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Sample records for atm abr service

  1. Intelligent Flow Control Technique of ABR Service in ATM Networks Based on Fuzzy Neural Networks

    Institute of Scientific and Technical Information of China (English)

    ZhangLiangjie; LiYanda; 等

    1997-01-01

    The ATM Forum voted to implement the rate-based flow control(RBFC)scheme to manage traffic in asynchronous transfer mode(ATM)networks.RBFC will be used specifically to manage available bit rate(ABR)service.Through the study of the transmission rate adjusting of the ABR traffic source,we propose and enhanced bit rate feedback(EBRF)scheme,which is the dynamic bit rate adjusting scheme based on fuzzy neural network(FNN).Simulation results show that it can enhance the switch buffer utilization on the premise of a full link utilization.

  2. A Fuzzy Flow Control Approach for ABR Service in ATM Networks%ATM网络中面向ABR服务的一种模糊流量控制方法

    Institute of Scientific and Technical Information of China (English)

    张孝林; 张飒兵; 吴介一

    2002-01-01

    The explicit rate flow control mechanisms for ABR service are used to share the available bandwidth of a bottleneck link fairly and reasonably among many competitive users and to maintain the buffer queue length of a bottleneck switch connected to the link at a desired level in order to avoid and control congestion in ATM networks. However, designing effective flow control mechanisms for the service is known to be difficult because of the variety of dynamic parameters involved such as available link bandwidth, burst of the traffic, the distances between ABR sources and switches. In this paper, we present a fuzzy explicit rate flow control mechanism for ABR service. The mechanism has a simple structure and is robust in the sense that the mechanism's stability is not sensitive to the change in the number of active virtual connections (VCs). Many simulations show that this mechanism can not only effectively avoid network congestion, but also ensure fair share of the bandwidth for all active VCs regardless of the number of hops they traverse. Additionally, it has the advantages of fast convergence, low oscillation, and high link bandwidth utilization.%面向ABR服务的显式速率流量控制机制用于公平和合理地分配瓶颈链路可提供的带宽,保持与瓶颈链路连接的交换机缓冲区队列长度在所希望的程度,从而可以预防和控制ATM网络中的拥塞.然而,设计有效的流量控制机制较为困难,这主要是由于网络中的动态参数,如可提供的链路带宽、业务量的并发以及ABR源-目的之间距离等变化的影响.对此,本文提出了一种面向ABR服务的模糊显式速率控制机制,该机制结构简单,鲁棒性强.仿真实验表明:该机制可以有效地避免网络拥塞,公平地分配链路带宽并且具有快速收敛、低振荡、高链路带宽利用率的特点.

  3. THE DDTCI SWITCH ALGORITHM FOR ABR TRAFFIC CONTROL IN ATM NETWORKS

    Institute of Scientific and Technical Information of China (English)

    Lu Zhaoyi; Ning Yuxin

    2005-01-01

    For the issue of flow control for Available Bit Rate (ABR) traffic in ATM network,a new improved Explicit Rate (ER) algorithm named Dynamic Double Threshold Congestion Indication (DDTCI) algorithm is presented based on the Explicit Forward Congestion Indication (EFCI) Current Cell Rate (CCR) algorithm and Relative Rate (RR) algorithm. Different from the early ER algorithm, both the high-level and the low-level threshold is dynamically changing according to the state of the bottleneck node. We determinate the congestion state with the information of the two dynamic threshold, and control the cell rate of the source by feed back mechanism. Except for the well performance in both link utilization and fairness in distribution of available bandwidth, the improved algorithm can alleviate the fluctuation of sending rate dramatically. The mechanism is modeled by a fluid model, and the useful expressions are derived.Simulation results show up our conclusion.

  4. Efficient Bandwidth Allocation for Integrated Services in Broadband Wireless ATM Networks

    DEFF Research Database (Denmark)

    Liu, Hong; Dittmann, Lars; Gliese, Ulrik Bo

    1999-01-01

    An efficient bandwidth allocation scheme is proposed for supporting intergrated services in wireless ATM networks. These include CBR, VBR amd ABR types of traffic. The proposed scheme is based om A-PRMA for carrying ATM traffic in a dynamic TDMA type access system. It allows mobile users to adjust...

  5. ATM

    Directory of Open Access Journals (Sweden)

    Boo Yong Ahn

    1999-01-01

    Full Text Available We model the error control of the partial buffer sharing of ATM by a queueing system M1,M2/G/1/K+1 with threshold and instantaneous Bernoulli feedback. We first derive the system equations and develop a recursive method to compute the loss probabilities at an arbitrary time epoch. We then build an approximation scheme to compute the mean waiting time of each class of cells. An algorithm is developed for finding the optimal threshold and queue capacity for a given quality of service.

  6. ATM Quality of Service Tests for Digitized Video Using ATM Over Satellite: Laboratory Tests

    Science.gov (United States)

    Ivancic, William D.; Brooks, David E.; Frantz, Brian D.

    1997-01-01

    A digitized video application was used to help determine minimum quality of service parameters for asynchronous transfer mode (ATM) over satellite. For these tests, binomially distributed and other errors were digitally inserted in an intermediate frequency link via a satellite modem and a commercial gaussian noise generator. In this paper, the relation- ship between the ATM cell error and cell loss parameter specifications is discussed with regard to this application. In addition, the video-encoding algorithms, test configurations, and results are presented in detail.

  7. Preslikavanje parametara kvaliteta usluga na protokole ATM mreža / Quality of service mapping to ATM network protocols

    Directory of Open Access Journals (Sweden)

    Milojko Jevtović

    2005-11-01

    Full Text Available Preslikavanje parametara kvaliteta usluga (Quality of Service - QoS jedan je od bitnih elemenata u koncepciji ATM (Asynchronous Transfer Mode širokopojasnih mreža. U radu su opisani parametri QoS-a (verovatnoće pogrešnih ramova i ćelija, propusni opseg, kašnjenje ćelija, varijacija kašnjenja koji se preslikavaju na protokole ATM mreža. Preslikavanje se izvodi između korisničkog i aplikacionog QoS-a, a aplikacioni QoS se preslikava na QoS prenosa i komutacije, odnosno na ATM protokole, tzv. protokole ATM adaptacionog sloja i, konačno, preslikava se (mapira na ATM mrežne performanse (ATM sloj. Analiza procesa preslikavanja parametara kvaliteta usluga značajna je sa stanovišta korisnika usluga ATM mreža pri izboru klasa usluga koje će koristiti u komunikaciji preko date ATM mreže. / Quality of service mapping is one of the crucial elements in ATM concept of wide networks. In this paper QoS parameters mapping to ATM network protocols are described. Mapping is made between QoS user and QoS application, and application QoS is mapped to QoS transfer and commutation i.e. to ATM protocols - ATM adaptation layer protocols and finally it is mapped to ATM network performances. Analysis of this QoS mapping parameters process is very important for ATM users when they are choosing classes of service that can be used in communication process through ATM network.

  8. Design Issues for Traffic Management for the ATM UBR + Service for TCP Over Satellite Networks

    Science.gov (United States)

    Jain, Raj

    1999-01-01

    This project was a comprehensive research program for developing techniques for improving the performance of Internet protocols over Asynchronous Transfer Mode (ATM) based satellite networks. Among the service categories provided by ATM networks, the most commonly used category for data traffic is the unspecified bit rate (UBR) service. UBR allows sources to send data into the network without any feedback control. The project resulted in the numerous ATM Forum contributions and papers.

  9. ATM Quality of Service Parameters at 45 Mbps Using a Satellite Emulator: Laboratory Measurements

    Science.gov (United States)

    Ivancic, William D.; Bobinsky, Eric A.

    1997-01-01

    Results of 45-Mbps DS3 intermediate-frequency loopback measurements of asynchronous transfer mode (ATM) quality of service parameters (cell error ratio and cell loss ratio) are presented. These tests, which were conducted at the NASA Lewis Research Center in support of satellite-ATM interoperability research, represent initial efforts to quantify the minimum parameters for stringent ATM applications, such as MPEG-1 and MPEG-2 video transmission. Portions of these results were originally presented to the International Telecommunications Union's ITU-R Working Party 4B in February 1996 in support of their Draft Preliminary Recommendation on the Transmission of ATM Traffic via Satellite.

  10. Multiple access protocol for supporting multimedia services in wireless ATM networks

    DEFF Research Database (Denmark)

    Liu, Hong; Dittmann, Lars; Gliese, Ulrik Bo

    1999-01-01

    The furture broadband wireless asynchronous transfer mode (ATM) networks must provide seamless extension of multimedia services from the wireline ATM networks. This requires an effecient wireless access protocol to fulfill varying Quality-og-Service (QoS) requirements for multimedia applications....... In this paper, we propose a multiple access protocol using centralized and distributed channel access control techniques to provide QoS guarantees for multimedia services by taking advantage of the characteristics of different kinds of ATM traffics. Multimedia traffic, including constant bit rate (CBR...

  11. MEASUREMENT OF ATM LAYER QUALITY OF SERVICE PARAMETERS USING OAM CELLS

    Directory of Open Access Journals (Sweden)

    J. García-Hernández

    2004-08-01

    Full Text Available The measurement of the quality of service in ATM* networks involves the activation of the ATM layer managementOAM functions. Once an ATM connection is set up, in-service performance monitoring based on OAM cells can beused to measure and estimate the ATM layer QoS parameters. In-service measurement of ATM layer QoS parameterssuch as cell delay variation, cell transfer delay, cell loss ratio, etc., is necessary to verify on one hand, if the networkis meeting the requested QoS and on the other hand, if the users are receiving their promised QoS. Congestionconditions in ATM switches may cause gradual deteriorations in the quality of virtual paths or virtual channelconnections in an ATM network. QoS measurement using OAM cells can accurately measure the overall quality ofmonitored ATM layer QoS parameters in order to detect such deteriorations before the service quality has droppedbellow an acceptable level. Several factors such as network load, congestion, bottlenecks, and incremenTS innetwork load may affect the cell delay variation of video transmissions in an ATM network. In this work, several ATMlayer QoS parameters have been measured on a VBR video source using OAM cells. The simulation resulTS obtainedshow that with low network loads, the contribution of each individual ATM switch to the local and to the end-to-endCDV is not significant. In the presence of a bottleneck switch, the CDV presented by this switch becomes thedominant one at both local and end-to-end sides. When the network load is between 0.5 and 0.6, small incremenTSin network load do not alter the buffer performance of the non-congested ATM switches, and low values of CDVcan be obtained. In contrast, it was found that there is a critical load between 0.65 and 0.7 where small incremenTSin network load may force the CDV to grow abruptly.

  12. Design and evaluation of a connection management mechanism for an ATM-based connectionless service

    NARCIS (Netherlands)

    Heijenk, Geert; Haverkort, Boudewijn R.

    1996-01-01

    The Asynchronous Transfer Mode (ATM) has been developed as a connection-oriented technique for the transfer of fixed-size cells over high-speed networks. Many applications, however, require a connectionless network service. In order to provide such a technique, one can built a connectionless service

  13. Analysis of a multi-server queueing model of ABR

    Directory of Open Access Journals (Sweden)

    R. Núñez-Queija

    1998-01-01

    Full Text Available In this paper we present a queueing model for the performance analysis of Available Bit Rate (ABR traffic in Asynchronous Transfer Mode (ATM networks. We consider a multi-channel service station with two types of customers, denoted by high priority and low priority customers. In principle, high priority customers have preemptive priority over low priority customers, except on a fixed number of channels that are reserved for low priority traffic. The arrivals occur according to two independent Poisson processes, and service times are assumed to be exponentially distributed. Each high priority customer requires a single server, whereas low priority customers are served in processor sharing fashion. We derive the joint distribution of the numbers of customers (of both types in the system in steady state. Numerical results illustrate the effect of high priority traffic on the service performance of low priority traffic.

  14. ATM technology and beyond

    Science.gov (United States)

    Cheung, Nim K.

    1993-01-01

    Networks based on Asynchronous Transfer Mode (ATM) are expected to provide cost-effective and ubiquitous infrastructure to support broadband and multimedia services. In this paper, we give an overview of the ATM standards and its associated physical layer transport technologies. We use the experimental HIPPI-ATM-SONET (HAS) interface in the Nectar Gigabit Testbed to illustrate how one can use the SONET/ATM public network to provide transport for bursty gigabit applications.

  15. Impact of ATM Service on Customer Perception and Satisfaction of Indian Banks

    Directory of Open Access Journals (Sweden)

    Garima Malik

    2015-12-01

    Full Text Available Indian banking sector has completely changed. It has undergone much technological advancement that makes banking easy. Technological advancements are important but at the end what build customer satisfaction is proper management, employee behavior and customer relationship handling. Customer satisfaction is a sum of many variables that is many factors together leads to customer satisfaction. This modern electronic banking has completely changed the concept and functioning of banking system in India. Indian banking has moved from cash economy to cheque to and finally to the use of plastic cards. The customer satisfaction is dependent on customer awareness to a lot of extent. An unaware customer has less knowledge and therefore they cannot use the facilities completely even if they have it at their disposal. Customers prefer public sector banks when they are looking for trust and security and reliability. When it comes to speed, advancements and up gradation people shits from public sector banks to private sector banks. Customer gets satisfied only when they get quality service from the brand they are dealing with. This is very important for the marketers or the service providers as this leads to consumer satisfaction which benefits them and this brings loyalty to the brand enhancing the brand positioning. This research is important because new modern era has made people technology savvy they start their day with technology and end with technology therefore it is important to see the perception of users towards various factors of ATM. This research is conducted to see the highlighting factors that have direct impact on ATM services.

  16. Improving the Quality of Service Guarantee in an Asynchronous Transfer Mode (ATM Network

    Directory of Open Access Journals (Sweden)

    Francis J. Ogwu

    2007-01-01

    Full Text Available This study presents a technique for improving the quality of service (QoS guarantee in an ATM network. In the proposed model, it was assumed that high priority traffic have been allocated a switch resource to guarantee a given QoS and low priority cells are allowed to enter the buffer, to improve the exploitation of reserved resources. The proposed technique was backed up with an exact analytical model for evaluating the cell loss probability of high and low priority cells. The performance of the proposed model was evaluated using C++ programming language. The results of the simulation shows that the loss probability of both high and low cells reduces as the buffer capacity increase and that the performance of high priority cell is better than that of low priority cell.

  17. 在ATM网络中如何管理SLA%How to Manage Service Level Agreements for ATM Networks

    Institute of Scientific and Technical Information of China (English)

    谢喜秋; 黄娟

    2001-01-01

    ATM的不断增长的需求和ATM网络的操作复杂性推动了ATM SLA(Service Level Agreement:ATM服务水平协议)的发展.ATM SLA顺应了网络管理者的要求,它包括对网络的设计、执行、监视、维护和日常管理等方面的内容.介绍了ATM网络中SLA的基本组成,并举例说明国外大公司如何将SLA应用在ATM网络中.

  18. Integrated Service Provisioning in an Ipv6 over ATM Research Network

    Energy Technology Data Exchange (ETDEWEB)

    Eli Dart; Helen Chen; Jerry Friesen; Jim Brandt; Jim Hutchins; Perry Robertson

    1999-02-01

    During the past few years, the worldwide Internet has grown at a phenomenal rate, which has spurred the proposal of innovative network technologies to support the fast, efficient and low-latency transport of a wide spectrum of multimedia traffic types. Existing network infrastructures have been plagued by their inability to provide for real-time application traffic as well as their general lack of resources and resilience to congestion. This work proposes to address these issues by implementing a prototype high-speed network infrastructure consisting of Internet Protocol Version 6 (IPv6) on top of an Asynchronous Transfer Mode (ATM) transport medium. Since ATM is connection-oriented whereas IP uses a connection-less paradigm, the efficient integration of IPv6 over ATM is especially challenging and has generated much interest in the research community. We propose, in collaboration with an industry partner, to implement IPv6 over ATM using a unique approach that integrates IP over fast A TM hardware while still preserving IP's connection-less paradigm. This is achieved by replacing ATM's control software with IP's routing code and by caching IP's forwarding decisions in ATM's VPI/VCI translation tables. Prototype ''VR'' and distributed-parallel-computing applications will also be developed to exercise the realtime capability of our IPv6 over ATM network.

  19. Main: ABRE2HVA1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available ound in barley (H.v.) HVA1 gene encoding a class 3 late embryogenesis-abundant protein; stress response; ABRE; ABA; HVA1; ABRE2; seed; embryo; barley (Hordeum vulgare); CCTACGTGGCGG ... ...ABRE2HVA1 S000134 29-Sep-1999 (last modified) kehi ABA responsive element, ABRE2, f

  20. Main: ABRE3HVA1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available ound in barley (H.v.) HVA1 gene encoding a class 3 late embryogenesis-abundant protein; stress response; ABRE; ABA; HVA1; ABRE3; seed; embryo; barley (Hordeum vulgare); GCAACGTGTC ... ...ABRE3HVA1 S000135 29-Sep-1999 (last modified) kehi ABA responsive element, ABRE3, f

  1. The Wireless ATM Architecture

    Directory of Open Access Journals (Sweden)

    R. Palitefka

    1998-06-01

    Full Text Available An overview of the proposed wireless ATM structure is provided. Wireless communication have been developed to a level where offered services can now be extended beyond voice and data. There are already wireless LANs, cordless systems offering data services and mobile data. Wireless LAN systems are basically planned for local, on-promises and in-house networking providing short distance radio or infrared links between computer system. The main challenge of wireless ATM is to harmonise the development of broadband wireless system with service B -ISDN/ATM and ATM LANs, and offer multimedia multiservice features for the support of time-sensitive voice communication, video, desktop multimedia applications, and LAN data traffic for the wireless user.

  2. Wireless ATM : handover issues

    OpenAIRE

    Jiang, Fan; Käkölä, Timo

    1998-01-01

    Basic aspects of cellular systems and the ATM transmission technology are introduced. Wireless ATM is presented as a combination of radio ATM and mobile ATM. Radio ATM is a wireless extension of an ATM connection while mobile ATM contains the necessary extensions to ATM to support mobility. Because the current ATM technology does not support mobility, handover becomes one of the most important research issues for wireless ATM. Wireless ATM handover requirements are thus analysed. A handover s...

  3. Congestion control scheme in ATM networks based on fast tracing-queue

    Institute of Scientific and Technical Information of China (English)

    Liu Zhixin; Guan Xinping

    2007-01-01

    One of the more challenging and unresolved issues in ATM networks is the congestion control of available bit rate (ABR). The dynamic controller is designed based on the control theory and the feedback mechanism of explicit rates.With the given method of a chosen parameter, it can guarantee the stability of the controller and closed loop system with propagation delay and bandwidth oscillation. It needs less parameters(only one) to be designed. The queue length can converge to the given value in the least steps. The fairness of different connections is considered further. The simulations show better performance and good quality of service(QoS) is achieved.

  4. Main: ABRE3HVA22 [PLACE

    Lifescience Database Archive (English)

    Full Text Available gene; see S0117 (ABRE2 of HVA22 gene); see CE1 (coupling element 1 = TGCCACCGG); See S000014; ABA response complex 1(ABRC1)=A3(previ...ously designated ABRE3)+CE1 (Shen et al., Plant Cell 8:1

  5. Satellite Communications for ATM

    Science.gov (United States)

    Shamma, Mohammed A.

    2003-01-01

    This presentation is an overview on Satellite Communication for the Aeronautical Telecommunication Management (ATM) research. Satellite Communications are being considered by the FAA and NASA as a possible alternative to the present and future ground systems supporting Air Traffic Communications. The international Civil Aviation Organization (ICAO) have in place Standards and Recommended Practices (SARPS) for the Aeronautical Mobile Satellite Services (AMSS) which is mainly derived from the pre-existing Inmarsat service that has been in service since the 1980s. The Working Group A of the Aeronautical Mobile Communication Panel of ICAO has also been investigating SARPS for what is called the Next Generation Satellite Service (NGSS) which conforms less to the Inmarsat based architecture and explores wider options in terms of satellite architectures. Several designs are being proposed by Firms such as Boeing, ESA, NASA that are geared toward full or secondary usage of satellite communications for ATM. Satellite communications for ATM can serve several purposes ranging from primary usage where ground services would play a minimal backup role, to an integrated solution where it will be used to cover services, or areas that are less likely to be supported by the proposed and existing ground infrastructure. Such Integrated roles can include usage of satellite communications for oceanic and remote land areas for example. It also can include relieving the capacity of the ground network by providing broadcast based services of Traffic Information Services messages (TIS-B), or Flight Information Services (FIS-B) which can take a significant portion of the ground system capacity. Additionally, satellite communication can play a backup role to support any needs for ground replacement, or additional needed capacity even after the new digital systems are in place. The additional bandwidth that can be provided via satellite communications can also open the door for many new

  6. ATM and Internet protocol

    CERN Document Server

    Bentall, M; Turton, B

    1998-01-01

    Asynchronous Transfer Mode (ATM) is a protocol that allows data, sound and video being transferred between independent networks via ISDN links to be supplied to, and interpreted by, the various system protocols.ATM and Internet Protocol explains the working of the ATM and B-ISDN network for readers with a basic understanding of telecommunications. It provides a handy reference to everyone working with ATM who may not require the full standards in detail, but need a comprehensive guide to ATM. A substantial section is devoted to the problems of running IP over ATM and there is some discussion o

  7. Performance of a connectionless protocol over ATM

    NARCIS (Netherlands)

    Heijenk, Geert J.; Moorsel, van Aad P.A.; Niemegeers, Ignas G.

    1992-01-01

    Recent studies show the existence of a demand for a connectionless broadband service. In order to cope with this demand, a connectionless protocol for the B-ISDN needs to be designed. Such a protocol should make use of ATM and the ATM Adaptation Layer. It needs to specify destination and bandwidth o

  8. Reference: ABRE2HVA22 [PLACE

    Lifescience Database Archive (English)

    Full Text Available ABRE2HVA22 Shen Q, Ho TH Functional dissection of an abscisic acid(ABA)-inducible gene re...veals two independent ABA-responsive complexes each containing a G-box and a novel cis-acting element. Plant Cell 7:295-307 (1995) PubMed: 7734964; ...

  9. MSFC institutional area network and ATM technology

    Science.gov (United States)

    Amin, Ashok T.

    1994-10-01

    The New Institutional Area Network (NEWIAN) at Marshall supports over 5000 end users with access to 26 file servers providing work presentation services. It is comprised of some 150 Ethernet LAN's interconnected by bridges/routers which are in turn connected to servers over two dual FDDI rings. The network supports various higher level protocols such as IP, IPX, AppleTalk (AT), and DECNet. At present IPX and AT protocols packets are routed, and IP protocol packets are bridged; however, work is in progress to route all IP packets. The impact of routing IP packets on network operation is examined. Broadband Integrated Services Data Network (BISDN), presently at various stages of development, is intended to provide voice, video, and data transfer services over a single network. BISDN will use asynchronous transfer mode (ATM) as a data transfer technique which provides for transmission, multiplexing, switching, and relaying of small size data units called cells. Limited ATM Wide Area Network (WAN) services are offered by Wiltel, AT&T, Sprint, and others. NASA is testing a pilot ATM WAN with a view to provide Program Support Communication Network services using ATM. ATM supports wide range of data rates and quality of service requirements. It is expected that ATM switches will penetrate campus networks as well. However, presently products in these areas are at various stages of development and standards are not yet complete. We examine development of ATM to help assess its role in the evolution of NEWIAN.

  10. ATM encryption testing

    Science.gov (United States)

    Capell, Joyce; Deeth, David

    1996-01-01

    This paper describes why encryption was selected by Lockheed Martin Missiles & Space as the means for securing ATM networks. The ATM encryption testing program is part of an ATM network trial provided by Pacific Bell under the California Research Education Network (CalREN). The problem being addressed is the threat to data security which results when changing from a packet switched network infrastructure to a circuit switched ATM network backbone. As organizations move to high speed cell-based networks, there is a break down in the traditional security model which is designed to protect packet switched data networks from external attacks. This is due to the fact that most data security firewalls filter IP packets, restricting inbound and outbound protocols, e.g. ftp. ATM networks, based on cell-switching over virtual circuits, does not support this method for restricting access since the protocol information is not carried by each cell. ATM switches set up multiple virtual connections, thus there is no longer a single point of entry into the internal network. The problem is further complicated by the fact that ATM networks support high speed multi-media applications, including real time video and video teleconferencing which are incompatible with packet switched networks. The ability to restrict access to Lockheed Martin networks in support of both unclassified and classified communications is required before ATM network technology can be fully deployed. The Lockheed Martin CalREN ATM testbed provides the opportunity to test ATM encryption prototypes with actual applications to assess the viability of ATM encryption methodologies prior to installing large scale ATM networks. Two prototype ATM encryptors are being tested: (1) `MILKBUSH' a prototype encryptor developed by NSA for transmission of government classified data over ATM networks, and (2) a prototype ATM encryptor developed by Sandia National Labs in New Mexico, for the encryption of proprietary data.

  11. ATM cash management using genetic algorithm

    Directory of Open Access Journals (Sweden)

    Ahmadreza Ghodrati

    2013-07-01

    Full Text Available Automatic teller machine (ATM is one of the most popular banking facilities to do daily financial transactions. People use ATM services to pay bills, transfer funds and withdraw cash. Therefore, we can treat ATM as a tradition inventory problem and use simulation technique to analysis the amount of cash required on different occasions such as regular days, holidays, etc. The proposed model of this paper uses genetic algorithm to determine the replenishment cash strategy for each ATM. The survey uses all transactions accomplished during the fiscal years of 2011-2012 on one of Iranian banks named Ayande. The study categorizes various ATM based on the average daily transactions into three groups of low, medium and high levels. The preliminary results of our survey indicate that it is possible to do setup different strategies to manage cash in various banks, optimally.

  12. Satellite ATM Networks: Architectures and Guidelines Developed

    Science.gov (United States)

    vonDeak, Thomas C.; Yegendu, Ferit

    1999-01-01

    An important element of satellite-supported asynchronous transfer mode (ATM) networking will involve support for the routing and rerouting of active connections. Work published under the auspices of the Telecommunications Industry Association (http://www.tiaonline.org), describes basic architectures and routing protocol issues for satellite ATM (SATATM) networks. The architectures and issues identified will serve as a basis for further development of technical specifications for these SATATM networks. Three ATM network architectures for bent pipe satellites and three ATM network architectures for satellites with onboard ATM switches were developed. The architectures differ from one another in terms of required level of mobility, supported data rates, supported terrestrial interfaces, and onboard processing and switching requirements. The documentation addresses low-, middle-, and geosynchronous-Earth-orbit satellite configurations. The satellite environment may require real-time routing to support the mobility of end devices and nodes of the ATM network itself. This requires the network to be able to reroute active circuits in real time. In addition to supporting mobility, rerouting can also be used to (1) optimize network routing, (2) respond to changing quality-of-service requirements, and (3) provide a fault tolerance mechanism. Traffic management and control functions are necessary in ATM to ensure that the quality-of-service requirements associated with each connection are not violated and also to provide flow and congestion control functions. Functions related to traffic management were identified and described. Most of these traffic management functions will be supported by on-ground ATM switches, but in a hybrid terrestrial-satellite ATM network, some of the traffic management functions may have to be supported by the onboard satellite ATM switch. Future work is planned to examine the tradeoffs of placing traffic management functions onboard a satellite as

  13. The Research and Application of ATM Testing

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The advantage of ATM technology for statistically multiplexingnetwork resources by different users invokes the competition of network resources. This competition has some damaging effects on message transmitting.The research for testing methods and technology of ATM is important for us to develop ATM networks, to promote their construction, to ensure that various ATM devices provided by different providers interoperate properly and to provide excellent services for telecommunication users. After discussing the abstract testing method of conformance testing and the abstract description of protocol testing, the thesis puts forward a kind of abstract testing configuration for ATM testing and a kind of abstract description method for testing case. From the angle of application, the thesis discusses the basic rules for ATM testing. After that, the thesis points out that the ATM testing must be made from the four aspects of normal testing, conformance testing, performance testing and interoperability testing. The general testing methods, general configuration and connection for ATM testing and the selection of ATM testing items are discussed, respectively, in the four aspects. Combined with the characteristics of the traffics supported by ATM systems, the thesis discusses several kinds of traffic models for conducting ATM testing. On the basis of studying various traffic models, the author classifies traffic models for ATM testing as three kinds: periodic traffic models, stochastic traffic models and manual traffic models. The parameters of describing traffic models and their calculating method are discussed in the thesis. A new kind of periodic cell-sequence traffic model is proposed in this thesis. The periodic cell-sequence traffic model has excellent linearly descending characteristics in the cell interval. The traffic models discussed in this thesis can be applied to various ATM testing cases. From the point of normal testing, physical layer testing, ATM layer

  14. Knowledge-Based Multiple Access Protocol in Broadband Wireless ATM Networks

    DEFF Research Database (Denmark)

    Liu, Hong; Gliese, Ulrik Bo; Dittmann, Lars

    1999-01-01

    characteristics of the traffic for allocating bandwidth effeciently to CBR, VBR and ABR/UBR connections by a compromise of assignment, contetion, reservation and polling access techniques. Simulation results show that the proposed protocol can achieve a very high channel utilization of 90 % while providing...... guaranteed QoS requirements to a variety of ATM applications....

  15. A queueing system with queue length dependent service times, with applications to cell discarding in ATM networks

    Directory of Open Access Journals (Sweden)

    Doo Il Choi

    1999-01-01

    Full Text Available A queueing system (M/G1,G2/1/K is considered in which the service time of a customer entering service depends on whether the queue length, N(t, is above or below a threshold L. The arrival process is Poisson, and the general service times S1 and S2 depend on whether the queue length at the time service is initiated is service time of the customer currently in service. Exact solutions for the stationary probabilities are constructed for both infinite and finite capacity systems. Asymptotic approximations of the solutions are given, which yield simple formulas for performance measures such as loss rates and tail probabilities. The numerical accuracy of the asymptotic results is tested.

  16. Defence Mechanism for SYBIL Attacks in MANETS using ABR Protocol

    Directory of Open Access Journals (Sweden)

    Sowmya P

    2014-06-01

    Full Text Available Security is of paramount concern in any adhoc network. In Mobile Adhoc NETworks (MANETs, mobility of the nodes poses a problem for providing security services [1]. The ad-hoc network is more vulnerable to attacks, since it uses wireless communication link between the mobile nodes. Sybil Attack is a spoofing attack, where a malicious node illegitimately creates multiple fake identities (called the Sybil nodes to impersonate as normal nodes. It is observed that most of the existing protocols fail to defend against Sybil attack. Associativity Based Routing (ABR protocol is an on-demand active routing protocol. It chooses the most long lived and stable route for communication rather than the shortest route. In this paper, using ABR protocol, we show that a legitimate node in the network along with the Local Server (LS can detect the Sybil attacker. We show through simulation that using the concept of a PKI secured SESSION KEY (SESS_KEY, we can detect the presence of a Sybil attacker in the network. The empirical results show that there is an increase of 10% in the throughput and 60% in good put and the integrity of the network. This would lead to a more secure communication network with a reduced overall delay.

  17. Simulation of ATM multiplexer for bursty sources

    OpenAIRE

    Conger, Chen

    1993-01-01

    Asynchronous transfer mode ( ATM ) is a promising multiplexing and switching technique for implementing an integrated access as well as transport network and has been adopted by CCITT as a basis for the future broadband integrated services digital network ( BISDN ). The ATM technique allows digital communication of any type to share common transmission links and switching devices on a statistical multiplexing basis. Information is transmitted in the form of constant le...

  18. Biological Imaging Capability in the ABRS Facility on ISS

    Science.gov (United States)

    Cox, David R.; Murdoch, T.; Regan, M. F.; Meshlberger, R. J.; Mortenson, T. E.; Albino, S. A.; Paul, A. L.; Ferl, R. J.

    2010-01-01

    This slide presentation reviews the Advanced Biological Research System (ABRS) on the International Space Station (ISS) and its biological imaging capability. The ABRS is an environmental control chamber. It has two indpendently controlled Experiment Research Chambers (ERCs) with temperature, relative humidity and carbon dioxide controls. ABRS is a third generation plant growth system. Several experiments are reviewed, with particular interest in the use of Green Fluorescent Protein (GFP) a non-destructive plant stress reporting mechanism, naturally found in jellyfish.

  19. OPEN ISSUES AND CHALLENGES IN PROVIDING TESTING AND SIGNALING IN HIGH SPEED ATM NETWORKS

    Directory of Open Access Journals (Sweden)

    Dr.S.S.Riaz Ahamed

    2011-01-01

    Full Text Available Testing asynchronous transfer mode (ATM communications and network equipment is the function of performing the testing phases required for complete evaluation of ATM products. The test phases measure andanalyze all aspects of ATM—from the characteristics of lower-layer cell transmission through to the complex ATM services used to transmit multimedia over ATM networks. ATM technology has become inextricably linked to promises of a global communications infrastructure. The expectation is that seamless integration ofvoice data and video across high-speed ATM links will provide universal access to multimedia services. ATM equipment developers, service providers, and end users are all faced with these same challenges when testing ATM products.

  20. ATMS Step By Step.

    Science.gov (United States)

    National Library of Australia, Canberra.

    This manual is designed to provide an introduction and basic guide to the use of IBM's Advanced Text Management System (ATMS), the text processing system to be used for the creation of Australian data bases within AUSINET. Instructions are provided for using the system to enter, store, retrieve, and modify data, which may then be displayed at the…

  1. Locating ATMs in Urban Areas

    Directory of Open Access Journals (Sweden)

    Mehdi MoradiTabar

    2013-08-01

    Full Text Available In recent years, the banks and financial institutions have considerably attempted to provide better and more varied services to the customers. These varied services may satisfy needs of differentgroup of customers. In this regard, the location of these services as well as their level of accessibility (access to these services is greatly important. The importance of these issues is well recognized by responsible managers of the financial firms. In other words, the managers accept the importance of these services and they know that the quality and location of these services significantly affect their success in the business. Therefore, bank managers sought scientific methods, which may facilitate the locating process for their services. How to select the most effective methods and how to use these methods in this regard depend on following factors: the customers' demands, local capacities and fair distribution of theservices, etc. The effective impact of these factors as well as the interactive relationship between them should also be noted in the application. This study is a descriptive kind of research, which is applicable in various areas. Library and environmental studies were used to conduct the study. Considering the parameters that considerably affect the level of acceptability of ATMs services and analyzing the importance of these parameters according to this criterion, the researchers tried to use multiple attribute decision-making model. a heuristic algorithm was used in the context of this approach. Then, the most appropriate locations around the optimal locations were introduced based on fuzzy concept as well as quantitative and qualitative factors, including the minimum cost and maximum coverage according to the customers’ demands. The case study was located in the 13th district of Tehran city.

