tank Retrieval Systems (ITRS) is to provide systems for retrieval of radioactive wastes stored in underground double-shell tanks (DSTS) for transfer to alternate storage, evaporation, pretreatment or treatment, while concurrently reducing risks associated with safety watch list and other DSTs. This Description of Operations (DOO) defines the control philosophy for the waste retrieval system for tanks 241-AP-102 (AP-102) and 241-AP-104 (AP-104). This DOO will provide a basis for the detailed design of the Retrieval Control System (RCS) for AP-102 and AP-104 and establishes test criteria for the RCS. The test criteria will be usedmore » during qualification testing and acceptance testing to verify operability.« less

  11. Functional Analysis of AP-2 α and μ2 Subunits

    PubMed Central

    Motley, Alison M.; Berg, Nicola; Taylor, Marcus J.; Sahlender, Daniela A.; Hirst, Jennifer; Owen, David J.

    2006-01-01

    The AP-2 adaptor complex plays a key role in cargo recognition and clathrin-coated vesicle formation at the plasma membrane. To investigate the functions of individual binding sites and domains of the AP-2 complex in vivo, we have stably transfected HeLa cells with wild-type and mutant small interfering RNA–resistant α and μ2 subunits and then used siRNA knockdowns to deplete the endogenous proteins. Mutating the PtdIns(4,5)P2 binding site of α, the phosphorylation site of μ2, or the YXXΦ binding site of μ2 impairs AP-2 function, as assayed by transferrin uptake. In contrast, removing the C-terminal appendage domain of α, or mutating the PtdIns(4,5)P2 binding site of μ2, has no apparent effect. However, adding a C-terminal GFP tag to α renders it completely nonfunctional. These findings demonstrate that there is some functional redundancy in the binding sites of the various AP-2 subunits, because no single mutation totally abolishes function. They also help to explain why GFP-tagged AP-2 never appears to leave the plasma membrane in some live cell imaging studies. Finally, they establish a new model system that can be used both for additional structure-function analyses, and as a way of testing tagged constructs for function in vivo. PMID:17035630

  12. BLOC-2, AP-3, and AP-1 Proteins Function in Concert with Rab38 and Rab32 Proteins to Mediate Protein Trafficking to Lysosome-related Organelles*

    PubMed Central

    Bultema, Jarred J.; Ambrosio, Andrea L.; Burek, Carolyn L.; Di Pietro, Santiago M.

    2012-01-01

    Lysosome-related organelles (LROs) are synthesized in specialized cell types where they largely coexist with conventional lysosomes. Most of the known cellular transport machinery involved in biogenesis are ubiquitously expressed and shared between lysosomes and LROs. Examples of common components are the adaptor protein complex-3 (AP-3) and biogenesis of lysosome-related organelle complex (BLOC)-2. These protein complexes control sorting and transport of newly synthesized integral membrane proteins from early endosomes to both lysosomes and LROs such as the melanosome. However, it is unknown what factors cooperate with the ubiquitous transport machinery to mediate transport to LROs in specialized cells. Focusing on the melanosome, we show that the ubiquitous machinery interacts with cell type-specific Rab proteins, Rab38 and Rab32, to facilitate transport to the maturing organelle. BLOC-2, AP-3, and AP-1 coimmunoprecipitated with Rab38 and Rab32 from MNT-1 melanocytic cell extracts. BLOC-2, AP-3, AP-1, and clathrin partially colocalized with Rab38 and Rab32 by confocal immunofluorescence microscopy in MNT-1 cells. Rab38- and Rab32-deficient MNT-1 cells displayed abnormal trafficking and steady state levels of known cargoes of the BLOC-2, AP-3, and AP-1 pathways, the melanin-synthesizing enzymes tyrosinase and tyrosinase-related protein-1. These observations support the idea that Rab38 and Rab32 are the specific factors that direct the ubiquitous machinery to mediate transport from early endosomes to maturing LROs. Additionally, analysis of tyrosinase-related protein-2 and total melanin production indicates that Rab32 has unique functions that cannot be carried out by Rab38 in melanosome biogenesis. PMID:22511774

  13. BLOC-2, AP-3, and AP-1 proteins function in concert with Rab38 and Rab32 proteins to mediate protein trafficking to lysosome-related organelles.

    PubMed

    Bultema, Jarred J; Ambrosio, Andrea L; Burek, Carolyn L; Di Pietro, Santiago M

    2012-06-01

    Lysosome-related organelles (LROs) are synthesized in specialized cell types where they largely coexist with conventional lysosomes. Most of the known cellular transport machinery involved in biogenesis are ubiquitously expressed and shared between lysosomes and LROs. Examples of common components are the adaptor protein complex-3 (AP-3) and biogenesis of lysosome-related organelle complex (BLOC)-2. These protein complexes control sorting and transport of newly synthesized integral membrane proteins from early endosomes to both lysosomes and LROs such as the melanosome. However, it is unknown what factors cooperate with the ubiquitous transport machinery to mediate transport to LROs in specialized cells. Focusing on the melanosome, we show that the ubiquitous machinery interacts with cell type-specific Rab proteins, Rab38 and Rab32, to facilitate transport to the maturing organelle. BLOC-2, AP-3, and AP-1 coimmunoprecipitated with Rab38 and Rab32 from MNT-1 melanocytic cell extracts. BLOC-2, AP-3, AP-1, and clathrin partially colocalized with Rab38 and Rab32 by confocal immunofluorescence microscopy in MNT-1 cells. Rab38- and Rab32-deficient MNT-1 cells displayed abnormal trafficking and steady state levels of known cargoes of the BLOC-2, AP-3, and AP-1 pathways, the melanin-synthesizing enzymes tyrosinase and tyrosinase-related protein-1. These observations support the idea that Rab38 and Rab32 are the specific factors that direct the ubiquitous machinery to mediate transport from early endosomes to maturing LROs. Additionally, analysis of tyrosinase-related protein-2 and total melanin production indicates that Rab32 has unique functions that cannot be carried out by Rab38 in melanosome biogenesis.

  14. How to Improve the Peer Review Method: Free-Selection vs Assigned-Pair Protocol Evaluated in a Computer Networking Course

    ERIC Educational Resources Information Center

    Papadopoulos, Pantelis M.; Lagkas, Thomas D.; Demetriadis, Stavros N.

    2012-01-01

    This study provides field research evidence on the efficiency of a "free-selection" peer review assignment protocol as compared to the typically implemented "assigned-pair" protocol. The study employed 54 sophomore students who were randomly assigned into three groups: Assigned-Pair (AP) (the teacher assigns student works for review to student…

  15. An AP Calculus Classroom Amusement Park

    ERIC Educational Resources Information Center

    Ferguson, Sarah

    2016-01-01

    Throughout the school year, AP Calculus teachers strive to teach course content comprehensively and swiftly in an effort to finish all required material before the AP Calculus exam. As early May approaches and the AP Calculus test looms, students and teachers nervously complete lessons, assignments, and assessments to ensure student preparation.…

  16. AP1000{sup R} licensing and deployment in the United States

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

    Jordan, R. P.; Russ, P. A.; Filiak, P. P.

    2012-07-01

    In recent years, both domestic and foreign utilities have turned to the standardized Westinghouse AP1000 plant design in satisfying their near - and long-term - sustainable energy needs. As direct support to these actions, licensing the AP1000 design has played a significant role by providing one of the fundamental bases in clearing regulatory hurdles leading to the start of new plant construction. Within the U.S. alone, Westinghouse AP1000 licensing activities have reached unprecedented milestones with the approvals of both AP1000 Design Certification and Southern Company's combined construction permit and operating license (COL) application directly supporting the construction of two newmore » nuclear plants in Georgia. Further COL application approvals are immediately pending for an additional two AP1000 plants in South Carolina. And, across the U.S. nuclear industry spectrum, there are 10 other COL applications under regulatory review representing some 16 new plants at 10 sites. In total, these actions represent the first wave of new plant licensing under the regulatory approval process since 1978. Fundamental to the Nuclear Regulatory Commission's AP1000 Design Certification is the formal recognition of the AP1000 passive safety design through regulatory acceptance rulemaking. Through recognition and deployment of the AP1000 Design Certification, the utility licensee / operator of this reactor design are now offered an opportunity to use a simplified 'one-step' combined license process, thereby managing substantial back-end construction schedule risk from regulatory and intervention delays. Application of this regulatory philosophy represents both acceptance and encouragement of standardized reactor designs like the AP1000. With the recent AP1000 Design Certification and utility COL acceptances, the fundamental licensing processes of this philosophy have successfully proven the attainment of significant milestones with the next stage licensing actions

  17. Advanced APS impacts on vehicle payloads

    NASA Technical Reports Server (NTRS)

    Schneider, Steven J.; Reed, Brian D.

    1989-01-01

    Advanced auxiliary propulsion system (APS) technology has the potential to both, increase the payload capability of earth-to-orbit (ETO) vehicles by reducing APS propellant mass, and simplify ground operations and logistics by reducing the number of fluids on the vehicle and eliminating toxic, corrosive propellants. The impact of integrated cryogenic APS on vehicle payloads is addressed. In this system, launch propulsion system residuals are scavenged from integral launch propulsion tanks for use in the APS. Sufficient propellant is preloaded into the APS to return to earth with margin and noncomplete scavenging assumed. No propellant conditioning is required by the APS, but ambient heat soak is accommodated. High temperature rocket materials enable the use of the unconditioned hydrogen/oxygen in the APS and are estimated to give APS rockets specific impulse of up to about 444 sec. The payload benefits are quantified and compared with an uprated monomethylhydrazine/nitrogen tetroxide system in a conservative fashion, by assuming a 25.5 percent weight growth for the hydrogen/oxygen system and a 0 percent weight growth for the uprated system. The combination of scavenging and high performance gives payload impacts which are highly mission specific. A payload benefit of 861 kg (1898 lbm) was estimated for a Space Station Freedom rendezvous mission and 2099 kg (4626 lbm) for a sortie mission, with payload impacts varying with the amount of launch propulsion residual propellants. Missions without liquid propellant scavenging were estimated to have payload penalties, however, operational benefits were still possible.

  18. Advanced APS Impacts on Vehicle Payloads

    NASA Technical Reports Server (NTRS)

    Schneider, Steven J.; Reed, Brian D.

    1989-01-01

    Advanced auxiliary propulsion system (APS) technology has the potential to both, increase the payload capability of earth-to-orbit (ETO) vehicles by reducing APS propellant mass, and simplify ground operations and logistics by reducing the number of fluids on the vehicle and eliminating toxic, corrosive propellants. The impact of integrated cryogenic APS on vehicle payloads is addressed. In this system, launch propulsion system residuals are scavenged from integral launch propulsion tanks for use in the APS. Sufficient propellant is preloaded into the APS to return to earth with margin and noncomplete scavenging assumed. No propellant conditioning is required by the APS, but ambient heat soak is accommodated. High temperature rocket materials enable the use of the unconditioned hydrogen/oxygen in the APS and are estimated to give APS rockets specific impulse of up to about 444 sec. The payload benefits are quantified and compared with an uprated monomethyl hydrazine/nitrogen tetroxide system in a conservative fashion, by assuming a 25.5 percent weight growth for the hydrogen/oxygen system and a 0 percent weight growth for the uprated system. The combination and scavenging and high performance gives payload impacts which are highly mission specific. A payload benefit of 861 kg (1898 lbm) was estimated for a Space Station Freedom rendezvous mission and 2099 kg (4626 lbm) for a sortie mission, with payload impacts varying with the amount of launch propulsion residual propellants. Missions without liquid propellant scavenging were estimated to have payload penalties, however, operational benefits were still possible.

  19. An Updated AP2 Beamline TURTLE Model

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

    Gormley, M.; O'Day, S.

    1991-08-23

    This note describes a TURTLE model of the AP2 beamline. This model was created by D. Johnson and improved by J. Hangst. The authors of this note have made additional improvements which reflect recent element and magnet setting changes. The magnet characteristics measurements and survey data compiled to update the model will be presented. A printout of the actual TURTLE deck may be found in appendix A.

  20. 77 FR 24480 - Application for New Awards; Advanced Placement (AP) Test Fee Program-Reopening the AP Test Fee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-24

    ... DEPARTMENT OF EDUCATION Application for New Awards; Advanced Placement (AP) Test Fee Program--Reopening the AP Test Fee Fiscal Year 2012 Competition AGENCY: Office of Elementary and Secondary Education (OESE), Department of Education. ACTION: Notice reopening the AP Test Fee fiscal year 2012 competition...

  1. Structural characterization of the N-terminal mineral modification domains from the molluscan crystal-modulating biomineralization proteins, AP7 and AP24.

    PubMed

    Wustman, Brandon A; Morse, Daniel E; Evans, John Spencer

    2004-08-05

    The AP7 and AP24 proteins represent a class of mineral-interaction polypeptides that are found in the aragonite-containing nacre layer of mollusk shell (H. rufescens). These proteins have been shown to preferentially interfere with calcium carbonate mineral growth in vitro. It is believed that both proteins play an important role in aragonite polymorph selection in the mollusk shell. Previously, we demonstrated the 1-30 amino acid (AA) N-terminal sequences of AP7 and AP24 represent mineral interaction/modification domains in both proteins, as evidenced by their ability to frustrate calcium carbonate crystal growth at step edge regions. In this present report, using free N-terminal, C(alpha)-amide "capped" synthetic polypeptides representing the 1-30 AA regions of AP7 (AP7-1 polypeptide) and AP24 (AP24-1 polypeptide) and NMR spectroscopy, we confirm that both N-terminal sequences possess putative Ca (II) interaction polyanionic sequence regions (2 x -DD- in AP7-1, -DDDED- in AP24-1) that are random coil-like in structure. However, with regard to the remaining sequences regions, each polypeptide features unique structural differences. AP7-1 possesses an extended beta-strand or polyproline type II-like structure within the A11-M10, S12-V13, and S28-I27 sequence regions, with the remaining sequence regions adopting a random-coil-like structure, a trait common to other polyelectrolyte mineral-associated polypeptide sequences. Conversely, AP24-1 possesses random coil-like structure within A1-S9 and Q14-N16 sequence regions, and evidence for turn-like, bend, or loop conformation within the G10-N13, Q17-N24, and M29-F30 sequence regions, similar to the structures identified within the putative elastomeric proteins Lustrin A and sea urchin spicule matrix proteins. The similarities and differences in AP7 and AP24 N-terminal domain structure are discussed with regard to joint AP7-AP24 protein modification of calcium carbonate growth. Copyright 2004 Wiley Periodicals, Inc.

  2. Observational studies of roAp stars

    NASA Astrophysics Data System (ADS)

    Sachkov, M.

    2014-11-01

    Rapidly oscillating Ap (roAp) stars are high-overtone, low-degree p-mode pulsators that are also chemically peculiar magnetic A stars. Until recently the classical asteroseismic analysis i.e. frequency analysis, of these stars was based on ground and space photometric observations. Significant progress was achieved through access to uninterrupted, ultra-high-precision data from MOST, COROT and Kepler satellites. Over the last ten years the study of roAp stars has been altered drastically from an observational point of view through studies of time-resolved, high-resolution spectra. Their unusual pulsational characteristics, caused by an interplay between the short vertical lengths of the pulsation waves and strong stratification of chemical elements, allow us to examine the upper roAp atmosphere in more detail than is possible for any star except the Sun. In this paper I review the results of recent studies of the pulsations of roAp stars.

  3. Comparative Ballistic Performance of 20mm AP M95 and 20mm AP M75 Projectiles against Rolled Homogeneous Steel Armor

    DTIC Science & Technology

    1960-05-01

    Dominic A. Piccione, " Comparative Ballistic Performanceof 20mm AP M95 and 20mm AP M75 Projectiles againstRolled Homogeneous Steel Armor (U)’\\ WAL-TR-160.1/1... COMPARATIVE BALLISTIC PERFORMANCE OF 20MM AP M95 AND 20MM AP M75 PROJECTILES AGAINST ROLLED HOMOGENEOUS STEEL ARMOR (U) TECHNICAL REPORT NO. WAL TR I60.l/I(c...o > -< Abt9sortf bl O *_, o o -o WATERTOWN ARSENAL LABORATORIES co COMPARATIVE BALLISTIC PERFORMANCE OF 20MM AP M95 AND 20MM AP M75

  4. SU-F-207-02: Use of Postmortem Subjects for Subjective Image Quality Assessment in Abdominal CT Protocols with Iterative Reconstruction

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

    Mench, A; Lipnharski, I; Carranza, C

    Purpose: New radiation dose reduction technologies are emerging constantly in the medical imaging field. The latest of these technologies, iterative reconstruction (IR) in CT, presents the ability to reduce dose significantly and hence provides great opportunity for CT protocol optimization. However, without effective analysis of image quality, the reduction in radiation exposure becomes irrelevant. This work explores the use of postmortem subjects as an image quality assessment medium for protocol optimizations in abdominal CT. Methods: Three female postmortem subjects were scanned using the Abdomen-Pelvis (AP) protocol at reduced minimum tube current and target noise index (SD) settings of 12.5, 17.5,more » 20.0, and 25.0. Images were reconstructed using two strengths of iterative reconstruction. Radiologists and radiology residents from several subspecialties were asked to evaluate 8 AP image sets including the current facility default scan protocol and 7 scans with the parameters varied as listed above. Images were viewed in the soft tissue window and scored on a 3-point scale as acceptable, borderline acceptable, and unacceptable for diagnosis. The facility default AP scan was identified to the reviewer while the 7 remaining AP scans were randomized and de-identified of acquisition and reconstruction details. The observers were also asked to comment on the subjective image quality criteria they used for scoring images. This included visibility of specific anatomical structures and tissue textures. Results: Radiologists scored images as acceptable or borderline acceptable for target noise index settings of up to 20. Due to the postmortem subjects’ close representation of living human anatomy, readers were able to evaluate images as they would those of actual patients. Conclusion: Postmortem subjects have already been proven useful for direct CT organ dose measurements. This work illustrates the validity of their use for the crucial evaluation of image

  5. APS Education and Diversity Efforts

    NASA Astrophysics Data System (ADS)

    Prestridge, Katherine; Hodapp, Theodore

    2015-11-01

    American Physical Society (APS) has a wide range of education and diversity programs and activities, including programs that improve physics education, increase diversity, provide outreach to the public, and impact public policy. We present the latest programs spearheaded by the Committee on the Status of Women in Physics (CSWP), with highlights from other diversity and education efforts. The CSWP is working to increase the fraction of women in physics, understand and implement solutions for gender-specific issues, enhance professional development opportunities for women in physics, and remedy issues that impact gender inequality in physics. The Conferences for Undergraduate Women in Physics, Professional Skills Development Workshops, and our new Professional Skills program for students and postdocs are all working towards meeting these goals. The CSWP also has site visit and conversation visit programs, where department chairs request that the APS assess the climate for women in their departments or facilitate climate discussions. APS also has two significant programs to increase participation by underrepresented minorities (URM). The newest program, the APS National Mentoring Community, is working to provide mentoring to URM undergraduates, and the APS Bridge Program is an established effort that is dramatically increasing the number of URM PhDs in physics.

  6. Ap4A induces apoptosis in human cultured cells.

    PubMed

    Vartanian, A; Alexandrov, I; Prudowski, I; McLennan, A; Kisselev, L

    1999-07-30

    Diadenosine oligophosphates (Ap(n)A) have been proposed as intracellular and extracellular signaling molecules in animal cells. The ratio of diadenosine 5',5'''-P1,P3-triphosphate to diadenosine 5',5'''-P1,P4-tetraphosphate (Ap3A/Ap4A) is sensitive to the cellular status and alters when cultured cells undergo differentiation or are treated with interferons. In cells undergoing apoptosis induced by DNA topoisomerase II inhibitor VP16, the concentration of Ap3A decreases significantly while that of Ap4A increases. Here, we have examined the effects of exogenously added Ap3A and Ap4A on apoptosis and morphological differentiation. Penetration of Ap(n)A into cells was achieved by cold shock. Ap4A at 10 microM induced programmed cell death in human HL60, U937 and Jurkat cells and mouse VMRO cells and this effect appeared to require Ap4A breakdown as hydrolysis-resistant analogues of Ap4A were inactive. On its own, Ap3A induced neither apoptosis nor cell differentiation but did display strong synergism with the protein kinase C activators 12-deoxyphorbol-13-O-phenylacetate and 12-deoxyphorbol-13-O-phenylacetate-20-acetate in inducing differentiation of HL60 cells. We propose that Ap4A and Ap3A are physiological antagonists in determination of the cellular status: Ap4A induces apoptosis whereas Ap3A is a co-inductor of differentiation. In both cases, the mechanism of signal transduction remains unknown.

  7. Health in All Policies (HiAP) governance: lessons from network governance.

    PubMed

    Khayatzadeh-Mahani, Akram; Ruckert, Arne; Labonté, Ronald; Kenis, Patrick; Akbari-Javar, Mohammad Reza

    2018-05-25

    The Health in All Policies (HiAP) approach requires formal and sustained governance structures and mechanisms to ensure that the policies of various non-health sectors maximize positive and minimize negative impacts on population health. In this paper, we demonstrate the usefulness of a network perspective in understanding and contributing to the effectiveness of HiAP. We undertook an exploratory, qualitative case study of a HiAP structure in Iran, the Kerman province Council of Health and Food Security (CHFS) with diverse members from health and non-health sectors. We analyzed relevant policy texts and interviewed 32 policy actors involved in the CHFS. Data were analyzed using within-case analysis and constant comparative methodology. Our findings suggest that CHFS governance from a network perspective drew in practice on elements of two competing network governance modes: the network administrative organization (NAO) and the lead organization mode. Our results also show that a shift from a hierarchical and market-based mode of interaction to a network logic within CHFS has not yet taken place. In addition, CHFS suffers from large membership and an inability to address complex 'wicked problems', as well as low trust, legitimacy and goal consensus among its members. Drawing on other HiAP studies and commentaries, insights from organization network theory, and in-depth findings from our case study, we conclude that a NAO may be the most effective mode of governance for tackling complex social problems in HiAP structures. Since similar studies are limited, and our single case study may not be transferable across all contexts, we suggest that further research be undertaken to explore HiAP structures from a network perspective in different institutional and cultural settings. With increasing emphasis given to HiAP approaches in national and international health policy discourse, it is important that comparative knowledge about the effectiveness of HiAP governance

  8. Cardioprotective effect of diadenosine tetraphosphate (AP4A) cardioplegia in isolated rat hearts.

    PubMed

    Ahmet, I; Sawa, Y; Nishimura, M; Matsuda, H

    2000-01-01

    Preischemic administration of diadenosine tetraphosphate (AP4A) has been shown to be cardioprotective. We evaluated the protective effect of AP4A when used as a cardioplegic adjuvant and tested contributions of the ATP-sensitive potassium channel (K ATP channel), adenosine receptor (AR), and purine 2y receptor (P2yR) to the effect of AP4A. Isolated buffer-perfused rat hearts were subjected to 23 min of ischemia (37 degrees C) followed by 20 min of reperfusion. Cardioplegia solution (St. Thomas Hospital solution) was infused during the first 3 min of ischemia. AP4A (10 microM) or AP4A with glibenclamide (K ATP channel blocker, 100 microM), 8-SPT (AR antagonist, 300 microM) or reactive blue (P2yR antagonist, 13 nM) were added to the cardioplegia solution. Compared with the cardioplegia solution alone, administration of AP4A with the solution significantly increased the recovery of rate-pressure production (75% +/- 11% vs 58% +/- 10%; P < 0.05) and dp/dt at the end of reperfusion, and reduced the leakage of creatine kinase (3.2 +/- 3.7 vs 13.2 +/- 10.1 IU/g; P < 0.05) during reperfusion. This effect was reversed by coadministration of glibenclamide or reactive blue but not 8-SPT. The addition of AP4A into the cardioplegia solution led to an added cardioprotective effect, either by opening the K ATP channel or by activating P2yR.

  9. Periodic variation in the geomagnetic activity - A study based on the Ap index

    NASA Technical Reports Server (NTRS)

    De Gonzalez, Alicia L. C.; Gonzalez, Walter D.; Dutra, Severino L. G.; Tsurutani, Bruce T.

    1993-01-01

    The monthly and daily samples of the Ap index for the interval from 1932 through 1982 were studied using the power spectrum technique. Results obtained for Bartel's period (about 27 days), the semiannual period, the dual-peak solar cycle distribution of geomagnetic storms, and certain other medium-scale periodicities are examined in detail. In addition, results on the cumulative occurrence number of storms per decade as a function of the Ap and Dst indices for the storm are presented.

  10. APS Science 2007.

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

    Not Available

    2008-05-30

    This report provides research highlights from the Advanced Photon Source (APS). Although these highlights represent less than 10% of the published work from the APS in 2007, they give a flavor of the diversity and impact of user research at the facility. In the strategic planning the aim is to foster the growth of existing user communities and foresee new areas of research. This coming year finds the APS engaged in putting together, along with the users, a blueprint for the next five years, and making the case for a set of prioritized investments in beamlines, the accelerator, and infrastructure,more » each of which will be transformational in terms of scientific impact. As this is written plans are being formulated for an important user workshop on October 20-21, 2008, to prioritize strategic plans. The fruit from past investments can be seen in this report. Examples include the creation of a dedicated beamline for x-ray photon correlation spectroscopy at Sector 8, the evolution of dedicated high-energy x-ray scattering beamlines at sectors 1 and 11, a dedicated imaging beamline at Sector 32, and new beamlines for inelastic scattering and powder diffraction. A single-pulse facility has been built in collaboration with Sector 14 (BioCARS) and Phil Anfinrud at the National Institutes of Health, which will offer exceptionally high flux for single-pulse diffraction. The nanoprobe at Sector 26, built and operated jointly by the Argonne Center for Nanoscale Materials and the X-ray Operations and Research (XOR) section of the APS X-ray Science Division, has come on line to define the state of the art in nanoscience.« less

  11. Numerical Test of the Additivity Principle in Anomalous Transport

    NASA Astrophysics Data System (ADS)

    Tamaki, Shuji

    2017-10-01

    The additivity principle (AP) is one of the remarkable predictions that systematically generates all information on current fluctuations once the value of average current in the linear response regime is input. However, conditions to justify the AP are still ambiguous. We hence consider three tractable models, and discuss possible conditions. The models include the harmonic chain (HC), momentum exchange (ME) model, and momentum flip (MF) model, which respectively show ballistic, anomalous, and diffusive transport. We compare the heat current cumulants predicted by the AP with exact numerical data obtained for these models. The HC does not show the AP, whereas the MF model satisfies it, as expected, since the AP was originally proposed for diffusive systems. Surprisingly, the ME model also shows the AP. The ME model is known to show the anomalous transport similar to that shown in nonlinear systems such as the Fermi-Pasta-Ulam model. Our finding indicates that general nonlinear systems may satisfy the AP. Possible conditions for satisfying the AP are discussed.

  12. Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of human AP endonuclease 1

    PubMed Central

    Malina, Jaroslav; Scott, Peter; Brabec, Viktor

    2015-01-01

    Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo–helical ‘flexicate’ complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3]4+ incorporating the common NN–NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo–helical complexes for cancer chemotherapy. PMID:25940617

  13. High concentrations of intracellular Ap4A and/or Ap5A in developing Myxococcus xanthus cells inhibit sporulation.

    PubMed

    Kimura, Yoshio; Tanaka, Chihiro; Sasaki, Katsuho; Sasaki, Masashi

    2017-01-01

    Diadenosine polyphosphates (ApnA) are thought to act as signalling molecules regulating stress responses and biofilm formation in prokaryotes. However, ApnA function in Myxococcus xanthus remains unknown. Here, we investigated the role of ApnA in M. xanthus, using the wild-type and ApnA hydrolase (apaH) mutant strains exposed to various stress conditions. In both wild-type and apaH mutant cells cultured on starvation medium (CF agar), the levels of intracellular diadenosine tetraphosphate (Ap4A) and pentaphosphate (Ap5A) increased several fold during the first 16 h of development and decreased gradually thereafter. The levels of Ap4A and Ap5A in the apaH mutant were about 5- and 11-fold higher than those in the wild-type strain at 16 h, respectively. ApnA hydrolase activity of the wild-type strain increased 1.5-fold during the first 8 h of development, and it then gradually decreased. The apaH mutant formed spores 1-2 days after the wild-type strain did, and the yield of viable spores was 5.5 % of that in the wild-type strain 5 days after inoculation onto CF agar. These results suggest the possibility that high intracellular levels of Ap4A and/or Ap5A may inhibit M. xanthus sporulation at the early stage of development and that the bacteria reduce intracellular Ap4A and Ap5A accumulation through ApnA hydrolase activity.

  14. Component Database for the APS Upgrade

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

    Veseli, S.; Arnold, N. D.; Jarosz, D. P.

    The Advanced Photon Source Upgrade (APS-U) project will replace the existing APS storage ring with a multi-bend achromat (MBA) lattice to provide extreme transverse coherence and extreme brightness x-rays to its users. As the time to replace the existing storage ring accelerator is of critical concern, an aggressive one-year removal/installation/testing period is being planned. To aid in the management of the thousands of components to be installed in such a short time, the Component Database (CDB) application is being developed with the purpose to identify, document, track, locate, and organize components in a central database. Three major domains are beingmore » addressed: Component definitions (which together make up an exhaustive "Component Catalog"), Designs (groupings of components to create subsystems), and Component Instances (“Inventory”). Relationships between the major domains offer additional "system knowledge" to be captured that will be leveraged with future tools and applications. It is imperative to provide sub-system engineers with a functional application early in the machine design cycle. Topics discussed in this paper include the initial design and deployment of CDB, as well as future development plans.« less

  15. Human Papillomavirus Type 16 E6 Induces Self-Ubiquitination of the E6AP Ubiquitin-Protein Ligase

    PubMed Central

    Kao, Wynn H.; Beaudenon, Sylvie L.; Talis, Andrea L.; Huibregtse, Jon M.; Howley, Peter M.

    2000-01-01

    The E6 protein of the high-risk human papillomaviruses (HPVs) and the cellular ubiquitin-protein ligase E6AP form a complex which causes the ubiquitination and degradation of p53. We show here that HPV16 E6 promotes the ubiquitination and degradation of E6AP itself. The half-life of E6AP is shorter in HPV-positive cervical cancer cells than in HPV-negative cervical cancer cells, and E6AP is stabilized in HPV-positive cancer cells when expression of the viral oncoproteins is repressed. Expression of HPV16 E6 in cells results in a threefold decrease in the half-life of transfected E6AP. E6-mediated degradation of E6AP requires (i) the binding of E6 to E6AP, (ii) the catalytic activity of E6AP, and (iii) activity of the 26S proteasome, suggesting that E6-E6AP interaction results in E6AP self-ubiquitination and degradation. In addition, both in vitro and in vivo experiments indicate that E6AP self-ubiquitination results primarily from an intramolecular transfer of ubiquitin from the active-site cysteine to one or more lysine residues; however, intermolecular transfer can also occur in the context of an E6-mediated E6AP multimer. Finally, we demonstrate that an E6 mutant that is able to immortalize human mammary epithelial cells but is unable to degrade p53 retains its ability to bind and degrade E6AP, raising the possibility that E6-mediated degradation of E6AP contributes to its ability to transform mammalian cells. PMID:10864652

  16. Comparison of Spectral and Scintillation Properties of LuAP:Ce and LuAP:Ce,Sc Single Crystals

    NASA Astrophysics Data System (ADS)

    Petrosyan, Ashot G.; Derdzyan, Marina; Ovanesyan, Karine; Shirinyan, Grigori; Lecoq, Paul; Auffray, Etiennette; Kronberger, Matthias; Frisch, Benjamin; Pedrini, Christian; Dujardin, Christophe

    2009-10-01

    Scintillation properties of LuAP:Ce and LuAP:Ce,Sc crystal series were studied under excitation by gamma-rays from a 137Cs source. Both series demonstrated comparable optical quality in terms of underlying absorption at 260 nm, slope of the optical edge and transmission in the range of emission. The light yield of LuAP:Ce crystals measured in 0.2 cm times 0.2 cm times 0.8 cm pixels increases linearly with the Ce concentration reaching at 0.58 at. % 6448 plusmn 322 ph/MeV and 9911 plusmn 496 ph/MeV in the long and in the short directions respectively (the light yield ratio is 65%) and shows no sign of light saturation. The energy resolution is found to depend, among other factors, on the uniformity of Ce concentration within the pixels and is improved to 7.1 plusmn 0.4% (I = 0.2 cm), 9.5 plusmn 0.5% (I = 0.8 cm). Intentional co-doping with Sc + ions was tested and resulted in increase of the Ce distribution coefficient to about 0.3. This enabled to increase the concentration of Ce in LuAP:Ce,Sc crystals up to 0.7 at. %, while conserving high optical quality. In contrast to LuAP:Ce, the light yield in LuAP:Ce,Sc crystals does not increase with Ce concentration, the photo peak being gradually suppressed. The involved mechanisms are discussed basing on measurements of the unit cell volumes, Ce concentration uniformity, x-ray rocking spectra, absorption spectra of pure and variously doped LuAP crystals, and emission spectra under different excitations.

  17. ParamAP: Standardized Parameterization of Sinoatrial Node Myocyte Action Potentials.

    PubMed

    Rickert, Christian; Proenza, Catherine

    2017-08-22

    Sinoatrial node myocytes act as cardiac pacemaker cells by generating spontaneous action potentials (APs). Much information is encoded in sinoatrial AP waveforms, but both the analysis and the comparison of AP parameters between studies is hindered by the lack of standardized parameter definitions and the absence of automated analysis tools. Here we introduce ParamAP, a standalone cross-platform computational tool that uses a template-free detection algorithm to automatically identify and parameterize APs from text input files. ParamAP employs a graphic user interface with automatic and user-customizable input modes, and it outputs data files in text and PDF formats. ParamAP returns a total of 16 AP waveform parameters including time intervals such as the AP duration, membrane potentials such as the maximum diastolic potential, and rates of change of the membrane potential such as the diastolic depolarization rate. ParamAP provides a robust AP detection algorithm in combination with a standardized AP parameter analysis over a wide range of AP waveforms and firing rates, owing in part to the use of an iterative algorithm for the determination of the threshold potential and the diastolic depolarization rate that is independent of the maximum upstroke velocity, a parameter that can vary significantly among sinoatrial APs. Because ParamAP is implemented in Python 3, it is also highly customizable and extensible. In conclusion, ParamAP is a powerful computational tool that facilitates quantitative analysis and enables comparison of sinoatrial APs by standardizing parameter definitions and providing an automated work flow. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  18. Zinc as a second messenger of mitogenic induction. Effects on diadenosine tetraphosphate (Ap4A) and DNA synthesis.

    PubMed

    Grummt, F; Weinmann-Dorsch, C; Schneider-Schaulies, J; Lux, A

    1986-03-01

    DNA synthesis and adenosine(5')tetraphosphate(5')adenosine (Ap4A) levels decrease in cells treated with EDTA. The inhibitory effect of EDTA can be reversed with micromolar amounts of ZnCl2. ZnCl2 in micromolar concentrations also inhibits Ap4A hydrolase and stimulates amino acid-dependent Ap4A synthesis, suggesting that Zn2+ is modulating intracellular Ap4A pools. Serum addition to G1-arrested cells enhances uptake of Zn, whereas serum depletion leads to a fivefold decrease of the rates of zinc uptake. These results are discussed by regarding Zn2+ as a putative 'second messenger' of mitogenic induction and Ap4A as a possible 'third messenger' and trigger of DNA synthesis.

  19. 5',5'''-P1, P4 diadenosine tetraphosphate (Ap4A): a putative initiator of DNA replication.

    PubMed

    Baril, E F; Coughlin, S A; Zamecnik, P C

    1985-01-01

    The proposal that Ap4A acts as an inducer of DNA replication is based primarily on two pieces of evidence (7). The intracellular levels of Ap4A increase ten- to 1000-fold as cells progress into S phase and the introduction of Ap4A into nonproliferating cells stimulated DNA synthesis. There is also some additional suggestive evidence such as the binding of Ap4A to a protein that is associated with multiprotein forms of the replicative DNA polymerase alpha and the ability of this enzyme to use Ap4A as a primer for DNA synthesis in vitro with single-stranded DNA templates. These observations have stimulated interest in the cellular metabolism of Ap4A. This is well since there is a great need for additional experimentation in order to clearly establish Ap4A as an inducer of DNA replication. Microinjection experiments of Ap4A into quiescent cells are needed in order to ascertain if Ap4A will stimulate DNA replication and possibly cell division in intact cells. Studies of the effects of nonhydrolyzable analogs of Ap4A on DNA replication in intact quiescent cells could also prove valuable. Although Ap4A can function as a primer for in vitro DNA synthesis by DNA polymerase alpha this may not be relevant in regard to its in vivo role in DNA replication. Ap4A in vivo could interact with key protein(s) in DNA replication and in this way act as an effector molecule in the initiation of DNA replication. In this regard the interaction of Ap4A with a protein associated with a multiprotein form of DNA polymerase alpha isolated from S-phase cells is of interest. More experiments are required to determine if there is a specific target protein(s) for Ap4A in vivo and what its role in DNA replication is. The cofractionation of tryptophanyl-tRNA synthetase with the replicative DNA polymerase alpha from animal and plant cells is of interest. The DNA polymerase alpha from synchronized animal cells also interacted with Ap4A. Although the plant cell alpha-like DNA polymerase did not

  20. Preparing Students for the AP Psychology Exam

    ERIC Educational Resources Information Center

    Whitlock, Kristin

    2013-01-01

    The Advanced Placement Psychology exam is one of the fastest growing exams offered by the College Board. The average percent of change in the number of students taking this exam over the past five years is 12.4%. With 238,962 students taking the exam in 2013, the AP Psychology exam is the sixth largest exam, surpassing AP Biology and AP World…

  1. Power Saving Control for Battery-Powered Portable WLAN APs

    NASA Astrophysics Data System (ADS)

    Ogawa, Masakatsu; Hiraguri, Takefumi

    This paper proposes a power saving control function for battery-powered portable wireless LAN (WLAN) access points (APs) to extend the battery life. The IEEE802.11 standard does not support power saving control for APs. To enable a sleep state for an AP, the AP forces the stations (STAs) to refrain from transmitting frames using the network allocation vector (NAV) while the AP is sleeping. Thus the sleep state for the AP can be employed without causing frame loss at the STAs. Numerical analysis and computer simulation reveal that the newly proposed control technique conserves power compared to the conventional control.

  2. Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of human AP endonuclease 1.

    PubMed

    Malina, Jaroslav; Scott, Peter; Brabec, Viktor

    2015-06-23

    Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo-helical 'flexicate' complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3](4+) incorporating the common NN-NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo-helical complexes for cancer chemotherapy. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Brain suppression of AP-1 by inhaled diesel exhaust and reversal by cerium oxide nanoparticles.

    PubMed

    Lung, Shyang; Cassee, Flemming R; Gosens, Ilse; Campbell, Arezoo

    2014-08-01

    One of the uses of cerium oxide nanoparticles (nanoceria, CeO2) is as a diesel fuel additive to improve fuel efficiency. Gene/environment interactions are important determinants in the etiology of age-related disorders. Thus, it is possible that individuals on high-fat diet and genetic predisposition to vascular disease may be more vulnerable to the adverse health effects of particle exposure. The aim of this pilot study was to test the hypothesis that inhalation of diesel exhaust (DE) or diesel exhaust-containing cerium oxide nanoparticles (DCeE) induces stress in the brain of a susceptible animal model. Atherosclerotic prone, apolipoprotein E knockout (ApoE(-/-)) mice fed a high-fat diet, were exposed by inhalation to purified air (control), DE or DCeE. The stress-responsive transcription factor, activator protein-1 (AP-1), was significantly decreased in the cortical and subcortical fraction of the brain after DE exposure. The addition of nanoceria to the diesel fuel reversed this effect. The activation of another stress-related transcription factor (NF-κB) was not inhibited. AP-1 is composed of complexes of the Jun and/or Fos family of proteins. Exposure to DCeE caused c-Jun activation and this may be a mechanism by which addition of nanoceria to the fuel reversed the effect of DE exposure on AP-1 activation. This pilot study demonstrates that exposure to DE does impact the brain and addition of nanoceria may be protective. However, more extensive studies are necessary to determine how DE induced reduction of AP-1 activity and compensation by nanoceria impacts normal function of the brain.

  4. AP Powerhouse Creates High Expectations for Dallas Students: Spreading the AP Challenge to Students and Teachers.

    ERIC Educational Resources Information Center

    Nelson, Colleen McCain

    2001-01-01

    Describes how veteran teacher Joan Vinson has made Advanced Placement (AP) a "cool thing to do" for minority students. With the help of private funding and a Texas-size enthusiasm, she is also convincing more teachers to take on the AP challenge, with a focus on quality over quantity. (EV)

  5. Expansion and stress responses of the AP2/EREBP superfamily in cotton.

    PubMed

    Liu, Chunxiao; Zhang, Tianzhen

    2017-01-31

    . In addition, some homoeologous genes showed biased expression toward either A-or D-subgenome. The AP2/EREBP genes were obviously expanded in Gossypium. The GhDREB and GhERF genes play crucial roles in cotton stress responses. Our genome-wide analysis of AP2/EREBP genes in cotton provides valuable information for characterizing the molecular functions of AP2/EREBP genes and reveals insights into their evolution in polyploid plants.

  6. AP-1 subunits: quarrel and harmony among siblings.

    PubMed

    Hess, Jochen; Angel, Peter; Schorpp-Kistner, Marina

    2004-12-01

    The AP-1 transcription factor is mainly composed of Jun, Fos and ATF protein dimers. It mediates gene regulation in response to a plethora of physiological and pathological stimuli, including cytokines, growth factors, stress signals, bacterial and viral infections, as well as oncogenic stimuli. Studies in genetically modified mice and cells have highlighted a crucial role for AP-1 in a variety of cellular events involved in normal development or neoplastic transformation causing cancer. However, emerging evidence indicates that the contribution of AP-1 to determination of cell fates critically depends on the relative abundance of AP-1 subunits, the composition of AP-1 dimers, the quality of stimulus, the cell type and the cellular environment. Therefore, AP-1-mediated regulation of processes such as proliferation, differentiation, apoptosis and transformation should be considered within the context of a complex dynamic network of signalling pathways and other nuclear factors that respond simultaneously.

  7. Peculiar Traits of Coarse AP

    DTIC Science & Technology

    2014-01-01

    propellant. Since coarse AP in particles larger than about 150 microns are used in great majority for AP oxidized solid propellants, the nature of...Microscopic amounts of liquid containing water were contained in the reactive centers. The maximum size for reactive centers was reasoned to be...bond in the original chlorate ion. Oxygen atom swapping between chlorate and perchlorate ions would provide chlorate migration without use of forces

  8. CT protocol management: simplifying the process by using a master protocol concept.

    PubMed

    Szczykutowicz, Timothy P; Bour, Robert K; Rubert, Nicholas; Wendt, Gary; Pozniak, Myron; Ranallo, Frank N

    2015-07-08

    This article explains a method for creating CT protocols for a wide range of patient body sizes and clinical indications, using detailed tube current information from a small set of commonly used protocols. Analytical expressions were created relating CT technical acquisition parameters which can be used to create new CT protocols on a given scanner or customize protocols from one scanner to another. Plots of mA as a function of patient size for specific anatomical regions were generated and used to identify the tube output needs for patients as a function of size for a single master protocol. Tube output data were obtained from the DICOM header of clinical images from our PACS and patient size was measured from CT localizer radiographs under IRB approval. This master protocol was then used to create 11 additional master protocols. The 12 master protocols were further combined to create 39 single and multiphase clinical protocols. Radiologist acceptance rate of exams scanned using the clinical protocols was monitored for 12,857 patients to analyze the effectiveness of the presented protocol management methods using a two-tailed Fisher's exact test. A single routine adult abdominal protocol was used as the master protocol to create 11 additional master abdominal protocols of varying dose and beam energy. Situations in which the maximum tube current would have been exceeded are presented, and the trade-offs between increasing the effective tube output via 1) decreasing pitch, 2) increasing the scan time, or 3) increasing the kV are discussed. Out of 12 master protocols customized across three different scanners, only one had a statistically significant acceptance rate that differed from the scanner it was customized from. The difference, however, was only 1% and was judged to be negligible. All other master protocols differed in acceptance rate insignificantly between scanners. The methodology described in this paper allows a small set of master protocols to be

  9. CT protocol management: simplifying the process by using a master protocol concept

    PubMed Central

    Bour, Robert K.; Rubert, Nicholas; Wendt, Gary; Pozniak, Myron; Ranallo, Frank N.

    2015-01-01

    This article explains a method for creating CT protocols for a wide range of patient body sizes and clinical indications, using detailed tube current information from a small set of commonly used protocols. Analytical expressions were created relating CT technical acquisition parameters which can be used to create new CT protocols on a given scanner or customize protocols from one scanner to another. Plots of mA as a function of patient size for specific anatomical regions were generated and used to identify the tube output needs for patients as a function of size for a single master protocol. Tube output data were obtained from the DICOM header of clinical images from our PACS and patient size was measured from CT localizer radiographs under IRB approval. This master protocol was then used to create 11 additional master protocols. The 12 master protocols were further combined to create 39 single and multiphase clinical protocols. Radiologist acceptance rate of exams scanned using the clinical protocols was monitored for 12,857 patients to analyze the effectiveness of the presented protocol management methods using a two‐tailed Fisher's exact test. A single routine adult abdominal protocol was used as the master protocol to create 11 additional master abdominal protocols of varying dose and beam energy. Situations in which the maximum tube current would have been exceeded are presented, and the trade‐offs between increasing the effective tube output via 1) decreasing pitch, 2) increasing the scan time, or 3) increasing the kV are discussed. Out of 12 master protocols customized across three different scanners, only one had a statistically significant acceptance rate that differed from the scanner it was customized from. The difference, however, was only 1% and was judged to be negligible. All other master protocols differed in acceptance rate insignificantly between scanners. The methodology described in this paper allows a small set of master protocols to be

  10. AP Human Geography and Success on the AP Test

    ERIC Educational Resources Information Center

    Roncone, John; Newhalfen, Nate

    2013-01-01

    Classroom projects that explore culture and globalization enhance the curriculum and help students see how geography directly connects to their lives. These authors contend that a project-based approach can supplement the teaching of an AP Human Geography course, and visualize this course as an essential tool for students to truly understand how…

  11. 75 FR 4323 - Additional Quantitative Fit-testing Protocols for the Respiratory Protection Standard

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-27

    ... respirators (500 and 1000 for protocols 1 and 2, respectively). However, OSHA could not evaluate the results... the values of these descriptive statistics for revised PortaCount[supreg] QNFT protocols 1 (at RFFs of 100 and 500) and 2 (at RFFs of 200 and 1000). Table 2--Descriptive Statistics for RFFs of 100 and 200...

  12. Degraded λ-carrageenan activates NF-κB and AP-1 pathways in macrophages and enhances LPS-induced TNF-α secretion through AP-1.

    PubMed

    Chen, Haimin; Wang, Feng; Mao, Haihua; Yan, Xiaojun

    2014-07-01

    Carrageenan (CGN), a high molecular weight sulfated polysaccharide, is a traditional ingredient used in food industry. Its degraded forms have been identified as potential carcinogens, although the mechanism remains unclear. The effects of degraded λ-carrageenan (λ-dCGN) on murine RAW264.7 cells and human THP-1-derived macrophage cells were investigated by studying its actions on tumor necrosis factor alpha (TNF-α) secretion, Toll-like receptor 4 (TLR4) expression, and activation of nuclear factor-κb (NF-κB) and activation protein-1 (AP-1) pathways. We found that λ-dCGN was much stronger than native λ-CGN in the activation of macrophages to secrete TNF-α. Treatment of RAW264.7 cells with λ-dCGN resulted in the upregulation of TLR4, CD14 and MD-2 expressions, but it did not increase the binding of lipopolysacchride (LPS) with macrophages. Meanwhile, λ-dCGN treatment activated NF-κB via B-cell lymphoma/leukemia 10 (Bcl10) and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation. In addition, λ-dCGN induced extracellular signal-regulated kinases/1/2/mitogen-activated protein kinases (ERK1/2/MAPK) and AP-1 activation. Interestingly, pretreatment of RAW264.7 cells with λ-dCGN markedly enhanced LPS-stimulated TNF-α secretion. This pretreatment resulted in the enhanced phosphorylation of ERK1/2 and c-Jun N-terminal kinase (JNK) and intensified activation of AP-1. λ-dCGN induced an inflammatory reaction via both NF-κB and AP-1, and enhanced the inflammatory effect of LPS through AP-1 activation. The study demonstrated the role of λ-dCGN to induce the inflammatory reaction and to aggravate the effect of LPS on macrophages, suggesting that λ-dCGN produced during food processing and gastric digestion may be a safety concern. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Crystal structures of Salmonella typhimurium propionate kinase and its complex with Ap4A: evidence for a novel Ap4A synthetic activity.

    PubMed

    Simanshu, Dhirendra K; Savithri, H S; Murthy, M R N

    2008-03-01

    Propionate kinase catalyses the last step in the anaerobic breakdown of L-threonine to propionate in which propionyl phosphate and ADP are converted to propionate and ATP. Here we report the structures of propionate kinase (TdcD) in the native form as well as in complex with diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) by X-ray crystallography. Structure of TdcD obtained after cocrystallization with ATP showed Ap4A bound to the active site pocket suggesting the presence of Ap4A synthetic activity in TdcD. Binding of Ap4A to the enzyme was confirmed by the structure determination of a TdcD-Ap4A complex obtained after cocrystallization of TdcD with commercially available Ap4A. Mass spectroscopic studies provided further evidence for the formation of Ap4A by propionate kinase in the presence of ATP. In the TdcD-Ap4A complex structure, Ap4A is present in an extended conformation with one adenosine moiety present in the nucleotide binding site and other in the proposed propionate binding site. These observations tend to support direct in-line transfer of phosphoryl group during the kinase reaction. 2007 Wiley-Liss, Inc.

  14. Genome-wide investigation and expression analysis of AP2-ERF gene family in salt tolerant common bean

    PubMed Central

    Kavas, Musa; Kizildogan, Aslihan; Gökdemir, Gökhan; Baloglu, Mehmet Cengiz

    2015-01-01

    Apetala2-ethylene-responsive element binding factor (AP2-ERF) superfamily with common AP2-DNA binding domain have developmentally and physiologically important roles in plants. Since common bean genome project has been completed recently, it is possible to identify all of the AP2-ERF genes in the common bean genome. In this study, a comprehensive genome-wide in silico analysis identified 180 AP2-ERF superfamily genes in common bean (Phaseolus vulgaris). Based on the amino acid alignment and phylogenetic analyses, superfamily members were classified into four subfamilies: DREB (54), ERF (95), AP2 (27) and RAV (3), as well as one soloist. The physical and chemical characteristics of amino acids, interaction between AP2-ERF proteins, cis elements of promoter region of AP2-ERF genes and phylogenetic trees were predicted and analyzed. Additionally, expression levels of AP2-ERF genes were evaluated by in silico and qRT-PCR analyses. In silico micro-RNA target transcript analyses identified nearly all PvAP2-ERF genes as targets of by 44 different plant species' miRNAs were identified in this study. The most abundant target genes were PvAP2/ERF-20-25-62-78-113-173. miR156, miR172 and miR838 were the most important miRNAs found in targeting and BLAST analyses. Interactome analysis revealed that the transcription factor PvAP2-ERF78, an ortholog of Arabidopsis At2G28550, was potentially interacted with at least 15 proteins, indicating that it was very important in transcriptional regulation. Here we present the first study to identify and characterize the AP2-ERF transcription factors in common bean using whole-genome analysis, and the findings may serve as a references for future functional research on the transcription factors in common bean. PMID:27152109

  15. Protocols — EDRN Public Portal

    Cancer.gov

    EDRN investigators protocols. The following is a list of the EDRN protocols that have been captured and curated. Additional information will be added as it is available. Contact information is provided as part of the detail for each protocol.

  16. Comparison of jump-landing protocols with Biodex Balance System as measures of dynamic postural stability in athletes.

    PubMed

    Krkeljas, Zarko

    2017-07-21

    The objective of the study was to determine whether a relationship exists between the two common methods for assessing postural stability in athletes: the time-to-stabilisation (TTS) via force-plate and the Biodex Balance System (BBS). The conditions under which these measurements assess dynamic postural control may not provide sufficient feedback to practitioners. Fourty-four amateur soccer players with no history of musculoskeletal disorders volunteered for the study. Pearson correlation was used to compare the anterior-posterior (AP), medio-lateral (ML), and the overall stability indexes measured by BBS, with the corresponding parameters of TTS assessed via force plate. There was no significant correlation between any parameters of dynamic stability measured by force-plate and the stability indexes. However, there was a significant correlation between the resulting vectors and the AP component of TTS for each jump protocol. Furthermore, forward drop landing exhibited shortest TTS in AP direction, while lateral drop landing resulted in longer ML TTS relative to both forward jumps (p < 0.001). These results demonstrate that the TTS and BBS stability indexes should be used as distinct measures of dynamic postural stability. TTS protocols may be modified to target a specific training conditions or athletic population.

  17. Free factor XIII activation peptide (fAP-FXIII) is a regulator of factor XIII activity via factor XIII-B.

    PubMed

    Dodt, Johannes; Pasternack, Ralf; Seitz, Rainer; Volkers, Peter

    2016-02-01

    In a factor XIIIa (FXIIIa) generation assay with recombinant FXIII-A2 (rFXIII-A2 ) free FXIII activation peptide (fAP-FXII) prolonged the time to peak (TTP) but did not affect the area under the curve (AUC) or concentration at peak (CP). Addition of recombinant factorXIII-B2 (rFXIII-B2 ) restored the characteristics of the FXIIIa generation parameters (AUC, TTP and CP) to those observed for plasma FXIII (FXIII-A2 B2 ). FXIII-A2 B2 reconstituted from rFXIII-A2 and rFXIII-B2 showed a similar effect on AUC, TTP and CP in the presence of fAP-FXII as observed for plasma FXIII-A2 B2 , indicating a role for FXIII-B in this observation. An effect of fAP-FXIII on thrombin, the proteolytic activator of FXIII, was excluded by thrombin generation assays and clotting experiments. In a purified system, fAP-FXIII did not interfere with the FXIIIa activity development of thrombin-cleaved rFXIII-A2 (rFXIII-A2 ') also excluding direct inhibition of FXIIIa. However, FXIIIa activity development of FXIII-A2 'B2 was inhibited in a concentration-dependent manner by fAP-FXIII, indicating that an interaction between AP-FXIII and FXIII-B2 contributes to the overall stability of FXIII-A2 'B2 . In addition to its well-known role, FXIII-B also contributes to FXIII-A2 B2 stability or dissociation depending on fAP-FXIII and calcium concentrations. © 2015 John Wiley & Sons Ltd.

  18. Obstetrical APS: is there a place for hydroxychloroquine to improve the pregnancy outcome?

    PubMed

    Mekinian, Arsene; Costedoat-Chalumeau, Nathalie; Masseau, Agathe; Tincani, Angela; De Caroli, Sara; Alijotas-Reig, Jaume; Ruffatti, Amelia; Ambrozic, Ales; Botta, Angela; Le Guern, Véronique; Fritsch-Stork, Ruth; Nicaise-Roland, Pascale; Carbonne, Bruno; Carbillon, Lionel; Fain, Olivier

    2015-01-01

    The use of the conventional APS treatment (the combination of low-dose aspirin and LMWH) dramatically improved the obstetrical prognosis in primary obstetrical APS (OAPS). The persistence of adverse pregnancy outcome raises the need to find other drugs to improve obstetrical outcome. Hydroxychloroquine is widely used in patients with various autoimmune diseases, particularly SLE. Antimalarials have many anti-inflammatory, anti-aggregant and immune-regulatory properties: they inhibit phospholipase activity, stabilize lysosomal membranes, block the production of several pro-inflammatory cytokines and, in addition, impair complement-dependent antigen-antibody reactions. There is ample evidence of protective effects of hydroxychloroquine in OAPS similar to the situation in SLE arising from in vitro studies of pathophysiological working mechanism of hydroxychloroquine. However, the clinical data on the use of hydroxychloroquine in primary APS are lacking and prospective studies are necessary. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. AP Courses Get Audited for Quality

    ERIC Educational Resources Information Center

    Ashford, Ellie

    2007-01-01

    As the college admissions process has gotten much more competitive, the number of high school students taking Advanced Placement (AP) courses has soared. At the same time, policymakers and education leaders seek to get more minorities and students not on the college track to sign up for AP and other rigorous classes. But as high schools have…

  20. Translocation pathway of protein substrates in ClpAP protease

    PubMed Central

    Ishikawa, Takashi; Beuron, Fabienne; Kessel, Martin; Wickner, Sue; Maurizi, Michael R.; Steven, Alasdair C.