  2. 400-Mbps, 8 times 8 ATM switch LSI. 400Mbps 8 times 8 ATM switch LSI

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, S.; Tanaka, S.; Noda, M. (Toshiba Corp., Tokyo (Japan))

    1991-08-01

    Was developed at Toshiba, an asynchronous transfer mode (ATM) switch large scale integrated circuit (LSI), which can be used for next-generation telecommunication network systems, such as broadband-integrated services digital network (B-ISDN) For this ATM switch LSI, the common buffer method, which has a good buffer operation efficiency, was adopted as a switch architecture. The flow control and the cell incorporation sequential method were also adopted to improve the cell-loss rate. Furthermore, the BiCMOS (bipolar complimentary MOS) process was applied to the fabrication of this LSI. Consequently, a one-chip 8 input/8 output ATM switch LSI was realized. In addition, the operation speed per channel of this LSI was 400Mbps, and the throughput was 3.2Gbps. 3 refs., 4 figs., 1 tab.

  3. ABrIL - Advanced Brain Imaging Lab : a cloud based computation environment for cooperative neuroimaging projects.

    Science.gov (United States)

    Neves Tafula, Sérgio M; Moreira da Silva, Nádia; Rozanski, Verena E; Silva Cunha, João Paulo

    2014-01-01

    Neuroscience is an increasingly multidisciplinary and highly cooperative field where neuroimaging plays an important role. Neuroimaging rapid evolution is demanding for a growing number of computing resources and skills that need to be put in place at every lab. Typically each group tries to setup their own servers and workstations to support their neuroimaging needs, having to learn from Operating System management to specific neuroscience software tools details before any results can be obtained from each setup. This setup and learning process is replicated in every lab, even if a strong collaboration among several groups is going on. In this paper we present a new cloud service model - Brain Imaging Application as a Service (BiAaaS) - and one of its implementation - Advanced Brain Imaging Lab (ABrIL) - in the form of an ubiquitous virtual desktop remote infrastructure that offers a set of neuroimaging computational services in an interactive neuroscientist-friendly graphical user interface (GUI). This remote desktop has been used for several multi-institution cooperative projects with different neuroscience objectives that already achieved important results, such as the contribution to a high impact paper published in the January issue of the Neuroimage journal. The ABrIL system has shown its applicability in several neuroscience projects with a relatively low-cost, promoting truly collaborative actions and speeding up project results and their clinical applicability.

  4. Final report for the protocol extensions for ATM Security Laboratory Directed Research and Development Project

    Energy Technology Data Exchange (ETDEWEB)

    Tarman, T.D.; Pierson, L.G.; Brenkosh, J.P. [and others

    1996-03-01

    This is the summary report for the Protocol Extensions for Asynchronous Transfer Mode project, funded under Sandia`s Laboratory Directed Research and Development program. During this one-year effort, techniques were examined for integrating security enhancements within standard ATM protocols, and mechanisms were developed to validate these techniques and to provide a basic set of ATM security assurances. Based on our experience during this project, recommendations were presented to the ATM Forum (a world-wide consortium of ATM product developers, service providers, and users) to assist with the development of security-related enhancements to their ATM specifications. As a result of this project, Sandia has taken a leading role in the formation of the ATM Forum`s Security Working Group, and has gained valuable alliances and leading-edge experience with emerging ATM security technologies and protocols.

  5. ABR and auditory P300 findings inchildren with ADHD

    OpenAIRE

    Schochat Eliane; Scheuer Claudia Ines; Andrade Ênio Roberto de

    2002-01-01

    Auditory processing disorders (APD), also referred as central auditory processing disorders (CAPD) and attention deficit hyperactivity disorders (ADHD) have become popular diagnostic entities for school age children. It has been demonstrated a high incidence of comorbid ADHD with communication disorders and auditory processing disorder. The aim of this study was to investigate ABR and P300 auditory evoked potentials in children with ADHD, in a double-blind study. Twenty-one children, ages bet...

  6. Abre tu nevera! Aplicación para Android

    OpenAIRE

    Cañizares Fernandez, Rosa

    2014-01-01

    Aquí presento mi PFC Abre tu nevera! Consiste en un recetario paso a paso basado en los productos que tenemos en la despensa. Además cuenta de una gestión de listas de la compra. En el código fuente podremos encontrar una carpeta con el código fuente del proyecto Android y la app lista para instalar.

  7. Is Your ATM Dispensing Bacteria?

    Science.gov (United States)

    ... news/fullstory_162067.html Is Your ATM Dispensing Bacteria? Study in New York City found most of ... keypads in New York City were covered in bacteria, researchers reported, with most of the microbes coming ...

  8. Connecting Remote Clusters with ATM

    Energy Technology Data Exchange (ETDEWEB)

    Hu, T.C.; Wyckoff, P.S.

    1998-10-01

    Sandia's entry into utilizing clusters of networked workstations is called Computational Plant or CPlant for short. The design of CPlant uses Ethernet to boot the individual nodes, Myrinet to communicate within a node cluster, and ATM to connect between remote clusters. This SAND document covers the work done to enable the use of ATM on the CPlant nodes in the Fall of 1997.

  9. Using ATM over SATCOM links

    Science.gov (United States)

    Comparetto, Gary M.

    1995-01-01

    The Asynchronous Transfer Mode (ATM) protocol is studied from the standpoint of determining what limitations, if any, exist in using it over satellite links. It is concluded that, while there is nothing intrinsic about ATM that would generally preclude its use over satellite links, there are, however, several intrinsic characteristics of satellite links, as well as some satellite system configuration-specific issues, that must be taken into account.

  10. NEW HOPE AND TECHNOLOGICAL ISSUES ON VOICE AND VIDEO OVER ATM

    Directory of Open Access Journals (Sweden)

    Dr.S.S.Riaz Ahamed

    2010-12-01

    Full Text Available Changes in the structure of the telecommunications industry and market conditions have brought new opportunities and challenges for network operators and public service providers. Networks that have been primarily focused on providing better voice services are evolving to meet new multimedia communications challenges and competitive pressures. Services based on asynchronous transfer mode (ATM provide the flexible infrastructure essential for success in this evolving market. ATM, which was once envisioned as the technology of future public networks, is now a reality, with service providers around the world introducing and rolling out ATM and ATM–based services.

  11. [Progress of the ATM Crew

    Science.gov (United States)

    2003-01-01

    Activities for each of the following programs are discussed in separate sections for the bimonthly reporting period: Airborne Oceanographic Lidar (AOL); Airborne Topographic Mapper (ATM); Other Mission Support Activities, including modeling activities, EAARL activities, and the Scanning Radar Altimeter (SAR); Tropical Rain Measuring Mission (TRMM). The tasks undertaken for each program are discussed in the pertinent section of the report.

  12. NPP ATMS Snowfall Rate Product

    Science.gov (United States)

    Meng, Huan; Ferraro, Ralph; Kongoli, Cezar; Wang, Nai-Yu; Dong, Jun; Zavodsky, Bradley; Yan, Banghua

    2015-01-01

    Passive microwave measurements at certain high frequencies are sensitive to the scattering effect of snow particles and can be utilized to retrieve snowfall properties. Some of the microwave sensors with snowfall sensitive channels are Advanced Microwave Sounding Unit (AMSU), Microwave Humidity Sounder (MHS) and Advance Technology Microwave Sounder (ATMS). ATMS is the follow-on sensor to AMSU and MHS. Currently, an AMSU and MHS based land snowfall rate (SFR) product is running operationally at NOAA/NESDIS. Based on the AMSU/MHS SFR, an ATMS SFR algorithm has been developed recently. The algorithm performs retrieval in three steps: snowfall detection, retrieval of cloud properties, and estimation of snow particle terminal velocity and snowfall rate. The snowfall detection component utilizes principal component analysis and a logistic regression model. The model employs a combination of temperature and water vapor sounding channels to detect the scattering signal from falling snow and derive the probability of snowfall (Kongoli et al., 2015). In addition, a set of NWP model based filters is also employed to improve the accuracy of snowfall detection. Cloud properties are retrieved using an inversion method with an iteration algorithm and a two-stream radiative transfer model (Yan et al., 2008). A method developed by Heymsfield and Westbrook (2010) is adopted to calculate snow particle terminal velocity. Finally, snowfall rate is computed by numerically solving a complex integral. NCEP CMORPH analysis has shown that integration of ATMS SFR has improved the performance of CMORPH-Snow. The ATMS SFR product is also being assessed at several NWS Weather Forecast Offices for its usefulness in weather forecast.

  13. Molecular Imaging of the ATM Kinase Activity

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Terence M. [Department of Radiation Oncology, Ohio State University, Columbus, Ohio (United States); Nyati, Shyam [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Center for Molecular Imaging, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Ross, Brian D. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Rehemtulla, Alnawaz, E-mail: alnawaz@umich.edu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Center for Molecular Imaging, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan (United States)

    2013-08-01

    Purpose: Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase critical to the cellular DNA-damage response, including from DNA double-strand breaks. ATM activation results in the initiation of a complex cascade of events including DNA damage repair, cell cycle checkpoint control, and survival. We sought to create a bioluminescent reporter that dynamically and noninvasively measures ATM kinase activity in living cells and subjects. Methods and Materials: Using the split luciferase technology, we constructed a hybrid cDNA, ATM-reporter (ATMR), coding for a protein that quantitatively reports on changes in ATM kinase activity through changes in bioluminescence. Results: Treatment of ATMR-expressing cells with ATM inhibitors resulted in a dose-dependent increase in bioluminescence activity. In contrast, induction of ATM kinase activity upon irradiation resulted in a decrease in reporter activity that correlated with ATM and Chk2 activation by immunoblotting in a time-dependent fashion. Nuclear targeting improved ATMR sensitivity to both ATM inhibitors and radiation, whereas a mutant ATMR (lacking the target phosphorylation site) displayed a muted response. Treatment with ATM inhibitors and small interfering (si)RNA-targeted knockdown of ATM confirm the specificity of the reporter. Using reporter expressing xenografted tumors demonstrated the ability of ATMR to report in ATM activity in mouse models that correlated in a time-dependent fashion with changes in Chk2 activity. Conclusions: We describe the development and validation of a novel, specific, noninvasive bioluminescent reporter that enables monitoring of ATM activity in real time, in vitro and in vivo. Potential applications of this reporter include the identification and development of novel ATM inhibitors or ATM-interacting partners through high-throughput screens and in vivo pharmacokinetic/pharmacodynamic studies of ATM inhibitors in preclinical models.

  14. Running TCP/IP over ATM Networks.

    Science.gov (United States)

    Witt, Michael

    1995-01-01

    Discusses Internet protocol (IP) and subnets and describes how IP may operate over asynchronous transfer mode (ATM). Topics include TCP (transmission control protocol), ATM cells and adaptation layers, a basic architectural model for IP over ATM, address resolution, mapping IP to a subnet technology, and connection management strategy. (LRW)

  15. Assessment of Startup Fuel Options for the GNEP Advanced Burner Reactor (ABR)

    Energy Technology Data Exchange (ETDEWEB)

    Jon Carmack (062056); Kemal O. Pasamehmetoglu (103171); David Alberstein

    2008-02-01

    The Global Nuclear Energy Program (GNEP) includes a program element for the development and construction of an advanced sodium cooled fast reactor to demonstrate the burning (transmutation) of significant quantities of minor actinides obtained from a separations process and fabricated into a transuranic bearing fuel assembly. To demonstrate and qualify transuranic (TRU) fuel in a fast reactor, an Advanced Burner Reactor (ABR) prototype is needed. The ABR would necessarily be started up using conventional metal alloy or oxide (U or U, Pu) fuel. Startup fuel is needed for the ABR for the first 2 to 4 core loads of fuel in the ABR. Following start up, a series of advanced TRU bearing fuel assemblies will be irradiated in qualification lead test assemblies in the ABR. There are multiple options for this startup fuel. This report provides a description of the possible startup fuel options as well as possible fabrication alternatives available to the program in the current domestic and international facilities and infrastructure.

  16. Evaluation of ATM Functioning Using VHDL and FPGA

    Directory of Open Access Journals (Sweden)

    Manali Dhar

    2015-06-01

    Full Text Available It has been almost four decades that banks and other financial organizations have been gradually computerised, in order to improve service and efficiency and to reduce cost. The birth of Electronic Fund Transfer and Automated Teller Machines has given rise to 24-hour banking and a greater variety of services for the customer. This method uses a computer to transfer debits and credits, with the help of electronic pulses, which are carried through wires either to a magnetic disk or tape. ATM (Automated Teller Machine has become an important part in our daily lives. People use ATM for various purposes such as money withdrawal, checking balance, changing password etc. Since it mainly deals with people's money, it has to be a secure system on which we can rely. We have taken a step towards increasing this security and integrity by trying to implement the functioning of an ATM using VLSI-based programming, HDL(Hardware Description Language.The conventional coding languages such as C,C++ are replaced by VHDL(Very High Speed Integrated Circuit Hardware Description Language so that the code cannot be easily hacked or changed. This article consists of an insight into the various functions that can be performed using an ATM, a brief description of the Coding and the obtained simulation results. It also consists of the implementation of the code using FPGA Kit (Spartan3; Model no.-XC 3S50.

  17. Buffer management optimization strategy for satellite ATM

    Institute of Scientific and Technical Information of China (English)

    Lu Rong; Cao Zhigang

    2006-01-01

    ECTD (erroneous cell tail drop), a buffer management optimization strategy is suggested which can improve the utilization of buffer resources in satellite ATM (asynchronous transfer mode) networks. The strategy, in which erroneous cells caused by satellite channel and the following cells that belong to the same PDU (protocol data Unit) are discarded, concerns non-real-time data services that use higher layer protocol for retransmission. Based on EPD (early packet drop) policy, mathematical models are established with and without ECTD. The numerical results show that ECTD would optimize buffer management and improve effective throughput (goodput), and the increment of goodput is relative to the CER (cell error ratio) and the PDU length. The higher their values are, the greater the increment. For example,when the average PDU length values are 30 and 90, the improvement of goodput are respectively about 4% and 10%.

  18. ATM

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ ATM的出现 通信网络,特别是传统的网络都具有业务特定性的特点,某一特点的通信网络总是为满足某种特点的业务需求而设计的.例如:TELEX是用于传送文字信息的;CHINAPAC是用于数据传输的;PSTN用于话音业务;CATV用于视频服务.这些网络用于提供非特定业务时均存在诸多问题.

  19. Behavior of transition state regulator AbrB in batch cultures of Bacillus thuringiensis.

    Science.gov (United States)

    Lozano Goné, Astrid Magdalena; Dinorín Téllez Girón, Jabel; Jiménez Montejo, Fabiola Eloisa; Hidalgo-Lara, María Eugenia; López Y López, Víctor Eric

    2014-11-01

    The transition state regulator AbrB is involved in the regulation of various cellular functions such as exponential growth, transition state and sporulation onset, due to its ability to activate, suppress or prevent the inappropriate expression of various genes in Bacillus subtilis. In order to understand combined behavior in batch cultures of AbrB in Bacillus thuringiensis, we cloned and expressed the abrB gene of B. thuringiensis in Escherichia coli. The deduced sequence of abrB gene coded for a protein consisting of 94 amino acids with ~10.5 kDa protein that shares 100 and 85 % identity with those from Bacillus cereus and Bacillus subtilis. The recombinant AbrB protein was used as antigen for the production of rabbit polyclonal antibodies anti-AbrB. Two media cultures with carbon: nitrogen ratios of 7.0, but varying access to nutrients were tested in batch cultures. In the case of both media, AbrB accumulation occurred from the beginning of the process and was maximal during early exponential growth. Thereafter, the level of AbrB decreased when there were no nutrient limitations and coincided with a decreased value in specific growth rate, although growth continued exponentially. Nonetheless, sporulation onset was determined 3 h and 4 h later, in media with highly metabolizable nutrients clean medium and Farrera medium, respectively. Hence, the maximal level of AbrB accumulation in batch cultures of B. thuringiensis is not influenced by limiting nutrients; however, nutrient availability affects the required time lapse for transition state regulator accumulation.

  20. Enhanced ATM Security System using Biometrics

    Directory of Open Access Journals (Sweden)

    Selina Oko

    2012-09-01

    Full Text Available Because biometrics-based authentication offers several advantages over other authentication methods, there hasbeen a significant surge in the use of biometrics for user authentication in recent years. In this paper the existing security of the ATM (Automated Teller Machine system has been improved by integrating the fingerprint of the user into the banks database as to further authenticate it. This was achieved by modelling and building an ATM simulator that will mimic a typical ATM system. The end result is an enhanced biometric authenticated ATM system that ensures greater security and increased customers confidence in the banking sector.

  1. DNA Damage-Induced Acetylation of Lysine 3016 of ATM Activates ATM Kinase Activity▿ †

    OpenAIRE

    Sun, Yingli; Xu, Ye; Roy, Kanaklata; Price, Brendan D.

    2007-01-01

    The ATM protein kinase is essential for cells to repair and survive genotoxic events. The activation of ATM's kinase activity involves acetylation of ATM by the Tip60 histone acetyltransferase. In this study, systematic mutagenesis of lysine residues was used to identify regulatory ATM acetylation sites. The results identify a single acetylation site at lysine 3016, which is located in the highly conserved C-terminal FATC domain adjacent to the kinase domain. Antibodies specific for acetyl-ly...

  2. Structure and DNA-binding traits of the transition state regulator AbrB.

    Science.gov (United States)

    Olson, Andrew L; Tucker, Ashley T; Bobay, Benjamin G; Soderblom, Erik J; Moseley, M Arthur; Thompson, Richele J; Cavanagh, John

    2014-11-04

    The AbrB protein from Bacillus subtilis is a DNA-binding global regulator controlling the onset of a vast array of protective functions under stressful conditions. Such functions include biofilm formation, antibiotic production, competence development, extracellular enzyme production, motility, and sporulation. AbrB orthologs are known in a variety of prokaryotic organisms, most notably in all infectious strains of Clostridia, Listeria, and Bacilli. Despite its central role in bacterial response and defense, its structure has been elusive because of its highly dynamic character. Orienting its N- and C-terminal domains with respect to one another has been especially problematic. Here, we have generated a structure of full-length, tetrameric AbrB using nuclear magnetic resonance, chemical crosslinking, and mass spectrometry. We note that AbrB possesses a strip of positive electrostatic potential encompassing its DNA-binding region and that its C-terminal domain aids in DNA binding.

  3. Preslikavanje parametara kvaliteta usluga na protokole ATM mreža

    OpenAIRE

    Milojko Jevtović

    2005-01-01

    Preslikavanje parametara kvaliteta usluga (Quality of Service - QoS) jedan je od bitnih elemenata u koncepciji ATM (Asynchronous Transfer Mode) širokopojasnih mreža. U radu su opisani parametri QoS-a (verovatnoće pogrešnih ramova i ćelija, propusni opseg, kašnjenje ćelija, varijacija kašnjenja) koji se preslikavaju na protokole ATM mreža. Preslikavanje se izvodi između korisničkog i aplikacionog QoS-a, a aplikacioni QoS se preslikava na QoS prenosa i komutacije, odnosno na ATM protokole, tzv....

  4. Lack of bcr and abr promotes hypoxia-induced pulmonary hypertension in mice.

    Directory of Open Access Journals (Sweden)

    Min Yu

    Full Text Available BACKGROUND: Bcr and Abr are GTPase activating proteins that specifically downregulate activity of the small GTPase Rac in restricted cell types in vivo. Rac1 is expressed in smooth muscle cells, a critical cell type involved in the pathogenesis of pulmonary hypertension. The molecular mechanisms that underlie hypoxia-associated pulmonary hypertension are not well-defined. METHODOLOGY/PRINCIPAL FINDINGS: Bcr and abr null mutant mice were compared to wild type controls for the development of pulmonary hypertension after exposure to hypoxia. Also, pulmonary arterial smooth muscle cells from those mice were cultured in hypoxia and examined for proliferation, p38 activation and IL-6 production. Mice lacking Bcr or Abr exposed to hypoxia developed increased right ventricular pressure, hypertrophy and pulmonary vascular remodeling. Perivascular leukocyte infiltration in the lungs was increased, and under hypoxia bcr-/- and abr-/- macrophages generated more reactive oxygen species. Consistent with a contribution of inflammation and oxidative stress in pulmonary hypertension-associated vascular damage, Bcr and Abr-deficient animals showed elevated endothelial leakage after hypoxia exposure. Hypoxia-treated pulmonary arterial smooth muscle cells from Bcr- or Abr-deficient mice also proliferated faster than those of wild type mice. Moreover, activated Rac1, phosphorylated p38 and interleukin 6 were increased in these cells in the absence of Bcr or Abr. Inhibition of Rac1 activation with Z62954982, a novel Rac inhibitor, decreased proliferation, p38 phosphorylation and IL-6 levels in pulmonary arterial smooth muscle cells exposed to hypoxia. CONCLUSIONS: Bcr and Abr play a critical role in down-regulating hypoxia-induced pulmonary hypertension by deactivating Rac1 and, through this, reducing both oxidative stress generated by leukocytes as well as p38 phosphorylation, IL-6 production and proliferation of pulmonary arterial smooth muscle cells.

  5. Recording of electrically evoked auditory brainstem responses (E-ABR) with an integrated stimulus generator in Matlab.

    Science.gov (United States)

    Bahmer, Andreas; Peter, Otto; Baumann, Uwe

    2008-08-30

    Electrical auditory brainstem responses (E-ABRs) of subjects with cochlear implants are used for monitoring the physiologic responses of early signal processing of the auditory system. Additionally, E-ABR measurements allow the diagnosis of retro-cochlear diseases. Therefore, E-ABR should be available in every cochlear implant center as a diagnostic tool. In this paper, we introduce a low-cost setup designed to perform an E-ABR as well as a conventional ABR for research purposes. The distributable form was developed with Matlab and the Matlab Compiler (The Mathworks Inc.). For the ABR, only a PC with a soundcard, conventional system headphones, and an EEG pre-amplifier are necessary; for E-ABR, in addition, an interface to the cochlea implant is required. For our purposes, we implemented an interface for the Combi 40+/Pulsar implant (MED-EL, Innsbruck).

  6. The anaerobic baffled reactor (ABR) treating communal wastewater under mesophilic conditions: a review.

    Science.gov (United States)

    Reynaud, N; Buckley, C A

    2016-01-01

    A review concerning the anaerobic baffled reactor (ABR) treating communal wastewater under mesophilic conditions is presented. Existing studies indicate strong resilience of the reactor towards loading variations and shock-loads. The compartmentalisation of the ABR is a strongly stabilising factor with feed fluctuations being evened out across reactor chambers. Significant chemical oxygen demand (COD) reduction occurs almost exclusively in the first three chambers. The hydraulic rather than the organic loading rate is treatment limiting. Laboratory-scale studies show high treatment efficiencies of above 80% COD removal. It was found that most laboratory-scale studies do not factor in important aspects of field operation, such as diurnal fluctuations of feed characteristics, adequate start-up periods and periods of constant loading and optimised chamber outlet design, and never studied the effect of loading on sludge digestion. Performance data on full-scale ABR implementations, however, are extremely scarce, and existing studies are without exception affected by site-specific treatment-limiting factors hindering the extrapolation of generally valid conclusions. In view of a large-scale roll-out, communal ABRs are not sufficiently understood. Current challenges concerning the optimisation of reactor design require numerous well-monitored long-term full-scale reactor investigations. Existing ABR investigations yield encouraging results, supporting that the ABR may be one of the solutions answering the global call for low-maintenance, robust treatment systems.

  7. Activation of ATM by DNA Damaging Agents

    Science.gov (United States)

    2004-09-01

    activate ATM and/or ATM-dependent pathways 15 [61]. Indeed, phosphorylation of p53 on serines 20 and include quercetin [65], kaempferol , apigenin, and...protein [67] Phosphorylation on serine 15 [67] Kaempferol DSBf, SSBe Stimulation of kinase activity [67] Accumulation of p53 protein [67] Phosphorylation

  8. ATM: Restructing Learning for Deaf Students.

    Science.gov (United States)

    Keefe, Barbara; Stockford, David

    Governor Baxter School for the Deaf is one of six Maine pilot sites chosen by NYNEX to showcase asynchronous transfer mode (ATM) technology. ATM is a network connection that allows high bandwidth transmission of data, voice, and video. Its high speed capability allows for high quality two-way full-motion video, which is especially beneficial to a…

  9. Buffer Management Simulation in ATM Networks

    Science.gov (United States)

    Yaprak, E.; Xiao, Y.; Chronopoulos, A.; Chow, E.; Anneberg, L.

    1998-01-01

    This paper presents a simulation of a new dynamic buffer allocation management scheme in ATM networks. To achieve this objective, an algorithm that detects congestion and updates the dynamic buffer allocation scheme was developed for the OPNET simulation package via the creation of a new ATM module.

  10. DESIGNING A CAN BASED ATM FIELDBUS

    Directory of Open Access Journals (Sweden)

    Mahmut TENRUH

    2006-03-01

    Full Text Available The Controller Area Network (CAN bus was initially introduced for automotive applications, but due to its low cost, high speed and high reliability, it has also become a standard in industrial distributed real-time control applications. Asynchronous Transfer Mode (ATM is a high speed network technology that aims to combine all types of communication, that is, data, voice, and image in a single network structure. Various studies have been carried to incorporate existing network types such as Ethernet and Token Ring with ATM. It is also important to cover the FieldBus communication in this concept. This study aims to incorporate ATM technology with the FieldBus communication. In this concept, CAN based ATM bus structure is introduced. This structure also introduces an opportunity to connect FieldBus networks with ATM seamlessly. Simulation studies have been carried out to validate the introduced model and the results showed that it is feasible to implement the system.

  11. The versatile functions of ATM kinase

    Directory of Open Access Journals (Sweden)

    Rebecca J Boohaker

    2014-02-01

    Full Text Available Ataxia-telangiectasia mutated (ATM kinase, the mutation of which causes the autosomal recessive disease ataxia-telangiectasia, plays an essential role in the maintenance of genome stability. Extensive studies have revealed that activated ATM signals to a massive list of proteins to facilitate cell cycle checkpoints, DNA repair, and many other aspects of physiological responses in the event of DNA double-strand breaks. ATM also plays functional roles beyond the well-characterized DNA damage response (DDR. In this review article, we discuss the recent findings on the molecular mechanisms of ATM in DDR, the mitotic spindle checkpoint, as well as hyperactive ATM signaling in cancer invasion and metastasis.

  12. Dynamics of TCP traffic over ATM networks

    Energy Technology Data Exchange (ETDEWEB)

    Floyd, S. [Lawrence Berkeley Lab., CA (United States). Information and Computing Sciences Div.; Romanow, A. [Sun Microsystems Inc., Mountain View, CA (United States)

    1994-08-01

    The authors investigate the performance of TCP (Transport Control Protocol) connections over ATM (Asynchronous Transfer Mode) networks without ATM-level congestion control, and compare it to the performance of TCP over packet-based networks. For simulations of congested networks, the effective throughput of TCP over ATM can be quite low when cells are dropped at the congested ATM switch. The low throughput is due to wasted bandwidth as the congested link transmits cells from ``corrupted`` packets, i.e., packets in which at least one cell is dropped by the switch. This fragmentation effect can be corrected and high throughput can be achieved if the switch drops whole packets prior to buffer overflow; they call this strategy Early Packet Discard. They also discuss general issues of congestion avoidance for best-effort traffic in ATM networks.

  13. ATMs, Coffee Shops Ideal Spots for Heart Defibrillators

    Science.gov (United States)

    ... coffee shop chains, such as Tim Hortons and Starbucks, and ATMs connected to large banks. In fact, ... usually know where is the nearest ATM or Starbucks. "If people generally knew that ATMs and coffee ...

  14. Transputer-based architecture for ATM LAN protocol testing

    Science.gov (United States)

    Di Concetto, M.; Crocetti, P.; Marino, G.; Merli, E.; Pavesi, M.; Zizza, F.

    1993-10-01

    Local Area Networks (LANs) have completed two generations of development (Ethernet and Token Ring the first, and FDDI and DQDB the second); the large volumes of traffic involved in the emerging multimedia applications, however, lead towards a third generation of LANs. This generation must provide real-time capabilities needed by new services and solve the problems of interworking with ATM-based B-ISDN. Moreover the possibility to vary the subscribed bandwidth with the B-ISDN will be given to the LAN interfaces. This paper focuses on an architecture for protocol testing of a Dynamic Bandwidth Allocation Protocol inserted in a LAN environment based on ATM technology. In fact, the technology of the third LAN generation will be the Asynchronous Transfer Mode solving every interface problem with the public B-ISDN. A testing and debugging environment which checks the implementation of the Dynamic Bandwidth Allocation Protocol at the interface host/LAN- ATM is discussed. The main concepts of the overall system architecture are analyzed, evidencing both software and hardware issues.

  15. Asynchronous Transfer Mode (ATM) Switch Technology and Vendor Survey

    Science.gov (United States)

    Berry, Noemi

    1995-01-01

    Asynchronous Transfer Mode (ATM) switch and software features are described and compared in order to make switch comparisons meaningful. An ATM switch's performance cannot be measured solely based on its claimed switching capacity; traffic management and congestion control are emerging as the determining factors in an ATM network's ultimate throughput. Non-switch ATM products and experiences with actual installations of ATM networks are described. A compilation of select vendor offerings as of October 1994 is provided in chart form.

  16. ATM QoS Experiments Using TCP Applications: Performance of TCP/IP Over ATM in a Variety of Errored Links

    Science.gov (United States)

    Frantz, Brian D.; Ivancic, William D.

    2001-01-01

    Asynchronous Transfer Mode (ATM) Quality of Service (QoS) experiments using the Transmission Control Protocol/Internet Protocol (TCP/IP) were performed for various link delays. The link delay was set to emulate a Wide Area Network (WAN) and a Satellite Link. The purpose of these experiments was to evaluate the ATM QoS requirements for applications that utilize advance TCP/IP protocols implemented with large windows and Selective ACKnowledgements (SACK). The effects of cell error, cell loss, and random bit errors on throughput were reported. The detailed test plan and test results are presented herein.

  17. Airborne and underwater hearing in the great cormorant (Phalacrocorax carbo) studied with ABR and laser vibrometry

    DEFF Research Database (Denmark)

    Huulvej, Tina; Wahlberg, Magnus; Christensen-Dalsgaard, Jakob;

    in a (90x100x60 cm) water filled tank while being artificially ventilated. The ABR-response to calibrated tone bursts was measured at different intensities and frequencies (500, 1000, 2000, 4000, and 6000 Hz) to obtain hearing threshold values in air and under water. The bird was overdosed immediately...

  18. ATM kinase sustains HER2 tumorigenicity in breast cancer.

    Science.gov (United States)

    Stagni, Venturina; Manni, Isabella; Oropallo, Veronica; Mottolese, Marcella; Di Benedetto, Anna; Piaggio, Giulia; Falcioni, Rita; Giaccari, Danilo; Di Carlo, Selene; Sperati, Francesca; Cencioni, Maria Teresa; Barilà, Daniela

    2015-04-16

    ATM kinase preserves genomic stability by acting as a tumour suppressor. However, its identification as a component of several signalling networks suggests a dualism for ATM in cancer. Here we report that ATM expression and activity promotes HER2-dependent tumorigenicity in vitro and in vivo. We reveal a correlation between ATM activation and the reduced time to recurrence in patients diagnosed with invasive HER2-positive breast cancer. Furthermore, we identify ATM as a novel modulator of HER2 protein stability that acts by promoting a complex of HER2 with the chaperone HSP90, therefore preventing HER2 ubiquitination and degradation. As a consequence, ATM sustains AKT activation downstream of HER2 and may modulate the response to therapeutic approaches, suggesting that the status of ATM activity may be informative for the treatment and prognosis of HER2-positive tumours. Our findings provide evidence for ATM's tumorigenic potential revising the canonical role of ATM as a pure tumour suppressor.

  19. ABR and auditory P300 findings inchildren with ADHD Achados em ABR e P300 auditivo em crianças com TDAH

    Directory of Open Access Journals (Sweden)

    Eliane Schochat

    2002-09-01

    Full Text Available Auditory processing disorders (APD, also referred as central auditory processing disorders (CAPD and attention deficit hyperactivity disorders (ADHD have become popular diagnostic entities for school age children. It has been demonstrated a high incidence of comorbid ADHD with communication disorders and auditory processing disorder. The aim of this study was to investigate ABR and P300 auditory evoked potentials in children with ADHD, in a double-blind study. Twenty-one children, ages between 7 and 10 years, with a primary diagnosis of ADHD, participated in this experiment. Results showed that all children had normal ABR with normal latency for wave V. Results also showed that among 42 ears combined 52.38% did not have P300. For the medicated subjects we observed that among 28 ears, 42.85% did not have P300 and for the non-medicated 71.43% (N = 14 ears did not have P300. Our results suggest that the medicated subjects had more presence of P300 (57.15% than the non-medicated group (28.57%, though the absence of these potentials were high among the group - 52.38%.Alterações do processamento auditivo, também chamadas alterações no processamento auditivo central e o transtorno do deficit de atenção/ hiperatividade (TDAH, tornaram-se entidades populares nos diagnósticos de crianças escolares. Uma grande incidência de TDAH em comorbidade com alterações na comunicação e com o processamento auditivo central tem sido demonstrada. O objetivo deste estudo foi investigar potenciais evocados auditivos, ABR e P300, em crianças com TDAH, em um estudo duplo cego. Vinte e uma crianças, idades entre 7 e 10 anos, com diagnostico primário de TDAH, participaram deste experimento. Os resultados mostraram que todas as crianças tinham ABR com latência normal para a onda V e que, entre 42 orelhas, 52,38% não tinham P300. Para os sujeitos medicados observou-se que entre 28 orelhas, 42,85% não tinham P300 e para os não medicados 71,43% (N = 14

  20. User-centered design with illiterate persons : The case of the ATM user interface

    NARCIS (Netherlands)

    Cremers, A.H.M.; Jong, J.G.M. de; Balken, J.S. van

    2008-01-01

    One of the major challenges in current user interface research and development is the accommodation of diversity in users and contexts of use in order to improve the self-efficacy of citizens. A common banking service, which should be designed for diversity, is the Automated Teller Machine (ATM). Th

  1. Link Enhancer for Vehicular Wireless ATM Communications

    CERN Document Server

    Arun Kumar, S P; Kumar, Amrendra

    2008-01-01

    Majority of the applications used in defense are voice, video and data oriented and has strict QoS requirements. One of the technologies that enabled this is Asynchronous Transfer Mode (ATM) networking. Traditional ATM networks are wired networks. But Tactical networks are meant to be mobile and this necessitates the use of radio relays for Vehicle-to-Infrastructure (V2I) and Vehicle-to-Vehicle (V2V) communications. ATM networks assume a physical link layer BER of 10^-9 or better because of the availability of reliable media like optical fiber links. But this assumption is no longer valid when ATM switches are connected through radio relay where error rates are in the rage of 10^-3. This paper presents the architecture of a Link Enhancer meant to improve the Bit Error Rate of the Wireless links used for V2I and V2V communications from 1 in 10^4 to 1 in 10^8

  2. Terminal Area ATM Research at NASA Ames

    Science.gov (United States)

    Tobias, Leonard

    1997-01-01

    The presentation will highlight the following: (1) A brief review of ATC research underway 15 years ago; (2) A summary of Terminal Area ATM Tool Development ongoing at NASA Ames; and (3) A projection of research activities 10-15 years from now.