    2001-01-01

    Intracellular protein degradation, which must be tightly controlled to protect normal proteins, is carried out by ATP-dependent proteases. These multicomponent enzymes have chaperone-like ATPases that recognize and unfold protein substrates and deliver them to the proteinase components for digestion. In ClpAP, hexameric rings of the ClpA ATPase stack axially on either face of the ClpP proteinase, which consists of two apposed heptameric rings. We have used cryoelectron microscopy to characterize interactions of ClpAP with the model substrate, bacteriophage P1 protein, RepA. In complexes stabilized by ATPγS, which bind but do not process substrate, RepA dimers are seen at near-axial sites on the distal surface of ClpA. On ATP addition, RepA is translocated through ≈150 Å into the digestion chamber inside ClpP. Little change is observed in ClpAP, implying that translocation proceeds without major reorganization of the ClpA hexamer. When translocation is observed in complexes containing a ClpP mutant whose digestion chamber is already occupied by unprocessed propeptides, a small increase in density is observed within ClpP, and RepA-associated density is also seen at other axial sites. These sites appear to represent intermediate points on the translocation pathway, at which segments of unfolded RepA subunits transiently accumulate en route to the digestion chamber. PMID:11287666

  1. Altered distribution of ATG9A and accumulation of axonal aggregates in neurons from a mouse model of AP-4 deficiency syndrome

    PubMed Central

    De Pace, Raffaella; Damme, Markus; Mattera, Rafael; Jarnik, Michal; Hoffmann, Victoria; Morris, H. Douglas; Han, Tae-Un; Mancini, Grazia M. S.; Buonanno, Andrés

    2018-01-01

    The hereditary spastic paraplegias (HSP) are a clinically and genetically heterogeneous group of disorders characterized by progressive lower limb spasticity. Mutations in subunits of the heterotetrameric (ε-β4-μ4-σ4) adaptor protein 4 (AP-4) complex cause an autosomal recessive form of complicated HSP referred to as “AP-4 deficiency syndrome”. In addition to lower limb spasticity, this syndrome features intellectual disability, microcephaly, seizures, thin corpus callosum and upper limb spasticity. The pathogenetic mechanism, however, remains poorly understood. Here we report the characterization of a knockout (KO) mouse for the AP4E1 gene encoding the ε subunit of AP-4. We find that AP-4 ε KO mice exhibit a range of neurological phenotypes, including hindlimb clasping, decreased motor coordination and weak grip strength. In addition, AP-4 ε KO mice display a thin corpus callosum and axonal swellings in various areas of the brain and spinal cord. Immunohistochemical analyses show that the transmembrane autophagy-related protein 9A (ATG9A) is more concentrated in the trans-Golgi network (TGN) and depleted from the peripheral cytoplasm both in skin fibroblasts from patients with mutations in the μ4 subunit of AP-4 and in various neuronal types in AP-4 ε KO mice. ATG9A mislocalization is associated with increased tendency to accumulate mutant huntingtin (HTT) aggregates in the axons of AP-4 ε KO neurons. These findings indicate that the AP-4 ε KO mouse is a suitable animal model for AP-4 deficiency syndrome, and that defective mobilization of ATG9A from the TGN and impaired autophagic degradation of protein aggregates might contribute to neuroaxonal dystrophy in this disorder. PMID:29698489

  2. Analogs of diadenosine tetraphosphate (Ap4A).

    PubMed

    Guranowski, Andrzej

    2003-01-01

    This review summarizes our knowledge of analogs and derivatives of diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A), the most extensively studied member of the dinucleoside 5',5"'-P1,Pn-polyphosphate (NpnN) family. After a short discussion of enzymes that may be responsible for the accumulation and degradation of Np4)N's in the cell, this review focuses on chemically and/or enzymatically produced analogs and their practical applications. Particular attention is paid to compounds that have aided the study of enzymes involved in the metabolism of Ap4A (Np4N'). Certain Ap4A analogs were alternative substrates of Ap4A-degrading enzymes and/or acted as enzyme inhibitors, some other helped to establish enzyme mechanisms, increased the sensitivity of certain enzyme assays or produced stable enzyme:ligand complexes for structural analysis.

  3. Additional considerations are required when preparing a protocol for a systematic review with multiple interventions.

    PubMed

    Chaimani, Anna; Caldwell, Deborah M; Li, Tianjing; Higgins, Julian P T; Salanti, Georgia

    2017-03-01

    The number of systematic reviews that aim to compare multiple interventions using network meta-analysis is increasing. In this study, we highlight aspects of a standard systematic review protocol that may need modification when multiple interventions are to be compared. We take the protocol format suggested by Cochrane for a standard systematic review as our reference and compare the considerations for a pairwise review with those required for a valid comparison of multiple interventions. We suggest new sections for protocols of systematic reviews including network meta-analyses with a focus on how to evaluate their assumptions. We provide example text from published protocols to exemplify the considerations. Standard systematic review protocols for pairwise meta-analyses need extensions to accommodate the increased complexity of network meta-analysis. Our suggested modifications are widely applicable to both Cochrane and non-Cochrane systematic reviews involving network meta-analyses. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Comparative transcriptome profiling of upland (VS16) and lowland (AP13) ecotypes of switchgrass.

    PubMed

    Ayyappan, Vasudevan; Saha, Malay C; Thimmapuram, Jyothi; Sripathi, Venkateswara R; Bhide, Ketaki P; Fiedler, Elizabeth; Hayford, Rita K; Kalavacharla, Venu Kal

    2017-01-01

    Transcriptomes of two switchgrass genotypes representing the upland and lowland ecotypes will be key tools in switchgrass genome annotation and biotic and abiotic stress functional genomics. Switchgrass (Panicum virgatum L.) is an important bioenergy feedstock for cellulosic ethanol production. We report genome-wide transcriptome profiling of two contrasting tetraploid switchgrass genotypes, VS16 and AP13, representing the upland and lowland ecotypes, respectively. A total of 268 million Illumina short reads (50 nt) were generated, of which, 133 million were obtained in AP13 and the rest 135 million in VS16. More than 90% of these reads were mapped to the switchgrass reference genome (V1.1). We identified 6619 and 5369 differentially expressed genes in VS16 and AP13, respectively. Gene ontology and KEGG pathway analysis identified key genes that regulate important pathways including C4 photosynthesis, photorespiration and phenylpropanoid metabolism. A series of genes (33) involved in photosynthetic pathway were up-regulated in AP13 but only two genes showed higher expression in VS16. We identified three dicarboxylate transporter homologs that were highly expressed in AP13. Additionally, genes that mediate drought, heat, and salinity tolerance were also identified. Vesicular transport proteins, syntaxin and signal recognition particles were seen to be up-regulated in VS16. Analyses of selected genes involved in biosynthesis of secondary metabolites, plant-pathogen interaction, membrane transporters, heat, drought and salinity stress responses confirmed significant variation in the relative expression reflected in RNA-Seq data between VS16 and AP13 genotypes. The phenylpropanoid pathway genes identified here are potential targets for biofuel conversion.

  5. ONLINE MINIMIZATION OF VERTICAL BEAM SIZES AT APS

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

    Sun, Yipeng

    In this paper, online minimization of vertical beam sizes along the APS (Advanced Photon Source) storage ring is presented. A genetic algorithm (GA) was developed and employed for the online optimization in the APS storage ring. A total of 59 families of skew quadrupole magnets were employed as knobs to adjust the coupling and the vertical dispersion in the APS storage ring. Starting from initially zero current skew quadrupoles, small vertical beam sizes along the APS storage ring were achieved in a short optimization time of one hour. The optimization results from this method are briefly compared with the onemore » from LOCO (Linear Optics from Closed Orbits) response matrix correction.« less

  6. apGA: An adaptive parallel genetic algorithm

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

    Liepins, G.E.; Baluja, S.

    1991-01-01

    We develop apGA, a parallel variant of the standard generational GA, that combines aggressive search with perpetual novelty, yet is able to preserve enough genetic structure to optimally solve variably scaled, non-uniform block deceptive and hierarchical deceptive problems. apGA combines elitism, adaptive mutation, adaptive exponential scaling, and temporal memory. We present empirical results for six classes of problems, including the DeJong test suite. Although we have not investigated hybrids, we note that apGA could be incorporated into other recent GA variants such as GENITOR, CHC, and the recombination stage of mGA. 12 refs., 2 figs., 2 tabs.

  7. APS deposition facility upgrades and future plans

    NASA Astrophysics Data System (ADS)

    Conley, Ray; Shi, Bing; Erdmann, Mark; Izzo, Scott; Assoufid, Lahsen; Goetze, Kurt; Mooney, Tim; Lauer, Kenneth

    2014-09-01

    The Advanced Photon Source (APS) has recently invested resources to upgrade or replace aging deposition systems with modern equipment. Of the three existing deposition systems, one will receive an upgrade, while two are being replaced. A design which adds a three-substrate planetary for the APS rotary deposition system is almost complete. The replacement for the APS large deposition system, dubbed the "Modular Deposition System", has been conceptually designed and is in the procurement process. Eight cathodes will sputter horizontally on mirrors up to 1.5 meters in length. This new instrument is designed to interface with ion-milling instruments and various metrology equipment for ion-beam figuring. A third linear machine, called the APS Profile Coating System, has two cathodes and is designed to accept substrates up to 200mm in length. While this machine is primarily intended for fabrication of figured KB mirrors using the profile-coating technique, it has also been used to produce multilayer monochromators for beamline use.

  8. 75 FR 75666 - Advanced Placement (AP) Test Fee Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-06

    ... DEPARTMENT OF EDUCATION [CFDA No. 84.330B] Advanced Placement (AP) Test Fee Program AGENCY: Office... AP Test Fee fiscal year (FY) 2011 competition. SUMMARY: On September 1, 2010, we published in the Federal Register (75 FR 53681) a notice inviting applications for the AP Test Fee FY 2011 competition...

  9. X Linkage of AP3A, a Homolog of the Y-Linked MADS-Box Gene AP3Y in Silene latifolia and S. dioica

    PubMed Central

    Penny, Rebecca H.; Montgomery, Benjamin R.; Delph, Lynda F.

    2011-01-01

    Background The duplication of autosomal genes onto the Y chromosome may be an important element in the evolution of sexual dimorphism.A previous cytological study reported on a putative example of such a duplication event in a dioecious tribe of Silene (Caryophyllaceae): it was inferred that the Y-linked MADS-box gene AP3Y originated from a duplication of the reportedly autosomal orthologAP3A. However, a recent study, also using cytological methods, indicated that AP3A is X-linked in Silenelatifolia. Methodology/Principal Findings In this study, we hybridized S. latifolia and S. dioicato investigate whether the pattern of X linkage is consistent among distinct populations, occurs in both species, and is robust to genetic methods. We found inheritance patterns indicative of X linkage of AP3A in widely distributed populations of both species. Conclusions/Significance X linkage ofAP3A and Y linkage of AP3Yin both species indicates that the genes' ancestral progenitor resided on the autosomes that gave rise to the sex chromosomesand that neither gene has moved between chromosomes since species divergence.Consequently, our results do not support the contention that inter-chromosomal gene transfer occurred in the evolution of SlAP3Y from SlAP3A. PMID:21533056

  10. Limitations in electrophysiological model development and validation caused by differences between simulations and experimental protocols.

    PubMed

    Carro, Jesús; Rodríguez-Matas, José F; Monasterio, Violeta; Pueyo, Esther

    2017-10-01

    Models of ion channel dynamics are usually built by fitting isolated cell experimental values of individual parameters while neglecting the interaction between them. Another shortcoming regards the estimation of ionic current conductances, which is often based on quantification of Action Potential (AP)-derived markers. Although this procedure reduces the uncertainty in the calculation of conductances, many studies evaluate electrophysiological AP-derived markers from single cell simulations, whereas experimental measurements are obtained from tissue preparations. In this work, we explore the limitations of these approaches to estimate ion channel dynamics and maximum current conductances and how they could be overcome by using multiscale simulations of experimental protocols. Four human ventricular cell models, namely ten Tusscher and Panfilov (2006), Grandi et al. (2010), O'Hara et al. (2011), and Carro et al. (2011), were used. Two problems involving scales from ion channels to tissue were investigated: 1) characterization of L-type calcium voltage-dependent inactivation I Ca,L ; 2) identification of major ionic conductance contributors to steady-state AP markers, including APD 90 , APD 75 , APD 50 , APD 25 , Triangulation and maximal and minimal values of V and dV/dt during the AP (V max , V min , dV/dt max , dV/dt min ). Our results show that: 1) I Ca,L inactivation characteristics differed significantly when calculated from model equations and from simulations reproducing the experimental protocols. 2) Large differences were found in the ionic currents contributors to APD 25 , Triangulation, V max , dV/dt max and dV/dt min between single cells and 1D-tissue. When proposing any new model formulation, or evaluating an existing model, consistency between simulated and experimental data should be verified considering all involved effects and scales. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. AP214, an analogue of α-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality

    PubMed Central

    Doi, Kent; Hu, Xuzhen; Yuen, Peter S.T.; Leelahavanichkul, Asada; Yasuda, Hideo; Kim, Soo Mi; Schnermann, Jürgen; Jonassen, Thomas E.N.; Frøkiær, Jørgen; Nielsen, Søren; Star, Robert A.

    2008-01-01

    Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. α-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new α-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 hr after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-α and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-κB activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis. PMID:18354376

  12. Diadenosine polyphosphates (Ap3A and Ap4A) behave as alarmones triggering the synthesis of enzymes of the phenylpropanoid pathway in Arabidopsis thaliana.

    PubMed

    Pietrowska-Borek, Małgorzata; Nuc, Katarzyna; Zielezińska, Małgorzata; Guranowski, Andrzej

    2011-12-01

    It is known that cells under stress accumulate various dinucleoside polyphosphates, compounds suggested to function as alarmones. In plants, the phenylpropanoid pathways yield metabolites protecting these organisms against various types of stress. Observations reported in this communication link these two phenomena and provide an example of a metabolic "addressee" for an "alarm" signaled by diadenosine triphosphate (Ap3A) or diadenosine tetraphosphate (Ap4A). In response to added Ap3A or Ap4A, seedlings of Arabidopsis thaliana incubated in full nutrition medium increased both the expression of the genes for and the specific activity of phenylalanine ammonia-lyase and 4-coumarate:coenzyme A ligase, enzymes that control the beginning of the phenylpropanoid pathway. Neither adenine mononucleotides (AMP, ADP or ATP) nor adenosine evoked such effects. Reactions catalyzed in vitro by these enzymes were not affected by Ap3A or Ap4A.

  13. Multipurpose active pixel sensor (APS)-based microtracker

    NASA Astrophysics Data System (ADS)

    Eisenman, Allan R.; Liebe, Carl C.; Zhu, David Q.

    1998-12-01

    A new, photon-sensitive, imaging array, the active pixel sensor (APS) has emerged as a competitor to the CCD imager for use in star and target trackers. The Jet Propulsion Laboratory (JPL) has undertaken a program to develop a new generation, highly integrated, APS-based, multipurpose tracker: the Programmable Intelligent Microtracker (PIM). The supporting hardware used in the PIM has been carefully selected to enhance the inherent advantages of the APS. Adequate computation power is included to perform star identification, star tracking, attitude determination, space docking, feature tracking, descent imaging for landing control, and target tracking capabilities. Its first version uses a JPL developed 256 X 256-pixel APS and an advanced 32-bit RISC microcontroller. By taking advantage of the unique features of the APS/microcontroller combination, the microtracker will achieve about an order-of-magnitude reduction in mass and power consumption compared to present state-of-the-art star trackers. It will also add the advantage of programmability to enable it to perform a variety of star, other celestial body, and target tracking tasks. The PIM is already proving the usefulness of its design concept for space applications. It is demonstrating the effectiveness of taking such an integrated approach in building a new generation of high performance, general purpose, tracking instruments to be applied to a large variety of future space missions.

  14. Automated Plasma Spray (APS) process feasibility study

    NASA Technical Reports Server (NTRS)

    Fetheroff, C. W.; Derkacs, T.; Matay, I. M.

    1981-01-01

    An automated plasma spray (APS) process was developed to apply two layer (NiCrAlY and ZrO2-12Y2O3) thermal barrier coatings to aircraft and stationary gas turbine engine blade airfoils. The APS process hardware consists of four subsystems: a mechanical positioning subsystem incorporating two interlaced six degree of freedom assemblies (one for coating deposition and one for coating thickness monitoring); a noncoherent optical metrology subsystem (for in process gaging of the coating thickness buildup at specified points on the specimen); a microprocessor based adaptive system controller (to achieve the desired overall thickness profile on the specimen); and commerical plasma spray equipment. Over fifty JT9D first stage aircraft turbine blade specimens, ten W501B utility turbine blade specimens and dozens of cylindrical specimens were coated with the APS process in preliminary checkout and evaluation studies. The best of the preliminary turbine blade specimens achieved an overall coating thickness uniformity of 53 micrometers (2.1 mils), much better than is achievable manually. Comparative evaluations of coating thickness uniformity for manually sprayed and APS coated specimens were performed. One of the preliminary turbine blade evaluation specimens was subjected to a torch test and metallographic evaluation. Some cylindrical specimens coated with the APS process survived up to 2000 cycles in subsequent burner rig testing.

  15. Army and Marine Corps Active Protection System (APS) Efforts

    DTIC Science & Technology

    2016-08-30

    efforts—the Expedited, Non-Developmental Item (NDI) APS effort and the Modular Active Protection System (MAPS) effort. The Marines describe their...17 Modular Active Protection System (MAPS) Effort .......................................................... 18 The Marine Corps APS...Merkava Mark 4 tank was designed around the Trophy APS. 32 The Army’s Modular Active Protection System (MAPS) effort, described below, is intended to

  16. Additivity Principle in High-Dimensional Deterministic Systems

    NASA Astrophysics Data System (ADS)

    Saito, Keiji; Dhar, Abhishek

    2011-12-01

    The additivity principle (AP), conjectured by Bodineau and Derrida [Phys. Rev. Lett. 92, 180601 (2004)PRLTAO0031-900710.1103/PhysRevLett.92.180601], is discussed for the case of heat conduction in three-dimensional disordered harmonic lattices to consider the effects of deterministic dynamics, higher dimensionality, and different transport regimes, i.e., ballistic, diffusive, and anomalous transport. The cumulant generating function (CGF) for heat transfer is accurately calculated and compared with the one given by the AP. In the diffusive regime, we find a clear agreement with the conjecture even if the system is high dimensional. Surprisingly, even in the anomalous regime the CGF is also well fitted by the AP. Lower-dimensional systems are also studied and the importance of three dimensionality for the validity is stressed.

  17. Overexpression of BpAP1 induces early flowering and produces dwarfism in Betula platyphylla × Betula pendula.

    PubMed

    Huang, Haijiao; Wang, Shan; Jiang, Jing; Liu, Guifeng; Li, Huiyu; Chen, Su; Xu, Huanwen

    2014-08-01

    The involvement of APETALA1 (AP1) in the flowering transition has been the focus of much research. Here, we produced Betula platyphylla × Betula pendula (birch) lines that overexpressed BpAP1 using Agrobacterium-mediated transformation; we obtained five independent 35S::BpAP1 transgenic lines. Polymerase chain reaction (PCR), Southern, northern and western analyses were used to identify the transformants. As determined by quantitative real-time PCR (qRT-PCR), BpAP1 expression in roots, shoots, leaves and terminal buds of 35S::BpAP1 transgenic lines was significantly higher than that in the wild type (WT, P < 0.01). The average height of 2-year-old 35S::BpAP1 plants was significantly lower (41.17%) than that of non-transgenic plants. In the 35S::BpAP1 lines, inflorescences emerged successively beginning 2 months after transplanting. In addition, the length-diameter ratio of fully developed male and female inflorescences were both significantly less than those of the WT (P < 0.05), i.e. the morphological characteristic was stubby. The male inflorescences emerged early, with empty, draped anthers, and pollen was rarely produced, whereas the female floret structure was not different from WT. The pistils developed normally and could accept pollen, leading to the production of hybrid progeny (F1 ). F1 plants completed flowering within only 1 year after sowing. We demonstrate that BpAP1 can be inherited through sexual reproduction. Overexpression of BpAP1 caused early flowering and dwarfism; these lines had an obviously shortened juvenile phase. These results greatly increase our understanding of the mechanisms underlying the flowering transition and enhance genetic studies of birch traits, and they open up new possibilities for the breeding of birch and other woody plants. © 2013 Scandinavian Plant Physiology Society.

  18. Brain synaptosomes display a diadenosine tetraphosphate (Ap4A)-mediated Ca2+ influx distinct from ATP-mediated influx.

    PubMed

    Pivorun, E B; Nordone, A

    1996-06-01

    Studies undertaken to compare the effects of Ap4A and ATP on altering intrasynaptosomal Ca2+ levels from deermouse brain reveal that both ligands induce a rapid influx of extracellular Ca2+. The Ca2+ profile elicited by 167 microM Ap4A is "spike-like" (half-time for decline to baseline, 19.1 +/- 1.2 sec), in contrast to the gradual decline observed with ATP (104.0 +/- 7.4 sec). DIDS (4-4'-diisothiocyano-2,2'-disulfonic acid stilbene) and suramin preincubation alter only the ATP-induced Ca2+ profile. Cross-desensitization studies indicate that prior application of ATP does not significantly affect the Ca2+ influx elicited by Ap4A, and that prior application of Ap4A does not affect the Ca2+ influx elicited by ATP. These results demonstrate that extracellular Ap4A and ATP elicit distinct intrasynaptosomal Ca2+ influx profiles, and suggest that these two nucleotides may be interacting with distinct purinoceptor subclasses or purinoceptor-effector complexes. Subjecting the synaptosomes simultaneously to depolarization and Ap4A, or to depolarization and ATP, induces an additive effect on Ca2+ influx. Preincubation with verapamil negates the effects of depolarization without modifying the ligand-elicited Ca2+ fluxes. These results indicate the presence of Ap4A and ATP ligand-gated channels that may function as modulators of neuronal activity.

  19. Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly

    PubMed Central

    Hardies, Katia; May, Patrick; Djémié, Tania; Tarta-Arsene, Oana; Deconinck, Tine; Craiu, Dana; Helbig, Ingo; Suls, Arvid; Balling, Rudy; Weckhuysen, Sarah; De Jonghe, Peter; Hirst, Jennifer; Afawi, Zaid; Barisic, Nina; Baulac, Stéphanie; Caglayan, Hande; Depienne, Christel; De Kovel, Carolien G.F.; Dimova, Petia; Guerrero-López, Rosa; Guerrini, Renzo; Hjalgrim, Helle; Hoffman-Zacharska, Dorota; Jahn, Johanna; Klein, Karl Martin; Koeleman, Bobby P.C.; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes; Lerche, Holger; Marini, Carla; Muhle, Hiltrud; Rosenow, Felix; Serratosa, Jose M.; Møller, Rikke S.; Stephani, Ulrich; Striano, Pasquale; Talvik, Tiina; Von Spiczak, Sarah; Weber, Yvonne; Zara, Federico

    2015-01-01

    We report two siblings with infantile onset seizures, severe developmental delay and spastic paraplegia, in whom whole-genome sequencing revealed compound heterozygous mutations in the AP4S1 gene, encoding the σ subunit of the adaptor protein complex 4 (AP-4). The effect of the predicted loss-of-function variants (p.Gln46Profs*9 and p.Arg97*) was further investigated in a patient's fibroblast cell line. We show that the premature stop mutations in AP4S1 result in a reduction of all AP-4 subunits and loss of AP-4 complex assembly. Recruitment of the AP-4 accessory protein tepsin, to the membrane was also abolished. In retrospect, the clinical phenotype in the family is consistent with previous reports of the AP-4 deficiency syndrome. Our study reports the second family with mutations in AP4S1 and describes the first two patients with loss of AP4S1 and seizures. We further discuss seizure phenotypes in reported patients, highlighting that seizures are part of the clinical manifestation of the AP-4 deficiency syndrome. We also hypothesize that endosomal trafficking is a common theme between heritable spastic paraplegia and some inherited epilepsies. PMID:25552650

  20. A Comparison of Van Allen Belt Radiation Environment Modeling Programs: AE8/AP8 Legacy, AE9/AP9, and SPENVIS

    NASA Technical Reports Server (NTRS)

    Reed, Evan; Pellish, Jonathan

    2016-01-01

    In the space surrounding Earth there exists an active radiation environment consisting mostly of electrons and protons that have been trapped by Earths magnetic field. This radiation, also known as the Van Allen Belts, has the potential to damage man-made satellites in orbit; thus, proper precautions must be taken to shield NASA assets from this phenomenon. Data on the Van Allen Belts has been collected continuously by a multitude of space-based instruments since the beginning of space exploration. Subsequently, using theory to fill in the gaps in the collected data, computer models have been developed that take in the orbital information of a hypothetical mission and output the expected particle fluence and flux for that orbit. However, as new versions of the modeling system are released, users are left wondering how the new version differs from the old. Therefore, we performed a comparison of three different editions of the modeling system: AE8/AP8 (legacy), which is included in the model 9 graphical user interface as an option for ones calculations, AE9/AP9, and the Space Environment Information System (SPENVIS), which is an online-based form of AE8/AP8 developed by NASA and the European Space Agency that changed the code to allow the program to extrapolate data to predict fluence and flux at higher energies. Although this evaluation is still ongoing, it is predicted that the model 8 (legacy) and SPENVIS version will have identical outputs with the exception of the extended energy levels from SPENVIS, while model 9 will provide different fluences than model 8 based on additional magnetic field descriptions and on-orbit data.

  1. Sorting of Pmel17 to melanosomes through the plasma membrane by AP1 and AP2: evidence for the polarized nature of melanocytes

    PubMed Central

    Valencia, Julio C.; Watabe, Hidenori; Chi, An; Rouzaud, Francois; Chen, Kevin G.; Vieira, Wilfred D.; Takahashi, Kaoruko; Yamaguchi, Yuji; Berens, Werner; Nagashima, Kunio; Shabanowitz, Jeffrey; Hunt, Donald F.; Appella, Ettore; Hearing, Vincent J.

    2015-01-01

    Summary Adaptor proteins (AP) play important roles in the sorting of proteins from the trans-Golgi network, but how they function in the sorting of various melanosome-specific proteins such as Pmel17, an essential structural component of melanosomes, in melanocytes is unknown. We characterized the processing and trafficking of Pmel17 via adaptor protein complexes within melanocytic cells. Proteomics analysis detected Pmel17, AP1 and AP2, but not AP3 or AP4 in early melanosomes. Real-time PCR, immunolabeling and tissue in-situ hybridization confirmed the coexpression of AP1 isoforms μ1A and μ1B (expressed only in polarized cells) in melanocytes and keratinocytes, but expression of μ1B is missing in some melanoma cell lines. Transfection with AP1 isoforms (μ1A or μ1B) showed two distinct distribution patterns that involved Pmel17, and only μ1B was able to restore the sorting of Pmel17 to the plasma membrane in cells lacking μ1B expression. Finally, we established that expression of μ1B is regulated physiologically in melanocytes by UV radiation or DKK1. These results show that Pmel17 is sorted to melanosomes by various intracellular routes, directly or indirectly through the plasma membrane, and the presence of basolateral elements in melanocytes suggests their polarized nature. PMID:16492709

  2. Neuronal Activity and the Expression of Clathrin Assembly Protein AP180

    PubMed Central

    Wu, Fangbai; Mattson, Mark P.; Yao, Pamela J.

    2010-01-01

    The clathrin assembly protein AP180 is known to promote the assembly of clathrin-coated vesicles in the neuron. However, it is unknown whether the expression of AP180 is influenced by neuronal activity. In this study, we report that chronic depolarization results in a reduction of AP180 from hippocampal neurons, while acute depolarization causes a dispersed synaptic distribution of AP180. Activity-induced effects are observed only for AP180, but not for the structurally-related clathrin assembly proteins CALM, epsin1, or HIP1. These findings suggest that AP180 levels and synaptic distribution are highly sensitive to neuronal activity. PMID:20937255

  3. Low Earth orbit assessment of proton anisotropy using AP8 and AP9 trapped proton models

    NASA Astrophysics Data System (ADS)

    Badavi, Francis F.; Walker, Steven A.; Santos Koos, Lindsey M.

    2015-04-01

    The completion of the International Space Station (ISS) in 2011 has provided the space research community with an ideal evaluation and testing facility for future long duration human activities in space. Ionized and secondary neutral particles radiation measurements inside ISS form the ideal tool for validation of radiation environmental models, nuclear reaction cross sections and transport codes. Studies using thermo-luminescent detectors (TLD), tissue equivalent proportional counter (TPEC), and computer aided design (CAD) models of early ISS configurations confirmed that, as input, computational dosimetry at low Earth orbit (LEO) requires an environmental model with directional (anisotropic) capability to properly describe the exposure of trapped protons within ISS. At LEO, ISS encounters exposure from trapped electrons, protons and geomagnetically attenuated galactic cosmic rays (GCR). For short duration studies at LEO, one can ignore trapped electrons and ever present GCR exposure contributions during quiet times. However, within the trapped proton field, a challenge arises from properly estimating the amount of proton exposure acquired. There exist a number of models to define the intensity of trapped particles. Among the established trapped models are the historic AE8/AP8, dating back to the 1980s and the recently released AE9/AP9/SPM. Since at LEO electrons have minimal exposure contribution to ISS, this work ignores the AE8 and AE9 components of the models and couples a measurement derived anisotropic trapped proton formalism to omnidirectional output from the AP8 and AP9 models, allowing the assessment of the differences between the two proton models. The assessment is done at a target point within the ISS-11A configuration (circa 2003) crew quarter (CQ) of Russian Zvezda service module (SM), during its ascending and descending nodes passes through the south Atlantic anomaly (SAA). The anisotropic formalism incorporates the contributions of proton narrow

  4. Low Earth orbit assessment of proton anisotropy using AP8 and AP9 trapped proton models.

    PubMed

    Badavi, Francis F; Walker, Steven A; Santos Koos, Lindsey M

    2015-04-01

    The completion of the International Space Station (ISS) in 2011 has provided the space research community with an ideal evaluation and testing facility for future long duration human activities in space. Ionized and secondary neutral particles radiation measurements inside ISS form the ideal tool for validation of radiation environmental models, nuclear reaction cross sections and transport codes. Studies using thermo-luminescent detectors (TLD), tissue equivalent proportional counter (TPEC), and computer aided design (CAD) models of early ISS configurations confirmed that, as input, computational dosimetry at low Earth orbit (LEO) requires an environmental model with directional (anisotropic) capability to properly describe the exposure of trapped protons within ISS. At LEO, ISS encounters exposure from trapped electrons, protons and geomagnetically attenuated galactic cosmic rays (GCR). For short duration studies at LEO, one can ignore trapped electrons and ever present GCR exposure contributions during quiet times. However, within the trapped proton field, a challenge arises from properly estimating the amount of proton exposure acquired. There exist a number of models to define the intensity of trapped particles. Among the established trapped models are the historic AE8/AP8, dating back to the 1980s and the recently released AE9/AP9/SPM. Since at LEO electrons have minimal exposure contribution to ISS, this work ignores the AE8 and AE9 components of the models and couples a measurement derived anisotropic trapped proton formalism to omnidirectional output from the AP8 and AP9 models, allowing the assessment of the differences between the two proton models. The assessment is done at a target point within the ISS-11A configuration (circa 2003) crew quarter (CQ) of Russian Zvezda service module (SM), during its ascending and descending nodes passes through the south Atlantic anomaly (SAA). The anisotropic formalism incorporates the contributions of proton narrow

  5. AccuNet/AP (Associated Press) Multimedia Archive

    ERIC Educational Resources Information Center

    Young, Terrence E., Jr.

    2004-01-01

    The AccuNet/AP Multimedia Archive is an electronic library containing the AP's current photos and a selection of pictures from their enormous print and negative library, as well as text and graphic material. It is composed of two photo databases as well as graphics, text, and audio databases. The features of this database are briefly described in…

  6. The APS in Public Affairs

    NASA Astrophysics Data System (ADS)

    Lustig, Harry

    2000-04-01

    Although the American Physical Society was created for the interchange of scientific ideas, the call to the founding meeting included the observation that the organization "could not fail to have an important influence in all matters affecting the interest of physicists". However for most of its history APS did not behave like "just another interest group in American society". Instead, at the beginning, it limited itself to such successful initiatives as the creation of the Bureau of Standards and such unsuccessful ones as adoption of the metric system. After World War II, speaking out on behalf of the freedom of science and scientists, such as Astin, Condon, and Oppenheimer, became important. In the 1970's, pushed by members, the Society became more "political", sponsoring sessions and studies on defense issues, taking a stand for the Equal Rights Amendment and creating the Panel on Public Affairs and the Forum on Physics and Society. Only in the last fifteen years has the APS unabashedly lobbied for the economic interests of physics and physicists. Adopting this new, if unavoidable role may have unintended consequences for the willingness and effectiveness of APS in speaking out on other public issues.

  7. Influence of diadenosine tetraphosphate (Ap4A) on lipid metabolism.

    PubMed

    Rüsing, D; Verspohl, E J

    2004-01-01

    Diadenosine polyphosphates (Ap(x)A) are physiologically released and may be partly involved in the pathogenesis of diabetes mellitus. Ap(4)A (diadenosine tetraphosphate) leads to an increase in blood glucose while it decreases insulin levels in plasma. A possible link between Ap(x)A and diabetes mellitus-associated diseases such as insulin resistance and hyperlipidemia (plasma free fatty acids, cholesterol and its biosynthesis, triacylglycerols) has not been investigated yet. Parameters such as free fatty acid and cholesterol content in blood were determined enzymically. The biosynthesis of cholesterol and triacylglycerols was determined in HepG2 cells using the radioactive precursor [(14)C]-acetate and by using gas chromatography. Plasma free fatty acids were significantly decreased 5 and 10 min after an Ap(4)A bolus (0.75 mg kg(-1) b.w.) given to rats. Plasma cholesterol was reduced 5 and 60 min after Ap(4)A administration. LPDS (lipoprotein-deficient serum)-stimulated cholesterol biosynthesis in HepG2 cells was significantly reduced after 1 h incubation with Ap(4)A. Triacylglycerol (TAG) biosynthesis in HepG2 cells was not significantly influenced by Ap(4)A; there was just a tendency for a concentration-dependent decrease in TAG levels. In conclusion Ap(4)A as a diabetogenetic compound is not likely to be responsible for the development of insulin resistance or of hyperlipidemia. Parameters such as free fatty acids, cholesterol and triacylglycerols are not elevated by Ap(4)A, but are even decreased. Ap(4)A seems to be involved in the development of diabetes mellitus by increasing blood glucose and decreasing plasma insulin as shown earlier, but not in diabetes mellitus-associated diseases such as insulin resistance or hyperlipidemia.

  8. Final report for tank 241-AP-108, grab samples 8AP-96-1, 8AP-96-2 and 8AP-96-FB

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

    Esch, R.A.

    1996-04-19

    This document is the final report deliverable for the tank 241-AP-108 grab samples. The samples were subsampled and analyzed in accordance with the TSAP. Included in this report are the results for the Waste Compatibility analyses, with the exception of DSC and thermogravimetric analysis (TGA) results which were presented in the 45 Day report (Part 2 of this document). The raw data for all analyses, with the exception of DSC and TGA, are also included in this report.

  9. Free and ATP-bound structures of Ap4A hydrolase from Aquifex aeolicus V5.

    PubMed

    Jeyakanthan, Jeyaraman; Kanaujia, Shankar Prasad; Nishida, Yuya; Nakagawa, Noriko; Praveen, Surendran; Shinkai, Akeo; Kuramitsu, Seiki; Yokoyama, Shigeyuki; Sekar, Kanagaraj

    2010-02-01

    Asymmetric diadenosine tetraphosphate (Ap(4)A) hydrolases degrade the metabolite Ap(4)A back into ATP and AMP. The three-dimensional crystal structure of Ap(4)A hydrolase (16 kDa) from Aquifex aeolicus has been determined in free and ATP-bound forms at 1.8 and 1.95 A resolution, respectively. The overall three-dimensional crystal structure of the enzyme shows an alphabetaalpha-sandwich architecture with a characteristic loop adjacent to the catalytic site of the protein molecule. The ATP molecule is bound in the primary active site and the adenine moiety of the nucleotide binds in a ring-stacking arrangement equivalent to that observed in the X-ray structure of Ap(4)A hydrolase from Caenorhabditis elegans. Binding of ATP in the active site induces local conformational changes which may have important implications in the mechanism of substrate recognition in this class of enzymes. Furthermore, two invariant water molecules have been identified and their possible structural and/or functional roles are discussed. In addition, modelling of the substrate molecule at the primary active site of the enzyme suggests a possible path for entry and/or exit of the substrate and/or product molecule.

  10. Predictive Validity Study of the APS Writing and Reading Tests [and] Validating Placement Rules for the APS Writing Test.

    ERIC Educational Resources Information Center

    College of the Canyons, Valencia, CA. Office of Institutional Development.

    California's College of the Canyons has used the College Board Assessment and Placement Services (APS) test to assess students' abilities in basic and college English since spring 1993. These two reports summarize data from a May 1994 study of the predictive validity of the APS writing and reading tests and a June 1994 effort to validate the cut…

  11. P4-ATPase Requirement for AP-1/Clathrin Function in Protein Transport from the trans-Golgi Network and Early Endosomes

    PubMed Central

    Liu, Ke; Surendhran, Kavitha; Nothwehr, Steven F.

    2008-01-01

    Drs2p is a resident type 4 P-type ATPase (P4-ATPase) and potential phospholipid translocase of the trans-Golgi network (TGN) where it has been implicated in clathrin function. However, precise protein transport pathways requiring Drs2p and how it contributes to clathrin-coated vesicle budding remain unclear. Here we show a functional codependence between Drs2p and the AP-1 clathrin adaptor in protein sorting at the TGN and early endosomes of Saccharomyces cerevisiae. Genetic criteria indicate that Drs2p and AP-1 operate in the same pathway and that AP-1 requires Drs2p for function. In addition, we show that loss of AP-1 markedly increases Drs2p trafficking to the plasma membrane, but does not perturb retrieval of Drs2p from the early endosome back to the TGN. Thus AP-1 is required at the TGN to sort Drs2p out of the exocytic pathway, presumably for delivery to the early endosome. Moreover, a conditional allele that inactivates Drs2p phospholipid translocase (flippase) activity disrupts its own transport in this AP-1 pathway. Drs2p physically interacts with AP-1; however, AP-1 and clathrin are both recruited normally to the TGN in drs2Δ cells. These results imply that Drs2p acts independently of coat recruitment to facilitate AP-1/clathrin-coated vesicle budding from the TGN. PMID:18508916

  12. Satellite Communications Using Commercial Protocols

    NASA Technical Reports Server (NTRS)

    Ivancic, William D.; Griner, James H.; Dimond, Robert; Frantz, Brian D.; Kachmar, Brian; Shell, Dan

    2000-01-01

    NASA Glenn Research Center has been working with industry, academia, and other government agencies in assessing commercial communications protocols for satellite and space-based applications. In addition, NASA Glenn has been developing and advocating new satellite-friendly modifications to existing communications protocol standards. This paper summarizes recent research into the applicability of various commercial standard protocols for use over satellite and space- based communications networks as well as expectations for future protocol development. It serves as a reference point from which the detailed work can be readily accessed. Areas that will be addressed include asynchronous-transfer-mode quality of service; completed and ongoing work of the Internet Engineering Task Force; data-link-layer protocol development for unidirectional link routing; and protocols for aeronautical applications, including mobile Internet protocol routing for wireless/mobile hosts and the aeronautical telecommunications network protocol.

  13. Shock loading and reactive flow modeling studies of void induced AP/AL/HTPB propellant

    NASA Astrophysics Data System (ADS)

    Miller, P. J.; Lindfors, A. J.

    1998-07-01

    The unreactive Hugoniot of a class 1.3 propellant has been investigated by shock compression experiments. The results are analyzed in terms of an ignition and growth reactive flow model using the DYNA2D hydrocode. The calculated shock ignition parameters of the model show a linear dependence on measured void volume which appears to reproduce the observed gauge records well. Shock waves were generated by impact in a 75 mm single stage powder gun. Manganin and PVDF pressure gauges provided pressure-time histories to 140 kbar. The propellants were of similar formulation differing only in AP particle size and the addition of a burn rate modifer (Fe2O3) from that of previous investigations. Results show neglible effect of AP particle size on shock response in contrast to the addition of Fe2O3 which appears to `stiffen' the unreactive Hugoniot and enhances significantly the reactive rates under shock. The unreactive Hugoniot, within experimental error, compares favorably to the solid AP Hugoniot. Shock experiments were performed on propellant samples strained to induce insitu voids. The material state was quantified by uniaxial tension dialatometry. The experimental records show a direct correlation between void volume (0 to 1.7%) and chemical reactivity behind the shock front. These results are discussed in terms of `hot spot' ignition resulting from the shock collapse of the voids.

  14. AP Physics 1 & 2; Some Things Old and Some Things New

    NASA Astrophysics Data System (ADS)

    Morse, Robert

    2015-04-01

    In fall September 2014, AP Physics 1 and AP Physics 2 replaced the AP Physics B curriculum, with the first exams in the new courses coming up in May 2015. In this talk I will give an overview of the history and rationale for the changes, describe the process of developing the new Curriculum Framework, discuss changes in emphasis compared to AP Physics B, including the emphasis on laboratory work. Finally, I will give examples of the difference in the style of the questions to be used in the new AP exams.

  15. Acute Pain Service and multimodal therapy for postsurgical pain control: evaluation of protocol efficacy.

    PubMed

    Moizo, E; Berti, M; Marchetti, C; Deni, F; Albertin, A; Muzzolon, F; Antonino, A

    2004-11-01

    The institution of a postoperative Acute Pain Control Service is mandatory to improve the control of pain induced by surgical injury. Treatment of postoperative pain may be achieved using a combination of analgesic agents and techniques, reducing the incidence of side effects owing to the lower doses of the individual drugs. In 1997 we established an Acute Pain Service (APS) at the San Raffaele Hospital in Milan. The aim of this study was to assess the efficacy and safety of our APS both in terms of treatment protocols and organisational issues. In this prospective observational study we included 592 patients undergoing abdominal, gynecological, or orthopedic surgery with severe expected pain. According to general guidelines on pain treatment, the patients were assigned to different treatment protocols based on the kind of operation. All protocols were based on the multimodal therapy, with the association of nonsteroidal anti-inflammatory drugs (NSAIDS), opioids and regional anesthesia techniques. During the first 48 h of the postoperative period we recorded vital signs, level of pain and occurrence of any side effect. Our analgesic protocols proved to be effective and safe (low incidence of side effects) for every surgery. The incidence of postoperative nausea and vomiting was higher in patients receiving patient-controlled morphine than that with continuous epidural or nerve block. After lower abdominal surgery, pain at movement at 24 h was significantly lower in the epidural group than in the Patient Control Analgesia group. Nausea and vomiting, numbness and paresthesias at the lower limbs were higher in gynecological patients. A larger percentage of orthopedic patients in the epidural group reported numbness and paresthesias at the lower limbs in comparison with patients receiving continuous peripheral nerve block. In agreement with previous literature, this study confirmed that a multimodal approach to pain treatment provides an adequate control of

  16. 77 FR 2713 - Agency Information Collection Extension

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-19

    ...) Package Title: U.S. Declaration under the Protocol Additional to the U.S.-IAEA Safeguards Agreement... Declaration to the International Atomic Energy Agency (IAEA) under Articles 2 and 3 of the Protocol Additional... performing activities at DOE Locations that would be declarable to the IAEA under the U.S. AP are affected by...

  17. NECAPs are negative regulators of the AP2 clathrin adaptor complex

    PubMed Central

    Beacham, Gwendolyn M; Partlow, Edward A; Lange, Jeffrey J

    2018-01-01

    Eukaryotic cells internalize transmembrane receptors via clathrin-mediated endocytosis, but it remains unclear how the machinery underpinning this process is regulated. We recently discovered that membrane-associated muniscin proteins such as FCHo and SGIP initiate endocytosis by converting the AP2 clathrin adaptor complex to an open, active conformation that is then phosphorylated (Hollopeter et al., 2014). Here we report that loss of ncap-1, the sole C. elegans gene encoding an adaptiN Ear-binding Coat-Associated Protein (NECAP), bypasses the requirement for FCHO-1. Biochemical analyses reveal AP2 accumulates in an open, phosphorylated state in ncap-1 mutant worms, suggesting NECAPs promote the closed, inactive conformation of AP2. Consistent with this model, NECAPs preferentially bind open and phosphorylated forms of AP2 in vitro and localize with constitutively open AP2 mutants in vivo. NECAPs do not associate with phosphorylation-defective AP2 mutants, implying that phosphorylation precedes NECAP recruitment. We propose NECAPs function late in endocytosis to inactivate AP2. PMID:29345618

  18. The History of the APS Shock Compression of Condensed Matter Topical Group

    NASA Astrophysics Data System (ADS)

    Forbes, Jerry W.

    2001-06-01

    To provide broader scientific recognition and to advance the science of shock-compressed condensed matter, a group of APS members worked within the Society to make this technical field an active part of APS. Individual papers were given at APS meetings starting in the 1950’s and then later whole sessions were organized starting at the 1967 Pasadena meeting. Topical conferences began in 1979 in Pullman, WA where George Duvall and Dennis Hayes were co-chairs. Most all early topical conferences were sanctioned by the APS while those held after 1985 were official APS meetings. In 1984, after consulting with a number of people in the shock wave field, Robert Graham circulated a petition to form an APS topical group. He obtained signatures from a balanced cross-section of the community. William Havens, the executive secretary of APS, informed Robert Graham by letter on November 28, 1984 that the APS Council had officially accepted the formation of this topical group at its October 28, 1984 meeting. The first election occurred July 23, 1985 where Robert Graham was elected chairman, William Nellis vice-chairman, and Jerry Forbes secretary/treasurer. The topical group remains viable today by holding a topical conference in odd numbered years and shock wave sessions at APS general meetings in even numbered years A major benefit of being an official unit of APS is the allotment of APS fellows every year. The APS shock compression award established in 1987, has also provided broad recognition of many major scientific accomplishments in this field.

  19. Delay Tolerant Networking - Bundle Protocol Simulation

    NASA Technical Reports Server (NTRS)

    SeGui, John; Jenning, Esther

    2006-01-01

    In this paper, we report on the addition of MACHETE models needed to support DTN, namely: the Bundle Protocol (BP) model. To illustrate the useof MACHETE with the additional DTN model, we provide an example simulation to benchmark its performance. We demonstrate the use of the DTN protocol and discuss statistics gathered concerning the total time needed to simulate numerous bundle transmissions.

  20. Systematic CRISPR-Cas9-Mediated Modifications of Plasmodium yoelii ApiAP2 Genes Reveal Functional Insights into Parasite Development

    PubMed Central

    Zhang, Cui; Li, Zhenkui; Cui, Huiting; Jiang, Yuanyuan; Yang, Zhenke; Wang, Xu; Gao, Han; Liu, Cong; Zhang, Shujia

    2017-01-01

    ABSTRACT Malaria parasites have a complex life cycle with multiple developmental stages in mosquito and vertebrate hosts, and different developmental stages express unique sets of genes. Unexpectedly, many transcription factors (TFs) commonly found in eukaryotic organisms are absent in malaria parasites; instead, a family of genes encoding proteins similar to the plant Apetala2 (ApiAP2) transcription factors is expanded in the parasites. Several malaria ApiAP2 genes have been shown to play a critical role in parasite development; however, the functions of the majority of the ApiAP2 genes remain to be elucidated. In particular, no study on the Plasmodium yoelii ApiAP2 (PyApiAP2) gene family has been reported so far. This study systematically investigated the functional roles of PyApiAP2 genes in parasite development. Twenty-four of the 26 PyApiAP2 genes were selected for disruption, and 12 were successfully knocked out using the clustered regularly interspaced short palindromic repeat–CRISPR-associated protein 9 (CRISPR-Cas9) method. The effects of gene knockout (KO) on parasite development in mouse and mosquito stages were evaluated. Ten of 12 successfully disrupted genes, including two genes that have not been functionally characterized in any Plasmodium species previously, were shown to be critical for P. yoelii development of sexual and mosquito stages. Additionally, seven of the genes were labeled for protein expression analysis, revealing important information supporting their functions. This study represents the first systematic functional characterization of the P. yoelii ApiAP2 gene family and discovers important insights on the roles of the ApiAP2 genes in parasite development. PMID:29233900

  1. AP2 hemicomplexes contribute independently to synaptic vesicle endocytosis

    PubMed Central

    Gu, Mingyu; Liu, Qiang; Watanabe, Shigeki; Sun, Lin; Hollopeter, Gunther; Grant, Barth D; Jorgensen, Erik M

    2013-01-01

    The clathrin adaptor complex AP2 is thought to be an obligate heterotetramer. We identify null mutations in the α subunit of AP2 in the nematode Caenorhabditis elegans. α-adaptin mutants are viable and the remaining μ2/β hemicomplex retains some function. Conversely, in μ2 mutants, the alpha/sigma2 hemicomplex is localized and is partially functional. α-μ2 double mutants disrupt both halves of the complex and are lethal. The lethality can be rescued by expression of AP2 components in the skin, which allowed us to evaluate the requirement for AP2 subunits at synapses. Mutations in either α or μ2 subunits alone reduce the number of synaptic vesicles by about 30%; however, simultaneous loss of both α and μ2 subunits leads to a 70% reduction in synaptic vesicles and the presence of large vacuoles. These data suggest that AP2 may function as two partially independent hemicomplexes. DOI: http://dx.doi.org/10.7554/eLife.00190.001 PMID:23482940

  2. PREFACE: Asia-Pacific Interdisciplinary Research Conference 2011 (AP-IRC 2011)

    NASA Astrophysics Data System (ADS)

    Sandhu, Adarsh; Okada, Hiroshi; Maekawa, Toru; Okano, Ken

    2012-03-01

    ; a novel method for the synthesis of graphene using bacteria extracted from a riverside in Toyohashi by Toyohashi Tech scientists; and ambitious plans to harvest energy by laying massive numbers of solar cells in North Africa as part of the 'Sahara Solar Breeder (SSB) Plan' for a global clean-energy superhighway, described by Hideomi Koinuma. In addition to the technical sessions, the conference banquet included a short session during which the invited speakers described notable trends in research and policy in their part of the world. The short speeches led to animated discussions between the delegates, particularly the young scientists and graduate students, who were able to talk directly with veteran researchers for a first-hand view of the issues raised during the day's presentations. In closing the conference, Professor Makoto Ishida, co-chair of the conference and vice-president of Toyohashi Tech announced that this conference will be held annually at the same time each year, with AP-IRC 2012 scheduled for 15-16 November 2012 at the Irago Sea-Park & Spa Hotel in Aichi Prefecture, Japan. AP-IRC group The PDF also contains lists of the Committees involved.

  3. Teaching Materials and Strategies for the AP Music Theory Exam

    ERIC Educational Resources Information Center

    Lively, Michael T.

    2017-01-01

    Each year, many students take the Advanced Placement (AP) Music Theory Exam, and the majority of these students enroll in specialized AP music theory classes as part of the preparation process. For the teachers of these AP music theory classes, a number of challenges are presented by the difficulty and complexity of the exam subject material as…

  4. bZIP transcription factor CgAP1 is essential for oxidative stress tolerance and full virulence of the poplar anthracnose fungus Colletotrichum gloeosporioides.

    PubMed

    Sun, Yingjiao; Wang, Yonglin; Tian, Chengming

    2016-10-01

    Yeast AP1 transcription factor is a regulator of oxidative stress response. Here, we report the identification and characterization of CgAP1, an ortholog of YAP1 in poplar anthracnose fungus Colletotrichum gloeosporioides. The expression of CgAP1 was highly induced by reactive oxygen species. CgAP1 deletion mutants displayed enhanced sensitivity to oxidative stress compared with the wild-type strain, and their poplar leaf virulence was obviously reduced. However, the mutants exhibited no obvious defects in aerial hyphal growth, conidia production, and appressoria formation. CgAP1::eGFP fusion protein localized to the nucleus after TBH (tert-Butyl hydroperoxide) treatment, suggesting that CgAP1 functions as a redox sensor in C. gloeosporioides. In addition, CgAP1 prevented the accumulation of ROS during early stages of biotrophic growth. CgAP1 also acted as a positive regulator of several ROS-related genes (i.e., Glr1, Hyr1, and Cyt1) involved in the antioxidative response. These results highlight the key regulatory role of CgAP1 transcription factor in oxidative stress response and provide insights into the function of ROS detoxification in virulence of C. gloeosporioides. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Overexpression of AtAP1M3 regulates flowering time and floral development in Arabidopsis and effects key flowering-related genes in poplar.

    PubMed

    Chen, Zhong; Ye, Meixia; Su, Xiaoxing; Liao, Weihua; Ma, Huandi; Gao, Kai; Lei, Bingqi; An, Xinmin

    2015-08-01

    APETALA1 plays a crucial role in the transition from vegetative to reproductive phase and in floral development. In this study, to determine the effect of AP1 expression on flowering time and floral organ development, transgenic Arabidopsis and poplar overexpressing of AtAP1M3 (Arabidopsis AP1 mutant by dominant negative mutation) were generated. Transgenic Arabidopsis with e35Spro::AtAP1M3 displayed phenotypes with delayed-flowering compared to wild-type and flowers with abnormal sepals, petals and stamens. In addition, transgenic Arabidopsis plants exhibited reduced growth vigor compared to the wild-type plants. Ectopic expression of AtAP1M3 in poplar resulted in up- or down-regulation of some endogenous key flowering-related genes, including floral meristems identity gene LFY, B-class floral organ identity genes AP3 and PI, flowering pathway integrator FT1 and flower repressors TFL1 and SVP. These results suggest that AtAP1M3 regulates flowering time and floral development in plants.

  6. NECAPs are negative regulators of the AP2 clathrin adaptor complex.

    PubMed

    Beacham, Gwendolyn M; Partlow, Edward A; Lange, Jeffrey J; Hollopeter, Gunther

    2018-01-18

    Eukaryotic cells internalize transmembrane receptors via clathrin-mediated endocytosis, but it remains unclear how the machinery underpinning this process is regulated. We recently discovered that membrane-associated muniscin proteins such as FCHo and SGIP initiate endocytosis by converting the AP2 clathrin adaptor complex to an open, active conformation that is then phosphorylated (Hollopeter et al., 2014). Here we report that loss of ncap-1 , the sole C. elegans gene encoding an adaptiN Ear-binding Coat-Associated Protein (NECAP), bypasses the requirement for FCHO-1. Biochemical analyses reveal AP2 accumulates in an open, phosphorylated state in ncap-1 mutant worms, suggesting NECAPs promote the closed, inactive conformation of AP2. Consistent with this model, NECAPs preferentially bind open and phosphorylated forms of AP2 in vitro and localize with constitutively open AP2 mutants in vivo. NECAPs do not associate with phosphorylation-defective AP2 mutants, implying that phosphorylation precedes NECAP recruitment. We propose NECAPs function late in endocytosis to inactivate AP2. © 2018, Beacham et al.

  7. Is the Shine off the A.P. Apple?

    ERIC Educational Resources Information Center

    Hurwitz, Nina; Hurwitz, Sol

    2003-01-01

    Describes challenges facing College Board's efforts to expand Advanced Placement (A.P.) courses to provide equal access to previously underserved low-performing urban and rural school students while maintaining the program's high academic standards. Includes list of strategies school boards can use to achieve greater access to A.P. courses while…

  8. The Role of AP and the Composition Program.

    ERIC Educational Resources Information Center

    Mahala, Daniel; Vivion, Michael

    1993-01-01

    Suggests that most programs have not based their acceptance of advanced placement credit on reasoned endorsement of the views of language, literature, and rhetoric that AP exams present. Criticizes the views implicit in the AP program and shows how they conflict with the goals of one particular college composition program. (RS)

  9. Prevention of Breast Cell Transformation by Blockade of the AP-1 Transcription Factor

    DTIC Science & Technology

    2000-10-01

    Distribution Unlimited 13. ABSTRACT (Maximum 200 Words) In this study, we are investigating the role of AP- M in controlling breast cell growth and...serum and these growth factors depend on AP-1 to transduce proliferative signal. AP- M blockade induced by the expression of TAM67 inhibits breast...demonstrated that TAM67 inhibits basal AP-1 activity and AP- M activity stimulated by several different growth factors. We have also discovered that AP-1

  10. L-Cysteine and L-AP4 microinjections in the rat caudal ventrolateral medulla decrease arterial blood pressure.

    PubMed

    Takemoto, Yumi

    2014-12-01

    The thiol amino acid L-cysteine increases arterial blood pressure (ABP) when injected into the cerebrospinal fluid space in conscious rats, indicating a pressor response to centrally acting L-cysteine. A prior synaptic membrane binding assay suggests that L-cysteine has a strong affinity for the L-2-amino-4-phosphonobutyric acid (L-AP4) binding site. The central action of L-cysteine may be vial-AP4 sensitive receptors. The present study investigated cardiovascular responses to L-cysteine and L-ap4 microinjected into the autonomic area of the caudal ventrolateral medulla (CVLM) where inhibitory neurons regulate ABP via pre-sympathetic vasomotor neurons. Both the injection of L-cysteine and L-AP4 in the CVLM sites identified with L-glutamate produced the same depressor and bradycardic responses in urethane-anesthetized rats. Neither a prior antagonist microinjection of MK801 for the N-methyl-D-aspartate (NMDA) receptor nor CNQX for the non-NMDA receptor attenuated the responses to L-cysteine, but the combination of the two receptor blocking with an additional prior injection abolished the response. In contrast, either receptor blockade alone abolished the response to L-AP4, indicating distinct mechanisms between responses to L-cysteine and L-AP4 in the CVLM. The results indicate that the CVLM is a central active site for L-cysteine's cardiovascular response. Central L-cysteine's action could be independent of the L-AP4 sensitive receptors. Cardiovascular regulation may involve endogenous L-cysteine in the CVLM. Further multidisciplinary examinations are required to elaborate on L-cysteine's functional roles in the CVLM. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Study of Pulsations in the Atmosphere of the roAp star HD 137949

    NASA Astrophysics Data System (ADS)

    Sachkov, M.; Hareter, M.; Ryabchikova, T.; Wade, G.; Kochukhov, O.; Weiss, W. W.

    The roAp star HD 137949 (33 Lib) shows the most complex pulsational behaviour among all roAp stars. Mkrtichian et al. (2003) found nearly anti-phase pulsations of Nd II and Nd III lines, which they attribute to the presence of a pulsation node high in the atmosphere of HD 137949. This was confirmed by Kurtz at al. (2005), who also find that in some REE lines the main frequency, corresponding to 8.27 min, and its harmonic have almost equal RV amplitudes. Based on high accuracy observations Ryabchikova et al. (2007a) studied pulsational characteristics of the HD 137949 atmosphere in detail. In general, spectroscopy provides 3D resolution of modes and allows to search for the photometrically undetectable frequencies. The high-accuracy space photometry provides very high-precision measurements of detected pulsation frequencies and enables an accurate phasing of multi-site spectroscopic data. A combination of simultaneous spectroscopy and photometry represents the most sophisticated asteroseismic dataset for any roAp star. In 2009 the star HD 137949 became a target of an intense observing campaign that combined ground-based spectroscopy with space photometry, obtained with the MOST satellite. We collected 780 spectra using the ESPaDOnS spectrograph mounted on the 3.6 m CFHT telescope; 374 spectra were obtained with the FIES spectrograph mounted on the 2.56-m NOT to perform the time-resolved spectroscopy of HD 137949. In addition, we used 111 UVES spectra (2004) from the ESO archive to check the mode stability. The frequency analysis of the new radial velocity (RV) measurements confirmed the previously reported frequency pattern (two frequencies and the first harmonic of the main frequency), and revealed an additional frequency at 1.991 mHz. The new frequency solution fits perfectly the RV variations from the 2004 and 2009 observational sets providing a strong support for the p-mode stability in the roAp star HD 137949 for at least 5 years.

  12. Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration

    PubMed Central

    Dubos, Aline; Castells-Nobau, Anna; Meziane, Hamid; Oortveld, Merel A.W.; Houbaert, Xander; Iacono, Giovanni; Martin, Christelle; Mittelhaeuser, Christophe; Lalanne, Valérie; Kramer, Jamie M.; Bhukel, Anuradha; Quentin, Christine; Slabbert, Jan; Verstreken, Patrik; Sigrist, Stefan J.; Messaddeq, Nadia; Birling, Marie-Christine; Selloum, Mohammed; Stunnenberg, Henk G.; Humeau, Yann; Schenck, Annette; Herault, Yann

    2015-01-01

    ATP6AP2, an essential accessory component of the vacuolar H+ ATPase (V-ATPase), has been associated with intellectual disability (ID) and Parkinsonism. ATP6AP2 has been implicated in several signalling pathways; however, little is known regarding its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional knockdowns of ATP6AP2 in the nervous system of Drosophila and mouse models. In Drosophila, ATP6AP2 knockdown induced defective phototaxis and vacuolated photoreceptor neurons and pigment cells when depleted in eyes and altered short- and long-term memory when depleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2Camk2aCre/0 mice) caused increased spontaneous locomotor activity and altered fear memory. Both Drosophila ATP6AP2 knockdown and Atp6ap2Camk2aCre/0 mice presented with presynaptic transmission defects, and with an abnormal number and morphology of synapses. In addition, Atp6ap2Camk2aCre/0 mice showed autophagy defects that led to axonal and neuronal degeneration in the cortex and hippocampus. Surprisingly, axon myelination was affected in our mutant mice, and axonal transport alterations were observed in Drosophila. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2Camk2aCre/0 mouse hippocampi revealed dysregulation of genes involved in myelination, action potential, membrane-bound vesicles and motor behaviour. In summary, ATP6AP2 disruption in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. PMID:26376863

  13. Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration.

    PubMed

    Dubos, Aline; Castells-Nobau, Anna; Meziane, Hamid; Oortveld, Merel A W; Houbaert, Xander; Iacono, Giovanni; Martin, Christelle; Mittelhaeuser, Christophe; Lalanne, Valérie; Kramer, Jamie M; Bhukel, Anuradha; Quentin, Christine; Slabbert, Jan; Verstreken, Patrik; Sigrist, Stefan J; Messaddeq, Nadia; Birling, Marie-Christine; Selloum, Mohammed; Stunnenberg, Henk G; Humeau, Yann; Schenck, Annette; Herault, Yann

    2015-12-01

    ATP6AP2, an essential accessory component of the vacuolar H+ ATPase (V-ATPase), has been associated with intellectual disability (ID) and Parkinsonism. ATP6AP2 has been implicated in several signalling pathways; however, little is known regarding its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional knockdowns of ATP6AP2 in the nervous system of Drosophila and mouse models. In Drosophila, ATP6AP2 knockdown induced defective phototaxis and vacuolated photoreceptor neurons and pigment cells when depleted in eyes and altered short- and long-term memory when depleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2(Camk2aCre/0) mice) caused increased spontaneous locomotor activity and altered fear memory. Both Drosophila ATP6AP2 knockdown and Atp6ap2(Camk2aCre/0) mice presented with presynaptic transmission defects, and with an abnormal number and morphology of synapses. In addition, Atp6ap2(Camk2aCre/0) mice showed autophagy defects that led to axonal and neuronal degeneration in the cortex and hippocampus. Surprisingly, axon myelination was affected in our mutant mice, and axonal transport alterations were observed in Drosophila. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2(Camk2aCre/0) mouse hippocampi revealed dysregulation of genes involved in myelination, action potential, membrane-bound vesicles and motor behaviour. In summary, ATP6AP2 disruption in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. © The Author 2015. Published by Oxford University Press.

  14. AP@home: a novel European approach to bring the artificial pancreas home.

    PubMed

    Heinemann, Lutz; Benesch, Carsten; DeVries, J Hans

    2011-11-01

    The development of an artificial pancreas (AP) made huge strides from 2006 to 2008 and a large number of activities are going on in this area of research. Until now, most AP systems under development were tested only under highly controlled conditions. The aim of our project, funded by the European Union, is to develop an AP system to such a level that it can be studied under daily life conditions at the home of patients with diabetes (hence AP@home). Based on a subcutaneous-subcutaneous closed-loop strategy (i.e., glucose sensing and insulin infusion in the subcutaneous tissue), two different approaches will be taken to achieve this aim: a two-port AP system and a single-port AP system. The two-port AP system will use off-the-shelf-components for the glucose sensor and insulin pump in combination with closed-loop algorithms generated in Europe. As to the single-port AP system, two different innovative single-port systems will be developed; in this case, continuous glucose monitoring and insulin infusion will take place via a single catheter. The first clinical trials with the two-port AP system under controlled clinical conditions have started and good progress has been made in the development of the single-port AP systems. We believe that our consortium of 12 European partners, which builds on existing achievements and close cooperation between academic centers and industry, can contribute substantially to the development of an AP system that can be used by patients in daily life. © 2011 Diabetes Technology Society.

  15. Glossary for the implementation of Health in All Policies (HiAP).

    PubMed

    Freiler, Alix; Muntaner, Carles; Shankardass, Ketan; Mah, Catherine L; Molnar, Agnes; Renahy, Emilie; O'Campo, Patricia

    2013-12-01

    Health in All Policies (HiAP) is becoming increasingly popular as a governmental strategy to improve population health by coordinating action across health and non-health sectors. A variety of intersectoral initiatives may be used in HiAP that frame health determinants as the bridge between policies and health outcomes. The purpose of this glossary is to present concepts and terms useful in understanding the implementation of HiAP as a cross-sectoral policy. The concepts presented here were applied and elaborated over the course of case studies of HiAP in multiple jurisdictions, which used key informant interviews and the systematic review of literature to study the implementation of specific HiAP initiatives.

  16. AP1000{sup R} nuclear power plant safety overview for spent fuel cooling

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

    Gorgemans, J.; Mulhollem, L.; Glavin, J.

    2012-07-01

    possible pool heat load conditions. - After 3 days, several different means are provided to continue spent fuel cooling using installed plant equipment as well as off-site equipment with built-in connections. Even for beyond design basis accidents with postulated pool damage and multiple failures in the passive safety-related systems and in the defense-in-depth active systems, the AP1000 multiple spent fuel pool spray and fill systems provide additional lines of defense to prevent spent fuel damage. (authors)« less

  17. The APS SASE FEL : modeling and code comparison.

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

    Biedron, S. G.

    A self-amplified spontaneous emission (SASE) free-electron laser (FEL) is under construction at the Advanced Photon Source (APS). Five FEL simulation codes were used in the design phase: GENESIS, GINGER, MEDUSA, RON, and TDA3D. Initial comparisons between each of these independent formulations show good agreement for the parameters of the APS SASE FEL.

  18. AP39, a mitochondria‐targeting hydrogen sulfide (H2S) donor, protects against myocardial reperfusion injury independently of salvage kinase signalling

    PubMed Central

    Karwi, Qutuba G; Bornbaum, Julia; Boengler, Kerstin; Torregrossa, Roberta; Whiteman, Matthew; Wood, Mark E; Schulz, Rainer

    2017-01-01

    Background and Purpose H2S protects myocardium against ischaemia/reperfusion injury. This protection may involve the cytosolic reperfusion injury salvage kinase (RISK) pathway, but direct effects on mitochondrial function are possible. Here, we investigated the potential cardioprotective effect of a mitochondria‐specific H2S donor, AP39, at reperfusion against ischaemia/reperfusion injury. Experimental Approach Anaesthetized rats underwent myocardial ischaemia (30 min)/reperfusion (120 min) with randomization to receive interventions before reperfusion: vehicle, AP39 (0.01, 0.1, 1 μmol·kg−1), or control compounds AP219 and ADT‐OH (1 μmol·kg−1). LY294002, L‐NAME or ODQ were used to investigate the involvement of the RISK pathway. Myocardial samples harvested 5 min after reperfusion were analysed for RISK protein phosphorylation and isolated cardiac mitochondria were used to examine the direct mitochondrial effects of AP39. Key Results AP39, dose‐dependently, reduced infarct size. Inhibition of either PI3K/Akt, eNOS or sGC did not affect this effect of AP39. Western blot analysis confirmed that AP39 did not induce phosphorylation of Akt, eNOS, GSK‐3β or ERK1/2. In isolated subsarcolemmal and interfibrillar mitochondria, AP39 significantly attenuated mitochondrial ROS generation without affecting respiratory complexes I or II. Furthermore, AP39 inhibited mitochondrial permeability transition pore (PTP) opening and co‐incubation of mitochondria with AP39 and cyclosporine A induced an additive inhibitory effect on the PTP. Conclusion and Implications AP39 protects against reperfusion injury independently of the cytosolic RISK pathway. This cardioprotective effect could be mediated by inhibiting PTP via a cyclophilin D‐independent mechanism. Thus, selective delivery of H2S to mitochondria may be therapeutically applicable for employing the cardioprotective utility of H2S. PMID:27930802

  19. Prevention & treatment of obstetrical complications in APS: Is hydroxychloroquine the Holy Grail we are looking for?

    PubMed

    Meroni, Pier Luigi

    2016-12-01

    Pregnancy morbidity is part of the clinical spectrum of the anti-phospholipid syndrome (APS), with an important social and economical cost. Antiplatelet and anticoagulant agents are effective in preventing the clinical manifestations in the majority of the patients. However, a consistent proportion of the pregnant women present recurrences in spite of the standard therapy. Observational studies and anecdotal reports raised the issue of additional therapeutic strategies in these refractory cases. Among these, anti-malarials (AMs) and in particular hydroxychloroquine (HCQ) are becoming more and more popular in APS as well as in other systemic autoimmune rheumatic conditions. AMs display a pleiotropic activity spanning from immunomodulation effect to anti-inflammatory and anti-thrombotic activities, all of which potentially useful in APS. The well-known safety of HCQ in pregnancy encouraged its use in pregnant women with autoimmune rheumatic disorders including APS and observational reports suggested a protective effect on obstetrical recurrences. Since thrombosis does not seem to be the main pathogenic mechanism in obstetric APS, effectiveness of the treatment with HCQ should be related to other pharmacological effects rather than to the anti-platelet or anti-thrombotic activity of the molecule. Experimental models showed that HCQ may restore some defective biological functions induced by anti-phospholipid antibodies (aPL) on trophoblasts and a recent study reported a protective effect on in vivo aPL-mediated placental and foetal neurodevelopmental abnormalities. Although the rational behind the use of HCQ in obstetric APS is sound, the evidence from the real life is not conclusive and a critical appraisal through clinical trials is mandatory. Copyright © 2016. Published by Elsevier Ltd.

  20. EPA’s AP-42 development methodology: Converting or rerating current AP-42 datasets

    USDA-ARS?s Scientific Manuscript database

    In August 2013, the U.S. Environmental Protection Agency’s (EPA) published their new methodology for updating the Compilation of Air Pollution Emission Factors (AP-42). The “Recommended Procedures for Development of Emissions Factors and Use of the WebFIRE Database” instructs that the ratings of the...

  1. Targeting War-Sustaining Capability at Sea: Compatibility with Additional Protocol I

    DTIC Science & Technology

    2009-07-01

    however, it is an aspirational “model code ” proposed by a non- governmental organization, not a binding international agreement. See SAN REMO MANUAL...limits of the law of war at sea. Moreover, the Nuremburg court’s decision to convict Dönitz of violating international law but not to inflict... Nuremburg charged Dönitz with waging “unrestricted submarine warfare contrary to the Naval Protocol of 1936 . . . which reaffirmed the rules of submarine

  2. A seven-year northern sky survey of Ap stars for rapid variability

    NASA Technical Reports Server (NTRS)

    Nelson, Matthew J.; Kreidl, Tobias J.

    1993-01-01

    A high-speed photometric survey of 120 Ap stars in the northern sky, has been conducted, between 1985 and 1991, in order to search for rapid variability. Stars of spectral types, namely from B8 to F4, have been selected for the survey. The selected pulsational variable stars occupy the hotter regions of the instability strip of the Hertzsprung-Russel diagram. Noted is the absence of pulsations in the hotter B8-A3 Ap stars; this does not, however, preclude the existence of pulsations, since HD 218495 was recently discovered to be a rapidly oscillating Ap (roAp) star. The primary result of this study is that various combinations of photometric indices, while pointing towards roAp stars having the characteristic signatures of cool, SrCrEu stars, still fail to isolate the roAp phenomenon from similar nonpulsating Ap stars. Color-magnitude and color-color diagrams are presented in order to complete this survey.

  3. SEPTUM MAGNET DESIGN FOR THE APS-U

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

    Abliz, M.; Jaski, M.; Xiao, A.

    2017-06-25

    The Advanced Photon Source is in the process of upgrading its storage ring from a double-bend to a multi-bend lattice as part of the APS Upgrade Project (APS-U). A swap-out injection scheme is planned for the APS-U to keep a constant beam current and to enable a small dynamic aperture. A septum magnet with a minimum thickness of 2 mm and an injection field of 1.06 T has been designed, delivering the required total deflecting angle is 89 mrad with a ring energy of 6 GeV. The stored beam chamber has an 8 mm x 6 mm super-ellipsoidal aperture. Themore » magnet is straight; however, it is tilted in yaw, roll, and pitch from the stored beam chamber to meet the on axis swap out injection requirements for the APS-U lattice. In order to minimize the leakage field inside the stored beam chamber, four different techniques were utilized in the design. As a result, the horizontal deflecting angle of the stored beam was held to only 5 µrad, and the integrated skew quadrupole inside the stored beam chamber was held to 0.09 T. The detailed techniques that were applied to the design, field multipoles, and resulting trajectories of the injected and stored beams are reported.« less

  4. Mechanism of action of novel lung edema therapeutic AP301 by activation of the epithelial sodium channel.

    PubMed

    Shabbir, Waheed; Scherbaum-Hazemi, Parastoo; Tzotzos, Susan; Fischer, Bernhard; Fischer, Hendrik; Pietschmann, Helmut; Lucas, Rudolf; Lemmens-Gruber, Rosa

    2013-12-01

    AP301 [Cyclo(CGQRETPEGAEAKPWYC)], a cyclic peptide comprising the human tumor necrosis factor lectin-like domain (TIP domain) sequence, is currently being developed as a treatment for lung edema and has been shown to reduce extravascular lung water and improve lung function in mouse, rat, and pig models. The current paradigm for liquid homeostasis in the adult mammalian lung is that passive apical uptake of sodium via the amiloride-sensitive epithelial Na⁺ channel (ENaC) and nonselective cyclic-nucleotide-gated cation channels creates the major driving force for reabsorption of water through the alveolar epithelium in addition to other ion channels such as potassium and chloride channels. AP301 can increase amiloride-sensitive current in A549 cells as well as in freshly isolated type II alveolar epithelial cells from different species. ENaC is expressed endogenously in all of these cell types. Consequently, this study was undertaken to determine whether ENaC is the specific target of AP301. The effect of AP301 in A549 cells as well as in human embryonic kidney cells and Chinese hamster ovary cells heterologously expressing human ENaC subunits (α, β, γ, and δ) was measured in patch clamp experiments. The congener TIP peptide AP318 [Cyclo(4-aminobutanoic acid-GQRETPEGAEAKPWYD)] activated ENaC by increasing single-channel open probability. AP301 increased current in proteolytically activated (cleaved) but not near-silent (uncleaved) ENaC in a reversible manner. αβγ- or δβγ-ENaC coexpression was required for maximal activity. No increase in current was observed after deglycosylation of extracellular domains of ENaC. Thus, our data suggest that the specific interaction of AP301 with both endogenously and heterologously expressed ENaC requires precedent binding to glycosylated extracellular loop(s).

  5. Cardioprotective effect of diadenosine tetraphosphate (AP4A) preservation in hypothermic storage and its relation with mitochondrial ATP-sensitive potassium channels.

    PubMed

    Ahmet, I; Sawa, Y; Nishimura, M; Kitakaze, M; Matsuda, H

    2000-01-15

    The preconditioning effect of diadenosine tetraphosphate (AP4A) was reported in ischemia/reperfused hearts, but its effect in heart preservation was unknown. According to the possible role of mitochondrial ATP-sensitive potassium channel (mK(ATP) channel) in the effect of ischemic preconditioning, the contribution of mK(ATP) channel to the effect of AP4A was tested. Isolated rat hearts were arrested and preserved by Eurocollin's (EC) solution at 4 degrees C for 8 hr. AP4A (80 microM) or AP4A with the 5-hydroxydecanoic acid (100 microM), a selective inhibitor of the mK(ATP) channel, was added into the EC solution. The preischemic and postischemic cardiac functions were evaluated on a buffer-perfused Langendorff apparatus before storage and after 20 min of reperfusion. AP4A administration improved the recovery of poststorage cardiac functions (the rate-pressure production, left ventricular systolic pressure, heart rate, coronary flow rate, and derivative of left ventricular systolic pressure; P<0.05) and reduced the leakage of lactate dehydrate and creatine kinase during reperfusion, compared with EC alone. Those effects of AP4A were completely reversed by 5-hydroxydecanoic acid administration in combination subjects. AP4A administration protects the heart through opening of the mK(ATP) channel during hypothermic preservation. Thus, addition of AP4A into cardioplegia may be a novel method of ischemic preconditioning in the transplantation context.

  6. Radioactive air emissions notice of construction for installation and operation of a waste retrieval system and tanks 241-AP-102 and 241-AP-104 project

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

    DEXTER, M.L.

    1999-11-15

    This document serves as a notice of construction (NOC) pursuant to the requirements of Washington Administrative Code (WAC) 246 247-060, and as a request for approval to modify pursuant to 40 Code of Federal Regulations (CFR) 61 07 for the installation and operation of one waste retrieval system in the 24 1 AP-102 Tank and one waste retrieval system in the 241 AP 104 Tank Pursuant to 40 CFR 61 09 (a)( 1) this application is also intended to provide anticipated initial start up notification Its is requested that EPA approval of this application will also constitute EPA acceptance ofmore » the initial start up notification Project W 211 Initial Tank Retrieval Systems (ITRS) is scoped to install a waste retrieval system in the following double-shell tanks 241-AP 102-AP 104 AN 102, AN 103, AN-104, AN 105, AY 102 AZ 102 and SY-102 between now and the year 2011. Because of the extended installation schedules and unknowns about specific activities/designs at each tank, it was decided to submit NOCs as that information became available This NOC covers the installation and operation of a waste retrieval system in tanks 241 AP-102 and 241 AP 104 Generally this includes removal of existing equipment installation of new equipment and construction of new ancillary equipment and buildings Tanks 241 AP 102 and 241 AP 104 will provide waste feed for immobilization into a low activity waste (LAW) product (i.e. glass logs) The total effective dose equivalent (TEDE) to the offsite maximally exposed individual (MEI) from the construction activities is 0 045 millirem per year The unabated TEDE to the offsite ME1 from operation of the mixer pumps is 0 042 millirem per year.« less

  7. AP-2α and AP-2β cooperatively orchestrate homeobox gene expression during branchial arch patterning.

    PubMed

    Van Otterloo, Eric; Li, Hong; Jones, Kenneth L; Williams, Trevor

    2018-01-25

    The evolution of a hinged moveable jaw with variable morphology is considered a major factor behind the successful expansion of the vertebrates. DLX homeobox transcription factors are crucial for establishing the positional code that patterns the mandible, maxilla and intervening hinge domain, but how the genes encoding these proteins are regulated remains unclear. Herein, we demonstrate that the concerted action of the AP-2α and AP-2β transcription factors within the mouse neural crest is essential for jaw patterning. In the absence of these two proteins, the hinge domain is lost and there are alterations in the size and patterning of the jaws correlating with dysregulation of homeobox gene expression, with reduced levels of Emx, Msx and Dlx paralogs accompanied by an expansion of Six1 expression. Moreover, detailed analysis of morphological features and gene expression changes indicate significant overlap with various compound Dlx gene mutants. Together, these findings reveal that the AP-2 genes have a major function in mammalian neural crest development, influencing patterning of the craniofacial skeleton via the DLX code, an effect that has implications for vertebrate facial evolution, as well as for human craniofacial disorders. © 2018. Published by The Company of Biologists Ltd.

  8. FIRST BEAM TESTS OF THE APS MBA UPGRADE ORBIT FEEDBACK CONTROLLER

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

    Sereno, N. S.; Arnold, N.; Brill, A.

    The new orbit feedback system required for the APS multi-bend acromat (MBA) ring must meet challenging beam stability requirements. The AC stability requirement is to correct rms beam motion to 10 % the rms beam size at the insertion device source points from 0.01 to 1000 Hz. The vertical plane represents the biggest challenge for AC stability which is required to be 400 nm rms for a 4 micron vertical beam size. In addition long term drift over a period of 7 days is required to be 1 micron or less at insertion de- vice BPMs and 2 microns formore » arc bpms. We present test re- sults of theMBA prototype orbit feedback controller (FBC) in the APS storage ring. In this test, four insertion device BPMs were configured to send data to the FBC for process- ing into four fast corrector setpoints. The configuration of four bpms and four fast correctors creates a 4-bump and the configuration of fast correctors is similar to what will be implemented in the MBA ring. We report on performance benefits of increasing the sampling rate by a factor of 15 to 22.6 kHz over the existing APS orbit feedback system, lim- itations due to existing storage ring hardware and extrapo- lation to theMBA orbit feedback design. FBC architecture, signal flow and processing design will also be discussed.« less

  9. 15 CFR 782.1 - Overview of reporting requirements under the APR.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL... (see § 782.5 of the APR). In addition, forms may be downloaded from the Internet at http://www.ap.gov. ...

  10. 15 CFR 782.1 - Overview of reporting requirements under the APR.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL... (see § 782.5 of the APR). In addition, forms may be downloaded from the Internet at http://www.ap.gov. ...

  11. 15 CFR 782.1 - Overview of reporting requirements under the APR.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL... (see § 782.5 of the APR). In addition, forms may be downloaded from the Internet at http://www.ap.gov. ...

  12. 15 CFR 782.1 - Overview of reporting requirements under the APR.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL... (see § 782.5 of the APR). In addition, forms may be downloaded from the Internet at http://www.ap.gov. ...

  13. Advancing beyond AP Courses

    ERIC Educational Resources Information Center

    Hammond, Bruce G.

    2009-01-01

    A quiet revolution is picking up steam in the nation's private secondary schools, with broad implications for college admissions and for teaching and learning on both sides of the transition from high school to college. About 50 of the nation's leading college-preparatory schools have opted out of the College Board's Advanced Placement (AP)…

  14. An improved model for the combustion of AP composite propellants

    NASA Technical Reports Server (NTRS)

    Cohen, N. S.; Strand, L. D.

    1981-01-01

    This paper presents several improvements to the BDP model of steady-state burning of AP composite solid propellants. The Price-Boggs-Derr model of AP monopropellant burning is incorporated to represent the AP. A separate energy equation is written for the binder to permit a different surface temperature from the AP; this includes an analysis of the sharing of primary diffusion flame energy, and correction of a BDP model inconsistency in treating the binder regression rate. A method for assembling component contributions to calculate the burning rates of multimodal propellants is also presented. Results are shown in the form of representative burning rate curves, comparisons with data, and calculated internal details of interest. Ideas for future work are discussed in an Appendix.

  15. NOS1 mediates AP1 nuclear translocation and inflammatory response.

    PubMed

    Srivastava, Mansi; Baig, Mirza S

    2018-06-01

    A hallmark of the AP1 functioning is its nuclear translocation, which induces proinflammatory cytokine expression and hence the inflammatory response. After endotoxin shock AP1 transcription factor, which comprises Jun, ATF2, and Fos family of proteins, translocates into the nucleus and induces proinflammatory cytokine expression. In the current study, we found, NOS1 inhibition prevents nuclear translocation of the AP1 transcription factor subunits. Pharmacological inhibition of NOS1 impedes translocation of subunits into the nucleus, suppressing the transcription of inflammatory genes causing a diminished inflammatory response. In conclusion, the study shows the novel mechanism of NOS1- mediated AP1 nuclear translocation, which needs to be further explored. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. Nonblocking and orphan free message logging protocols

    NASA Technical Reports Server (NTRS)

    Alvisi, Lorenzo; Hoppe, Bruce; Marzullo, Keith

    1992-01-01

    Currently existing message logging protocols demonstrate a classic pessimistic vs. optimistic tradeoff. We show that the optimistic-pessimistic tradeoff is not inherent to the problem of message logging. We construct a message-logging protocol that has the positive features of both optimistic and pessimistic protocol: our protocol prevents orphans and allows simple failure recovery; however, it requires no blocking in failure-free runs. Furthermore, this protocol does not introduce any additional message overhead as compared to one implemented for a system in which messages may be lost but processes do not crash.

  17. Nonblocking and orphan free message logging protocols

    NASA Astrophysics Data System (ADS)

    Alvisi, Lorenzo; Hoppe, Bruce; Marzullo, Keith

    1992-12-01

    Currently existing message logging protocols demonstrate a classic pessimistic vs. optimistic tradeoff. We show that the optimistic-pessimistic tradeoff is not inherent to the problem of message logging. We construct a message-logging protocol that has the positive features of both optimistic and pessimistic protocol: our protocol prevents orphans and allows simple failure recovery; however, it requires no blocking in failure-free runs. Furthermore, this protocol does not introduce any additional message overhead as compared to one implemented for a system in which messages may be lost but processes do not crash.

  18. APS Conference on Understanding the Biological Clock: From Genetics to Physiology

    NASA Technical Reports Server (NTRS)

    Frank, Martin

    1996-01-01

    The Conference was designed to take advantage of the fusion of two intellectually dominant but heretofore separate lines of clock research, vertebrate physiology and invertebrate and microbial genetics. The APS Conference attracted 251 scientists, 68 of whom were students. In addition to the excellent speaker program organized by Dunlap and Loros, the attendees also submitted 93 volunteer abstracts that were programmed in poster sessions. Thirty-four percent of the submitted abstracts were first authorized by a female student or scientist.

  19. Incorporating Ninth-Grade PSAT/NMSQT® Scores into AP Potential™ Predictions for AP® European History and AP World History. Statistical Report 2014-1

    ERIC Educational Resources Information Center

    Zhang, Xiuyuan; Patel, Priyank; Ewing, Maureen

    2015-01-01

    Historically, AP Potential™ correlations and expectancy tables have been based on 10th-and 11th-grade PSAT/NMSQT® examinees and 11th-and 12th-grade AP® examinees for all subjects (Zhang, Patel, & Ewing,2014; Ewing, Camara, & Millsap, 2006; Camara & Millsap, 1998). However, a large number of students take AP European History and AP…

  20. Isolation and characterization of diadenosine tetraphosphate (Ap4A) hydrolase from Schizosaccharomyces pombe.

    PubMed

    Robinson, A K; de la Peña, C E; Barnes, L D

    1993-02-13

    An enzyme that catalyzes the asymmetric hydrolysis of Ap4A has been partially purified from the fission yeast, Schizosaccharomyces pombe. The crude supernatant fraction from log-phase cells was fractionated by (NH4)2SO4 precipitation followed by chromatography on DEAE-cellulose, Red A dye-ligand and QAE-Sepharose resins. Two peaks of Ap4A hydrolase activity, designated major and minor, were separated on the Red A dye-ligand resin. Both the major and minor Ap4A hydrolase have an apparent molecular mass of 49 kDa based on gel filtration chromatography. On a SDS polyacrylamide gel, a protein of 22 kDa exhibited Ap4A hydrolase activity. Both forms of the enzyme have a Km value in the range of 22 to 36 microM for Ap4A. Both forms of the enzyme asymmetrically hydrolyze Ap4A to AMP and ATP as determined by HPLC. Ap4A is the optimal substrate among several nucleotides and dinucleoside polyphosphates tested at 10 microM. A divalent metal cation is required for activity. Concentrations of Pi below 30 mM stimulate Ap4A hydrolase while higher concentrations inhibit the activity. Pi is not a substrate for this Ap4A-degradative enzyme. Fluoride, from 50 microM to 20 mM, has no significant effect on Ap4A hydrolase activity.

  1. AP: A Critical Examination of the Advanced Placement Program

    ERIC Educational Resources Information Center

    Sadler, Philip M.; Sonnert, Gerhard; Tai, Robert; Klopfenstein, Kirstin

    2016-01-01

    The Advanced Placement (AP) program was created to enhance the experience of gifted students as they transition from high school to college. "AP: A Critical Examination of the Advanced Placement Program," edited by Philip M. Sadler, Gerhard Sonnert, Robert Tai, and Kirstin Klopfenstein (2010, Harvard Education Press), questions the…

  2. ANKRD1 Acts as a Transcriptional Repressor of MMP13 via the AP-1 Site

    PubMed Central

    Almodóvar-García, Karinna; Kwon, Minjae; Samaras, Susan E.

    2014-01-01

    The transcriptional cofactor ANKRD1 is sharply induced during wound repair, and its overexpression enhances healing. We recently found that global deletion of murine Ankrd1 impairs wound contraction and enhances necrosis of ischemic wounds. A quantitative PCR array of Ankrd1−/− (KO) fibroblasts indicated that ANKRD1 regulates MMP genes. Yeast two-hybrid and coimmunoprecipitation analyses associated ANKRD1 with nucleolin, which represses AP-1 activation of MMP13. Ankrd1 deletion enhanced both basal and phorbol 12-myristate 13-acetate (PMA)-induced MMP13 promoter activity; conversely, Ankrd1 overexpression in control cells decreased PMA-induced MMP13 promoter activity. Ankrd1 reconstitution in KO fibroblasts decreased MMP13 mRNA, while Ankrd1 knockdown increased these levels. MMP13 mRNA and protein were elevated in intact skin and wounds of KO versus Ankrd1fl/fl (FLOX) mice. Electrophoretic mobility shift assay gel shift patterns suggested that additional transcription factors bind to the MMP13 AP-1 site in the absence of Ankrd1, and this concept was reinforced by chromatin immunoprecipitation analysis as greater binding of c-Jun to the AP-1 site in extracts from FLOX versus KO fibroblasts. We propose that ANKRD1, in association with factors such as nucleolin, represses MMP13 transcription. Ankrd1 deletion additionally relieved MMP10 transcriptional repression. Nuclear ANKRD1 appears to modulate extracellular matrix remodeling by MMPs. PMID:24515436

  3. AP Studio Art as an Enabling Constraint for Secondary Art Education

    ERIC Educational Resources Information Center

    Graham, Mark A.

    2009-01-01

    Advanced Placement (AP) Studio Art is an influential force in secondary art education as is evident in the 31,800 portfolios submitted for review in 2008. From the perspectives of a high school educator and AP Reader, this author has observed how the constraints of the AP program can be used to generate support for high school art programs and…

  4. MULTI-OBJECTIVE ONLINE OPTIMIZATION OF BEAM LIFETIME AT APS

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

    Sun, Yipeng

    In this paper, online optimization of beam lifetime at the APS (Advanced Photon Source) storage ring is presented. A general genetic algorithm (GA) is developed and employed for some online optimizations in the APS storage ring. Sextupole magnets in 40 sectors of the APS storage ring are employed as variables for the online nonlinear beam dynamics optimization. The algorithm employs several optimization objectives and is designed to run with topup mode or beam current decay mode. Up to 50\\% improvement of beam lifetime is demonstrated, without affecting the transverse beam sizes and other relevant parameters. In some cases, the top-upmore » injection efficiency is also improved.« less

  5. Shuttle APS propellant thermal conditioner study

    NASA Technical Reports Server (NTRS)

    Pearson, W. E.

    1971-01-01

    A study program was performed to allow selection of thermal conditioner assemblies for superheating O2 and H2 at supercritical pressures. The application was the auxiliary propulsion system (APS) for the space shuttle vehicle. The O2/H2 APS propellant feed system included propellant conditioners, of which the thermal conditioner assemblies were a part. Cryogens, pumped to pressures above critical, were directed to the thermal conditioner assembly included: (1) a gas generator assembly with ignition system and bipropellant valves, which burned superheated O2 and H2 at rich conditions; (2) a heat exchanger assembly for thermal conditioning of the cryogenic propellant; and (3) a dump nozzle for heat exchanger exhaust.

  6. HIV-1 Nef-induced Down-Regulation of MHC Class I Requires AP-1 and Clathrin but Not PACS-1 and Is Impeded by AP-2

    PubMed Central

    Lubben, Nienke B.; Sahlender, Daniela A.; Motley, Alison M.; Lehner, Paul J.; Benaroch, Philippe

    2007-01-01

    Major histocompatibility complex class I is down-regulated from the surface of human immunodeficiency virus (HIV)-1-infected cells by Nef, a virally encoded protein that is thought to reroute MHC-I to the trans-Golgi network (TGN) in a phosphofurin acidic cluster sorting protein (PACS) 1, adaptor protein (AP)-1, and clathrin-dependent manner. More recently, an alternative model has been proposed, in which Nef uses AP-1 to direct MHC-I to endosomes and lysosomes. Here, we show that knocking down either AP-1 or clathrin with small interfering RNA inhibits the down-regulation of HLA-A2 (an MHC-I isotype) by Nef in HeLa cells. However, knocking down PACS-1 has no effect, not only on Nef-induced down-regulation of HLA-A2 but also on the localization of other proteins containing acidic cluster motifs. Surprisingly, knocking down AP-2 actually enhances Nef activity. Immuno-electron microscopy labeling of Nef-expressing cells indicates that HLA-A2 is rerouted not to the TGN, but to endosomes. In AP-2–depleted cells, more of the HLA-A2 localizes to the inner vesicles of multivesicular bodies. We propose that depleting AP-2 potentiates Nef activity by altering the membrane composition and dynamics of endosomes and causing increased delivery of HLA-A2 to a prelysosomal compartment. PMID:17581864

  7. The History of the APS Topical Group on Shock Compression of Condensed Matter

    NASA Astrophysics Data System (ADS)

    Forbes, Jerry W.

    2002-07-01

    In order to provide broader scientific recognition and to advance the science of shock compressed condensed matter, a group of American Physical Society (APS) members worked within the Society to make this field an active part of the APS. Individual papers were presented at APS meetings starting in the 1940's and shock wave sessions were organized starting with the 1967 Pasadena meeting. Shock wave topical conferences began in 1979 in Pullman, WA. Signatures were obtained on a petition in 1984 from a balanced cross-section of the shock wave community to form an APS Topical Group (TG). The APS Council officially accepted the formation of the Shock Compression of Condensed Matter (SCCM) TG at its October 1984 meeting. This action firmly aligned the shock wave field with a major physical science organization. Most early topical conferences were sanctioned by the APS while those held after 1992 were official APS meetings. The topical group organizes a shock wave topical conference in odd numbered years while participating in shock wave/high pressure sessions at APS general meetings in even numbered years.

  8. An application protocol for CAD to CAD transfer of electronic information

    NASA Technical Reports Server (NTRS)

    Azu, Charles C., Jr.

    1993-01-01

    The exchange of Computer Aided Design (CAD) information between dissimilar CAD systems is a problem. This is especially true for transferring electronics CAD information such as multi-chip module (MCM), hybrid microcircuit assembly (HMA), and printed circuit board (PCB) designs. Currently, there exists several neutral data formats for transferring electronics CAD information. These include IGES, EDIF, and DXF formats. All these formats have limitations for use in exchanging electronic data. In an attempt to overcome these limitations, the Navy's MicroCIM program implemented a project to transfer hybrid microcircuit design information between dissimilar CAD systems. The IGES (Initial Graphics Exchange Specification) format is used since it is well established within the CAD industry. The goal of the project is to have a complete transfer of microelectronic CAD information, using IGES, without any data loss. An Application Protocol (AP) is being developed to specify how hybrid microcircuit CAD information will be represented by IGES entity constructs. The AP defines which IGES data items are appropriate for describing HMA geometry, connectivity, and processing as well as HMA material characteristics.

  9. The GREENH-City interventional research protocol on health in all policies.

    PubMed

    Porcherie, Marion; Vaillant, Zoé; Faure, Emmanuelle; Rican, Stéphane; Simos, Jean; Cantoreggi, Nicola Luca; Heritage, Zoé; Le Gall, Anne Roue; Cambon, Linda; Diallo, Thierno Amadou; Vidales, Eva; Pommier, Jeanine

    2017-10-18

    This paper presents the research protocol of the GoveRnance for Equity, EnviroNment and Health in the City (GREENH-City) project funded by the National Institute for Cancer (Subvention N°2017-003-INCA). In France, health inequities have tended to increase since the late 1980s. Numerous studies show the influence of social, economic, geographic and political determinants on health inequities across the life course. Exposure to environmental factors is uneven across the population and may impact on health and health inequities. In cities, green spaces contribute to creating healthy settings which may help tackle health inequities. Health in All Policies (HiAP) represents one of the key strategies for addressing social and environmental determinants of health inequities. The objective of this research is to identify the most promising interventions to operationalize the HiAP approaches at the city level to tackle health inequities through urban green spaces. It is a participatory interventional research to analyze public policy in real life setting (WHO Healthy Cities). It is a mixed method systemic study with a quantitative approach for the 80 cities and a comparative qualitative multiple case-studies of 6 cities. The research combines 3 different lens: 1/a political analysis of how municipalities apply HiAP to reduce social inequities of health through green space policies and interventions 2/a geographical and topological characterization of green spaces and 3/ on-site observations of the use of green spaces by the inhabitants. City profiles will be identified regarding their HiAP approaches and the extent to which these cities address social inequities in health as part of their green space policy action. The analysis of the transferability of the results will inform policy recommendations in the rest of the Health City Network and widely for the French municipalities. The study will help identify factors enabling the implementation of the HiAP approach at a

  10. Diadenosine tetraphosphate (Ap4A) - an E. coli alarmone or a damage metabolite?

    PubMed

    Despotović, Dragana; Brandis, Alexander; Savidor, Alon; Levin, Yishai; Fumagalli, Laura; Tawfik, Dan S

    2017-07-01

    Under stress, metabolism is changing: specific up- or down-regulation of proteins and metabolites occurs as well as side effects. Distinguishing specific stress-signaling metabolites (alarmones) from side products (damage metabolites) is not trivial. One example is diadenosine tetraphosphate (Ap4A) - a side product of aminoacyl-tRNA synthetases found in all domains of life. The earliest observations suggested that Ap4A serves as an alarmone for heat stress in Escherichia coli. However, despite 50 years of research, the signaling mechanisms associated with Ap4A remain unknown. We defined a set of criteria for distinguishing alarmones from damage metabolites to systematically classify Ap4A. In a nutshell, no indications for a signaling cascade that is triggered by Ap4A were found; rather, we found that Ap4A is efficiently removed in a constitutive, nonregulated manner. Several fold perturbations in Ap4A concentrations have no effect, yet accumulation at very high levels is toxic due to disturbance of zinc homeostasis, and also because Ap4A's structural overlap with ATP can result in spurious binding and inactivation of ATP-binding proteins. Overall, Ap4A met all criteria for a damage metabolite. While we do not exclude any role in signaling, our results indicate that the damage metabolite option should be considered as the null hypothesis when examining Ap4A and other metabolites whose levels change upon stress. © 2017 Federation of European Biochemical Societies.

  11. Raising Rigor, Getting Results: Lessons Learned from AP Expansion

    ERIC Educational Resources Information Center

    Wakelyn, David

    2009-01-01

    Advanced Placement (AP), which enables high school students to take introductory college-level courses, is the nation's oldest example of a rigorous, common curriculum. Students who score well on AP exams are more likely to persist in college and earn a degree. The Advanced Placement Expansion project of the National Governors Association Center…

  12. Data-Based Decision Making: The Road to AP Equity

    ERIC Educational Resources Information Center

    Edwards, Kelcey; Duggan, Odette

    2012-01-01

    Presented at the Advanced Placement Annual Conference (APAC) in Lake Buena Vista, FL in July 2012. This presentation reviews concepts central to achieving equitable AP access and success for all willing and academically prepared students. We analyze trends in participation and performance by race/ethnicity from the AP Report to the Nation and…

  13. Genome-Wide Identification of AP2/ERF Transcription Factors in Cauliflower and Expression Profiling of the ERF Family under Salt and Drought Stresses

    PubMed Central

    Li, Hui; Wang, Yu; Wu, Mei; Li, Lihong; Li, Cong; Han, Zhanpin; Yuan, Jiye; Chen, Chengbin; Song, Wenqin; Wang, Chunguo

    2017-01-01

    The AP2/ERF transcription factors (TFs) comprise one of the largest gene superfamilies in plants. These TFs perform vital roles in plant growth, development, and responses to biotic and abiotic stresses. In this study, 171 AP2/ERF TFs were identified in cauliflower (Brassica oleracea L. var. botrytis), one of the most important horticultural crops in Brassica. Among these TFs, 15, 9, and 1 TFs were classified into the AP2, RAV, and Soloist family, respectively. The other 146 TFs belong to ERF family, which were further divided into the ERF and DREB subfamilies. The ERF subfamily contained 91 TFs, while the DREB subfamily contained 55 TFs. Phylogenetic analysis results indicated that the AP2/ERF TFs can be classified into 13 groups, in which 25 conserved motifs were confirmed. Some motifs were group- or subgroup- specific, implying that they are significant to the functions of the AP2/ERF TFs of these clades. In addition, 35 AP2/ERF TFs from the 13 groups were selected randomly and then used for expression pattern analysis under salt and drought stresses. The majority of these AP2/ERF TFs exhibited positive responses to these stress conditions. In specific, Bra-botrytis-ERF054a, Bra-botrytis-ERF056, and Bra-botrytis-CRF2a demonstrated rapid responses. By contrast, six AP2/ERF TFs were showed to delay responses to both stresses. The AP2/ERF TFs exhibiting specific expression patterns under salt or drought stresses were also confirmed. Further functional analysis indicated that ectopic overexpression of Bra-botrytis-ERF056 could increase tolerance to both salt and drought treatments. These findings provide new insights into the AP2/ERF TFs present in cauliflower, and offer candidate AP2/ERF TFs for further studies on their roles in salt and drought stress tolerance. PMID:28642765

  14. The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

    PubMed Central

    Diccianni, M B; Imagawa, M; Muramatsu, M

    1992-01-01

    Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis. Images PMID:1408831

  15. The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

    PubMed

    Diccianni, M B; Imagawa, M; Muramatsu, M

    1992-10-11

    Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis.

  16. MTP: An atomic multicast transport protocol

    NASA Technical Reports Server (NTRS)

    Freier, Alan O.; Marzullo, Keith

    1990-01-01

    Multicast transport protocol (MTP); a reliable transport protocol that utilizes the multicast strategy of applicable lower layer network architectures is described. In addition to transporting data reliably and efficiently, MTP provides the client synchronization necessary for agreement on the receipt of data and the joining of the group of communicants.

  17. Crystal structures of eosinophil-derived neurotoxin (EDN) in complex with the inhibitors 5'-ATP, Ap3A, Ap4A, and Ap5A.

    PubMed

    Baker, Matthew D; Holloway, Daniel E; Swaminathan, G Jawahar; Acharya, K Ravi

    2006-01-17

    Eosinophil-derived neurotoxin (EDN) is a catalytically proficient member of the pancreatic ribonuclease superfamily secreted along with other eosinophil granule proteins during innate host defense responses and various eosinophil-related inflammatory and allergic diseases. The ribonucleolytic activity of EDN is central to its antiviral and neurotoxic activities and possibly to other facets of its biological activity. To probe the importance of this enzymatic activity further, specific inhibitors will be of great aid. Derivatives of 5'-ADP are among the most potent inhibitors currently known. Here, we use X-ray crystallography to investigate the binding of four natural nucleotides containing this moiety. 5'-ATP binds in two alternative orientations, one occupying the B2 subsite in a conventional manner and one being a retro orientation with no ordered adenosine moiety. Diadenosine triphosphate (Ap3A) and diadenosine tetraphosphate (Ap4A) bind with one adenine positioned at the B2 subsite, the polyphosphate chain extending across the P1 subsite in an ill-defined conformation, and a disordered second adenosine moiety. Diadenosine pentaphosphate (Ap5A), the most avid inhibitor of this series, binds in a completely ordered fashion with one adenine positioned conventionally at the B2 subsite, the polyphosphate chain occupying the P1 and putative P(-1) subsites, and the other adenine bound in a retro-like manner at the edge of the B1 subsite. The binding mode of each of these inhibitors has features seen in previously determined structures of adenosine diphosphates. We examine the structure-affinity relationships of these inhibitors and discuss the implications for the design of improved inhibitors.

  18. Modeling Instruction in AP Physics C: Mechanics and Electricity and Magnetism

    NASA Astrophysics Data System (ADS)

    Belcher, Nathan Tillman

    This action research study used data from multiple assessments in Mechanics and Electricity and Magnetism to determine the viability of Modeling Instruction as a pedagogy for students in AP Physics C: Mechanics and Electricity and Magnetism. Modeling Instruction is a guided-inquiry approach to teaching science in which students progress through the Modeling Cycle to develop a fully-constructed model for a scientific concept. AP Physics C: Mechanics and Electricity and Magnetism are calculus-based physics courses, approximately equivalent to first-year calculus-based physics courses at the collegiate level. Using a one-group pretest-posttest design, students were assessed in Mechanics using the Force Concept Inventory, Mechanics Baseline Test, and 2015 AP Physics C: Mechanics Practice Exam. With the same design, students were assessed in Electricity and Magnetism on the Brief Electricity and Magnetism Assessment, Electricity and Magnetism Conceptual Assessment, and 2015 AP Physics C: Electricity and Magnetism Practice Exam. In a one-shot case study design, student scores were collected from the 2017 AP Physics C: Mechanics and Electricity and Magnetism Exams. Students performed moderately well on the assessments in Mechanics and Electricity and Magnetism, demonstrating that Modeling Instruction is a viable pedagogy in AP Physics C: Electricity and Magnetism.

  19. The Role of the Clathrin Adaptor AP-1: Polarized Sorting and Beyond

    PubMed Central

    Nakatsu, Fubito; Hase, Koji; Ohno, Hiroshi

    2014-01-01

    The selective transport of proteins or lipids by vesicular transport is a fundamental process supporting cellular physiology. The budding process involves cargo sorting and vesicle formation at the donor membrane and constitutes an important process in vesicular transport. This process is particularly important for the polarized sorting in epithelial cells, in which the cargo molecules need to be selectively sorted and transported to two distinct destinations, the apical or basolateral plasma membrane. Adaptor protein (AP)-1, a member of the AP complex family, which includes the ubiquitously expressed AP-1A and the epithelium-specific AP-1B, regulates polarized sorting at the trans-Golgi network and/or at the recycling endosomes. A growing body of evidence, especially from studies using model organisms and animals, demonstrates that the AP-1-mediated polarized sorting supports the development and physiology of multi-cellular units as functional organs and tissues (e.g., cell fate determination, inflammation and gut immune homeostasis). Furthermore, a possible involvement of AP-1B in the pathogenesis of human diseases, such as Crohn’s disease and cancer, is now becoming evident. These data highlight the significant contribution of AP-1 complexes to the physiology of multicellular organisms, as master regulators of polarized sorting in epithelial cells. PMID:25387275

  20. Molecular Basis for Enhancement of the Meiotic DMCI Recombinase by RAD51AP1

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

    Dray, Eloise; Dunlop, Myun Hwa; Kauppi, Liisa

    Homologous recombination is needed for meiotic chromosome segregation, genome maintenance, and tumor suppression. RAD51AP1 (RAD51 Associated Protein 1) has been shown to interact with and enhance the recombinase activity of RAD51. Accordingly, genetic ablation of RAD51AP1 leads to enhanced sensitivity to and also chromosome aberrations upon DNA damage, demonstrating a role for RAD51AP1 in mitotic homologous recombination. Here we show physical association of RAD51AP1 with the meiosis-specific recombinase DMC1 and a stimulatory effect of RAD51AP1 on the DMC1-mediated D-loop reaction. Mechanistic studies have revealed that RAD51AP1 enhances the ability of the DMC1 presynaptic filament to capture the duplex DNA partnermore » and to assemble the synaptic complex, in which the recombining DNA strands are homologously aligned. We also provide evidence that functional co-operation is dependent on complex formation between DMC1 and RAD51AP1, and that distinct epitopes in RAD51AP1 mediate interactions with RAD51 and DMC1. Finally, we show that RAD51AP1 is expressed in mouse testes, and that RAD51AP1 foci co-localize with a subset of DMC1 foci in spermatocytes. These results suggest that RAD51AP1 also serves an important role in meiotic homologous recombination.« less

  1. Molecular and functional characterization of clathrin- and AP-2-binding determinants within a disordered domain of auxilin.

    PubMed

    Scheele, Urte; Alves, Jurgen; Frank, Ronald; Duwel, Michael; Kalthoff, Christoph; Ungewickell, Ernst

    2003-07-11

    Uncoating of clathrin-coated vesicles requires the J-domain protein auxilin for targeting hsc70 to the clathrin coats and for stimulating the hsc70 ATPase activity. This results in the release of hsc70-complexed clathrin triskelia and concomitant dissociation of the coat. To understand the complex role of auxilin in uncoating and clathrin assembly in more detail, we analyzed the molecular organization of its clathrin-binding domain (amino acids 547-813). CD spectroscopy of auxilin fragments revealed that the clathrin-binding domain is almost completely disordered in solution. By systematic mapping using synthetic peptides and by site-directed mutagenesis, we identified short peptide sequences involved in clathrin heavy chain and AP-2 binding and evaluated their significance for the function of auxilin. Some of the binding determinants, including those containing sequences 674DPF and 636WDW, showed dual specificity for both clathrin and AP-2. In contrast, the two DLL motifs within the clathrin-binding domain were exclusively involved in clathrin binding. Surprisingly, they interacted not only with the N-terminal domain of the heavy chain, but also with the distal domain. Moreover, both DLL peptides proved to be essential for clathrin assembly and uncoating. In addition, we found that the motif 726NWQ is required for efficient clathrin assembly activity. Auxilin shares a number of protein-protein interaction motifs with other endocytic proteins, including AP180. We demonstrate that AP180 and auxilin compete for binding to the alpha-ear domain of AP-2. Like AP180, auxilin also directly interacts with the ear domain of beta-adaptin. On the basis of our data, we propose a refined model for the uncoating mechanism of clathrin-coated vesicles.

  2. Implementation and Initial Validation of the APS English Test [and] The APS English-Writing Test at Golden West College: Evidence for Predictive Validity.

    ERIC Educational Resources Information Center

    Isonio, Steven

    In May 1991, Golden West College (California) conducted a validation study of the English portion of the Assessment and Placement Services for Community Colleges (APS), followed by a predictive validity study in July 1991. The initial study was designed to aid in the implementation of the new test at GWC by comparing data on APS use at other…

  3. Clinical and serologic parallels to APS-I in patients with thymomas, and autoantigen transcripts in their tumors1

    PubMed Central

    Wolff, Anette S. B.; Kärner, Jaanika; Owe, Jone F.; Oftedal, Bergithe E.V.; Gilhus, Nils Erik; Erichsen, Martina M.; Kämpe, Olle; Meager, Anthony; Peterson, Pärt; Kisand, Kai; Willcox, Nick; Husebye, Eystein S.

    2014-01-01

    Patients with the autoimmune polyendocrine syndrome type I (APS-I), caused by mutations in the autoimmune regulator (AIRE) gene, and myasthenia gravis (MG) with thymoma, show intriguing but unexplained parallels. They include uncommon manifestations like autoimmune adrenal insufficiency (AI), hypoparathyroidism (HP), and chronic mucocutaneous candidiasis (CMC) plus autoantibodies neutralizing IL-17, IL-22 and type I interferons. Thymopoiesis in the absence of AIRE is implicated in both syndromes. To test whether these parallels extend further, we screened 247 patients with MG and/or thymoma for clinical features and organ-specific autoantibodies characteristic of APS-I patients, and assayed 26 thymoma samples for transcripts for AIRE and 16 peripheral tissue-specific autoantigens (TSAgs) by quantitative PCR. We found APS-I-typical autoantibodies and clinical manifestations, including CMC, AI and asplenia, respectively in 49/121 (40%) and 10/121 (8%) thymoma patients, but clinical features seldom co-occurred with the corresponding autoantibodies. Both were rare in other MG subgroups (N=126). In 38 APS-I patients, by contrast, we observed neither autoantibodies against muscle antigens nor any neuromuscular disorders. Whereas relative transcript levels for AIRE and 7 of 16 TSAgs showed the expected under-expression in thymomas, levels were increased for 4 of the 5 TSAgs most frequently targeted by these patients’ autoAbs. Hence the clinical and serologic parallels to APS-I in patients with thymomas are not explained purely by deficient TSAg transcription in these aberrant AIRE-deficient tumors. We therefore propose additional explanations for the unusual autoimmune biases they provoke. Thymoma patients should be monitored for potentially life-threatening APS-I manifestations such as AI and HP. PMID:25230752

  4. NOS1AP is associated with increased severity of PTSD and depression in untreated combat veterans.

    PubMed

    Lawford, Bruce R; Morris, Charles P; Swagell, Christopher D; Hughes, Ian P; Young, Ross McD; Voisey, Joanne

    2013-05-01

    Posttraumatic stress disorder (PTSD) and depressive disorder are over represented in combat veterans. Veterans with both disorders have an increased risk of suicide. The nitric oxide synthase 1 adaptor protein (NOS1AP) gene, which modulates stress-evoked N-methyl-d-aspartate (NMDA) activity, was investigated in combat veterans. A comprehensive genetic analysis of NOS1AP and its association with PTSD was investigated in Vietnam combat veterans with PTSD (n=121) and a group of healthy control individuals (n=237). PTSD patients were assessed for symptom severity and level of depression using the Mississippi Scale for Combat-Related PTSD and the Beck Depression Inventory-II (BDI). The G allele of NOS1AP SNP rs386231 was significantly associated with PTSD (p=0.002). Analysis of variance revealed significant differences in BDI-II and Mississippi scores between genotypes for rs386231 with the GG genotype associated with increased severity of depression (p=0.002 F=6.839) and higher Mississippi Scale for Combat-Related PTSD scores (p=0.033). Haplotype analysis revealed that the C/G haplotype (rs451275/rs386231) was significantly associated with PTSD (p=0.001). The sample sizes in our study were not sufficient to detect SNP associations with very small effects. In addition the study was limited by its cross sectional design. This is the first study reporting that a variant of the NOS1AP gene is associated with PTSD. Our data also suggest that a genetic variant in NOS1AP may increase the susceptibility to severe depression in patients with PTSD and increased risk for suicide. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  5. AP-102/104 Retrieval control system qualification test procedure

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

    RIECK, C.A.

    1999-05-18

    This Qualification Test Procedure documents the results of the qualification testing that was performed on the Project W-211, ''Initial Tank Retrieval Systems,'' retrieval control system (RCS) for tanks 241-AP-102 and 241-AP-104. The results confirm that the RCS has been programmed correctly and that the two related hardware enclosures have been assembled in accordance with the design documents.