  3. Performance analysis of ATM/DQDB interworking

    DEFF Research Database (Denmark)

    Christiansen, Henning; Kvols, Kenn

    1992-01-01

    The cell loss ratio and cell delay variation of a distributed-queue dual-bus (DQDB) network receiving traffic from a number of asynchronous transfer mode (ATM) connections are considered. Every connection carries either connection oriented or connectionless traffic. In the analysis of the access...

  4. Leo Satellite Communication through a LEO Constellation using TCP/IP Over ATM

    Science.gov (United States)

    Foore, Lawrence R.; Konangi, Vijay K.; Wallett, Thomas M.

    1999-01-01

    The simulated performance characteristics for communication between a terrestrial client and a Low Earth Orbit (LEO) satellite server are presented. The client and server nodes consist of a Transmission Control Protocol /Internet Protocol (TCP/IP) over ATM configuration. The ATM cells from the client or the server are transmitted to a gateway, packaged with some header information and transferred to a commercial LEO satellite constellation. These cells are then routed through the constellation to a gateway on the globe that allows the client/server communication to take place. Unspecified Bit Rate (UBR) is specified as the quality of service (QoS). Various data rates are considered.

  5. Remote facility sharing with ATM networks [PC based ATM Link Delay Simulator (LDS)]. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Kung, H. T.

    2001-06-01

    The ATM Link Delay Simulator (LDS) adds propagation delay to the ATM link on which it is installed, to allow control of link propagation delay in network protocol experiments simulating an adjustable piece of optical fiber. Our LDS simulates a delay of between 1.5 and 500 milliseconds and is built with commodity PC hardware, only the ATM network interface card is not generally available. Our implementation is special in that it preserves the exact spacing of ATM data cells a feature that requires sustained high performance. Our implementation shows that applications demanding sustained high performance are possible on commodity PC hardware. This illustrates the promise that PC hardware has for adaptability to demanding specialized testing of high speed network.

  6. FACET: Future ATM Concepts Evaluation Tool

    Science.gov (United States)

    Bilmoria, Karl D.; Banavar, Sridhar; Chatterji, Gano B.; Sheth, Kapil S.; Grabbe, Shon

    2000-01-01

    FACET (Future ATM Concepts Evaluation Tool) is an Air Traffic Management research tool being developed at the NASA Ames Research Center. This paper describes the design, architecture and functionalities of FACET. The purpose of FACET is to provide E simulation environment for exploration, development and evaluation of advanced ATM concepts. Examples of these concepts include new ATM paradigms such as Distributed Air-Ground Traffic Management, airspace redesign and new Decision Support Tools (DSTs) for controllers working within the operational procedures of the existing air traffic control system. FACET is currently capable of modeling system-wide en route airspace operations over the contiguous United States. Airspace models (e.g., Center/sector boundaries, airways, locations of navigation aids and airports) are available from databases. A core capability of FACET is the modeling of aircraft trajectories. Using round-earth kinematic equations, aircraft can be flown along flight plan routes or great circle routes as they climb, cruise and descend according to their individual aircraft-type performance models. Performance parameters (e.g., climb/descent rates and speeds, cruise speeds) are obtained from data table lookups. Heading, airspeed and altitude-rate dynamics are also modeled. Additional functionalities will be added as necessary for specific applications. FACET software is written in Java and C programming languages. It is platform-independent, and can be run on a variety of computers. FACET has been designed with a modular software architecture to enable rapid integration of research prototype implementations of new ATM concepts. There are several advanced ATM concepts that are currently being implemented in FACET airborne separation assurance, dynamic density predictions, airspace redesign (re-sectorization), benefits of a controller DST for direct-routing, and the integration of commercial space transportation system operations into the U.S. National

  7. A proposed medical physics curriculum: preparing for the 2013 ABR examination.

    Science.gov (United States)

    Nachiappan, Arun C; Wynne, David M; Katz, David P; Willis, Marc H; Bushong, Stewart C

    2011-01-01

    The upcoming ABR examination format for radiology residents is undergoing significant changes in 2013. This requires adaptation of the didactic curriculum for radiology residents entering in July 2010 to meet these changes. Physics will now be incorporated into the core (qualifying) examination during the third year of residency, instead of being tested as a separate examination that was often taken earlier in residency training in past years. In this article, the authors discuss the past, present, and future of medical physics instruction and outline a revised medical physics curriculum for radiology residents that has been internally approved for implementation at the authors' institution and has not been advocated by any society or by the ABR. Starting with this article, the authors hope to encourage a discussion of physics curriculum revision with other institutions.

  8. Interim progress report on safety and licensing strategy support for the ABR prototype.

    Energy Technology Data Exchange (ETDEWEB)

    Cahalan, J .E.; Nuclear Engineering Division

    2007-06-26

    Argonne National Laboratory is providing support to the U.S. Department of Energy in the Global Nuclear Energy Partnership (GNEP) in certification of an advanced, sodium-cooled fast reactor. The reactor is to be constructed as a prototype for future commercial power reactors that will produce electricity while consuming actinides recovered from light water reactor spent fuel. This prototype reactor has been called the ABR, or Advanced Burner Reactor.

  9. Design of a Regenerable Air Revitalization Control System for the ABRS Plant Growth Facility

    Science.gov (United States)

    Monje, Oscar; Monje, Oscar; Shellack, James; Mortenson, Todd; Wells, Howard

    Design of a Regenerable Air Revitalization Control System for the ABRS Plant Growth Facility. O. Monje Space Life Sciences Laboratory, Dynamac Corp., DYN-3, Kennedy Space Center, FL 32899, USA J.L. Shellack, T.E. Mortenson, and H.W. Wells. Bionetics Corporation, BIO-1, Kennedy Space Center, FL 32899, USA The Advanced Biological Research System (ABRS) is a rear-breathing, single middeck locker equivalent plant growth system. ABRS is composed of two independently controlled growth chambers (each with 330 cm2 of growth area). The air revitalization system in each chamber is composed of two subsystems: CO2 Control and a Ethylene/VOC Control. The CO2 Control subsystem must control chamber [CO2] within a range of 300-2000 ppm, with a nominal setpoint of 1500 ppm. The Ethylene/VOC Control subsystem is required to maintain chamber ethylene concentration at ¡50 ppb. Previous spaceflight plant payloads have used non-regenerable cartridges for CO2 control and photocatalytic scrubbers for controlling concentrations of volatile organic compounds (VOCs). Non-regenerable systems have used LiOH cartridges for [CO2] control with a combination of Purafil (KMnO4)/Activated charcoal for scrubbing VOCs. Regenerable air revitalization systems offer the potential for reducing the mass and volume of consumables used during spaceflight plant experiments. A system utilizing technologies employing regenerable adsorbents: zeolites 13X and 5A for CO2 control and Carbosieve SIII (C molecular sieve) for VOC control has been designed for ABRS. The filter cartridges were sized using expected chamber leak rates, measurements of adsorptive capacities, and measured CO2 consumption and VOC generation rates.

  10. Performance analysis and comparison of PTOP and LANE for IP transmission over ATM networks

    Science.gov (United States)

    Zubairi, Junaid A.; Al-Irhayim, Sufyan; Al-Khateeb, Wajdi; Wajdi, Yahya

    1998-12-01

    Due to its traffic control and performance assurance characteristics, ATM is being employed as the core network in most campuses. However, bulk of the workstations remain on Ethernet, generating IP traffic that passes through ATM using special schemes such as PTOP or LANE. In such a network, the performance is affected due to the extra overheads in multiple conversions between cells and packets and managing virtual circuits. The aim of this paper is to compare the performance of PTOP and LANE in passing the IP traffic under various conditions. This study helps in understanding the various performance issues in these environments in order to define the end-to-end quality of service for Ethernet-ATM networks.

  11. Improved virtual queuing and dynamic EPD techniques for TCP over ATM

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Y.; Siu, K.Y.; Ren, W.

    1998-11-01

    It is known that TCP throughput can degrade significantly over UBR service in a congested ATM network, and the early packet discard (EPD) technique has been proposed to improve the performance. However, recent studies show that EPD cannot ensure fairness among competing VCs in a congested network, but the degree of fairness can be improved using various forms of fair buffer allocation techniques. The authors propose an improved scheme that utilizes only a single shared FIFO queue for all VCs and admits simple implementation for high speed ATM networks. The scheme achieves nearly perfect fairness and throughput among multiple TCP connections, comparable to the expensive per-VC queuing technique. Analytical and simulation results are presented to show the validity of this new scheme and significant improvement in performance as compared with existing fair buffer allocation techniques for TCP over ATM.

  12. A Managerial Analysis of ATM in Facilitating Distance Education.

    Science.gov (United States)

    Littman, Marlyn Kemper

    In this paper, the fundamental characteristics and capabilities of ATM (Asynchronous Transfer Mode) networks in a distance learning environment are examined. Current and projected ATM applications are described, and issues and challenges associated with developing ATM networking solutions for instructional delivery are explored. Other topics…

  13. ATM protein is deficient in over 40% of lung adenocarcinomas.

    Science.gov (United States)

    Villaruz, Liza C; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F; Stabile, Laura P; Siegfried, Jill M; Conrads, Thomas P; Smith, Neil R; O'Connor, Mark J; Pierce, Andrew J; Bakkenist, Christopher J

    2016-09-06

    Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

  14. Self-adaptive trust based ABR protocol for MANETs using Q-learning.

    Science.gov (United States)

    Kumar, Anitha Vijaya; Jeyapal, Akilandeswari

    2014-01-01

    Mobile ad hoc networks (MANETs) are a collection of mobile nodes with a dynamic topology. MANETs work under scalable conditions for many applications and pose different security challenges. Due to the nomadic nature of nodes, detecting misbehaviour is a complex problem. Nodes also share routing information among the neighbours in order to find the route to the destination. This requires nodes to trust each other. Thus we can state that trust is a key concept in secure routing mechanisms. A number of cryptographic protection techniques based on trust have been proposed. Q-learning is a recently used technique, to achieve adaptive trust in MANETs. In comparison to other machine learning computational intelligence techniques, Q-learning achieves optimal results. Our work focuses on computing a score using Q-learning to weigh the trust of a particular node over associativity based routing (ABR) protocol. Thus secure and stable route is calculated as a weighted average of the trust value of the nodes in the route and associativity ticks ensure the stability of the route. Simulation results show that Q-learning based trust ABR protocol improves packet delivery ratio by 27% and reduces the route selection time by 40% over ABR protocol without trust calculation.

  15. Self-Adaptive Trust Based ABR Protocol for MANETs Using Q-Learning

    Directory of Open Access Journals (Sweden)

    Anitha Vijaya Kumar

    2014-01-01

    Full Text Available Mobile ad hoc networks (MANETs are a collection of mobile nodes with a dynamic topology. MANETs work under scalable conditions for many applications and pose different security challenges. Due to the nomadic nature of nodes, detecting misbehaviour is a complex problem. Nodes also share routing information among the neighbours in order to find the route to the destination. This requires nodes to trust each other. Thus we can state that trust is a key concept in secure routing mechanisms. A number of cryptographic protection techniques based on trust have been proposed. Q-learning is a recently used technique, to achieve adaptive trust in MANETs. In comparison to other machine learning computational intelligence techniques, Q-learning achieves optimal results. Our work focuses on computing a score using Q-learning to weigh the trust of a particular node over associativity based routing (ABR protocol. Thus secure and stable route is calculated as a weighted average of the trust value of the nodes in the route and associativity ticks ensure the stability of the route. Simulation results show that Q-learning based trust ABR protocol improves packet delivery ratio by 27% and reduces the route selection time by 40% over ABR protocol without trust calculation.

  16. Self-Adaptive Trust Based ABR Protocol for MANETs Using Q-Learning

    Science.gov (United States)

    Jeyapal, Akilandeswari

    2014-01-01

    Mobile ad hoc networks (MANETs) are a collection of mobile nodes with a dynamic topology. MANETs work under scalable conditions for many applications and pose different security challenges. Due to the nomadic nature of nodes, detecting misbehaviour is a complex problem. Nodes also share routing information among the neighbours in order to find the route to the destination. This requires nodes to trust each other. Thus we can state that trust is a key concept in secure routing mechanisms. A number of cryptographic protection techniques based on trust have been proposed. Q-learning is a recently used technique, to achieve adaptive trust in MANETs. In comparison to other machine learning computational intelligence techniques, Q-learning achieves optimal results. Our work focuses on computing a score using Q-learning to weigh the trust of a particular node over associativity based routing (ABR) protocol. Thus secure and stable route is calculated as a weighted average of the trust value of the nodes in the route and associativity ticks ensure the stability of the route. Simulation results show that Q-learning based trust ABR protocol improves packet delivery ratio by 27% and reduces the route selection time by 40% over ABR protocol without trust calculation. PMID:25254243

  17. ATM traffic-policing and traffic-shaping measurements

    Science.gov (United States)

    Pugaczewski, Jack T.; Sanderson, Dave; Hoffman, David W.

    1997-10-01

    ATM (Asynchronous Transfer Mode) defines several Quality of Service (QoS) levels such as CBR (Constant Bit Rate) and VBR (Variable Bit Rate). Each service has parameters that are associated with its performance characteristic. The parameters used for specifying CBR service are Peak Cell Rate (PCR) and Cell Delay Variation Tolerance (CDVTOL). The parameters used for specifying VBR service are PCR, SCR (Sustainable Cell Rate), and BT (Burst Tolerance). The network takes responsibility for monitoring and policing the traffic of each VCC/VPC at the ingress of the network. The CPE needs to traffic shape at the ingress of the network in order to meet the contracted QoS requirements. Measurement procedures and tools are required in order to provide a means of tuning the CPE and network service to meet the customer's end-to-end QoS expectations. The following paper describes how the Generic Cell Rate Algorithm variables can be adjusted to provide acceptable levels of QoS in a mixed VBR, and CBR environment. In addition, the paper examines a methodology for measuring the performance of VBR and CBR services. The authors uses this information to build a QoS measurement tool.

  18. Enhanced root colonization and biocontrol activity of Bacillus amyloliquefaciens SQR9 by abrB gene disruption.

    Science.gov (United States)

    Weng, Jun; Wang, Yang; Li, Juan; Shen, Qirong; Zhang, Ruifu

    2013-10-01

    Root colonization by antagonistic bacteria is a prerequisite for successful biological control, and the instability of colonization under varying environmental conditions has accentuated the need to improve the colonization activity. Root colonization by Bacillus spp. is mainly determined by chemotaxis and biofilm formation, and both functions are negatively controlled by the global transcription regulator AbrB. Here, we disrupted the gene abrB in Bacillus amyloliquefaciens SQR9, which has been proven to be a promising biocontrol agent of cucumber and watermelon wilt disease. Chemotaxis, biofilm formation, and colonization activities as well as biocontrol efficiency were measured and compared between the wild-type strain of SQR9 and the abrB mutant. The data presented in this article demonstrate that the colonization and biocontrol activity of B. amyloliquefaciens SQR9 could be significantly improved by abrB gene disruption. The results offer a new strategy to enhance the biocontrol efficacy of B. amyloliquefaciens SQR9.

  19. Synthetic studies on taxanes: A domino-enyne metathesis/Diels-Alder approach to the AB-ring

    Indian Academy of Sciences (India)

    Krishna P Kaliappan; Velayutham Ravikumar; Sandip A Pujari

    2008-01-01

    A domino enyne cross-metathesis/intramolecular Diels-Alder reaction has been successfully used to synthesize a bicyclo[5.3.1] undecene, corresponding to AB-ring of taxol without the gem dimethyl group.

  20. MODELING OF THE PRIORITY SCHEDULING INPUT-LINE GROUP OUTPUT WITH MULTI-CHANNEL IN ATM EXCHANGE SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In this paper, an extended Kendall model for the priority scheduling input-line group output with multi-channel in Asynchronous Transfer Mode (ATM) exchange system is proposed and then the mean method is used to model mathematically the non-typical non-anticipative PRiority service (PR) model. Compared with the typical and non-anticipative PR model, it expresses the characteristics of the priority scheduling input-line group output with multi-channel in ATM exchange system. The simulation experiment shows that this model can improve the HOL block and the performance of input-queued ATM switch network dramatically. This model has a better developing prospect in ATM exchange system.

  1. 采用ABR-MBR处理豆制品废水的工程实践%Engineering practice of bean products wastewater treatment by ABR-MBR

    Institute of Scientific and Technical Information of China (English)

    周曦; 刘迎九; 陈朝猛; 周书葵; 左洪泽

    2015-01-01

    豆制品废水具有污染物浓度高、成分复杂、水质多变、色度高的特点,采用ABR-MBR工艺对其进行处理:在进水COD≤8 000 mg/L、NH3-N≤200 mg/L情况下,出水水质COD≤60 mg/L、NH3-N≤14 mg/L,去除率分别达到98.87%和93.15%以上.工程实践运行表明:该工艺具有工程费用低、运行稳定、维护简单、操作方便等优点,处理后出水达到了《污水综合排放标准》(GB 8978—2002)一级排放标准.%Bean products wastewater are characterized by high-concentrations pollutants,complex composition,multi-variant water quality and high chroma.The ABR-MBR process has been used for its treatment.The effluent COD is≤60 mg/L,NH3-N≤14 mg/L and their removal rates are 98.87%and 93.15%respectively.When influent COD is 8 000 mg/L and NH3-N 200 mg/L.The engineering practice proved that this process has advantages,such as low engineering cost,stable operation,simple maintenance,convenient operation,etc.The treated effluent by this process can reach the first level requirements specified in the Integrated Wastewater Discharge Standard (GB 8978—2002).

  2. Preservation of methane hydrate at 1 atm

    Science.gov (United States)

    Stern, L.A.; Circone, S.; Kirby, S.H.; Durham, W.B.

    2001-01-01

    A "pressure-release" method that enables reproducible bulk preservation of pure, porous, methane hydrate at conditions 50 to 75 K above its equilibrium T (193 K) at 1 atm is refined. The amount of hydrate preserved by this method appears to be greatly in excess of that reported in the previous citations, and is likely the result of a mechanism different from ice shielding.

  3. ATM Coastal Topography-Alabama 2001

    Science.gov (United States)

    Nayegandhi, Amar; Yates, Xan; Brock, John C.; Sallenger, A.H.; Bonisteel, Jamie M.; Klipp, Emily S.; Wright, C. Wayne

    2009-01-01

    These remotely sensed, geographically referenced elevation measurements of Lidar-derived first surface (FS) topography were produced collaboratively by the U.S. Geological Survey (USGS), Florida Integrated Science Center (FISC), St. Petersburg, FL, and the National Aeronautics and Space Administration (NASA), Wallops Flight Facility, VA. This project provides highly detailed and accurate datasets of the Alabama coastline, acquired October 3-4, 2001. The datasets are made available for use as a management tool to research scientists and natural resource managers. An innovative scanning Lidar instrument originally developed by NASA, and known as the Airborne Topographic Mapper (ATM), was used during data acquisition. The ATM system is a scanning Lidar system that measures high-resolution topography of the land surface, and incorporates a green-wavelength laser operating at pulse rates of 2 to 10 kilohertz. Measurements from the laser ranging device are coupled with data acquired from inertial navigation system (INS) attitude sensors and differentially corrected global positioning system (GPS) receivers to measure topography of the surface at accuracies of +/-15 centimeters. The nominal ATM platform is a Twin Otter or P-3 Orion aircraft, but the instrument may be deployed on a range of light aircraft. Elevation measurements were collected over the survey area using the ATM system, and the resulting data were then processed using the Airborne Lidar Processing System (ALPS), a custom-built processing system developed in a NASA-USGS collaboration. ALPS supports the exploration and processing of Lidar data in an interactive or batch mode. Modules for pre-survey flight line definition, flight path plotting, Lidar raster and waveform investigation, and digital camera image playback have been developed. Processing algorithms have been developed to extract the range to the first and last significant return within each waveform. ALPS is routinely used to create maps that

  4. ATM Coastal Topography-Mississippi, 2001

    Science.gov (United States)

    Nayegandhi, Amar; Yates, Xan; Brock, John C.; Sallenger, A.H.; Klipp, Emily S.; Wright, C. Wayne

    2009-01-01

    These remotely sensed, geographically referenced elevation measurements of lidar-derived first-surface (FS) topography were produced collaboratively by the U.S. Geological Survey (USGS), Florida Integrated Science Center (FISC), St. Petersburg, FL, and the National Aeronautics and Space Administration (NASA), Wallops Flight Facility, VA. This project provides highly detailed and accurate datasets of the Mississippi coastline, from Lakeshore to Petit Bois Island, acquired September 9-10, 2001. The datasets are made available for use as a management tool to research scientists and natural-resource managers. An innovative scanning lidar instrument originally developed by NASA, and known as the Airborne Topographic Mapper (ATM), was used during data acquisition. The ATM system is a scanning lidar system that measures high-resolution topography of the land surface and incorporates a green-wavelength laser operating at pulse rates of 2 to 10 kilohertz. Measurements from the laser-ranging device are coupled with data acquired from inertial navigation system (INS) attitude sensors and differentially corrected global positioning system (GPS) receivers to measure topography of the surface at accuracies of +/-15 centimeters. The nominal ATM platform is a Twin Otter or P-3 Orion aircraft, but the instrument may be deployed on a range of light aircraft. Elevation measurements were collected over the survey area using the ATM system, and the resulting data were then processed using the Airborne Lidar Processing System (ALPS), a custom-built processing system developed in a NASA-USGS collaboration. ALPS supports the exploration and processing of lidar data in an interactive or batch mode. Modules for presurvey flight-line definition, flight-path plotting, lidar raster and waveform investigation, and digital camera image playback have been developed. Processing algorithms have been developed to extract the range to the first and last significant return within each waveform. ALPS

  5. ATM and ATR:Sensing DNA damage

    Institute of Scientific and Technical Information of China (English)

    Jun Yang; Zheng-Ping Xu; Yun Huang; Hope E. Hamrick; Penelope J. Duerksen-Hughes; Ying-Nian Yu

    2004-01-01

    Cellular response to genotoxic stress is a very complex process, and it usually starts with the "sensing" or "detection" of the DNA damage, followed by a series of events that include signal transduction and activation of transcription factors. The activated transcription factors induce expressions of many genes which are involved in cellular functions such as DNA repair, cell cycle arrest, and cell death. There have been extensive studies from multiple disciplines exploring the mechanisms of cellular genotoxic responses, which have resulted in the identification of many cellular components involved in this process, including the mitogen-activated protein kinases (MAPKs) cascade. Although the initial activation of protein kinase cascade is not fully understood,human protein kinases ATM (ataxia-telangiectasia, mutated) and ATR (ATM and Rad3-related) are emerging as potential sensors of DNA damage. Current progresses in ATM/ATR research and related signaling pathways are discussed in this review, in an effort to facilitate a better understanding of genotoxic stress response.

  6. Intercalibrating and Validating Saphir and Atms Observations

    Science.gov (United States)

    Moradi, I.; Ferraro, R. R.

    2014-12-01

    We present the results of evaluating observations from microwave instruments aboard the Suomi National Polar-orbiting Partnership (NPP, ATMS instrument) and Megha-Tropiques (SAPHIR instrument) satellites. ATMS is a cross-track microwave sounder that currently flying on the Suomi National Polar-orbiting Partnership (S-NPP) satellite, launched in October 2011, which is in a Sun-synchronous orbit with the ascending equatorial crossing time at 01:30 a.m. Megha-Tropiques, launched in Nov 2011, is a low-inclination satellite meaning that the satellite only visits the tropical band between 30 S and 30 N. SAPHIR is a microwave humidity sounder with 6 channels operating at the frequencies close to the water vapor absorption line at 183 GHz. Megha-Tropiques revisits the tropical regions several times a day and provide a great capability for inter-calibrating the observations with the polar orbiting satellites. The study includes inter-comparison and inter-calibration of observations of similar channels from the two instruments, evaluation of the satellite data using high-quality radiosonde data from Atmospheric Radiation Measurement Program and GPS Radio Occultaion Observations from COSMIC mission, as well as geolocation error correction. The results of this study are valuable for generating climate data records from these instruments as well as for extending current climate data records from similar instruments such as AMSU-B and MHS to the ATMS and SAPHIR instruments.

  7. Linking ATM Promoter Methylation to Cell Cycle Protein Expression in Brain Tumor Patients: Cellular Molecular Triangle Correlation in ATM Territory.

    Science.gov (United States)

    Mehdipour, P; Karami, F; Javan, Firouzeh; Mehrazin, M

    2015-08-01

    Ataxia telangiectasia mutated (ATM) is a key gene in DNA double-strand break (DSB), and therefore, most of its disabling genetic alterations play an important initiative role in many types of cancer. However, the exact role of ATM gene and its epigenetic alterations, especially promoter methylation in different grades of brain tumors, remains elusive. The current study was conducted to query possible correlations among methylation statue of ATM gene, ATM/ retinoblastoma (RB) protein expression, D1853N ATM polymorphism, telomere length (TL), and clinicopathological characteristics of various types of brain tumors. Isolated DNA from 30 fresh tissues was extracted from different types of brain tumors and two brain tissues from deceased normal healthy individuals. DNAs were treated with bisulfate sodium using DNA modification kit (Qiagen). Methylation-specific polymerase chain reaction (MSP-PCR) was implicated to determine the methylation status of treated DNA templates confirmed by promoter sequencing. Besides, the ATM and RB protein levels were determined by immunofluorescence (IF) assay using monoclonal mouse antihuman against ATM, P53, and RB proteins. To achieve an interactive correlation, the methylation data were statistically analyzed by considering TL and D1853N ATM polymorphism. More than 73% of the brain tumors were methylated in ATM gene promoter. There was strong correlation between ATM promoter methylation and its protein expression (p ATM promoter and ATM protein expression with D1853N ATM polymorphism (p = 0.01). ATM protein expression was not in line with RB protein expression while it was found to be significantly correlated with ATM promoter methylation (p = 0.01). There was significant correlation between TL neither with ATM promoter methylation nor with ATM protein expression nor with D1853N polymorphism. However, TL has shown strong correlation with patient's age and tumor grade (p = 0.01). Given the important role of cell cycle checkpoint

  8. Prognostic Significance of Nuclear Phospho-ATM Expression in Melanoma.

    Science.gov (United States)

    Bhandaru, Madhuri; Martinka, Magdalena; McElwee, Kevin J; Rotte, Anand

    2015-01-01

    UV radiation induced genomic instability is one of the leading causes for melanoma. Phosphorylation of Ataxia Telangiectasia Mutated (ATM) is one of the initial events that follow DNA damage. Phospho-ATM (p-ATM) plays a key role in the activation of DNA repair and several oncogenic pathways as well as in the maintenance of genomic integrity. The present study was therefore performed to understand the significance of p-ATM in melanoma progression and to correlate it with patient prognosis. Tissue microarray and immunohistochemical analysis were employed to study the expression of p-ATM in melanoma patients. A total of 366 melanoma patients (230 primary melanoma and 136 metastatic melanoma) were used for the study. Chi-square test, Kaplan-Meier, univariate and multivariate Cox regression analysis were used to elucidate the prognostic significance of p-ATM expression. Results revealed that both loss of, and gain in, p-ATM expression were associated with progression of melanoma from normal nevi to metastatic melanoma. Patients whose samples showed negative or strong p-ATM staining had significantly worse 5-year survival compared to patients who had weak to moderate expression. Loss of p-ATM expression was associated with relatively better 5-year survival, but the corresponding 10-year survival curve almost overlapped with that of strong p-ATM expression. p-ATM expression was found to be an independent prognostic factor for 5-year but not for 10-year patient survival. In conclusion our findings show that loss of p-ATM expression and gain-in p-ATM expression are indicators of worse melanoma patient survival.

  9. 5'-Hydroxyzearalenol, a new β-resorcylic macrolide from Fusarium sp. 05ABR26

    Institute of Scientific and Technical Information of China (English)

    Ling Ling Zhao; Yue Gai; Hisayoshi Kobayashi; Chang Qi Hu; Hui Ping Zhang

    2008-01-01

    A new β-resorcylic maerolide, 5'-hydroxyzearalenol (1), was isolated from the culture broth of a marine-derived fungus Fusarium sp. 05ABR26. Three known compounds, zearalenone (2), 8'-hydroxyzearalenone (3) and zearalenol (4) were also isolated. The structure and relative stereochemistry of 1 were elucidated on the basis of spectroscopic data and single-crystal X-ray diffraction data. Compound 2 displayed potent inhibitory activity against Pyricularia oryzae with a MIC value of 6.25 μg/mL, while compound 3 was much less active; however, 1 and 4 showed no obvious activity.

  10. Prevalence of deleterious ATM germline mutations in gastric cancer patients.

    Science.gov (United States)

    Huang, Dong-Sheng; Tao, Hou-Quan; He, Xu-Jun; Long, Ming; Yu, Sheng; Xia, Ying-Jie; Wei, Zhang; Xiong, Zikai; Jones, Sian; He, Yiping; Yan, Hai; Wang, Xiaoyue

    2015-12-01

    Besides CDH1, few hereditary gastric cancer predisposition genes have been previously reported. In this study, we discovered two germline ATM mutations (p.Y1203fs and p.N1223S) in a Chinese family with a history of gastric cancer by screening 83 cancer susceptibility genes. Using a published exome sequencing dataset, we found deleterious germline mutations of ATM in 2.7% of 335 gastric cancer patients of different ethnic origins. The frequency of deleterious ATM mutations in gastric cancer patients is significantly higher than that in general population (p=0.0000435), suggesting an association of ATM mutations with gastric cancer predisposition. We also observed biallelic inactivation of ATM in tumors of two gastric cancer patients. Further evaluation of ATM mutations in hereditary gastric cancer will facilitate genetic testing and risk assessment.

  11. [Formation Mechanism of Aerobic Granular Sludge and Removal Efficiencies in Integrated ABR-CSTR Reactor].

    Science.gov (United States)

    Wu, Kai-cheng; Wu, Peng; Xu, Yue-zhong; Li, Yue-han; Shen, Yao-liang

    2015-08-01

    Anaerobic Baffled Reactor (ABR) was altered to make an integrated anaerobic-aerobic reactor. The research investigated the mechanism of aerobic sludge granulation, under the condition of continuous-flow. The last two compartments of the ABR were altered into aeration tank and sedimentation tank respectively with seeded sludge of anaerobic granular sludge in anaerobic zone and conventional activated sludge in aerobic zone. The HRT was gradually decreased in sedimentation tank from 2.0 h to 0.75 h and organic loading rate was increased from 1.5 kg x (M3 x d)(-1) to 2.0 kg x (M3 x d)(-1) while the C/N of 2 was controlled in aerobic zone. When the system operated for 110 days, the mature granular sludge in aerobic zone were characterized by compact structure, excellent sedimentation performance (average sedimentation rate was 20.8 m x h(-1)) and slight yellow color. The system performed well in nitrogen and phosphorus removal under the conditions of setting time of 0.75 h and organic loading rate of 2.0 kg (m3 x d)(-1) in aerobic zone, the removal efficiencies of COD, NH4+ -N, TP and TN were 90%, 80%, 65% and 45%, respectively. The results showed that the increasing selection pressure and the high organic loading rate were the main propulsions of the aerobic sludge granulation.

  12. Mode of ATM-dependent suppression of chromosome translocation

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, Motohiro, E-mail: motoyama@nagasaki-u.ac.jp [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

  13. Research on cultivation of aerobic granular sludge in ABR-CSTR%ABR-CSTR反应器培养好氧颗粒污泥的研究

    Institute of Scientific and Technical Information of China (English)

    丁玲玲; 沈耀良; 刘伟

    2015-01-01

    以醋酸盐做碳源的人工配水为原水,在常温条件下采用连续流式运行的ABR-CSTR反应器培养好氧颗粒污泥.结果表明,通过逐步缩短水力停留时间和提升进水负荷的方法,在114 d内培养出成熟的好氧颗粒污泥,好氧颗粒污泥反应器的运行高效而稳定,在沉淀时间为0.5 h,有机负荷与氨氮容积负荷均为2.4 kg/(m3·d)条件下,对COD和NH4+-N的去除率达90%以上,具有明显的去碳脱氮效果.

  14. Video Coding and Modeling with Applications to ATM Multiplexing

    Science.gov (United States)

    Nguyen, Hien

    A new vector quantization (VQ) coding method based on optimized concentric shell partitioning of the image space is proposed. The advantages of using the concentric shell partition vector quantizer (CSPVQ) are that it is very fast and the image patterns found in each different subspace can be more effectively coded by using a codebook that is best matched to that particular subspace. For intra-frame coding, the CSPVQ is shown to have the same performance, if not better, than the optimized gain-shape VQ in terms of encoded picture quality while it definitely surpasses the gain-shape VQ in term of computational complexity. A variable bit rate (VBR) video coder for moving video is then proposed where the idea of CSPVQ is coupled with the idea of regular quadtree decomposition to further reduce the bit rate of the encoded picture sequence. The usefulness of a quadtree coding technique comes from the fact that different homogeneous regions occurring within an image can be compactly represented by various nodes in a quadtree. It is found that this image representation technique is particularly useful in providing a low bit rate video encoder without compromising the image quality when it is used in conjunction with the CSPVQ. The characteristics of the VBR coder's output as applied to ATM transmission are investigated. Three video models are used to study the performance of the ATM multiplexer. These models are the auto regressive (AR) model, the auto regressive hidden Markov model (AR-HMM), and the fluid flow uniform arrival and service (UAS) model. The AR model is allowed to have arbitrary order and is used to model a video source which has a constant amount of motion, that is, a stationary video source. The AR-HMM is a more general video model which is based on the idea of auto regressive hidden Markov chain formulated by Baum and is used to describe highly non-stationary sources. Hence, it is expected that the AR-HMM model may also be used top represent a video

  15. A safety assessment methodology applied to CNS/ATM-based air traffic control system

    Energy Technology Data Exchange (ETDEWEB)

    Vismari, Lucio Flavio, E-mail: lucio.vismari@usp.b [Safety Analysis Group (GAS), School of Engineering at University of Sao Paulo (Poli-USP), Av. Prof. Luciano Gualberto, Trav.3, n.158, Predio da Engenharia de Eletricidade, Sala C2-32, CEP 05508-900, Sao Paulo (Brazil); Batista Camargo Junior, Joao, E-mail: joaocamargo@usp.b [Safety Analysis Group (GAS), School of Engineering at University of Sao Paulo (Poli-USP), Av. Prof. Luciano Gualberto, Trav.3, n.158, Predio da Engenharia de Eletricidade, Sala C2-32, CEP 05508-900, Sao Paulo (Brazil)

    2011-07-15

    In the last decades, the air traffic system has been changing to adapt itself to new social demands, mainly the safe growth of worldwide traffic capacity. Those changes are ruled by the Communication, Navigation, Surveillance/Air Traffic Management (CNS/ATM) paradigm , based on digital communication technologies (mainly satellites) as a way of improving communication, surveillance, navigation and air traffic management services. However, CNS/ATM poses new challenges and needs, mainly related to the safety assessment process. In face of these new challenges, and considering the main characteristics of the CNS/ATM, a methodology is proposed at this work by combining 'absolute' and 'relative' safety assessment methods adopted by the International Civil Aviation Organization (ICAO) in ICAO Doc.9689 , using Fluid Stochastic Petri Nets (FSPN) as the modeling formalism, and compares the safety metrics estimated from the simulation of both the proposed (in analysis) and the legacy system models. To demonstrate its usefulness, the proposed methodology was applied to the 'Automatic Dependent Surveillance-Broadcasting' (ADS-B) based air traffic control system. As conclusions, the proposed methodology assured to assess CNS/ATM system safety properties, in which FSPN formalism provides important modeling capabilities, and discrete event simulation allowing the estimation of the desired safety metric.