  6. Quantum-key-distribution protocol with pseudorandom bases

    NASA Astrophysics Data System (ADS)

    Trushechkin, A. S.; Tregubov, P. A.; Kiktenko, E. O.; Kurochkin, Y. V.; Fedorov, A. K.

    2018-01-01

    Quantum key distribution (QKD) offers a way for establishing information-theoretical secure communications. An important part of QKD technology is a high-quality random number generator for the quantum-state preparation and for post-processing procedures. In this work, we consider a class of prepare-and-measure QKD protocols, utilizing additional pseudorandomness in the preparation of quantum states. We study one of such protocols and analyze its security against the intercept-resend attack. We demonstrate that, for single-photon sources, the considered protocol gives better secret key rates than the BB84 and the asymmetric BB84 protocols. However, the protocol strongly requires single-photon sources.

  7. N-methyl-d-aspartate receptors, learning and memory: chronic intraventricular infusion of the NMDA receptor antagonist d-AP5 interacts directly with the neural mechanisms of spatial learning.

    PubMed

    Morris, R G M; Steele, R J; Bell, J E; Martin, S J

    2013-03-01

    Three experiments were conducted to contrast the hypothesis that hippocampal N-methyl-d-aspartate (NMDA) receptors participate directly in the mechanisms of hippocampus-dependent learning with an alternative view that apparent impairments of learning induced by NMDA receptor antagonists arise because of drug-induced neuropathological and/or sensorimotor disturbances. In experiment 1, rats given a chronic i.c.v. infusion of d-AP5 (30 mm) at 0.5 μL/h were selectively impaired, relative to aCSF-infused animals, in place but not cued navigation learning when they were trained during the 14-day drug infusion period, but were unimpaired on both tasks if trained 11 days after the minipumps were exhausted. d-AP5 caused sensorimotor disturbances in the spatial task, but these gradually worsened as the animals failed to learn. Histological assessment of potential neuropathological changes revealed no abnormalities in d-AP5-treated rats whether killed during or after chronic drug infusion. In experiment 2, a deficit in spatial learning was also apparent in d-AP5-treated rats trained on a spatial reference memory task involving two identical but visible platforms, a task chosen and shown to minimise sensorimotor disturbances. HPLC was used to identify the presence of d-AP5 in selected brain areas. In Experiment 3, rats treated with d-AP5 showed a delay-dependent deficit in spatial memory in the delayed matching-to-place protocol for the water maze. These data are discussed with respect to the learning mechanism and sensorimotor accounts of the impact of NMDA receptor antagonists on brain function. We argue that NMDA receptor mechanisms participate directly in spatial learning. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  8. Building Reading, Writing and Analysis in the AP U.S. History Classroom

    ERIC Educational Resources Information Center

    Heller, Stephen; Stacy, Jason

    2013-01-01

    The building of historical thinking skills has historically been a lonely endeavor for AP U.S. history teachers. Many often generate their own pedagogy, perhaps modified from an AP workshop or generally gleaned from released exam essay questions. However, as currently scheduled, in 2014, the AP U.S. history exam will undergo a redesign that will…

  9. Glaucoma patients present increased levels of diadenosine tetraphosphate, Ap(4)A, in the aqueous humour.

    PubMed

    Castany, Marta; Jordi, Isabel; Catala, Jaume; Gual, Arcadi; Morales, Miguel; Gasull, Xavier; Pintor, Jesus

    2011-03-01

    Previous studies have shown the presence of diadenosine tetraphosphate (Ap(4)A) and pentaphosphate (Ap(5)A) in the aqueous humour (AH) of different species. When topically applied to the rabbit cornea, Ap(4)A decreased IOP while Ap(5)A increased it. Here we study the presence of dinucleoside polyphosphates in the AH from human patients with or without glaucoma. AH was obtained at the time of cataract surgery from patients with (n=16) or without (n=10) primary open-angle glaucoma. AH (0.1-0.2 ml) was collected at the beginning of surgery through a corneal paracentesis and immediately cooled in liquid nitrogen, kept frozen and protected from light. AH aliquots were analyzed by HPLC for the presence of Ap(4)A and Ap(5)A. Both, Ap(4)A and Ap(5)A were detected in the AH of both experimental groups. No significant differences were found for Ap(5)A. In contrast, Ap(4)A levels were increased by ∼15-fold in the AH from glaucomatous eyes ranging from 19.5±9.2 nM in normal individuals to 286.03±30.9 nM in glaucomatous patients. In conclusion, both Ap(4)A and Ap(5)A were detected for the first time in human AH. Interestingly, glaucomatous eyes presented elevated concentrations of Ap(4)A compared to controls. The role of Ap(4)A needs to be elucidated but it may help to protect the autonomic innervation in the ciliary body/trabecular meshwork. Also, because of its higher levels in glaucoma patients it may be considered as a possible glaucoma biomarker. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Responses of soil hydrolase kinetics to nitrogen and phosphorus additions in Chinese fir plantations of subtropical China

    NASA Astrophysics Data System (ADS)

    Zhang, X.; Zhang, C.; Yang, Y.; Wang, H.; Chen, F.; Fu, X.; Fang, X.; Sun, X.

    2016-12-01

    Nitrogen (N) deposition and low soil phosphorus (P) content aggravate the P limitation in subtropical forest soils. However, the responses of soil organic matter related hydrolyase kinetics to N and P additions in subtropical plantations are still not clear. We tested the hypothesis that P application can improve the potential maximum activities of soil carbon (C) and N related hydrolayase but substrate demand (Km) may tradeoff the catalytic efficiency of the enzymes. Thirty 20m×20m plots were established in November 2011 and six different treatments were randomly distributed with five replicates in the Chinese fir plantations in subtropical China. The ongoing treatments are control (CK, no N and P application), low N addition (N1:50 kg N ha-1 yr-1), high N addition (N2: 100 kg N ha-1 yr-1), P addition (P: 50 kg P ha-1 yr-1), low N andP addition (N1P: 50 kg N ha-1 yr-1 and 50 kg P ha-1 yr-1) and high N and P addition (N2P: 100 kg N ha-1yr-1and 50 kg P ha-1 yr-1). Soil enzyme kinetic parameters for b-1,4-glucosidase (βG), β-1,4-N-acetylglucosaminidase (NAG), and acid phosphatase (aP) were measured in November 2015. The substrate affinities (Km) of βG and NAG were not affected by N or /and P additions. However, the substrate affinities of aP were decreased by N additions (N1, N2) with higher Km values than the other treatments. N additions (N1, N2) or higher N combined P additions (N2P) increased Vmax and catalytic efficiencies for βG, while with P addition treatments (N1P, N2P, and P) decreased Vmax and catalytic efficiencies for aP. The effects of N combined P treatments (N1P and N2P) on kinetic parameters (Vmax, Km) and catalytic efficiencies for AP were similar to P treatment, indicating that P had stronger effects on organic phosphorus hydrolysis than N in the research site. The N additions (N1 and N2) did not affect the catalytic efficiencies for NAG despite of their positive responses to Vmax for NAG compared with CK. The catalytic efficiencies of aP and

  11. Development, implementation, and experimentation of parametric routing protocol for sensor networks

    NASA Astrophysics Data System (ADS)

    Nassr, Matthew S.; Jun, Jangeun; Eidenbenz, Stephan J.; Frigo, Janette R.; Hansson, Anders A.; Mielke, Angela M.; Smith, Mark C.

    2006-09-01

    The development of a scalable and reliable routing protocol for sensor networks is traced from a theoretical beginning to positive simulation results to the end of verification experiments in large and heavily loaded networks. Design decisions and explanations as well as implementation hurdles are presented to give a complete picture of protocol development. Additional software and hardware is required to accurately test the performance of our protocol in field experiments. In addition, the developed protocol is tested in TinyOS on Mica2 motes against well-established routing protocols frequently used in sensor networks. Our protocol proves to outperform the standard (MINTRoute) and the trivial (Gossip) in a variety of different scenarios.

  12. X-ray optics simulation and beamline design for the APS upgrade

    NASA Astrophysics Data System (ADS)

    Shi, Xianbo; Reininger, Ruben; Harder, Ross; Haeffner, Dean

    2017-08-01

    The upgrade of the Advanced Photon Source (APS) to a Multi-Bend Achromat (MBA) will increase the brightness of the APS by between two and three orders of magnitude. The APS upgrade (APS-U) project includes a list of feature beamlines that will take full advantage of the new machine. Many of the existing beamlines will be also upgraded to profit from this significant machine enhancement. Optics simulations are essential in the design and optimization of these new and existing beamlines. In this contribution, the simulation tools used and developed at APS, ranging from analytical to numerical methods, are summarized. Three general optical layouts are compared in terms of their coherence control and focusing capabilities. The concept of zoom optics, where two sets of focusing elements (e.g., CRLs and KB mirrors) are used to provide variable beam sizes at a fixed focal plane, is optimized analytically. The effects of figure errors on the vertical spot size and on the local coherence along the vertical direction of the optimized design are investigated.

  13. Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal cardiac preparations.

    PubMed

    Vahlensieck, U; Bokník, P; Gombosová, I; Huke, S; Knapp, J; Linck, B; Lüss, H; Müller, F U; Neumann, J; Deng, M C; Scheld, H H; Jankowski, H; Schlüter, H; Zidek, W; Zimmermann, N; Schmitz, W

    1999-02-01

    Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to 158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.

  14. Role of ubiquitin and the HPV E6 oncoprotein in E6AP-mediated ubiquitination

    PubMed Central

    Mortensen, Franziska; Schneider, Daniel; Barbic, Tanja; Sladewska-Marquardt, Anna; Kühnle, Simone; Marx, Andreas; Scheffner, Martin

    2015-01-01

    Deregulation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with three different clinical pictures. Hijacking of E6AP by the E6 oncoprotein of distinct human papillomaviruses (HPV) contributes to the development of cervical cancer, whereas loss of E6AP expression or function is the cause of Angelman syndrome, a neurodevelopmental disorder, and increased expression of E6AP has been involved in autism spectrum disorders. Although these observations indicate that the activity of E6AP has to be tightly controlled, only little is known about how E6AP is regulated at the posttranslational level. Here, we provide evidence that the hydrophobic patch of ubiquitin comprising Leu-8 and Ile-44 is important for E6AP-mediated ubiquitination, whereas it does not affect the catalytic properties of the isolated catalytic HECT domain of E6AP. Furthermore, we show that the HPV E6 oncoprotein rescues the disability of full-length E6AP to use a respective hydrophobic patch mutant of ubiquitin for ubiquitination and that it stimulates E6AP-mediated ubiquitination of Ring1B, a known substrate of E6AP, in vitro and in cells. Based on these data, we propose that E6AP exists in at least two different states, an active and a less active or latent one, and that the activity of E6AP is controlled by noncovalent interactions with ubiquitin and allosteric activators such as the HPV E6 oncoprotein. PMID:26216987

  15. Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice.

    PubMed

    Hwang, S-K; Jin, H; Kwon, J T; Chang, S-H; Kim, T H; Cho, C-S; Lee, K H; Young, M R; Colburn, N H; Beck, G R; Yang, H-S; Cho, M-H

    2007-09-01

    The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the re-emergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor in the future.

  16. APS-U LATTICE DESIGN FOR OFF-AXIS ACCUMULATION

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

    Sun, Yipeng; Borland, M.; Lindberg, R.

    2017-06-25

    A 67-pm hybrid-seven-bend achromat (H7BA) lattice is being proposed for a future Advanced Photon Source (APS) multi-bend-achromat (MBA) upgrade project. This lattice design pushes for smaller emittance and requires use of a swap-out (on-axis) injection scheme due to limited dynamic acceptance. Alternate lattice design work has also been performed for the APS upgrade to achieve better beam dynamics performance than the nominal APS MBA lattice, in order to allow off-axis accumulation. Two such alternate H7BA lattice designs, which target a still-low emittance of 90 pm, are discussed in detail in this paper. Although the single-particle-dynamics performance is good, simulations ofmore » collective effects indicate that surprising difficulty would be expected accumulating high single-bunch charge in this lattice. The brightness of the 90-pm lattice is also a factor of two lower than the 67-pm H7BA lattice.« less

  17. A paradoxical increase of a metabolite upon increased expression of its catabolic enzyme: the case of diadenosine tetraphosphate (Ap4A) and Ap4A phosphorylase I in Saccharomyces cerevisiae.

    PubMed Central

    Avila, D M; Robinson, A K; Kaushal, V; Barnes, L D

    1991-01-01

    The APA1 gene in Saccharomyces cerevisiae encodes Ap4A phosphorylase I, the catabolic enzyme for diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A). APA1 has been inserted into a multicopy plasmid and into a centromeric plasmid with a GAL1 promoter. Enhanced expression of APA1 via the plasmids resulted in 10- and 90-fold increases in Ap4A phosphorylase activity, respectively, as assayed in vitro. However, the intracellular concentration of Ap4A exhibited increases of 2- and 15-fold, respectively, from the two different plasmids. Intracellular Ap4A increased 3- to 20-fold during growth on galactose of a transformant with APA1 under the control of the GAL1 promoter. Intracellular adenosine 5'-P1-tetraphospho-P4-5"'-guanosine (Ap4G) and diguanosine 5',5"'-P1,P4-tetraphosphate (Gp4G) also increased in the transformant under these conditions. The chromosomal locus of APA1 has been disrupted in a haploid strain. The Ap4A phosphorylase activity decreased by 80% and the intracellular Ap4A concentration increased by a factor of five in the null mutant. These results with the null mutant agree with previous results reported by Plateau et al. (P. Plateau, M. Fromant, J.-M. Schmitter, J.-M. Buhler, and S. Blancquet, J. Bacteriol. 171:6437-6445, 1989). The paradoxical increase in Ap4A upon enhanced expression of APA1 indicates that the metabolic consequences of altered gene expression may be more complex than indicated solely by assay of enzymatic activity of the gene product. PMID:1660456

  18. A paradoxical increase of a metabolite upon increased expression of its catabolic enzyme: the case of diadenosine tetraphosphate (Ap4A) and Ap4A phosphorylase I in Saccharomyces cerevisiae.

    PubMed

    Avila, D M; Robinson, A K; Kaushal, V; Barnes, L D

    1991-12-01

    The APA1 gene in Saccharomyces cerevisiae encodes Ap4A phosphorylase I, the catabolic enzyme for diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A). APA1 has been inserted into a multicopy plasmid and into a centromeric plasmid with a GAL1 promoter. Enhanced expression of APA1 via the plasmids resulted in 10- and 90-fold increases in Ap4A phosphorylase activity, respectively, as assayed in vitro. However, the intracellular concentration of Ap4A exhibited increases of 2- and 15-fold, respectively, from the two different plasmids. Intracellular Ap4A increased 3- to 20-fold during growth on galactose of a transformant with APA1 under the control of the GAL1 promoter. Intracellular adenosine 5'-P1-tetraphospho-P4-5"'-guanosine (Ap4G) and diguanosine 5',5"'-P1,P4-tetraphosphate (Gp4G) also increased in the transformant under these conditions. The chromosomal locus of APA1 has been disrupted in a haploid strain. The Ap4A phosphorylase activity decreased by 80% and the intracellular Ap4A concentration increased by a factor of five in the null mutant. These results with the null mutant agree with previous results reported by Plateau et al. (P. Plateau, M. Fromant, J.-M. Schmitter, J.-M. Buhler, and S. Blancquet, J. Bacteriol. 171:6437-6445, 1989). The paradoxical increase in Ap4A upon enhanced expression of APA1 indicates that the metabolic consequences of altered gene expression may be more complex than indicated solely by assay of enzymatic activity of the gene product.

  19. Utilizing Additional Measures of High School Academic Preparation to Support Students in Their Math Self-Assessment

    ERIC Educational Resources Information Center

    Fong, Kristen E.; Melguizo, Tatiana

    2017-01-01

    This study describes student behavior through the actual assessment and placement (A&P) process. It then uses an alternative A&P policy that utilizes an additional measure that assesses prior math preparedness alongside subtest choice. Utilizing data from a community college that allows its' students to choose the assessment subtest used…

  20. Clinical application of diadenosine tetraphosphate (Ap4A:F-1500) for controlled hypotension.

    PubMed

    Kikuta, Y; Ohiwa, E; Okada, K; Watanabe, A; Haruki, S

    1999-01-01

    In our animal study, it was revealed that diadenosine tetraphosphate (Ap4A:F-1500) has a dose-dependent hypotension effect of up to 60% decrease in mean arterial pressure compared to control value. Furthermore, in healthy male volunteers, the safety of Ap4A up to 4 mg.min-1 was confirmed. In patients who require surgical procedures under general anesthesia together with controlled hypotension, hypotension was induced by Ap4A in order to examine its hypotensive effect and modulating action on the blood pressure. Ten patients who required controlled hypotension and who were scheduled for elective surgery under general anesthesia were studied. Anesthesia was maintained with isoflurane (n = 7) or sevoflurane (n = 3) in oxygen-nitrous oxide. Controlled hypotension was induced by Ap4A administered at a rate of 10-20 micrograms.kg-1.min-1. The dose was adjusted at a maximum rate of 80 micrograms.kg-1.min-1 until the target blood pressure was achieved. Arterial blood pressure and heart rate were monitored. Arterial samples were drawn at 4 separate time points to measure the concentration of Ap4A in the plasma. The time required for attaining the target blood pressure after initiation of Ap4A infusion was about 16 min, and the time lapse between withdrawal of infusion to recovery of blood pressure was about 18 min. No reflex tachycardia was observed during infusion of Ap4A and no rebound hypertension was evident after withdrawal. The plasma Ap4A concentration increased in response to the acceleration rate of Ap4A administration with a tendency of augmented hypotensive effect. As it produces an excellent hypotensive effect together with a modulating action on blood pressure, Ap4A was assessed as useful in producing controlled hypotension.

  1. Army and Marine Corps Active Protection System (APS) Efforts

    DTIC Science & Technology

    2016-08-30

    safe enough for operational use, the benefits of MAPS relative to non-developmental efforts, MAPS’ impacts on NDI APS performance and costs, the Army’s...APSs Effective and Safe Enough for Operational Use? .............................. 24 What are the Benefits of MAPS Relative to Non-Developmental...corrosion—which will also factor into their eventual APS plans. Potential issues for Congress include whether current NDI APSs are effective and

  2. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2018-02-21

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  3. AE8/AP8 Implementations in AE9/AP9, IRBEM, and SPENVIS

    DTIC Science & Technology

    2014-02-18

    period applies to orbit generation only; AE8/AP8 utilizes geomagnetic field models from other epochs as specified in the table below.) SHIELDOSE2 model...finite and semi- infinite slab data tables for Bremsstrahlung have been reversed [Heynderickx, private communication, May 2013]. This correction is...Cain, J. C., S. J. Hendricks, R. A. Langel, and W. V. Hudson (1967), A proposed model for the international geomagnetic reference field, 1965, J

  4. Army and Marine Corps Active Protection System (APS) Efforts

    DTIC Science & Technology

    2016-08-23

    with hard or soft kill capabilities to a variety of threats, including rocket -propelled grenades (RPGs) and anti-tank guided missiles (ATGMs). APS...of threats, including rocket -propelled grenades (RPGs) and anti-tank guided missiles (ATGMs). APS technologies are not new, and a number of nations...training. 1 RPGs are basically single man-portable, shoulder-fired, unguided rockets . RPGs have been widely proliferated but can be mitigated to a

  5. ION EFFECTS IN THE APS PARTICLE ACCUMULATOR RING

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

    Calvey, J.; Harkay, K.; Yao, CY.

    2017-06-25

    Trapped ions in the APS Particle Accumulator Ring (PAR) lead to a positive coherent tune shift in both planes, which increases along the PAR cycle as more ions accumulate. This effect has been studied using an ion simulation code developed at SLAC. After modifying the code to include a realistic vacuum profile, multiple ionization, and the effect of shaking the beam to measure the tune, the simulation agrees well with our measurements. This code has also been used to evaluate the possibility of ion instabilities at the high bunch charge needed for the APS-Upgrade.

  6. Coaching in the AP Classroom

    ERIC Educational Resources Information Center

    Fornaciari, Jim

    2013-01-01

    Many parallels exist between quality coaches and quality classroom teachers--especially AP teachers, who often feel the pressure to produce positive test results. Having developed a series of techniques and strategies for building a team-oriented winning culture on the field, Jim Fornaciari writes about how he adapted those methods to work in the…

  7. Molecular dynamics simulations of AP/HMX composite with a modified force field.

    PubMed

    Zhu, Wei; Wang, Xijun; Xiao, Jijun; Zhu, Weihua; Sun, Huai; Xiao, Heming

    2009-08-15

    An all-atom force field for ammonium perchlorate (AP) is developed with the framework of pcff force field. The structural parameters of AP obtained with the modified force field are in good agreement with experimental values. Molecular dynamics (MD) simulations have been performed to investigate AP/HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocane) composite at different temperatures. The binding energies, thermal expansion coefficient, and the trigger bond lengths of HMX in the AP/HMX composite have been obtained. The binding energies of the system increase slightly with temperature increasing, peak at 245K, and then gradually decrease. The volume thermal expansion coefficient of the AP/HMX composite has been derived from the volume variation with temperature. As the temperature rises, the maximal lengths of the trigger bond N-NO(2) of HMX increase gradually. The simulated results indicate that the maximal length of trigger bond can be used as a criterion for judging the sensitivity of energetic composite.

  8. Ten Things to Consider When Teaching AP U.S. History

    ERIC Educational Resources Information Center

    Libresco, Andrea S.

    2013-01-01

    This article describes 10 recommendations for creativity, higher-order thinking, and meaningful learning activities that can be used to guide teachers in constructing an engaging AP course: (1) Be on the committee that decides how students will be selected for AP; (2) Maximize time and connections through blocks of time with an English colleague;…

  9. The APETALA-2-like transcription factor OsAP2-39 controls key interactions between abscisic acid and gibberellin in rice.

    PubMed

    Yaish, Mahmoud W; El-Kereamy, Ashraf; Zhu, Tong; Beatty, Perrin H; Good, Allen G; Bi, Yong-Mei; Rothstein, Steven J

    2010-09-09

    The interaction between phytohormones is an important mechanism which controls growth and developmental processes in plants. Deciphering these interactions is a crucial step in helping to develop crops with enhanced yield and resistance to environmental stresses. Controlling the expression level of OsAP2-39 which includes an APETALA 2 (AP2) domain leads to phenotypic changes in rice. Overexpression of OsAP2-39 leads to a reduction in yield by decreasing the biomass and the number of seeds in the transgenic rice lines. Global transcriptome analysis of the OsAP2-39 overexpression transgenic rice revealed the upregulation of a key abscisic acid (ABA) biosynthetic gene OsNCED-I which codes for 9-cis-epoxycarotenoid dioxygenase and leads to an increase in the endogenous ABA level. In addition to OsNCED-1, the gene expression analysis revealed the upregulation of a gene that codes for the Elongation of Upper most Internode (EUI) protein, an enzyme that catalyzes 16α, 17-epoxidation of non-13-hydroxylated GAs, which has been shown to deactivate gibberellins (GAs) in rice. The exogenous application of GA restores the wild-type phenotype in the transgenic line and ABA application induces the expression of EUI and suppresses the expression of OsAP2-39 in the wild-type line. These observations clarify the antagonistic relationship between ABA and GA and illustrate a mechanism that leads to homeostasis of these hormones. In vivo and in vitro analysis showed that the expression of both OsNCED-1 and EUI are directly controlled by OsAP2-39. Together, these results reveal a novel mechanism for the control of the ABA/GA balance in rice which is regulated by OsAP2-39 that in turn regulates plant growth and seed production.

  10. The APETALA-2-Like Transcription Factor OsAP2-39 Controls Key Interactions between Abscisic Acid and Gibberellin in Rice

    PubMed Central

    Yaish, Mahmoud W.; El-kereamy, Ashraf; Zhu, Tong; Beatty, Perrin H.; Good, Allen G.; Bi, Yong-Mei; Rothstein, Steven J.

    2010-01-01

    The interaction between phytohormones is an important mechanism which controls growth and developmental processes in plants. Deciphering these interactions is a crucial step in helping to develop crops with enhanced yield and resistance to environmental stresses. Controlling the expression level of OsAP2-39 which includes an APETALA 2 (AP2) domain leads to phenotypic changes in rice. Overexpression of OsAP2-39 leads to a reduction in yield by decreasing the biomass and the number of seeds in the transgenic rice lines. Global transcriptome analysis of the OsAP2-39 overexpression transgenic rice revealed the upregulation of a key Abscisic Acid (ABA) biosynthetic gene OsNCED-I which codes for 9-cis-epoxycarotenoid dioxygenase and leads to an increase in the endogenous ABA level. In addition to OsNCED-1, the gene expression analysis revealed the upregulation of a gene that codes for the Elongation of Upper most Internode (EUI) protein, an enzyme that catalyzes 16α, 17-epoxidation of non-13-hydroxylated GAs, which has been shown to deactivate gibberellins (GAs) in rice. The exogenous application of GA restores the wild-type phenotype in the transgenic line and ABA application induces the expression of EUI and suppresses the expression of OsAP2-39 in the wild-type line. These observations clarify the antagonistic relationship between ABA and GA and illustrate a mechanism that leads to homeostasis of these hormones. In vivo and in vitro analysis showed that the expression of both OsNCED-1 and EUI are directly controlled by OsAP2-39. Together, these results reveal a novel mechanism for the control of the ABA/GA balance in rice which is regulated by OsAP2-39 that in turn regulates plant growth and seed production. PMID:20838584

  11. APS Goes to ComicCon and Other Tales: Reaching out for Physics

    NASA Astrophysics Data System (ADS)

    Kirby, Kate

    2012-10-01

    Broadly interpreting the core mission of APS ``to advance and diffuse the knowledge of physics", APS carries out programmatic activities in Education, Outreach, International Affairs, Public Affairs, and Advocacy, which benefit the physics community as well as society at large. These programs are highly valued by APS members who know about them, but the challenge has been to find ways to effectively communicate to our members about all the good things we are doing. APS programs have also achieved significant recognition in the external community for their outstanding quality and success. I will describe several examples of how we ``reach out" to promote physics and physics education in a variety of venues.

  12. Background Information Document for Updating AP42 Section 2.4 for Estimating Emissions from Municipal Solid Waste Landfills

    EPA Science Inventory

    This revised draft document was prepared for U.S. EPA's Office of Research and Development, and describes the data analysis undertaken to update the Municipal Solid Waste (MSW) Landfill section of AP-42. This 2008 update includes the addition of data from 62 landfill gas emission...

  13. AP Geography, Environmental Science Thrive

    ERIC Educational Resources Information Center

    Robelen, Erik W.

    2012-01-01

    Geography may not be particularly known as a hot topic among today's students--even some advocates suggest it suffers from an image problem--but by at least one measure, the subject is starting to come into its own. Across more than 30 topics covered in the Advanced Placement (AP) program, participation in geography is rising faster than any…

  14. Synthesis and binding properties of new selective ligands for the nucleobase opposite the AP site.

    PubMed

    Abe, Yukiko; Nakagawa, Osamu; Yamaguchi, Rie; Sasaki, Shigeki

    2012-06-01

    DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3'-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; that is A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Mutational Analysis of the Adaptor Protein 2 Sigma Subunit (AP2S1) Gene: Search for Autosomal Dominant Hypocalcemia Type 3 (ADH3)

    PubMed Central

    Rogers, Angela; Nesbit, M. Andrew; Hannan, Fadil M.; Howles, Sarah A.; Gorvin, Caroline M.; Cranston, Treena; Allgrove, Jeremy; Bevan, John S.; Bano, Gul; Brain, Caroline; Datta, Vipan; Grossman, Ashley B.; Hodgson, Shirley V.; Izatt, Louise; Millar-Jones, Lynne; Pearce, Simon H.; Robertson, Lisa; Selby, Peter L.; Shine, Brian; Snape, Katie; Warner, Justin

    2014-01-01

    Context: Autosomal dominant hypocalcemia (ADH) types 1 and 2 are due to calcium-sensing receptor (CASR) and G-protein subunit-α11 (GNA11) gain-of-function mutations, respectively, whereas CASR and GNA11 loss-of-function mutations result in familial hypocalciuric hypercalcemia (FHH) types 1 and 2, respectively. Loss-of-function mutations of adaptor protein-2 sigma subunit (AP2σ 2), encoded by AP2S1, cause FHH3, and we therefore sought for gain-of-function AP2S1 mutations that may cause an additional form of ADH, which we designated ADH3. Objective: The objective of the study was to investigate the hypothesis that gain-of-function AP2S1 mutations may cause ADH3. Design: The sample size required for the detection of at least one mutation with a greater than 95% likelihood was determined by binomial probability analysis. Nineteen patients (including six familial cases) with hypocalcemia in association with low or normal serum PTH concentrations, consistent with ADH, but who did not have CASR or GNA11 mutations, were ascertained. Leukocyte DNA was used for sequence and copy number variation analysis of AP2S1. Results: Binomial probability analysis, using the assumption that AP2S1 mutations would occur in hypocalcemic patients at a prevalence of 20%, which is observed in FHH patients without CASR or GNA11 mutations, indicated that the likelihood of detecting at least one AP2S1 mutation was greater than 95% and greater than 98% in sample sizes of 14 and 19 hypocalcemic patients, respectively. AP2S1 mutations and copy number variations were not detected in the 19 hypocalcemic patients. Conclusion: The absence of AP2S1 abnormalities in hypocalcemic patients, suggests that ADH3 may not occur or otherwise represents a rare hypocalcemic disorder. PMID:24708097

  16. SARS coronavirus protein 7a interacts with human Ap4A-hydrolase.

    PubMed

    Vasilenko, Natalia; Moshynskyy, Igor; Zakhartchouk, Alexander

    2010-02-09

    The SARS coronavirus (SARS-CoV) open reading frame 7a (ORF 7a) encodes a 122 amino acid accessory protein. It has no significant sequence homology with any other known proteins. The 7a protein is present in the virus particle and has been shown to interact with several host proteins; thereby implicating it as being involved in several pathogenic processes including apoptosis, inhibition of cellular protein synthesis, and activation of p38 mitogen activated protein kinase. In this study we present data demonstrating that the SARS-CoV 7a protein interacts with human Ap4A-hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17). Ap4A-hydrolase is responsible for metabolizing the "allarmone" nucleotide Ap4A and therefore likely involved in regulation of cell proliferation, DNA replication, RNA processing, apoptosis and DNA repair. The interaction between 7a and Ap4A-hydrolase was identified using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation from cultured human cells transiently expressing V5-His tagged 7a and HA tagged Ap4A-hydrolase. Human tissue culture cells transiently expressing 7a and Ap4A-hydrolase tagged with EGFP and Ds-Red2 respectively show these proteins co-localize in the cytoplasm.

  17. The 8th Annual AP[R] Report to the Nation

    ERIC Educational Resources Information Center

    College Board, 2012

    2012-01-01

    In classrooms around the country, AP (Advanced Placement) teachers are preparing students for tomorrow by teaching them how to think and learn today. AP students learn to construct solid arguments, test theories, and see many sides of an issue--the kind of thinking that solves tough problems both in and outside the classroom, in college and…

  18. Amphioxus and lamprey AP-2 genes: implications for neural crest evolution and migration patterns

    NASA Technical Reports Server (NTRS)

    Meulemans, Daniel; Bronner-Fraser, Marianne

    2002-01-01

    The neural crest is a uniquely vertebrate cell type present in the most basal vertebrates, but not in cephalochordates. We have studied differences in regulation of the neural crest marker AP-2 across two evolutionary transitions: invertebrate to vertebrate, and agnathan to gnathostome. Isolation and comparison of amphioxus, lamprey and axolotl AP-2 reveals its extensive expansion in the vertebrate dorsal neural tube and pharyngeal arches, implying co-option of AP-2 genes by neural crest cells early in vertebrate evolution. Expression in non-neural ectoderm is a conserved feature in amphioxus and vertebrates, suggesting an ancient role for AP-2 genes in this tissue. There is also common expression in subsets of ventrolateral neurons in the anterior neural tube, consistent with a primitive role in brain development. Comparison of AP-2 expression in axolotl and lamprey suggests an elaboration of cranial neural crest patterning in gnathostomes. However, migration of AP-2-expressing neural crest cells medial to the pharyngeal arch mesoderm appears to be a primitive feature retained in all vertebrates. Because AP-2 has essential roles in cranial neural crest differentiation and proliferation, the co-option of AP-2 by neural crest cells in the vertebrate lineage was a potentially crucial event in vertebrate evolution.

  19. Routing Protocols in Wireless Sensor Networks

    PubMed Central

    Villalba, Luis Javier García; Orozco, Ana Lucila Sandoval; Cabrera, Alicia Triviño; Abbas, Cláudia Jacy Barenco

    2009-01-01

    The applications of wireless sensor networks comprise a wide variety of scenarios. In most of them, the network is composed of a significant number of nodes deployed in an extensive area in which not all nodes are directly connected. Then, the data exchange is supported by multihop communications. Routing protocols are in charge of discovering and maintaining the routes in the network. However, the appropriateness of a particular routing protocol mainly depends on the capabilities of the nodes and on the application requirements. This paper presents a review of the main routing protocols proposed for wireless sensor networks. Additionally, the paper includes the efforts carried out by Spanish universities on developing optimization techniques in the area of routing protocols for wireless sensor networks. PMID:22291515

  20. Routing protocols in wireless sensor networks.

    PubMed

    Villalba, Luis Javier García; Orozco, Ana Lucila Sandoval; Cabrera, Alicia Triviño; Abbas, Cláudia Jacy Barenco

    2009-01-01

    The applications of wireless sensor networks comprise a wide variety of scenarios. In most of them, the network is composed of a significant number of nodes deployed in an extensive area in which not all nodes are directly connected. Then, the data exchange is supported by multihop communications. Routing protocols are in charge of discovering and maintaining the routes in the network. However, the appropriateness of a particular routing protocol mainly depends on the capabilities of the nodes and on the application requirements. This paper presents a review of the main routing protocols proposed for wireless sensor networks. Additionally, the paper includes the efforts carried out by Spanish universities on developing optimization techniques in the area of routing protocols for wireless sensor networks.

  1. Problematic protocols: An overview of medical research protocols not approved by the LUMC medical ethics review committee.

    PubMed

    Tersmette, Derek Gideon; Engberts, Dirk Peter

    2017-01-01

    The Committee for Medical Ethics (CME) of Leiden University Medical Center (LUMC) was established as the first medical ethics reviewing committee (MREC) in the Netherlands. In the period 2000-2010 the CME received 2,162 protocols for review. Some of these protocols were never approved. Until now, there has existed neither an overview of these failed protocols nor an overview of the reasons for their failure. This report draws on data from the digital database, the physical archives, and the minutes of the meetings of the CME. Additional information has been obtained from the Central Committee on Research involving Human Subjects (CCRH) and survey-based research. Protocols were itemized based on characteristic features and their reviewing procedures were analyzed. In total, 1,952 out of 2,162 research protocols submitted during 2000-2010 (90.3%) were approved by the CME; 210 of 2,162 protocols (9.7%) were not approved. Of these 210 protocols, 177 failed due to reasons not related to CME reviewing. In 15 cases CME reviewing led to protocol failure, while another 10 protocols were rejected outright. Eight of the 210 submitted protocols without approval had been conducted prior to submission. In the aforementioned period, little protocol failure occurred. For the most part, protocol failure was caused by problems that are not CME related. This type of failure has several identifiable factors, none of which have anything to do with the ethical reviewing procedure by the CME. A mere 1.2% of protocols failed due to ethical review. Unacceptable burden and risks to the subject and an inadequate methodology are the most common reasons for this CME-related protocol failure.

  2. Magnetic Doppler imaging of Ap stars

    NASA Astrophysics Data System (ADS)

    Silvester, J.; Wade, G. A.; Kochukhov, O.; Landstreet, J. D.; Bagnulo, S.

    2008-04-01

    Historically, the magnetic field geometries of the chemically peculiar Ap stars were modelled in the context of a simple dipole field. However, with the acquisition of increasingly sophisticated diagnostic data, it has become clear that the large-scale field topologies exhibit important departures from this simple model. Recently, new high-resolution circular and linear polarisation spectroscopy has even hinted at the presence of strong, small-scale field structures, which were completely unexpected based on earlier modelling. This project investigates the detailed structure of these strong fossil magnetic fields, in particular the large-scale field geometry, as well as small scale magnetic structures, by mapping the magnetic and chemical surface structure of a selected sample of Ap stars. These maps will be used to investigate the relationship between the local field vector and local surface chemistry, looking for the influence the field may have on the various chemical transport mechanisms (i.e., diffusion, convection and mass loss). This will lead to better constraints on the origin and evolution, as well as refining the magnetic field model for Ap stars. Mapping will be performed using high resolution and signal-to-noise ratio time-series of spectra in both circular and linear polarisation obtained using the new-generation ESPaDOnS (CFHT, Mauna Kea, Hawaii) and NARVAL spectropolarimeters (Pic du Midi Observatory). With these data we will perform tomographic inversion of Doppler-broadened Stokes IQUV Zeeman profiles of a large variety of spectral lines using the INVERS10 magnetic Doppler imaging code, simultaneously recovering the detailed surface maps of the vector magnetic field and chemical abundances.

  3. Optimizing the Protocol for Pulmonary Cryoablation: A Comparison of a Dual- and Triple-Freeze Protocol

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

    Hinshaw, J. Louis, E-mail: jhinshaw@uwhealth.or; Littrup, Peter J.; Durick, Nathan

    2010-12-15

    The purpose of this study was to compare a double freeze-thaw protocol to a triple freeze-thaw protocol for pulmonary cryoablation utilizing an in vivo porcine lung model. A total of 18 cryoablations were performed in normal porcine lung utilizing percutaneous technique with 9 each in a double- (10-5-10) and triple-freeze (3-3-7-7-5) protocol. Serial noncontrast CT images were obtained during the ablation. CT imaging findings and pathology were reviewed. No imaging changes were identified during the initial freeze cycle with either protocol. However, during the first thaw cycle, a region of ground glass opacity developed around the probe with both protocols.more » Because the initial freeze was shorter with the triple freeze-thaw protocol, the imaging findings were apparent sooner with this protocol (6 vs. 13 min). Also, despite a shorter total freeze time (15 vs. 20 min), the ablation zone identified with the triple freeze-thaw protocol was not significantly different from the double freeze-thaw protocol (mean diameter: 1.67 {+-} 0.41 cm vs. 1.66 {+-} 0.21 cm, P = 0.77; area: 2.1 {+-} 0.48 cm{sup 2} vs. 1.99 {+-} 0.62 cm{sup 2}, P = 0.7; and circularity: 0.95 {+-} 0.04 vs. 0.96 {+-} 0.03, P = 0.62, respectively). This study suggests that there may be several advantages of a triple freeze-thaw protocol for pulmonary cryoablation, including earlier identification of the imaging findings associated with the ablation, the promise of a shorter procedure time or larger zones of ablation, and theoretically, more effective cytotoxicity related to the additional freeze-thaw cycle.« less

  4. Effects of NOS1AP rs12742393 polymorphism on repaglinide response in Chinese patients with type 2 diabetes mellitus.

    PubMed

    Wang, Tao; Wang, Yan; Lv, Dong-Mei; Song, Jin-Fang; Lu, Qian; Gao, Xing; Zhang, Fan; Guo, Hao; Li, Wei; Yin, Xiao-Xing

    2014-02-01

    To investigate the associations of NOS1AP rs12742393 polymorphism with the risk of type 2 diabetes mellitus (T2DM) and repaglinide therapeutic efficacy in Chinese patients with T2DM. Prospective case-control study. Academic medical center. A total of 300 patients with T2DM and 200 healthy volunteers were enrolled to identify NOS1AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay. Eighty-four patients with various genotypes were randomly selected to receive oral repaglinide as a single-agent therapy (3 mg/day) for 8 weeks. Anthropometric measurements and fasting plasma glucose (FPG), postprandial plasma glucose, hemoglobin A1c , fasting serum insulin (FINS), postprandial serum insulin, homeostasis model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol tests were obtained before and after repaglinide treatment. The risk C allelic frequency of NOS1AP rs12742393 was higher in patients with T2DM than in healthy volunteers (p<0.001). Patients with T2DM and genotypes AA and AC at NOS1AP rs12742393 had a significant reduction in FPG (mmol/l) compared with those with genotype CC (p<0.01). Patients with CC homozygotes and AC heterozygotes had a greater increase in FINS (mU/l) than those with wild-type AA (p<0.05). In addition, the carriers of genotype CC at NOS1AP rs12742393 had higher differential values of HOMA-IR compared with genotypes AC and AA carriers (p<0.001). The effects of repaglinide treatment on FPG (p<0.01), FINS (p<0.05) and HOMA-IR (p<0.001) were reduced in patients with T2DM carrying the NOS1AP rs12742393 risk C allele compared with the AA genotype carriers. The NOS1AP rs12742393 polymorphism is associated with therapeutic efficacy of repaglinide in Chinese T2DM patients. © 2013 Pharmacotherapy Publications, Inc.

  5. ARF1·GTP, Tyrosine-based Signals, and Phosphatidylinositol 4,5-Bisphosphate Constitute a Minimal Machinery to Recruit the AP-1 Clathrin Adaptor to Membranes

    PubMed Central

    Crottet, Pascal; Meyer, Daniel M.; Rohrer, Jack; Spiess, Martin

    2002-01-01

    At the trans-Golgi network, clathrin coats containing AP-1 adaptor complexes are formed in an ARF1-dependent manner, generating vesicles transporting cargo proteins to endosomes. The mechanism of site-specific targeting of AP-1 and the role of cargo are poorly understood. We have developed an in vitro assay to study the recruitment of purified AP-1 adaptors to chemically defined liposomes presenting peptides corresponding to tyrosine-based sorting motifs. AP-1 recruitment was found to be dependent on myristoylated ARF1, GTP or nonhydrolyzable GTP-analogs, tyrosine signals, and small amounts of phosphoinositides, most prominently phosphatidylinositol 4,5-bisphosphate, in the absence of any additional cytosolic or membrane bound proteins. AP-1 from cytosol could be recruited to a tyrosine signal independently of the lipid composition, but the rate of recruitment was increased by phosphatidylinositol 4,5-bisphosphate. The results thus indicate that cargo proteins are involved in coat recruitment and that the local lipid composition contributes to specifying the site of vesicle formation. PMID:12388765

  6. Metal- and additive-free photoinduced borylation of haloarenes.

    PubMed

    Mfuh, Adelphe M; Schneider, Brett D; Cruces, Westley; Larionov, Oleg V

    2017-03-01

    Boronic acids and esters have critical roles in the areas of synthetic organic chemistry, molecular sensors, materials science, drug discovery, and catalysis. Many of the current applications of boronic acids and esters require materials with very low levels of transition metal contamination. Most of the current methods for the synthesis of boronic acids, however, require transition metal catalysts and ligands that must be removed via additional purification procedures. This protocol describes a simple, metal- and additive-free method of conversion of haloarenes directly to boronic acids and esters. This photoinduced borylation protocol does not require expensive and toxic metal catalysts or ligands, and it produces innocuous and easy-to-remove by-products. Furthermore, the reaction can be carried out on multigram scales in common-grade solvents without the need for reaction mixtures to be deoxygenated. The setup and purification steps are typically accomplished within 1-3 h. The reactions can be run overnight, and the protocol can be completed within 13-16 h. Two representative procedures that are described in this protocol provide details for preparation of a boronic acid (3-cyanopheylboronic acid) and a boronic ester (1,4-benzenediboronic acid bis(pinacol)ester). We also discuss additional details of the method that will be helpful in the application of the protocol to other haloarene substrates.

  7. [Cloning, subcellular localization, and heterologous expression of ApNAC1 gene from Andrographis paniculata].

    PubMed

    Wang, Jian; Qi, Meng-Die; Guo, Juan; Shen, Ye; Lin, Hui-Xin; Huang, Lu-Qi

    2017-03-01

    Andrographis paniculata is widely used as medicinal herb in China for a long time and andrographolide is its main medicinal constituent. To investigate the underlying andrographolide biosynthesis mechanisms, RNA-seq for A. paniculata leaves with MeJA treatment was performed. In A. paniculata transcriptomic data, the expression pattern of one member of NAC transcription factor family (ApNAC1) matched with andrographolide accumulation. The coding sequence of ApNAC1 was cloned by RT-PCR, and GenBank accession number was KY196416. The analysis of bioinformatics showed that the gene encodes a peptide of 323 amino acids, with a predicted relative molecular weight of 35.9 kDa and isoelectric point of 6.14. To confirm the subcellular localization, ApNAC1-GFP was transiently expressed in A. paniculata protoplast. The results indicated that ApNAC1 is a nucleus-localized protein. The analysis of real-time quantitative PCR revealed that ApNAC1 gene predominantly expresses in leaves. Compared with control sample, its expression abundance sharply increased with methyl jasmonate treatment. Based on its expression pattern, ApNAC1 gene might involve in andrographolide biosynthesis. ApNAC1 was heterologously expressed in Escherichia coli and recombinant protein was purified by Ni-NTA agarose. Further study will help us to understand the function of ApNAC1 in andrographolide biosynthesis. Copyright© by the Chinese Pharmaceutical Association.

  8. IKKα contributes to UVB-induced VEGF expression by regulating AP-1 transactivation

    PubMed Central

    Dong, Wen; Li, Yi; Gao, Ming; Hu, Meiru; Li, Xiaoguang; Mai, Sanyue; Guo, Ning; Yuan, Shengtao; Song, Lun

    2012-01-01

    Exposure to ultraviolet B (UVB) irradiation from sunlight induces the upregulation of VEGF, a potent angiogenic factor that is critical for mediating angiogenesis-associated photodamage. However, the molecular mechanisms related to UVB-induced VEGF expression have not been fully defined. Here, we demonstrate that one of the catalytic subunits of the IκB kinase complex (IKK), IKKα, plays a critical role in mediating UVB-induced VEGF expression in mouse embryonic fibroblasts (MEFs), which requires IKKα kinase activity but is independent of IKKβ, IKKγ and the transactivation of NF-κB. We further show that the transcriptional factor AP-1 functions as the downstream target of IKKα that is responsible for VEGF induction under UVB exposure. Both the accumulation of AP-1 component, c-Fos and the transactivation of AP-1 by UVB require the activated IKKα located within the nucleus. Moreover, nuclear IKKα can associate with c-Fos and recruit to the vegf promoter regions containing AP-1-responsive element and then trigger phosphorylation of the promoter-bound histone H3. Thus, our results have revealed a novel independent role for IKKα in controlling VEGF expression during the cellular UVB response by regulating the induction of the AP-1 component and phosphorylating histone H3 to facilitate AP-1 transactivation. Targeting IKKα shows promise for the prevention of UVB-induced angiogenesis and the associated photodamage. PMID:22169952

  9. Magnetic Measurements of Storage Ring Magnets for the APS Upgrade Project

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

    Doose, C.; Dejus, R.; Jaski, M.

    2017-06-01

    Extensive prototyping of storage ring magnets is ongoing at the Advanced Photon Source (APS) in support of the APS Multi-Bend Achromat (MBA) upgrade project (APS-U) [1]. As part of the R&D activities four quadrupole magnets with slightly different geometries and pole tip materials, and one sextupole magnet with vanadium permendur (VP) pole tips were designed, built and tested. Magnets were measured individually using a rotating coil and a Hall probe for detailed mapping of the magnetic field. Magnets were then assembled and aligned relative to each other on a steel support plate and concrete plinth using precision machined surfaces tomore » gain experience with the alignment method chosen for the APS-U storage ring magnets. The required alignment of magnets on a common support structure is 30 μm rms. Measurements of magnetic field quality, strength and magnet alignment after subjecting the magnets and assemblies to different tests are presented.« less

  10. P alpha-chiral phosphorothioate analogues of bis(5'-adenosyl)tetraphosphate (Ap4A); their enzymatic synthesis and degradation.

    PubMed Central

    Lazewska, D; Guranowski, A

    1990-01-01

    Synthesis of Sp and Rp diastereomers of Ap4A alpha S has been characterized in two enzymatic systems, the lysyl-tRNA synthetase from Escherichia coli and the Ap4A alpha, beta-phosphorylase from Saccharomyces cerevisiae. The synthetase was able to use both (Sp)ATP alpha S and (Rp)ATP alpha S as acceptors of adenylate thus yielding corresponding monothioanalogues of Ap4A,(Sp) Ap4A alpha S and (Rp)Ap4A alpha S. No dithiophosphate analogue was formed. Relative synthetase velocities of the formation of Ap4A,(Sp) Ap4A alpha S and (Rp)Ap4A alpha S were 1:0.38:0.15, and the computed Km values for (Sp)ATP alpha S and (Rp)ATP alpha S were 0.48 and 1.34 mM, respectively. The yeast Ap4A phosphorylase synthesized (Sp)Ap4A alpha S and (Rp)Ap4A alpha S using adenosine 5'-phosphosulfate (APS) as source of adenylate. The adenylate was accepted by corresponding thioanalogues of ATP. In that system, relative velocities of Ap4A, (Sp)Ap4A alpha S and (Rp)Ap4A alpha S formation were 1:0.15:0.60. The two isomeric phosphorothioate analogues of Ap4A were tested as substrates for the following specific Ap4A-degrading enzymes: (asymmetrical) Ap4A hydrolase (EC 3.6.1.17) from yellow lupin (Lupinus luteus) seeds hydrolyzed each of the analogues to AMP and the corresponding isomer of ATP alpha S; (symmetrical) Ap4A hydrolase (EC 3.6.1.41) from E. coli produced ADP and the corresponding diastereomer of ADP alpha S; and Ap4A phosphorylase (EC 2.7.7.53) from S. cerevisiae cleaved the Rp isomer only at the unmodified end yielding ADP and (Rp)ATP alpha S whereas the Sp isomer was degraded non-specifically yielding a mixture of ADP, (Sp)ADP alpha S, ATP and (Sp)ATP alpha S. For all the Ap4A-degrading enzymes, the Rp isomer of Ap4A alpha S appeared to be a better substrate than its Sp counterpart; stereoselectivity of the three enzymes for the Ap4A alpha S diastereomers is 51, 6 and 2.5, respectively. Basic kinetic parameters of the degradation reactions are presented and structural requirements of

  11. Understanding and Using the New Guided-Inquiry AP Chemistry Laboratory Manual

    ERIC Educational Resources Information Center

    Cacciatore, Kristen L.

    2014-01-01

    To support teaching and learning in the advanced placement (AP) chemistry laboratory, the College Board published a laboratory manual, "AP Chemistry Guided-Inquiry Experiments: Applying the Science Practices," in 2013 as part of the redesigned course. This article provides a discussion of the rationale for the existence of the manual as…

  12. Panel Discussion : Report of the APS Ad-Hoc Committee on LGBT Issues

    NASA Astrophysics Data System (ADS)

    Atherton, Tim; Barthelemy, Ramon; Garmon, Savannah; Reeves, Kyle; APS Ad-Hoc Committee on LGBT Issues Team

    Following the presentation of the findings and recommendations of the APS Ad-Hoc Committee on LGBT Issues (C-LGBT) by Committee Chair Michael Falk, a panel discussion will be held featuring several members of the committee. The discussion will focus on how APS can best ensure the recommendations of the committee are carried out in a timely fashion and other ideas on future APS efforts toward LGBT inclusion in physics. Discussion topics will also include the research and other input that shaped the committee's findings and recommendations.

  13. Joint Test Protocol for Validation of Alternative Low-Emission Surface Preparation/Depainting Technologies for Structural Steel

    NASA Technical Reports Server (NTRS)

    Lewis, Pattie

    2005-01-01

    Headquarters National Aeronautics and Space Administration (NASA) chartered the Acquisition Pollution Prevention (AP2) Office to coordinate agency activities affecting pollution prevention issues identified during system and component acquisition and sustainment processes. The primary objectives of the AP2 Office are to: (1) Reduce or eliminate the use of hazardous materials (HazMats) or hazardous processes at manufacturing, remanufacturing, and sustainment locations. (2) A void duplication of effort in actions required to reduce or eliminate HazMats through joint center cooperation and technology sharing. This project will identify, evaluate and approve alternative surface preparation technologies for use at NASA and Air Force Space Command (AFSPC) installations. Materials and processes will be evaluated with the goal of selecting those processes that will improve corrosion protection at critical systems, facilitate easier maintenance activity, extend maintenance cycles, eliminate flight hardware contamination and reduce the amount of hazardous waste generated. This Joint Test Protocol (JTP) contains the critical requirements and tests necessary to qualify alternative Low-Emission Surface Preparation/Depainting Technologies for Structural Steel Applications. These tests were derived from engineering, performance, and operational impact (supportability) requirements defined by a consensus of NASA and Air Force Space Command (AFSPC) participants. The Field Test Plan (FTP), entitled Joint Test Protocol for Validation of Alternative Low Emission Surface Preparation/Depainting Technologies for Structural Steel, prepared by ITB, defines the field evaluation and testing requirements for validating alternative surface preparation/depainting technologies and supplements the JTP.

  14. Randomized controlled trial of accelerated rehabilitation versus standard protocol following surgical repair of ruptured Achilles tendon.

    PubMed

    Porter, Mark D; Shadbolt, Bruce

    2015-05-01

    There is no consensus regarding the optimal management of the acutely ruptured Achilles tendon (TA). Functional bracing alone achieves outcomes similar to those of surgical repair. Surgical repair combined with immediate mobilization may improve the clinical outcome further. The purpose of our study was to determine if an accelerated rehabilitation programme following surgical repair of the ruptured TA could improve clinical outcome, relative to the standard protocol. Patients with an acutely ruptured TA were randomly allocated to undergo an accelerated programme (AP) or standard programme (SP), following surgery. Outcome was assessed at 12 months post-surgery using the Achilles tendon Total Rupture Score (ATRS), the heel-raise height and the time taken to return to running. Fifty-one patients completed the study, 25 in the AP group and 26 in the SP group. At 12 months post-surgery, the ATRS results were similar in the two treatment groups (87.46 in AP with standard error (SE) of 0.735 versus 87.12 in SP with SE of 0.75) while the AP group had less lengthening of the TA (0.385 cm, SE 0.166 versus 1.00 cm, SE 0.169) and a more rapid return to running (17.231 weeks, SE 0.401 versus 21.08 weeks, SE 0.409), than the SP group. The accelerated rehabilitation programme resulted in less tendon lengthening, more rapid return to running, but similar ATRS relative to the standard rehabilitation. Immobilization following TA repair may prolong recovery. © 2014 Royal Australasian College of Surgeons.

  15. Using a Classroom Response System to Improve Multiple-Choice Performance in AP[R] Physics

    ERIC Educational Resources Information Center

    Bertrand, Peggy

    2009-01-01

    Participation in rigorous high school courses such as Advanced Placement (AP[R]) Physics increases the likelihood of college success, especially for students who are traditionally underserved. Tackling difficult multiple-choice exams should be part of any AP program because well-constructed multiple-choice questions, such as those on AP exams and…

  16. Role of the AP-5 adaptor protein complex in late endosome-to-Golgi retrieval

    PubMed Central

    Hirst, Jennifer; Itzhak, Daniel N.; Antrobus, Robin; Borner, Georg H. H.

    2018-01-01

    The AP-5 adaptor protein complex is presumed to function in membrane traffic, but so far nothing is known about its pathway or its cargo. We have used CRISPR-Cas9 to knock out the AP-5 ζ subunit gene, AP5Z1, in HeLa cells, and then analysed the phenotype by subcellular fractionation profiling and quantitative mass spectrometry. The retromer complex had an altered steady-state distribution in the knockout cells, and several Golgi proteins, including GOLIM4 and GOLM1, were depleted from vesicle-enriched fractions. Immunolocalisation showed that loss of AP-5 led to impaired retrieval of the cation-independent mannose 6-phosphate receptor (CIMPR), GOLIM4, and GOLM1 from endosomes back to the Golgi region. Knocking down the retromer complex exacerbated this phenotype. Both the CIMPR and sortilin interacted with the AP-5–associated protein SPG15 in pull-down assays, and we propose that sortilin may act as a link between Golgi proteins and the AP-5/SPG11/SPG15 complex. Together, our findings suggest that AP-5 functions in a novel sorting step out of late endosomes, acting as a backup pathway for retromer. This provides a mechanistic explanation for why mutations in AP-5/SPG11/SPG15 cause cells to accumulate aberrant endolysosomes, and highlights the role of endosome/lysosome dysfunction in the pathology of hereditary spastic paraplegia and other neurodegenerative disorders. PMID:29381698

  17. Comparison of a CCD and an APS for soft X-ray diffraction

    NASA Astrophysics Data System (ADS)

    Stewart, Graeme; Bates, R.; Blue, A.; Clark, A.; Dhesi, S. S.; Maneuski, D.; Marchal, J.; Steadman, P.; Tartoni, N.; Turchetta, R.

    2011-12-01

    We compare a new CMOS Active Pixel Sensor (APS) to a Princeton Instruments PIXIS-XO: 2048B Charge Coupled Device (CCD) with soft X-rays tested in a synchrotron beam line at the Diamond Light Source (DLS). Despite CCDs being established in the field of scientific imaging, APS are an innovative technology that offers advantages over CCDs. These include faster readout, higher operational temperature, in-pixel electronics for advanced image processing and reduced manufacturing cost. The APS employed was the Vanilla sensor designed by the MI3 collaboration and funded by an RCUK Basic technology grant. This sensor has 520 x 520 square pixels, of size 25 μm on each side. The sensor can operate at a full frame readout of up to 20 Hz. The sensor had been back-thinned, to the epitaxial layer. This was the first time that a back-thinned APS had been demonstrated at a beam line at DLS. In the synchrotron experiment soft X-rays with an energy of approximately 708 eV were used to produce a diffraction pattern from a permalloy sample. The pattern was imaged at a range of integration times with both sensors. The CCD had to be operated at a temperature of -55°C whereas the Vanilla was operated over a temperature range from 20°C to -10°C. We show that the APS detector can operate with frame rates up to two hundred times faster than the CCD, without excessive degradation of image quality. The signal to noise of the APS is shown to be the same as that of the CCD at identical integration times and the response is shown to be linear, with no charge blooming effects. The experiment has allowed a direct comparison of back thinned APS and CCDs in a real soft x-ray synchrotron experiment.

  18. Molecular Basis for Association of PIPKIγ-p90 with Clathrin Adaptor AP-2*

    PubMed Central

    Kahlfeldt, Nina; Vahedi-Faridi, Ardeschir; Koo, Seong Joo; Schäfer, Johannes G.; Krainer, Georg; Keller, Sandro; Saenger, Wolfram; Krauss, Michael; Haucke, Volker

    2010-01-01

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is an essential determinant in clathrin-mediated endocytosis (CME). In mammals three type I phosphatidylinositol-4-phosphate 5-kinase (PIPK) enzymes are expressed, with the Iγ-p90 isoform being highly expressed in the brain where it regulates synaptic vesicle (SV) exo-/endocytosis at nerve terminals. How precisely PI(4,5)P2 metabolism is controlled spatially and temporally is still uncertain, but recent data indicate that direct interactions between type I PIPK and components of the endocytic machinery, in particular the AP-2 adaptor complex, are involved. Here we demonstrated that PIPKIγ-p90 associates with both the μ and β2 subunits of AP-2 via multiple sites. Crystallographic data show that a peptide derived from the splice insert of the human PIPKIγ-p90 tail binds to a cognate recognition site on the sandwich subdomain of the β2 appendage. Partly overlapping aromatic and hydrophobic residues within the same peptide also can engage the C-terminal sorting signal binding domain of AP-2μ, thereby potentially competing with the sorting of conventional YXXØ motif-containing cargo. Biochemical and structure-based mutagenesis analysis revealed that association of the tail domain of PIPKIγ-p90 with AP-2 involves both of these sites. Accordingly the ability of overexpressed PIPKIγ tail to impair endocytosis of SVs in primary neurons largely depends on its association with AP-2β and AP-2μ. Our data also suggest that interactions between AP-2 and the tail domain of PIPKIγ-p90 may serve to regulate complex formation and enzymatic activity. We postulate a model according to which multiple interactions between PIPKIγ-p90 and AP-2 lead to spatiotemporally controlled PI(4,5)P2 synthesis during clathrin-mediated SV endocytosis. PMID:19903820

  19. Structural modeling and molecular simulation analysis of HvAP2/EREBP from barley.

    PubMed

    Pandey, Bharati; Sharma, Pradeep; Tyagi, Chetna; Goyal, Sukriti; Grover, Abhinav; Sharma, Indu

    2016-06-01

    AP2/ERF transcription factors play a critical role in plant development and stress adaptation. This study reports the three-dimensional ab initio-based model of AP2/EREBP protein of barley and its interaction with DNA. Full-length coding sequence of HvAP2/EREBP gene isolated from two Indian barley cultivars, RD 2503 and RD 31, was used to model the protein. Of five protein models obtained, the one with lowest C-score was chosen for further analysis. The N- and C-terminal regions of HvAP2 protein were found to be highly disordered. The dynamic properties of AP2/EREBP and its interaction with DNA were investigated by molecular dynamics simulation. Analysis of trajectories from simulation yielded the equilibrated conformation between 2-10ns for protein and 7-15ns for protein-DNA complex. We established relationship between DNA having GCC box and DNA-binding domain of HvAP2/EREBP was established by modeling 11-base-pair-long nucleotide sequence and HvAP2/EREBP protein using ab initio method. Analysis of protein-DNA interaction showed that a β-sheet motif constituting amino acid residues THR105, ARG100, ARG93, and ARG83 seems to play important role in stabilizing the complex as they form strong hydrogen bond interactions with the DNA motif. Taken together, this study provides first-hand comprehensive information detailing structural conformation and interactions of HvAP2/EREBP proteins in barley. The study intensifies the role of computational approaches for preliminary examination of unknown proteins in the absence of experimental information. It also provides molecular insight into protein-DNA binding for understanding and enhancing abiotic stress resistance for improving the water use efficiency in crop plants.

  20. CMOS-APS Detectors for Solar Physics: Lessons Learned during the SWAP Preflight Calibration

    NASA Astrophysics Data System (ADS)

    de Groof, A.; Berghmans, D.; Nicula, B.; Halain, J.-P.; Defise, J.-M.; Thibert, T.; Schühle, U.

    2008-05-01

    CMOS-APS imaging detectors open new opportunities for remote sensing in solar physics beyond what classical CCDs can provide, offering far less power consumption, simpler electronics, better radiation hardness, and the possibility of avoiding a mechanical shutter. The SWAP telescope onboard the PROBA2 technology demonstration satellite of the European Space Agency will be the first actual implementation of a CMOS-APS detector for solar physics in orbit. One of the goals of the SWAP project is precisely to acquire experience with the CMOS-APS technology in a real-live space science context. Such a precursor mission is essential in the preparation of missions such as Solar Orbiter where the extra CMOS-APS functionalities will be hard requirements. The current paper concentrates on specific CMOS-APS issues that were identified during the SWAP preflight calibration measurements. We will discuss the different readout possibilities that the CMOS-APS detector of SWAP provides and their associated pros and cons. In particular we describe the “image lag” effect, which results in a contamination of each image with a remnant of the previous image. We have characterised this effect for the specific SWAP implementation and we conclude with a strategy on how to successfully circumvent the problem and actually take benefit of it for solar monitoring.

  1. Ecto-diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A)-hydrolase is expressed as an ectoenzyme in a variety of mammalian and human cells and adds new aspects to the turnover of Ap4A.

    PubMed

    von Drygalski, A; Ogilvie, A

    2000-01-01

    Ap4A and other dinucleotides participate in the regulation of hemostasis and blood pressure control. With the exception of two previously reported surface anchored ectoAp4A-hydrolases on bovine aortic endothelial and chromaffine cells, all Ap4A-hydrolases reported are intracellular or freely soluble. We demonstrated that ectoAp4A-hydrolases are present on a broad variety of cell types of different species: rat mesangial, bovine corneal epithelial, human Hep-G2 and peridontal cells. Ectoenzyme properties were evaluated on rat mesangium cells. Chromatography of purified plasma membranes on Sephacel 300 resulted in enrichment of ectoAp4A-hydrolase and in separation from ectoATPase. In contrast to ATPase, Ap4A-hydrolase was stable at room temperature. EctoAp4A-hydrolase also recognized ATP as substrate, and therefore is not highly specific. The molecular weight was 180 kD. Unlike ectoAMPase ectoAp4A-hydrolase was not attached via a glycosyl-phosphatidylinositol (GPI)-moiety. Concentrations of PI-PLC 10-100-fold higher than effective for ectoAMPase cleavage (10-100 mU/ml) plus extensively extended incubation times up to eight hours did not result in cleavage of ectoAp4A-hydrolase. The enzyme ectoAp4A-hydrolase might presage a direction for pharmaceutical manipulation in the control of blood pressure and hemostasis.

  2. In silico toxicology protocols.

    PubMed

    Myatt, Glenn J; Ahlberg, Ernst; Akahori, Yumi; Allen, David; Amberg, Alexander; Anger, Lennart T; Aptula, Aynur; Auerbach, Scott; Beilke, Lisa; Bellion, Phillip; Benigni, Romualdo; Bercu, Joel; Booth, Ewan D; Bower, Dave; Brigo, Alessandro; Burden, Natalie; Cammerer, Zoryana; Cronin, Mark T D; Cross, Kevin P; Custer, Laura; Dettwiler, Magdalena; Dobo, Krista; Ford, Kevin A; Fortin, Marie C; Gad-McDonald, Samantha E; Gellatly, Nichola; Gervais, Véronique; Glover, Kyle P; Glowienke, Susanne; Van Gompel, Jacky; Gutsell, Steve; Hardy, Barry; Harvey, James S; Hillegass, Jedd; Honma, Masamitsu; Hsieh, Jui-Hua; Hsu, Chia-Wen; Hughes, Kathy; Johnson, Candice; Jolly, Robert; Jones, David; Kemper, Ray; Kenyon, Michelle O; Kim, Marlene T; Kruhlak, Naomi L; Kulkarni, Sunil A; Kümmerer, Klaus; Leavitt, Penny; Majer, Bernhard; Masten, Scott; Miller, Scott; Moser, Janet; Mumtaz, Moiz; Muster, Wolfgang; Neilson, Louise; Oprea, Tudor I; Patlewicz, Grace; Paulino, Alexandre; Lo Piparo, Elena; Powley, Mark; Quigley, Donald P; Reddy, M Vijayaraj; Richarz, Andrea-Nicole; Ruiz, Patricia; Schilter, Benoit; Serafimova, Rositsa; Simpson, Wendy; Stavitskaya, Lidiya; Stidl, Reinhard; Suarez-Rodriguez, Diana; Szabo, David T; Teasdale, Andrew; Trejo-Martin, Alejandra; Valentin, Jean-Pierre; Vuorinen, Anna; Wall, Brian A; Watts, Pete; White, Angela T; Wichard, Joerg; Witt, Kristine L; Woolley, Adam; Woolley, David; Zwickl, Craig; Hasselgren, Catrin

    2018-07-01

    The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  3. NGSI student activities in open source information analysis in support of the training program of the U.S. DOE laboratories for the entry into force of the additional protocol

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

    Sandoval, M Analisa; Uribe, Eva C; Sandoval, Marisa N

    2009-01-01

    In 2008 a joint team from Los Alamos National Laboratory (LANL) and Brookhaven National Laboratory (BNL) consisting of specialists in training of IAEA inspectors in the use of complementary access activities formulated a training program to prepare the U.S. Doe laboratories for the entry into force of the Additional Protocol. As a major part of the support of the activity, LANL summer interns provided open source information analysis to the LANL-BNL mock inspection team. They were a part of the Next Generation Safeguards Initiative's (NGSI) summer intern program aimed at producing the next generation of safeguards specialists. This paper describesmore » how they used open source information to 'backstop' the LANL-BNL team's effort to construct meaningful Additional Protocol Complementary Access training scenarios for each of the three DOE laboratories, Lawrence Livermore National Laboratory, Idaho National Laboratory, and Oak Ridge National Laboratory.« less

  4. AP1000{sup R} severe accident features and post-Fukushima considerations

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

    Scobel, J. H.; Schulz, T. L.; Williams, M. G.

    2012-07-01

    The AP1000{sup R} passive nuclear power plant is uniquely equipped to withstand an extended station blackout scenario such as the events following the earthquake and tsunami at Fukushima without compromising core and containment integrity. The AP1000 plant shuts down the reactor, cools the core, containment and spent fuel pool for more than 3 days using passive systems that do not require AC or DC power or operator actions. Following this passive coping period, minimal operator actions are needed to extend the operation of the passive features to 7 days using installed equipment. To provide defense-in-depth for design extension conditions, themore » AP1000 plant has engineered features that mitigate the effects of core damage. Engineered features retain damaged core debris within the reactor vessel as a key feature. Other aspects of the design protect containment integrity during severe accidents, including unique features of the AP1000 design relative to passive containment cooling with water and air, and hydrogen management. (authors)« less

  5. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

    PubMed Central

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  6. Aviation Safety Program: Weather Accident Prevention (WxAP) Development of WxAP System Architecture And Concepts of Operation

    NASA Technical Reports Server (NTRS)

    Grantier, David

    2003-01-01

    This paper presents viewgraphs on the development of the Weather Accident Prevention (WxAP) System architecture and Concept of Operation (CONOPS) activities. The topics include: 1) Background Information on System Architecture/CONOPS Activity; 2) Activity Work in Progress; and 3) Anticipated By-Products.

  7. AP-1 Oligodeoxynucleotides Reduce Aortic Elastolysis in a Murine Model of Marfan Syndrome.

    PubMed

    Arif, Rawa; Zaradzki, Marcin; Remes, Anca; Seppelt, Philipp; Kunze, Reiner; Schröder, Hannes; Schwill, Simon; Ensminger, Stephan M; Robinson, Peter N; Karck, Matthias; Müller, Oliver J; Hecker, Markus; Wagner, Andreas H; Kallenbach, Klaus

    2017-12-15

    Marfan syndrome is characterized by high expression of matrix metalloproteinases (MMPs) in aortic smooth muscle cells (AoSMCs) associated with medial elastolysis and aortic root aneurysm. We aimed to reduce aortic elastolysis through decrease of MMP expression with decoy oligodeoxynucleotides (dODNs) neutralizing the transcription factor activating factor-1 (AP-1). AP-1 abundance in nuclear extracts as well as MMP-2 and MMP-9 expression were significantly increased in isolated mAoSMC of mgR/mgR Marfan mice compared to wild-type cells. Exposure to AP-1 neutralizing dODNs resulted in a significant reduction of basal and interleukin-1β-stimulated MMP expression and activity in mAoSMCs. Moreover, increased migration and formation of superoxide radical anions was substantially decreased in mAoSMCs by AP-1 dODN treatment. Aortic grafts from donor Marfan mice were treated with AP-1- dODN ex vivo and implanted as infrarenal aortic interposition grafts in mgR/mgR mice. Pretreatment of aortic grafts with AP-1 dODN led to reduced elastolysis, macrophage infiltration, and MMP activity. Permeability of the endothelial monolayer was increased for dODN in mgR/mgR aortae with observed loss of tight junction proteins ZO-1 and occludin, enabling dODN to reach the tunica media. Targeting AP-1 activity offers a new potential strategy to treat the vascular phenotype associated with Marfan syndrome. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Structural Determinants of DNA Binding by a P. falciparum ApiAP2 Transcriptional Regulator

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

    Lindner, Scott E.; De Silva, Erandi K.; Keck, James L.

    2010-11-05

    Putative transcription factors have only recently been identified in the Plasmodium spp., with the major family of regulators comprising the Apicomplexan Apetala2 (AP2) proteins. To better understand the DNA-binding mechanisms of these transcriptional regulators, we characterized the structure and in vitro function of an AP2 DNA-binding domain from a prototypical Apicomplexan AP2 protein, PF14{_}0633 from Plasmodium falciparum. The X-ray crystal structure of the PF14{_}0633 AP2 domain bound to DNA reveals a {beta}-sheet fold that binds the DNA major groove through base-specific and backbone contacts; a prominent {alpha}-helix supports the {beta}-sheet structure. Substitution of predicted DNA-binding residues with alanine weakened ormore » eliminated DNA binding in solution. In contrast to plant AP2 domains, the PF14{_}0633 AP2 domain dimerizes upon binding to DNA through a domain-swapping mechanism in which the {alpha}-helices of the AP2 domains pack against the {beta}-sheets of the dimer mates. DNA-induced dimerization of PF14{_}0633 may be important for tethering two distal DNA loci together in the nucleus and/or for inducing functional rearrangements of its domains to facilitate transcriptional regulation. Consistent with a multisite binding mode, at least two copies of the consensus sequence recognized by PF14{_}0633 are present upstream of a previously identified group of sporozoite-stage genes. Taken together, these findings illustrate how Plasmodium has adapted the AP2 DNA-binding domain for genome-wide transcriptional regulation.« less

  9. Di-Adenosine Tetraphosphate (Ap4A) Metabolism Impacts Biofilm Formation by Pseudomonas fluorescens via Modulation of c-di-GMP-Dependent Pathways▿

    PubMed Central

    Monds, Russell D.; Newell, Peter D.; Wagner, Jeffrey C.; Schwartzman, Julia A.; Lu, Wenyun; Rabinowitz, Joshua D.; O'Toole, George A.

    2010-01-01

    Dinucleoside tetraphosphates are common constituents of the cell and are thought to play diverse biological roles in organisms ranging from bacteria to humans. In this study we characterized two independent mechanisms by which di-adenosine tetraphosphate (Ap4A) metabolism impacts biofilm formation by Pseudomonas fluorescens. Null mutations in apaH, the gene encoding nucleoside tetraphosphate hydrolase, resulted in a marked increase in the cellular level of Ap4A. Concomitant with this increase, Pho regulon activation in low-inorganic-phosphate (Pi) conditions was severely compromised. As a consequence, an apaH mutant was not sensitive to Pho regulon-dependent inhibition of biofilm formation. In addition, we characterized a Pho-independent role for Ap4A metabolism in regulation of biofilm formation. In Pi-replete conditions Ap4A metabolism was found to impact expression and localization of LapA, the major adhesin regulating surface commitment by P. fluorescens. Increases in the level of c-di-GMP in the apaH mutant provided a likely explanation for increased localization of LapA to the outer membrane in response to elevated Ap4A concentrations. Increased levels of c-di-GMP in the apaH mutant were associated with increases in the level of GTP, suggesting that elevated levels of Ap4A may promote de novo purine biosynthesis. In support of this suggestion, supplementation with adenine could partially suppress the biofilm and c-di-GMP phenotypes of the apaH mutant. We hypothesize that changes in the substrate (GTP) concentration mediated by altered flux through nucleotide biosynthetic pathways may be a significant point of regulation for c-di-GMP biosynthesis and regulation of biofilm formation. PMID:20154123

  10. Di-adenosine tetraphosphate (Ap4A) metabolism impacts biofilm formation by Pseudomonas fluorescens via modulation of c-di-GMP-dependent pathways.

    PubMed

    Monds, Russell D; Newell, Peter D; Wagner, Jeffrey C; Schwartzman, Julia A; Lu, Wenyun; Rabinowitz, Joshua D; O'Toole, George A

    2010-06-01

    Dinucleoside tetraphosphates are common constituents of the cell and are thought to play diverse biological roles in organisms ranging from bacteria to humans. In this study we characterized two independent mechanisms by which di-adenosine tetraphosphate (Ap4A) metabolism impacts biofilm formation by Pseudomonas fluorescens. Null mutations in apaH, the gene encoding nucleoside tetraphosphate hydrolase, resulted in a marked increase in the cellular level of Ap4A. Concomitant with this increase, Pho regulon activation in low-inorganic-phosphate (P(i)) conditions was severely compromised. As a consequence, an apaH mutant was not sensitive to Pho regulon-dependent inhibition of biofilm formation. In addition, we characterized a Pho-independent role for Ap4A metabolism in regulation of biofilm formation. In P(i)-replete conditions Ap4A metabolism was found to impact expression and localization of LapA, the major adhesin regulating surface commitment by P. fluorescens. Increases in the level of c-di-GMP in the apaH mutant provided a likely explanation for increased localization of LapA to the outer membrane in response to elevated Ap4A concentrations. Increased levels of c-di-GMP in the apaH mutant were associated with increases in the level of GTP, suggesting that elevated levels of Ap4A may promote de novo purine biosynthesis. In support of this suggestion, supplementation with adenine could partially suppress the biofilm and c-di-GMP phenotypes of the apaH mutant. We hypothesize that changes in the substrate (GTP) concentration mediated by altered flux through nucleotide biosynthetic pathways may be a significant point of regulation for c-di-GMP biosynthesis and regulation of biofilm formation.

  11. Clathrin Terminal Domain-Ligand Interactions Regulate Sorting of Mannose 6-Phosphate Receptors Mediated by AP-1 and GGA Adaptors*

    PubMed Central

    Stahlschmidt, Wiebke; Robertson, Mark J.; Robinson, Phillip J.; McCluskey, Adam; Haucke, Volker

    2014-01-01

    Clathrin plays important roles in intracellular membrane traffic including endocytosis of plasma membrane proteins and receptors and protein sorting between the trans-Golgi network (TGN) and endosomes. Whether clathrin serves additional roles in receptor recycling, degradative sorting, or constitutive secretion has remained somewhat controversial. Here we have used acute pharmacological perturbation of clathrin terminal domain (TD) function to dissect the role of clathrin in intracellular membrane traffic. We report that internalization of major histocompatibility complex I (MHCI) is inhibited in cells depleted of clathrin or its major clathrin adaptor complex 2 (AP-2), a phenotype mimicked by application of Pitstop® inhibitors of clathrin TD function. Hence, MHCI endocytosis occurs via a clathrin/AP-2-dependent pathway. Acute perturbation of clathrin also impairs the dynamics of intracellular clathrin/adaptor complex 1 (AP-1)- or GGA (Golgi-localized, γ-ear-containing, Arf-binding protein)-coated structures at the TGN/endosomal interface, resulting in the peripheral dispersion of mannose 6-phosphate receptors. By contrast, secretory traffic of vesicular stomatitis virus G protein, recycling of internalized transferrin from endosomes, or degradation of EGF receptor proceeds unperturbed in cells with impaired clathrin TD function. These data indicate that clathrin is required for the function of AP-1- and GGA-coated carriers at the TGN but may be dispensable for outward traffic en route to the plasma membrane. PMID:24407285

  12. Back to the Future: Merit or Equity in AP Social Studies?

    ERIC Educational Resources Information Center

    Stevens, Robert

    2013-01-01

    In an effort to address severe budget deficits at both the state and local levels, schools and educational programs are being asked to trim budgets. The Advanced Placement Program is one program that will certainly be scrutinized. This article presents a general overview of AP social studies, a brief history of the AP social studies program, and…

  13. Airborne Precision Spacing (APS) Dependent Parallel Arrivals (DPA)

    NASA Technical Reports Server (NTRS)

    Smith, Colin L.

    2012-01-01

    The Airborne Precision Spacing (APS) team at the NASA Langley Research Center (LaRC) has been developing a concept of operations to extend the current APS concept to support dependent approaches to parallel or converging runways along with the required pilot and controller procedures and pilot interfaces. A staggered operations capability for the Airborne Spacing for Terminal Arrival Routes (ASTAR) tool was developed and designated as ASTAR10. ASTAR10 has reached a sufficient level of maturity to be validated and tested through a fast-time simulation. The purpose of the experiment was to identify and resolve any remaining issues in the ASTAR10 algorithm, as well as put the concept of operations through a practical test.

  14. COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer.

    PubMed

    Gao, Shujun; Fang, Lekun; Phan, Liem Minh; Qdaisat, Aiham; Yeung, Sai-Ching J; Lee, Mong-Hong

    2015-09-29

    Cervical cancer is one of the leading causes of cancer death in women. Human papillomaviruses (HPVs) are the major cause in almost 99.7% of cervical cancer. E6 oncoprotein of HPV and E6-associated protein (E6AP) are critical in causing p53 degradation and malignancy. Understanding the E6AP regulation is critical to develop treating strategy for cervical cancer patients. The COP9 signalosome subunit 6 (CSN6) is involved in ubiquitin-mediated protein degradation. We found that both CSN6 and E6AP are overexpressed in cervical cancer. We characterized that CSN6 associated with E6AP and stabilized E6AP expression by reducing E6AP poly-ubiquitination, thereby regulating p53 activity in cell proliferation and apoptosis. Mechanistic studies revealed that CSN6-E6AP axis can be regulated by EGF/Akt signaling. Furthermore, inhibition of CSN6-E6AP axis hinders cervical cancer growth in mice. Taken together, our results indicate that CSN6 is a positive regulator of E6AP and is important for cervical cancer development.

  15. Effects of Astragalus polysaccharides (APS) and chitooligosaccharides (COS) on growth, immune response and disease resistance of juvenile largemouth bass, Micropterus salmoides.

    PubMed

    Lin, Shi-Mei; Jiang, Yu; Chen, Yong-Jun; Luo, Li; Doolgindachbaporn, Sompong; Yuangsoi, Bundit

    2017-11-01

    The effects of oral administration of Astragalus polysaccharides (APS) and chitooligosaccharides (COS), single or combined, on the growth performance, immunity and disease resistance of M. salmoides were investigated. Largemouth bass juvenile were divided into 4 groups and each group was fed with diets supplemented with or without immunostimulant for 8 weeks. After 8 weeks of feeding trial, five fish per tank were sampled for immunity determination, ten fish per tank were challenged by A. hydrophila. The results showed that the largemouth bass fed with two immunostimulants alone or in combination significantly enhanced the final weight and specific growth rate (SGR), decreased feed conversion ratio (FCR) (P < 0.05). However, there were no significant differences (P < 0.05) in specific growth rate (SGR) between dietary COS and dietary APS. In addition, both COS and APS upregulated respiratory burst activity (RBA), phagocytic activity (PA), lysozyme activity and superoxide dismutase (SOD) activity. Meanwhile, COS also exhibited a increase in total leukocyte count, nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity compared to the control. When challenged with A. hydrophila, the mortality of groups fed with COS and/or APS was lower than the control (P < 0.05). Under the experimental conditions, dietary APS and COS had a synergistic effect on lysozme activity, iNOS activity, NO content and disease resistance of fish (P < 0.05). Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. A method of semi-quantifying β-AP in brain PET-CT 11C-PiB images.

    PubMed

    Jiang, Jiehui; Lin, Xiaoman; Wen, Junlin; Huang, Zhemin; Yan, Zhuangzhi

    2014-01-01

    Alzheimer's disease (AD) is a common health problem for elderly populations. Positron emission tomography-computed tomography (PET-CT)11C-PiB for beta-P (amyloid-β peptide, β-AP) imaging is an advanced method to diagnose AD in early stage. However, in practice radiologists lack a standardized value to semi-quantify β-AP. This paper proposes such a standardized value: SVβ-AP. This standardized value measures the mean ratio between the dimension of β-AP areas in PET and CT images. A computer aided diagnosis approach is also proposed to achieve SVβ-AP. A simulation experiment was carried out to pre-test the technical feasibility of the CAD approach and SVβ-AP. The experiment results showed that it is technically feasible.

  17. 241-AP Tank Farm Construction Extent of Condition Review for Tank Integrity

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

    Barnes, Travis J.; Gunter, Jason R.; Reeploeg, Gretchen E.

    2014-04-04

    This report provides the results of an extent of condition construction history review for the 241-AP tank farm. The construction history of the 241-AP tank farm has been reviewed to identify issues similar to those experienced during tank AY-102 construction. Those issues and others impacting integrity are discussed based on information found in available construction records, using tank AY-102 as the comparison benchmark. In the 241-AP tank farm, the sixth double-shell tank farm constructed, tank bottom flatness, refractory material quality, post-weld stress relieving, and primary tank bottom weld rejection were improved.

  18. WCPSS Advanced Placement (AP) Test Results, 2009-10. E&R Report No. 10.29

    ERIC Educational Resources Information Center

    McMillen, Brad

    2010-01-01

    Analysis of WCPSS' 2009-10 AP reports from the College Board reveal that the number and proportion of WCPSS students taking AP courses and exams continues to grow. Between 1996-97 and 2009-10, the number of students enrolled in WCPSS grew by approximately 63% and the number taking AP exams increased by 238% with a corresponding increase in exams…

  19. 78 FR 21817 - Amendment of Restricted Area R-6601; Fort A.P. Hill, VA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ...; Airspace Docket No. 12-AEA-7] RIN 2120-AA66 Amendment of Restricted Area R-6601; Fort A.P. Hill, VA AGENCY... limits and time of designation of restricted area R-6601, Fort A.P. Hill, VA. The U.S. Army requested... limits and increase the time of designation of restricted area R-6601, Fort A.P. Hill, VA, (77 FR 35308...

  20. Near-optimal protocols in complex nonequilibrium transformations

    DOE PAGES

    Gingrich, Todd R.; Rotskoff, Grant M.; Crooks, Gavin E.; ...

    2016-08-29

    The development of sophisticated experimental means to control nanoscale systems has motivated efforts to design driving protocols that minimize the energy dissipated to the environment. Computational models are a crucial tool in this practical challenge. In this paper, we describe a general method for sampling an ensemble of finite-time, nonequilibrium protocols biased toward a low average dissipation. In addition, we show that this scheme can be carried out very efficiently in several limiting cases. As an application, we sample the ensemble of low-dissipation protocols that invert the magnetization of a 2D Ising model and explore how the diversity of themore » protocols varies in response to constraints on the average dissipation. In this example, we find that there is a large set of protocols with average dissipation close to the optimal value, which we argue is a general phenomenon.« less

  1. HIV-1 Nef hijacks clathrin coats by stabilizing AP-1:Arf1 polygons.

    PubMed

    Shen, Qing-Tao; Ren, Xuefeng; Zhang, Rui; Lee, Il-Hyung; Hurley, James H

    2015-10-23

    The lentiviruses HIV and simian immunodeficiency virus (SIV) subvert intracellular membrane traffic as part of their replication cycle. The lentiviral Nef protein helps viruses evade innate and adaptive immune defenses by hijacking the adaptor protein 1 (AP-1) and AP-2 clathrin adaptors. We found that HIV-1 Nef and the guanosine triphosphatase Arf1 induced trimerization and activation of AP-1. Here we report the cryo-electron microscopy structures of the Nef- and Arf1-bound AP-1 trimer in the active and inactive states. A central nucleus of three Arf1 molecules organizes the trimers. We combined the open trimer with a known dimer structure and thus predicted a hexagonal assembly with inner and outer faces that bind the membranes and clathrin, respectively. Hexagons were directly visualized and the model validated by reconstituting clathrin cage assembly. Arf1 and Nef thus play interconnected roles in allosteric activation, cargo recruitment, and coat assembly, revealing an unexpectedly intricate organization of the inner AP-1 layer of the clathrin coat. Copyright © 2015, American Association for the Advancement of Science.

  2. Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

    PubMed Central

    Hirst, Jennifer; Madeo, Marianna; Smets, Katrien; Edgar, James R.; Schols, Ludger; Li, Jun; Yarrow, Anna; Deconinck, Tine; Baets, Jonathan; Van Aken, Elisabeth; De Bleecker, Jan; Datiles, Manuel B.; Roda, Ricardo H.; Liepert, Joachim; Züchner, Stephan; Mariotti, Caterina; De Jonghe, Peter; Blackstone, Craig

    2016-01-01

    Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype–phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious. Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1. Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material. Conclusions: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders. PMID:27606357

  3. Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis

    PubMed Central

    Worth, Danielle; Huang, Sherri

    2018-01-01

    Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important transcriptional repressor mechanism controlling bradyzoite differentiation that operates in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the expression of a subset of bradyzoite-specific proteins in replicating tachyzoites that included tissue cyst wall components BPK1, MCP4, CST1 and the surface antigen SRS9. In the murine animal model, the mis-timing of bradyzoite antigens in tachyzoites lacking AP2IV-4 caused a potent inflammatory monocyte immune response that effectively eliminated this parasite and prevented tissue cyst formation in mouse brain tissue. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to successfully establish a chronic infection in the immune-competent host. PMID:29718996

  4. Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis.

    PubMed

    Radke, Joshua B; Worth, Danielle; Hong, David; Huang, Sherri; Sullivan, William J; Wilson, Emma H; White, Michael W

    2018-05-01

    Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important transcriptional repressor mechanism controlling bradyzoite differentiation that operates in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the expression of a subset of bradyzoite-specific proteins in replicating tachyzoites that included tissue cyst wall components BPK1, MCP4, CST1 and the surface antigen SRS9. In the murine animal model, the mis-timing of bradyzoite antigens in tachyzoites lacking AP2IV-4 caused a potent inflammatory monocyte immune response that effectively eliminated this parasite and prevented tissue cyst formation in mouse brain tissue. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to successfully establish a chronic infection in the immune-competent host.

  5. A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling.

    PubMed

    Beautrait, Alexandre; Paradis, Justine S; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M; Khoury, Etienne; Audet, Martin; Roux, Philippe P; Veprintsev, Dmitry B; Laporte, Stéphane A; Bouvier, Michel

    2017-04-18

    In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes. This selective β-arrestin/β2-adaptin inhibitor (Barbadin) blocks agonist-promoted endocytosis of the prototypical β2-adrenergic (β2AR), V2-vasopressin (V2R) and angiotensin-II type-1 (AT1R) receptors, but does not affect β-arrestin-independent (transferrin) or AP2-independent (endothelin-A) receptor internalization. Interestingly, Barbadin fully blocks V2R-stimulated ERK1/2 activation and blunts cAMP accumulation promoted by both V2R and β2AR, supporting the concept of β-arrestin/AP2-dependent signalling for both G protein-dependent and -independent pathways.

  6. A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling

    NASA Astrophysics Data System (ADS)

    Beautrait, Alexandre; Paradis, Justine S.; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M.; Khoury, Etienne; Audet, Martin; Roux, Philippe P.; Veprintsev, Dmitry B.; Laporte, Stéphane A.; Bouvier, Michel

    2017-04-01

    In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes. This selective β-arrestin/β2-adaptin inhibitor (Barbadin) blocks agonist-promoted endocytosis of the prototypical β2-adrenergic (β2AR), V2-vasopressin (V2R) and angiotensin-II type-1 (AT1R) receptors, but does not affect β-arrestin-independent (transferrin) or AP2-independent (endothelin-A) receptor internalization. Interestingly, Barbadin fully blocks V2R-stimulated ERK1/2 activation and blunts cAMP accumulation promoted by both V2R and β2AR, supporting the concept of β-arrestin/AP2-dependent signalling for both G protein-dependent and -independent pathways.

  7. A Survey on Underwater Acoustic Sensor Network Routing Protocols.

    PubMed

    Li, Ning; Martínez, José-Fernán; Meneses Chaus, Juan Manuel; Eckert, Martina

    2016-03-22

    Underwater acoustic sensor networks (UASNs) have become more and more important in ocean exploration applications, such as ocean monitoring, pollution detection, ocean resource management, underwater device maintenance, etc. In underwater acoustic sensor networks, since the routing protocol guarantees reliable and effective data transmission from the source node to the destination node, routing protocol design is an attractive topic for researchers. There are many routing algorithms have been proposed in recent years. To present the current state of development of UASN routing protocols, we review herein the UASN routing protocol designs reported in recent years. In this paper, all the routing protocols have been classified into different groups according to their characteristics and routing algorithms, such as the non-cross-layer design routing protocol, the traditional cross-layer design routing protocol, and the intelligent algorithm based routing protocol. This is also the first paper that introduces intelligent algorithm-based UASN routing protocols. In addition, in this paper, we investigate the development trends of UASN routing protocols, which can provide researchers with clear and direct insights for further research.

  8. A Survey on Underwater Acoustic Sensor Network Routing Protocols

    PubMed Central

    Li, Ning; Martínez, José-Fernán; Meneses Chaus, Juan Manuel; Eckert, Martina

    2016-01-01

    Underwater acoustic sensor networks (UASNs) have become more and more important in ocean exploration applications, such as ocean monitoring, pollution detection, ocean resource management, underwater device maintenance, etc. In underwater acoustic sensor networks, since the routing protocol guarantees reliable and effective data transmission from the source node to the destination node, routing protocol design is an attractive topic for researchers. There are many routing algorithms have been proposed in recent years. To present the current state of development of UASN routing protocols, we review herein the UASN routing protocol designs reported in recent years. In this paper, all the routing protocols have been classified into different groups according to their characteristics and routing algorithms, such as the non-cross-layer design routing protocol, the traditional cross-layer design routing protocol, and the intelligent algorithm based routing protocol. This is also the first paper that introduces intelligent algorithm-based UASN routing protocols. In addition, in this paper, we investigate the development trends of UASN routing protocols, which can provide researchers with clear and direct insights for further research. PMID:27011193

  9. Protocol for a Delay-Tolerant Data-Communication Network

    NASA Technical Reports Server (NTRS)

    Torgerson, Jordan; Hooke, Adrian; Burleigh, Scott; Fall, Kevin

    2004-01-01

    As its name partly indicates, the Delay-Tolerant Networking (DTN) Bundle Protocol is a protocol for delay-tolerant transmission of data via communication networks. This protocol was conceived as a result of studies of how to adapt Internet protocols so that Internet-like services could be provided across interplanetary distances in support of deep-space exploration. The protocol, and software to implement the protocol, is being developed in collaboration among experts at NASA's Jet Propulsion Laboratory and other institutions. No current Internet protocols can accommodate long transmission delay times or intermittent link connectivity. The DTN Bundle Protocol represents a departure from the standard Internet assumption that a continuous path is available from a host computer to a client computer: It provides for routing of data through networks that may be disjointed and may be characterized by long transmission delays. In addition to networks that include deepspace communication links, examples of such networks include terrestrial ones within which branches are temporarily disconnected. The protocol is based partly on the definition of a message-based overlay above the transport layers of the networks on which it is hosted.

  10. Atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry of friction modifier additives analyzed directly from base oil solutions.

    PubMed

    Widder, Lukas; Brennerb, Josef; Huttera, Herbert

    2014-01-01

    To develop new products and to apply measures of quality control quick and simple accessibility of additive composition in automo- tive lubrication is important. The aim of this study was to investigate the possibility of analyzing organic friction modifier additives by means of atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry [AP-MALDI-MS] from lubricant solu- tions without the use of additional separation techniques. Analyses of selected friction modifier ethoxylated tallow amines and oleic acid amide were compared using two ionization methods, positive-ion electrospray ionization (ESI) and AP-MALDI, using a LTQ Orbitrap mass spectrometer. Pure additives were characterized from solvent solutions, as well as from synthetic and mineral base oil mixtures. Detected ions of pure additive samples consisted mainly of [M + H]+, but also alkaLi metal adducts [M + Na]+ and [M + K]+ could be seen. Characterizations of blends of both friction modifiers from the base oil mixtures were carried out as well and showed significant inten- sities for several additive peaks. Thus, this work shows a method to directly analyze friction modifier additives used in the automotive industry from an oil blend via the use of AP-MALDI without any further separation steps. The method presented will further simplify the acquisition of data on lubricant composition and additives. Furthermore, it allows the perspective of analyzing additive reaction products directly from formulated oil blends.

  11. Foundations for College and Beyond: Looking Back on AP Art History

    ERIC Educational Resources Information Center

    Schoenbohm, Laurel

    2013-01-01

    It was years after this author's AP Art History course in high school, and two years after college. She and some friends decided to fill a day during the Thanksgiving visits appreciating fine art. Prior to that AP course her senior year of high school, touring an art museum had seemed like the equivalent of going to the dentist. But after…

  12. Protein-phosphotyrosine proteome profiling by superbinder-SH2 domain affinity purification mass spectrometry, sSH2-AP-MS.

    PubMed

    Tong, Jiefei; Cao, Biyin; Martyn, Gregory D; Krieger, Jonathan R; Taylor, Paul; Yates, Bradley; Sidhu, Sachdev S; Li, Shawn S C; Mao, Xinliang; Moran, Michael F

    2017-03-01

    Recently, "superbinder" SH2 domain variants with three amino acid substitutions (sSH2) were reported to have 100-fold or greater affinity for protein-phosphotyrosine (pY) than natural SH2 domains. Here we report a protocol in which His-tagged Src sSH2 efficiently captures pY-peptides from protease-digested HeLa cell total protein extracts. Affinity purification of pY-peptides by this method shows little bias for pY-proximal amino acid sequences, comparable to that achieved by using antibodies to pY, but with equal or higher yield. Superbinder-SH2 affinity purification mass spectrometry (sSH2-AP-MS) therefore provides an efficient and economical approach for unbiased pY-directed phospho-proteome profiling without the use of antibodies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. ATP6AP2 over-expression causes morphological alterations in the hippocampus and in hippocampus-related behaviour.

    PubMed

    Bracke, A; Schäfer, S; von Bohlen Und Halbach, V; Klempin, F; Bente, K; Bracke, K; Staar, D; van den Brandt, J; Harzsch, S; Bader, M; Wenzel, U O; Peters, J; von Bohlen Und Halbach, O

    2018-02-23

    The (pro)renin receptor [(P)RR], also known as ATP6AP2 [ATPase 6 accessory protein 2], is highly expressed in the brain. ATP6AP2 plays a role in early brain development, adult hippocampal neurogenesis and in cognitive functions. Lack of ATP6AP2 has deleterious effects, and mutations of ATP6AP2 in humans are associated with, e.g. X-linked intellectual disability. However, little is known about the effects of over-expression of ATP6AP2 in the adult brain. We hypothesized that mice over-expressing ATP6AP2 in the brain might exhibit altered neuroanatomical features and behavioural responses. To this end, we investigated heterozygous transgenic female mice and confirmed increased levels of ATP6AP2 in the brain. Our data show that over-expression of ATP6AP2 does not affect adult hippocampal neurogenesis, exercise-induced cell proliferation, or dendritic spine densities in the hippocampus. Only a reduced ventricular volume on the gross morphological level was found. However, ATP6AP2 over-expressing mice displayed altered exploratory behaviour with respect to the hole-board and novel object recognition tests. Moreover, primary adult hippocampal neural stem cells over-expressing ATP6AP2 exhibit a faster cell cycle progression and increased cell proliferation. Together, in contrast to the known deleterious effects of ATP6AP2 depletion, a moderate over-expression results in moderate behavioural changes and affects cell proliferation rate in vitro.

  14. Ultraviolet photometry from the orbiting astronomical observatory. 8: The blue Ap stars

    NASA Technical Reports Server (NTRS)

    Leckrone, D. S.

    1973-01-01

    The filter photometers in the Wisconsin Experiment Package on OAO-2 were used to obtain data for a carefully selected set of 24 blue Ap stars and 31 comparison standard B and A dwarfs and giants for a program of relative photometry. Observations were made in seven bandpasses over the effective wavelength range 1430A-4250A. The Ap stars observed include members of the Si, Hg-Mn and Sr-Cr-Eu peculiarity classes. Most of them are too blue in B-V for their published MK spectral classes. The blue Ap stars are markedly deficient in emitted ultraviolet flux and are underluminous as compared to normal stars with the same UBV colors. The Hg-Mn stars appear less flux deficient in the ultraviolet for their UBV colors than do Si or Sr-cr-Eu stars. Most of the Ap stars observed possess ultraviolet flux distributions, or ultraviolet color temperatures, consistent with their published MK spectral classes to well within the classification uncertainties.

  15. Regional Seminars to Address Current Nuclear Export Control Issues

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

    Killinger, Mark H.

    2002-07-01

    The control of nuclear-related exports, a critical component of the nonproliferation regime, is facing several opportunities and challenges. As countries sign and ratify the International Atomic Energy Agency's (IAEA) safeguards Additional Protocol (AP), they will begin to report far more export information, including exports of a list of items similar to the Nuclear Supplier Group's Trigger List that existed when the AP was developed in the mid-1990s. This positive development contrasts with challenges such as globalization, transshipments, and tracking of end-uses. Pacific Northwest National Laboratory is proposing that the US Department of Energy (DOE) develop regional seminars that address thesemore » types of issues related to export/import controls. The DOE seminars would be designed to supplement regional seminars sponsored by the IAEA and member states on topics related to the Additional Protocol (referred to as "IAEA seminars"). The topic of nuclear export/import controls is not thoroughly addressed in the IAEA seminars. The proposed DOE seminars would therefore have two objectives: familiarizing countries with the export/import provisions of the Additional Protocol, and addressing challenges such as those noted above. The seminars would be directed particularly at countries that have not ratified the AP, and at regions where export-related problems are particularly prevalent. The intent is to encourage governments to implement more effective nuclear export control systems that meet the challenges of the 21st century.« less

  16. A second-generation superconducting undulator cryostat for the APS

    NASA Astrophysics Data System (ADS)

    Fuerst, J.; Hasse, Q.; Ivanyushenkov, Y.; Kasa, M.; Shiroyanagi, Y.

    2017-12-01

    A second-generation cryocooler-based cryostat has been designed and built to support a new helically wound superconducting undulator (SCU) magnet for the Advanced Photon Source (APS) at Argonne National Laboratory (ANL). The design represents an evolution of existing SCU cryostats currently in operation in the APS storage ring. Value engineering and lessons learned have resulted in a smaller, cheaper, and simpler cryostat design compatible with existing planar magnets as well as the new helically wound device. We describe heat load and quench response results, design and operational details, and the “build-to-spec” procurement strategy.

  17. Structuring the AP Art History Course

    ERIC Educational Resources Information Center

    Herscher, Walter R.

    2013-01-01

    While AP (Advanced Placement) Art History may be taught within the art department in many schools, social studies teachers are equally capable of teaching the course well. They have the historical background to discuss the reasons for changes in art styles. A teacher's preparation is similar to teaching a course stressing political history,…

  18. The Promise of AP World History

    ERIC Educational Resources Information Center

    Saldaña, Cristóbal T.

    2013-01-01

    AP World History is the ideal history course. It introduces students to 10,000 years of world history, and demands critical reading, critical writing, and critical thinking skills on the part of both the teacher and the students. It requires students to build their expertise in reading their textbook, and places demands on the teacher to assign…

  19. Baseline water quality of Long Meadow Lake, Ponds AP-9 and AP-10, and Black Dog Creek, Hennepin and Dakota counties, Minnesota

    USGS Publications Warehouse

    Payne, G.A.

    1977-01-01

    Long Meadow Lake, Black Dog Creek, and Ponds AP-9 and AP-10 which lie in an area designated for a trunk highway bridge crossing the Minnesota River, were sampled for baseline water quality prior to construction of the bridge. Data collected show that dissolved solids fluctuate seasonally. Dissolved oxygen:/ranged from less than 1 milligram per liter under an ice cover to 13-9 milligrams per liter in the September sample at site 4 in Long Meadow Lake. The phytoplankton analyses showed pulses in algae populations, blue-green algae being the dominant type in at least one sample from each of the water courses.

  20. An economic and feasible Quantum Sealed-bid Auction protocol

    NASA Astrophysics Data System (ADS)

    Zhang, Rui; Shi, Run-hua; Qin, Jia-qi; Peng, Zhen-wan

    2018-02-01

    We present an economic and feasible Quantum Sealed-bid Auction protocol using quantum secure direct communication based on single photons in both the polarization and the spatial-mode degrees of freedom, where each single photon can carry two bits of classical information. Compared with previous protocols, our protocol has higher efficiency. In addition, we propose a secure post-confirmation mechanism without quantum entanglement to guarantee the security and the fairness of the auction.

  1. Ectopic expression of Jatropha curcas APETALA1 (JcAP1) caused early flowering in Arabidopsis, but not in Jatropha

    PubMed Central

    Tang, Mingyong; Tao, Yan-Bin

    2016-01-01

    Jatropha curcas is a promising feedstock for biofuel production because Jatropha oil is highly suitable for the production of biodiesel and bio-jet fuels. However, Jatropha exhibits a low seed yield as a result of unreliable and poor flowering. APETALA1 (AP1) is a floral meristem and organ identity gene in higher plants. The flower meristem identity genes of Jatropha have not yet been identified or characterized. To better understand the genetic control of flowering in Jatropha, an AP1 homolog (JcAP1) was isolated from Jatropha. An amino acid sequence analysis of JcAP1 revealed a high similarity to the AP1 proteins of other perennial plants. JcAP1 was expressed in inflorescence buds, flower buds, sepals and petals. The highest expression level was observed during the early developmental stage of the flower buds. The overexpression of JcAP1 using the cauliflower mosaic virus (CaMV) 35S promoter resulted in extremely early flowering and abnormal flowers in transgenic Arabidopsis plants. Several flowering genes downstream of AP1 were up-regulated in the JcAP1-overexpressing transgenic plant lines. Furthermore, JcAP1 overexpression rescued the phenotype caused by the Arabidopsis AP1 loss-of-function mutant ap1-11. Therefore, JcAP1 is an ortholog of AtAP1, which plays a similar role in the regulation of flowering in Arabidopsis. However, the overexpression of JcAP1 in Jatropha using the same promoter resulted in little variation in the flowering time and floral organs, indicating that JcAP1 may be insufficient to regulate flowering by itself in Jatropha. This study helps to elucidate the function of JcAP1 and contributes to the understanding of the molecular mechanisms of flower development in Jatropha. PMID:27168978

  2. Physical interaction between the strawberry allergen Fra a 1 and an associated partner FaAP: Interaction of Fra a 1 proteins and FaAP.

    PubMed

    Franz-Oberdorf, Katrin; Langer, Andreas; Strasser, Ralf; Isono, Erika; Ranftl, Quirin L; Wunschel, Christian; Schwab, Wilfried

    2017-10-01

    The strawberry fruit allergens Fra a 1.01E, Fra a 1.02 and Fra a 1.03 belong to the group of pathogenesis-related 10 (PR-10) proteins and are homologs of the major birch pollen Bet v 1 and apple allergen Mal d 1. Bet v 1 related proteins are the most extensively studied allergens but their physiological function in planta remains elusive. Since Mal d 1-Associated Protein has been previously identified as interaction partner of Mal d 1 we studied the binding of the orthologous Fra a 1-Associated Protein (FaAP) to Fra a 1.01E/1.02/1.03. As the C-terminal sequence of FaAP showed strong auto-activation activity in yeast 2-hybrid analysis a novel time resolved DNA-switching system was successfully applied. Fra a 1.01E, Fra a 1.02, and Fra a 1.03 bind to FaAP with K D of 4.5 ± 1.1, 15 ± 3, and 11 ± 2 nM, respectively. Fra a 1.01E forms a dimer, whereas Fra a 1.02 and Fra a 1.03 bind as monomer. The results imply that PR-10 proteins might be integrated into a protein-interaction network and FaAP binding appears to be essential for the physiological function of the Fra a 1 proteins. © 2017 Wiley Periodicals, Inc.

  3. Point-to-Point Multicast Communications Protocol

    NASA Technical Reports Server (NTRS)

    Byrd, Gregory T.; Nakano, Russell; Delagi, Bruce A.

    1987-01-01

    This paper describes a protocol to support point-to-point interprocessor communications with multicast. Dynamic, cut-through routing with local flow control is used to provide a high-throughput, low-latency communications path between processors. In addition multicast transmissions are available, in which copies of a packet are sent to multiple destinations using common resources as much as possible. Special packet terminators and selective buffering are introduced to avoid a deadlock during multicasts. A simulated implementation of the protocol is also described.

  4. Mars Communication Protocols

    NASA Technical Reports Server (NTRS)

    Kazz, G. J.; Greenberg, E.

    2000-01-01

    Over the next decade, international plans and commitments are underway to develop an infrastructure at Mars to support future exploration of the red planet. The purpose of this infrastructure is to provide reliable global communication and navigation coverage for on-approach, landed, roving, and in-flight assets at Mars. The claim is that this infrastructure will: 1) eliminate the need of these assets to carry Direct to Earth (DTE) communications equipment, 2) significantly increase data return and connectivity, 3) enable small mission exploration of Mars without DTE equipment, 4) provide precision navigation i.e., 10 to 100m position resolution, 5) supply timing reference accurate to 10ms. This paper in particular focuses on two CCSDS recommendations for that infrastructure: CCSDS Proximity-1 Space Link Protocol and CCSDS File Delivery Protocol (CFDP). A key aspect of Mars exploration will be the ability of future missions to interoperate. These protocols establish a framework for interoperability by providing standard communication, navigation, and timing services. In addition, these services include strategies to recover gracefully from communication interruptions and interference while ensuring backward compatibility with previous missions from previous phases of exploration.

  5. Building a world-class A/P function: how UPMC went paperless.

    PubMed

    DeLuca, Michael; Smith, Corey

    2010-03-01

    UPMC engaged people, processes, and technology to move its A/P function from a highly manual, paper-based operation to a completely automated process. UPMC's CFO hired a chief supply chain officer to develop a strategic plan, and UPMC named a value analysis team to gain clinician buy-in. UPMC automated A/P by enabling receipt of electronic invoices. UPMC streamlined its processes for invoices.

  6. P1,P4-diadenosine tetraphosphate (Ap4A) inhibits proximal tubular reabsorption of sodium in rats.

    PubMed

    Stiepanow-Trzeciak, Anna; Jankowski, Maciej; Angielski, Stefan; Szczepanska-Konkel, Miroslawa

    2007-01-01

    P1,P4-diadenosine tetraphosphate (Ap4A) is a vasoactive dinucleotide possessing natriuretic activity. It is unclear, however, which part of the nephron is the target site of action for Ap4A. We evaluated the tubular sites of Ap4A action using the lithium clearance technique. Ap4A at a priming dose of 2 micromol/kg with subsequent infusion at 20 nmol/kg/min increased fractional water and sodium excretion 2.5- and 5.6-fold, respectively. Moreover, Ap4A increased lithium clearance 1.9-fold and fractional lithium excretion 2.8-fold. Fractional water and sodium excretion from distal nephron segments was not significantly affected by Ap4A. These results suggest that Ap4A induces natriuresis mainly through inhibition of proximal tubular reabsorption of sodium. Copyright 2007 S. Karger AG, Basel.

  7. AP1S2 is mutated in X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome).

    PubMed

    Cacciagli, Pierre; Desvignes, Jean-Pierre; Girard, Nadine; Delepine, Marc; Zelenika, Diana; Lathrop, Mark; Lévy, Nicolas; Ledbetter, David H; Dobyns, William B; Villard, Laurent

    2014-03-01

    MRXS5 or Pettigrew syndrome was described 20 years ago in a four generation family including nine affected individuals presenting with facial dysmorphism, intellectual disability, Dandy-Walker malformation and inconstant choreoathetosis. Four individuals had iron deposition in the basal ganglia seen on MRI or at autopsy. The mutation causing Pettigrew has remained elusive since the initial description of the condition. We report the identification of a mutation in the X-linked AP1S2 gene in the original Pettigrew syndrome family using X-chromosome exome sequencing. We report additional phenotype details for several of the affected individuals, allowing us to further refine the phenotype corresponding to this X-linked intellectual disability syndrome. The AP1S2 c.426+1 G>T mutation segregates with the disease in the Pettigrew syndrome family and results in loss of 46 amino acids in the clathrin adaptor complex small chain domain that spans most of the AP1S2 protein sequence. The mutation reported here in AP1S2 is the first mutation that is not predicted to cause a premature termination of the coding sequence or absence of the AP1S2 protein. Although most of the families affected by a mutation in AP1S2 were initially described as having different disorders assigned to at least three different OMIM numbers (MIM 300629, 300630 and 304340), our analysis of the phenotype shows that they are all the same syndrome with recognition complicated by highly variable expressivity that is seen within as well as between families and is probably not explained by differences in mutation severity.

  8. AP1S2 is mutated in X-linked Dandy–Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome)

    PubMed Central

    Cacciagli, Pierre; Desvignes, Jean-Pierre; Girard, Nadine; Delepine, Marc; Zelenika, Diana; Lathrop, Mark; Lévy, Nicolas; Ledbetter, David H; Dobyns, William B; Villard, Laurent

    2014-01-01

    MRXS5 or Pettigrew syndrome was described 20 years ago in a four generation family including nine affected individuals presenting with facial dysmorphism, intellectual disability, Dandy–Walker malformation and inconstant choreoathetosis. Four individuals had iron deposition in the basal ganglia seen on MRI or at autopsy. The mutation causing Pettigrew has remained elusive since the initial description of the condition. We report the identification of a mutation in the X-linked AP1S2 gene in the original Pettigrew syndrome family using X-chromosome exome sequencing. We report additional phenotype details for several of the affected individuals, allowing us to further refine the phenotype corresponding to this X-linked intellectual disability syndrome. The AP1S2 c.426+1 G>T mutation segregates with the disease in the Pettigrew syndrome family and results in loss of 46 amino acids in the clathrin adaptor complex small chain domain that spans most of the AP1S2 protein sequence. The mutation reported here in AP1S2 is the first mutation that is not predicted to cause a premature termination of the coding sequence or absence of the AP1S2 protein. Although most of the families affected by a mutation in AP1S2 were initially described as having different disorders assigned to at least three different OMIM numbers (MIM 300629, 300630 and 304340), our analysis of the phenotype shows that they are all the same syndrome with recognition complicated by highly variable expressivity that is seen within as well as between families and is probably not explained by differences in mutation severity. PMID:23756445

  9. Co-expression analysis identifies CRC and AP1 the regulator of Arabidopsis fatty acid biosynthesis.

    PubMed

    Han, Xinxin; Yin, Linlin; Xue, Hongwei

    2012-07-01

    Fatty acids (FAs) play crucial rules in signal transduction and plant development, however, the regulation of FA metabolism is still poorly understood. To study the relevant regulatory network, fifty-eight FA biosynthesis genes including de novo synthases, desaturases and elongases were selected as "guide genes" to construct the co-expression network. Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT) identifies 797 candidate FA-correlated genes. Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism, and function in many processes. Interestingly, 63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched. Two TF genes, CRC and AP1, both correlating with 8 FA guide genes, were further characterized. Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds. The contents of palmitoleic acid, stearic acid, arachidic acid and eicosadienoic acid are decreased, whereas that of oleic acid is increased in ap1 and crc seeds, which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes. In addition, yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15, indicating that CRC may directly regulate FA biosynthesis. © 2012 Institute of Botany, Chinese Academy of Sciences.

  10. Validation of the new trapped environment AE9/AP9/SPM at low Earth orbit

    NASA Astrophysics Data System (ADS)

    Badavi, Francis F.