  16. Accelerating ATM Optimization Algorithms Using High Performance Computing Hardware Project

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA is developing algorithms and methodologies for efficient air-traffic management (ATM). Several researchers have adopted an optimization framework for solving...

  17. ATM and KAT5 safeguard replicating chromatin against formaldehyde damage.

    Science.gov (United States)

    Ortega-Atienza, Sara; Wong, Victor C; DeLoughery, Zachary; Luczak, Michal W; Zhitkovich, Anatoly

    2016-01-08

    Many carcinogens damage both DNA and protein constituents of chromatin, and it is unclear how cells respond to this compound injury. We examined activation of the main DNA damage-responsive kinase ATM and formation of DNA double-strand breaks (DSB) by formaldehyde (FA) that forms histone adducts and replication-blocking DNA-protein crosslinks (DPC). We found that low FA doses caused a strong and rapid activation of ATM signaling in human cells, which was ATR-independent and restricted to S-phase. High FA doses inactivated ATM via its covalent dimerization and formation of larger crosslinks. FA-induced ATM signaling showed higher CHK2 phosphorylation but much lower phospho-KAP1 relative to DSB inducers. Replication blockage by DPC did not produce damaged forks or detectable amounts of DSB during the main wave of ATM activation, which did not require MRE11. Chromatin-monitoring KAT5 (Tip60) acetyltransferase was responsible for acetylation and activation of ATM by FA. KAT5 and ATM were equally important for triggering of intra-S-phase checkpoint and ATM signaling promoted recovery of normal human cells after low-dose FA. Our results revealed a major role of the KAT5-ATM axis in protection of replicating chromatin against damage by the endogenous carcinogen FA.

  18. Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction.

    Science.gov (United States)

    Resseguie, Emily A; Staversky, Rhonda J; Brookes, Paul S; O'Reilly, Michael A

    2015-08-01

    High levels of oxygen (hyperoxia) are often used to treat individuals with respiratory distress, yet prolonged hyperoxia causes mitochondrial dysfunction and excessive reactive oxygen species (ROS) that can damage molecules such as DNA. Ataxia telangiectasia mutated (ATM) kinase is activated by nuclear DNA double strand breaks and delays hyperoxia-induced cell death through downstream targets p53 and p21. Evidence for its role in regulating mitochondrial function is emerging, yet it has not been determined if mitochondrial dysfunction or ROS activates ATM. Because ATM maintains mitochondrial homeostasis, we hypothesized that hyperoxia induces both mitochondrial dysfunction and ROS that activate ATM. In A549 lung epithelial cells, hyperoxia decreased mitochondrial respiratory reserve capacity at 12h and basal respiration by 48 h. ROS were significantly increased at 24h, yet mitochondrial DNA double strand breaks were not detected. ATM was not required for activating p53 when mitochondrial respiration was inhibited by chronic exposure to antimycin A. Also, ATM was not further activated by mitochondrial ROS, which were enhanced by depleting manganese superoxide dismutase (SOD2). In contrast, ATM dampened the accumulation of mitochondrial ROS during exposure to hyperoxia. Our findings suggest that hyperoxia-induced mitochondrial dysfunction and ROS do not activate ATM. ATM more likely carries out its canonical response to nuclear DNA damage and may function to attenuate mitochondrial ROS that contribute to oxygen toxicity.

  19. CUSTOMER SATISFACTION REGARDING BANK’S DISTRIBUTION CHANNELS – THE ATM NETWORK

    Directory of Open Access Journals (Sweden)

    Zaharie Monica Maria

    2010-07-01

    Full Text Available In addition to traditional distribution methods (network of territorial units, to better meet market requirements in terms of speed and efficiency of services, banks have developed interactive electronic and computerized systems for clients: banking services via telephone, internet banking, network of automatic teller machines (ATMs, Electronic Funds Transfer at point of sale (EFTPOS. Automatic Teller Machines have become in recent years one of the common instruments through which banks offer the possibility of conducting routine operations such as: cash withdrawals, bill payments, transfer between accounts. This article presents the results obtained following a research that focused on determining the customers’ degree of satisfaction with the distribution channels used by a Top Five Romanian Bank, in particular the ATMs distribution network.

  20. Study on the Bioremediation of Petroleum Contaminated Soil by Wastewater Treatment Agent ABR Hydrocarbon%废水处理剂ABR Hydrocarbon对石油污染土壤生物修复的研究

    Institute of Scientific and Technical Information of China (English)

    杜国丰

    2016-01-01

    The application conditions of wastewater treatment agent ABR Hydrocarbon and the microbial remediation of petroleum contaminated soil were studied. The results showed that the optimal fermentation temperature of wastewater treatment agent ABR Hydrocarbon was 40 ℃, and the optimal fermentation pH was 7. 0 , surfactants produced in the fermentation liquid, there was a good correlation between the activity of dehydrogenase activity and the degradation rate of petroleum hydrocarbons in soil. After continuous cultivation for 32 days, petroleum hydrocarbon degradation rate reached 33. 4%, soil microbial dehydrogenase activity was 83. 0 μg/( g · h ) . The experiments showed that the wastewater treatment agent ABR Hydrocarbon had good petroleum hydrocarbon degradation ability.%对废水处理剂ABR Hydrocarbon的应用条件及其对石油污染土壤的微生物修复进行了研究。结果表明:废水处理剂ABR Hydrocarbon的最佳发酵温度为40益、最佳发酵pH为7.0,发酵液中有表面活性物质产生,土壤中微生物的脱氢酶活性与石油烃降解率之间存在较好的相关性。连续培养32天,石油烃的降解率达到了33.4%,土壤微生物脱氢酶活性为83.0μg/( g·h)。试验表明废水处理剂ABR Hydrocarbon具有较好的石油烃降解能力。

  1. Study on the treatment of wastewater from rice wine production by ABR-CSTR combined process%ABR-CSTR组合工艺处理黄酒生产废水研究

    Institute of Scientific and Technical Information of China (English)

    付玉洁; 吴鹏; 徐乐中; 沈耀良

    2016-01-01

    采用ABR-CSTR组合工艺对黄酒生产废水处理进行了研究.结果表明,采用低负荷启动并逐步提高容积负荷是ABR-CSTR组合工艺成功启动的关键,在温度为(30±2)℃时,COD容积负荷从0.3 kg/(m3·d)增至4.0 kg/(m3·d),历时100 d启动成功.系统总去除率保持在95%~98%,出水平均氨氮、总氮分别为0.57、20.4 mg/L,表明ABR-CSTR组合工艺能有效处理黄酒生产废水.%The research on the treatment of wastewater from rice wine production by the combined process ,ABR-CSTR,has been accomplished. The results show that the key of starting up the ABR-CSTR process successfully is by means of using low load start-up and then increasing the volume load gradually. When the operation temperature is (30±2)℃,the COD volume load increases from 0.3 kg/(m3·d) to 4.0 kg/(m3·d). The start-up is successful in 100 d. The total removing rate of the system stays constant at 95%-98%. The average effluent concentration of NH4+-N and TN are 0.57 mg/L and 20.4 mg/L,respectively. The results indicate that ABR-CSTR process can effectively treat the wastewater from rice wine production.

  2. The AbrB2 autorepressor, expressed from an atypical promoter, represses the hydrogenase operon to regulate hydrogen production in Synechocystis strain PCC6803.

    Science.gov (United States)

    Dutheil, Jérémy; Saenkham, Panatda; Sakr, Samer; Leplat, Christophe; Ortega-Ramos, Marcia; Bottin, Hervé; Cournac, Laurent; Cassier-Chauvat, Corinne; Chauvat, Franck

    2012-10-01

    We have thoroughly investigated the abrB2 gene (sll0822) encoding an AbrB-like regulator in the wild-type strain of the model cyanobacterium Synechocystis strain PCC6803. We report that abrB2 is expressed from an active but atypical promoter that possesses an extended -10 element (TGTAATAT) that compensates for the absence of a -35 box. Strengthening the biological significance of these data, we found that the occurrence of an extended -10 promoter box and the absence of a -35 element are two well-conserved features in abrB2 genes from other cyanobacteria. We also show that AbrB2 is an autorepressor that is dispensable to cell growth under standard laboratory conditions. Furthermore, we demonstrate that AbrB2 also represses the hox operon, which encodes the Ni-Fe hydrogenase of biotechnological interest, and that the hox operon is weakly expressed even though it possesses the two sequences resembling canonical -10 and -35 promoter boxes. In both the AbrB2-repressed promoters of the abrB2 gene and the hox operon, we found a repeated DNA motif [TT-(N(5))-AAC], which could be involved in AbrB2 repression. Supporting this hypothesis, we found that a TT-to-GG mutation of one of these elements increased the activity of the abrB2 promoter. We think that our abrB2-deleted mutant with increased expression of the hox operon and hydrogenase activity, together with the reporter plasmids we constructed to analyze the abrB2 gene and the hox operon, will serve as useful tools to decipher the function and the regulation of hydrogen production in Synechocystis.

  3. Impact assessment of ATM on customer satisfaction of banks in Ghana:a case study of Kumasi,Ghana.

    OpenAIRE

    Boateng, Elliot; Amponsah, Mary; Serwaa-Adomako, Akosua

    2014-01-01

    Bank customers are selective with the banks to transact with since everyone wants the best service for their money. Asa result, there is competition in the banking sector. Each bank wants to give quality services and products to keep up existing customers and broaden their customer base as well. The purpose of this study is to find out if customer needs for direct service transactions with bank employees in the banking halls has reduced due to Automated Teller Machines (ATM) provided for Ghan...

  4. A Case Study of Employing A Single Server Nonpreemptive Priority Queuing Model at ATM Machine

    Directory of Open Access Journals (Sweden)

    Abdullah Furquan

    2015-08-01

    Full Text Available This paper discusses a case study of employing a single server nonpreemptivepriorityqueuing model [1]at ATM machine which originally operates on M/M/1 model. In this study we have taken two priority classes of people in following order:- .Priority class 1- woman .Priority class 2- man Sometimea long queue is formed at ATMmachine (single serverbut the bank management don’t have enough money to invest on installing new ATM machine.In this situation we want to apply single server nonpreemptive priority queuing model.The security guard at the ATM will divide the customers in two category and arrange the customers in the above said priority order Thuspriority class 1 people willreceive theatm service ahead of priority class 2 people.This will reduce the waiting time of priority class 1 people. Of course by doing this the waiting time of priority class 2will increase. This is ok as long as the increment in waiting time of priority class2 people is reasonable and within the tolerable limitof priority class 2people.This will be true when percentage of priority class 1 people is relatively less as compared to priority class 2 people To know the attitude and tolerable limit of priority class 2 people towards the single server non preemtive priority model a sample survey has been done on the incomingpriority class 2 population at the atm machine.Against this background, the queuing process is employed with emphasis to Poisson distribution to assess the waiting time. The data for this study was collected from primary source and is limited to ATM service point of state bank of India located at Ramesh chowk, Aurangabad, bihar, India.. The assistance of three colleague was sought in collecting the data. The Interarrival time and service time data was collected during busy working hours (i.e. 10.30am to 4:00pm during the first 60 days. A sample survey was done to know the attitude and tolerable limit of priority class 2people towards the single server

  5. ATM: The Key To Harnessing the Power of Networked Multimedia.

    Science.gov (United States)

    Gross, Rod

    1996-01-01

    ATM (Asynchronous Transfer Mode) network technology handles the real-time continuous traffic flow necessary to support desktop multimedia applications. Describes network applications already used: desktop video collaboration, distance learning, and broadcasting video delivery. Examines the architecture of ATM technology, video delivery and sound…

  6. ATM Technology Adoption in U.S. Campus Networking.

    Science.gov (United States)

    Yao, Engui; Perry, John F.; Anderson, Larry S.; Brook, R. Dan; Hare, R. Dwight; Moore, Arnold J.; Xu, Xiaohe

    This study examined the relationships between ATM (asynchronous transfer mode) adoption in universities and four organizational variables: university size, type, finances, and information processing maturity. Another purpose of the study was to identify the current status of ATM adoption in campus networking. Subjects were university domain LAN…

  7. ATM LAN Emulation: Getting from Here to There.

    Science.gov (United States)

    Learn, Larry L., Ed.

    1995-01-01

    Discusses current LAN (local area network) configuration and explains ATM (asynchronous transfer mode) as the future telecommunications transport. Highlights include LAN emulation, which enables the interconnection of legacy LANs and the new ATM environment; virtual LANs; broadcast servers; and standards. (LRW)

  8. ATM Tactical Network - a challenge for the military networks

    NARCIS (Netherlands)

    Waveren, C.J. van; Luiijf, H.A.M.; Burakowski, W.; Kopertowski, Z.

    1997-01-01

    The next generation of tactical networks will be based on the ATM technology. The POST-2000 tactical network is just in the designing phase. The objective of this paper is to point out the main problems which should be solved to adopt ATM technology into the tactical network environment. The barrier

  9. Audiometria de tronco encefálico (abr: o uso do mascaramento na avaliação de indivíduos portadores de perda auditiva unilateral Auditory brainstem response (abr: use of masking in unilateral hearing loss patients

    Directory of Open Access Journals (Sweden)

    Melissa M. T. Toma

    2003-06-01

    Full Text Available A necessidade do mascaramento na avaliação da audição por meio da ABR ainda é um assunto consideravelmente debatido (Durrant & Ferraro, 2001. OBJETIVO: O presente estudo propôs investigar a necessidade do mascaramento contralateral, empregado na orelha normal, ao realizar a ABR em indivíduos portadores de perda auditiva neurossensorial unilateral. FORMA DE ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: A amostra constituiu-se de 22 indivíduos portadores de perda auditiva neurossensorial unilateral de grau profundo, sendo 10 do sexo feminino e 12 do sexo masculino, com idades variando entre 9 e 44 anos. Todos os indivíduos foram submetidos a: audiometria tonal liminar, logoaudiometria (SRT, IPRF e SDT, medidas de imitância acústica (incluindo a pesquisa dos reflexos acústicos - modo ipsilateral e contralateral e audiometria de tronco encefálico na ausência e na presença do mascaramento. RESULTADOS: Todos os indivíduos apresentaram perda auditiva neurossensorial unilateral de grau profundo e curvas timpanométricas do tipo A bilateralmente. Na avaliação da ABR, 100% da amostra apresentou presença da Onda V na orelha comprometida, sendo que ao introduzir o mascaramento contralateral tais respostas não foram observadas. CONCLUSÕES: O mascaramento é um procedimento necessário para a avaliação da audição por meio da ABR em indivíduos portadores de perdas auditivas unilaterais, visando a obtenção de resultados fidedignos. Na ABR, a atenuação interaural para clicks foi maior (65 dB do que a observada na audiometria tonal liminar, sendo necessário, portanto, uma menor intensidade de mascaramento para eliminar a resposta da via auditiva contralateral.The need of masking in auditory brainstem response (ABR evaluation is still considerably debated issue (Durrant and Ferraro, 2001. AIM: In addition, the present study was to investigate the need of masking in ABR with unilateral hearing loss. STUDY DESIGN: Clinical

  10. A Survey of ATM Security Implementation within the Nigerian Banking Environment

    Directory of Open Access Journals (Sweden)

    Falaye Adeyinka Adesuyi

    2013-05-01

    Full Text Available This research work reviews the current practices in Nigeria’s customer banking services with an empirical investigation into ATM fraud as well as a physical and technical implementation of security.The survey was conducted using questionnaire as the research instrument. Four hundred 400 questionnaires were distributed among Entrepreneurs, Civil servants and Students from four states of the federation namely Lagos, Abuja, Kaduna and Jos. Three hundred and twenty seven (327 were retrieved successfully while three hundred and three (303 were properly responded. The data collected was analyzed using Chi-Square test and one way ANOVA. The results obtained shows there is no statistically significant difference in the perception of entrepreneurs, civil servants and students on the positive impact of ATM on banking. The perceptions of the three variables on security challenges of ATM services are equal. It was concluded in the research that the current security implementation does not proffer the adequate security necessary to secure electronic transactions, customers’ information and funds.

  11. Motion picture experts group (MPEG) over ATM issues: a scenario overview

    Science.gov (United States)

    Bernabei, F.; Moscatelli, M.; Russo, Giuseppe; Talone, Paolo

    1995-02-01

    Specific mechanisms are required to carry MPEG coded information over an ATM network. After a brief description of the MPEG-2 video coding algorithm, this paper discusses the `isochronism' related requirements for the transmission of the coded data and the problems associated with the use of an anisochronous transmission mechanism. The main problems, concerning the choice of the ATM adaptation layer (AAL) for each level of interaction, are discussed. Even if the MPEG stream is inherently bursty, the technical literature considers both the constant bit rate (CBR) and variable bit rate (VBR) solutions. The paper reports on a study concerning the AAL choice, in relation with the degree of interactivity required by the application and with the delay constraints. A further issue is an overview of different scenarios for the provision of video services, by `MPEG or ATM.' Different possible network and service architectures are analyzed, and various solutions for storing video information are proposed. Three different service architectures are discussed: the fully centralized, the quasi- centralized, and the fully distributed. The last issue dealt with in the paper concerns a very attractive class of interactive video services, video-on-demand (VoD). In particular, the impact of the digital storage media-control command (DSM-CC) in the provision of a particular VoD service, the `video rental' service, is described. The network requirements to support DSM- CC commands allowing the user to perform the typical video cassette recorder (VCR) functions (freeze frame, fast forward, fast reverse) are stressed. Alternative approaches for the implementation of each command are discussed together with their impact on the traffic network.

  12. A COMBINED ADMISSION CONTROL ALGORITHM WITH DA PROTOCOL FOR SATELLITE ATM NETWORKS

    Institute of Scientific and Technical Information of China (English)

    Lu Rong; Cao Zhigang

    2006-01-01

    Admission control is an important strategy for Quality of Service (QoS) provisioning in Asynchronous Transfer Mode (ATM) networks. Based on a control-theory model of resources on-Demand Allocation (DA) protocol, the paper studies the effect of the protocol on the statistical characteristics of network traffic,and proposes a combined connection admission control algorithm with the DA protocol to achieve full utilization of link resources in satellite communication systems. The proposed algorithm is based on the cross-layer-design approach. Theoretical analysis and system simulation results show that the proposed algorithm can admit more connections within certain admission thresholds than one that does not take into account the DA protocol. Thus, the proposed algorithm can increase admission ratio of traffic sources for satellite ATM networks and improve satellite link utilization.

  13. Structure of the intact ATM/Tel1 kinase.

    Science.gov (United States)

    Wang, Xuejuan; Chu, Huanyu; Lv, Mengjuan; Zhang, Zhihui; Qiu, Shuwan; Liu, Haiyan; Shen, Xuetong; Wang, Weiwu; Cai, Gang

    2016-05-27

    The ataxia-telangiectasia mutated (ATM) protein is an apical kinase that orchestrates the multifaceted DNA-damage response. Normally, ATM kinase is in an inactive, homodimer form and is transformed into monomers upon activation. Besides a conserved kinase domain at the C terminus, ATM contains three other structural modules, referred to as FAT, FATC and N-terminal helical solenoid. Here we report the first cryo-EM structure of ATM kinase, which is an intact homodimeric ATM/Tel1 from Schizosaccharomyces pombe. We show that two monomers directly contact head-to-head through the FAT and kinase domains. The tandem N-terminal helical solenoid tightly packs against the FAT and kinase domains. The structure suggests that ATM/Tel1 dimer interface and the consecutive HEAT repeats inhibit the binding of kinase substrates and regulators by steric hindrance. Our study provides a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents.

  14. Mode of ATM-dependent suppression of chromosome translocation.

    Science.gov (United States)

    Yamauchi, Motohiro; Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi

    2011-12-09

    It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

  15. A Study of MPLS Hybrid Switch Based on ATM Switch

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    MPLS is the most successful integrating model of IP over ATM. The paper discusses some problems and their possible solutions when MPLS is supported by ATM switch. How to design the hardware, software and network management systems of such a switch device that has only one switching platform and one NMS but two sets of control planes at the same time, ATM and MPLS, is studied in details. The application of such a hybrid switch is presented in the last part of the paper.

  16. 3rd ENRI International Workshop on ATM/CNS

    CERN Document Server

    2014-01-01

    The Electronic Navigation Research Institute (ENRI) held its third International Workshop on ATM / CNS in 2013 with the theme of "Drafting the future sky". There is worldwide activity taking place in the research and development of modern air traffic management (ATM) and its enabling technologies in Communication, Navigation and Surveillance (CNS). Pioneering work is necessary to contribute to the global harmonization of air traffic management and control. At this workshop, leading experts in  research, industry and academia from around the world met to share their ideas and approaches on ATM/CNS related topics.

  17. [Research on Cultivation and Stability of Nitritation Granular Sludge in Integrated ABR-CSTR Reactor].

    Science.gov (United States)

    Wu, Kai-cheng; Wu, Peng; Shen, Yao-liang; Li, Yue-han; Wang, Han-fang; Xu, Yue-zhong

    2015-11-01

    Abstract: The last two compartments of the Anaerobic Baffled Readtor ( ABR) were altered into aeration tank and sedimentation tank respectively to get an integrated anaerobic-aerobic reactor, using anaerobic granular sludge in anaerobic zone and aerobic granular sludge in aerobic zone as seed sludge. The research explored the condition to cultivate nitritation granular sludge, under the condition of continuous flow. The C/N rate was decreased from 1 to 0.4 and the ammonia nitrogen volumetric loading rate was increased from 0.89 kg x ( m3 x d)(-1) to 2.23 kg x (m3 x d)(-1) while the setting time of 1 h was controlled in the aerobic zone. After the system was operated for 45 days, the mature nitritation granular sludge in aerobic zone showed a compact structure and yellow color while the nitrite accumulation rate was about 80% in the effluent. The associated inhibition of free ammonia (FA) and free nitrous acid (FNA) dominated the nitritation. Part of granules lost stability during the initial period of operation and flocs appeared in the aerobic zone. However, the flocs were transformed into newly generated small particles in the following reactor operation, demonstrating that organic carbon was benefit to granulation and the enrichment of slow-growing nitrifying played an important role in the stability of granules.

  18. Medical Physics Residency Consortium: collaborative endeavors to meet the ABR 2014 certification requirements.

    Science.gov (United States)

    Parker, Brent C; Duhon, John; Yang, Claus C; Wu, H Terry; Hogstrom, Kenneth R; Gibbons, John P

    2014-03-06

    In 2009, Mary Bird Perkins Cancer Center (MBPCC) established a Radiation Oncology Physics Residency Program to provide opportunities for medical physics residency training to MS and PhD graduates of the CAMPEP-accredited Louisiana State University (LSU)-MBPCC Medical Physics Graduate Program. The LSU-MBPCC Program graduates approximately six students yearly, which equates to a need for up to twelve residency positions in a two-year program. To address this need for residency positions, MBPCC has expanded its Program by developing a Consortium consisting of partnerships with medical physics groups located at other nearby clinical institutions. The consortium model offers the residents exposure to a broader range of procedures, technology, and faculty than available at the individual institutions. The Consortium institutions have shown a great deal of support from their medical physics groups and administrations in developing these partnerships. Details of these partnerships are specified within affiliation agreements between MBPCC and each participating institution. All partner sites began resident training in 2011. The Consortium is a network of for-profit, nonprofit, academic, community, and private entities. We feel that these types of collaborative endeavors will be required nationally to reach the number of residency positions needed to meet the 2014 ABR certification requirements and to maintain graduate medical physics training programs.

  19. The Integrated Control-Mechanism in ATM-Based Networks

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Survivability is one of the important issues in ATM-based networks since even a single network element failure may cause a serious data loss. This paper introduces a new restoration mechanism based on multi-layer ATM survivable network management architecture. This mechanism integrates the general control and restoration control by establishing the Working VPs logical network, Backup VPs logical network and spare logical network in order to optimally utilize the network resources while maintaining the restoration requirements.

  20. 4th ENRI International Workshop on ATM/CNS

    CERN Document Server

    2017-01-01

    This book is a compilation of selected papers from the 4th ENRI International Workshop on ATM/CNS (EIWAC2015). The work focuses on novel techniques for aviation infrastructure in air traffic management (ATM) and communications, navigation, surveillance, and informatics (CNSI) domains. The contents make valuable contributions to academic researchers, engineers in the industry, and regulators of aviation authorities. As well, readers will encounter new ideas for realizing a more efficient and safer aviation system. .

  1. Aplikasi Peta ATM Dengan Menggunakan Aplikasi GPS Pada Handphone Android

    Directory of Open Access Journals (Sweden)

    Tantan Taryono

    2013-05-01

    Full Text Available Seiring meningkatnya mobilitas masyarakat dan tingginya kebutuhan informasi berupa peta, Geographic Information System (GIS bukan hanya sekadar tren teknologi, tetapi telah menjadi sebuah kebutuhan. Ketatnya persaingan para vendor perangkat bergerak (mobile device dengan berbagai fitur dan keunggulan, secara tidak langsung berdampak positif bagi konsumen teknologi  mobile salah satunya operating system (OS Android. Dengan adanya operating system (OS Android yang memberikan banyak keuntungan salah satunya adalah OS Android yang bersifat open source, para pengembang aplikasi Android dapat membuat sebuah aplikasi sesuai kebutuhan termasuk pembuatan aplikasi Peta ATM. Disamping itu pada handphone Android juga telah tersedia GPS sebagai penetuan posisi pengguna. Peta ATM dengan menggunakan aplikasi GPS merupakan sebuah aplikasi yang dapat digunakan oleh banyak kalangan. Banyak manfaat yang dapat dirasakan dengan menggunakan aplikasi ini, diantaranya adalah dengan mengetahui sebuah lokasi dimana posisi user berada. Begitu juga dengan aplikasi peta Automatic Teller Machine (ATM dapat memberikan kemudahan bagi para pengguna handphone berbasis operating system Android untuk mengetahui dimana letak posisi ATM BNI yang berada di wilayah Purwokerto dan sekitarnya. Dengan adanya aplikasi peta ATM BNI diharapkan para pengguna yang belum mengetahui secara lengkap kota Purwokerto dapat dengan mudah dalam mencari lokasi ATM.

  2. ATM kinase: Much more than a DNA damage responsive protein.

    Science.gov (United States)

    Guleria, Ayushi; Chandna, Sudhir

    2016-03-01

    ATM, mutation of which causes Ataxia telangiectasia, has emerged as a cardinal multifunctional protein kinase during past two decades as evidenced by various studies from around the globe. Further to its well established and predominant role in DNA damage response, ATM has also been understood to help in maintaining overall functional integrity of cells; since its mutation, inactivation or deficiency results in a variety of pathological manifestations besides DNA damage. These include oxidative stress, metabolic syndrome, mitochondrial dysfunction as well as neurodegeneration. Recently, high throughput screening using proteomics, metabolomics and transcriptomic studies revealed several proteins which might be acting as substrates of ATM. Studies that can help in identifying effective regulatory controls within the ATM-mediated pathways/mechanisms can help in developing better therapeutics. In fact, more in-depth understanding of ATM-dependent cellular signals could also help in the treatment of variety of other disease conditions since these pathways seem to control many critical cellular functions. In this review, we have attempted to put together a detailed yet lucid picture of the present-day understanding of ATM's role in various pathophysiological conditions involving DNA damage and beyond.

  3. Sistema mecánico abre bolsas: un ejemplo práctico para la enseñanza

    Directory of Open Access Journals (Sweden)

    Ervin Alvarez-Sánchez

    2015-01-01

    Full Text Available En este artículo se presenta la manera de obtener un modelo matemático simplificado de un sistema mecánico abre bolsas, con la finalidad de ejemplificar los conocimientos que se obtienen usualmente en el curso de dinámica de mecanismos, tales como: equilibrio dinámico de partículas, movimiento de proyectiles y fuerzas de fricción. Con la ayuda de este modelo, se puede llevar a cabo el diseño mecánico del sistema abre bolsas para que sea posteriormente implementado en una planta de reciclaje de residuos sólidos.

  4. ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion.

    Science.gov (United States)

    Chen, Wei-Ta; Ebelt, Nancy D; Stracker, Travis H; Xhemalce, Blerta; Van Den Berg, Carla L; Miller, Kyle M

    2015-06-01

    Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression.

  5. Mobile phone signal exposure triggers a hormesis-like effect in Atm(+/+) and Atm(-/-) mouse embryonic fibroblasts.

    Science.gov (United States)

    Sun, Chuan; Wei, Xiaoxia; Fei, Yue; Su, Liling; Zhao, Xinyuan; Chen, Guangdi; Xu, Zhengping

    2016-11-18

    Radiofrequency electromagnetic fields (RF-EMFs) have been classified by the International Agency for Research on Cancer as possible carcinogens to humans; however, this conclusion is based on limited epidemiological findings and lacks solid support from experimental studies. In particular, there are no consistent data regarding the genotoxicity of RF-EMFs. Ataxia telangiectasia mutated (ATM) is recognised as a chief guardian of genomic stability. To address the debate on whether RF-EMFs are genotoxic, we compared the effects of 1,800 MHz RF-EMF exposure on genomic DNA in mouse embryonic fibroblasts (MEFs) with proficient (Atm(+/+)) or deficient (Atm(-/-)) ATM. In Atm(+/+) MEFs, RF-EMF exposure for 1 h at an average special absorption rate of 4.0 W/kg induced significant DNA single-strand breaks (SSBs) and activated the SSB repair mechanism. This effect reduced the DNA damage to less than that of the background level after 36 hours of exposure. In the Atm(-/-) MEFs, the same RF-EMF exposure for 12 h induced both SSBs and double-strand breaks and activated the two repair processes, which also reduced the DNA damage to less than the control level after prolonged exposure. The observed phenomenon is similar to the hormesis of a toxic substance at a low dose. To the best of our knowledge, this study is the first to report a hormesis-like effect of an RF-EMF.

  6. SU-E-E-02: An Excel-Based Study Tool for ABR-Style Exams

    Energy Technology Data Exchange (ETDEWEB)

    Cline, K; Stanley, D; Defoor, D; Stathakis, S; Gutierrez, A; Papanikolaou, N; Kirby, N [University of Texas Health Science Center at San Antonio, Cancer Therapy and Research Center, San Antonio, TX (United States)

    2015-06-15

    Purpose: As the landscape of learning and testing shifts toward a computer-based environment, a replacement for paper-based methods of studying is desirable. Using Microsoft Excel, a study tool was developed that allows the user to populate multiple-choice questions and then generate an interactive quiz session to answer them. Methods: The code for the tool was written using Microsoft Excel Visual Basic for Applications with the intent that this tool could be implemented by any institution with Excel. The base tool is a template with a setup macro, which builds out the structure based on user’s input. Once the framework is built, the user can input sets of multiple-choice questions, answer choices, and even add figures. The tool can be run in random-question or sequential-question mode for single or multiple courses of study. The interactive session allows the user to select answer choices and immediate feedback is provided. Once the user is finished studying, the tool records the day’s progress by reporting progress statistics useful for trending. Results: Six doctoral students at UTHSCSA have used this tool for the past two months to study for their qualifying exam, which is similar in format and content to the American Board of Radiology (ABR) Therapeutic Part II exam. The students collaborated to create a repository of questions, met weekly to go over these questions, and then used the tool to prepare for their exam. Conclusion: The study tool has provided an effective and efficient way for students to collaborate and be held accountable for exam preparation. The ease of use and familiarity of Excel are important factors for the tool’s use. There are software packages to create similar question banks, but this study tool has no additional cost for those that already have Excel. The study tool will be made openly available.

  7. A queueing model for error control of partial buffer sharing in ATM

    Directory of Open Access Journals (Sweden)

    Ahn Boo Yong

    1999-01-01

    Full Text Available We model the error control of the partial buffer sharing of ATM by a queueing system M 1 , M 2 / G / 1 / K + 1 with threshold and instantaneous Bernoulli feedback. We first derive the system equations and develop a recursive method to compute the loss probabilities at an arbitrary time epoch. We then build an approximation scheme to compute the mean waiting time of each class of cells. An algorithm is developed for finding the optimal threshold and queue capacity for a given quality of service.

  8. Design of ATM Networks Congestion Controller Based on the Virtual Queue

    Institute of Scientific and Technical Information of China (English)

    LIU Zhi-xin; GUAN Xin-ping; LONG Cheng-nian

    2004-01-01

    The single bottleneck node of ATM networks is considered. The virtual queue mechanism and the method of proportion-integral-differential(PID) control are adopted in the congestion control. The sufficient condition of the considered system's stability is given. The method of determining the PID parameters is given further. To quicken the speed of startup and remove the congestion rapidly, the factors of increase and decrease are set according to the length of queue. The result of simulation shows that the system, given an appropriate group of parameters, can acquire good robustness and dynamic performance, and guarantees the quality of service at the same time.

  9. "ATR activation in response to ionizing radiation: still ATM territory"

    Directory of Open Access Journals (Sweden)

    Cuadrado Myriam

    2006-05-01

    Full Text Available Abstract Unrepaired DNA double-strand breaks (DSBs are a major cause for genomic instability. Therefore, upon detection of a DSB a rapid response must be assembled to coordinate the proper repair/signaling of the lesion or the elimination of cells with unsustainable amounts of DNA damage. Three members of the PIKK family of protein kinases -ATM, ATR and DNA-PKcs- take the lead and initiate the signaling cascade emanating from DSB sites. Whereas DNA-PKcs activity seems to be restricted to the phosphorylation of targets involved in DNA repair, ATM and ATR phosphorylate a broad spectrum of cell cycle regulators and DNA repair proteins. In the canonical model, ATM and ATR are activated by two different types of lesions and signal through two independent and alternate pathways. Specifically, ATR is activated by various forms of DNA damage, including DSBs, arising at stalled replication forks ("replication stress", and ATM is responsible for the signaling of DSBs that are not associated with the replication machinery throughout the cell cycle. Recent evidence suggests that this model might be oversimplified and that coordinated crosstalk between ATM and ATR activation routes goes on at the core of the DNA damage response.

  10. The role of ATM mutations and 11q deletions in disease progression in chronic lymphocytic leukemia.

    Science.gov (United States)

    Stankovic, Tatjana; Skowronska, Anna

    2014-06-01

    Abstract ATM gene alteration is a frequent event in pathogenesis of chronic lymphocytic leukemia (CLL) and occurs as monoallelic loss in the form of 11q23 deletion, with and without mutation in the remaining ATM allele. ATM is a principal DNA damage response gene and biallelic ATM alterations lead to ATM functional loss and chemoresistance. The introduction of new therapies, such as intensive chemoimmunotherapy and inhibition of B-cell receptor (BCR) signaling, has changed clinical responses for the majority of CLL tumors including those with 11q deletion, but it remains to be determined whether these strategies can prevent clonal evolution of tumors with biallelic ATM alterations. In this review we discuss ATM function and the consequences of its loss during CLL pathogenesis, differences in clinical behavior of tumors with monoallelic and biallelic ATM alterations, and we outline possible approaches for targeting the ATM null CLL phenotype.