    2014-09-01

    The completion of the international space station (ISS) in 2011 has provided the space research community an ideal proving ground for future long duration human activities in space. Ionizing radiation measurements in ISS form the ideal tool for the validation of radiation environmental models, nuclear transport codes and nuclear reaction cross sections. Indeed, prior measurements on the space transportation system (STS; shuttle) provided vital information impacting both the environmental models and the nuclear transport code developments by indicating the need for an improved dynamic model of the low Earth orbit (LEO) trapped environment. Additional studies using thermo-luminescent detector (TLD), tissue equivalent proportional counter (TEPC) area monitors, and computer aided design (CAD) model of earlier ISS configurations, confirmed STS observations that, as input, computational dosimetry requires an environmental model with dynamic and directional (anisotropic) behavior, as well as an accurate six degree of freedom (DOF) definition of the vehicle attitude and orientation along the orbit of ISS. At LEO, a vehicle encounters exposure from trapped particles and attenuated galactic cosmic rays (GCR). Within the trapped field, a challenge arises from properly estimating the amount of exposure acquired. There exist a number of models to define the intensities of the trapped particles during the solar quiet and active times. At active times, solar energetic particles (SEP) generated by solar flare or coronal mass ejection (CME) also contribute to the exposure at high northern and southern latitudes. Among the more established trapped models are the historic and popular AE8/AP8, dating back to the 1980s, the historic and less popular CRRES electron/proton, dating back to 1990s and the recently released AE9/AP9/SPM. The AE9/AP9/SPM model is a major improvement over the older AE8/AP8 and CRRES models. This model is derived from numerous measurements acquired over four

  11. Diagnostic utility of aP2/FABP4 expression in soft tissue tumours.

    PubMed

    Kashima, T G; Turley, H; Dongre, A; Pezzella, F; Athanasou, N A

    2013-04-01

    Adipocyte P2 (aP2), also known as fatty acid-binding protein 4 (FABP4), is a fatty acid-binding protein found in the cytoplasm of cells of adipocyte differentiation. In this study, we examined a large number of soft tissue tumours with a commercial polyclonal anti-aP2/FABP4 antibody and a newly developed mouse monoclonal antibody raised against this protein to determine the diagnostic utility of aP2/FABP4 as a marker of tumours of adipose differentiation. A mouse monoclonal antibody, clone 175d, was raised against a mixture of synthetic peptides corresponding to the amino acid sequence of residues 10-28 and 121-132 of the human aP2/FABP4 protein. Antigen expression with polyclonal and monoclonal antibodies was immunohistochemically determined in paraffin sections of normal adipose tissue and a wide range of benign and malignant primary soft tissue tumours (n = 200). aP2/FABP4 was expressed around the cytoplasmic lipid vacuole in white and brown fat cells in benign lipomas and hibernomas. Immature fat cells and lipoblasts in spindle cell/pleomorphic lipoma, atypical lipomatous tumour/well-differentiated liposarcoma, myxoid/round cell liposarcoma and pleomorphic liposarcoma also reacted strongly for aP2/FABP4. No specific staining was seen in non-adipose benign and malignant mesenchymal and non-mesenchymal tumours. aP2/FABP4 is expressed by mature and immature fat cells and is a marker of tumours of adipose differentiation. Immunophenotypic aP2/FABP4 expression is useful in identifying lipoblasts, and immunohistochemistry with polyclonal/monoclonal anti-aP2/FABP4 antibodies should be useful in distinguishing liposarcoma from other malignancies, particularly round cell, myxoid and pleomorphic soft tissue sarcomas.

  12. AP4M1 is abnormally expressed in oxygen-glucose deprived hippocampal neurons.

    PubMed

    Zhang, J; Cheng, X Y; Sheng, G Y

    2014-03-20

    AP4M1 mutations have been suggested to be associated with autosomal recessive cerebral palsy syndrome. But the pathogenic mechanism remains uncertain. The purpose of this study is to investigate whether and how AP4M1 expression is changed in injured neurons. Primary cultured hippocampal neurons were prepared for this experiment. They were subjected to oxygen-glucose deprivation (OGD) leading to apoptosis, mimicking brain ischemia. Neuron-specific enolase (NSE) was labeled immunofluorescently to confirm that the purity of neuron was higher than 90%. Real-time PCR and western blotting were performed to measure the gene expression. AP4M1 was labeled with MAP2 or Tau-1 to observe the distribution. We found that the AP4M1 protein levels immediately after the procedure were similar between the OGD group and the sham group. However, down-regulation was observed 12h after the reperfusion, and became more notable at 24h. The real-time PCR showed similar results, except that the down-regulation of mRNA was able to be detected immediately after the OGD. Immunofluorescent labeling revealed AP4M1 distributed in the dendrites of normal neurons, but it redistributed to the axons after the OGD procedure. In conclusion, AP4M1 is not only down-regulated at both the mRNA and protein levels, but also redistributed from dendrites to axons in oxygen-glucose deprived hippocampal neurons. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Chlamydia trachomatis CT771 (nudH) is an asymmetric Ap4A hydrolase.

    PubMed

    Barta, Michael L; Lovell, Scott; Sinclair, Amy N; Battaile, Kevin P; Hefty, P Scott

    2014-01-14

    Asymmetric diadenosine 5',5‴-P(1),P(4)-tetraphosphate (Ap4A) hydrolases are members of the Nudix superfamily that asymmetrically cleave the metabolite Ap4A into ATP and AMP while facilitating homeostasis. The obligate intracellular mammalian pathogen Chlamydia trachomatis possesses a single Nudix family protein, CT771. As pathogens that rely on a host for replication and dissemination typically have one or zero Nudix family proteins, this suggests that CT771 could be critical for chlamydial biology and pathogenesis. We identified orthologues to CT771 within environmental Chlamydiales that share active site residues suggesting a common function. Crystal structures of both apo- and ligand-bound CT771 were determined to 2.6 Å and 1.9 Å resolution, respectively. The structure of CT771 shows a αβα-sandwich motif with many conserved elements lining the putative Nudix active site. Numerous aspects of the ligand-bound CT771 structure mirror those observed in the ligand-bound structure of the Ap4A hydrolase from Caenorhabditis elegans. These structures represent only the second Ap4A hydrolase enzyme member determined from eubacteria and suggest that mammalian and bacterial Ap4A hydrolases might be more similar than previously thought. The aforementioned structural similarities, in tandem with molecular docking, guided the enzymatic characterization of CT771. Together, these studies provide the molecular details for substrate binding and specificity, supporting the analysis that CT771 is an Ap4A hydrolase (nudH).

  14. Multiple Independent Genetic Factors at NOS1AP Modulate the QT Interval in a Multi-Ethnic Population

    PubMed Central

    Arking, Dan E.; Khera, Amit; Xing, Chao; Kao, W. H. Linda; Post, Wendy; Boerwinkle, Eric; Chakravarti, Aravinda

    2009-01-01

    Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6×10−5) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP × sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63×10−8), as well as the sex-interaction with rs16847548 (P = 8.68×10−6). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval. PMID:19180230

  15. BDNF mRNA abundance regulated by antidromic action potentials and AP-LTD in hippocampus.

    PubMed

    Bukalo, Olena; Lee, Philip R; Fields, R Douglas

    2016-12-02

    Action-potential-induced LTD (AP-LTD) is a form of synaptic plasticity that reduces synaptic strength in CA1 hippocampal neurons firing antidromically during sharp-wave ripples. This firing occurs during slow-wave sleep and quiet moments of wakefulness, which are periods of offline replay of neural sequences learned during encoding sensory information. Here we report that rapid and persistent down-regulation of different mRNA transcripts of the BDNF gene accompanies AP-LTD, and that AP-LTD is abolished in mice with the BDNF gene knocked out in CA1 hippocampal neurons. These findings increase understanding of the mechanism of AP-LTD and the cellular mechanisms of memory consolidation. Published by Elsevier Ireland Ltd.

  16. Physical Therapy Protocols for Arthroscopic Bankart Repair.

    PubMed

    DeFroda, Steven F; Mehta, Nabil; Owens, Brett D

    Outcomes after arthroscopic Bankart repair can be highly dependent on compliance and participation in physical therapy. Additionally, there are many variations in physician-recommended physical therapy protocols. The rehabilitation protocols of academic orthopaedic surgery departments vary widely despite the presence of consensus protocols. Descriptive epidemiology study. Level 3. Web-based arthroscopic Bankart rehabilitation protocols available online from Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedic surgery programs were included for review. Individual protocols were reviewed to evaluate for the presence or absence of recommended therapies, goals for completion of ranges of motion, functional milestones, exercise start times, and recommended time to return to sport. Thirty protocols from 27 (16.4%) total institutions were identified out of 164 eligible for review. Overall, 9 (30%) protocols recommended an initial period of strict immobilization. Variability existed between the recommended time periods for sling immobilization (mean, 4.8 ± 1.8 weeks). The types of exercises and their start dates were also inconsistent. Goals to full passive range of motion (mean, 9.2 ± 2.8 weeks) and full active range of motion (mean, 12.2 ± 2.8 weeks) were consistent with other published protocols; however, wide ranges existed within the reviewed protocols as a whole. Only 10 protocols (33.3%) included a timeline for return to sport, and only 3 (10%) gave an estimate for return to game competition. Variation also existed when compared with the American Society of Shoulder and Elbow Therapists' (ASSET) consensus protocol. Rehabilitation protocols after arthroscopic Bankart repair were found to be highly variable. They also varied with regard to published consensus protocols. This discrepancy may lead to confusion among therapists and patients. This study highlights the importance of attending surgeons being very clear and specific with

  17. Copernicus observations of the Ap star Epsilon Ursae Majoris

    NASA Technical Reports Server (NTRS)

    Mallama, A. D.; Molnar, M. R.

    1977-01-01

    Spectral scans of the Ap star Epsilon UMa made with the Copernicus satellite show strong line blanketing from profuse Cr II and Fe II lines. In the spectral region covering 1900 to 3000 A, about 500 lines are present which suppress the apparent continuum by at least 15-30%. An accurate line-identification list is compiled showing Eu II present in addition to Mn II and Ni II. The identification of Eu II, however, rests on very stringent identification limits for Fe II. If these are relaxed, the existence of Eu II is dubious. There are no broad features in this spectral region which would suggest strong photoionization discontinuities by metals, but one feature near 2137 A might contain the photoionization edge due to Cr I 5S lying 0.94 eV above the ground level. However, a significant correlation between the line-blanketing strength and the amplitude of the OAO-2 ultraviolet light curves was found such that both monotonically increase in the same proportion toward shorter wavelengths. This gives additional strength to the suggestion that variations in the metal line-blanketing cause the observed photometric variations.

  18. Adaptor Protein Complex-2 (AP-2) and Epsin-1 Mediate Protease-activated Receptor-1 Internalization via Phosphorylation- and Ubiquitination-dependent Sorting Signals*

    PubMed Central

    Chen, Buxin; Dores, Michael R.; Grimsey, Neil; Canto, Isabel; Barker, Breann L.; Trejo, JoAnn

    2011-01-01

    Signaling by protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is regulated by desensitization and internalization. PAR1 desensitization is mediated by β-arrestins, like most classic GPCRs. In contrast, internalization of PAR1 occurs through a clathrin- and dynamin-dependent pathway independent of β-arrestins. PAR1 displays two modes of internalization. Constitutive internalization of unactivated PAR1 is mediated by the clathrin adaptor protein complex-2 (AP-2), where the μ2-adaptin subunit binds directly to a tyrosine-based motif localized within the receptor C-tail domain. However, AP-2 depletion only partially inhibits agonist-induced internalization of PAR1, suggesting a function for other clathrin adaptors in this process. Here, we now report that AP-2 and epsin-1 are both critical mediators of agonist-stimulated PAR1 internalization. We show that ubiquitination of PAR1 and the ubiquitin-interacting motifs of epsin-1 are required for epsin-1-dependent internalization of activated PAR1. In addition, activation of PAR1 promotes epsin-1 de-ubiquitination, which may increase its endocytic adaptor activity to facilitate receptor internalization. AP-2 also regulates activated PAR1 internalization via recognition of distal C-tail phosphorylation sites rather than the canonical tyrosine-based motif. Thus, AP-2 and epsin-1 are both required to promote efficient internalization of activated PAR1 and recognize discrete receptor sorting signals. This study defines a new pathway for internalization of mammalian GPCRs. PMID:21965661

  19. MR efficiency using automated MRI-desktop eProtocol

    NASA Astrophysics Data System (ADS)

    Gao, Fei; Xu, Yanzhe; Panda, Anshuman; Zhang, Min; Hanson, James; Su, Congzhe; Wu, Teresa; Pavlicek, William; James, Judy R.

    2017-03-01

    MRI protocols are instruction sheets that radiology technologists use in routine clinical practice for guidance (e.g., slice position, acquisition parameters etc.). In Mayo Clinic Arizona (MCA), there are over 900 MR protocols (ranging across neuro, body, cardiac, breast etc.) which makes maintaining and updating the protocol instructions a labor intensive effort. The task is even more challenging given different vendors (Siemens, GE etc.). This is a universal problem faced by all the hospitals and/or medical research institutions. To increase the efficiency of the MR practice, we designed and implemented a web-based platform (eProtocol) to automate the management of MRI protocols. It is built upon a database that automatically extracts protocol information from DICOM compliant images and provides a user-friendly interface to the technologists to create, edit and update the protocols. Advanced operations such as protocol migrations from scanner to scanner and capability to upload Multimedia content were also implemented. To the best of our knowledge, eProtocol is the first MR protocol automated management tool used clinically. It is expected that this platform will significantly improve the radiology operations efficiency including better image quality and exam consistency, fewer repeat examinations and less acquisition errors. These protocols instructions will be readily available to the technologists during scans. In addition, this web-based platform can be extended to other imaging modalities such as CT, Mammography, and Interventional Radiology and different vendors for imaging protocol management.

  20. AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking

    PubMed Central

    Setta-Kaffetzi, Niovi; Simpson, Michael A.; Navarini, Alexander A.; Patel, Varsha M.; Lu, Hui-Chun; Allen, Michael H.; Duckworth, Michael; Bachelez, Hervé; Burden, A. David; Choon, Siew-Eng; Griffiths, Christopher E.M.; Kirby, Brian; Kolios, Antonios; Seyger, Marieke M.B.; Prins, Christa; Smahi, Asma; Trembath, Richard C.; Fraternali, Franca; Smith, Catherine H.; Barker, Jonathan N.; Capon, Francesca

    2014-01-01

    Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis. PMID:24791904

  1. IVOA Credential Delegation Protocol Version 1.0

    NASA Astrophysics Data System (ADS)

    Plante, Raymond; Graham, Matthew; Rixon, Guy; Taffoni, Giuliano; Plante, Raymond; Graham, Matthew

    2010-02-01

    The credential delegation protocol allows a client program to delegate a user's credentials to a service such that that service may make requests of other services in the name of that user. The protocol defines a REST service that works alongside other IVO services to enable such a delegation in a secure manner. In addition to defining the specifics of the service protocol, this document describes how a delegation service is registered in an IVOA registry along with the services it supports. The specification also explains how one can determine from a service registration that it requires the use of a supporting delegation service.

  2. An Abbreviated Protocol for High-Risk Screening Breast MRI Saves Time and Resources.

    PubMed

    Harvey, Susan C; Di Carlo, Phillip A; Lee, Bonmyong; Obadina, Eniola; Sippo, Dorothy; Mullen, Lisa

    2016-04-01

    To review the ability of an abbreviated, high-risk, screening, breast MRI protocol to detect cancer and save resources. High-risk screening breast MR images were reviewed, from both an abbreviated protocol and a full diagnostic protocol. Differences in cancer detection, scanner utilization, interpretation times, and need for additional imaging were recorded in an integrated data form, and reviewed and compared. A total of 568 MRI cases were reviewed, with the abbreviated and full protocols. No difference was found in the number of cancers detected. Scan times were decreased by 18.8 minutes per case, for a total of 10,678 minutes (178 hours). Interpretation time, on average, was 1.55 minutes for the abbreviated protocol, compared with 6.43 minutes for the full protocol. Review of the full protocol led to a significant change in the final BI-RADS(®) assessment in 12 of 568 (2.1%) cases. Abbreviated MRI is as effective as full-protocol MRI for demonstration of cancers in the high-risk screening setting, with only 12 (2.1%) cases recommended for additional MRI evaluation. The efficiency and resource savings of an abbreviated protocol would be significant, and would allow for opportunities to provide MRI for additional patients, as well as improved radiologist time management and workflow, with the potential to add real-time MRI interpretation or double reading. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  3. An Abbreviated Protocol for High-Risk Screening Breast MRI Saves Time and Resources.

    PubMed

    Harvey, Susan C; Di Carlo, Phillip A; Lee, Bonmyong; Obadina, Eniola; Sippo, Dorothy; Mullen, Lisa

    2016-11-01

    To review the ability of an abbreviated, high-risk, screening, breast MRI protocol to detect cancer and save resources. High-risk screening breast MR images were reviewed, from both an abbreviated protocol and a full diagnostic protocol. Differences in cancer detection, scanner utilization, interpretation times, and need for additional imaging were recorded in an integrated data form, and reviewed and compared. A total of 568 MRI cases were reviewed, with the abbreviated and full protocols. No difference was found in the number of cancers detected. Scan times were decreased by 18.8 minutes per case, for a total of 10,678 minutes (178 hours). Interpretation time, on average, was 1.55 minutes for the abbreviated protocol, compared with 6.43 minutes for the full protocol. Review of the full protocol led to a significant change in the final BI-RADS ® assessment in 12 of 568 (2.1%) cases. Abbreviated MRI is as effective as full-protocol MRI for demonstration of cancers in the high-risk screening setting, with only 12 (2.1 %) cases recommended for additional MRI evaluation. The efficiency and resource savings of an abbreviated protocol would be significant, and would allow for opportunities to provide MRI for additional patients, as well as improved radiologist time management and workflow, with the potential to add real-time MRI interpretation or double reading. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  4. The Adaptor Protein CD2AP Is a Coordinator of Neurotrophin Signaling-Mediated Axon Arbor Plasticity

    PubMed Central

    Harrison, Benjamin J.; Venkat, Gayathri; Lamb, James L.; Hutson, Tom H.; Drury, Cassa; Rau, Kristofer K.; Bunge, Mary Barlett; Mendell, Lorne M.; Gage, Fred H.; Johnson, Richard D.; Hill, Caitlin E.; Rouchka, Eric C.; Moon, Lawrence D.F.

    2016-01-01

    Growth of intact axons of noninjured neurons, often termed collateral sprouting, contributes to both adaptive and pathological plasticity in the adult nervous system, but the intracellular factors controlling this growth are largely unknown. An automated functional assay of genes regulated in sensory neurons from the rat in vivo spared dermatome model of collateral sprouting identified the adaptor protein CD2-associated protein (CD2AP; human CMS) as a positive regulator of axon growth. In non-neuronal cells, CD2AP, like other adaptor proteins, functions to selectively control the spatial/temporal assembly of multiprotein complexes that transmit intracellular signals. Although CD2AP polymorphisms are associated with increased risk of late-onset Alzheimer's disease, its role in axon growth is unknown. Assessments of neurite arbor structure in vitro revealed CD2AP overexpression, and siRNA-mediated knockdown, modulated (1) neurite length, (2) neurite complexity, and (3) growth cone filopodia number, in accordance with CD2AP expression levels. We show, for the first time, that CD2AP forms a novel multiprotein complex with the NGF receptor TrkA and the PI3K regulatory subunit p85, with the degree of TrkA:p85 association positively regulated by CD2AP levels. CD2AP also regulates NGF signaling through AKT, but not ERK, and regulates long-range signaling though TrkA+/RAB5+ signaling endosomes. CD2AP mRNA and protein levels were increased in neurons during collateral sprouting but decreased following injury, suggesting that, although typically considered together, these two adult axonal growth processes are fundamentally different. These data position CD2AP as a major intracellular signaling molecule coordinating NGF signaling to regulate collateral sprouting and structural plasticity of intact adult axons. SIGNIFICANCE STATEMENT Growth of noninjured axons in the adult nervous system contributes to adaptive and maladaptive plasticity, and dysfunction of this process may

  5. The Evolution of Children's Mental Addition.

    ERIC Educational Resources Information Center

    Ashcraft, Mark H.; Hamann, Mary Sue

    Students in grades 1, 4, 7, and 10 were tested in a two-part investigation of simple and complex mental addition (with college students as a reference point). One session involved a normal reaction time task in which children made true/false judgments about a series of addition examples. The other session involved a verbal protocol interview, the…

  6. Firemaster® 550 and its components isopropylated triphenyl phosphate and triphenyl phosphate enhance adipogenesis and transcriptional activity of peroxisome proliferator activated receptor (Pparγ) on the adipocyte protein 2 (aP2) promoter

    PubMed Central

    Peshdary, Vian

    2017-01-01

    Firemaster® 550 (FM550) is a chemical mixture currently used as an additive flame retardant in commercial products, and is comprised of 2-ethylhexyl-2,3,4,5-tertrabromobenzoate (TBB), bis(2-ethylhexyl) tetrabromophthalate (TBPH), triphenyl phosphate (TPP), and isopropylated triphenyl phosphate (IPTP). Animal and in vitro studies suggest that FM550, TPP and IPTP may have adipogenic effects and may exert these effects through PPARγ activation. Using murine 3T3-L1 preadipocytes, we investigated the detailed expression of transcription factors and adipogenic markers in response to FM550 and its components. Further we investigated the mechanism of action of the peroxisome proliferator-activated receptor gamma (PPARγ) on downstream targets of the receptor by focussing on the mature adipocyte marker, adipocyte protein 2 (aP2). In addition, we set to elucidate the components responsible for the adipogenic effects seen in the FM550 mixture. We show that FM550 and its components TPP, IPTP, and TBPH, but not TBB induced lipid accumulation in a dose-dependent manner. Interestingly, despite displaying enhanced lipid accumulation, TBPH did not alter the mRNA or protein expression of terminal differentiation markers. In contrast, FM550, TPP, and IPTP treatment enhanced lipid accumulation, and mRNA and protein expression of terminal differentiation markers. To further delineate the mechanisms of action of FM550 and its components we focussed on aP2 promoter activity. For this purpose we used the enhancer region of the mouse aP2 promoter using a 584-bp reporter construct containing an active PPRE located 5.4 kb away from the transcription start site of aP2. Exposure to FM550, IPTP, and TPP significantly increased PPARγ mediated aP2 enhancer activity. Furthermore, we show that TPP- and IPTP-dependent upregulation of aP2 was significantly inhibited by the selective PPARγ antagonist GW9662. In addition, chromatin immunoprecipitation experiments showed that IPTP and TPP treatment

  7. Three-step semiquantum secure direct communication protocol

    NASA Astrophysics Data System (ADS)

    Zou, XiangFu; Qiu, DaoWen

    2014-09-01

    Quantum secure direct communication is the direct communication of secret messages without need for establishing a shared secret key first. In the existing schemes, quantum secure direct communication is possible only when both parties are quantum. In this paper, we construct a three-step semiquantum secure direct communication (SQSDC) protocol based on single photon sources in which the sender Alice is classical. In a semiquantum protocol, a person is termed classical if he (she) can measure, prepare and send quantum states only with the fixed orthogonal quantum basis {|0>, |1>}. The security of the proposed SQSDC protocol is guaranteed by the complete robustness of semiquantum key distribution protocols and the unconditional security of classical one-time pad encryption. Therefore, the proposed SQSDC protocol is also completely robust. Complete robustness indicates that nonzero information acquired by an eavesdropper Eve on the secret message implies the nonzero probability that the legitimate participants can find errors on the bits tested by this protocol. In the proposed protocol, we suggest a method to check Eves disturbing in the doves returning phase such that Alice does not need to announce publicly any position or their coded bits value after the photons transmission is completed. Moreover, the proposed SQSDC protocol can be implemented with the existing techniques. Compared with many quantum secure direct communication protocols, the proposed SQSDC protocol has two merits: firstly the sender only needs classical capabilities; secondly to check Eves disturbing after the transmission of quantum states, no additional classical information is needed.

  8. Comparative hemodynamic effects of hypotension induced by diadenosine tetraphosphate (AP4A) and ATP in dogs.

    PubMed

    Takeda, Shohei; Inada, Yutaka; Fukui, Noriyuki; Tomaru, Teruaki

    1997-03-01

    ATP and diadenosine tetraphosphate (AP 4 A) have been shown to produce vasodilation mediated by P 1 - and P 2 -purinoceptor, respectively. The differing mechanisms involved in this vasodilating activity may induce different systemic hemodynamic changes. We compared the hemodynamic effects of AP 4 A-induced hypotension with those induced by ATP. Fourteen mongrel dogs were anesthetized with 0.87% halothane in oxygen (1 MAC). After the baseline period, mean arterial pressure was reduced to 60 mmHg for 60 min by the infusion of AP 4 A or ATP. The ATP- and AP 4 A-induced hypotension resulted in a maximum reduction in systemic vascular resistance of 43% and 46%, respectively (P<0.01), associated with a significant increase in stroke volume index. With ATP, a 20% of maximum increase (P<0.05) in cardiac index (CI) was observed during the induced hypotension. In contrast, AP 4 A-induced hypotension did not result in any changes in CI throughout the observation period. The varying results concerning CI during the ATP- and AP 4 A-induced hypotension were probably due to differences in ventricular filling pressure, since AP 4 A-induced hypotension was associated with decreases (P<0.01) in both right atrial and pulmonary capillary wedge pressures, whereas neither of these variables significantly changed with ATP. The hypotension induced by either ATP or AP 4 A was associated with a significant decrease in heart rate (HR). However, both the magnitude and duration of decreases in HR due to ATP-induced hypotension were more pronounced than those seen with AP 4 A. In conclusion, while both drugs were equally capable of inducing hypotension, our results suggest that AP 4 A was more suitable for induced hypotension because of its potent vasodilatory action with venodilation and less negative chronotropic action.

  9. Aps and Tep Chemical Characterization: Link Between The Dom and Pom Pools

    NASA Astrophysics Data System (ADS)

    Gogou, A.; Repeta, D. J.

    The ocean inventory of dissolved organic carbon (DOC) is approximately 750 GT, comprising one of the Earth's largest carbon reservoirs on Earth. Despite its potential significance, the mechanisms that lead to DOM production and to spatial and temporal variations of DOM concentration in the world ocean are poorly understood. Chemical characterization studies show that up to 50% of HMW DOM is a structurally well-defined class of acylated polysaccharides (APS), which exhibits novel molecular-level characteris tics. Although APS synthesis occurs in the euphotic zone, a large fraction of the marine inventory of APS (appr. 10-30 GT C), resides in the deep ocean, and is approximately equal in mass to the total marine inventory of particulate organic carbon. While radiocarbon dating of deep sea DOC yields very old apparent ages (4000-6000 ybp), radiocarbon measurements made by our group on individual APS sugars shows that APS in the deep ocean has a radiocarbon value of +56 per mil, equivalent to surface water POC and DIC. This is the first clear evidence for the presence of "young" DOC in the deep ocean. One mechanism that could be important for the rapid removal of APS from surface seawater is physical removal by macroaggregates. To investigate the significance of this mechanism, we studied the chemical composition of surface-active POM (TEP) produced naturally on surface waters and in laboratory experiments, after bubbling of HMW DOM isolated from algal cultures. 1H-NMR spectral properties and molecular-level distribution of neutral sugars in natural and artificially produced TEP closely resembled those observed for cultured and oceanic HMW DOM, while they are significantly different from those of suspended particulate matter in the ocean (Gogou and Repeta, 2000). The results of these experiments provide evidence that POM with similar chemical characteristics to HMW DOM can be produced from algal-derived DOM in the surface ocean.

  10. AP American History and the History Major: Keeping Body and Soul Together.

    ERIC Educational Resources Information Center

    Holbo, Paul S.

    For college-level American History, in the high school advanced placement (AP) program and on university campuses, these are the best of times and the worst of times. For the American History AP program, the early 1970's were difficult times, with the examinations under attack as elitist and irrelevant to contemporary problems. The program…

  11. Health in All Policies (HiAP) framework for country action.

    PubMed

    2014-06-01

    This document serves as a 'starter's kit' for applying Health in All Policies (HiAP) in decision-making and implementation at national and subnational levels. It can be easily adapted for use in different country contexts and at the regional and global levels. WHAT IS HIAP?: HiAP is an approach to public policies across sectors that systematically takes into account the health implications of decisions, seeks synergies and avoids harmful health impacts in order to improve population health and health equity. As a concept, it reflects the principles of: legitimacy, accountability, transparency and access to information, participation, sustainability and collaboration across sectors and levels of government. Health and health equity are values in their own right and are also important prerequisites for achieving many other societal goals. Many of the determinants of health and health inequities in populations have social, environmental and economic origins that extend beyond the direct influence of the health sector and health policies. Thus, public policies in all sectors and at different levels of governance can have a significant impact on population health and health equity. The Framework sets out six key components that should be addressed in order to put the HiAP approach into action: (1) establish the need and priorities for HiAP, (2) frame planned action, (3) identify supportive structures and processes, (4) facilitate assessment and engagement, (5) ensure monitoring, evaluation and reporting, (6) build capacity. These components are not fixed in order or priority. Rather, individual countries will adopt and adjust the components in ways that are most relevant for their specific governance, economic and social contexts. Although governments as a whole bear the ultimate responsibility for the health of their citizens, health authorities at all levels are key actors in promoting HiAP. They should therefore actively seek opportunities to collaborate with and

  12. Synthesis and properties of ApA analogues with shortened phosphonate internucleotide linkage.

    PubMed

    Králíková, Sárka; Buděšínský, Miloš; Barvík, Ivan; Masojídková, Milena; Točík, Zdeněk; Rosenberg, Ivan

    2011-01-01

    A complete series of the 2 '-5 ' and 3 '-5 ' regioisomeric types of r(ApA) and 2 '-d(ApA) analogues with the α-hydroxy-phosphonate C3 '-O-P-CH(OH)-C4 ″ internucleotide linkage, isopolar but non-isosteric with the phosphodiester one, were synthesized and their hybridization properties with polyU studied. Due to the chirality on the 5 '-carbon atom of the modified internucleotide linkage bearing phosphorus and hydroxy moieties, each regioisomeric type of ApA dimer is split into epimeric pairs. To examine the role of the 5 '-hydroxyl of the α-hydroxy-phosphonate moiety during hybridization, the appropriate r(ApA) analogues with 3 '(2 ')-O-P-CH(2)-C4 ″ linkage lacking the 5 '-hydroxyl were synthesized. Nuclear magnetic resonance (NMR) spectroscopy study on the conformation of the modified sugar-phosphate backbone, along with the hybridization measurements, revealed remarkable differences in the stability of complexes with polyU, depending on the 5 '-carbon atom configuration. Potential usefulness of the α-hydroxy-phosphonate linkage in modified oligoribonucleotides is discussed.

  13. Internet-Protocol-Based Satellite Bus Architecture Designed

    NASA Technical Reports Server (NTRS)

    Slywczak, Richard A.

    2004-01-01

    NASA is designing future complex satellite missions ranging from single satellites and constellations to space networks and sensor webs. These missions require more interoperability, autonomy, and coordination than previous missions; in addition, a desire exists to have scientists retrieve data directly from the satellite rather than a central distribution source. To meet these goals, NASA has been studying the possibility of extending the Transmission Control Protocol/Internet Protocol (TCP/IP) suite for spacebased applications.

  14. Determination of the influence of C24 D/(2R)- and L/(2S)-isomers of the CER[AP] on the lamellar structure of stratum corneum model systems using neutron diffraction.

    PubMed

    Schmitt, Thomas; Lange, Stefan; Sonnenberger, Stefan; Dobner, Bodo; Demé, Bruno; Neubert, Reinhard H H; Gooris, Gert; Bouwstra, Joke A

    2017-12-01

    This study was able to investigate the different influence of the d- and l-ceramide [AP] on the lamellar as well as molecular nanostructure of stratum corneum simulating lipid model mixtures. In this case, neutron diffraction together with specifically deuterated ceramide was used as an effective tool to investigate the lamellar and the molecular nanostructure of the mixtures. It could clearly be demonstrated, that both isomers show distinctly different characteristics, even though the variation between both is only a single differently arranged OH-group. The l-ceramide [AP] promotes a crystalline like phase behaviour even if mixed with ceramide [NP], cholesterol and free fatty acids. The d-ceramide [AP] only shows crystalline-like features if mixed only with cholesterol and free fatty acids but adopts a native-like behaviour if additionally mixed with ceramide [NP]. It furthermore demonstrates that the l-ceramide [AP] should not be used for any applications concerning ceramide substitution. It could however possibly serve its own purpose, if this crystalline like behaviour has some kind of positive influence on the SC or can be utilized for any practical applications. The results obtained in this study demonstrate that the diastereomers of ceramide [AP] are an attractive target for further research because their influence on the lamellar as well as the nanostructure is exceptionally strong. Additionally, the results furthermore show a very strong influence on hydration of the model membrane. With these properties, the d-ceramide [AP] could be effectively used to simulate native like behaviour even in very simple mixtures and could also have a strong impact on the native stratum corneum as well as high relevance for dermal ceramide substitution. The unnatural l-ceramide [AP] on the other hand should be investigated further, to assess its applicability. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Crystal structure of wild-type and mutant human Ap4A hydrolase.

    PubMed

    Ge, Honghua; Chen, Xiaofang; Yang, Weili; Niu, Liwen; Teng, Maikun

    2013-03-01

    Ap4A hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17), an enzyme involved in a number of biological processes, is characterized as cleaving the polyphosphate chain at the fourth phosphate from the bound adenosine moiety. This paper presents the crystal structure of wild-type and E58A mutant human Ap4A hydrolase. Similar to the canonical Nudix fold, human Ap4A hydrolase shows the common αβα-sandwich architecture. Interestingly, two sulfate ions and one diphosphate coordinated with some conserved residues were observed in the active cleft, which affords a better understanding of a possible mode of substrate binding. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Kinetic and thermodynamic studies of bovine serum albumin interaction with ascorbyl palmitate and ascorbyl stearate food additives using surface plasmon resonance.

    PubMed

    Fathi, Farzaneh; Mohammadzadeh-Aghdash, Hossein; Sohrabi, Yousef; Dehghan, Parvin; Ezzati Nazhad Dolatabadi, Jafar

    2018-04-25

    Ascorbyl palmitate (AP) and ascorbyl stearate (AS) are examples of food additives, which have extensive use in food industry. In this study, we evaluated the interaction of bovine serum albumin (BSA) with AP and AS using surface plasmon resonance (SPR). In order to immobilize BSA, carboxymethyl dextran hydrogel (CMD) Au chip was used. After activation of carboxylic groups, BSA was immobilized onto the CMD chip through covalent amide binding formation. AP and AS binding to immobilized BSA at different concentrations was assessed. The dose-response sensorgrams of BSA upon increasing concentration of AP and AS have been shown. The low value of equilibrium dissociation constant or affinity unit (K D ) showed high affinity of both AP and AS to BSA. The K D value for binding of AP and AS to BSA were 4.09 × 10 -5 and 1.89 × 10 -5 , at 25 °C. Overall, the attained results showed that AP and AS molecules can bind to BSA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Engaging Cuban Physicists Through the APS/CPS Partnership

    NASA Astrophysics Data System (ADS)

    Lerch, Irving A.; Lerch, Irving A.

    In his reflections on Cuban physics, Marcelo Alonso urges APS to take steps to promote interactions between Cuban and US physicists. As an introduction to Marcello's essay, this note will summarize past and current activities.

  18. Development of an HPV Educational Protocol for Adolescents

    PubMed Central

    Wetzel, Caitlin; Tissot, Abbigail; Kollar, Linda M.; Hillard, Paula A.; Stone, Rachel; Kahn, Jessica A.

    2007-01-01

    Study Objectives To develop an educational protocol about HPV and Pap tests for adolescents, to evaluate the protocol for understandability and clarity, and to evaluate the protocol for its effectiveness in increasing knowledge about HPV. Design In phase 1, investigators and adolescents developed the protocol. In phase 2, adolescents evaluated the protocol qualitatively, investigators evaluated its effectiveness in increasing HPV knowledge in a sample of adolescents, and the protocol was revised. In phase 3, investigators evaluated the effectiveness of the revised protocol in an additional adolescent sample. Setting Urban, hospital-based teen health center. Participants A total of 252 adolescent girls and boys in the three study phases. Main Outcome Measures Pre- and post-protocol knowledge about HPV, measured using a 10- or 11-item scale. Results Scores on the HPV knowledge scale increased significantly (p<.0001) among adolescents who participated in phases 2 and 3 after they received the protocol. Initial differences in scores based on race, insurance type and condom use were not noted post-protocol. Conclusion The protocol significantly increased knowledge scores about HPV in this population, regardless of sociodemographic characteristics and risk behaviors. Effective, developmentally appropriate educational protocols about HPV and Pap tests are particularly important in clinical settings as cervical cancer screening guidelines evolve, HPV DNA testing is integrated into screening protocols, and HPV vaccines become available. In-depth, one-on-one education about HPV may also prevent adverse psychosocial responses and promote healthy sexual and Pap screening behaviors in adolescents with abnormal HPV or Pap test results. Synopsis The investigators developed an educational protocol about HPV and Pap tests and evaluated its effectiveness in increasing knowledge about HPV among adolescents. PMID:17868894

  19. MAPK/AP-1-Targeted Anti-Inflammatory Activities of Xanthium strumarium.

    PubMed

    Hossen, Muhammad Jahangir; Kim, Mi-Yeon; Cho, Jae Youl

    2016-01-01

    Xanthium strumarium L. (Asteraceae), a traditional Chinese medicine, is prescribed to treat arthritis, bronchitis, and rhinitis. Although the plant has been used for many years, the mechanism by which it ameliorates various inflammatory diseases is not yet fully understood. To explore the anti-inflammatory mechanism of methanol extracts of X. strumarium (Xs-ME) and its therapeutic potential, we used lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells and human monocyte-like U937 cells as well as a LPS/D-galactosamine (GalN)-induced acute hepatitis mouse model. To find the target inflammatory pathway, we used holistic immunoblotting analysis, reporter gene assays, and mRNA analysis. Xs-ME significantly suppressed the up-regulation of both the activator protein (AP)-1-mediated luciferase activity and the production of LPS-induced proinflammatory cytokines, including interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor (TNF)-[Formula: see text]. Moreover, Xs-ME strongly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW264.7 and U937 cells. Additionally, these results highlighted the hepatoprotective and curative effects of Xs-ME in a mouse model of LPS/D-GalN-induced acute liver injury, as assessed by elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and histological damage. Therefore, our results strongly suggest that the ethnopharmacological roles of Xs-ME in hepatitis and other inflammatory diseases might result from its inhibitory activities on the inflammatory signaling of MAPK and AP-1.

  20. AP1S3 mutations are associated with pustular psoriasis and impaired Toll-like receptor 3 trafficking.

    PubMed

    Setta-Kaffetzi, Niovi; Simpson, Michael A; Navarini, Alexander A; Patel, Varsha M; Lu, Hui-Chun; Allen, Michael H; Duckworth, Michael; Bachelez, Hervé; Burden, A David; Choon, Siew-Eng; Griffiths, Christopher E M; Kirby, Brian; Kolios, Antonios; Seyger, Marieke M B; Prins, Christa; Smahi, Asma; Trembath, Richard C; Fraternali, Franca; Smith, Catherine H; Barker, Jonathan N; Capon, Francesca

    2014-05-01

    Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  1. Genomic and transcriptomic analysis of the AP2/ERF superfamily in Vitis vinifera

    PubMed Central

    2010-01-01

    Background The AP2/ERF protein family contains transcription factors that play a crucial role in plant growth and development and in response to biotic and abiotic stress conditions in plants. Grapevine (Vitis vinifera) is the only woody crop whose genome has been fully sequenced. So far, no detailed expression profile of AP2/ERF-like genes is available for grapevine. Results An exhaustive search for AP2/ERF genes was carried out on the Vitis vinifera genome and their expression profile was analyzed by Real-Time quantitative PCR (qRT-PCR) in different vegetative and reproductive tissues and under two different ripening stages. One hundred and forty nine sequences, containing at least one ERF domain, were identified. Specific clusters within the AP2 and ERF families showed conserved expression patterns reminiscent of other species and grapevine specific trends related to berry ripening. Moreover, putative targets of group IX ERFs were identified by co-expression and protein similarity comparisons. Conclusions The grapevine genome contains an amount of AP2/ERF genes comparable to that of other dicot species analyzed so far. We observed an increase in the size of specific groups within the ERF family, probably due to recent duplication events. Expression analyses in different aerial tissues display common features previously described in other plant systems and introduce possible new roles for members of some ERF groups during fruit ripening. The presented analysis of AP2/ERF genes in grapevine provides the bases for studying the molecular regulation of berry development and the ripening process. PMID:21171999

  2. Should particle size analysis data be combined with EPA approved sampling method data in the development of AP-42 emission factors?

    USDA-ARS?s Scientific Manuscript database

    A cotton ginning industry-supported project was initiated in 2008 and completed in 2013 to collect additional data for U.S. Environmental Protection Agency’s (EPA) Compilation of Air Pollution Emission Factors (AP-42) for PM10 and PM2.5. Stack emissions were collected using particle size distributio...

  3. [Atp6ap2/ (Pro) renin Receptor is Required for Laminar Formation during Retinal Development in Mice].

    PubMed

    Kanda, Atsuhiro

    2015-11-01

    (Pro) renin receptor [(P) RR], a key molecule for tissue renin-angiotensin system, was originally identified as Atp6ap2, an accessory subunit for vacuolar H(+)-ATPase that is a multi-subunit proton pump involved in fundamental cellular physiology. In this study, to elucidate the physiological functions of Atp6ap2/ (P) RR during retinal development in mammals, we used Cre-LoxP system to generate photoreceptor-specific conditional knock-out (CKO) mice, and revealed a critical role of Atp6ap2/(P) RR in photoreceptor development. Deletion of photoreceptor Atp6ap2/ (P) RR did not affect retinal cell differentiation, but led to laminar disorganization in the photoreceptor layer with dysfunction of photoreceptors. Cell adhesion and polarity molecules, all of which were co-localized with Atp6ap2 at the apical edge of the developing retina, were dispersed together with mislocalization of retinal progenitors apart from the apical surface in Atp6ap2 conditional knockout mice. Among these molecules, co-immunoprecipitation using retinal homogenates and Atp6ap2/(P) RR-transfected cells showed that Atp6ap2/(P) RR interacted with partitioning defective 3 homolog (Par3) protein, known to play a pivotal role in planar cell polarity in the Par-atypical protein kinase C system. Atp6ap2 interacted with Par3 protein that plays a pivotal role in planar cell polarity. Our data provide a novel function of Atp6ap2 required as a cell polarity determinant for retinal laminar formation.

  4. Cultural Diversity in AP Art History

    ERIC Educational Resources Information Center

    Bolte, Frances R.

    2006-01-01

    Teaching AP Art History is like running on a treadmill that is moving faster than a teacher can run. Many teachers are out of breath before the end of the term and wonder how in the world they can cover every chapter. Because time is short and art from pre-history through to the present, including the non-European traditions, must be covered, this…

  5. An Insider's History of Some of the Significant Changes In the APS from the 1960s to Today

    NASA Astrophysics Data System (ADS)

    Schwartz, Brian

    2014-03-01

    It has been over 50 years since I first joined the American Physical Society. A lot has changed. The APS in the 60s did not have a single Forum and all divisions were related to sub-field of physics research plus the History of Physics Division. The APS governance and meeting's structure did not provide for issues relate to physics and society, undergraduate and graduate education, minorities, women, industrial physics, international physics, communication of science, and many more subjects quite typical of APS in 2014. From the start, I was a very active member of APS and one of the original petitioners for the Division on Physics and Society. Ultimately this led to the APS Forum structure, the Panel on Public Affairs and many APS formal committees. Two of the major impetuses for change in the late 60s were the need to debate the role of science in the unpopular war in Vietnam and the overproduction and poor employment prospects for new Ph.D.s. I, and colleagues, (with little original encouragement from the APS leadership), arranged for the discussion on many new topics at the meeting and proposed changes within the governance of the Society. In the late 1980s I joined the APS and was involved in many changes over the next 20 years. ultimately as Associate Executive Officer and Director of the APS Centennial in 1999. As indicated earlier, I've been with the APS for over 50 years and will present its history as a participant-insider. Topic covered include my surprise election to the APS governance in 1972, the establishment of the Forum on Physics and Society (and the restrictions imposed on its governance), my role as the father (or mother) of the women's movement at APS, the complexities and politics of the move of APS headquarters from New York to College Park, the establishment of the tabloid APS News and many more subjects. Currently I am producing staged-readings of science-based plays at the March and April 2014 APS meetings for the Forum on History of

  6. 78 FR 19691 - Applications for New Awards; Advanced Placement (AP) Test Fee Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-02

    ... DEPARTMENT OF EDUCATION Applications for New Awards; Advanced Placement (AP) Test Fee Program... Information Advanced Placement Test Fee Program. Notice inviting applications for new awards for fiscal year... Program: The AP Test Fee program awards grants to eligible State educational agencies (SEAs) to enable...

  7. 77 FR 8848 - Application for New Awards; Advanced Placement (AP) Test Fee Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-15

    ... DEPARTMENT OF EDUCATION Application for New Awards; Advanced Placement (AP) Test Fee Program... Information: Advanced Placement Test Fee Program. Notice inviting applications for new awards for fiscal year... Description Purpose of Program: The AP Test Fee program awards grants to eligible State educational agencies...

  8. A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling

    PubMed Central

    Beautrait, Alexandre; Paradis, Justine S.; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M.; Khoury, Etienne; Audet, Martin; Roux, Philippe P.; Veprintsev, Dmitry B.; Laporte, Stéphane A.; Bouvier, Michel

    2017-01-01

    In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes. This selective β-arrestin/β2-adaptin inhibitor (Barbadin) blocks agonist-promoted endocytosis of the prototypical β2-adrenergic (β2AR), V2-vasopressin (V2R) and angiotensin-II type-1 (AT1R) receptors, but does not affect β-arrestin-independent (transferrin) or AP2-independent (endothelin-A) receptor internalization. Interestingly, Barbadin fully blocks V2R-stimulated ERK1/2 activation and blunts cAMP accumulation promoted by both V2R and β2AR, supporting the concept of β-arrestin/AP2-dependent signalling for both G protein-dependent and -independent pathways. PMID:28416805

  9. Protocol biopsies in renal transplantation: prognostic value of structural monitoring.

    PubMed

    Serón, D; Moreso, F

    2007-09-01

    The natural history of renal allograft damage has been characterized in serial protocol biopsies. The prevalence of subclinical rejection (SCR) is maximal during the first months and it is associated with the progression of interstitial fibrosis/tubular atrophy (IF/TA) and a decreased graft survival. IF/TA rapidly progress during the first months and constitutes an independent predictor of graft survival. IF/TA associated with transplant vasculopathy, SCR, or transplant glomerulopathy implies a poorer prognosis than IF/TA without additional lesions. These observations suggest that protocol biopsies could be considered a surrogate of graft survival. Preliminary data suggest that the predictive value of protocol biopsies is not inferior to acute rejection or renal function. Additionally, protocol biopsies have been employed as a secondary efficacy variable in clinical trials. This strategy has been useful to demonstrate a decrease in the progression of IF/TA in some calcineurin-free regimens. Quantification of renal damage is associated with graft survival suggesting that quantitative parameters might improve the predictive value of protocol biopsies. Validation of protocol biopsies as a surrogate of graft survival is actively pursued, as the utility of classical surrogates of graft outcome such as acute rejection has become less useful because of its decreased prevalence with actual immunosuppression.

  10. Preparation and characterization of superfine ammonium perchlorate (AP) crystals through ceramic membrane anti-solvent crystallization

    NASA Astrophysics Data System (ADS)

    Ma, Zhenye; Li, Cheng; Wu, Rujun; Chen, Rizhi; Gu, Zhenggui

    2009-10-01

    In this paper, a novel ceramic membrane anti-solvent crystallization (CMASC) method was proposed for the safe and rapid preparation ammonium perchlorate (AP) crystals, in which the acetone and ethyl acetate were chosen as solvent and anti-solvent, respectively. Comparing with the conventional liquid anti-solvent crystallization (LASC), CMASC which successfully introduces ceramic membrane with regular pore structure to the LASC as feeding medium, is favorable to control the rate of feeding rate and, therefore, to obtain size and morphology controllable AP. Several kinds of micro-sized AP particles with different morphology were obtained including polyhedral-like, quadrate-like to rod-like. The effect of processing parameters on the crystal size and shape of AP crystals such as volume ratio of anti-solvent to solvent, feeding pressure and crystallization temperature were investigated. It is found that higher volume ratio of anti-solvent to solvent, higher feeding pressure and higher temperature result in smaller particle size. Scaning electron microscopy (SEM) and X-ray diffraction (XRD) were used to characterize the resulting AP crystals. The nucleation and growth kinetic of the resulting AP crystals were also discussed.

  11. Overexpression of two PsnAP1 genes from Populus simonii × P. nigra causes early flowering in transgenic tobacco and Arabidopsis.

    PubMed

    Zheng, Tangchun; Li, Shuang; Zang, Lina; Dai, Lijuan; Yang, Chuanping; Qu, Guan-Zheng

    2014-01-01

    In Arabidopsis, AP1 is a floral meristem identity gene and plays an important role in floral organ development. In this study, PsnAP1-1 and PsnAP1-2 were isolated from the male reproductive buds of poplar (Populus simonii × P. nigra), which are the orthologs of AP1 in Arabidopsis, by sequence analysis. Northern blot and qRT-PCR analysis showed that PsnAP1-1 and PsnAP1-2 exhibited high expression level in early inflorescence development of poplar. Subcellular localization showed the PsnAP1-1 and PsnAP1-2 proteins are localized in the nucleus. Overexpression of PsnAP1-1 and PsnAP1-2 in tobacco under the control of a CaMV 35S promoter significantly enhanced early flowering. These transgenic plants also showed much earlier stem initiation and higher rates of photosynthesis than did wild-type tobacco. qRT-PCR analysis further indicated that overexpression of PsnAP1-1 and PsnAP1-2 resulted in up-regulation of genes related to flowering, such as NtMADS4, NtMADS5 and NtMADS11. Overexpression of PsnAP1-1 and PsnAP1-2 in Arabidopsis also induced early flowering, but did not complement the ap1-10 floral morphology to any noticeable extent. This study indicates that PsnAP1-1 and PsnAP1-2 play a role in floral transition of poplar.

  12. Overexpression of Two PsnAP1 Genes from Populus simonii × P. nigra Causes Early Flowering in Transgenic Tobacco and Arabidopsis

    PubMed Central

    Zheng, Tangchun; Li, Shuang; Zang, Lina; Dai, Lijuan; Yang, Chuanping; Qu, Guan-Zheng

    2014-01-01

    In Arabidopsis, AP1 is a floral meristem identity gene and plays an important role in floral organ development. In this study, PsnAP1-1 and PsnAP1-2 were isolated from the male reproductive buds of poplar (Populus simonii × P. nigra), which are the orthologs of AP1 in Arabidopsis, by sequence analysis. Northern blot and qRT-PCR analysis showed that PsnAP1-1 and PsnAP1-2 exhibited high expression level in early inflorescence development of poplar. Subcellular localization showed the PsnAP1-1 and PsnAP1-2 proteins are localized in the nucleus. Overexpression of PsnAP1-1 and PsnAP1-2 in tobacco under the control of a CaMV 35S promoter significantly enhanced early flowering. These transgenic plants also showed much earlier stem initiation and higher rates of photosynthesis than did wild-type tobacco. qRT-PCR analysis further indicated that overexpression of PsnAP1-1 and PsnAP1-2 resulted in up-regulation of genes related to flowering, such as NtMADS4, NtMADS5 and NtMADS11. Overexpression of PsnAP1-1 and PsnAP1-2 in Arabidopsis also induced early flowering, but did not complement the ap1-10 floral morphology to any noticeable extent. This study indicates that PsnAP1-1 and PsnAP1-2 play a role in floral transition of poplar. PMID:25360739

  13. College Board Readies Plans for AP Audits

    ERIC Educational Resources Information Center

    Klein, Alyson

    2006-01-01

    This article describes the educators mixed reviews regarding the audit system planned by the College Board to scrutinize high school Advanced Placement courses. Teachers of AP courses are required to submit materials to the College Board proving that their course syllabuses meet the program's curricular requirements. It is the most extensive…

  14. Broadening and Simplifying the First SETI Protocol

    NASA Astrophysics Data System (ADS)

    Michaud, M. A. G.

    The Declaration of Principles Concerning Activities Following the Detection of Extraterrestrial Intelligence, known informally as the First SETI Protocol, is the primary existing international guidance on this subject. During the fifteen years since the document was issued, several people have suggested revisions or additional protocols. This article proposes a broadened and simplified text that would apply to the detection of alien technology in our solar system as well as to electromagnetic signals from more remote sources.

  15. Automated Plasma Spray (APS) process feasibility study: Plasma spray process development and evaluation

    NASA Technical Reports Server (NTRS)

    Fetheroff, C. W.; Derkacs, T.; Matay, I. M.

    1979-01-01

    An automated plasma spray (APS) process was developed to apply two layer (NiCrAlY and ZrO2-12Y2O3) thermal-barrier coatings to aircraft gas turbine engine blade airfoils. The APS process hardware consists of four subsystems: a mechanical blade positioner incorporating two interlaced six-degree-of-freedom assemblies; a noncoherent optical metrology subsystem; a microprocessor-based adaptive system controller; and commercial plasma spray equipment. Over fifty JT9D first stage turbine blades specimens were coated with the APS process in preliminary checkout and evaluation studies. The best of the preliminary specimens achieved an overall coating thickness uniformity of + or - 53 micrometers, much better than is achievable manually. Factors limiting this performance were identified and process modifications were initiated accordingly. Comparative evaluations of coating thickness uniformity for manually sprayed and APS coated specimens were initiated. One of the preliminary evaluation specimens was subjected to a torch test and metallographic evaluation.

  16. A Secure Authenticated Key Exchange Protocol for Credential Services

    NASA Astrophysics Data System (ADS)

    Shin, Seonghan; Kobara, Kazukuni; Imai, Hideki

    In this paper, we propose a leakage-resilient and proactive authenticated key exchange (called LRP-AKE) protocol for credential services which provides not only a higher level of security against leakage of stored secrets but also secrecy of private key with respect to the involving server. And we show that the LRP-AKE protocol is provably secure in the random oracle model with the reduction to the computational Difie-Hellman problem. In addition, we discuss about some possible applications of the LRP-AKE protocol.

  17. PKC-dependent stimulation of the human MCT1 promoter involves transcription factor AP2.

    PubMed

    Saksena, Seema; Dwivedi, Alka; Gill, Ravinder K; Singla, Amika; Alrefai, Waddah A; Malakooti, Jaleh; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K

    2009-02-01

    Monocarboxylate transporter (MCT1) plays an important role in the absorption of short-chain fatty acids (SCFA) such as butyrate in the human colon. Previous studies from our laboratory have demonstrated that phorbol ester, PMA (1 microM, 24 h), upregulates butyrate transport and MCT1 protein expression in human intestinal Caco-2 cells. However, the molecular mechanisms involved in the transcriptional regulation of MCT1 gene expression by PMA in the intestine are not known. In the present study, we showed that PMA (0.1 microM, 24 h) increased the MCT1 promoter activity (-871/+91) by approximately fourfold. A corresponding increase in MCT1 mRNA abundance in response to PMA was also observed. PMA-induced stimulation of MCT1 promoter activity was observed as early as 1 h and persisted until 24 h, suggesting that the effects of PMA are attributable to initial PKC activation. Kinase inhibitor and phosphorylation studies indicated that these effects may be mediated through activation of the atypical PKC-zeta isoform. 5'-deletion studies demonstrated that the MCT1 core promoter region (-229/+91) is the PMA-responsive region. Site-directed mutagenesis studies showed the predominant involvement of potential activator protein 2 (AP2) binding site in the activation of MCT1 promoter activity by PMA. In addition, overexpression of AP2 in Caco-2 cells significantly increased MCT1 promoter activity in a dose-dependent manner. These findings showing the regulation of MCT1 promoter by PKC and AP2 are of significant importance for an understanding of the molecular regulation of SCFA absorption in the human intestine.

  18. An Ap-Structure with Finslerian Flavor II:. Torsion, Curvature and Other Objects

    NASA Astrophysics Data System (ADS)

    Wanas, M. I.; Kamal, Mona M.

    An absolute parallelism (AP-) space having Finslerian properties is called FAP-space. This FAP-structure is wider than both conventional AP and Finsler structures. In the present work, more geometric objects as curvature and torsion tensors are derived in the context of this structure. Also second order tensors, usually needed for physical applications, are derived and studied. Furthermore, the anti-curvature and the W-tensor are defined for the FAP-structure. Relations between Riemannian, AP, Finsler and FAP structures are given. These relations facilitate comparison between results of applications carried out in the framework of these structures. We hope that the use of the FAP-structure, in applications may throw some light on some of the problems facing geometric field theories.