  11. A New SDH-Based ATM Network Survivability Escalation Mechanism

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    This paper investigates survivability escalation strategies in multi-layers transport networks such as ATM/SDH/WDM networks, and presents oriented-failures and oriented-traffic escalation mechanisms. Furthermore, We present a new survivability Escalation strategy for SDH-Based ATM transport networks, which addresses difficult problem for resources sharing pool(RSP) among different layers restoration mechanisms. In this paper, we also present integer programming (IP) model for the resources sharing pool (RSP) design problem and the node simulation model for escalation Node. The simulation results show that the proposed ESP is very efficient. The proposed model can be easily extended for other types of multi-layer networks, such as WDM-based ATM networks or WDM-based SDH networks.

  12. Homeostatic regulation of meiotic DSB formation by ATM/ATR.

    Science.gov (United States)

    Cooper, Tim J; Wardell, Kayleigh; Garcia, Valerie; Neale, Matthew J

    2014-11-15

    Ataxia-telangiectasia mutated (ATM) and RAD3-related (ATR) are widely known as being central players in the mitotic DNA damage response (DDR), mounting responses to DNA double-strand breaks (DSBs) and single-stranded DNA (ssDNA) respectively. The DDR signalling cascade couples cell cycle control to damage-sensing and repair processes in order to prevent untimely cell cycle progression while damage still persists [1]. Both ATM/ATR are, however, also emerging as essential factors in the process of meiosis; a specialised cell cycle programme responsible for the formation of haploid gametes via two sequential nuclear divisions. Central to achieving accurate meiotic chromosome segregation is the introduction of numerous DSBs spread across the genome by the evolutionarily conserved enzyme, Spo11. This review seeks to explore and address how cells utilise ATM/ATR pathways to regulate Spo11-DSB formation, establish DSB homeostasis and ensure meiosis is completed unperturbed.

  13. Homeostatic regulation of meiotic DSB formation by ATM/ATR

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Tim J.; Wardell, Kayleigh; Garcia, Valerie; Neale, Matthew J., E-mail: m.neale@sussex.ac.uk

    2014-11-15

    Ataxia–telangiectasia mutated (ATM) and RAD3-related (ATR) are widely known as being central players in the mitotic DNA damage response (DDR), mounting responses to DNA double-strand breaks (DSBs) and single-stranded DNA (ssDNA) respectively. The DDR signalling cascade couples cell cycle control to damage-sensing and repair processes in order to prevent untimely cell cycle progression while damage still persists [1]. Both ATM/ATR are, however, also emerging as essential factors in the process of meiosis; a specialised cell cycle programme responsible for the formation of haploid gametes via two sequential nuclear divisions. Central to achieving accurate meiotic chromosome segregation is the introduction of numerous DSBs spread across the genome by the evolutionarily conserved enzyme, Spo11. This review seeks to explore and address how cells utilise ATM/ATR pathways to regulate Spo11-DSB formation, establish DSB homeostasis and ensure meiosis is completed unperturbed.

  14. Enhanced ATM Security with PII Using Otpip Algorithm

    Directory of Open Access Journals (Sweden)

    K. Ram Kumar

    2012-12-01

    Full Text Available Biometric verification system is the crux of almost every security mechanism these days and failure of a biometric system can lead to grievous issues. The objective of this study is to identify the consequences when biometric verification fails during ATM transaction and hence suggest a novel enhancement mechanism for it. The security of ATM transactions can be further strengthened using the PII (Personal Identification Image method. The proposed security algorithm is called OTPIP (One Time Password using Image Processing and involves two phases. The first one is a verification phase which is done using biometric systems. In case of failure of biometrics, code verification is done. This is followed by the PII phase. These two phases ensure two-tier security of ATM machine and thereby introduce a foolproof safety mechanism.

  15. IP over ATM Implementation with Local Switch Mode

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    In classical IPOA, the communication of two users between local Asynchronous Transfer Mode(ATM) ports needs a VCC, however, it is not an elegant solution to the ATM access equipments design when the performance of the whole system is considered. Thus, we investigate the way to provide the improved IPOA protocol that uses switching way in local ports. And it is fully compatible with the CIPOA by using the same protocol for ARP and IP forwarding. In addition, we also present the design of one 10/100 Mbit/s auto adaptive IPOA client board with local switch ability idea and CAM mechanism for our project.

  16. Simulation of the Tree Algorthm in ATM Networks

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    This paper proposes an algorithm for multicast routing in ATM networks. We define the network cost of a routing as the combination of the cost. If establishing connections, the cost of the overall bandwidth and overall switchings, our routing algorithm works on the original topology of ATM networks with physical switches and physical links, and different switching functionalities of Virtual Path(VP) switches and Virtual Channel(VC) switches in the networks. It generates an optimal multicast routing with the minimal overall network cost. Simulations with MATLAB have been made to compare the quality of the routing generated by our algorithm with those of other two major algorithms.

  17. ATM Security Using Fingerprint Biometric Identifer: An Investigative Study

    Directory of Open Access Journals (Sweden)

    Moses Okechukwu Onyesolu

    2012-04-01

    Full Text Available The growth in electronic transactions has resulted in a greater demand for fast and accurate user identification and authentication. Access codes for buildings, banks accounts and computer systems often use personal identification numbers (PIN's for identification and security clearances. Conventional method of identification based on possession of ID cards or exclusive knowledge like a social security number or a password are not all together reliable. An embedded fingerprint biometric authentication scheme for automated teller machine (ATM banking systems is proposed in this paper. In this scheme, a fingerprint biometric technique is fused with the ATM for person authentication to ameliorate the security level.

  18. Improved EPRCA Congestion Control Scheme for ATM Networks

    Directory of Open Access Journals (Sweden)

    Dr. M.Sreenivasulu

    2015-01-01

    Full Text Available Traffic management and congestion control are major issues in Asynchronous Transfer Mode(ATM networks. Congestion arises when traffic in the network is more than offered load. The primary function of congestion control is to ensure good throughput and low delay performance while maintaining a fair allocation of network resources to users. In this paper, Enhanced Proportional Rate based Congestion Avoidance (EPRCA scheme proposed by ATM forum has been considered. But this scheme has limitation of higher cell drop problem for the bursty traffic. Improvements to EPRCA scheme have been proposed to reduce cell drop problem and results of improved EPRCA schemes were analyzed with basic EPRCA scheme.

  19. Process evaluation of the health education resource Abre los Ojos for street-involved youth in Medellín

    Directory of Open Access Journals (Sweden)

    John L. Wylie

    2012-02-01

    Full Text Available Objective: Conduct a process evaluation of a health education resource (pamphlet¸ Abre los Ojos, designed for street-involved youth in Medellín. The primary foci of the evaluation were the process of developing the resource and youth’s subsequent perception of the resource. Methodology: Drawing upon both qualitative and quantitative data, a process evaluation was undertaken. Ninety four street-involved youth between the ages of 14–24 years completed surveys about the resource. These semi-structured interviews were key for the information about youth perception of the resource. In addition to individual interviews, prior to resource creation, a series of focus groups were integral for the development of the resource. Results: The process of consulting with the target population through the focus groups was effective in obtaining their ideas and feedback about what type of content they would like to see in a health education resource, and how they wanted that content presented. After distribution, participants described that Abre los Ojos contained information that was valuable and relevant to their experiences. While not a primary focus of this evaluation, the individual interviews were also able to provide some preliminary insight into whether Abre los Ojos was an effective means for participants to increase their knowledge of content included in the resource. Conclusion: The collaborative process of jointly developing the resource content in partnership with the youth proved very worthwhile. While our research team chose to include information about HIV, through focus group dialogue, the youth themselves determined the additional content themes (piercings, use of solvents, and description of life on the street. The resulting resource was well-received by members of the street-involved population who had not been involved in its design.

  20. Bombensicher ohne Bombe? Die nukleare Abrüstung der Ukraine aus Sich des Waltzâ schen Neorealismus

    OpenAIRE

    Schäfer, Martin

    2014-01-01

    Für die Theorieentwicklung in den Internationalen Beziehungen (IB) war und ist Kenneth N. Waltz eine Schlüsselfigur. Sein Werk â Theory of International Politicsâ begründete den Neorealismus, der die Systemdynamiken zwischenstaatlicher Beziehungen fokussiert. Auch mit Fragen nuklearer Aufrüstung setzte Waltz sich eingehend auseinander. Doch wie steht es um nukleare Abrüstung? Ein Blick auf den akademischen Diskurs zeigt, dass Waltzâ Theorie der internationalen Politik für diesen Bereich keine...

  1. Effects of nitrobenzene concentration and hydraulic retention time on the treatment of nitrobenzene in sequential anaerobic baffled reactor (ABR)/continuously stirred tank reactor (CSTR) system.

    Science.gov (United States)

    Kuscu, Ozlem Selcuk; Sponza, Delia Teresa

    2009-04-01

    The effects of increasing nitrobenzene (NB) concentrations and hydraulic retention times (HRT) on the treatment of NB were investigated in a sequential anaerobic baffled reactor (ABR)/aerobic completely stirred tank reactor (CSTR) system. In the first step of the study, the maximum COD removal efficiencies were found as 88% and 92% at NB concentrations varying between 30 mg L(-1) and 210 mg L(-1) in ABR. The minimum COD removal efficiency was 79% at a NB concentration of 700 mg L(-1). The removal efficiency of NB was nearly 100% for all NB concentrations in the ABR reactor. The methane gas production and the methane gas percentage remained stable (1500 mL day(-1) and 48-50%, respectively) as the NB concentration was increased from 30 to 210 mg L(-1). In the second step of the study it was found that as the HRT decreased from 10.38 days to 2.5 days the COD removal efficiencies decreased slightly from 94% to 92% in the ABR. For maximum COD and NB removal efficiencies the optimum HRT was found as 2.5 days in the ABR. The total COD removal efficiency was 95% in sequential anaerobic (ABR)/aerobic (CSTR) reactor system at a minimum HRT of 1 day. When the HRT was decreased from 10.38 days to 1 day, the methane percentage decreased from 42% to 29% in an ABR reactor treating 100 mg L(-1) NB. Nitrobenzene was reduced to aniline under anaerobic conditions while aniline was mineralized to catechol with meta cleavage under aerobic conditions.

  2. VLSI implementation of a fairness ATM buffer system

    DEFF Research Database (Denmark)

    Nielsen, J.V.; Dittmann, Lars; Madsen, Jens Kargaard

    1996-01-01

    This paper presents a VLSI implementation of a resource allocation scheme, based on the concept of weighted fair queueing. The design can be used in asynchronous transfer mode (ATM) networks to ensure fairness and robustness. Weighted fair queueing is a scheduling and buffer management scheme...

  3. ATM Couples Replication Stress and Metabolic Reprogramming during Cellular Senescence

    Directory of Open Access Journals (Sweden)

    Katherine M. Aird

    2015-05-01

    Full Text Available Replication stress induced by nucleotide deficiency plays an important role in cancer initiation. Replication stress in primary cells typically activates the cellular senescence tumor-suppression mechanism. Senescence bypass correlates with development of cancer, a disease characterized by metabolic reprogramming. However, the role of metabolic reprogramming in the cellular response to replication stress has been little explored. Here, we report that ataxia telangiectasia mutated (ATM plays a central role in regulating the cellular response to replication stress by shifting cellular metabolism. ATM inactivation bypasses senescence induced by replication stress triggered by nucleotide deficiency. This was due to restoration of deoxyribonucleotide triphosphate (dNTP levels through both upregulation of the pentose phosphate pathway via increased glucose-6-phosphate dehydrogenase (G6PD activity and enhanced glucose and glutamine consumption. These phenotypes were mediated by a coordinated suppression of p53 and upregulation of c-MYC downstream of ATM inactivation. Our data indicate that ATM status couples replication stress and metabolic reprogramming during senescence.

  4. HIPPI, Fibre Channel, and ATM as gigabit/s LANs

    Energy Technology Data Exchange (ETDEWEB)

    Tolmie, D.

    1993-12-31

    Computer networks that operate in the gigabit per second speed range are becoming very important for interconnecting supercomputers and other high end equipment. Some trends and applications are examined and criteria for selecting an interconnection technology are developed. HIPPI is the current interface of choice, while Fibre Channel and ATM are emerging standards. These systems are examined as to their backgrounds, advantages, and shortcomings.

  5. Performance Analysis of Using ATM-LSR to Implement MPLS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The explosive growth of Internet traffic has imposed tremendous stress on today's routers. Labelswitching is a new technique in network interconnection, which presents attractive performance of scalable, traffic engineering and large processing capability. This paper discusses the MPLS architecture, mainly focuses on the analysis of some problems in using Multiprotocol Label Switching (MPLS) based on the ATM backbone network and its solving mechanisms.

  6. Characterization of spent fuel approved testing material--ATM-104

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, R.J.; Blahnik, D.E.; Jenquin, U.P.; Mendel, J.E.; Thomas, L.E.; Thornhill, C.K.

    1991-12-01

    The characterization data obtained to date are described for Approved Testing Material 104 (ATM-104), which is spent fuel from Assembly DO47 of the Calvert Cliffs Nuclear Power Plant (Unit 1), a pressurized-water reactor. This report is one in a series being prepared by the Materials Characterization Center at Pacific Northwest Laboratory (PNL) on spent fuel ATMs. The ATMs are receiving extensive examinations to provide a source of well-characterized spent fuel for testing in the US Department of Energy Office of Civilian Radioactive Waste Management (OCRWM) Program. ATM-104 consists of 128 full-length irradiated fuel rods with rod-average burnups of about 42 MWd/kgM and expected fission gas release of about 1%. A variety of analyses were performed to investigate cladding characteristics, radionuclide inventory, and redistribution of fission products. Characterization data include (1) fabricated fuel design, irradiation history, and subsequent storage and handling history; (2) isotopic gamma scans; (3) fission gas analyses; (4) ceramography of the fuel and metallography of the cladding; (5) special fuel studies involving analytical transmission electron microscopy (AEM) and electron probe microanalyses (EPMA); (6) calculated nuclide inventories and radioactivities in the fuel and cladding; and (7) radiochemical analyses of the fuel and cladding.

  7. Characterization of spent fuel approved testing material---ATM-105

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, R.J.; Blahnik, D.E.; Campbell, T.K.; Jenquin, U.P.; Mendel, J.E.; Thomas, L.E.; Thornhill, C.K.

    1991-12-01

    The characterization data obtained to data are described for Approved Testing Material 105 (ATM-105), which is spent fuel from Bundles CZ346 and CZ348 of the Cooper Nuclear Power Plant, a boiling-water reactor. This report is one in a series being prepared by the Materials Characterization Center at Pacific Northwest Laboratory (PNL) on spent fuel ATMs. The ATMs are receiving extensive examinations to provide a source of well-characterized spent fuel for testing in the US Department of Energy Office of Civilian Radioactive Waste Management (OCRWM) Program. ATM-105 consists of 88 full-length irradiated fuel rods with rod-average burnups of about 2400 GJ/kgM (28 MWd/kgM) and expected fission gas release of about 1%. Characterization data include (1) descriptions of as-fabricated fuel design, irradiation history, and subsequent storage and handling; (2) isotopic gamma scans; (3) fission gas analyses; (4) ceramography of the fuel and metallography of the cladding; (5) special fuel studies involving analytical transmission electron microscopy (AEM); (6) calculated nuclide inventories and radioactivities in the fuel and cladding; and (7) radiochemical analyses of the fuel and cladding. Additional analyses of the fuel are being conducted and will be included in planned revisions of this report.

  8. ATM技术的应用实现%Application and realization of ATM techniques

    Institute of Scientific and Technical Information of China (English)

    向传杰; 许占文

    2001-01-01

    从ATM网络技术的发展过程人手,较全面地详细地介绍了ATM网络代表技术的功能实现和应用以及当前IP与ATM之争的发展情况,对ATM应用前景给出了正确客观的分析,为了解当前ATM技术提供了一个简捷的途径.%This paper introduces concept, new network techniques and its realization including ATM PON, voice over ATM, Mac over ATM, IP over ATM, ATM multimedia, ATM wireless net, and future of ATM. It offers readers an easy access to ATM.

  9. ATM facilitates mouse gammaherpesvirus reactivation from myeloid cells during chronic infection.

    Science.gov (United States)

    Kulinski, Joseph M; Darrah, Eric J; Broniowska, Katarzyna A; Mboko, Wadzanai P; Mounce, Bryan C; Malherbe, Laurent P; Corbett, John A; Gauld, Stephen B; Tarakanova, Vera L

    2015-09-01

    Gammaherpesviruses are cancer-associated pathogens that establish life-long infection in most adults. Insufficiency of Ataxia-Telangiectasia mutated (ATM) kinase leads to a poor control of chronic gammaherpesvirus infection via an unknown mechanism that likely involves a suboptimal antiviral response. In contrast to the phenotype in the intact host, ATM facilitates gammaherpesvirus reactivation and replication in vitro. We hypothesized that ATM mediates both pro- and antiviral activities to regulate chronic gammaherpesvirus infection in an immunocompetent host. To test the proposed proviral activity of ATM in vivo, we generated mice with ATM deficiency limited to myeloid cells. Myeloid-specific ATM deficiency attenuated gammaherpesvirus infection during the establishment of viral latency. The results of our study uncover a proviral role of ATM in the context of gammaherpesvirus infection in vivo and support a model where ATM combines pro- and antiviral functions to facilitate both gammaherpesvirus-specific T cell immune response and viral reactivation in vivo.

  10. ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas

    DEFF Research Database (Denmark)

    Bueno, R C; Canevari, R A; Villacis, R A R

    2014-01-01

    hybridization (aCGH) in 42 tumours. RESULTS: Low ATM levels were associated with tumour grade. Absence of ATM protein expression was associated with distant metastasis (P survival (DFS, P cancer-specific survival (CSS, P analysis indicated ATM......BACKGROUND: Ataxia telangiectasia-mutated (ATM) gene downexpression has been reported in sporadic breast carcinomas (BC); however, the prognostic value and mechanisms of ATM deregulation remain unclear. PATIENTS AND METHODS: ATM and miRNAs (miR-26a, miR-26b, miR-203, miR-421, miR-664, miR-576-5p...... and miR-18a) expression levels were evaluated by quantitative real-time PCR (RT-qPCR) in 52 BC and 3 normal breast samples. ATM protein expression was assessed by immunohistochemistry in 968 BC and 35 adjacent normal breast tissues. ATM copy number alteration was detected by array comparative genomic...

  11. ACCORD Broadband ATM Satellite Experiment (BASE)-DS3 Ku-band channel

    Science.gov (United States)

    1997-12-01

    broadband ATM traf- fic. ATM was initially designed for fibre - optic media, i.e. a random error, low delay, and virtually error free channel...satellite links will soon be required to support broadband ATM traffic. ATM was initially designed for fibre - optic media, i.e. a random error, low...traffic generator and analyser. - Fibre Loop Converter: converts a DS-3 signal into a single-mode fibre optic signal and vice-versa. - EF Data Modem

  12. Satellite/Terrestrial Networks: End-to-End Communication Interoperability Quality of Service Experiments

    Science.gov (United States)

    Ivancic, William D.

    1998-01-01

    Various issues associated with satellite/terrestrial end-to-end communication interoperability are presented in viewgraph form. Specific topics include: 1) Quality of service; 2) ATM performance characteristics; 3) MPEG-2 transport stream mapping to AAL-5; 4) Observation and discussion of compressed video tests over ATM; 5) Digital video over satellites status; 6) Satellite link configurations; 7) MPEG-2 over ATM with binomial errors; 8) MPEG-2 over ATM channel characteristics; 8) MPEG-2 over ATM over emulated satellites; 9) MPEG-2 transport stream with errors; and a 10) Dual decoder test.

  13. Stimulus-response characteristics of a harbor porpoise during active echolocation and passive hearing studied with auditory brain stem recordings (ABR)

    Science.gov (United States)

    Beedholm, Kristian; Miller, Lee A.

    2005-04-01

    We evaluated the stimulus-response characteristics of hearing by a harbor porpoise using narrow band pulses resembling the animal's own echolocation pulse (130 kHz, 100 us), but shifted in frequency (80, 100, 125, 160 kHz). Our animal was trained to accept two suction cup electrodes and to station 1 m below the water surface. Stimuli could be presented either as simulated echoes at a fixed delay (5 ms) relative to the animal's echolocation signals, or at a constant rate chosen by the experimenter. Stimulus levels were varied between 90 and 150 dB re 1uPa and the ABR responses were averaged (16 or more responses) at each level. The relationship between input level (in dB) and ABR amplitude was reasonably linear for simulated echo and constant rate experiments. Regression lines were calculated to determine the level at which the response met the noise, defining the ABR threshold. There was little difference in the ABR threshold (100 to 110 dB re 1uPa) for the four frequencies. The rate of growth of the ABR response with increasing stimulus level was steepest at 125 kHz, which could well reflect a relatively denser population of neurons tuned to this frequency area. [Work done at Fjord & Baelt, Kerteminde, Denmark, and supported by ONR.

  14. Pilot Study on Combined Process of ABR/MBBR for Treatment of Straw-pulp Middle-stage Wastewater%ABR/MBBR组合工艺处理草浆中段废水的中试研究

    Institute of Scientific and Technical Information of China (English)

    孙玲玲; 何仕均; 王建龙; 李坤豪; 解明曙

    2007-01-01

    通过现场中试考察了ABR/MBBR组合工艺处理草浆中段废水的效果.结果表明,当ABR进水COD为1 339~2 948 mg/L、HRT为24~48 h时,其对COD的去除率约为50%;ABR出水流入MBBR.当MBBR的HRT为6~12 h时,其对COD的去除率约为60%,MBBR出水COD稳定在350 mg/L左右.在Fe2(SO4)3投量为1 250~1 750 mg/L的情况下,经混凝、沉淀处理后出水COD<100 mg/.

  15. ATM solar array in-flight performance analysis

    Science.gov (United States)

    Thornton, J. P.; Crabtree, L. W.

    1974-01-01

    The physical and electrical characteristics of the Apollo Telescope Mount (ATM) solar array are described and in-flight performance data are analyzed and compared with predicted results. Two solar cell module configurations were used. Type I module consists of 228 2 x 6 cm solar cells with two cells in parallel and 114 cells in series. Type II modules contain 684 2 x 2 cm cells with six cells in parallel and 114 cells in series. A different interconnection scheme was used for each type. Panels using type II modules with mesh interconnect system performed marginally better than those using type I module with loop interconnect system. The average degradation rate for the ATM array was 8.2% for a 271-day mission.

  16. Atm Client Authentication System Using Biometric Identifier & Otp

    Directory of Open Access Journals (Sweden)

    Jaydeep Shamdasani

    2014-04-01

    Full Text Available In this paper we propose a design, to add more security to the current ATM systems by using biometric and GSM technology. In conventional method identification is done based on ID cards and static 4 digit password. Whereas in our purposed system, Bankers will collect the customer fingerprints and mobile number at the time of opening the accounts then only customer will be able to access ATM machine. The primary step of this project is to verify currently scanned fingerprint with the fingerprint which is registered in the bank during the account opening time. If the two fingerprints get matched, then a message will be delivered to the user’s mobile which is the random 4 digit pin number to access the account. For every transaction new pin numbers will be send to the user’s mobile thus there will not be fixed pin number for every transaction. Thus, Pin number will vary during each transaction .

  17. Digital Coin Business Model Using the Coin ATM

    Science.gov (United States)

    Jung, Won-Gyo; Park, Sang-Sung; Shin, Young-Geun; Jang, Dong-Sik

    2009-08-01

    Because about 83.6 billion won worth coins are not collected annually, 35 billion won of government money is being wasted for producing new coins in Korea. In order to improve unnecessary government money leakage, we now have to develop a proper way of managing small valued money such as coins. We have already developed the coin ATM to solve such problem in the previous study. In this study, we proposed business model, which enables users to deposit or consume such small amount of money with the coin ATM. The proposed business model has advantages that enable to connect various payment system and is efficient to consume such small amount of money. This business model improves not only the way of managing small valued money but also the way of consuming small valued money. Furthermore, our business model can contribute to activating circulation of coins as well as preventing leakage of government money.

  18. ATM-Deficient Colorectal Cancer Cells Are Sensitive to the PARP Inhibitor Olaparib.

    Science.gov (United States)

    Wang, Chen; Jette, Nicholas; Moussienko, Daniel; Bebb, D Gwyn; Lees-Miller, Susan P

    2017-02-06

    The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), and we previously showed that MCL cell lines with loss of ATM are sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Next-generation sequencing of patient tumors has revealed that ATM is altered in many human cancers including colorectal, lung, prostate, and breast. Here, we show that the colorectal cancer cell line SK-CO-1 lacks detectable ATM protein expression and is sensitive to the PARP inhibitor olaparib. Similarly, HCT116 colorectal cancer cells with shRNA depletion of ATM are sensitive to olaparib, and depletion of p53 enhances this sensitivity. Moreover, HCT116 cells are sensitive to olaparib in combination with the ATM inhibitor KU55933, and sensitivity is enhanced by deletion of p53. Together our studies suggest that PARP inhibitors may have potential for treating colorectal cancer with ATM dysfunction and/or colorectal cancer with mutation of p53 when combined with an ATM kinase inhibitor.

  19. ATM Coastal Topography-Florida 2001: Western Panhandle

    Science.gov (United States)

    Yates, Xan; Nayegandhi, Amar; Brock, John C.; Sallenger, A.H.; Bonisteel, Jamie M.; Klipp, Emily S.; Wright, C. Wayne

    2009-01-01

    These remotely sensed, geographically referenced elevation measurements of Lidar-derived first surface (FS) topography were produced collaboratively by the U.S. Geological Survey (USGS), Florida Integrated Science Center (FISC), St. Petersburg, FL, and the National Aeronautics and Space Administration (NASA), Wallops Flight Facility, VA. This project provides highly detailed and accurate datasets of the western Florida panhandle coastline, acquired October 2-4 and 7-10, 2001. The datasets are made available for use as a management tool to research scientists and natural resource managers. An innovative scanning Lidar instrument originally developed by NASA, and known as the Airborne Topographic Mapper (ATM), was used during data acquisition. The ATM system is a scanning Lidar system that measures high-resolution topography of the land surface and incorporates a green-wavelength laser operating at pulse rates of 2 to 10 kilohertz. Measurements from the laser-ranging device are coupled with data acquired from inertial navigation system (INS) attitude sensors and differentially corrected global positioning system (GPS) receivers to measure topography of the surface at accuracies of +/-15 centimeters. The nominal ATM platform is a Twin Otter or P-3 Orion aircraft, but the instrument may be deployed on a range of light aircraft. Elevation measurements were collected over the survey area using the ATM system, and the resulting data were then processed using the Airborne Lidar Processing System (ALPS), a custom-built processing system developed in a NASA-USGS collaboration. ALPS supports the exploration and processing of Lidar data in an interactive or batch mode. Modules for presurvey flight line definition, flight path plotting, Lidar raster and waveform investigation, and digital camera image playback have been developed. Processing algorithms have been developed to extract the range to the first and last significant return within each waveform. ALPS is routinely used

  20. ATM Coastal Topography-Florida 2001: Eastern Panhandle

    Science.gov (United States)

    Yates, Xan; Nayegandhi, Amar; Brock, John C.; Sallenger, A.H.; Bonisteel, Jamie M.; Klipp, Emily S.; Wright, C. Wayne

    2009-01-01

    These remotely sensed, geographically referenced elevation measurements of Lidar-derived first surface (FS) topography were produced collaboratively by the U.S. Geological Survey (USGS), Florida Integrated Science Center (FISC), St. Petersburg, FL, and the National Aeronautics and Space Administration (NASA), Wallops Flight Facility, VA. This project provides highly detailed and accurate datasets of the eastern Florida panhandle coastline, acquired October 2, 2001. The datasets are made available for use as a management tool to research scientists and natural resource managers. An innovative scanning Lidar instrument originally developed by NASA, and known as the Airborne Topographic Mapper (ATM), was used during data acquisition. The ATM system is a scanning Lidar system that measures high-resolution topography of the land surface and incorporates a green-wavelength laser operating at pulse rates of 2 to 10 kilohertz. Measurements from the laser-ranging device are coupled with data acquired from inertial navigation system (INS) attitude sensors and differentially corrected global positioning system (GPS) receivers to measure topography of the surface at accuracies of +/-15 centimeters. The nominal ATM platform is a Twin Otter or P-3 Orion aircraft, but the instrument may be deployed on a range of light aircraft. Elevation measurements were collected over the survey area using the ATM system, and the resulting data were then processed using the Airborne Lidar Processing System (ALPS), a custom-built processing system developed in a NASA-USGS collaboration. ALPS supports the exploration and processing of Lidar data in an interactive or batch mode. Modules for presurvey flight line definition, flight path plotting, Lidar raster and waveform investigation, and digital camera image playback have been developed. Processing algorithms have been developed to extract the range to the first and last significant return within each waveform. ALPS is routinely used to create

  1. ATM Coastal Topography-Texas, 2001: UTM Zone 15

    Science.gov (United States)

    Klipp, Emily S.; Nayegandhi, Amar; Brock, John C.; Sallenger, A.H.; Bonisteel, Jamie M.; Yates, Xan; Wright, C. Wayne

    2009-01-01

    These remotely sensed, geographically referenced elevation measurements of lidar-derived first-surface (FS) topography were produced collaboratively by the U.S. Geological Survey (USGS), Florida Integrated Science Center (FISC), St. Petersburg, FL, and the National Aeronautics and Space Administration (NASA), Wallops Flight Facility, VA. This project provides highly detailed and accurate datasets of a portion of the Texas coastline within UTM zone 15, from Matagorda Peninsula to Galveston Island, acquired October 12-13, 2001. The datasets are made available for use as a management tool to research scientists and natural-resource managers. An innovative scanning lidar instrument originally developed by NASA, and known as the Airborne Topographic Mapper (ATM), was used during data acquisition. The ATM system is a scanning lidar system that measures high-resolution topography of the land surface and incorporates a green-wavelength laser operating at pulse rates of 2 to 10 kilohertz. Measurements from the laser-ranging device are coupled with data acquired from inertial navigation system (INS) attitude sensors and differentially corrected global positioning system (GPS) receivers to measure topography of the surface at accuracies of +/-15 centimeters. The nominal ATM platform is a Twin Otter or P-3 Orion aircraft, but the instrument may be deployed on a range of light aircraft. Elevation measurements were collected over the survey area using the ATM system, and the resulting data were then processed using the Airborne Lidar Processing System (ALPS), a custom-built processing system developed in a NASA-USGS collaboration. ALPS supports the exploration and processing of lidar data in an interactive or batch mode. Modules for presurvey flight-line definition, flight-path plotting, lidar raster and waveform investigation, and digital camera image playback have been developed. Processing algorithms have been developed to extract the range to the first and last significant

  2. ATM Coastal Topography-Texas, 2001: UTM Zone 14

    Science.gov (United States)

    Klipp, Emily S.; Nayegandhi, Amar; Brock, John C.; Sallenger, A.H.; Bonisteel, Jamie M.; Yates, Xan; Wright, C. Wayne

    2009-01-01

    These remotely sensed, geographically referenced elevation measurements of lidar-derived first-surface (FS) topography were produced collaboratively by the U.S. Geological Survey (USGS), Florida Integrated Science Center (FISC), St. Petersburg, FL, and the National Aeronautics and Space Administration (NASA), Wallops Flight Facility, VA. This project provides highly detailed and accurate datasets of a portion of the Texas coastline within UTM zone 14, acquired October 12-13, 2001. The datasets are made available for use as a management tool to research scientists and natural-resource managers. An innovative scanning lidar instrument originally developed by NASA, and known as the Airborne Topographic Mapper (ATM), was used during data acquisition. The ATM system is a scanning lidar system that measures high-resolution topography of the land surface and incorporates a green-wavelength laser operating at pulse rates of 2 to 10 kilohertz. Measurements from the laser-ranging device are coupled with data acquired from inertial navigation system (INS) attitude sensors and differentially corrected global positioning system (GPS) receivers to measure topography of the surface at accuracies of +/-15 centimeters. The nominal ATM platform is a Twin Otter or P-3 Orion aircraft, but the instrument may be deployed on a range of light aircraft. Elevation measurements were collected over the survey area using the ATM system, and the resulting data were then processed using the Airborne Lidar Processing System (ALPS), a custom-built processing system developed in a NASA-USGS collaboration. ALPS supports the exploration and processing of lidar data in an interactive or batch mode. Modules for presurvey flight-line definition, flight-path plotting, lidar raster and waveform investigation, and digital camera image playback have been developed. Processing algorithms have been developed to extract the range to the first and last significant return within each waveform. ALPS is used

  3. Enhanced ATM Security using Biometric Authentication and Wavelet Based AES

    Directory of Open Access Journals (Sweden)

    Sreedharan Ajish

    2016-01-01

    Full Text Available The traditional ATM terminal customer recognition systems rely only on bank cards, passwords and such identity verification methods are not perfect and functions are too single. Biometrics-based authentication offers several advantages over other authentication methods, there has been a significant surge in the use of biometrics for user authentication in recent years. This paper presents a highly secured ATM banking system using biometric authentication and wavelet based Advanced Encryption Standard (AES algorithm. Two levels of security are provided in this proposed design. Firstly we consider the security level at the client side by providing biometric authentication scheme along with a password of 4-digit long. Biometric authentication is achieved by considering the fingerprint image of the client. Secondly we ensure a secured communication link between the client machine to the bank server using an optimized energy efficient and wavelet based AES processor. The fingerprint image is the data for encryption process and 4-digit long password is the symmetric key for the encryption process. The performance of ATM machine depends on ultra-high-speed encryption, very low power consumption, and algorithmic integrity. To get a low power consuming and ultra-high speed encryption at the ATM machine, an optimized and wavelet based AES algorithm is proposed. In this system biometric and cryptography techniques are used together for personal identity authentication to improve the security level. The design of the wavelet based AES processor is simulated and the design of the energy efficient AES processor is simulated in Quartus-II software. Simulation results ensure its proper functionality. A comparison among other research works proves its superiority.

  4. Phosphorylation of p300 by ATM controls the stability of NBS1

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Eun Ryoung [Department of Molecular Science and Technology, College of Natural Sciences, Ajou University, Suwon 443-749 (Korea, Republic of); Choi, Jae Duk [Department of Molecular Science and Technology, College of Natural Sciences, Ajou University, Suwon 443-749 (Korea, Republic of); School of Biological Sciences, Seoul National University, Seoul 151 (Korea, Republic of); Jeong, Gajin [School of Biological Sciences, Seoul National University, Seoul 151 (Korea, Republic of); Lee, Jong-Soo, E-mail: jsjlee@mail.ajou.ac.kr [Department of Molecular Science and Technology, College of Natural Sciences, Ajou University, Suwon 443-749 (Korea, Republic of)

    2010-07-09

    Acetyltransferase, p300 is a transcriptional cofactor of signal-responsive transcriptional regulation. The surveillance kinase ataxia-telangiectasia mutated (ATM) plays a central role in regulation of a wide range of cellular DNA damage responses. Here, we investigated whether and how ATM mediates phosphorylation of p300 in response to DNA damage and how p300 phosphorylation is functionally linked to DNA damage. ATM-phosphorylated p300 in vitro and in vivo, in response to DNA damage. Phosphorylation of p300 proteins was observed upon {gamma}-irradiation in ATM{sup +} cells but not ATM{sup -} cells. Importantly, expression of nonphosphorylatable serine to alanine form of p300 (S106A) destabilized both p300 and NBS1 proteins, after DNA damage. These data demonstrate that ATM transduces a DNA damage signal to p300, and that ATM-dependent phosphorylation of p300 is required for stabilization of NBS1 proteins in response to DNA damage.