  19. The Robinson Protocol: a treadmill anaerobic performance test.

    PubMed

    Robinson, Ellyn M; Graham, Louise B; Headley, Samuel A

    2004-08-01

    The current investigation was designed to further examine the reliability of the Robinson protocol, which is a run-to-exhaustion treadmill test. Robinson (10) originally examined this protocol with 5 subjects. The significance of the initial exploratory study was the impetus for expanding the study to examine the reliability of the protocol with a larger sample. Fifteen male subjects participated in 3 trial runs on the treadmill. The first trial was a modified McConnell (7) test to determine the aerobic capacity of each subject. The second and third trials were identical Robinson protocols (10). The first trial run mean, in seconds (262.04 +/- 74.50), was not significantly different from the second trial run mean (257.30 +/- 72.65), p = 0.526 (2 tailed). As expected, trial 1 and trial 2 were highly correlated (intraclass) (r = 0.927, p < 0.001). These results provide additional support for the hypothesis that the Robinson protocol with a greater subject pool is a reliable protocol that can be used in research studies interested in examining various physiological interventions or anaerobic training.

  20. Design and Verification of a Distributed Communication Protocol

    NASA Technical Reports Server (NTRS)

    Munoz, Cesar A.; Goodloe, Alwyn E.

    2009-01-01

    The safety of remotely operated vehicles depends on the correctness of the distributed protocol that facilitates the communication between the vehicle and the operator. A failure in this communication can result in catastrophic loss of the vehicle. To complicate matters, the communication system may be required to satisfy several, possibly conflicting, requirements. The design of protocols is typically an informal process based on successive iterations of a prototype implementation. Yet distributed protocols are notoriously difficult to get correct using such informal techniques. We present a formal specification of the design of a distributed protocol intended for use in a remotely operated vehicle, which is built from the composition of several simpler protocols. We demonstrate proof strategies that allow us to prove properties of each component protocol individually while ensuring that the property is preserved in the composition forming the entire system. Given that designs are likely to evolve as additional requirements emerge, we show how we have automated most of the repetitive proof steps to enable verification of rapidly changing designs.

  1. Automated Procurement System (APS): Project management plan (DS-03), version 1.2

    NASA Technical Reports Server (NTRS)

    Murphy, Diane R.

    1994-01-01

    The National Aeronautics and Space Administration (NASA) Marshall Space Flight Center (MSFC) is implementing an Automated Procurement System (APS) to streamline its business activities that are used to procure goods and services. This Project Management Plan (PMP) is the governing document throughout the implementation process and is identified as the APS Project Management Plan (DS-03). At this point in time, the project plan includes the schedules and tasks necessary to proceed through implementation. Since the basis of APS is an existing COTS system, the implementation process is revised from the standard SDLC. The purpose of the PMP is to provide the framework for the implementation process. It discusses the roles and responsibilities of the NASA project staff, the functions to be performed by the APS Development Contractor (PAI), and the support required of the NASA computer support contractor (CSC). To be successful, these three organizations must work together as a team, working towards the goals established in this Project Plan. The Project Plan includes a description of the proposed system, describes the work to be done, establishes a schedule of deliverables, and discusses the major standards and procedures to be followed.

  2. A Study of Shared-Memory Mutual Exclusion Protocols Using CADP

    NASA Astrophysics Data System (ADS)

    Mateescu, Radu; Serwe, Wendelin

    Mutual exclusion protocols are an essential building block of concurrent systems: indeed, such a protocol is required whenever a shared resource has to be protected against concurrent non-atomic accesses. Hence, many variants of mutual exclusion protocols exist in the shared-memory setting, such as Peterson's or Dekker's well-known protocols. Although the functional correctness of these protocols has been studied extensively, relatively little attention has been paid to their non-functional aspects, such as their performance in the long run. In this paper, we report on experiments with the performance evaluation of mutual exclusion protocols using Interactive Markov Chains. Steady-state analysis provides an additional criterion for comparing protocols, which complements the verification of their functional properties. We also carefully re-examined the functional properties, whose accurate formulation as temporal logic formulas in the action-based setting turns out to be quite involved.

  3. 75 FR 20774 - Establishment of Class E Airspace; Fort A.P. Hill, VA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    ...-0739; Airspace Docket No. 09-AEA-14] Establishment of Class E Airspace; Fort A.P. Hill, VA AGENCY... December 7, 2009 that establishes Class E airspace at Fort A.P. Hill, VA. DATES: Effective Date: 0901 UTC... Service Center, Federal Aviation Administration, P.O. Box 20636, Atlanta, Georgia 30320; telephone (404...

  4. A glossary of terms for understanding political aspects in the implementation of Health in All Policies (HiAP).

    PubMed

    Oneka, Goldameir; Vahid Shahidi, Faraz; Muntaner, Carles; Bayoumi, Ahmed M; Mahabir, Deb Finn; Freiler, Alix; O'Campo, Patricia; Shankardass, Ketan

    2017-08-01

    Health in All Policies (HiAP) is a strategy that seeks to integrate health considerations into the development, implementation and evaluation of policies across various non-health sectors of the government. Over the past 15 years, there has been an increase in the uptake of HiAP by local, regional and national governments. Despite the growing popularity of this approach, most existing literature on HiAP implementation remains descriptive rather than explanatory in its orientation. Moreover, prior research has focused on the more technical aspects of the implementation process. Thus, studies that aim to 'build capacity to promote, implement and evaluate HiAP' abound. Conversely, there is little emphasis on the political aspects of HiAP implementation. Neglecting the role of politics in shaping the use of HiAP is problematic, since health and the strategies by which it is promoted are partially political.This glossary addresses the politics gap in the existing literature by drawing on theoretical concepts from political, policy, and public health sciences to articulate a framework for studying how political mechanisms influence HiAP implementation. To this end, the glossary forms part of an on-going multiple explanatory case study of HiAP implementation, HARMONICS (HiAP Analysis using Realist Methods on International Case Studies, harmonics-hiap.ca), and is meant to expand on a previously published glossary addressing the topic of HiAP implementation more broadly. Collectively, these glossaries offer a conceptual toolkit for understanding how politics explains implementation outcomes of HiAP. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection

    PubMed Central

    Pérez-Núñez, Daniel; García-Urdiales, Eduardo; Martínez-Bonet, Marta; Nogal, María L.; Barroso, Susana; Revilla, Yolanda; Madrid, Ricardo

    2015-01-01

    African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN) protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity. PMID:25915900

  6. CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection.

    PubMed

    Pérez-Núñez, Daniel; García-Urdiales, Eduardo; Martínez-Bonet, Marta; Nogal, María L; Barroso, Susana; Revilla, Yolanda; Madrid, Ricardo

    2015-01-01

    African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN) protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity.

  7. AP-Cloud: Adaptive particle-in-cloud method for optimal solutions to Vlasov–Poisson equation

    DOE PAGES

    Wang, Xingyu; Samulyak, Roman; Jiao, Xiangmin; ...

    2016-04-19

    We propose a new adaptive Particle-in-Cloud (AP-Cloud) method for obtaining optimal numerical solutions to the Vlasov–Poisson equation. Unlike the traditional particle-in-cell (PIC) method, which is commonly used for solving this problem, the AP-Cloud adaptively selects computational nodes or particles to deliver higher accuracy and efficiency when the particle distribution is highly non-uniform. Unlike other adaptive techniques for PIC, our method balances the errors in PDE discretization and Monte Carlo integration, and discretizes the differential operators using a generalized finite difference (GFD) method based on a weighted least square formulation. As a result, AP-Cloud is independent of the geometric shapes ofmore » computational domains and is free of artificial parameters. Efficient and robust implementation is achieved through an octree data structure with 2:1 balance. We analyze the accuracy and convergence order of AP-Cloud theoretically, and verify the method using an electrostatic problem of a particle beam with halo. Here, simulation results show that the AP-Cloud method is substantially more accurate and faster than the traditional PIC, and it is free of artificial forces that are typical for some adaptive PIC techniques.« less

  8. AP-Cloud: Adaptive Particle-in-Cloud method for optimal solutions to Vlasov–Poisson equation

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

    Wang, Xingyu; Samulyak, Roman, E-mail: roman.samulyak@stonybrook.edu; Computational Science Initiative, Brookhaven National Laboratory, Upton, NY 11973

    We propose a new adaptive Particle-in-Cloud (AP-Cloud) method for obtaining optimal numerical solutions to the Vlasov–Poisson equation. Unlike the traditional particle-in-cell (PIC) method, which is commonly used for solving this problem, the AP-Cloud adaptively selects computational nodes or particles to deliver higher accuracy and efficiency when the particle distribution is highly non-uniform. Unlike other adaptive techniques for PIC, our method balances the errors in PDE discretization and Monte Carlo integration, and discretizes the differential operators using a generalized finite difference (GFD) method based on a weighted least square formulation. As a result, AP-Cloud is independent of the geometric shapes ofmore » computational domains and is free of artificial parameters. Efficient and robust implementation is achieved through an octree data structure with 2:1 balance. We analyze the accuracy and convergence order of AP-Cloud theoretically, and verify the method using an electrostatic problem of a particle beam with halo. Simulation results show that the AP-Cloud method is substantially more accurate and faster than the traditional PIC, and it is free of artificial forces that are typical for some adaptive PIC techniques.« less

  9. AP-Cloud: Adaptive particle-in-cloud method for optimal solutions to Vlasov–Poisson equation

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

    Wang, Xingyu; Samulyak, Roman; Jiao, Xiangmin

    We propose a new adaptive Particle-in-Cloud (AP-Cloud) method for obtaining optimal numerical solutions to the Vlasov–Poisson equation. Unlike the traditional particle-in-cell (PIC) method, which is commonly used for solving this problem, the AP-Cloud adaptively selects computational nodes or particles to deliver higher accuracy and efficiency when the particle distribution is highly non-uniform. Unlike other adaptive techniques for PIC, our method balances the errors in PDE discretization and Monte Carlo integration, and discretizes the differential operators using a generalized finite difference (GFD) method based on a weighted least square formulation. As a result, AP-Cloud is independent of the geometric shapes ofmore » computational domains and is free of artificial parameters. Efficient and robust implementation is achieved through an octree data structure with 2:1 balance. We analyze the accuracy and convergence order of AP-Cloud theoretically, and verify the method using an electrostatic problem of a particle beam with halo. Here, simulation results show that the AP-Cloud method is substantially more accurate and faster than the traditional PIC, and it is free of artificial forces that are typical for some adaptive PIC techniques.« less

  10. How good are GPs at adhering to a pragmatic trial protocol in primary care? Results from the ADDITION-Cambridge cluster-randomised pragmatic trial

    PubMed Central

    Boothby, Clare E; Griffin, Simon J

    2018-01-01

    Objective To assess the fidelity of general practitioners’ (GPs) adherence to a long-term pragmatic trial protocol. Design Retrospective analyses of electronic primary care records of participants in the pragmatic cluster-randomised ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care)-Cambridge trial, comparing intensive multifactorial treatment (IT) versus routine care (RC). Data were collected from the date of diagnosis until December 2010. Setting Primary care surgeries in the East of England. Study sample/participants A subsample (n=189, RC arm: n=99, IT arm: n=90) of patients from the ADDITION-Cambridge cohort (867 patients), consisting of patients 40–69 years old with screen-detected diabetes mellitus. Interventions In the RC arm treatment was delivered according to concurrent treatment guidelines. Surgeries in the IT arm received funding for additional contacts between GPs/nurses and patients, and GPs were advised to follow more intensive treatment algorithms for the management of glucose, lipids and blood pressure and aspirin therapy than in the RC arm. Outcome measures The number of annual contacts between patients and GPs/nurses, the proportion of patients receiving prescriptions for cardiometabolic medication in years 1–5 after diabetes diagnosis and the adherence to prescription algorithms. Results The difference in the number of annual GP contacts (β=0.65) and nurse contacts (β=−0.15) between the study arms was small and insignificant. Patients in the IT arm were more likely to receive glucose-lowering (OR=3.27), ACE-inhibiting (OR=2.03) and lipid-lowering drugs (OR=2.42, all p values <0.01) than patients in the RC arm. The prescription adherence varied between medication classes, but improved in both trial arms over the 5-year follow-up. Conclusions The adherence of GPs to different aspects of the trial protocol was mixed. Background changes in healthcare policy need to be

  11. A Machine-to-Machine protocol benchmark for eHealth applications - Use case: Respiratory rehabilitation.

    PubMed

    Talaminos-Barroso, Alejandro; Estudillo-Valderrama, Miguel A; Roa, Laura M; Reina-Tosina, Javier; Ortega-Ruiz, Francisco

    2016-06-01

    M2M (Machine-to-Machine) communications represent one of the main pillars of the new paradigm of the Internet of Things (IoT), and is making possible new opportunities for the eHealth business. Nevertheless, the large number of M2M protocols currently available hinders the election of a suitable solution that satisfies the requirements that can demand eHealth applications. In the first place, to develop a tool that provides a benchmarking analysis in order to objectively select among the most relevant M2M protocols for eHealth solutions. In the second place, to validate the tool with a particular use case: the respiratory rehabilitation. A software tool, called Distributed Computing Framework (DFC), has been designed and developed to execute the benchmarking tests and facilitate the deployment in environments with a large number of machines, with independence of the protocol and performance metrics selected. DDS, MQTT, CoAP, JMS, AMQP and XMPP protocols were evaluated considering different specific performance metrics, including CPU usage, memory usage, bandwidth consumption, latency and jitter. The results obtained allowed to validate a case of use: respiratory rehabilitation of chronic obstructive pulmonary disease (COPD) patients in two scenarios with different types of requirement: Home-Based and Ambulatory. The results of the benchmark comparison can guide eHealth developers in the choice of M2M technologies. In this regard, the framework presented is a simple and powerful tool for the deployment of benchmark tests under specific environments and conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Gapminder: An AP Human Geography Lab Assignment

    ERIC Educational Resources Information Center

    Keller, Kenneth H.

    2012-01-01

    This lesson is designed as a lab assignment for Advanced Placement (AP) Human Geography students wherein they use the popular Gapminder web site to compare levels of development in countries from different world regions. For this lesson, it is important for the teacher to practice with Gapminder before giving the assignment to students. (Contains…

  13. The Demographic Wave: Rethinking Hispanic AP Trends

    ERIC Educational Resources Information Center

    Edwards, Kelcey; Sawtell, Ellen

    2013-01-01

    Presented at the Advanced Placement Annual Conference (APAC) in Las Vegas, NV in July 2013. This presentation reviews new research examining the AP® experience of Hispanic graduates over the past decade. Topics include an in-depth look at the AP Spanish Language and Culture gateway hypothesis and trends in family characteristics such as parent…

  14. The AP Descriptive Chemistry Question: Student Errors

    ERIC Educational Resources Information Center

    Crippen, Kent; Brooks, David W.

    2005-01-01

    For over a decade, the authors have been involved in a design theory experiment providing software for high school students preparing for the descriptive question on the Advanced Placement (AP) chemistry examination. Since 1997, the software has been available as a Web site offering repeatable practice. This study describes a 4-year project during…

  15. RNA polymerases react differently at d(ApG) and d(GpG) adducts in DNA modified by cis-diamminedichloroplatinum(II)

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

    Corda, Y.; Job, D.; Anin, M.F.

    1992-02-25

    Two duplexes (20-mers) were constructed containing either a single cis-(Pt(NH{sub 3}){sub 2}(d(GpG))) or cis-(Pt(NH{sub 3}){sub 2}(d(ApG))) intrastrand cross-link, the major DNA adducts of the antitumor drug cis-diamminedichloroplatinum(II). These synthetic duplexes were multimerized and the resultant polymers used as templates in single-step addition reactions of condensation of a single nucleoside triphosphate substrate to a dinucleotide primer (abortive elongation reaction) catalyzed by prokaryotic or eukaryotic RNA polymerases. Primer-substrate combinations were selected so as to direct trinucleotide product formation within the platinated bases of the templates. Transcription experiments established that cis-DDP-DNA adducts formed at d(ApG) or d(GpG) sites are not an absolute blockmore » to formation of a single phosphodiester bond by either Escherichia coli RNA polymerase or wheat germ RNA polymerase II. Furthermore, the kinetic data indicate that single-step addition reactions are much more impeded at the platinated d(GpG) than at the platinated d(ApG) site and that the mechanisms of inhibition of RNA polymerase activity are different at the two platinated sites. In particular, binding affinity between E. coli RNA polymerase and the d(GpG)-containing platinated template is lowered, as the apparent K{sub m} of enzyme for the platinated polymer is increased by a factor of 4-5. These results are discussed in reaction to the distortions induced in DNA by the two adducts.« less

  16. Preface: 18th Aps-Sccm and 24th Airapt

    NASA Astrophysics Data System (ADS)

    Collins, Gilbert; Moore, David S.; Yoo, Choong-Shik; Buttler, William; Furlanetto, Michael; Evans, William

    2014-05-01

    The 18th Biennial International Conference of the APS Topical Group on Shock Compression of Condensed Matter in conjunction with the 24th Biennial International Conference of the International Association for the Advancement of High Pressure Science & Technology (AIRAPT) was held at the Westin Hotel in Seattle, Washington from 7-12 July, 2013. This is only the second time that these two organizations have held a Joint Conference — the first was 20 years previous (1993) in Colorado Springs, Colorado. Seattle was chosen for this joint conference because of its central location for the world-wide attendees as well as its metropolitan vibrancy. The scientific program consisted of 858 scheduled presentations organized into 23 topical areas and included contributed (537), invited (95), and plenary (6) lectures, as well as two poster sessions with 110 posters each. The scientific focus of the Joint Conference was on fundamental and applied research topics related to the static or dynamic compression of condensed matter. This multidisciplinary field of research encompasses areas of physics, chemistry, materials science, mechanics, geophysics and planetary physics, and applied mathematics. Experimental, computational and theoretical studies all play important roles. The organizers endeavored to intertwine static and dynamic experimental alongside computational and theoretical studies of similar materials in the organization of the sessions. This goal was aided by the addition of three special focus sessions on deep carbon budget, high energy density materials, and dynamic response of materials. 722 scientists and engineers from 25 countries registered at the conference, including 132 students from 12 countries. The attendee countries represented included: Argentina (2), Australia (2), Brazil (3), Canada (25), China (22), Czech Republic (2), France (35), Germany (19), India (6), Israel (21), Italy (10), Japan (49), Netherlands (1), Poland (1), Portugal (2), Russia (26

  17. Arsenic may be involved in fluoride-induced bone toxicity through PTH/PKA/AP1 signaling pathway.

    PubMed

    Zeng, Qi-bing; Xu, Yu-yan; Yu, Xian; Yang, Jun; Hong, Feng; Zhang, Ai-hua

    2014-01-01

    Chronic exposure to combined fluoride and arsenic continues to be a major public health problem worldwide, affecting thousands of people. In recent years, more and more researchers began to focus on the interaction between the fluorine and the arsenic. In this study, the selected investigation site was located in China. The study group was selected from people living in fluoride-arsenic polluted areas due to burning coal. The total number of participants was 196; including the fluoride-arsenic anomaly group (130) and the fluoride-arsenic normal group (63). By observing the changes in gene and protein expression of PTH/PKA/AP1 signaling pathway, the results show that fluoride can increase the expression levels of PTH, PKA, and AP1, but arsenic can only affect the expression of AP1; fluoride and arsenic have an interaction on the expression of AP1. Further study found that fluoride and arsenic can affect the mRNA expression level of c-fos gene (AP1 family members), and have an interaction on the expression of c-fos, but not c-jun. The results indicate that PTH/PKA/AP1 signaling pathway may play an important role in bone toxicity of fluoride. Arsenic can affect the expression of c-fos, thereby affecting the expression of transcription factor AP1, indirectly involved in fluoride-induced bone toxicity. Copyright © 2013. Published by Elsevier B.V.

  18. Adipocyte fatty acid-binding protein, aP2, alters late atherosclerotic lesion formation in severe hypercholesterolemia.

    PubMed

    Boord, Jeffrey B; Maeda, Kazuhisa; Makowski, Liza; Babaev, Vladimir R; Fazio, Sergio; Linton, MacRae F; Hotamisligil, Gökhan S

    2002-10-01

    The adipocyte fatty acid-binding protein, aP2, has important effects on insulin resistance, lipid metabolism, and atherosclerosis. Its expression in macrophages enhances early foam cell formation and atherosclerosis in vivo. This study was designed to determine whether aP2 deficiency has a similar effect in the setting of advanced atherosclerosis and severe hypercholesterolemia. Mice deficient in aP2 and apolipoprotein E (aP2(-/-)apoE(-/-) mice) and apolipoprotein E-deficient control mice (apoE(-/-) mice) were fed a Western diet for 14 weeks. No significant differences in fasting serum levels of cholesterol, triglycerides, or free fatty acids were found between groups for each sex. Compared with apoE(-/-) control mice, male and female aP2(-/-)apoE(-/-) mice had significant reductions in mean atherosclerotic lesion size in the proximal aorta, en face aorta, and innominate/right carotid artery. Feeding the Western diet in the apoE-deficient background did not cause a significant reduction in insulin sensitivity in vivo, as determined by steady-state serum glucose levels and insulin tolerance testing. These data demonstrate an important role for aP2 expression in the advanced stages of atherosclerotic lesion formation. Thus, aP2 provides an important physiological link between different features of the metabolic syndrome and is a potential target for therapy of atherosclerosis.

  19. Modulation of KvAP Unitary Conductance and Gating by 1-Alkanols and Other Surface Active Agents

    PubMed Central

    Finol-Urdaneta, Rocio K.; McArthur, Jeffrey R.; Juranka, Peter F.; French, Robert J.; Morris, Catherine E.

    2010-01-01

    Abstract The actions of alcohols and anesthetics on ion channels are poorly understood. Controversy continues about whether bilayer restructuring is relevant to the modulatory effects of these surface active agents (SAAs). Some voltage-gated K channels (Kv), but not KvAP, have putative low affinity alcohol-binding sites, and because KvAP structures have been determined in bilayers, KvAP could offer insights into the contribution of bilayer mechanics to SAA actions. We monitored KvAP unitary conductance and macroscopic activation and inactivation kinetics in PE:PG/decane bilayers with and without exposure to classic SAAs (short-chain 1-alkanols, cholesterol, and selected anesthetics: halothane, isoflurane, chloroform). At levels that did not measurably alter membrane specific capacitance, alkanols caused functional changes in KvAP behavior including lowered unitary conductance, modified kinetics, and shifted voltage dependence for activation. A simple explanation is that the site of SAA action on KvAP is its entire lateral interface with the PE:PG/decane bilayer, with SAA-induced changes in surface tension and bilayer packing order combining to modulate the shape and stability of various conformations. The KvAP structural adjustment to diverse bilayer pressure profiles has implications for understanding desirable and undesirable actions of SAA-like drugs and, broadly, predicts that channel gating, conductance and pharmacology may differ when membrane packing order differs, as in raft versus nonraft domains. PMID:20197029

  20. Functional Identification and Characterization of the Brassica Napus Transcription Factor Gene BnAP2, the Ortholog of Arabidopsis Thaliana APETALA2

    PubMed Central

    Xiong, Zhiyong; Chen, Chunli; Wang, Lijun; Yu, Jingyin; Lu, Changming; Wei, Wenhui

    2012-01-01

    BnAP2, an APETALA2 (AP2)-like gene, has been isolated from Brassica napus cultivar Zhongshuang 9. The cDNA of BnAP2, with 1, 299 bp in length, encoded a transcription factor comprising of 432 amino acid residues. Results from complementary experiment indicated that BnAP2 was completely capable of restoring the phenotype of Arabidopsis ap2-11 mutant. Together with the sequence and expression data, the complementation data suggested that BnAP2 encodes the ortholog of AtAP2. To address the transcriptional activation of BnAP2, we performed transactivation assays in yeast. Fusion protein of BnAP2 with GAL4 DNA binding domain strongly activated transcription in yeast, and the transactivating activity of BnAP2 was localized to the N-terminal 100 amino acids. To further study the function of BnAP2 involved in the phenotype of B. napus, we used a transgenic approach that involved targeted RNA interference (RNAi) repression induced by ihp-RNA. Floral various phenotype defectives and reduced female fertility were observed in B. napus BnAP2-RNAi lines. Loss of the function of BnAP2 gene also resulted in delayed sepal abscission and senescence with the ethylene-independent pathway. In the strong BnAP2-RNAi lines, seeds showed defects in shape, structure and development and larger size. Strong BnAP2-RNAi and wild-type seeds initially did not display a significant difference in morphology at 10 DAF, but the development of BnAP2-RNAi seeds was slower than that of wild type at 20 DAF, and further at 30 DAF, wild-type seeds were essentially at their final size, whereas BnAP2-RNAi seeds stopped growing and developing and gradually withered. PMID:22479468

  1. Functional identification and characterization of the Brassica napus transcription factor gene BnAP2, the ortholog of Arabidopsis thaliana APETALA2.

    PubMed

    Yan, Xiaohong; Zhang, Lei; Chen, Bo; Xiong, Zhiyong; Chen, Chunli; Wang, Lijun; Yu, Jingyin; Lu, Changming; Wei, Wenhui

    2012-01-01

    BnAP2, an APETALA2 (AP2)-like gene, has been isolated from Brassica napus cultivar Zhongshuang 9. The cDNA of BnAP2, with 1, 299 bp in length, encoded a transcription factor comprising of 432 amino acid residues. Results from complementary experiment indicated that BnAP2 was completely capable of restoring the phenotype of Arabidopsis ap2-11 mutant. Together with the sequence and expression data, the complementation data suggested that BnAP2 encodes the ortholog of AtAP2. To address the transcriptional activation of BnAP2, we performed transactivation assays in yeast. Fusion protein of BnAP2 with GAL4 DNA binding domain strongly activated transcription in yeast, and the transactivating activity of BnAP2 was localized to the N-terminal 100 amino acids. To further study the function of BnAP2 involved in the phenotype of B. napus, we used a transgenic approach that involved targeted RNA interference (RNAi) repression induced by ihp-RNA. Floral various phenotype defectives and reduced female fertility were observed in B. napus BnAP2-RNAi lines. Loss of the function of BnAP2 gene also resulted in delayed sepal abscission and senescence with the ethylene-independent pathway. In the strong BnAP2-RNAi lines, seeds showed defects in shape, structure and development and larger size. Strong BnAP2-RNAi and wild-type seeds initially did not display a significant difference in morphology at 10 DAF, but the development of BnAP2-RNAi seeds was slower than that of wild type at 20 DAF, and further at 30 DAF, wild-type seeds were essentially at their final size, whereas BnAP2-RNAi seeds stopped growing and developing and gradually withered.

  2. Chemical synthesis of 5'-pyrophosphate and triphosphate derivatives of 3'-5' ApA, ApG, GpA and GpG. CD study of the effect of 5'-phosphate groups on the conformation of 3'-5' GpG.

    PubMed Central

    Tomasz, J; Simoncsits, A; Kajtár, M; Krug, R M; Shatkin, A J

    1978-01-01

    A simple, two-step method is described for the synthesis of the 5'-pyro- and triphosphate derivatives of 3'-5' ApA, ApG, GpA and GpG. The readily accessible 2'(3')-5' ApA, ApG, GpA and GpG were converted in one step to the corresponding 5'-phosphoramidate derivatives which were then transformed to the 5'-pyro- and triphosphates. CD spectra of 3'-5' pn GpG (n = 0,1,2 or 3) derivatives, measured at pH 1, indicated stabilization of the (syn) G+p (anti)G conformation by the 5'-phosphate groups. PMID:211490

  3. Loss of AP-5 results in accumulation of aberrant endolysosomes: defining a new type of lysosomal storage disease

    PubMed Central

    Hirst, Jennifer; Edgar, James R.; Esteves, Typhaine; Darios, Frédéric; Madeo, Marianna; Chang, Jaerak; Roda, Ricardo H.; Dürr, Alexandra; Anheim, Mathieu; Gellera, Cinzia; Li, Jun; Züchner, Stephan; Mariotti, Caterina; Stevanin, Giovanni; Blackstone, Craig; Kruer, Michael C.; Robinson, Margaret S.

    2015-01-01

    Adaptor proteins (AP 1–5) are heterotetrameric complexes that facilitate specialized cargo sorting in vesicular-mediated trafficking. Mutations in AP5Z1, encoding a subunit of the AP-5 complex, have been reported to cause hereditary spastic paraplegia (HSP), although their impact at the cellular level has not been assessed. Here we characterize three independent fibroblast lines derived from skin biopsies of patients harbouring nonsense mutations in AP5Z1 and presenting with spastic paraplegia accompanied by neuropathy, parkinsonism and/or cognitive impairment. In all three patient-derived lines, we show that there is complete loss of AP-5 ζ protein and a reduction in the associated AP-5 µ5 protein. Using ultrastructural analysis, we show that these patient-derived lines consistently exhibit abundant multilamellar structures that are positive for markers of endolysosomes and are filled with aberrant storage material organized as exaggerated multilamellar whorls, striated belts and ‘fingerprint bodies’. This phenotype can be replicated in a HeLa cell culture model by siRNA knockdown of AP-5 ζ. The cellular phenotype bears striking resemblance to features described in a number of lysosomal storage diseases (LSDs). Collectively, these findings reveal an emerging picture of the role of AP-5 in endosomal and lysosomal homeostasis, illuminates a potential pathomechanism that is relevant to the role of AP-5 in neurons and expands the understanding of recessive HSPs. Moreover, the resulting accumulation of storage material in endolysosomes leads us to propose that AP-5 deficiency represents a new type of LSDs. PMID:26085577

  4. Second metrology round-robin of APS, ESRF and SPring-8 laboratories of elliptical and spherical hard-x-ray mirrors.

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

    Rommeveaux, A.; Assoufid, L.; Ohashi, H.

    2007-01-01

    The first series of metrology round-robin measurements carried out in 2005 at the APS, ESRF and SPring-8 metrology laboratories involving two flat x-ray mirrors and a cylindrical x-ray mirror has shown excellent agreement among the three facilities Long Trace Profilers (LTP) despite their architectural differences. Because of the growing interest in diffraction-limited hard x-ray K-B focusing mirrors, it was decided to extend the round robin measurements to spherical and aspheric x-ray mirrors. The strong surface slope variation of these mirrors presents a real challenge to LTP. As a result, new LTP measurement protocol has to be developed and implemented tomore » ensure measurement accuracy and consistency. In this paper, different measurement techniques and procedures will be described, the results will be discussed, and comparison will be extended to micro-stitching interferometry measurements performed at Osaka University, Japan.« less

  5. A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle.

    PubMed

    Modrzynska, Katarzyna; Pfander, Claudia; Chappell, Lia; Yu, Lu; Suarez, Catherine; Dundas, Kirsten; Gomes, Ana Rita; Goulding, David; Rayner, Julian C; Choudhary, Jyoti; Billker, Oliver

    2017-01-11

    A family of apicomplexa-specific proteins containing AP2 DNA-binding domains (ApiAP2s) was identified in malaria parasites. This family includes sequence-specific transcription factors that are key regulators of development. However, functions for the majority of ApiAP2 genes remain unknown. Here, a systematic knockout screen in Plasmodium berghei identified ten ApiAP2 genes that were essential for mosquito transmission: four were critical for the formation of infectious ookinetes, and three were required for sporogony. We describe non-essential functions for AP2-O and AP2-SP proteins in blood stages, and identify AP2-G2 as a repressor active in both asexual and sexual stages. Comparative transcriptomics across mutants and developmental stages revealed clusters of co-regulated genes with shared cis promoter elements, whose expression can be controlled positively or negatively by different ApiAP2 factors. We propose that stage-specific interactions between ApiAP2 proteins on partly overlapping sets of target genes generate the complex transcriptional network that controls the Plasmodium life cycle. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. The Freshman Nine: Helping High School Freshmen Be Successful in AP Human Geography

    ERIC Educational Resources Information Center

    Garner, Jennifer

    2012-01-01

    Teaching AP Human Geography to freshmen seems like a daunting task and while there are many arguments both for and against offering the course to freshmen, for many teachers it is reality. In this article, the author offers nine tips to help high school freshmen be successful in the course and on the AP exam.

  7. Size response of an SMPS-APS system to commercial multi-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Lee, Seung-Bok; Lee, Jun-Hyun; Bae, Gwi-Nam

    2010-02-01

    Carbon nanotubes (CNTs) are representative-engineered nanomaterials with unique properties. The safe production of CNTs urgently requires reliable tools to assess inhalation exposure. In this study, on-line aerosol instruments were employed to detect the release of multi-walled CNTs (MWCNTs) in workplace environments. The size responses of aerosol instruments consisting of both a scanning mobility particle sizer (SMPS) and an aerodynamic particle sizer (APS) were examined using five types of commercial MWCNTs. A MWCNT solution and powder were aerosolized using atomizing and shaking methods, respectively. Regardless of the phase and purity, the aerosolized MWCNTs showed consistent size distributions with both SMPS and APS. The SMPS and APS measurements revealed a dominant broad peak at approximately 200-400 nm and a distinct narrow peak at approximately 2 μm, respectively. Comparing with field application of the two aerosol instruments, the APS response could be a fingerprint of the MWCNTs in a real workplace environment. A modification of the atomizing method is recommended for the long-term inhalation toxicity studies.

  8. Environmental and Sustainable Technology Evaluation: Mold-Resistant Armacell Insulation--Armacell LLC, AP Armaflex Black

    EPA Science Inventory

    The ESTE test program measured the mold resistance of Armacell AP Armaflex Black insulation. Tests for emissions of VOCs and formaldehyde were also performed. AP Armaflex Roll Insulation is a black flexible closed-cell, fiber-free elastomeric thermal insulation. The expanded clos...

  9. Hypermethylation of AP-2Alpha as a Prognostic Marker for DCIS

    DTIC Science & Technology

    2008-05-01

    Unfortunately, among the methylation status of the AP2, CYCLIN D, ECAD , GSTP, and SSOCS genes, either as individual genes, or in combinations, no...0.61 to 4.10) 1.00 (referent) 0.35 ECAD M UM 0 100 3 97 GSTP M UM 40 60 24 76 2.02 (0.72 to 5.64) 1.00...Missing data: 1.4% for AP2, CYCLIN D, ECAD , GSTP; 4.2% for SSOCS; 2.8% for nuclear grade. §M=methylated; UM=unmethylated; +Two-sided

  10. A Self-Stabilizing Synchronization Protocol for Arbitrary Digraphs

    NASA Technical Reports Server (NTRS)

    Malekpour, Mahyar R.

    2011-01-01

    This paper presents a self-stabilizing distributed clock synchronization protocol in the absence of faults in the system. It is focused on the distributed clock synchronization of an arbitrary, non-partitioned digraph ranging from fully connected to 1-connected networks of nodes while allowing for differences in the network elements. This protocol does not rely on assumptions about the initial state of the system, other than the presence of at least one node, and no central clock or a centrally generated signal, pulse, or message is used. Nodes are anonymous, i.e., they do not have unique identities. There is no theoretical limit on the maximum number of participating nodes. The only constraint on the behavior of the node is that the interactions with other nodes are restricted to defined links and interfaces. This protocol deterministically converges within a time bound that is a linear function of the self-stabilization period. We present an outline of a deductive proof of the correctness of the protocol. A bounded model of the protocol was mechanically verified for a variety of topologies. Results of the mechanical proof of the correctness of the protocol are provided. The model checking results have verified the correctness of the protocol as they apply to the networks with unidirectional and bidirectional links. In addition, the results confirm the claims of determinism and linear convergence. As a result, we conjecture that the protocol solves the general case of this problem. We also present several variations of the protocol and discuss that this synchronization protocol is indeed an emergent system.

  11. Suppressive effects of Lithospermum erythrorhizon extracts on lipopolysaccharide-induced activation of AP-1 and NF-kappaB via mitogen-activated protein kinase pathways in mouse macrophage cells.

    PubMed

    Han, Kyu Yeon; Kwon, Taek Hwan; Lee, Tae Hoon; Lee, Sung-Joon; Kim, Sung-Hoon; Kim, Jiyoung

    2008-04-30

    A variety of anti-inflammatory agents have been shown to exert chemopreventive activity via targeting of transcription factors such as NF-kappaB and AP-1. Lithospermum erythrorhizon (LE) has long been used in traditional oriental medicine. In this study, we demonstrated the inhibitory effects of LE extracts on lipopolysaccharide (LPS)-stimulated production of inflammatory cytokines. As an underlying mechanism of inhibition, LE extracts reduced LPS-induced transactivation of AP-1 as well as NF-kappaB in mouse macrophage cells. Electrophoretic mobility shift assays indicated that LE extracts inhibited the DNA binding activities of AP-1 and NF-kappaB. In addition, phosphorylation of IkappaB-alpha protein was suppressed by LE extracts. Moreover, LE extracts inhibited c-Jun N-terminal kinase and extracellular signal-regulated signaling pathways. Our results suggest that the anti-inflammatory activity of LE extracts may be mediated by the inhibition of signal transduction pathways that normally lead to the activation of AP-1and NF-kappaB. These inhibitory effects may be useful for chemoprevention of cancer or other chronic inflammatory diseases.

  12. APS-Workshop on Characterization of MMIC (Monolithic Microwave Integrated Circuit) Devices for Array Antenna

    NASA Technical Reports Server (NTRS)

    Smetana, Jerry (Editor); Mittra, Raj (Editor); Laprade, Nick; Edward, Bryan; Zaghloul, Amir

    1987-01-01

    The IEEE AP-S ADCOM is attempting to expand its educational, tutorial and information exchange activities as a further benefit to all members. To this end, ADCOM will be forming specialized workshops on topics of interest to its members. The first such workshop on Characterization and Packaging of MMIC Devices for Array Antennas was conceived. The workshop took place on June 13, 1986 as part of the 1986 International Symposium sponsored by IEEE AP-S and URSI in Philadelphia, PA, June 9-13, 1986. The workshop was formed to foster the interchange of ideas among MMIC device users and to provide a forum to collect and focus information among engineers experienced and interested in the topic. After brief presentations by the panelists and comments from attendees on several subtopics, the group was divided into working committees. Each committee evaluated and made recommendations on one of the subtopics.

  13. Nuclear Reactor Safety--The APS Submits its Report

    ERIC Educational Resources Information Center

    Physics Today, 1975

    1975-01-01

    Presents the summary section of the American Physical Society (APS) report on the safety features of the light-water reactor, reviews the design, construction, and operation of a reactor and outlines the primary engineered safety features. Summarizes the major recommendations of the study group. (GS)

  14. Geminivirus-encoded TrAP suppressor inhibits the histone methyltransferase SUVH4/KYP to counter host defense

    PubMed Central

    Castillo-González, Claudia; Liu, Xiuying; Huang, Changjun; Zhao, Changjiang; Ma, Zeyang; Hu, Tao; Sun, Feng; Zhou, Yijun; Zhou, Xueping; Wang, Xiu-Jie; Zhang, Xiuren

    2015-01-01

    Transcriptional gene silencing (TGS) can serve as an innate immunity against invading DNA viruses throughout Eukaryotes. Geminivirus code for TrAP protein to suppress the TGS pathway. Here, we identified an Arabidopsis H3K9me2 histone methyltransferase, Su(var)3-9 homolog 4/Kryptonite (SUVH4/KYP), as a bona fide cellular target of TrAP. TrAP interacts with the catalytic domain of KYP and inhibits its activity in vitro. TrAP elicits developmental anomalies phenocopying several TGS mutants, reduces the repressive H3K9me2 mark and CHH DNA methylation, and reactivates numerous endogenous KYP-repressed loci in vivo. Moreover, KYP binds to the viral chromatin and controls its methylation to combat virus infection. Notably, kyp mutants support systemic infection of TrAP-deficient Geminivirus. We conclude that TrAP attenuates the TGS of the viral chromatin by inhibiting KYP activity to evade host surveillance. These findings provide new insight on the molecular arms race between host antiviral defense and virus counter defense at an epigenetic level. DOI: http://dx.doi.org/10.7554/eLife.06671.001 PMID:26344546

  15. FABP4/aP2 Regulates Macrophage Redox Signaling and Inflammasome Activation via Control of UCP2.

    PubMed

    Steen, Kaylee A; Xu, Hongliang; Bernlohr, David A

    2017-01-15

    Obesity-linked metabolic disease is mechanistically associated with the accumulation of proinflammatory macrophages in adipose tissue, leading to increased reactive oxygen species (ROS) production and chronic low-grade inflammation. Previous work has demonstrated that deletion of the adipocyte fatty acid-binding protein (FABP4/aP2) uncouples obesity from inflammation via upregulation of the uncoupling protein 2 (UCP2). Here, we demonstrate that ablation of FABP4/aP2 regulates systemic redox capacity and reduces cellular protein sulfhydryl oxidation and, in particular, oxidation of mitochondrial protein cysteine residues. Coincident with the loss of FABP4/aP2 is the upregulation of the antioxidants superoxide dismutase (SOD2), catalase, methionine sulfoxide reductase A, and the 20S proteasome subunits PSMB5 and αβ. Reduced mitochondrial protein oxidation in FABP4/aP2 -/- macrophages attenuates the mitochondrial unfolded-protein response (mtUPR) as measured by expression of heat shock protein 60, Clp protease, and Lon peptidase 1. Consistent with a diminished mtUPR, FABP4/aP2 -/- macrophages exhibit reduced expression of cleaved caspase-1 and NLRP3. Secretion of interleukin 1β (IL-1β), in response to inflammasome activation, is ablated in FABP4/aP2 -/- macrophages, as well as in FABP4/aP2 inhibitor-treated cells, but partially rescued in FABP4/aP2-null macrophages when UCP2 is silenced. Collectively, these data offer a novel pathway whereby FABP4/aP2 regulates macrophage redox signaling and inflammasome activation via control of UCP2 expression. Copyright © 2017 American Society for Microbiology.

  16. A Weak Value Based QKD Protocol Robust Against Detector Attacks

    NASA Astrophysics Data System (ADS)

    Troupe, James

    2015-03-01

    We propose a variation of the BB84 quantum key distribution protocol that utilizes the properties of weak values to insure the validity of the quantum bit error rate estimates used to detect an eavesdropper. The protocol is shown theoretically to be secure against recently demonstrated attacks utilizing detector blinding and control and should also be robust against all detector based hacking. Importantly, the new protocol promises to achieve this additional security without negatively impacting the secure key generation rate as compared to that originally promised by the standard BB84 scheme. Implementation of the weak measurements needed by the protocol should be very feasible using standard quantum optical techniques.

  17. Renal Atp6ap2/(Pro)renin Receptor Is Required for Normal Vacuolar H+-ATPase Function but Not for the Renin-Angiotensin System.

    PubMed

    Trepiccione, Francesco; Gerber, Simon D; Grahammer, Florian; López-Cayuqueo, Karen I; Baudrie, Véronique; Păunescu, Teodor G; Capen, Diane E; Picard, Nicolas; Alexander, R Todd; Huber, Tobias B; Chambrey, Regine; Brown, Dennis; Houillier, Pascal; Eladari, Dominique; Simons, Matias

    2016-11-01

    ATPase H + -transporting lysosomal accessory protein 2 (Atp6ap2), also known as the (pro)renin receptor, is a type 1 transmembrane protein and an accessory subunit of the vacuolar H + -ATPase (V-ATPase) that may also function within the renin-angiotensin system. However, the contribution of Atp6ap2 to renin-angiotensin-dependent functions remains unconfirmed. Using mice with an inducible conditional deletion of Atp6ap2 in mouse renal epithelial cells, we found that decreased V-ATPase expression and activity in the intercalated cells of the collecting duct impaired acid-base regulation by the kidney. In addition, these mice suffered from marked polyuria resistant to desmopressin administration. Immunoblotting revealed downregulation of the medullary Na + -K + -2Cl - cotransporter NKCC2 in these mice compared with wild-type mice, an effect accompanied by a hypotonic medullary interstitium and impaired countercurrent multiplication. This phenotype correlated with strong autophagic defects in epithelial cells of medullary tubules. Notably, cells with high accumulation of the autophagosomal substrate p62 displayed the strongest reduction of NKCC2 expression. Finally, nephron-specific Atp6ap2 depletion did not affect angiotensin II production, angiotensin II-dependent BP regulation, or sodium handling in the kidney. Taken together, our results show that nephron-specific deletion of Atp6ap2 does not affect the renin-angiotensin system but causes a combination of renal concentration defects and distal renal tubular acidosis as a result of impaired V-ATPase activity. Copyright © 2016 by the American Society of Nephrology.

  18. Does the addition of hip strengthening exercises improve outcomes following total knee arthroplasty? A study protocol for a randomized trial.

    PubMed

    Schache, Margaret B; McClelland, Jodie A; Webster, Kate E

    2016-06-13

    Total knee arthroplasty (TKA) is effective in reducing pain and improving function for end-stage knee osteoarthritis. However, muscle weakness and functional limitations persist despite assistance from post-operative rehabilitation programs that traditionally focus on quadriceps strengthening and range of movement exercises. Hip abductor muscle weakness is evident in knee osteoarthritis and hip muscle strengthening reduces knee pain in this group. Following TKA, people with weak hip abductor strength perform more poorly on measures of physical function. However, very little is known of the effectiveness of including hip abductor strengthening exercises in post-operative rehabilitation. The aim of this trial is to compare the effects of targeted hip abductor strengthening to those of traditional care in a TKA rehabilitation program on muscle strength, patient reported outcomes and functional performance measures. This protocol describes a single-blinded randomized controlled trial, where 104 participants referred for inpatient rehabilitation following TKA will be recruited. Participants will be randomized using computer-generated numbers to one of two groups: usual care or usual care with additional hip strengthening exercises. Participants will attend physiotherapy daily during their inpatient length of stay, and will then attend between six and eight physiotherapy sessions as an outpatient. Primary outcomes are isometric hip abductor strength and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes are stair climb test, 6 min walk test, timed up and go, 40 m fast-paced walk test, 30 second chair stand test, isometric quadriceps strength, Lower Extremity Functional Scale (LEFS) and SF-12. Outcome measures will be recorded at baseline (admission to inpatient rehabilitation), and then 3 weeks, 6 weeks and 6 months post admission to rehabilitation. The findings of this study will determine whether the addition of targeted hip strengthening

  19. Decreased gene expression of CD2AP in Chinese patients with sporadic Alzheimer's disease.

    PubMed

    Tao, Qing-Qing; Liu, Zhi-Jun; Sun, Yi-Min; Li, Hong-Lei; Yang, Ping; Liu, De-Shan; Jiang, Bin; Li, Xiao-Yan; Xu, Jian-Feng; Wu, Zhi-Ying

    2017-08-01

    Many sporadic Alzheimer's disease (SAD) risk genes have been identified in the last decades, but most of them have not been consistently accepted. Here, we sought to identify SAD-associated genes and their potential mechanisms involved in SAD pathogenesis. A 2-stage design was employed. In stage 1, 95 variants in 75 genes that were previously reported as SAD-risk genes in Caucasian populations were evaluated in 1857 subjects (422 SAD patients and 1435 controls). In stage 2, a subset of promising variants found in stage 1 were further evaluated in an independent cohort of 1001 subjects (254 SAD and 747 controls). Variants in CD2AP were significantly associated with SAD risk in our subjects. Furthermore, CD2AP gene expression in peripheral blood lymphocytes (PBL) from 209 SAD patients and 213 controls was determined. CD2AP gene expression in PBL was significantly decreased in patients with SAD as compared with controls. Our study suggests that CD2AP is an SAD-risk gene in Chinese Han population and CD2AP gene expression is decreased in the PBL of patients with SAD, indicating its possible systemic involvement in SAD. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Gene Duplication and Transference of Function in the paleoAP3 Lineage of Floral Organ Identity Genes

    PubMed Central

    Galimba, Kelsey D.; Martínez-Gómez, Jesús; Di Stilio, Verónica S.

    2018-01-01

    The floral organ identity gene APETALA3 (AP3) is a MADS-box transcription factor involved in stamen and petal identity that belongs to the B-class of the ABC model of flower development. Thalictrum (Ranunculaceae), an emerging model in the non-core eudicots, has AP3 homologs derived from both ancient and recent gene duplications. Prior work has shown that petals have been lost repeatedly and independently in Ranunculaceae in correlation with the loss of a specific AP3 paralog, and Thalictrum represents one of these instances. The main goal of this study was to conduct a functional analysis of the three AP3 orthologs present in Thalictrum thalictroides, representing the paleoAP3 gene lineage, to determine the degree of redundancy versus divergence after gene duplication. Because Thalictrum lacks petals, and has lost the petal-specific AP3, we also asked whether heterotopic expression of the remaining AP3 genes contributes to the partial transference of petal function to the first whorl found in insect-pollinated species. To address these questions, we undertook functional characterization by virus-induced gene silencing (VIGS), protein–protein interaction and binding site analyses. Our results illustrate partial redundancy among Thalictrum AP3s, with deep conservation of B-class function in stamen identity and a novel role in ectopic petaloidy of sepals. Certain aspects of petal function of the lost AP3 locus have apparently been transferred to the other paralogs. A novel result is that the protein products interact not only with each other, but also as homodimers. Evidence presented here also suggests that expression of the different ThtAP3 paralogs is tightly integrated, with an apparent disruption of B function homeostasis upon silencing of one of the paralogs that codes for a truncated protein. To explain this result, we propose two testable alternative scenarios: that the truncated protein is a dominant negative mutant or that there is a compensational

  1. Experimental eavesdropping attack against Ekert's protocol based on Wigner's inequality

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

    Bovino, F. A.; Colla, A. M.; Castagnoli, G.

    2003-09-01

    We experimentally implemented an eavesdropping attack against the Ekert protocol for quantum key distribution based on the Wigner inequality. We demonstrate a serious lack of security of this protocol when the eavesdropper gains total control of the source. In addition we tested a modified Wigner inequality which should guarantee a secure quantum key distribution.

  2. Adipocyte Fatty Acid–Binding Protein, aP2, Alters Late Atherosclerotic Lesion Formation in Severe Hypercholesterolemia

    PubMed Central

    Boord, Jeffrey B.; Maeda, Kazuhisa; Makowski, Liza; Babaev, Vladimir R.; Fazio, Sergio; Linton, MacRae F.; Hotamisligil, Gökhan S.

    2014-01-01

    Objective The adipocyte fatty acid-binding protein, aP2, has important effects on insulin resistance, lipid metabolism, and atherosclerosis. Its expression in macrophages enhances early foam cell formation and atherosclerosis in vivo. This study was designed to determine whether aP2 deficiency has a similar effect in the setting of advanced atherosclerosis and severe hypercholesterolemia. Methods and Results Mice deficient in aP2 and apolipoprotein E (aP2−/−apoE−/− mice) and apolipoprotein E-deficient control mice (apoE−/− mice) were fed a Western diet for 14 weeks. No significant differences in fasting serum levels of cholesterol, triglycerides, or free fatty acids were found between groups for each sex. Compared with apoE−/− control mice, male and female aP2−/−apoE−/− mice had significant reductions in mean atherosclerotic lesion size in the proximal aorta, en face aorta, and innominate/right carotid artery. Feeding the Western diet in the apoE-deficient background did not cause a significant reduction in insulin sensitivity in vivo, as determined by steady-state serum glucose levels and insulin tolerance testing. Conclusions These data demonstrate an important role for aP2 expression in the advanced stages of atherosclerotic lesion formation. Thus, aP2 provides an important physiological link between different features of the metabolic syndrome and is a potential target for therapy of atherosclerosis. PMID:12377750

  3. Time Trials--An AP Physics Challenge Lab

    ERIC Educational Resources Information Center

    Jones, David

    2009-01-01

    I have come to the conclusion that for high school physics classroom and laboratory experiences, simpler is better! In this paper I describe a very simple and effective lab experience that my AP students have thoroughly enjoyed year after year. I call this lab exercise "Time Trials." The experiment is simple in design and it is a lot of fun for…

  4. De novo transcriptome sequence assembly and identification of AP2/ERF transcription factor related to abiotic stress in parsley (Petroselinum crispum).

    PubMed

    Li, Meng-Yao; Tan, Hua-Wei; Wang, Feng; Jiang, Qian; Xu, Zhi-Sheng; Tian, Chang; Xiong, Ai-Sheng

    2014-01-01

    Parsley is an important biennial Apiaceae species that is widely cultivated as herb, spice, and vegetable. Previous studies on parsley principally focused on its physiological and biochemical properties, including phenolic compound and volatile oil contents. However, little is known about the molecular and genetic properties of parsley. In this study, 23,686,707 high-quality reads were obtained and assembled into 81,852 transcripts and 50,161 unigenes for the first time. Functional annotation showed that 30,516 unigenes had sequence similarity to known genes. In addition, 3,244 putative simple sequence repeats were detected in curly parsley. Finally, 1,569 of the identified unigenes belonged to 58 transcription factor families. Various abiotic stresses have a strong detrimental effect on the yield and quality of parsley. AP2/ERF transcription factors have important functions in plant development, hormonal regulation, and abiotic response. A total of 88 putative AP2/ERF factors were identified from the transcriptome sequence of parsley. Seven AP2/ERF transcription factors were selected in this study to analyze the expression profiles of parsley under different abiotic stresses. Our data provide a potentially valuable resource that can be used for intensive parsley research.

  5. De Novo Transcriptome Sequence Assembly and Identification of AP2/ERF Transcription Factor Related to Abiotic Stress in Parsley (Petroselinum crispum)

    PubMed Central

    Wang, Feng; Jiang, Qian; Xu, Zhi-Sheng; Tian, Chang; Xiong, Ai-Sheng

    2014-01-01

    Parsley is an important biennial Apiaceae species that is widely cultivated as herb, spice, and vegetable. Previous studies on parsley principally focused on its physiological and biochemical properties, including phenolic compound and volatile oil contents. However, little is known about the molecular and genetic properties of parsley. In this study, 23,686,707 high-quality reads were obtained and assembled into 81,852 transcripts and 50,161 unigenes for the first time. Functional annotation showed that 30,516 unigenes had sequence similarity to known genes. In addition, 3,244 putative simple sequence repeats were detected in curly parsley. Finally, 1,569 of the identified unigenes belonged to 58 transcription factor families. Various abiotic stresses have a strong detrimental effect on the yield and quality of parsley. AP2/ERF transcription factors have important functions in plant development, hormonal regulation, and abiotic response. A total of 88 putative AP2/ERF factors were identified from the transcriptome sequence of parsley. Seven AP2/ERF transcription factors were selected in this study to analyze the expression profiles of parsley under different abiotic stresses. Our data provide a potentially valuable resource that can be used for intensive parsley research. PMID:25268141

  6. AP-IO: asynchronous pipeline I/O for hiding periodic output cost in CFD simulation.

    PubMed

    Xiaoguang, Ren; Xinhai, Xu

    2014-01-01

    Computational fluid dynamics (CFD) simulation often needs to periodically output intermediate results to files in the form of snapshots for visualization or restart, which seriously impacts the performance. In this paper, we present asynchronous pipeline I/O (AP-IO) optimization scheme for the periodically snapshot output on the basis of asynchronous I/O and CFD application characteristics. In AP-IO, dedicated background I/O processes or threads are in charge of handling the file write in pipeline mode, therefore the write overhead can be hidden with more calculation than classic asynchronous I/O. We design the framework of AP-IO and implement it in OpenFOAM, providing CFD users with a user-friendly interface. Experimental results on the Tianhe-2 supercomputer demonstrate that AP-IO can achieve a good optimization effect for the periodical snapshot output in CFD application, and the effect is especially better for massively parallel CFD simulations, which can reduce the total execution time up to about 40%.

  7. AP-IO: Asynchronous Pipeline I/O for Hiding Periodic Output Cost in CFD Simulation

    PubMed Central

    Xiaoguang, Ren; Xinhai, Xu

    2014-01-01

    Computational fluid dynamics (CFD) simulation often needs to periodically output intermediate results to files in the form of snapshots for visualization or restart, which seriously impacts the performance. In this paper, we present asynchronous pipeline I/O (AP-IO) optimization scheme for the periodically snapshot output on the basis of asynchronous I/O and CFD application characteristics. In AP-IO, dedicated background I/O processes or threads are in charge of handling the file write in pipeline mode, therefore the write overhead can be hidden with more calculation than classic asynchronous I/O. We design the framework of AP-IO and implement it in OpenFOAM, providing CFD users with a user-friendly interface. Experimental results on the Tianhe-2 supercomputer demonstrate that AP-IO can achieve a good optimization effect for the periodical snapshot output in CFD application, and the effect is especially better for massively parallel CFD simulations, which can reduce the total execution time up to about 40%. PMID:24955390

  8. Quantum cryptography: individual eavesdropping with the knowledge of the error-correcting protocol

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

    Horoshko, D B

    2007-12-31

    The quantum key distribution protocol BB84 combined with the repetition protocol for error correction is analysed from the point of view of its security against individual eavesdropping relying on quantum memory. It is shown that the mere knowledge of the error-correcting protocol changes the optimal attack and provides the eavesdropper with additional information on the distributed key. (fifth seminar in memory of d.n. klyshko)

  9. The complex magnetic field topology of the cool Ap star 49 Cam

    NASA Astrophysics Data System (ADS)

    Silvester, J.; Kochukhov, O.; Rusomarov, N.; Wade, G. A.