  5. Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors

    DEFF Research Database (Denmark)

    Raposo-Ferreira, T M M; Bueno, R C; Terra, E M;

    2016-01-01

    tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein......The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated...... with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry...

  6. The tumor targeted superantigen ABR-217620 selectively engages TRBV7-9 and exploits TCR-pMHC affinity mimicry in mediating T cell cytotoxicity.

    Directory of Open Access Journals (Sweden)

    Gunnar Hedlund

    Full Text Available The T lymphocytes are the most important effector cells in immunotherapy of cancer. The conceptual objective for developing the tumor targeted superantigen (TTS ABR-217620 (naptumomab estafenatox, 5T4Fab-SEA/E-120, now in phase 3 studies for advanced renal cell cancer, was to selectively coat tumor cells with cytotoxic T lymphocytes (CTL target structures functionally similar to natural CTL pMHC target molecules. Here we present data showing that the molecular basis for the anti-tumor activity by ABR-217620 resides in the distinct interaction between the T cell receptor β variable (TRBV 7-9 and the engineered superantigen (Sag SEA/E-120 in the fusion protein bound to the 5T4 antigen on tumor cells. Multimeric but not monomeric ABR-217620 selectively stains TRBV7-9 expressing T lymphocytes from human peripheral blood similar to antigen specific staining of T cells with pMHC tetramers. SEA/E-120 selectively activates TRBV7-9 expressing T lymphocytes resulting in expansion of the subset. ABR-217620 selectively triggers TRBV7-9 expressing cytotoxic T lymphocytes to kill 5T4 positive tumor cells. Furthermore, ABR-217620 activates TRBV7-9 expressing T cell line cells in the presence of cell- and bead-bound 5T4 tumor antigen. Surface plasmon resonance analysis revealed that ABR-217620 binds to 5T4 with high affinity, to TRBV7-9 with low affinity and to MHC class II with very low affinity. The T lymphocyte engagement by ABR-217620 is constituted by displaying high affinity binding to the tumor cells (KD approximately 1 nM and with the mimicry of natural productive immune TCR-pMHC contact using affinities of around 1 µM. This difference in kinetics between the two components of the ABR-217620 fusion protein will bias the binding towards the 5T4 target antigen, efficiently activating T-cells via SEA/E-120 only when presented by the tumor cells.

  7. Idle Object Detection in Video for Banking ATM Applications

    Directory of Open Access Journals (Sweden)

    K. Kausalya

    2012-12-01

    Full Text Available This study proposes a method to detect idle object and applies it for analysis of suspicious events. Partitioning and Normalized Cross Correlation (PNCC based algorithm is proposed for the detection of moving object. This algorithm takes less processing time, which increases the speed and also the detection rate. In this an approach is proposed for the detection and tracking of moving object in an image sequence. Two consecutive frames from image sequence are partitioned into four quadrants and then the Normalized Cross Correlation (NCC is applied to each sub frame. The sub frame which has minimum value of NCC, indicates the presence of moving object. The proposed system is going to use the suspicious tracking of human behaviour in video surveillance and it is mainly used for security purpose in ATM application. The suspicious object’s visual properties so that it can be accurately segmented from videos. After analyzing its subsequent motion features, different abnormal events like robbery can be effectively detected from videos. The suspicious action in ATM are many, such as using mobile phones, multiple persons trying to access the ATM machine in same time, kicking of each other, idle object and it shows event corresponding to Vandalism and robbery. In proposed system, idle object detection is used to identify by using PNCC algorithm with P-filter (Particle and by extracting the features of the object in an enhanced way by using the curvelet based transformation.

  8. Studies of ATM for ATLAS high level triggers

    CERN Document Server

    Bystrický, J; Huet, M; Le Dû, P; Mandjavidze, I D

    2001-01-01

    This paper presents some of the conclusions of our studies on ATM and Fast Ethernet in the ATLAS level-2 trigger Pilot project. We describe the general concept and principles of our data collection and event building scheme that could be transposed to various experiments in high energy and nuclear physics. To validate the approach in view of ATLAS High Level Triggers, we assembled a testbed composed of up to 48 computers linked by a 7.5 Gbit/s ATM switch. This modular switch is used as a single entity or is split into several smaller interconnected switches. This allows studying how to construct a large network from smaller units. Alternatively, the ATM network can be replaced by Fast Ethernet. We detail the operation of the system and present series of performance measurements made with event building traffic pattern. We extrapolate these results to show how today's commercial networking components could be used to build a 1000-port network adequate for ATLAS needs. Finally, we list the benefits and the limi...

  9. Studies of ATM for ATLAS high-level triggers

    CERN Document Server

    Bystrický, J; Huet, M; Le Dû, P; Mandjavidze, I D

    2001-01-01

    This paper presents some of the conclusions of our studies on asynchronous transfer mode (ATM) and fast Ethernet in the ATLAS level-2 trigger pilot project. We describe the general concept and principles of our data-collection and event-building scheme that could be transposed to various experiments in high-energy and nuclear physics. To validate the approach in view of ATLAS high-level triggers, we assembled a testbed composed of up to 48 computers linked by a 7.5-Gbit/s ATM switch. This modular switch is used as a single entity or is split into several smaller interconnected switches. This allows study of how to construct a large network from smaller units. Alternatively, the ATM network can be replaced by fast Ethernet. We detail the operation of the system and present series of performance measurements made with event-building traffic pattern. We extrapolate these results to show how today's commercial networking components could be used to build a 1000-port network adequate for ATLAS needs. Lastly, we li...

  10. The effect of pH and operation mode for COD removal of slaughterhouse wastewater with Anaerobic Batch Reactor (ABR

    Directory of Open Access Journals (Sweden)

    Maria Octoviane Dyan

    2015-01-01

    Full Text Available Disposal of industrial wastes in large quantities was not in accordance with today's standards of waste into environmental issues that must be overcome with proper treatment. Similarly, the abattoir wastewater that contains too high organic compounds and suspended solids. The amount of liquid waste disposal Slaughterhouse (SW with high volume also causes pollution. The research aim to resolve this problem by lowering the levels of BOD-COD to comply with effluent quality standard. Anaerobic process is the right process for slaughterhouse wastewater treatment because of high content of organic compounds that can be utilized by anaerobic bacteria as a growth medium. Some research has been conducted among abattoir wastewater treatment using anaerobic reactors such as ABR, UASB and ASBR. Our research focuses on the search for the optimum results decline effluent COD levels to match the quality standards limbah and cow rumen fluid with biodigester ABR (Anaerobic Batch Reactor. The variables used were PH of 6, 7, and 8, as well as the concentration ratio of COD: N is 400:7; 450:7, and 500:7. COD value is set by the addition of N derived from urea [CO(NH2 2]. COD levels will be measured daily by water displacement technique. The research’s result for 20 days seen that optimum PH for biogas production was PH 7,719 ml. The optimum PH for COD removal is PH 6, 72.39 %. The operation mode COD:N for biogas production and COD removal is 500:7, with the production value is 601 ml and COD removal value is 63.85 %. The research’s conclusion, the PH optimum for biogas production was PH 7, then the optimum PH for COD removal is PH 6. The optimum operation mode COD:N for biogas production and COD removal was 500:7

  11. Dynamic Bandwidth Allocation Technique in ATM Networks Based on Fuzzy Neural Networks and Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    ZhangLiangjie; LiYanda; 等

    1997-01-01

    In this paper,a dynamic bandwidth allocation technique based on fuzz neural networks(FNNs) and genetic algorithm(GA)is proposed for preventive congestion control in ATM network.The traffic model based on FNN does not need the descriptive traffic parameters in detail,which greatly depend on the user's terminal.Genetic algorithm is used to predict the equivalent bandwidth of the accepted traffic in real-time.Thus,the proposed scheme can estimate the dynamic bandwidth of the network in the time scale from the call arrival to the call admission/rejection due to the fuzzy-tech and GA hardware implementation.Simulation results show that the scheme can perform accurate dynamic bandwidth allocation to DN/OFF bursty traffic in accordance with the required quality of service(QOS),and the bandwidth utilization is improved from the overall point of view.

  12. NOTCH1 Inhibits Activation of ATM by Impairing the Formation of an ATM-FOXO3a-KAT5/Tip60 Complex.

    Science.gov (United States)

    Adamowicz, Marek; Vermezovic, Jelena; d'Adda di Fagagna, Fabrizio

    2016-08-23

    The DNA damage response (DDR) signal transduction pathway is responsible for sensing DNA damage and further relaying this signal into the cell. ATM is an apical DDR kinase that orchestrates the activation and the recruitment of downstream DDR factors to induce cell-cycle arrest and repair. We have previously shown that NOTCH1 inhibits ATM activation upon DNA damage, but the underlying mechanism remains unclear. Here, we show that NOTCH1 does not impair ATM recruitment to DNA double-strand breaks (DSBs). Rather, NOTCH1 prevents binding of FOXO3a and KAT5/Tip60 to ATM through a mechanism in which NOTCH1 competes with FOXO3a for ATM binding. Lack of FOXO3a binding to ATM leads to the loss of KAT5/Tip60 association with ATM. Moreover, expression of NOTCH1 or depletion of ATM impairs the formation of the FOXO3a-KAT5/Tip60 protein complex. Finally, we show that pharmacological induction of FOXO3a nuclear localization sensitizes NOTCH1-driven cancers to DNA-damage-induced cell death.

  13. ATM function and its relationship with ATM gene mutations in chronic lymphocytic leukemia with the recurrent deletion (11q22.3-23.2).

    Science.gov (United States)

    Jiang, Y; Chen, H-C; Su, X; Thompson, P A; Liu, X; Do, K-A; Wierda, W; Keating, M J; Plunkett, W

    2016-09-02

    Approximately 10-20% of chronic lymphocytic leukemia (CLL) patients exhibit del(11q22-23) before treatment, this cohort increases to over 40% upon progression following chemoimmunotherapy. The coding sequence of the DNA damage response gene, ataxia-telangiectasia-mutated (ATM), is contained in this deletion. The residual ATM allele is frequently mutated, suggesting a relationship between gene function and clinical response. To investigate this possibility, we sought to develop and validate an assay for the function of ATM protein in these patients. SMC1 (structural maintenance of chromosomes 1) and KAP1 (KRAB-associated protein 1) were found to be unique substrates of ATM kinase by immunoblot detection following ionizing radiation. Using a pool of eight fluorescence in situ hybridization-negative CLL samples as a standard, the phosphorylation of SMC1 and KAP1 from 46 del (11q22-23) samples was analyzed using normal mixture model-based clustering. This identified 13 samples (28%) that were deficient in ATM function. Targeted sequencing of the ATM gene of these samples, with reference to genomic DNA, revealed 12 somatic mutations and 15 germline mutations in these samples. No strong correlation was observed between ATM mutation and function. Therefore, mutation status may not be taken as an indicator of ATM function. Rather, a direct assay of the kinase activity should be used in the development of therapies.

  14. Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice.

    Science.gov (United States)

    Pietzner, J; Merscher, B M; Baer, P C; Duecker, R P; Eickmeier, O; Fußbroich, D; Bader, P; Del Turco, D; Henschler, R; Zielen, S; Schubert, R

    2016-04-01

    Ataxia telangiectasia is a genetic instability syndrome characterized by neurodegeneration, immunodeficiency, severe bronchial complications, hypersensitivity to radiotherapy and an elevated risk of malignancies. Repopulation with ATM-competent bone marrow-derived cells (BMDCs) significantly prolonged the lifespan and improved the phenotype of Atm-deficient mice. The aim of the present study was to promote BMDC engraftment after bone marrow transplantation using low-dose irradiation (IR) as a co-conditioning strategy. Atm-deficient mice were transplanted with green fluorescent protein-expressing, ATM-positive BMDCs using a clinically relevant non-myeloablative host-conditioning regimen together with TBI (0.2-2.0 Gy). IR significantly improved the engraftment of BMDCs into the bone marrow, blood, spleen and lung in a dose-dependent manner, but not into the cerebellum. However, with increasing doses, IR lethality increased even after low-dose IR. Analysis of the bronchoalveolar lavage fluid and lung histochemistry revealed a significant enhancement in the number of inflammatory cells and oxidative damage. A delay in the resolution of γ-H2AX-expression points to an insufficient double-strand break repair capacity following IR with 0.5 Gy in Atm-deficient splenocytes. Our results demonstrate that even low-dose IR results in ATM activation. In the absence of ATM, low-dose IR leads to increased inflammation, oxidative stress and lethality in the Atm-deficient mouse model.

  15. ATM is required for telomere maintenance and chromosome stability during Drosophila development.

    Science.gov (United States)

    Silva, Elizabeth; Tiong, Stanley; Pedersen, Michael; Homola, Ellen; Royou, Anne; Fasulo, Barbara; Siriaco, Giorgia; Campbell, Shelagh D

    2004-08-10

    ATM is a large, multifunctional protein kinase that regulates responses required for surviving DNA damage: including DNA repair, apoptosis, and cell cycle checkpoints. Here, we show that Drosophila ATM function is essential for normal adult development. Extensive, inappropriate apoptosis occurs in proliferating atm mutant tissues, and in clonally derived atm mutant embryos, frequent mitotic defects were seen. At a cellular level, spontaneous telomere fusions and other chromosomal abnormalities are common in atm larval neuroblasts, suggesting a conserved and essential role for dATM in the maintenance of normal telomeres and chromosome stability. Evidence from other systems supports the idea that DNA double-strand break (DSB) repair functions of ATM kinases promote telomere maintenance by inhibition of illegitimate recombination or fusion events between the legitimate ends of chromosomes and spontaneous DSBs. Drosophila will be an excellent model system for investigating how these ATM-dependent chromosome structural maintenance functions are deployed during development. Because neurons appear to be particularly sensitive to loss of ATM in both flies and humans, this system should be particularly useful for identifying cell-specific factors that influence sensitivity to loss of dATM and are relevant for understanding the human disease, ataxia-telangiectasia.

  16. Regulation of the DNA Damage Response by DNA-PKcs Inhibitory Phosphorylation of ATM.

    Science.gov (United States)

    Zhou, Yi; Lee, Ji-Hoon; Jiang, Wenxia; Crowe, Jennie L; Zha, Shan; Paull, Tanya T

    2017-01-05

    Ataxia-telangiectasia mutated (ATM) regulates the DNA damage response as well as DNA double-strand break repair through homologous recombination. Here we show that ATM is hyperactive when the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is chemically inhibited or when the DNA-PKcs gene is deleted in human cells. Pre-incubation of ATM protein with active DNA-PKcs also significantly reduces ATM activity in vitro. We characterize several phosphorylation sites in ATM that are targets of DNA-PKcs and show that phospho-mimetic mutations at these residues significantly inhibit ATM activity and impair ATM signaling upon DNA damage. In contrast, phospho-blocking mutations at one cluster of sites increase the frequency of apoptosis during normal cell growth. DNA-PKcs, which is integral to the non-homologous end joining pathway, thus negatively regulates ATM activity through phosphorylation of ATM. These observations illuminate an important regulatory mechanism for ATM that also controls DNA repair pathway choice.

  17. Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors.

    Science.gov (United States)

    Raposo-Ferreira, T M M; Bueno, R C; Terra, E M; Avante, M L; Tinucci-Costa, M; Carvalho, M; Cassali, G D; Linde, S D; Rogatto, S R; Laufer-Amorim, R

    2016-11-01

    The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively, in normal mammary gland samples (n = 10), benign mammary tumors (n = 11), nonmetastatic mammary carcinomas (n = 19), and metastatic mammary carcinomas (n = 11). Lower ATM transcript levels were detected in benign mammary tumors and carcinomas compared with normal mammary glands (P = .011). Similarly, lower ATM protein expression was observed in benign tumors (P = .0003), nonmetastatic mammary carcinomas (P ATM gene or protein levels were detected among benign tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein downregulation is involved in canine mammary gland tumorigenesis.

  18. ATM may be a protective factor in endometrial carcinogenesis with the progesterone pathway.

    Science.gov (United States)

    Shan, Weiwei; Wang, Chao; Zhang, Zhenbo; Luo, Xuezhen; Ning, Chengcheng; Yu, Yinhua; Feng, Youji; Gu, Chao; Chen, Xiaojun

    2015-03-01

    The purpose of the study was to explore the role and mechanism of ataxia-telangiectasia mutated (ATM) protein in endometrial carcinogenesis. A reverse-phase protein array (RPPA) was used to analyze the expression of ATM signal pathway proteins in Ishikawa and progesterone-insensitive Ishikawa. ATM expression was detected in endometrium specimens by immunohistochemistry, including 8 cases with proliferative endometrium, 6 cases with secretory endometrium, 10 cases with simple hyperplasia (SH), 13 cases of complex hyperplasia (CH), 11 cases of endometrial atypical hyperplasia (EAH), and 83 cases with type I endometrial cancer. The relationship between ATM expression and other clinicopathological indicators was also examined in type I endometrial cancer patients. The mechanisms of ATM were explored in vitro with the endometrial cell lines Ishikawa and RL95-2. A cell counting kit-8 (CCK-8) test and Western blot analysis were performed to test proliferation and protein expression. Statistical analysis was performed with SPSS19.0. The significance level was set at 0.05. ATM was increased with medroxyprogesterone acetate (MPA) stimulation in Ishikawa in RPPA. ATM expression gradually decreased in endometrial hyperplasic lesions compared with the normal proliferative and secretory endometrium and was the lowest in type I endometrial cancer. ATM expression was negatively correlated with pathological grades in type I endometrial cancer. In vitro, ATM silencing retarded proliferation inhibition in Ishikawa and RL95-2 treated with MPA. ATM silencing could down-regulate the MPA-stimulated signal proteins, including Chk2, P53, and caspase-3 in vitro. MPA might exert its role through activating the ATM-associated pathway, ATM-Chk2-P53-caspase-3 (active), preserving normal endometrium and protecting it from malignancies. ATM might be a promising indicator for endometrial hyperplasia and cancer.

  19. Brainstem response audiometry in the determination of low-frequency hearing loss : a study of various methods for frequency-specific ABR-threshold assessment

    NARCIS (Netherlands)

    E.A.G.J. Conijn

    1992-01-01

    textabstractBrainstem Electric Response Audiometry (BERA) is a method to visualize some of the electric activity generated in the auditory nerve and the brainstem during the processing of sound. The amplitude of the Auditory Brainstem Response (ABR) is very small (0.05-0.5 flV). The potentials origi

  20. Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors.

    Science.gov (United States)

    Yamamoto, Kenta; Wang, Jiguang; Sprinzen, Lisa; Xu, Jun; Haddock, Christopher J; Li, Chen; Lee, Brian J; Loredan, Denis G; Jiang, Wenxia; Vindigni, Alessandro; Wang, Dong; Rabadan, Raul; Zha, Shan

    2016-06-15

    Missense mutations in ATM kinase, a master regulator of DNA damage responses, are found in many cancers, but their impact on ATM function and implications for cancer therapy are largely unknown. Here we report that 72% of cancer-associated ATM mutations are missense mutations that are enriched around the kinase domain. Expression of kinase-dead ATM (Atm(KD/-)) is more oncogenic than loss of ATM (Atm(-/-)) in mouse models, leading to earlier and more frequent lymphomas with Pten deletions. Kinase-dead ATM protein (Atm-KD), but not loss of ATM (Atm-null), prevents replication-dependent removal of Topo-isomerase I-DNA adducts at the step of strand cleavage, leading to severe genomic instability and hypersensitivity to Topo-isomerase I inhibitors. Correspondingly, Topo-isomerase I inhibitors effectively and preferentially eliminate Atm(KD/-), but not Atm-proficientor Atm(-/-) leukemia in animal models. These findings identify ATM kinase-domain missense mutations as a potent oncogenic event and a biomarker for Topo-isomerase I inhibitor based therapy.

  1. A New Approach to VC Routing in ATM Networks

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A new ant-algorithm-based routing approach is proposed for the VC routing problem with considering the comprehensive effect between the resource utilization and the load balance in ATM networks. In the approach, the backup paths are calculated first, and then an ant algorithm based on the ability of ants to find the shortest path between their nest and the food source during their searching food, is constructed to optimize the VC global route.Simulation results show that the proposed approach can realize VC routing effectively according to the current traffic states in the networks and the user-specified delay requirements.

  2. Regulation of the AbrA1/A2 two-component system in Streptomyces coelicolor and the potential of its deletion strain as a heterologous host for antibiotic production.

    Directory of Open Access Journals (Sweden)

    Sergio Rico

    Full Text Available The Two-Component System (TCS AbrA1/A2 from Streptomyces coelicolor M145 is a negative regulator of antibiotic production and morphological differentiation. In this work we show that it is able to auto-regulate its expression, exerting a positive induction of its own operon promoter, and that its activation is dependent on the presence of iron. The overexpression of the abrA2 response regulator (RR gene in the mutant ΔabrA1/A2 results in a toxic phenotype. The reason is an excess of phosphorylated AbrA2, as shown by phosphoablative and phosphomimetic AbrA2 mutants. Therefore, non-cognate histidine kinases (HKs or small phospho-donors may be responsible for AbrA2 phosphorylation in vivo. The results suggest that in the parent strain S. coelicolor M145 the correct amount of phosphorylated AbrA2 is adjusted through the phosphorylation-dephosphorylation activity rate of the HK AbrA1. Furthermore, the ABC transporter system, which is part of the four-gene operon comprising AbrA1/A2, is necessary to de-repress antibiotic production in the TCS null mutant. Finally, in order to test the possible biotechnological applications of the ΔabrA1/A2 strain, we demonstrate that the production of the antitumoral antibiotic oviedomycin is duplicated in this strain as compared with the production obtained in the wild type, showing that this strain is a good host for heterologous antibiotic production. Thus, this genetically modified strain could be interesting for the biotechnology industry.

  3. Processamento auditivo e potenciais evocados auditivos de tronco cerebral (BERA Auditory precessing and auditory brainstem response (ABR

    Directory of Open Access Journals (Sweden)

    Marcela Pfeiffer

    2009-01-01

    Full Text Available OBJETIVO: verificar relação existente entre os potenciais auditivos de tronco cerebral e a avaliação comportamental do processamento auditivo. MÉTODOS: foi realizada em um grupo de 60 meninas residentes de Paraíba do Sul na idade de nove a 12 anos com limiares tonais dentro dos padrões de normalidade e timpanometria tipo A com presença dos reflexos acústicos. Os testes utilizados para a avaliação comportamental do processamento auditivo foram: avaliação simplificada do processamento auditivo, teste de fala no ruído, teste de dissílabos alternados e teste dicótico não verbal. Após a avaliação do processamento auditivo, as crianças foram subdivididas em dois grupos, G1 (sem alteração no processamento auditivo e G2 (com alteração no processamento auditivo e submetidas aos potenciais auditivos de tronco cerebral. Os parâmetros utilizados na comparação dos dois grupos foram: latência absoluta das ondas I, III e V; latência interpicos das ondas I-III, I-V, III-V; diferença interaural da latência interpico I-V; e diferença interaural da latência da onda V. RESULTADOS: foram encontradas diferenças estatísticas nos parâmetros de latência interpico das ondas I-V na orelha esquerda (p=0,009, diferença interaural da latência interpico de ondas I-V (p=0,020 e diferença da latência interpico de ondas I e V da orelha direita para a esquerda entre os grupos G1 e G2 (p=0,025. CONCLUSÃO: foi possível encontrar relação dos potenciais evocados auditivos de tronco cerebral com a avaliação comportamental do processamento auditivo nos parâmetros de latência interpico entre as ondas I e V da orelha esquerda e diferença interaural da latência interpico I-V na orelha esquerda.PURPOSE: to investigate the correlation of auditory brainstem response (ABR and behavioral auditory processing evaluation. METHODS: sixty girls, from Paraíba do Sul, ranging from 9 to 12-year-old were evaluated. In order to take part in the study

  4. Differential Roles of ATM- and Chk2-Mediated Phosphorylations of Hdmx in Response to DNA Damage†

    OpenAIRE

    Pereg, Yaron; Lam, Suzanne; Teunisse, Amina; Biton, Sharon; Meulmeester, Erik; Mittelman, Leonid; Buscemi, Giacomo; Okamoto, Koji; Taya, Yoichi; Shiloh, Yosef; Jochemsen, Aart G.

    2006-01-01

    The p53 tumor suppressor plays a major role in maintaining genomic stability. Its activation and stabilization in response to double strand breaks (DSBs) in DNA are regulated primarily by the ATM protein kinase. ATM mediates several posttranslational modifications on p53 itself, as well as phosphorylation of p53's essential inhibitors, Hdm2 and Hdmx. Recently we showed that ATM- and Hdm2-dependent ubiquitination and subsequent degradation of Hdmx following DSB induction are mediated by phosph...

  5. Loss of p53 Ser18 and Atm results in embryonic lethality without cooperation in tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Heather L Armata

    Full Text Available Phosphorylation at murine Serine 18 (human Serine 15 is a critical regulatory process for the tumor suppressor function of p53. p53Ser18 residue is a substrate for ataxia-telangiectasia mutated (ATM and ATM-related (ATR protein kinases. Studies of mice with a germ-line mutation that replaces Ser18 with Ala (p53(S18A mice have demonstrated that loss of phosphorylation of p53Ser18 leads to the development of tumors, including lymphomas, fibrosarcomas, leukemia and leiomyosarcomas. The predominant lymphoma is B-cell lymphoma, which is in contrast to the lymphomas observed in Atm(-/- animals. This observation and the fact that multiple kinases phosphorylate p53Ser18 suggest Atm-independent tumor suppressive functions of p53Ser18. Therefore, in order to examine p53Ser18 function in relationship to ATM, we analyzed the lifespan and tumorigenesis of mice with combined mutations in p53Ser18 and Atm. Surprisingly, we observed no cooperation in survival and tumorigenesis in compound p53(S18A and Atm(-/- animals. However, we observed embryonic lethality in the compound mutant animals. In addition, the homozygous p53Ser18 mutant allele impacted the weight of Atm(-/- animals. These studies examine the genetic interaction of p53Ser18 and Atm in vivo. Furthermore, these studies demonstrate a role of p53Ser18 in regulating embryonic survival and motor coordination.

  6. ATM Inhibition Potentiates Death of Androgen Receptor-inactivated Prostate Cancer Cells with Telomere Dysfunction.

    Science.gov (United States)

    Reddy, Vidyavathi; Wu, Min; Ciavattone, Nicholas; McKenty, Nathan; Menon, Mani; Barrack, Evelyn R; Reddy, G Prem-Veer; Kim, Sahn-Ho

    2015-10-16

    Androgen receptor (AR) plays a role in maintaining telomere stability in prostate cancer cells, as AR inactivation induces telomere dysfunction within 3 h. Since telomere dysfunction in other systems is known to activate ATM (ataxia telangiectasia mutated)-mediated DNA damage response (DDR) signaling pathways, we investigated the role of ATM-mediated DDR signaling in AR-inactivated prostate cancer cells. Indeed, the induction of telomere dysfunction in cells treated with AR-antagonists (Casodex or MDV3100) or AR-siRNA was associated with a dramatic increase in phosphorylation (activation) of ATM and its downstream effector Chk2 and the presenceof phosphorylated ATM at telomeres, indicating activation of DDR signaling at telomeres. Moreover, Casodex washout led to the reversal of telomere dysfunction, indicating repair of damaged telomeres. ATM inhibitor blocked ATM phosphorylation, induced PARP cleavage, abrogated cell cycle checkpoint activation and attenuated the formation of γH2AX foci at telomeres in AR-inactivated cells, suggesting that ATM inhibitor induces apoptosis in AR-inactivated cells by blocking the repair of damaged DNA at telomeres. Finally, colony formation assay revealed a dramatic decrease in the survival of cells co-treated with Casodex and ATM inhibitor as compared with those treated with either Casodex or ATM inhibitor alone. These observations indicate that inhibitors of DDR signaling pathways may offer a unique opportunity to enhance the potency of AR-targeted therapies for the treatment of androgen-sensitive as well as castration-resistant prostate cancer.

  7. ATM mediates spermidine-induced mitophagy via PINK1 and Parkin regulation in human fibroblasts.

    Science.gov (United States)

    Qi, Yongmei; Qiu, Qian; Gu, Xueyan; Tian, Yihong; Zhang, Yingmei

    2016-04-19

    The ATM (ataxia telangiectasia mutated) protein has recently been proposed to play critical roles in the response to mitochondrial dysfunction by initiating mitophagy. Here, we have used ATM-proficient GM00637 cells and ATM-deficient GM05849 cells to investigate the mitophagic effect of spermidine and to elucidate the role of ATM in spermdine-induced mitophagy. Our results indicate that spermidine induces mitophagy by eliciting mitochondrial depolarization, which triggers the formation of mitophagosomes and mitolysosomes, thereby promoting the accumulation of PINK1 and translocation of Parkin to damaged mitochondria, finally leading to the decreased mitochondrial mass in GM00637 cells. However, in GM05849 cells or GM00637 cells pretreated with the ATM kinase inhibitor KU55933, the expression of full-length PINK1 and the translocation of Parkin are blocked, and the colocalization of Parkin with either LC3 or PINK1 is disrupted. These results suggest that ATM drives the initiation of the mitophagic cascade. Our study demonstrates that spermidine induces mitophagy through ATM-dependent activation of the PINK1/Parkin pathway. These findings underscore the importance of a mitophagy regulatory network of ATM and PINK1/Parkin and elucidate a novel mechanism by which ATM influences spermidine-induced mitophagy.

  8. ABR反应器的水力特征研究%Study on Hydraulic Characteristics of ABR Reactor

    Institute of Scientific and Technical Information of China (English)

    沈耀良; 赵丹; 王承武; 王惠民

    2003-01-01

    采用LiCl示踪法对厌氧折流板反应器(ABR)在不同条件下的水力特征进行了研究.结果表明,ABR是一种各格室趋于CSTR流态而整体趋于推流流态的复合流态反应器.进水有机物浓度及HRT对水力流态均有影响,而前者为主要因素.进水有机物浓度越高则各格室的混合流态越好,ABR可在较低的上升流速下运行.当各格室去除有机物量相同时,HRT越长则其混合流态越趋于CSTR流态.进水底物浓度较低时,反应器的分格数宜控制在3~4格;进水底物浓度较高时,宜将分格数控制在6~8格.

  9. Increased oxidative stress in AOA3 cells disturbs ATM-dependent DNA damage responses.

    Science.gov (United States)

    Kobayashi, Junya; Saito, Yuichiro; Okui, Michiyo; Miwa, Noriko; Komatsu, Kenshi

    2015-04-01

    Ataxia telangiectasia (AT) is caused by a mutation in the ataxia-telangiectasia-mutated (ATM) gene; the condition is associated with hyper-radiosensitivity, abnormal cell-cycle checkpoints, and genomic instability. AT patients also show cerebellar ataxia, possibly due to reactive oxygen species (ROS) sensitivity in neural cells. The ATM protein is a key regulator of the DNA damage response. Recently, several AT-like disorders have been reported. The genes responsible for them are predicted to encode proteins that interact with ATM in the DNA-damage response. Ataxia with oculomotor apraxia types 1-3 (AOA1, 2, and 3) result in a neurodegenerative and cellular phenotype similar to AT; however, the basis of this phenotypic similarity is unclear. Here, we show that the cells of AOA3 patients display aberrant ATM-dependent phosphorylation and apoptosis following γ-irradiation. The ATM-dependent response to H2O2 treatment was abrogated in AOA3 cells. Furthermore, AOA3 cells had reduced ATM activity. Our results suggest that the attenuated ATM-related response is caused by an increase in endogenous ROS in AOA3 cells. Pretreatment of cells with pyocyanin, which induces endogenous ROS production, abolished the ATM-dependent response. Moreover, AOA3 cells had decreased homologous recombination (HR) activity, and pyocyanin pretreatment reduced HR activity in HeLa cells. These results indicate that excess endogenous ROS represses the ATM-dependent cellular response and HR repair in AOA3 cells. Since the ATM-dependent cell-cycle checkpoint is an important block to carcinogenesis, such inactivation of ATM may lead to tumorigenesis as well as neurodegeneration.

  10. Design of Bank ATM Machine Based on VHDL%基于 VHDL 的模拟自动取款机设计

    Institute of Scientific and Technical Information of China (English)

    赵杰

    2015-01-01

    This project is based on the VHDL and adopts top‐down design approach ,which simulates the basic func‐tionality of automatic teller machine(ATM ) .Quartus Ⅱ is used for the whole project ,which greatly saves the hardware re‐sources and shortens design cycles .It is relative independent to divide ATM into module partition .According to the basic principle of ATM ,the design divides the modules into the identify module ,the information module ,the password authentica‐tion module ,the service selection module ,the query module ,the modify password module ,and so on .Each module is de‐scribed by VHDL .All the modules and top‐level entity are simulated and debugged in Quartus Ⅱ .By virtue of module in‐stantiate ,top‐level file is created from each module of the corresponding produce components ,and achieves the basic func‐tions of the bank ATM machine through the software simulation .%以QuartusⅡ为开发环境、VHDL为描述语言,采用自顶向下的设计方法,对自动取款机的基本功能进行设计并仿真。自动取款机模块的设计具有相对独立性,可以根据 ATM 机的基本工作流程,将系统划分为识别模块、信息模块、密码验证模块、业务选择模块、取款模块、查询模块和密码修改模块等模块,依次对各模块进行语言描述、编译、仿真和调试。顶层文件设计采用元件例化的方完成,并进行硬件测试。

  11. PEATE automático em recém nascidos de risco: estudo da sensibilidade e especificidade Automatic ABR in newborns risk: study of sensitivity and specificity

    Directory of Open Access Journals (Sweden)

    Rosanna Mariangela Giaffredo Angrisani

    2012-04-01

    Full Text Available OBJETIVO: verificar a sensibilidade e especificidade do teste de potencial evocado auditivo de tronco encefálico em equipamento automático (PEATEa, comparando-o ao teste de potencial evocado auditivo de tronco encefálico em equipamento diagnóstico (PEATE em um programa de triagem auditiva neonatal em neonatos de risco. MÉTODO: foram avaliados 186 neonatos, 83 nascidos a termo e 103 pré-termo, sendo 88 do sexo masculino e 98 feminino. A triagem constou de emissões otoacústicas evocadas por estímulos transientes (EOAT, PEATEa e ao PEATE na mesma semana. RESULTADOS: dos 186 neonatos avaliados, 156 (83,9% apresentaram audição normal. A perda condutiva foi encontrada em 9 neonatos (4,8%,sendo 7 bilaterais e 2 unilaterais. A perda auditiva coclear foi observada em 5 neonatos (2,7% sendo um unilateral. Alteração central foi obtida em 11 neonatos (5,9% e um neonato foi diagnosticado como espectro da neuropatia auditiva -ENA(0,5%.Em 4 casos houve atraso maturacional na avaliação inicial com normalização das respostas no mês seguinte Comparando-se os resultados do PEATEa com o PEATE, observou-se alta sensibilidade ( superior a 99% para identificação de perda coclear,condutiva, central, atraso maturacional e ENA .A especificidade do PEATEa foi de 100% para ENA, mediana para perda coclear (75% na OD e 60% na OE, e para alterações centrais (54,5%OD e 63,6% OE. Para identificação de perdas condutivas (inferior a 43%. CONCLUSÃO: o PEATEa foi eficaz na identificação das neuropatias auditivas com elevada especificidade e sensibilidade. Contudo, falsos negativos foram observados para perdas cocleares, condutivas, para alterações centrais e atraso maturacional.PURPOSE: to study the sensitivity and specificity of automatic ABR in comparison to diagnostic ABR of newborns under risk in a neonatal hearing screening program. METHOD: one hundred and eighty six neonates were evaluated, 83 born at term and 103 were pre terms, 88 male and 98

  12. Gene cloning and function analysis of ABP9 protein which specifically binds to ABRE2 motif of maize Cat1 gene

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A cDNA library was constructed using mRNA extracted from 17 days post-pollination (dpp) maize embryos and was screened by employing a yeast one-hybrid system for proteins specifically interacting with ABRE2 motif of maize Cat1 gene. Three truncated overlapping positive clones designated ABP9 were obtained and the full-length cDNA was isolated by 5′ RACE. Searching the database revealed that ABP9 protein belongs to a bZIP-type transcription factor family. ABP9 protein specifically binds to ABRE2 motif and activates the expression of downstream reporter gene in yeast cells. Our results strongly suggest that the ABP9 protein functions as a transcription activator.