    2017-10-01

    49 Cam is a cool magnetic chemically peculiar star that has been noted for showing strong, complex Zeeman linear polarization signatures. This paper describes magnetic and chemical surface maps obtained for 49 Cam using the Invers10 magnetic Doppler imaging code and high-resolution spectropolarimetric data in all four Stokes parameters collected with the ESPaDOnS and Narval spectropolarimeters at the Canada-France-Hawaii Telescope and Pic du Midi Observatory. The reconstructed magnetic field maps of 49 Cam show a relatively complex structure. Describing the magnetic field topology in terms of spherical harmonics, we find significant contributions of modes up to ℓ = 3, including toroidal components. Observations cannot be reproduced using a simple low-order multipolar magnetic field structure. 49 Cam exhibits a level of field complexity that has not been seen in magnetic maps of other cool Ap stars. Hence, we concluded that relatively complex magnetic fields are observed in Ap stars at both low and high effective temperatures. In addition to mapping the magnetic field, we also derive surface abundance distributions of nine chemical elements, including Ca, Sc, Ti, Cr, Fe, Ce, Pr, Nd and Eu. Comparing these abundance maps with the reconstructed magnetic field geometry, we find no clear relationship of the abundance distributions with the magnetic field for some elements. However, for other elements some distinct patterns are found. We discuss these results in the context of other recent magnetic mapping studies and theoretical predictions of radiative diffusion.

  10. Promotion of Homologous Recombination and Genomic Stability byRAD51AP1 via RAD51 Recombinase Enhancement

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

    Wiese, Claudia; Dray, Eloise; Groesser, Torsten

    2007-04-11

    Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand pairing step in HR. RAD51AP1 (RAD51 Associated Protein 1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA damaging treatment. Purified RAD51AP1 binds dsDNA and RAD51, and it greatly stimulates the RAD51-mediated D-loop reaction. Biochemical and cytological results show that RAD51AP1more » functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide the first evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.« less

  11. Accurate age determinations of several nearby open clusters containing magnetic Ap stars

    NASA Astrophysics Data System (ADS)

    Silaj, J.; Landstreet, J. D.

    2014-06-01

    Context. To study the time evolution of magnetic fields, chemical abundance peculiarities, and other characteristics of magnetic Ap and Bp stars during their main sequence lives, a sample of these stars in open clusters has been obtained, as such stars can be assumed to have the same ages as the clusters to which they belong. However, in exploring age determinations in the literature, we find a large dispersion among different age determinations, even for bright, nearby clusters. Aims: Our aim is to obtain ages that are as accurate as possible for the seven nearby open clusters α Per, Coma Ber, IC 2602, NGC 2232, NGC 2451A, NGC 2516, and NGC 6475, each of which contains at least one magnetic Ap or Bp star. Simultaneously, we test the current calibrations of Te and luminosity for the Ap/Bp star members, and identify clearly blue stragglers in the clusters studied. Methods: We explore the possibility that isochrone fitting in the theoretical Hertzsprung-Russell diagram (i.e. log (L/L⊙) vs. log Te), rather than in the conventional colour-magnitude diagram, can provide more precise and accurate cluster ages, with well-defined uncertainties. Results: Well-defined ages are found for all the clusters studied. For the nearby clusters studied, the derived ages are not very sensitive to the small uncertainties in distance, reddening, membership, metallicity, or choice of isochrones. Our age determinations are all within the range of previously determined values, but the associated uncertainties are considerably smaller than the spread in recent age determinations from the literature. Furthermore, examination of proper motions and HR diagrams confirms that the Ap stars identified in these clusters are members, and that the presently accepted temperature scale and bolometric corrections for Ap stars are approximately correct. We show that in these theoretical HR diagrams blue stragglers are particularly easy to identify. Conclusions: Constructing the theoretical HR diagram

  12. A Novel GLP1 Receptor Interacting Protein ATP6ap2 Regulates Insulin Secretion in Pancreatic Beta Cells*

    PubMed Central

    Dai, Feihan F.; Bhattacharjee, Alpana; Liu, Ying; Batchuluun, Battsetseg; Zhang, Ming; Wang, Xinye Serena; Huang, Xinyi; Luu, Lemieux; Zhu, Dan; Gaisano, Herbert; Wheeler, Michael B.

    2015-01-01

    GLP1 activates its receptor, GLP1R, to enhance insulin secretion. The activation and transduction of GLP1R requires complex interactions with a host of accessory proteins, most of which remain largely unknown. In this study, we used membrane-based split ubiquitin yeast two-hybrid assays to identify novel GLP1R interactors in both mouse and human islets. Among these, ATP6ap2 (ATPase H+-transporting lysosomal accessory protein 2) was identified in both mouse and human islet screens. ATP6ap2 was shown to be abundant in islets including both alpha and beta cells. When GLP1R and ATP6ap2 were co-expressed in beta cells, GLP1R was shown to directly interact with ATP6ap2, as assessed by co-immunoprecipitation. In INS-1 cells, overexpression of ATP6ap2 did not affect insulin secretion; however, siRNA knockdown decreased both glucose-stimulated and GLP1-induced insulin secretion. Decreases in GLP1-induced insulin secretion were accompanied by attenuated GLP1 stimulated cAMP accumulation. Because ATP6ap2 is a subunit required for V-ATPase assembly of insulin granules, it has been reported to be involved in granule acidification. In accordance with this, we observed impaired insulin granule acidification upon ATP6ap2 knockdown but paradoxically increased proinsulin secretion. Importantly, as a GLP1R interactor, ATP6ap2 was required for GLP1-induced Ca2+ influx, in part explaining decreased insulin secretion in ATP6ap2 knockdown cells. Taken together, our findings identify a group of proteins that interact with the GLP1R. We further show that one interactor, ATP6ap2, plays a novel dual role in beta cells, modulating both GLP1R signaling and insulin processing to affect insulin secretion. PMID:26272612

  13. 76 FR 82079 - AP1000 Design Certification Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-30

    ... reference Revision 15 of the design control document (DCD) (ADAMS Accession No. ML053460400), which... to DAC in the areas of piping design (Chapter 3), instrumentation and control (I&C) systems (Chapter... Systems Manual, as described in the AP1000 Design Control Document, Revision 17, meets the criteria of...

  14. Structure and substrate-binding mechanism of human Ap4A hydrolase.

    PubMed

    Swarbrick, James D; Buyya, Smrithi; Gunawardana, Dilantha; Gayler, Kenwyn R; McLennan, Alexander G; Gooley, Paul R

    2005-03-04

    Asymmetric diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) hydrolases play a major role in maintaining homeostasis by cleaving the metabolite diadenosine tetraphosphate (Ap(4)A) back into ATP and AMP. The NMR solution structures of the 17-kDa human asymmetric Ap(4)A hydrolase have been solved in both the presence and absence of the product ATP. The adenine moiety of the nucleotide predominantly binds in a ring stacking arrangement equivalent to that observed in the x-ray structure of the homologue from Caenorhabditis elegans. The binding site is, however, markedly divergent to that observed in the plant/pathogenic bacteria class of enzymes, opening avenues for the exploration of specific therapeutics. Binding of ATP induces substantial conformational and dynamic changes that were not observed in the C. elegans structure. In contrast to the C. elegans homologue, important side chains that play a major role in substrate binding do not have to reorient to accommodate the ligand. This may have important implications in the mechanism of substrate recognition in this class of enzymes.

  15. 30 Years of APS Congressional Fellows: Looking Back and Looking Forward

    NASA Astrophysics Data System (ADS)

    2003-04-01

    In 1973 AAAS launched a Congressional Fellows Program, and APS was one of three founding participants. Since then, APS has funded one or two Fellows annually to work with a Congressional Committee or on the personal staff of a Member of Congress. These fellows individually and collectively have had and continue to have a large impact in Washington. Six Fellows from different periods of the 30-year program, including a current Member of Congress, will present their views and assessments of the Fellowship program. They will address how it affected them, what it has done for the country and how APS should plan for the future. There will be ample time for questions and discussion. Panelists: Ben Cooper, Association of Oil Pipe Lines (Fellow, 1973-74) Rush Holt, Member, House of Representatives (Fellow, 1982-83) Jane Alexander, Office of Naval Research (Fellow, 1986-87) Duncan Moore, University of Rochester (Fellow, 1993-94) Peter Rooney, House Committee on Science (Fellow, 1997-98) Sherri Stephan, Senate Committee on Government Affairs (Fellow, 2000-01)

  16. [Effects of nitrogen additions on soil hydrolase and oxidase activities in Pinus elliottii plantations.

    PubMed

    Zhang, Chuang; Zou, Hong Tao; Zhang, Xin Yu; Kou, Liang; Yang, Yang; Sun, Xiao Min; Li, Sheng Gong; Wang, Hui Min

    2016-11-18

    We evaluated responses of hydrolase and oxidase activities in a subtropical Pinus elliottii plantation through a nitrogen (N) addition field experiment (dosage level: 0, 40, 120 kg N·hm -2 ·a -1 ). The results showed that N additions significantly decreased the carbon, nitrogen and phosphorus related hydrolase and oxidase activities. The activities of β-1,4-glucosidase (BG), cellobiohydrolase (CBH), β-1,4-N-acetylglucosaminidase (NAG) and peroxidase (PER) activities were decreased by 16.5%-51.1% due to N additions, and the decrease was more remarkable in the higher N addition treatment. The activities of α-1,4-glucosidase (aG), β-1,4-xylosidase (BX), acid phosphatase (AP) and phenol oxidase (PPO) were decreased by 14.5%-38.6% by N additions, however, there was no significant difference among the different N addition treatments. Soil enzyme activities varied obviously in different seasons. The activities of BG, NAG, BX, CBH, AP and PPO were in the order of March > June > October, and aG and PER activities were in the order of October > March > June. Most of the soil hydrolase and oxidase activities were positively correlated with soil pH, but negatively with NO 3 - -N content. It indicated that N additions inhibited soil hydrolase and oxidase activities by reducing soil pH and increasing soil nitrification. N additions inhibited the soil organic matter mineralization and turnover in the subtropical area, and the effects were obvious with the increasing dosage of N additions.

  17. Draft Plan to Develop Non-Intrusive Load Monitoring Test Protocols

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

    Mayhorn, Ebony T.; Sullivan, Greg P.; Petersen, Joseph M.

    2015-09-29

    This document presents a Draft Plan proposed to develop a common test protocol that can be used to evaluate the performance requirements of Non-Intrusive Load Monitoring. Development on the test protocol will be focused on providing a consistent method that can be used to quantify and compare the performance characteristics of NILM products. Elements of the protocols include specifications for appliances to be used, metrics, instrumentation, and a procedure to simulate appliance behavior during tests. In addition, three priority use cases for NILM will be identified and their performance requirements will specified.

  18. Performance analysis of routing protocols for IoT

    NASA Astrophysics Data System (ADS)

    Manda, Sridhar; Nalini, N.

    2018-04-01

    Internet of Things (IoT) is an arrangement of advancements that are between disciplinary. It is utilized to have compelling combination of both physical and computerized things. With IoT physical things can have personal virtual identities and participate in distributed computing. Realization of IoT needs the usage of sensors based on the sector for which IoT is integrated. For instance, in healthcare domain, IoT needs to have integration with wearable sensors used by patients. As sensor devices produce huge amount of data, often called big data, there should be efficient routing protocols in place. To the extent remote systems is worried there are some current protocols, for example, OLSR, DSR and AODV. It additionally tosses light into Trust based routing protocol for low-power and lossy systems (TRPL) for IoT. These are broadly utilized remote directing protocols. As IoT is developing round the corner, it is basic to investigate routing protocols that and evaluate their execution regarding throughput, end to end delay, and directing overhead. The execution experiences can help in settling on very much educated choices while incorporating remote systems with IoT. In this paper, we analyzed different routing protocols and their performance is compared. It is found that AODV showed better performance than other routing protocols aforementioned.

  19. The importance of the Montreal Protocol in protecting climate.

    PubMed

    Velders, Guus J M; Andersen, Stephen O; Daniel, John S; Fahey, David W; McFarland, Mack

    2007-03-20

    The 1987 Montreal Protocol on Substances that Deplete the Ozone Layer is a landmark agreement that has successfully reduced the global production, consumption, and emissions of ozone-depleting substances (ODSs). ODSs are also greenhouse gases that contribute to the radiative forcing of climate change. Using historical ODSs emissions and scenarios of potential emissions, we show that the ODS contribution to radiative forcing most likely would have been much larger if the ODS link to stratospheric ozone depletion had not been recognized in 1974 and followed by a series of regulations. The climate protection already achieved by the Montreal Protocol alone is far larger than the reduction target of the first commitment period of the Kyoto Protocol. Additional climate benefits that are significant compared with the Kyoto Protocol reduction target could be achieved by actions under the Montreal Protocol, by managing the emissions of substitute fluorocarbon gases and/or implementing alternative gases with lower global warming potentials.

  20. The importance of the Montreal Protocol in protecting climate

    PubMed Central

    Velders, Guus J. M.; Andersen, Stephen O.; Daniel, John S.; Fahey, David W.; McFarland, Mack

    2007-01-01

    The 1987 Montreal Protocol on Substances that Deplete the Ozone Layer is a landmark agreement that has successfully reduced the global production, consumption, and emissions of ozone-depleting substances (ODSs). ODSs are also greenhouse gases that contribute to the radiative forcing of climate change. Using historical ODSs emissions and scenarios of potential emissions, we show that the ODS contribution to radiative forcing most likely would have been much larger if the ODS link to stratospheric ozone depletion had not been recognized in 1974 and followed by a series of regulations. The climate protection already achieved by the Montreal Protocol alone is far larger than the reduction target of the first commitment period of the Kyoto Protocol. Additional climate benefits that are significant compared with the Kyoto Protocol reduction target could be achieved by actions under the Montreal Protocol, by managing the emissions of substitute fluorocarbon gases and/or implementing alternative gases with lower global warming potentials. PMID:17360370

  1. Genome-Wide Investigation and Expression Profiling of AP2/ERF Transcription Factor Superfamily in Foxtail Millet (Setaria italica L.)

    PubMed Central

    Lata, Charu; Mishra, Awdhesh Kumar; Muthamilarasan, Mehanathan; Bonthala, Venkata Suresh; Khan, Yusuf; Prasad, Manoj

    2014-01-01

    The APETALA2/ethylene-responsive element binding factor (AP2/ERF) family is one of the largest transcription factor (TF) families in plants that includes four major sub-families, namely AP2, DREB (dehydration responsive element binding), ERF (ethylene responsive factors) and RAV (Related to ABI3/VP). AP2/ERFs are known to play significant roles in various plant processes including growth and development and biotic and abiotic stress responses. Considering this, a comprehensive genome-wide study was conducted in foxtail millet (Setaria italica L.). A total of 171 AP2/ERF genes were identified by systematic sequence analysis and were physically mapped onto nine chromosomes. Phylogenetic analysis grouped AP2/ERF genes into six classes (I to VI). Duplication analysis revealed that 12 (∼7%) SiAP2/ERF genes were tandem repeated and 22 (∼13%) were segmentally duplicated. Comparative physical mapping between foxtail millet AP2/ERF genes and its orthologs of sorghum (18 genes), maize (14 genes), rice (9 genes) and Brachypodium (6 genes) showed the evolutionary insights of AP2/ERF gene family and also the decrease in orthology with increase in phylogenetic distance. The evolutionary significance in terms of gene-duplication and divergence was analyzed by estimating synonymous and non-synonymous substitution rates. Expression profiling of candidate AP2/ERF genes against drought, salt and phytohormones revealed insights into their precise and/or overlapping expression patterns which could be responsible for their functional divergence in foxtail millet. The study showed that the genes SiAP2/ERF-069, SiAP2/ERF-103 and SiAP2/ERF-120 may be considered as potential candidate genes for further functional validation as well for utilization in crop improvement programs for stress resistance since these genes were up-regulated under drought and salinity stresses in ABA dependent manner. Altogether the present study provides new insights into evolution, divergence and systematic

  2. Genome-wide investigation and expression profiling of AP2/ERF transcription factor superfamily in foxtail millet (Setaria italica L.).

    PubMed

    Lata, Charu; Mishra, Awdhesh Kumar; Muthamilarasan, Mehanathan; Bonthala, Venkata Suresh; Khan, Yusuf; Prasad, Manoj

    2014-01-01

    The APETALA2/ethylene-responsive element binding factor (AP2/ERF) family is one of the largest transcription factor (TF) families in plants that includes four major sub-families, namely AP2, DREB (dehydration responsive element binding), ERF (ethylene responsive factors) and RAV (Related to ABI3/VP). AP2/ERFs are known to play significant roles in various plant processes including growth and development and biotic and abiotic stress responses. Considering this, a comprehensive genome-wide study was conducted in foxtail millet (Setaria italica L.). A total of 171 AP2/ERF genes were identified by systematic sequence analysis and were physically mapped onto nine chromosomes. Phylogenetic analysis grouped AP2/ERF genes into six classes (I to VI). Duplication analysis revealed that 12 (∼7%) SiAP2/ERF genes were tandem repeated and 22 (∼13%) were segmentally duplicated. Comparative physical mapping between foxtail millet AP2/ERF genes and its orthologs of sorghum (18 genes), maize (14 genes), rice (9 genes) and Brachypodium (6 genes) showed the evolutionary insights of AP2/ERF gene family and also the decrease in orthology with increase in phylogenetic distance. The evolutionary significance in terms of gene-duplication and divergence was analyzed by estimating synonymous and non-synonymous substitution rates. Expression profiling of candidate AP2/ERF genes against drought, salt and phytohormones revealed insights into their precise and/or overlapping expression patterns which could be responsible for their functional divergence in foxtail millet. The study showed that the genes SiAP2/ERF-069, SiAP2/ERF-103 and SiAP2/ERF-120 may be considered as potential candidate genes for further functional validation as well for utilization in crop improvement programs for stress resistance since these genes were up-regulated under drought and salinity stresses in ABA dependent manner. Altogether the present study provides new insights into evolution, divergence and systematic

  3. Novel fluorescent labelled affinity probes for diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A)-binding studies.

    PubMed

    Wright, Michael; Miller, Andrew D

    2006-02-15

    Tandem synthetic-biosynthetic procedures were used to prepare two novel fluorescent labelled affinity probes for diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A)-binding studies. These compounds (dial-mant-Ap4A and azido-mant-Ap4A) are shown to clearly distinguish known Ap4A-binding proteins from Escherichia coli (LysU and GroEL) and a variety of other control proteins. Successful labelling of chaperonin GroEL appears to be allosteric with respect to the well-characterized adenosine 5'-triphosphate (ATP)-binding site, suggesting that GroEL possesses a distinct Ap4A-binding site.

  4. Development of cotton gin PM2.5 emission factors for EPA’S AP-42

    USDA-ARS?s Scientific Manuscript database

    The Compilation of Air Pollution Emission Factors (AP-42) emission factors are assigned ratings, from A (Excellent) to E (Poor), based on the quality of data used to develop them. AP-42 currently contains no PM2.5 cotton gin emission factors. In an effort to develop science-based data for regulating...

  5. 15 CFR 782.5 - Where to obtain APR report forms.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS GENERAL... forms required by the APR may be downloaded from the Internet at http://www.ap.gov. You also may obtain these forms by contacting: Treaty Compliance Division, Bureau of Industry and Security, U.S. Department...

  6. 15 CFR 782.5 - Where to obtain APR report forms.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS GENERAL... forms required by the APR may be downloaded from the Internet at http://www.ap.gov. You also may obtain these forms by contacting: Treaty Compliance Division, Bureau of Industry and Security, U.S. Department...

  7. 15 CFR 782.5 - Where to obtain APR report forms.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS GENERAL... forms required by the APR may be downloaded from the Internet at http://www.ap.gov. You also may obtain these forms by contacting: Treaty Compliance Division, Bureau of Industry and Security, U.S. Department...

  8. 15 CFR 782.5 - Where to obtain APR report forms.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS GENERAL... forms required by the APR may be downloaded from the Internet at http://www.ap.gov. You also may obtain these forms by contacting: Treaty Compliance Division, Bureau of Industry and Security, U.S. Department...

  9. 15 CFR 782.5 - Where to obtain APR report forms.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS GENERAL... forms required by the APR may be downloaded from the Internet at http://www.ap.gov. You also may obtain these forms by contacting: Treaty Compliance Division, Bureau of Industry and Security, U.S. Department...

  10. Analysis of the AP-42, supplement 5 emission model.

    DOT National Transportation Integrated Search

    1976-01-01

    This report examines the performance of the source strength model presented in the U.S. Environmental Protection Agency publication AP-42, Supplement 5 relative to field data gathered during the AIRPOL project and relative to the previous source stre...

  11. Neuropsychological correlates of transcription factor AP-2Beta, and its interaction with COMT and MAOA in healthy females.

    PubMed

    Schabram, Ina; Eggermann, Thomas; Siegel, Steven J; Gründer, Gerhard; Zerres, Klaus; Vernaleken, Ingo

    2013-01-01

    The transcription factor AP-2β has been shown to impact clinical and neuropsychological properties. Apparently, it regulates the transcription of genes that code for molecules which are part of the catecholaminergic transmission system. This investigation focuses on possible effects of the transcription factor AP-2β intron 2 polymorphism on cognitive performance parameters. This hypothesis-driven investigation examined the effects and interactions of the transcription factor AP-2β intron 2 polymorphism, the Val158Met catechol-O-methyltransferase (COMT) polymorphism, and the variable number of tandem repeat polymorphism of monoamine oxidase A (MAOA) on cognitive performance parameters within a group of 200 healthy women (age: mean ± SD, 23.93 ± 3.33 years). The AP-2β polymorphism significantly influenced cognitive performance (in particular, the Trail Making Test part B), whereas the MAOA and COMT polymorphisms did not. However, there was an interaction effect of the AP-2β × MAOA × COMT genotypes on the decision bias β of the degraded-stimulus version of the continuous performance task. Only the Val158Met COMT polymorphism showed an influence on personality questionnaires (openness and self-transcendence; NEO Five-Factor Inventory, Temperament and Character Inventory). The transcription factor AP-2β intron 2 polymorphism had more influence on cognition than the MAOA and COMT polymorphisms. Possibly, the AP-2β genotype might influence cognition through pathways other than those that regulate MAOA and COMT transcription. Interactions of transcription factor AP-2β, COMT, and MAOA polymorphisms suggest higher leverage effects of transcription factor AP-2β in subjects with high dopamine availability. Copyright © 2013 S. Karger AG, Basel.

  12. The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair.

    PubMed

    Cukras, Scott; Lee, Euiho; Palumbo, Emily; Benavidez, Pamela; Moldovan, George-Lucian; Kee, Younghoon

    2016-10-01

    USP1 deubiquitinating enzyme and its stoichiometric binding partner UAF1 play an essential role in promoting DNA homologous recombination (HR) repair in response to various types of DNA damaging agents. Deubiquitination of FANCD2 may be attributed to the key role of USP1-UAF1 complex in regulating HR repair, however whether USP1-UAF1 promotes HR repair independently of FANCD2 deubiquitination is not known. Here we show evidence that the USP1-UAF1 complex has a FANCD2-independent function in promoting HR repair. Proteomic search of UAF1-interacting proteins revealed that UAF1 associates with RAD51AP1, a RAD51-interacting protein implicated in HR repair. We show that UAF1 mediates the interaction between USP1 and RAD51AP1, and that depletion of USP1 or UAF1 led to a decreased stability of RAD51AP1. Protein interaction mapping analysis identified some key residues within RAD51AP1 required for interacting with the USP1-UAF1 complex. Cells expressing the UAF1 interaction-deficient mutant of RAD51AP1 show increased chromosomal aberrations in response to Mitomycin C treatment. Moreover, similar to the RAD51AP1 depleted cells, the cells expressing UAF1-interaction deficient RAD51AP1 display persistent RAD51 foci following DNA damage exposure, indicating that these factors regulate a later step during the HR repair. These data altogether suggest that the USP1-UAF1 complex promotes HR repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1.

  13. The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair

    PubMed Central

    Cukras, Scott; Lee, Euiho; Palumbo, Emily; Benavidez, Pamela; Moldovan, George-Lucian; Kee, Younghoon

    2016-01-01

    ABSTRACT USP1 deubiquitinating enzyme and its stoichiometric binding partner UAF1 play an essential role in promoting DNA homologous recombination (HR) repair in response to various types of DNA damaging agents. Deubiquitination of FANCD2 may be attributed to the key role of USP1-UAF1 complex in regulating HR repair, however whether USP1-UAF1 promotes HR repair independently of FANCD2 deubiquitination is not known. Here we show evidence that the USP1-UAF1 complex has a FANCD2-independent function in promoting HR repair. Proteomic search of UAF1-interacting proteins revealed that UAF1 associates with RAD51AP1, a RAD51-interacting protein implicated in HR repair. We show that UAF1 mediates the interaction between USP1 and RAD51AP1, and that depletion of USP1 or UAF1 led to a decreased stability of RAD51AP1. Protein interaction mapping analysis identified some key residues within RAD51AP1 required for interacting with the USP1-UAF1 complex. Cells expressing the UAF1 interaction-deficient mutant of RAD51AP1 show increased chromosomal aberrations in response to Mitomycin C treatment. Moreover, similar to the RAD51AP1 depleted cells, the cells expressing UAF1-interaction deficient RAD51AP1 display persistent RAD51 foci following DNA damage exposure, indicating that these factors regulate a later step during the HR repair. These data altogether suggest that the USP1-UAF1 complex promotes HR repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1. PMID:27463890

  14. A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas.

    PubMed

    Attia, Steven; Kolesar, Jill; Mahoney, Michelle R; Pitot, Henry C; Laheru, Daniel; Heun, James; Huang, Wei; Eickhoff, Jens; Erlichman, Charles; Holen, Kyle D

    2008-08-01

    3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) is a novel small molecule inhibitor of ribonucleotide reductase (RR) with clinical signs of activity in pancreatic cancer. Therefore, the Phase 2 Consortium (P2C) initiated a trial (two single stage studies with planned interim analysis) of 3-AP at 96 mg/m(2) intravenously days 1-4 and 15-18 of a 28-day cycle in both chemotherapy-naive and gemcitabine-refractory (GR) patients with advanced pancreatic cancer. The primary endpoint was survival at six months (chemotherapy-naive) and four months (GR). Secondary endpoints were toxicity, response, overall survival, time to progression and mechanistic studies. Fifteen patients were enrolled including one chemotherapy-naïve and 14 GR. The chemotherapy-naïve patient progressed during cycle 1 with grade 3 and 4 toxicities. Of 14 GR patients, seven received two cycles, six received one cycle and one received eight cycles. Progression precluded further treatment in 11 GR patients. Additionally, one died of an ileus in cycle 1 considered related to treatment and two stopped treatment due to toxicity. Five GR patients had grade 4 toxicities possibly related to 3-AP and six GR patients had grade 3 fatigue. Toxicities and lack of meaningful clinical benefit prompted early study closure. Four-month survival in GR patients was 21% (95% CI: 8-58%). Correlative studies confirmed that 3-AP increased the percentage of S-phase buccal mucosal cells, the presence of multidrug resistance gene polymorphisms appeared to predict leukopenia, and baseline pancreatic tumor RR M2 expression was low relative to other tumors treated with 3-AP. In conclusion, this regimen appears inactive against predominantly GR pancreatic cancer. RR M2 protein may not have a critical role in the malignant potential of pancreatic cancer.

  15. A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas

    PubMed Central

    Attia, Steven; Kolesar, Jill; Mahoney, Michelle R.; Pitot, Henry C.; Laheru, Daniel; Heun, James; Huang, Wei; Eickhoff, Jens; Erlichman, Charles

    2015-01-01

    Summary 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) is a novel small molecule inhibitor of ribonucleotide reductase (RR) with clinical signs of activity in pancreatic cancer. Therefore, the Phase 2 Consortium (P2C) initiated a trial (two single stage studies with planned interim analysis) of 3-AP at 96 mg/m2 intravenously days 1–4 and 15–18 of a 28-day cycle in both chemotherapy-naive and gemcitabine-refractory (GR) patients with advanced pancreatic cancer. The primary endpoint was survival at six months (chemotherapy-naive) and four months (GR). Secondary endpoints were toxicity, response, overall survival, time to progression and mechanistic studies. Fifteen patients were enrolled including one chemotherapy-naïve and 14 GR. The chemotherapy-naïve patient progressed during cycle 1 with grade 3 and 4 toxicities. Of 14 GR patients, seven received two cycles, six received one cycle and one received eight cycles. Progression precluded further treatment in 11 GR patients. Additionally, one died of an ileus in cycle 1 considered related to treatment and two stopped treatment due to toxicity. Five GR patients had grade 4 toxicities possibly related to 3-AP and six GR patients had grade 3 fatigue. Toxicities and lack of meaningful clinical benefit prompted early study closure. Four-month survival in GR patients was 21% (95% CI: 8–58%). Correlative studies confirmed that 3-AP increased the percentage of S-phase buccal mucosal cells, the presence of multidrug resistance gene polymorphisms appeared to predict leukopenia, and baseline pancreatic tumor RR M2 expression was low relative to other tumors treated with 3-AP. In conclusion, this regimen appears inactive against predominantly GR pancreatic cancer. RR M2 protein may not have a critical role in the malignant potential of pancreatic cancer. PMID:18278438

  16. BLOC-1 Interacts with BLOC-2 and the AP-3 Complex to Facilitate Protein Trafficking on Endosomes

    PubMed Central

    Di Pietro, Santiago M.; Falcón-Pérez, Juan M.; Tenza, Danièle; Setty, Subba R.G.; Marks, Michael S.; Raposo, Graça

    2006-01-01

    The adaptor protein (AP)-3 complex is a component of the cellular machinery that controls protein sorting from endosomes to lysosomes and specialized related organelles such as melanosomes. Mutations in an AP-3 subunit underlie a form of Hermansky-Pudlak syndrome (HPS), a disorder characterized by abnormalities in lysosome-related organelles. HPS in humans can also be caused by mutations in genes encoding subunits of three complexes of unclear function, named biogenesis of lysosome-related organelles complex (BLOC)-1, -2, and -3. Here, we report that BLOC-1 interacts physically and functionally with AP-3 to facilitate the trafficking of a known AP-3 cargo, CD63, and of tyrosinase-related protein 1 (Tyrp1), a melanosomal membrane protein previously thought to traffic only independently of AP-3. BLOC-1 also interacts with BLOC-2 to facilitate Tyrp1 trafficking by a mechanism apparently independent of AP-3 function. Both BLOC-1 and -2 localize mainly to early endosome-associated tubules as determined by immunoelectron microscopy. These findings support the idea that BLOC-1 and -2 represent hitherto unknown components of the endosomal protein trafficking machinery. PMID:16837549

  17. The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling

    PubMed Central

    Chakraborty, Atanu; Diefenbacher, Markus E.; Mylona, Anastasia; Kassel, Olivier; Behrens, Axel

    2015-01-01

    The c-Jun/AP-1 transcription factor controls key cellular behaviours, including proliferation and apoptosis, in response to JNK and Ras/MAPK signalling. While the JNK pathway has been well characterised, the mechanism of activation by Ras was elusive. Here we identify the uncharacterised ubiquitin ligase Trim7 as a critical component of AP-1 activation via Ras. We found that MSK1 directly phosphorylates Trim7 in response to direct activation by the Ras–Raf–MEK–ERK pathway, and this modification stimulates Trim7 E3 ubiquitin ligase activity. Trim7 mediates Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilisation. Consequently, Trim7 depletion reduces RACO-1 levels and AP-1-dependent gene expression. Moreover, transgenic overexpression of Trim7 increases lung tumour burden in a Ras-driven cancer model, and knockdown of Trim7 in established xenografts reduces tumour growth. Thus, phosphorylation-ubiquitination crosstalk between MSK1, Trim7 and RACO-1 completes the long sought-after mechanism linking growth factor signalling and AP-1 activation. PMID:25851810

  18. The Role of Activator Protein-1 (AP-1) Family Members in CD30-Positive Lymphomas

    PubMed Central

    Garces de los Fayos Alonso, Ines; Lagger, Sabine; Merkel, Olaf; Kenner, Lukas

    2018-01-01

    The Activator Protein-1 (AP-1) transcription factor (TF) family, composed of a variety of members including c-JUN, c-FOS and ATF, is involved in mediating many biological processes such as proliferation, differentiation and cell death. Since their discovery, the role of AP-1 TFs in cancer development has been extensively analysed. Multiple in vitro and in vivo studies have highlighted the complexity of these TFs, mainly due to their cell-type specific homo- or hetero-dimerization resulting in diverse transcriptional response profiles. However, as a result of the increasing knowledge of the role of AP-1 TFs in disease, these TFs are being recognized as promising therapeutic targets for various malignancies. In this review, we focus on the impact of deregulated expression of AP-1 TFs in CD30-positive lymphomas including Classical Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma. PMID:29597249

  19. Molecular cloning of Rab5 (ApRab5) in Aiptasia pulchella and its retention in phagosomes harboring live zooxanthellae.

    PubMed

    Chen, Ming-Chyuan; Cheng, Ying-Min; Hong, Min-Chang; Fang, Lee-Shing

    2004-11-19

    The intracellular association of symbiotic dinoflagellates (zooxanthellae) with marine cnidarians is the very foundation of the highly productive and diversified coral reef ecosystems. To reveal its underlying molecular mechanisms, we previously cloned ApRab7, a Rab7 homologue of the sea anemone Aiptasia pulchella, and demonstrated its selective exclusion from phagosomes containing live zooxanthellae, but not from those containing either dead or photosynthesis-impaired algae. In this study, Rab5 was characterized, due to its key role in endocytosis and phagocytosis acting upstream of Rab7. The Aiptasia Rab5 homologue (ApRab5) is 79.5% identical to human Rab5C and contains all Rab-specific signature motifs. Subcellular fractionation study showed that ApRab5 is mainly cytosolic. EGFP reporter and phagocytosis studies indicated that membrane-associated ApRab5 is present in early endocytic and phagocytic compartments, and is able to promote their fusion. Significantly, immunofluorescence study showed that the majority of phagosomes containing either resident or newly internalized live zooxanthellae were labeled with ApRab5, while those containing either heat-killed or photosynthesis-impaired algae were mostly negative for ApRab5 staining whereas the opposite was observed for ApRab7. We propose that active phagosomal retention of ApRab5 is part of the mechanisms employed by live zooxanthellae to: (1) persist inside their host cells and (2) exclude ApRab7 from their phagosomes, thereby, establishing and/or maintaining an endosymbiotic relationship with their cnidarian hosts.

  20. Cold-fusion television show angers APS

    NASA Astrophysics Data System (ADS)

    Cartwright, Jon

    2009-06-01

    Cold fusion has been controversial since its inception on 23 March 1989, when chemists Martin Fleischmann and Stanley Pons at the University of Utah in the US announced that they had achieved a sustained nuclear-fusion reaction at room temperature. Two decades on, a US television documentary about the field has stirred up fresh debate after it linked the American Physical Society (APS) to an evaluation of some cold-fusion results by Robert Duncan, a physicist and vice chancellor of the University of Missouri.

  1. Microwave Protocols for Paraffin Microtechnique and In Situ Localization in Plants

    NASA Astrophysics Data System (ADS)

    Schichnes, Denise; Nemson, Jeff; Sohlberg, Lorraine; Ruzin, Steven E.

    1998-10-01

    : We have developed a microwave protocol for a paraffin-embedding microtechnique of the shoot apical meristem of ZEA MAYS and have successfully applied this protocol to other plant tissues. This protocol decreases the time required for all aspects of microtechnique tissue processing, including fixation (24 hr to 15 min), dehydration (73 hr to 10 min), and infiltration (96 hr to 3 hr). Additionally, the time required to adhere paraffin ribbons to gelatin-coated slides and for the Johanson's safranin O, fast green FCF staining protocol has been significantly decreased. Using this technique, the quality of tissue preservation and subsequent in situ localization of KNOTTED mRNA was increased by using microwaves.

  2. AP-8 trapped proton environment for solar maximum and solar minimum. [Computer accessible models

    NASA Technical Reports Server (NTRS)

    Sawyer, D. M.; Vette, J. I.

    1976-01-01

    Data sets from Ov-3 and Azur indicate a need for improvement in models of the stably trapped proton flux with energies between 0.1 and 400 MeV. Two computer accessible models are described: AP8MAX and AP8MIN. The models are presented in the form of nomographs, B-L plots, R-lambda plots, and equatorial radial profiles. Nomographs of the orbit-integrated fluxes are also discussed. The models are compared with each other, with the data, and with previous AP models. Requirements for future improvements include more complete data coverage and periodic comparisons with new data sets as they become available. The machine-sensible format in which the models are available are described.

  3. Proteomic identification of E6AP as a molecular target of tamoxifen in MCF7 cells.

    PubMed

    Lochab, Savita; Pal, Pooja; Kanaujiya, Jitendra K; Tripathi, Shashi B; Kapoor, Isha; Bhatt, Madan L B; Sanyal, Sabyasachi; Behre, Gerhard; Trivedi, Arun K

    2012-05-01

    Tamoxifen (Tam) is most widely used selective estrogen receptor modulator (SERM) for treatment of hormone-responsive breast cancer. Despite being regularly used in clinical therapy for breast cancer since 1971, the mechanism of Tam action remains largely unclear. In order to gain insights into Tam-mediated antibreast cancer actions, we applied 2DE and MS based proteomics approach to identify target proteins of Tam. We identified E6-associated protein, i.e. E6AP (UBE3A) among others to be regulated by Tam that otherwise is upregulated in breast tumors. We confirmed our 2DE finding by immunoblotting and further show that Tam leads to inhibition of E6AP expression presumably by promoting its autoubiquitination, which is coupled with nuclear export and subsequent proteasome-mediated degradation. Furthermore, we show that Tam- and siE6AP-mediated inhibition of E6AP leads to enhanced G0-G1 growth arrest and apoptosis, which is also evident from significant upregulation of cytochrome-c, Bax, p21, and PARP cleavage. Taken together, our data suggest that, Tam-targeted E6AP inhibition is in fact required for Tam-mediated antibreast cancer actions. Thus, E6AP may be a therapeutic target in breast cancer. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Protein phosphatase AP2C1 negatively regulates basal resistance and defense responses to Pseudomonas syringae.

    PubMed

    Shubchynskyy, Volodymyr; Boniecka, Justyna; Schweighofer, Alois; Simulis, Justinas; Kvederaviciute, Kotryna; Stumpe, Michael; Mauch, Felix; Balazadeh, Salma; Mueller-Roeber, Bernd; Boutrot, Freddy; Zipfel, Cyril; Meskiene, Irute

    2017-02-01

    Mitogen-activated protein kinases (MAPKs) mediate plant immune responses to pathogenic bacteria. However, less is known about the cell autonomous negative regulatory mechanism controlling basal plant immunity. We report the biological role of Arabidopsis thaliana MAPK phosphatase AP2C1 as a negative regulator of plant basal resistance and defense responses to Pseudomonas syringae. AP2C2, a closely related MAPK phosphatase, also negatively controls plant resistance. Loss of AP2C1 leads to enhanced pathogen-induced MAPK activities, increased callose deposition in response to pathogen-associated molecular patterns or to P. syringae pv. tomato (Pto) DC3000, and enhanced resistance to bacterial infection with Pto. We also reveal the impact of AP2C1 on the global transcriptional reprogramming of transcription factors during Pto infection. Importantly, ap2c1 plants show salicylic acid-independent transcriptional reprogramming of several defense genes and enhanced ethylene production in response to Pto. This study pinpoints the specificity of MAPK regulation by the different MAPK phosphatases AP2C1 and MKP1, which control the same MAPK substrates, nevertheless leading to different downstream events. We suggest that precise and specific control of defined MAPKs by MAPK phosphatases during plant challenge with pathogenic bacteria can strongly influence plant resistance. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  5. Long-term nitrogen addition leads to loss of species richness due to litter accumulation and soil acidification in a temperate steppe.

    PubMed

    Fang, Ying; Xun, Fen; Bai, Wenming; Zhang, Wenhao; Li, Linghao

    2012-01-01

    Although community structure and species richness are known to respond to nitrogen fertilization dramatically, little is known about the mechanisms underlying specific species replacement and richness loss. In an experiment in semiarid temperate steppe of China, manipulative N addition with five treatments was conducted to evaluate the effect of N addition on the community structure and species richness. Species richness and biomass of community in each plot were investigated in a randomly selected quadrat. Root element, available and total phosphorus (AP, TP) in rhizospheric soil, and soil moisture, pH, AP, TP and inorganic N in the soil were measured. The relationship between species richness and the measured factors was analyzed using bivariate correlations and stepwise multiple linear regressions. The two dominant species, a shrub Artemisia frigida and a grass Stipa krylovii, responded differently to N addition such that the former was gradually replaced by the latter. S. krylovii and A. frigida had highly-branched fibrous and un-branched tap root systems, respectively. S. krylovii had higher height than A. frigida in both control and N added plots. These differences may contribute to the observed species replacement. In addition, the analysis on root element and AP contents in rhizospheric soil suggests that different calcium acquisition strategies, and phosphorus and sodium responses of the two species may account for the replacement. Species richness was significantly reduced along the five N addition levels. Our results revealed a significant relationship between species richness and soil pH, litter amount, soil moisture, AP concentration and inorganic N concentration. Our results indicate that litter accumulation and soil acidification accounted for 52.3% and 43.3% of the variation in species richness, respectively. These findings would advance our knowledge on the changes in species richness in semiarid temperate steppe of northern China under N

  6. AP1 binding site is another target of FGF2 regulation of bone sialoprotein gene transcription.

    PubMed

    Takai, Hideki; Araki, Shouta; Mezawa, Masaru; Kim, Dong-Soon; Li, Xinyue; Yang, Li; Li, Zhengyang; Wang, Zhitao; Nakayama, Youhei; Ogata, Yorimasa

    2008-02-29

    Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. We previously reported that fibroblast growth factor 2 (FGF2) regulates BSP gene transcription via FGF2 response element (FRE) in the proximal promoter of rat BSP gene. We here report that activator protein 1 (AP1) binding site overlapping with glucocorticoid response element (GRE) AP1/GRE in the rat BSP gene promoter is another target of FGF2. Using the osteoblastic cell line ROS17/2.8, we determined that BSP mRNA levels increased by 10 ng/ml FGF2 at 6 and 12 h. Runx2 protein levels increased by FGF2 (10 ng/ml) at 3 h. Treatment of ROS17/2.8 cells with FGF2 (10 ng/ml, 12 h) increased luciferase activities of constructs including -116 to +60 and -938 to +60 of the rat BSP gene promoter. Effects of FGF2 abrogated in constructs included 2 bp mutations in the FRE and AP1/GRE elements. Luciferase activities induced by FGF2 were blocked by tyrosine kinase inhibitor herbimycin A, src-tyrosine kinase inhibitor PP1 and MAP kinase kinase inhibitor U0126. Gel shift analyses showed that FGF2 increased binding of FRE and AP1/GRE elements. Notably, the AP1/GRE-protein complexes were supershifted by Smad1 and c-Fos antibodies, c-Jun and Dlx5 antibodies disrupted the complexes formation, on the other hand AP1/GRE-protein complexes did not change by Runx2 antibody. These studies demonstrate that FGF2 stimulates BSP gene transcription by targeting the FRE and AP1/GRE elements in the rat BSP gene promoter.

  7. APS: 125 Years of Progress of Physiology as a Scientific Discipline and a Profession

    ERIC Educational Resources Information Center

    Carroll, Robert G.; Frank, Martin; Ra'anan, Alice; Matyas, Marsha L.

    2013-01-01

    The Experimental Biology 2012 meeting in San Diego, CA, included events to celebrate the 125th anniversary of the founding of the American Physiological Society (APS) and reflect on the recent accomplishments of the society. Most of the APS activities in the past quarter century were guided by a series of strategic plans. Membership in the APS…

  8. Predicting the Presence of Companions for Stripped-envelope Supernovae: The Case of the Broad-lined Type Ic SN 2002ap

    NASA Astrophysics Data System (ADS)

    Zapartas, E.; de Mink, S. E.; Van Dyk, S. D.; Fox, O. D.; Smith, N.; Bostroem, K. A.; de Koter, A.; Filippenko, A. V.; Izzard, R. G.; Kelly, P. L.; Neijssel, C. J.; Renzo, M.; Ryder, S.

    2017-06-01

    Many young, massive stars are found in close binaries. Using population synthesis simulations we predict the likelihood of a companion star being present when these massive stars end their lives as core-collapse supernovae (SNe). We focus on stripped-envelope SNe, whose progenitors have lost their outer hydrogen and possibly helium layers before explosion. We use these results to interpret new Hubble Space Telescope observations of the site of the broad-lined Type Ic SN 2002ap, 14 years post-explosion. For a subsolar metallicity consistent with SN 2002ap, we expect a main-sequence (MS) companion present in about two thirds of all stripped-envelope SNe and a compact companion (likely a stripped helium star or a white dwarf/neutron star/black hole) in about 5% of cases. About a quarter of progenitors are single at explosion (originating from initially single stars, mergers, or disrupted systems). All of the latter scenarios require a massive progenitor, inconsistent with earlier studies of SN 2002ap. Our new, deeper upper limits exclude the presence of an MS companion star >8-10 {M}⊙ , ruling out about 40% of all stripped-envelope SN channels. The most likely scenario for SN 2002ap includes nonconservative binary interaction of a primary star initially ≲ 23 {M}⊙ . Although unlikely (<1% of the scenarios), we also discuss the possibility of an exotic reverse merger channel for broad-lined Type Ic events. Finally, we explore how our results depend on the metallicity and the model assumptions and discuss how additional searches for companions can constrain the physics that govern the evolution of SN progenitors.

  9. PROTOCOL FOR EXAMINATION OF THE INNER CAN CLOSURE WELD REGION FOR 3013 DE CONTAINERS

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

    Mickalonis, J.

    2014-09-16

    The protocol for the examination of the inner can closure weld region (ICCWR) for 3013 DE containers is presented within this report. The protocol includes sectioning of the inner can lid section, documenting the surface condition, measuring corrosion parameters, and storing of samples. This protocol may change as the investigation develops since findings may necessitate additional steps be taken. Details of the previous analyses, which formed the basis for this protocol, are also presented.

  10. Tank 241-AP-103 08/1999 Compatibility Grab Samples and Analytical Results for the Final Report

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

    BELL, K.E.

    1999-12-09

    This document is the format IV, final report for the tank 241-AP-103 (AP-103) grab samples taken in August 1999 to address waste compatibility concerns. Chemical, radiochemical, and physical analyses on the tank AP-103 samples were performed as directed in ''Compatibility Grub Sampling and Analysis Plan for Fiscal Year 1999'' (Sasaki 1999a). Any deviations from the instructions provided in the tank sampling and analysis plan (TSAP) were discussed in this narrative. No notification limits were exceeded.

  11. Single d(ApG)/cis-diamminedichloroplatinum(II) adduct-induced mutagenesis in Escherichia coli

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

    Burnouf, D.; Fuchs, R.P.P.; Gauthier, C.

    1990-08-01

    The mutation spectrum induced by the widely used antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) showed that cisDDP(d(ApG)) adducts, although they account for only 25% of the lesions formed are {approx}5 times more mutagenic than the major GG adduct. The authors report the construction of vectors bearing a single cisDDP(d(ApG)) lesion and their use in mutagenesis experiments in Escherichia coli. The mutagenic processing of the lesion is found to depend strictly on induction of the SOS system of the bacterial host cells. In SOS-induced cells, mutation frequencies of 1-2% were detected. All these mutations are targeted to the 5{prime} base of the adduct.more » Single A {yields} T transversions are mainly observed (80%), whereas A {yields} G transitions account for 10% of the total mutations. Tandem base-pair substitutions involving the adenine residue and the thymine residue immediately 5{prime} to the adduct occur at a comparable frequency (10%). No selective loss of the strand bearing the platinum adduct was seen, suggesting that, in vivo, cisDDP(d(ApG)) adducts are not blocking lesions. The high mutation specificity of cisDDP-(d(ApG))-induced mutagenesis is discussed in relation to structural data.« less

  12. Studying Protein-Protein Interactions by Biotin AP-Tagged Pulldown and LTQ-Orbitrap Mass Spectrometry.

    PubMed

    Xie, Zhongqiu; Jia, Yuemeng; Li, Hui

    2017-01-01

    The study of protein-protein interactions represents a key aspect of biological research. Identifying unknown protein binding partners using mass spectrometry (MS)-based proteomics has evolved into an indispensable strategy in drug discovery. The classic approach of immunoprecipitation with specific antibodies against the proteins of interest has limitations, such as the need for immunoprecipitation-qualified antibody. The biotin AP-tag pull-down system has the advantage of high specificity, ease of use, and no requirement for antibody. It is based on the high specificity, high affinity interaction between biotin and streptavidin. After pulldown, in-gel tryptic digestion and tandem mass spectrometry (MS/MS) analysis of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) protein bands can be performed. In this work, we provide protocols that can be used for the identification of proteins that interact with FOXM1, a protein that has recently emerged as a potential biomarker and drug target in oncotherapy, as an example. We focus on the pull-down procedure and assess the efficacy of the pulldown with known FOXM1 interactors such as β-catenin. We use a high performance LTQ Orbitrap MSn system that combines rapid LTQ ion trap data acquisition with high mass accuracy Orbitrap analysis to identify the interacting proteins.

  13. A Generalized Model of E-trading for GSR Fair Exchange Protocol

    NASA Astrophysics Data System (ADS)

    Konar, Debajyoti; Mazumdar, Chandan

    In this paper we propose a generalized model of E-trading for the development of GSR Fair Exchange Protocols. Based on the model, a method is narrated to implement E-trading protocols that ensure fairness in true sense without using an additional trusted third party for which either party has to pay. The model provides the scope to include the correctness of the product, money atomicity and customer's anonymity properties within E-trading protocol. We conclude this paper by indicating the area of applicability for our model.

  14. Coming Soon: CADRE (Career Advancement and Development Resources and Education) website for all APS members

    USDA-ARS?s Scientific Manuscript database

    The Council of the American Phytopathological Society (APS) approved an initiative in February 2013 to create a web resource called CADRE (Career Advancement and Development Resources and Education). CADRE is to provide APS members an archive of articles, videos, and webinars about a variety of prof...

  15. Protection against oxidation of fish-oil-enriched milk emulsions through addition of rapeseed oil or antioxidants.

    PubMed

    Let, Mette B; Jacobsen, Charlotte; Pham, Kim A; Meyer, Anne S

    2005-06-29

    The ability of rapeseed oil and/or different antioxidants (alpha- and gamma-tocopherol mixture, ascorbyl palmitate, and EDTA) to protect fish-oil-enriched milk emulsions against oxidation was investigated. Tocopherol isomers in concentrations similar to those found in natural rapeseed oil were added to rapeseed oil stripped of natural tocopherols. The rapeseed oil with added tocopherols significantly inhibited oxidation in the fish-oil-enriched milk emulsions. In contrast, the emulsions with only fish oil and added alpha- and gamma-tocopherol were less stable than the emulsions with fish oil alone. When added individually, the gamma-tocopherol seemed to inhibit oxidation more efficiently than alpha-tocopherol. Ascorbyl palmitate (AP) almost completely retarded oxidation in the fish-oil-enriched milk emulsions, as determined by PV, volatile oxidation products, and sensory evaluation. AP also prevented the otherwise prooxidant effect of tocopherols added to fish oil before emulsification. No interactions between AP, tocopherols, and EDTA were observed, and EDTA added alone to fish oil did not show antioxidant properties in the milk emulsions. Overall, the results showed that addition of AP or rapeseed oil containing natural tocopherols to fish oil was equally efficient in inhibiting oxidation in the fish-oil-enriched milk emulsions.

  16. Isolation and characterization of the Jatropha curcas APETALA1 (JcAP1) promoter conferring preferential expression in inflorescence buds.

    PubMed

    Tao, Yan-Bin; He, Liang-Liang; Niu, Longjian; Xu, Zeng-Fu

    2016-08-01

    The 1.5 kb JcAP1 promoter from the biofuel plant Jatropha curcas is predominantly active in the inflorescence buds of transgenic plants, in which the -1313/-1057 region is essential for maintaining the activity. Arabidopsis thaliana APETALA1 (AP1) is a MADS-domain transcription factor gene that functions primarily in flower development. We isolated a homolog of AP1 from Jatropha curcas (designated JcAP1), which was shown to exhibit flower-specific expression in Jatropha. JcAP1 is first expressed in inflorescence buds and continues to be primarily expressed in the sepals. We isolated a 1.5 kb JcAP1 promoter and evaluated its activity in transgenic Arabidopsis and Jatropha using the β-glucuronidase (GUS) reporter gene. In transgenic Arabidopsis and Jatropha, the inflorescence buds exhibited notable GUS activity, whereas the sepals did not. Against expectations, the JcAP1 promoter was active in the anthers of Arabidopsis and Jatropha and was highly expressed in Jatropha seeds. An analysis of promoter deletions in transgenic Arabidopsis revealed that deletion of the -1313/-1057 region resulted in loss of JcAP1 promoter activity in the inflorescence buds and increased activity in the anthers. These results suggested that some regulatory sequences in the -1313/-1057 region are essential for maintaining promoter activity in inflorescence buds and can partly suppress activity in the anthers. Based on these findings, we hypothesized that other elements located upstream of the 1.5 kb JcAP1 promoter may be required for flower-specific activation. The JcAP1 promoter characterized in this study can be used to drive transgene expression in both the inflorescence buds and seeds of Jatropha.

  17. Evaluation of the new radiation belt AE9/AP9/SPM model for a cislunar mission

    NASA Astrophysics Data System (ADS)

    Badavi, Francis F.; Walker, Steven A.; Santos Koos, Lindsey M.

    2014-09-01

    this time. From a mission planning point of view, this date is ideal as the predictable GCR exposure will be at a maximum, while the sporadic SEP will be at a minimum. In addition, it is anticipated that by 2020 a vehicle capable of launching a crew of four will be operationally ready. During the LEO-GEO transit, the crew and cargo vehicles will encounter exposure from trapped particles and attenuated GCR, followed by free space exposure due to GCR and SEP during solar active times. Within the trapped field, a challenge arises from properly calculating the amount of exposure acquired. Within this field, in the absence of SEP (i.e. solar quiet times), the vehicles will have to transit through an inner proton belt, an inner and outer electron belts, and an attenuated GCR field. There exist a number of models to define the intensities of the trapped particles during the quiet and active SEP. Among the more established trapped models are the historic and popular electron/proton AE8/AP8 model dating back to the 1980s, the historic and less popular electron/proton CRRES model dating back to 1990s, and the recently released electron/proton/space plasma AE9/AP9/SPM model. The AE9/AP9/SPM model is a major improvement over the older AE8/AP8 and CRRES models. This model is derived from numerous measurements acquired over four solar cycles dating back to the 1970s, roughly representing 40 years of data collection. In contrast, the older AE8/AP8 and CRRES models were limited to only a few months of measurements taken during the prior solar minima and maxima. In this work, within the trapped field, along the design trajectory of the crew vehicle, the AE9/AP9/SPM model is evaluated against the older AE8/AP8 model during solar quiet times. The analysis is then extended to the GCR dominated en-route, cislunar L2 space and return trajectories in order to provide cumulative exposure estimates to the crew vehicle for the duration of the entire mission.

  18. Large amplitude change in spot-induced rotational modulation of the Kepler Ap star KIC 2569073

    NASA Astrophysics Data System (ADS)

    Drury, Jason A.; Murphy, Simon J.; Derekas, Aliz; Sódor, Ádám; Stello, Dennis; Kuehn, Charles A.; Bedding, Timothy R.; Bognár, Zsófia; Szigeti, László; Szakáts, Róbert; Sárneczky, Krisztián; Molnár, László

    2017-11-01

    An investigation of the 200 × 200 pixel `superstamp' images of the centres of the open clusters NGC 6791 and NGC 6819 allows for the identification and study of many variable stars that were not included in the Kepler target list. KIC 2569073 (V = 14.22), is a particularly interesting variable Ap star that we discovered in the NGC 6791 superstamp. With a rotational period of 14.67 d and 0.034 mag variability, it has one of the largest peak-to-peak variations of any known Ap star. Colour photometry reveals an antiphase correlation between the B band, and the V, R and I bands. This Ap star is a rotational variable, also known as an α2 CVn star, and is one of only a handful of Ap stars observed by Kepler. While no change in spot period or amplitude is observed within the 4 yr Kepler time series, the amplitude shows a large increase compared to ground-based photometry obtained two decades ago.

  19. Construction of a dictionary of laboratory tests mapped to LOINC at AP-HP.

    PubMed

    Cormont, Sylvie; Buemi, Antoine; Horeau, Thierry; Zweigenbaum, Pierre; Lepage, Eric

    2008-11-06

    We report on the ongoing process implemented at Assistance Publique-Hôpitaux de Paris (AP-HP), the largest hospital system in Europe, to build a common reference for laboratory tests in French with LOINC mappings. At the time of writing, it contained 24,000 tests, covering all fields of biology, in use in 19 AP-HP hospitals, 30% of which had a mapping to LOINC with a peak of over 60% in biochemistry.

  20. APS undulator and wiggler sources: Monte-Carlo simulation

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

    Xu, S.L.; Lai, B.; Viccaro, P.J.

    1992-02-01

    Standard insertion devices will be provided to each sector by the Advanced Photon Source. It is important to define the radiation characteristics of these general purpose devices. In this document,results of Monte-Carlo simulation are presented. These results, based on the SHADOW program, include the APS Undulator A (UA), Wiggler A (WA), and Wiggler B (WB).