  13. Loss of ATM kinase activity leads to embryonic lethality in mice

    DEFF Research Database (Denmark)

    Daniel, J.A.; Pellegrini, M.; Filsuf, D.

    2012-01-01

    Ataxia telangiectasia (A-T) mutated (ATM) is a key deoxyribonucleic acid (DNA) damage signaling kinase that regulates DNA repair, cell cycle checkpoints, and apoptosis. The majority of patients with A-T, a cancer-prone neurodegenerative disease, present with null mutations in Atm. To determine...

  14. Using attack-defense trees to analyze threats and countermeasures in an ATM: a case study

    NARCIS (Netherlands)

    Fraile, Marlon; Ford, Margaret; Gadyatskaya, Olga; Kumar, Rajesh; Stoelinga, Mariëlle; Trujillo-Rasua, Rolando

    2016-01-01

    Securing automated teller machines (ATMs), as critical and complex infrastructure, requires a precise understanding of the associated threats. This paper reports on the application of attack-defense trees to model and analyze the security of ATMs.We capture the most dangerous multi-stage attack scen

  15. Differential roles of ATM- and Chk2-mediated phosphorylations of Hdmx in response to DNA damage.

    Science.gov (United States)

    Pereg, Yaron; Lam, Suzanne; Teunisse, Amina; Biton, Sharon; Meulmeester, Erik; Mittelman, Leonid; Buscemi, Giacomo; Okamoto, Koji; Taya, Yoichi; Shiloh, Yosef; Jochemsen, Aart G

    2006-09-01

    The p53 tumor suppressor plays a major role in maintaining genomic stability. Its activation and stabilization in response to double strand breaks (DSBs) in DNA are regulated primarily by the ATM protein kinase. ATM mediates several posttranslational modifications on p53 itself, as well as phosphorylation of p53's essential inhibitors, Hdm2 and Hdmx. Recently we showed that ATM- and Hdm2-dependent ubiquitination and subsequent degradation of Hdmx following DSB induction are mediated by phosphorylation of Hdmx on S403, S367, and S342, with S403 being targeted directly by ATM. Here we show that S367 phosphorylation is mediated by the Chk2 protein kinase, a downstream kinase of ATM. This phosphorylation, which is important for subsequent Hdmx ubiquitination and degradation, creates a binding site for 14-3-3 proteins which controls nuclear accumulation of Hdmx following DSBs. Phosphorylation of S342 also contributed to optimal 14-3-3 interaction and nuclear accumulation of Hdmx, but phosphorylation of S403 did not. Our data indicate that binding of a 14-3-3 dimer and subsequent nuclear accumulation are essential steps toward degradation of p53's inhibitor, Hdmx, in response to DNA damage. These results demonstrate a sophisticated control by ATM of a target protein, Hdmx, which itself is one of several ATM targets in the ATM-p53 axis of the DNA damage response.

  16. ATM protein is located on presynaptic vesicles and its deficit leads to failures in synaptic plasticity.

    Science.gov (United States)

    Vail, Graham; Cheng, Aifang; Han, Yu Ray; Zhao, Teng; Du, Shengwang; Loy, Michael M T; Herrup, Karl; Plummer, Mark R

    2016-07-01

    Ataxia telangiectasia is a multisystemic disorder that includes a devastating neurodegeneration phenotype. The ATM (ataxia-telangiectasia mutated) protein is well-known for its role in the DNA damage response, yet ATM is also found in association with cytoplasmic vesicular structures: endosomes and lysosomes, as well as neuronal synaptic vesicles. In keeping with this latter association, electrical stimulation of the Schaffer collateral pathway in hippocampal slices from ATM-deficient mice does not elicit normal long-term potentiation (LTP). The current study was undertaken to assess the nature of this deficit. Theta burst-induced LTP was reduced in Atm(-/-) animals, with the reduction most pronounced at burst stimuli that included 6 or greater trains. To assess whether the deficit was associated with a pre- or postsynaptic failure, we analyzed paired-pulse facilitation and found that it too was significantly reduced in Atm(-/-) mice. This indicates a deficit in presynaptic function. As further evidence that these synaptic effects of ATM deficiency were presynaptic, we used stochastic optical reconstruction microscopy. Three-dimensional reconstruction revealed that ATM is significantly more closely associated with Piccolo (a presynaptic marker) than with Homer1 (a postsynaptic marker). These results underline how, in addition to its nuclear functions, ATM plays an important functional role in the neuronal synapse where it participates in the regulation of presynaptic vesicle physiology.

  17. Neurons in Vulnerable Regions of the Alzheimer's Disease Brain Display Reduced ATM Signaling.

    Science.gov (United States)

    Shen, Xuting; Chen, Jianmin; Li, Jiali; Kofler, Julia; Herrup, Karl

    2016-01-01

    Ataxia telangiectasia (A-T) is a multisystemic disease caused by mutations in the ATM (A-T mutated) gene. It strikes before 5 years of age and leads to dysfunctions in many tissues, including the CNS, where it leads to neurodegeneration, primarily in cerebellum. Alzheimer's disease (AD), by contrast, is a largely sporadic neurodegenerative disorder that rarely strikes before the 7th decade of life with primary neuronal losses in hippocampus, frontal cortex, and certain subcortical nuclei. Despite these differences, we present data supporting the hypothesis that a failure of ATM signaling is involved in the neuronal death in individuals with AD. In both, partially ATM-deficient mice and AD mouse models, neurons show evidence for a loss of ATM. In human AD, three independent indices of reduced ATM function-nuclear translocation of histone deacetylase 4, trimethylation of histone H3, and the presence of cell cycle activity-appear coordinately in neurons in regions where degeneration is prevalent. These same neurons also show reduced ATM protein levels. And though they represent only a fraction of the total neurons in each affected region, their numbers significantly correlate with disease stage. This previously unknown role for the ATM kinase in AD pathogenesis suggests that the failure of ATM function may be an important contributor to the death of neurons in AD individuals.

  18. Involvement of ATM in homologous recombination after end resection and RAD51 nucleofilament formation.

    Science.gov (United States)

    Bakr, A; Oing, C; Köcher, S; Borgmann, K; Dornreiter, I; Petersen, C; Dikomey, E; Mansour, W Y

    2015-03-31

    Ataxia-telangiectasia mutated (ATM) is needed for the initiation of the double-strand break (DSB) repair by homologous recombination (HR). ATM triggers DSB end resection by stimulating the nucleolytic activity of CtIP and MRE11 to generate 3'-ssDNA overhangs, followed by RPA loading and RAD51 nucleofilament formation. Here we show for the first time that ATM is also needed for later steps in HR after RAD51 nucleofilament formation. Inhibition of ATM after completion of end resection did not affect RAD51 nucleofilament formation, but resulted in HR deficiency as evidenced by (i) an increase in the number of residual RAD51/γH2AX foci in both S and G2 cells, (ii) the decrease in HR efficiency as detected by HR repair substrate (pGC), (iii) a reduced SCE rate and (iv) the radiosensitization of cells by PARP inhibition. This newly described role for ATM was found to be dispensable in heterochromatin-associated DSB repair, as KAP1-depletion did not alleviate the HR-deficiency when ATM was inhibited after end resection. Moreover, we demonstrated that ATR can partly compensate for the deficiency in early, but not in later, steps of HR upon ATM inhibition. Taken together, we describe here for the first time that ATM is needed not only for the initiation but also for the completion of HR.

  19. Conditional abrogation of Atm in osteoclasts extends osteoclast lifespan and results in reduced bone mass.

    Science.gov (United States)

    Hirozane, Toru; Tohmonda, Takahide; Yoda, Masaki; Shimoda, Masayuki; Kanai, Yae; Matsumoto, Morio; Morioka, Hideo; Nakamura, Masaya; Horiuchi, Keisuke

    2016-09-28

    Ataxia-telangiectasia mutated (ATM) kinase is a central component involved in the signal transduction of the DNA damage response (DDR) and thus plays a critical role in the maintenance of genomic integrity. Although the primary functions of ATM are associated with the DDR, emerging data suggest that ATM has many additional roles that are not directly related to the DDR, including the regulation of oxidative stress signaling, insulin sensitivity, mitochondrial homeostasis, and lymphocyte development. Patients and mice lacking ATM exhibit growth retardation and lower bone mass; however, the mechanisms underlying the skeletal defects are not fully understood. In the present study, we generated mutant mice in which ATM is specifically inactivated in osteoclasts. The mutant mice did not exhibit apparent developmental defects but showed reduced bone mass due to increased osteoclastic bone resorption. Osteoclasts lacking ATM were more resistant to apoptosis and showed a prolonged lifespan compared to the controls. Notably, the inactivation of ATM in osteoclasts resulted in enhanced NF-κB signaling and an increase in the expression of NF-κB-targeted genes. The present study reveals a novel function for ATM in regulating bone metabolism by suppressing the lifespan of osteoclasts and osteoclast-mediated bone resorption.

  20. Development of a cell-based, high-throughput screening assay for ATM kinase inhibitors.

    Science.gov (United States)

    Guo, Kexiao; Shelat, Anang A; Guy, R Kiplin; Kastan, Michael B

    2014-04-01

    The ATM (ataxia-telangiectasia, mutated) protein kinase is a major regulator of cellular responses to DNA double-strand breaks (DSBs), DNA lesions that can be caused by ionizing irradiation (IR), oxidative damage, or exposure to certain chemical agents. In response to DSBs, the ATM kinase is activated and subsequently phosphorylates numerous downstream substrates, including p53, Chk2, BRCA1, and KAP1, which affect processes such as cell cycle progression and DNA repair. Numerous studies have demonstrated that loss of ATM function results in enhanced sensitivity to ionizing irradiation in clinically relevant dose ranges, suggesting that ATM kinase is an attractive therapeutic target for enhancing tumor cell kill with radiotherapy. Previously identified small-molecule ATM kinase inhibitors, such as CP466722 and Ku55933, were identified using in vitro kinase assays carried out with recombinant ATM kinase isolated from mammalian cells. Since it has not been feasible to express full-length recombinant ATM in bacterial or baculovirus systems, a robust in vitro screening tool has been lacking. We have developed a cell-based assay that is robust, straightforward, and sensitive. Using this high-throughput assay, we screened more than 7000 compounds and discovered additional small molecules that inhibit the ATM kinase and further validated these hits by secondary assays.

  1. Absence of ERK5/MAPK7 delays tumorigenesis in Atm-/- mice.

    Science.gov (United States)

    Granados-Jaén, Alba; Angulo-Ibáñez, Maria; Rovira-Clavé, Xavier; Gamez, Celina Paola Vasquez; Soriano, Francesc X; Reina, Manuel; Espel, Enric

    2016-11-15

    Ataxia-telangiectasia mutated (ATM) is a cell cycle checkpoint kinase that upon activation by DNA damage leads to cell cycle arrest and DNA repair or apoptosis. The absence of Atm or the occurrence of loss-of-function mutations in Atm predisposes to tumorigenesis. MAPK7 has been implicated in numerous types of cancer with pro-survival and pro-growth roles in tumor cells, but its functional relation with tumor suppressors is not clear. In this study, we show that absence of MAPK7 delays death due to spontaneous tumor development in Atm-/- mice. Compared with Atm-/- thymocytes, Mapk7-/-Atm-/- thymocytes exhibited an improved response to DNA damage (increased phosphorylation of H2AX) and a restored apoptotic response after treatment of mice with ionizing radiation. These findings define an antagonistic function of ATM and MAPK7 in the thymocyte response to DNA damage, and suggest that the lack of MAPK7 inhibits thymic lymphoma growth in Atm-/- mice by partially restoring the DNA damage response in thymocytes.

  2. Missense Variants in ATM in 26,101 Breast Cancer Cases and 29,842 Controls

    DEFF Research Database (Denmark)

    Fletcher, O.; Johnson, N.; Silva, Andreá Lema Da;

    2010-01-01

    Background: Truncating mutations in ATM have been shown to increase the risk of breast cancer but the effect of missense variants remains contentious. Methods: We have genotyped five polymorphic (minor allele frequency, 0.9-2.6%) missense single nucleotide polymorphisms (SNP) in ATM (S49C, S707P,...

  3. A Framework for Applying Asynchronous Transfer Mode (ATM) Technology to Command, Control and Communications Systems

    Science.gov (United States)

    1994-06-01

    available they can be implemented in ATM LANs by using different reserved signaling channels ( Biagioni , Cooper, and Sansom, 1993, p. 35). An argument...conference, San Francisco, California, 12-14 April 1994. Biagioni , E., Cooper, E. and Sansom, R., "Designing a Practical ATM LAN", IEEE Network, v. 7, March

  4. The effects of mobile ATM switches on PNNI peer group operation

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, L.; Sholander, P.; Tolendino, L.

    1997-04-01

    This contribution discusses why, and how, mobile networks and mobile switches might be discussed during Phase 1 of the WATM standards process. Next, it reviews mobile routers within Mobile IP. That IP mobility architecture may not apply to the proposed mobile ATM switches. Finally, it discusses problems with PNNI peer group formation and operation when mobile ATM switches are present.

  5. Mitochondria are required for ATM activation by extranuclear oxidative stress in cultured human hepatoblastoma cell line Hep G2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Akinori, E-mail: morita@tokushima-u.ac.jp [Department of Radiation Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan); Department of Radiological Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509 (Japan); Tanimoto, Keiji; Murakami, Tomoki; Morinaga, Takeshi [Department of Radiation Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan); Hosoi, Yoshio, E-mail: hosoi@med.tohoku.ac.jp [Department of Radiation Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan); Department of Radiation Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575 (Japan)

    2014-01-24

    Highlights: • Oxidative ATM activation can occur in the absence of nuclear DNA damage response. • The oxidized Hep G2 cells were subjected to subcellular fractionation. • The obtained results suggest that the ATM activation occurs in mitochondria. • ATM failed to respond to oxidative stress in mitochondria-depleted Hep G2 cells. • Mitochondria are required for the oxidative activation of ATM. - Abstract: Ataxia–telangiectasia mutated (ATM) is a serine/threonine protein kinase that plays a central role in DNA damage response (DDR). A recent study reported that oxidized ATM can be active in the absence of DDR. However, the issue of where ATM is activated by oxidative stress remains unclear. Regarding the localization of ATM, two possible locations, namely, mitochondria and peroxisomes are possible. We report herein that ATM can be activated when exposed to hydrogen peroxide without inducing nuclear DDR in Hep G2 cells, and the oxidized cells could be subjected to subcellular fractionation. The first detergent-based fractionation experiment revealed that active, phosphorylated ATM was located in the second fraction, which also contained both mitochondria and peroxisomes. An alternative fractionation method involving homogenization and differential centrifugation, which permits the light membrane fraction containing peroxisomes to be produced, but not mitochondria, revealed that the light membrane fraction contained only traces of ATM. In contrast, the heavy membrane fraction, which mainly contained mitochondrial components, was enriched in ATM and active ATM, suggesting that the oxidative activation of ATM occurs in mitochondria and not in peroxisomes. In Rho 0-Hep G2 cells, which lack mitochondrial DNA and functional mitochondria, ATM failed to respond to hydrogen peroxide, indicating that mitochondria are required for the oxidative activation of ATM. These findings strongly suggest that ATM can be activated in response to oxidative stress in mitochondria

  6. Wireless optical communication for FDDI, fast Ethernet, and ATM connectivity

    Science.gov (United States)

    Medved, David B.; Azancot, Yossi

    1995-09-01

    The bandwidth limitations of spread spectrum RF technology are easily removed by use of optical carriers. A variety of wireless connectivity system applications have been achieved using IR LED (not laser) at data rates up to 125 Mbps and with low frequency corners below 100 Kbps. By use of the UWINTM principle it is possible to achieve wireless communications which are protocol independent. Thus, an urgent installation which must serve today as an Ethernet or Token Ring wireless connection in the future can be used at FDDI, Fast Ethernet, 100 VG Anylan or ATM without any modification to the original installation. In this paper we describe three separate applications of this principle where there are significant trade-offs between range and angular coverage.

  7. ATM Kinase Is Required for Telomere Elongation in Mouse and Human Cells

    Directory of Open Access Journals (Sweden)

    Stella Suyong Lee

    2015-11-01

    Full Text Available Short telomeres induce a DNA damage response, senescence, and apoptosis, thus maintaining telomere length equilibrium is essential for cell viability. Telomerase addition of telomere repeats is tightly regulated in cells. To probe pathways that regulate telomere addition, we developed the ADDIT assay to measure new telomere addition at a single telomere in vivo. Sequence analysis showed telomerase-specific addition of repeats onto a new telomere occurred in just 48 hr. Using the ADDIT assay, we found that ATM is required for addition of new repeats onto telomeres in mouse cells. Evaluation of bulk telomeres, in both human and mouse cells, showed that blocking ATM inhibited telomere elongation. Finally, the activation of ATM through the inhibition of PARP1 resulted in increased telomere elongation, supporting the central role of the ATM pathway in regulating telomere addition. Understanding this role of ATM may yield new areas for possible therapeutic intervention in telomere-mediated disease.

  8. New mutations in the ATM gene and clinical data of 25 AT patients.

    Science.gov (United States)

    Demuth, Ilja; Dutrannoy, Véronique; Marques, Wilson; Neitzel, Heidemarie; Schindler, Detlev; Dimova, Petja S; Chrzanowska, Krystyna H; Bojinova, Veneta; Gregorek, Hanna; Graul-Neumann, Luitgard M; von Moers, Arpad; Schulze, Ilka; Nicke, Marion; Bora, Elcin; Cankaya, Tufan; Oláh, Éva; Kiss, Csongor; Bessenyei, Beáta; Szakszon, Katalin; Gruber-Sedlmayr, Ursula; Kroisel, Peter Michael; Sodia, Sigrun; Goecke, Timm O; Dörk, Thilo; Digweed, Martin; Sperling, Karl; de Sá, Joaquim; Lourenco, Charles Marques; Varon, Raymonda

    2011-11-01

    Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar degeneration, immunodeficiency, oculocutaneous telangiectasias, chromosomal instability, radiosensitivity, and cancer predisposition. The gene mutated in the patients, ATM, encodes a member of the phosphatidylinositol 3-kinase family proteins. The ATM protein has a key role in the cellular response to DNA damage. Truncating and splice site mutations in ATM have been found in most patients with the classical AT phenotype. Here we report of our extensive ATM mutation screening on 25 AT patients from 19 families of different ethnic origin. Previously unknown mutations were identified in six patients including a new homozygous missense mutation, c.8110T>C (p.Cys2704Arg), in a severely affected patient. Comprehensive clinical data are presented for all patients described here along with data on ATM function generated by analysis of cell lines established from a subset of the patients.

  9. DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds.

    Science.gov (United States)

    Waterworth, Wanda M; Footitt, Steven; Bray, Clifford M; Finch-Savage, William E; West, Christopher E

    2016-08-23

    Genome integrity is crucial for cellular survival and the faithful transmission of genetic information. The eukaryotic cellular response to DNA damage is orchestrated by the DNA damage checkpoint kinases ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological roles for these sensor kinases in control of seed germination. We demonstrate that double-strand breaks (DSBs) are rate-limiting for germination. We identify that desiccation tolerant seeds exhibit a striking transcriptional DSB damage response during germination, indicative of high levels of genotoxic stress, which is induced following maturation drying and quiescence. Mutant atr and atm seeds are highly resistant to aging, establishing ATM and ATR as determinants of seed viability. In response to aging, ATM delays germination, whereas atm mutant seeds germinate with extensive chromosomal abnormalities. This identifies ATM as a major factor that controls germination in aged seeds, integrating progression through germination with surveillance of genome integrity. Mechanistically, ATM functions through control of DNA replication in imbibing seeds. ATM signaling is mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED 5, an essential factor required for the aging-induced delay to germination. In the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR, with changes in dormancy and germination potential modulated by environmental signals, including temperature and soil moisture. Collectively, our findings reveal physiological functions for these sensor kinases in linking genome integrity to germination, thereby influencing seed quality, crucial for plant survival in the natural environment and sustainable crop production.

  10. Characteristics and hydrogen production efficiency in anaerobic baffled reactor (ABR) system%ABR发酵系统运行特性及产氢效能研究

    Institute of Scientific and Technical Information of China (English)

    郑国臣; 李建政; 昌盛; 张照韩; 官涤; 金羽; 郭静波; 卢海凤

    2013-01-01

    To solve the continuous-flow stirred tank reactor (CSTR) hydrogen system has low efficient and waste energy,a 3-compartment anaerobic baffled reactor (ABR), with an effective volume of 27.8L, was adapted and its performing characteristics and hydrogen production efficiency were investigated,using diluted molasses as the material. ABR had higher efficiency and lower energy consumption comparing with CSTR. ABR achieved stable ethanol type fermentation within 26d with 35℃ and initial COD of 5000mg/L, and the specific hydrogen production rate was 0.13L/(gMLVSSd) while that of CSTR under the same conditions was 0.06L/g MLVSS-d. Results showed that ABR was an ideal facility for hydrogen production from organic wastewater fermentation.%为解决连续流搅拌槽式反应器(CSTR)发酵制氢系统存在的不足,如单位基质氢气转化率低、因搅拌带来的耗能,抗负荷冲击能力不强等问题,开展了厌氧折流板反应器(ABR)发酵产氢的研究.结果表明,在35℃和进水COD 5000mg/L等条件下,ABR系统可在26d达到乙醇型发酵,其比产氢速率为0.13L/(gMLVSS.d),而在同样条件下,CSTR达到乙醇型发酵后,比产氢速率仅为0.06L/(gMLVSS.d).ABR通过生物相的分离,使产氢系统梯级利用有机物并达到深度产氢的目的.与CSTR相比,ABR具有较高的产氢活性、较低能源消耗等优点,是一种较为理想的有机废水发酵制氢反应设备.

  11. Abréviations

    Directory of Open Access Journals (Sweden)

    2013-06-01

    Full Text Available AREU Afghanistan Research and Evaluation Unit BCS Badloon Consultancy and Civil Society BHC Basic Health Clinic BPRM Bureau of Populations, Movement and Refugees CSO Central Statistics Organization DCDA Dehsabz-Barikab City Development Authority IDKA Independent Directorate of Kuchi Affairs IDLG Independent Directorate of Local Governance IDP Internally Displaced Persons IOM International Organization for Migration ...

  12. Abréviations

    OpenAIRE

    2014-01-01

    S.T. : Straits Times, Singapour N.S.T. : New Straits Times, Kuala Lumpur F.T. : Financial Times ARB : Asian Research Bulletin AWSJ : Asian Wall Street Journal BIES : Bulletin of Indonesian Economic Studies FEER : Far Eastern Economic Review Les ouvrages, travaux et articles numérotés entre parenthèses dans les notes de bas de page renvoient à la classification bibliographique (nos 1 à 740, pp. 225-258). Statistiques Les statistiques présentées dans l'ouvrage reprennent les données officielles...

  13. Somatic inactivation of ATM in hematopoietic cells predisposes mice to cyclin D3 dependent T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Ehrlich, Lori A; Yang-Iott, Katherine; DeMicco, Amy; Bassing, Craig H

    2015-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of immature T cells that exhibits heterogeneity of oncogenic lesions, providing an obstacle for development of more effective and less toxic therapies. Inherited deficiency of ATM, a regulator of the cellular DNA damage response, predisposes young humans and mice to T-ALLs with clonal chromosome translocations. While acquired ATM mutation or deletion occurs in pediatric T-ALLs, the role of somatic ATM alterations in T-ALL pathogenesis remains unknown. We demonstrate here that somatic Atm inactivation in haematopoietic cells starting as these cells differentiate in utero predisposes mice to T-ALL at similar young ages and harboring analogous translocations as germline Atm-deficient mice. However, some T-ALLs from haematopoietic cell specific deletion of Atm were of more mature thymocytes, revealing that the developmental timing and celluar origin of Atm inactivation influences the phenotype of ATM-deficient T-ALLs. Although it has been hypothesized that ATM suppresses cancer by preventing deletion and inactivation of TP53, we find that Atm inhibits T-ALL independent of Tp53 deletion. Finally, we demonstrate that the Cyclin D3 protein that drives immature T cell proliferation is essential for transformation of Atm-deficient thymocytes. Our study establishes a pre-clinical model for pediatric T-ALLs with acquired ATM inactivation and identifies the cell cycle machinery as a therapeutic target for this aggressive childhood T-ALL subtype.

  14. Assessment of p53 and ATM functionality in chronic lymphocytic leukemia by multiplex ligation-dependent probe amplification.

    Science.gov (United States)

    te Raa, G D; Moerland, P D; Leeksma, A C; Derks, I A; Yigittop, H; Laddach, N; Loden-van Straaten, M; Navrkalova, V; Trbusek, M; Luijks, D M; Zenz, T; Skowronska, A; Hoogendoorn, M; Stankovic, T; van Oers, M H; Eldering, E; Kater, A P

    2015-08-06

    The ATM-p53 DNA-damage response (DDR) pathway has a crucial role in chemoresistance in CLL, as indicated by the adverse prognostic impact of genetic aberrations of TP53 and ATM. Identifying and distinguishing TP53 and ATM functional defects has become relevant as epigenetic and posttranscriptional dysregulation of the ATM/p53 axis is increasingly being recognized as the underlying cause of chemoresistance. Also, specific treatments sensitizing TP53- or ATM-deficient CLL cells are emerging. We therefore developed a new ATM-p53 functional assay with the aim to (i) identify and (ii) distinguish abnormalities of TP53 versus ATM and (iii) enable the identification of additional defects in the ATM-p53 pathway. Reversed transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) was used to measure ATM and/or p53-dependent genes at the RNA level following DNA damage using irradiation. Here, we showed that this assay is able to identify and distinguish three subgroups of CLL tumors (i.e., TP53-defective, ATM-defective and WT) and is also able to detect additional samples with a defective DDR, without molecular aberrations in TP53 and/or ATM. These findings make the ATM-p53 RT-MLPA functional assay a promising prognostic tool for predicting treatment responses in CLL.

  15. ATM-dependent phosphorylation of MEF2D promotes neuronal survival after DNA damage.

    Science.gov (United States)

    Chan, Shing Fai; Sances, Sam; Brill, Laurence M; Okamoto, Shu-Ichi; Zaidi, Rameez; McKercher, Scott R; Akhtar, Mohd W; Nakanishi, Nobuki; Lipton, Stuart A

    2014-03-26

    Mutations in the ataxia telangiectasia mutated (ATM) gene, which encodes a kinase critical for the normal DNA damage response, cause the neurodegenerative disorder ataxia-telangiectasia (AT). The substrates of ATM in the brain are poorly understood. Here we demonstrate that ATM phosphorylates and activates the transcription factor myocyte enhancer factor 2D (MEF2D), which plays a critical role in promoting survival of cerebellar granule cells. ATM associates with MEF2D after DNA damage and phosphorylates the transcription factor at four ATM consensus sites. Knockdown of endogenous MEF2D with a short-hairpin RNA (shRNA) increases sensitivity to etoposide-induced DNA damage and neuronal cell death. Interestingly, substitution of endogenous MEF2D with an shRNA-resistant phosphomimetic MEF2D mutant protects cerebellar granule cells from cell death after DNA damage, whereas an shRNA-resistant nonphosphorylatable MEF2D mutant does not. In vivo, cerebella in Mef2d knock-out mice manifest increased susceptibility to DNA damage. Together, our results show that MEF2D is a substrate for phosphorylation by ATM, thus promoting survival in response to DNA damage. Moreover, dysregulation of the ATM-MEF2D pathway may contribute to neurodegeneration in AT.

  16. Role of ataxia-telangiectasia mutated (ATM) in porcine oocyte in vitro maturation.

    Science.gov (United States)

    Lin, Zi-Li; Kim, Nam-Hyung

    2015-06-01

    Ataxia-telangiectasia mutated (ATM) is critical for the DNA damage response, cell cycle checkpoints, and apoptosis. Significant effort has focused on elucidating the relationship between ATM and other nuclear signal transducers; however, little is known about the connection between ATM and oocyte meiotic maturation. We investigated the function of ATM in porcine oocytes. ATM was expressed at all stages of oocyte maturation and localized predominantly in the nucleus. Furthermore, the ATM-specific inhibitor KU-55933 blocked porcine oocyte maturation, reducing the percentages of oocytes that underwent germinal vesicle breakdown (GVBD) and first polar body extrusion. KU-55933 also decreased the expression of DNA damage-related genes (breast cancer 1, budding uninhibited by benzimidazoles 1, and P53) and reduced the mRNA and protein levels of AKT and other cell cycle-regulated genes that are predominantly expressed during G2/M phase, including bone morphogenetic protein 15, growth differentiation factor 9, cell division cycle protein 2, cyclinB1, and AKT. KU-55933 treatment decreased the developmental potential of blastocysts following parthenogenetic activation and increased the level of apoptosis. Together, these data suggested that ATM influenced the meiotic and cytoplasmic maturation of porcine oocytes, potentially by decreasing their sensitivity to DNA strand breaks, stimulating the AKT pathway, and/or altering the expression of other maternal genes.

  17. The Relationships Between Selected Organizational Variables and ATM Technology Adoption in Campus Networking

    Science.gov (United States)

    Yao, Engui

    1998-06-01

    ATM (Asynchronous Transfer Mode) is an emerging technology in computer networking, which, in turn, is the physical media of information systems and networking/telecommunication systems. The technology provides potentiality for universities to build their networks based on the future vision of uniting voice, data, and video communications on ATM-technology-based equipment. A review of the literature revealed that minimal evidence exists to indicate whether the size, type, financial factors, and information processing maturity of a university affect a university's high-tech innovation adoptions. No research of this nature has been undertaken in the study of ATM adoption in any institutions of higher learning, nor has any research of this nature been found in other organizations, either. Such evidence is needed by university administrators, information systems managers, and LAN managers to understand their universities better, whether they have or have not adopted ATM, and to evaluate their current administrative, academic, and financial situations and current campus networking situations. The purpose of this study was to determine the relationships between ATM adoption and four organizational variables: university size, type, finances, and information processing maturity. Another purpose of the study was to identify the current status of ATM adoption in campus networking in the United States. Logistic regression was used as the statistical data analysis method. The results of the study provided evidence to show that ATM adoption in campus networking is significantly related to university size, university type, university finances, and university information processing maturity.

  18. Deregulation of mTOR signaling is involved in thymic lymphoma development in Atm-/- mice

    Energy Technology Data Exchange (ETDEWEB)

    Kuang, Xianghong; Shen, Jianjun; Wong, Paul K.Y. [Department of Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Science Park-Research Division, Park Road 1C, Smithville, TX 78957 (United States); Yan, Mingshan, E-mail: mingyan@mdanderson.org [Department of Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Science Park-Research Division, Park Road 1C, Smithville, TX 78957 (United States)

    2009-06-05

    Abnormal thymocyte development with thymic lymphomagenesis inevitably occurs in Atm-/- mice, indicating that ATM plays a pivotal role in regulating postnatal thymocyte development and preventing thymic lymphomagenesis. The mechanism for ATM controls these processes is unclear. We have shown previously that c-Myc, an oncoprotein regulated by the mammalian target of rapamycin (mTOR), is overexpressed in Atm-/- thymocytes. Here, we show that inhibition of mTOR signaling with its specific inhibitor, rapamycin, suppresses normal thymocyte DNA synthesis by downregulating 4EBP1, but not S6K, and that 4EBP1 phosphorylation and cyclin D1 expression are coordinately increased in Atm-/- thymocytes. Administration of rapamycin to Atm-/- mice attenuates elevated phospho-4EBP1, c-Myc and cyclin D1 in their thymocytes, and delays thymic lymphoma development. These results indicate that mTOR downstream effector 4EBP1 is essential for normal thymocyte proliferation, but deregulation of 4EBP1 in Atm deficiency is a major factor driving thymic lymphomagenesis in the animals.

  19. Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity

    Directory of Open Access Journals (Sweden)

    Wang Jufang

    2011-08-01

    Full Text Available Abstract Background Both epidemiological and experimental studies suggest that heterozygosity for a single gene is linked with tumorigenesis and heterozygosity for two genes increases the risk of tumor incidence. Our previous work has demonstrated that Atm/Brca1 double heterozygosity leads to higher cell transformation rate than single heterozygosity. However, the underlying mechanisms have not been fully understood yet. In the present study, a series of pathways were investigated to clarify the possible mechanisms of increased risk of tumorigenesis in Atm and Brca1 heterozygosity. Methods Wild type cells, Atm or Brca1 single heterozygous cells, and Atm/Brca1 double heterozygous cells were used to investigate DNA damage and repair, cell cycle, micronuclei, and cell transformation after photon irradiation. Results Remarkable high transformation frequency was confirmed in Atm/Brca1 double heterozygous cells compared to wild type cells. It was observed that delayed DNA damage recognition, disturbed cell cycle checkpoint, incomplete DNA repair, and increased genomic instability were involved in the biological networks. Haploinsufficiency of either ATM or BRCA1 negatively impacts these pathways. Conclusions The quantity of critical proteins such as ATM and BRCA1 plays an important role in determination of the fate of cells exposed to ionizing radiation and double heterozygosity increases the risk of tumorigenesis. These findings also benefit understanding of the individual susceptibility to tumor initiation.

  20. ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes.

    Directory of Open Access Journals (Sweden)

    Marco Barchi

    2008-05-01

    Full Text Available During meiosis in most sexually reproducing organisms, recombination forms crossovers between homologous maternal and paternal chromosomes and thereby promotes proper chromosome segregation at the first meiotic division. The number and distribution of crossovers are tightly controlled, but the factors that contribute to this control are poorly understood in most organisms, including mammals. Here we provide evidence that the ATM kinase or protein is essential for proper crossover formation in mouse spermatocytes. ATM deficiency causes multiple phenotypes in humans and mice, including gonadal atrophy. Mouse Atm-/- spermatocytes undergo apoptosis at mid-prophase of meiosis I, but Atm(-/- meiotic phenotypes are partially rescued by Spo11 heterozygosity, such that ATM-deficient spermatocytes progress to meiotic metaphase I. Strikingly, Spo11+/-Atm-/- spermatocytes are defective in forming the obligate crossover on the sex chromosomes, even though the XY pair is usually incorporated in a sex body and is transcriptionally inactivated as in normal spermatocytes. The XY crossover defect correlates with the appearance of lagging chromosomes at metaphase I, which may trigger the extensive metaphase apoptosis that is observed in these cells. In addition, control of the number and distribution of crossovers on autosomes appears to be defective in the absence of ATM because there is an increase in the total number of MLH1 foci, which mark the sites of eventual crossover formation, and because interference between MLH1 foci is perturbed. The axes of autosomes exhibit structural defects that correlate with the positions of ongoing recombination. Together, these findings indicate that ATM plays a role in both crossover control and chromosome axis integrity and further suggests that ATM is important for coordinating these features of meiotic chromosome dynamics.

  1. Reaction test revealed impaired performance at 6.0 atm abs but not at 1.9 atm abs in professional divers.

    Science.gov (United States)

    Tikkinen, Janne; Parkkola, Kai; Siimes, Martti A

    2013-01-01

    In order to evaluate the effects of ambient pressure on reaction and movement times we investigated 60 professional divers by a computerized test (Reaction Test). The experiments were carried out four times in a hyperbaric chamber: prior to pressure, at 6.0 and 1.9 atm abs and after decompression. Reaction time varied from 202 to 443 milliseconds (275 +/- 42 ms), but the individual levels remained similar. The reaction time increased between precompression and 6.0 atm abs (p abs (p abs after decompression. Ten divers had an increase of more than 1SD in the reaction time at 6.0 atm abs. The number of mistakes was small and not influenced by elevation of pressure. Further, the movement time remained unchanged throughout the experiment. We conclude that the response time increases due to ambient pressure and the increase in simple reaction time is detectable in professional divers at 6.0 atm not at 1.9 atm abs. At the same time accuracy stays constant. We speculate that our findings are caused by nitrogen narcosis in some divers.

  2. A New ATM Self-Healing Algorithm with Back-Routing Capacity

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The self-healing mechanism of ATM networks is one of the key techniques for ensuring the network survivability. Based on the consideration of the future development of ATM networks and the limitation of the former various algorithms, this paper proposed a new self-healing algorithm for ATM networks: back-routing self-healing back-routing self-healing. First, we show the basic principles about our scheme. Next, we give the concept of back-routing self-healing algorithm. Finally, we analyze the new mechanism and confirm the effectiveness and feasibility of the proposed scheme.

  3. ¡Abre los ojos! Un proyecto de mejora educativa para la prevención de drogas en adolescentes

    Directory of Open Access Journals (Sweden)

    Cecilia Mª AZORÍN ABELLÁN

    2016-01-01

    Full Text Available La Educación para la Salud (EpS es un tema transversal del currículo que adolece de propuestas didácticas novedosas para la intervención pedagógica. El objetivo del trabajo que se presenta es poner en marcha un plan de mejora para la prevención de drogadicciones en adolescentes. Para ello, se ha trabajado con un total de 142 estudiantes de 3º de Educación Secundaria Obligatoria (ESO con edades comprendidas entre los 14 y los 16 años que cursan estudios en el Instituto “Francisco Salzillo” de la localidad de Alcantarilla (Murcia. Concretamente, este artículo da luz al Proyecto ¡Abre los ojos!, que forma parte del Plan de Acción Tutorial (PAT y del Plan de Mejora para la Prevención de Drogas (PMPD propuesto desde el Departamento de Orientación. Se exponen ad hoc las actividades implementadas durante las 3 sesiones trabajadas con cada uno de los 6 grupos-clase escolarizados en este nivel. Haciendo uso de la reflexión-acción, el alumnado ha desarrollado una conciencia crítica acerca de los riesgos que entraña para la salud el consumo de drogas. Asimismo, mediante la técnica de grupos de discusión los discentes han realizado un interesante debate cuyas ideas han sido organizadas en torno a tres aspectos clave: causas por las que se empieza a consumir, cómo evitar caer en las drogas, y alternativas de ocio y tiempo libre para una vida saludable. Finalmente, se especifica la necesidad de abordar tareas de prevención en los centros educativos así como de facilitar información y de resolver las inquietudes de los jóvenes acerca de esta temática.

  4. Abacus switch: a new scalable multicast ATM switch

    Science.gov (United States)

    Chao, H. Jonathan; Park, Jin-Soo; Choe, Byeong-Seog

    1995-10-01

    This paper describes a new architecture for a scalable multicast ATM switch from a few tens to thousands of input ports. The switch, called Abacus switch, has a nonblocking memoryless switch fabric followed by small switch modules at the output ports; the switch has input and output buffers. Cell replication, cell routing, output contention resolution, and cell addressing are all performed distributedly in the Abacus switch so that it can be scaled up to thousnads input and output ports. A novel algorithm has been proposed to resolve output port contention while achieving input and output ports. A novel algorithm has been proposed to reolve output port contention while achieving input buffers sharing, fairness among the input ports, and multicast call splitting. The channel grouping concept is also adopted in the switch to reduce the hardware complexity and improve the switch's throughput. The Abacus switch has a regular structure and thus has the advantages of: 1) easy expansion, 2) relaxed synchronization for data and clock signals, and 3) building the switch fabric using existing CMOS technology.

  5. NASA's ATM Technology Demonstration-1: Integrated Concept of Arrival Operations

    Science.gov (United States)

    Baxley, Brian T.; Swenson, Harry N.; Prevot, Thomas; Callantine, Todd J.

    2012-01-01

    This paper describes operations and procedures envisioned for NASA s Air Traffic Management (ATM) Technology Demonstration #1 (ATD-1). The ATD-1 Concept of Operations (ConOps) demonstration will integrate three NASA technologies to achieve high throughput, fuel-efficient arrival operations into busy terminal airspace. They are Traffic Management Advisor with Terminal Metering (TMA-TM) for precise time-based schedules to the runway and points within the terminal area, Controller-Managed Spacing (CMS) decision support tools for terminal controllers to better manage aircraft delay using speed control, and Flight deck Interval Management (FIM) avionics and flight crew procedures to conduct airborne spacing operations. The ATD-1 concept provides de-conflicted and efficient operations of multiple arrival streams of aircraft, passing through multiple merge points, from top-of-descent (TOD) to touchdown. It also enables aircraft to conduct Optimized Profile Descents (OPDs) from en route altitude to the runway, using primarily speed control to maintain separation and schedule. The ATD-1 project is currently addressing the challenges of integrating the three technologies, and implantation into an operational environment. Goals of the ATD-1 demonstration include increasing the throughput of high-density airports, reducing controller workload, increasing efficiency of arrival operations and the frequency of trajectory-based operations, and promoting aircraft ADS-B equipage.

  6. Anomalous preservation of pure methane hydrate at 1 atm

    Science.gov (United States)

    Stern, L.A.; Circone, S.; Kirby, S.H.; Durham, W.B.

    2001-01-01

    Direct measurement of decomposition rates of pure, polycrystalline methane hydrate reveals a thermal regime where methane hydrate metastably `preserves' in bulk by as much as 75 K above its nominal equilibrium temperature (193 K at 1 atm). Rapid release of the sample pore pressure at isothermal conditions between 242 and 271 K preserves up to 93% of the hydrate for at least 24 h, reflecting the greatly suppressed rates of dissociation that characterize this regime. Subsequent warming through the H2O ice point then induces rapid and complete dissociation, allowing controlled recovery of the total expected gas yield. This behavior is in marked contrast to that exhibited by methane hydrate at both colder (193-240 K) and warmer (272-290 K) test conditions, where dissociation rates increase monotonically with increasing temperature. Anomalous preservation has potential application for successful retrieval of natural gas hydrate or hydrate-bearing sediments from remote settings, as well as for temporary low-pressure transport and storage of natural gas.

  7. Assessing the potential number of ATMs in banks, financial and credit institutions using Analytic Network Process (ANP) and Gray Clustering Analysis (GCA) Case study: between Enghelab Sq and Ferdowsi Sq- Enghelab Street of Tehran

    OpenAIRE

    H.A. Faraji Sabokbar; GH. Ashournejad; S. Rahimi; A. Farhadipoor

    2012-01-01

    Extended abstracts1- IntroductionMost organizations and financial institutions are facing with spatial decision makings. Optimum decision making affects the institutes’ success, achievement to their objectives and attracting customers. Modern banking services have evolved by the development of modern technologies. The most sensible aspect of banking services evolution is based on using the modern technologies of ATMs. The rapid growth in application of these devices could have been caused by ...

  8. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair.

    Science.gov (United States)

    Du, Fengxia; Zhang, Minjie; Li, Xiaohua; Yang, Caiyun; Meng, Hao; Wang, Dong; Chang, Shuang; Xu, Ye; Price, Brendan; Sun, Yingli

    2014-10-03

    The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair.

  9. ATM网络的配置与管理%Configuration and Management of ATM Network

    Institute of Scientific and Technical Information of China (English)

    李文芳

    2001-01-01

    The library network system is the basic construction project applied in the "211 Project" of Huazhong University of Science and Technology. This article mainly deals with the configuration method and the management of ATM network.

  10. ATM, ATR and DNA-PKcs expressions correlate to adverse clinical outcomes in epithelial ovarian cancers

    Directory of Open Access Journals (Sweden)

    Tarek M.A. Abdel-Fatah

    2014-12-01

    General significance: The data presented here provides evidence that ATM, ATR and DNA-PKcs involved in DDR are not only promising biomarkers but are also rational targets for personalized therapy in ovarian cancer.

  11. DNA double-strand breaks and ATM activation by transcription-blocking DNA lesions.

    Science.gov (United States)

    Sordet, Olivier; Nakamura, Asako J; Redon, Christophe E; Pommier, Yves

    2010-01-15

    A taxia telangiectasia mutated (ATM), the deficiency of which causes a severe neurodegenerative disease, is a crucial mediator for the DNA double-strand break (DSB) response. We recently showed that transcription-blocking topoisomerase I cleavage complexes (TOP1cc) produce DSBs related to R-loop formation and activate ATM in post-mitotic neurons and lymphocytes. Here we discuss how TOP1cc can produce transcription arrest with R-loop formation and generate DSBs that activate ATM, as well as data suggesting that those transcription-dependent DSBs tend to form at the IgH locus and at specific genomic sites. We also address the potential roles of ATM in response to transcription-blocking TOP1cc.

  12. NESDIS-Unique CrIS-ATMS Product System (NUCAPS) Cloud-Cleared Radiances

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset consists of Cloud-Cleared Radiances (CCRs) from the NOAA-Unique CrIS-ATMS Processing System (NUCAPS). NUCAPS was developed by the NOAA/NESDIS Center for...

  13. C68 from the Sulfolobus islandicus plasmid-virus pSSVx is a novel member of the AbrB-like transcription factor family

    DEFF Research Database (Denmark)

    Contursi, Patrizia; D'Ambrosio, Katia; Pirone, Luciano;

    2011-01-01

    The genetic element pSSVx from Sulfolobus islandicus, strain REY15/4, is a hybrid between a plasmid and a fusellovirus. This plasmid-virus hybrid infects several species of the hyperthermophilic acidophilic crenarchaeon Sulfolobus. The open reading frame orfc68 of pSSVx encodes a 7.7 kDa protein ...... factors, such as AbrB from Bacillus subtilis. Nevertheless, C68 constitutes a novel representative of this family because it shows several peculiar structural and functional features....

  14. Application of ATM technology to the Systems Management Department Computer Laboratory Network

    OpenAIRE

    Williams, Robert

    1996-01-01

    Approved for public release; distribution is unlimited. Since the appearance of Local Area Networks (LANs), their use and bandwidth consumption have increased considerably. Users are now seeking new technologies to satisfy their bandwidth demand. Many consider ATM as the solution to their needs. Though ATM is fairly new networking technology, it has made several strides, and is now considered a viable technology that is applicable LAN environment. However, migrating from today's shared-med...

  15. ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage

    OpenAIRE

    Chen, Lihong; Gilkes, Daniele M.; Pan, Yu; Lane, William S; Chen, Jiandong

    2005-01-01

    The p53 tumor suppressor is activated after DNA damage to maintain genomic stability and prevent transformation. Rapid activation of p53 by ionizing radiation is dependent on signaling by the ATM kinase. MDM2 and MDMX are important p53 regulators and logical targets for stress signals. We found that DNA damage induces ATM-dependent phosphorylation and degradation of MDMX. Phosphorylated MDMX is selectively bound and degraded by MDM2 preceding p53 accumulation and activation. Reduction of MDMX...

  16. Serine 249 phosphorylation by ATM protein kinase regulates hepatocyte nuclear factor-1α transactivation.

    Science.gov (United States)

    Zhao, Long; Chen, Hui; Zhan, Yi-Qun; Li, Chang-Yan; Ge, Chang-Hui; Zhang, Jian-Hong; Wang, Xiao-Hui; Yu, Miao; Yang, Xiao-Ming

    2014-07-01

    Hepatocyte nuclear factor-1 alpha (HNF1α) exerts important effects on gene expression in multiple tissues. Several studies have directly or indirectly supported the role of phosphorylation processes in the activity of HNF1α. However, the molecular mechanism of this phosphorylation remains largely unknown. Using microcapillary liquid chromatography MS/MS and biochemical assays, we identified a novel phosphorylation site in HNF1α at Ser249. We also found that the ATM protein kinase phosphorylated HNF1α at Ser249 in vitro in an ATM-dependent manner and that ATM inhibitor KU55933 treatment inhibited phosphorylation of HNF1α at Ser249 in vivo. Coimmunoprecipitation assays confirmed the association between HNF1α and ATM. Moreover, ATM enhanced HNF1α transcriptional activity in a dose-dependent manner, whereas the ATM kinase-inactive mutant did not. The use of KU55933 confirmed our observation. Compared with wild-type HNF1α, a mutation in Ser249 resulted in a pronounced decrease in HNF1α transactivation, whereas no dominant-negative effect was observed. The HNF1αSer249 mutant also exhibited normal nuclear localization but decreased DNA-binding activity. Accordingly, the functional studies of HNF1αSer249 mutant revealed a defect in glucose metabolism. Our results suggested that ATM regulates the activity of HNF1α by phosphorylation of serine 249, particularly in glucose metabolism, which provides valuable insights into the undiscovered mechanisms of ATM in the regulation of glucose homeostasis.

  17. Contribution of canonical nonhomologous end joining to chromosomal rearrangements is enhanced by ATM kinase deficiency.

    Science.gov (United States)

    Bhargava, Ragini; Carson, Caree R; Lee, Gabriella; Stark, Jeremy M

    2017-01-24

    A likely mechanism of chromosomal rearrangement formation involves joining the ends from two different chromosomal double-strand breaks (DSBs). These events could potentially be mediated by either of two end-joining (EJ) repair pathways [canonical nonhomologous end joining (C-NHEJ) or alternative end joining (ALT-EJ)], which cause distinct rearrangement junction patterns. The relative role of these EJ pathways during rearrangement formation has remained controversial. Along these lines, we have tested whether the DNA damage response mediated by the Ataxia Telangiectasia Mutated (ATM) kinase may affect the relative influence of C-NHEJ vs. ALT-EJ on rearrangement formation. We developed a reporter in mouse cells for a 0.4-Mbp deletion rearrangement that is formed by EJ between two DSBs induced by the Cas9 endonuclease. We found that disruption of the ATM kinase causes an increase in the frequency of the rearrangement as well as a shift toward rearrangement junctions that show hallmarks of C-NHEJ. Furthermore, ATM suppresses rearrangement formation in an experimental condition, in which C-NHEJ is the predominant EJ repair event (i.e., expression of the 3' exonuclease Trex2). Finally, several C-NHEJ factors are required for the increase in rearrangement frequency caused by inhibition of the ATM kinase. We also examined ATM effectors and found that H2AX shows a similar influence as ATM, whereas the influence of ATM on this rearrangement seems independent of 53BP1. We suggest that the contribution of the C-NHEJ pathway to the formation of a 0.4-Mbp deletion rearrangement is enhanced in ATM-deficient cells.

  18. ΔNp63 transcriptionally regulates ATM to control p53 Serine-15 phosphorylation

    Directory of Open Access Journals (Sweden)

    Smith Graeme

    2010-07-01

    Full Text Available Abstract Background ΔNp63α is an epithelial progenitor cell marker that maintains epidermal stem cell self-renewal capacity. Previous studies revealed that UV-damage induced p53 phosphorylation is confined to ΔNp63α-positive cells in the basal layer of human epithelium. Results We now report that phosphorylation of the p53 tumour suppressor is positively regulated by ΔNp63α in immortalised human keratinocytes. ΔNp63α depletion by RNAi reduces steady-state ATM mRNA and protein levels, and attenuates p53 Serine-15 phosphorylation. Conversely, ectopic expression of ΔNp63α in p63-null tumour cells stimulates ATM transcription and p53 Serine-15 phosphorylation. We show that ATM is a direct ΔNp63α transcriptional target and that the ΔNp63α response element localizes to the ATM promoter CCAAT sequence. Structure-function analysis revealed that the ΔNp63-specific TA2 transactivation domain mediates ATM transcription in coordination with the DNA binding and SAM domains. Conclusions Germline p63 point mutations are associated with a range of ectodermal developmental disorders, and targeted p63 deletion in the skin causes premature ageing. The ΔNp63α-ATM-p53 damage-response pathway may therefore function in epithelial development, carcinogenesis and the ageing processes.

  19. Downregulated Ku70 and ATM associated to poor prognosis in colorectal cancer among Chinese patients

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    Lu YF

    2014-10-01

    Full Text Available Yuanfang Lu,1,2 Jingyan Gao,1,3 Yuanming Lu,1 1Department of Toxicology, School of Public Health, Guilin Medical University, Guangxi, People's Republic of China; 2Department of Clinical Research Center, Affiliated 2nd Hospital of Nanjing Medical University, Nanjing, People's Republic of China; 3Department of Human Anatomy and Histo-Embryology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Background: Double-strand DNA breaks (DSBs are a key factor in carcinogenesis. The necessary repair of DSBs is pivotal in maintaining normal cell division. To address the relationship between altered expression of DSB repair of proteins Ku70 and ataxia-telangiectasia mutated (ATM in colorectal cancer (CRC, we examined the expression levels and patterns of Ku70 and ATM in CRC samples. Methods: Expression and coexpression of Ku70 and ATM were investigated by using real-time quantitative polymerase chain reaction assays and confirmed further with fluorescent immunohistochemistry in CRC and pericancerous samples from 112 Chinese patients. Results: Downexpression patterns for both Ku70 and ATM were found in the CRC samples and were significantly associated with advanced tumor node metastasis stage and decreased 5-year overall survival rate. Conclusion: Downregulated Ku70 and ATM were associated with poor disease-free survival. Loss of Ku70 and ATM expression might act as a biomarker to predict poor prognosis in patients with CRC. Keywords: DNA double-strand breaks, ataxia-telangiectasia mutated, Ku70, colorectal cancer

  20. Alteration in 5-hydroxymethylcytosine-mediated epigenetic regulation leads to Purkinje cell vulnerability in ATM deficiency.

    Science.gov (United States)

    Jiang, Dewei; Zhang, Ying; Hart, Ronald P; Chen, Jianmin; Herrup, Karl; Li, Jiali

    2015-12-01

    A long-standing mystery surrounding ataxia-telangiectasia is why it is mainly cerebellar neurons, Purkinje cells in particular, that appear vulnerable to ATM deficiency. Here we present data showing that 5-hydroxymethylcytosine (5hmC), a newly recognized epigenetic marker found at high levels in neurons, is substantially reduced in human ataxia-telangiectasia and Atm(-/-) mouse cerebellar Purkinje cells. We further show that TET1, an enzyme that converts 5-methylcytosine (5mC) to 5hmC, responds to DNA damage and manipulation of TET1 activity directly affects the DNA damage signalling and ATM-deficient neuronal cell cycle re-entry and death. Quantitative genome-wide analysis of 5hmC-containing sequences shows that in ATM deficiency there is a cerebellum- and Purkinje cell-specific shift in 5hmC enrichment in both regulatory elements and repeated sequences. Finally, we verify that TET1-mediated 5hmC production is linked to the degenerative process of Purkinje cells and behavioural deficits in Atm(-/-) mice. Taken together, the selective loss of 5hmC plays a critical role in driving Purkinje cell vulnerability in ATM deficiency.

  1. ATM-Dependent Phosphorylation of All Three Members of the MRN Complex: From Sensor to Adaptor.

    Science.gov (United States)

    Lavin, Martin F; Kozlov, Sergei; Gatei, Magtouf; Kijas, Amanda W

    2015-10-23

    The recognition, signalling and repair of DNA double strand breaks (DSB) involves the participation of a multitude of proteins and post-translational events that ensure maintenance of genome integrity. Amongst the proteins involved are several which when mutated give rise to genetic disorders characterised by chromosomal abnormalities, cancer predisposition, neurodegeneration and other pathologies. ATM (mutated in ataxia-telangiectasia (A-T) and members of the Mre11/Rad50/Nbs1 (MRN complex) play key roles in this process. The MRN complex rapidly recognises and locates to DNA DSB where it acts to recruit and assist in ATM activation. ATM, in the company of several other DNA damage response proteins, in turn phosphorylates all three members of the MRN complex to initiate downstream signalling. While ATM has hundreds of substrates, members of the MRN complex play a pivotal role in mediating the downstream signalling events that give rise to cell cycle control, DNA repair and ultimately cell survival or apoptosis. Here we focus on the interplay between ATM and the MRN complex in initiating signaling of breaks and more specifically on the adaptor role of the MRN complex in mediating ATM signalling to downstream substrates to control different cellular processes.

  2. Meeting Art with Art: Arts-Based Methods Enhance Researcher Reflexivity in Research with Mental Health Service Users.

    Science.gov (United States)

    McCaffrey, Tríona; Edwards, Jane

    2015-01-01

    This paper presents a rationale for arts-based practices in music therapy research, and provides an example of using ABR techniques in research. Arts-based materials are increasingly demonstrated to have the capacity to extend processes of reflexivity and analysis in a range of qualitative health research studies. By comparison, music therapy research studies have rarely employed arts-based methods or techniques. There is a need for more studies in music therapy that employ arts-based research to demystify and elaborate a wider range of creative approaches within music therapy inquiry. In the study described in this paper, ABR was used to reflect on the contribution of a service user in a community mental health context who participated in a focus group about his experiences of music therapy. ABR was found to offer a creative way to engage service users, and to deepen and extend the researcher's reflexivity when responding to materials created by research participants.

  3. Molecular and functional characterization of a human ATM gene analogue at Arabidopsis thaliana; Caracterisation moleculaire et Fonctionnelle d'un Homologue du gene humain ATM chez Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, V.

    2001-12-15

    The human ATM gene, whose inactivation is responsible for the human disease ataxia telangiectasia is conserved throughout the Eukaryotes and plays an important role in the cellular responses to DNA damage, in particular to DNA double-strand breaks (DSBs). Here we describe the identification of an Arabidopsis thaliana homologue of ATM (AtATM), and the molecular and cytological characterization of plants, hereafter called atm, carrying a disrupting T-DNA insertion in this gene. AtATM covers a 32 kb region on chromosome 3. The AtATM transcript has a complex structure, is 12 kb long and formed by 79 exons. The transcriptional level of AtATM is very low in all the tissues tested, and does not vary after exposure to ionizing radiations (IR). In atm plants, the protein is not detected suggesting the mutants are null. The atm mutants are partially sterile. Aberrant segregation of chromosomes during meiosis I on both male and female sides account for this sterility. However, meiotic recombination frequency is normal. Mutant plants are also hypersensitive to gamma rays and methyl methane sulfonate, but not to UV-B, pointing to a specific defect of atm mutants in the response to DNA DSBs. In plants, ionizing radiations induce a strong, rapid and transient transcriptional activation of genes involved in the cellular response to or the repair of DSBs. This transcriptional regulation of AtRAD51, AtPARP1, atGR1 and AtL1G4 is lost in the atm mutants . The absence of AtRAD51 induction associated with ionizing radiation sensitivity suggest that AtAtm play an important function in DSB repair by homologous recombination. In addition we show that homologous intra-chromosomal recombination frequency is elevated in the mutant comparing to wild-type, with or without gamma irradiation. These results show the implication of AtAtm in the genomic stability. (author)

  4. Integrated services to the home and small business over a service-independent HFC network

    Science.gov (United States)

    Counterman, Raymond

    1995-11-01

    This paper proposes three different approaches to providing integrated digital services to small businesses and residential customers over modern hybrid fiber and coaxial (HFC) access networks. The target delivery system is one that is flexible and forms a multiservice, service- independent platform capable of providing a wide range of services (voice, video, data, and multimedia). The merits and limitations of the three approaches are explored. In the first approach, the common facilities of an HFC access network may be shared by the frequency partitioning of the coaxial plant's radio frequency spectrum. video, data, and telephony services each use different portions of this spectrum -- a service-dependent network. In the second approach, asynchronous transfer mode (ATM) transmission is used as the information delivery vehicle all the way to the home or small business, creating a more flexible delivery system. The ATM-based architecture is expected to support any service or service mix -- a service-independent network. In the third approach, a common transport protocol composed of both asynchronous and synchronous transfer modes (ATM/STM) is used. Such an approach could (1) provide a common interface between home/small business premises equipment and both the circuit and ATM switching networks; (2) meet a wide range of delay and throughput requirements; and (3) allow for many network migration scenarios.

  5. Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks

    Energy Technology Data Exchange (ETDEWEB)

    Fukumoto, Yasunori, E-mail: fukumoto@faculty.chiba-u.jp; Kuki, Kazumasa; Morii, Mariko; Miura, Takahito; Honda, Takuya; Ishibashi, Kenichi; Hasegawa, Hitomi; Kubota, Sho; Ide, Yudai; Yamaguchi, Noritaka; Nakayama, Yuji; Yamaguchi, Naoto, E-mail: nyama@faculty.chiba-u.jp

    2014-09-26

    Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the process by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphorylation of Chk2 and Kap1. Src inhibition increased ATM signaling both in G2 phase and during asynchronous growth. shRNA knockdown of Lyn increased ATM signaling. Src-dependent nuclear tyrosine phosphorylation suppressed ATM-mediated Kap1 phosphorylation. These results suggest that Src family kinases are involved in upstream signaling that leads to inactivation of the ATM-dependent DNA damage checkpoint.

  6. Ataxia-telangiectasia mutated (ATM) deficiency decreases reprogramming efficiency and leads to genomic instability in iPS cells.

    Science.gov (United States)

    Kinoshita, Taisuke; Nagamatsu, Go; Kosaka, Takeo; Takubo, Keiyo; Hotta, Akitsu; Ellis, James; Suda, Toshio

    2011-04-08

    During cell division, one of the major features of somatic cell reprogramming by defined factors, cells are potentially exposed to DNA damage. Inactivation of the tumor suppressor gene p53 raised reprogramming efficiency but resulted in an increased number of abnormal chromosomes in established iPS cells. Ataxia-telangiectasia mutated (ATM), which is critical in the cellular response to DNA double-strand breaks, may also play an important role during reprogramming. To clarify the function of ATM in somatic cell reprogramming, we investigated reprogramming in ATM-deficient (ATM-KO) tail-tip fibroblasts (TTFs). Although reprogramming efficiency was greatly reduced in ATM-KO TTFs, ATM-KO iPS cells were successfully generated and showed the same proliferation activity as WT iPS cells. ATM-KO iPS cells had a gene expression profile similar to ES cells and WT iPS cells, and had the capacity to differentiate into all three germ layers. On the other hand, ATM-KO iPS cells accumulated abnormal genome structures upon continuous passages. Even with the abnormal karyotype, ATM-KO iPS cells retained pluripotent cell characteristics for at least 20 passages. These data indicate that ATM does participate in the reprogramming process, although its role is not essential.

  7. Ataxia-telangiectasia mutated (ATM) deficiency decreases reprogramming efficiency and leads to genomic instability in iPS cells

    Energy Technology Data Exchange (ETDEWEB)

    Kinoshita, Taisuke [Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582 (Japan); Nagamatsu, Go, E-mail: gonag@sc.itc.keio.ac.jp [Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582 (Japan); Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kosaka, Takeo [Department of Urology, School of Medicine, Keio University, Tokyo 160-8582 (Japan); Takubo, Keiyo [Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582 (Japan); Hotta, Akitsu [Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Department of Reprogramming Science, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto (Japan); Ellis, James [Ontario Human iPS Cell Facility, Molecular Genetics, University of Toronto, Developmental and Stem Cell Biology, SickKids, Toronto, Canada MG1L7 (Canada); Suda, Toshio, E-mail: sudato@sc.itc.keio.ac.jp [Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582 (Japan)

    2011-04-08

    Highlights: {yields} iPS cells were induced with a fluorescence monitoring system. {yields} ATM-deficient tail-tip fibroblasts exhibited quite a low reprogramming efficiency. {yields} iPS cells obtained from ATM-deficient cells had pluripotent cell characteristics. {yields} ATM-deficient iPS cells had abnormal chromosomes, which were accumulated in culture. -- Abstract: During cell division, one of the major features of somatic cell reprogramming by defined factors, cells are potentially exposed to DNA damage. Inactivation of the tumor suppressor gene p53 raised reprogramming efficiency but resulted in an increased number of abnormal chromosomes in established iPS cells. Ataxia-telangiectasia mutated (ATM), which is critical in the cellular response to DNA double-strand breaks, may also play an important role during reprogramming. To clarify the function of ATM in somatic cell reprogramming, we investigated reprogramming in ATM-deficient (ATM-KO) tail-tip fibroblasts (TTFs). Although reprogramming efficiency was greatly reduced in ATM-KO TTFs, ATM-KO iPS cells were successfully generated and showed the same proliferation activity as WT iPS cells. ATM-KO iPS cells had a gene expression profile similar to ES cells and WT iPS cells, and had the capacity to differentiate into all three germ layers. On the other hand, ATM-KO iPS cells accumulated abnormal genome structures upon continuous passages. Even with the abnormal karyotype, ATM-KO iPS cells retained pluripotent cell characteristics for at least 20 passages. These data indicate that ATM does participate in the reprogramming process, although its role is not essential.

  8. ATM-mediated transcriptional and developmental responses to gamma-rays in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Lilian Ricaud

    Full Text Available ATM (Ataxia Telangiectasia Mutated is an essential checkpoint kinase that signals DNA double-strand breaks in eukaryotes. Its depletion causes meiotic and somatic defects in Arabidopsis and progressive motor impairment accompanied by several cell deficiencies in patients with ataxia telangiectasia (AT. To obtain a comprehensive view of the ATM pathway in plants, we performed a time-course analysis of seedling responses by combining confocal laser scanning microscopy studies of root development and genome-wide expression profiling of wild-type (WT and homozygous ATM-deficient mutants challenged with a dose of gamma-rays (IR that is sublethal for WT plants. Early morphologic defects in meristematic stem cells indicated that AtATM, an Arabidopsis homolog of the human ATM gene, is essential for maintaining the quiescent center and controlling the differentiation of initial cells after exposure to IR. Results of several microarray experiments performed with whole seedlings and roots up to 5 h post-IR were compiled in a single table, which was used to import gene information and extract gene sets. Sequence and function homology searches; import of spatio-temporal, cell cycling, and mutant-constitutive expression characteristics; and a simplified functional classification system were used to identify novel genes in all functional classes. The hundreds of radiomodulated genes identified were not a random collection, but belonged to functional pathways such as those of the cell cycle; cell death and repair; DNA replication, repair, and recombination; and transcription; translation; and signaling, indicating the strong cell reprogramming and double-strand break abrogation functions of ATM checkpoints. Accordingly, genes in all functional classes were either down or up-regulated concomitantly with downregulation of chromatin deacetylases or upregulation of acetylases and methylases, respectively. Determining the early transcriptional indicators of

  9. Design and development of cell queuing, processing, and scheduling modules for the iPOINT input-buffered ATM testbed

    Science.gov (United States)

    Duan, Haoran

    1997-12-01

    This dissertation presents the concepts, principles, performance, and implementation of input queuing and cell-scheduling modules for the Illinois Pulsar-based Optical INTerconnect (iPOINT) input-buffered Asynchronous Transfer Mode (ATM) testbed. Input queuing (IQ) ATM switches are well suited to meet the requirements of current and future ultra-broadband ATM networks. The IQ structure imposes minimum memory bandwidth requirements for cell buffering, tolerates bursty traffic, and utilizes memory efficiently for multicast traffic. The lack of efficient cell queuing and scheduling solutions has been a major barrier to build high-performance, scalable IQ-based ATM switches. This dissertation proposes a new Three-Dimensional Queue (3DQ) and a novel Matrix Unit Cell Scheduler (MUCS) to remove this barrier. 3DQ uses a linked-list architecture based on Synchronous Random Access Memory (SRAM) to combine the individual advantages of per-virtual-circuit (per-VC) queuing, priority queuing, and N-destination queuing. It avoids Head of Line (HOL) blocking and provides per-VC Quality of Service (QoS) enforcement mechanisms. Computer simulation results verify the QoS capabilities of 3DQ. For multicast traffic, 3DQ provides efficient usage of cell buffering memory by storing multicast cells only once. Further, the multicast mechanism of 3DQ prevents a congested destination port from blocking other less- loaded ports. The 3DQ principle has been prototyped in the Illinois Input Queue (iiQueue) module. Using Field Programmable Gate Array (FPGA) devices, SRAM modules, and integrated on a Printed Circuit Board (PCB), iiQueue can process incoming traffic at 800 Mb/s. Using faster circuit technology, the same design is expected to operate at the OC-48 rate (2.5 Gb/s). MUCS resolves the output contention by evaluating the weight index of each candidate and selecting the heaviest. It achieves near-optimal scheduling and has a very short response time. The algorithm originates from a

  10. Physical-chemical and operational performance of an anaerobic baffled reactor (ABR treating swine wastewater - 10.4025/actascitechnol.v32i4.7203

    Directory of Open Access Journals (Sweden)

    Erlon Lopes Pereira

    2010-12-01

    Full Text Available Since hog raising concentrates a huge amount of swine manure in small areas, it is considered by the environmental government organizations to be one of the most potentially pollutant activities. Therefore the main objective of this research was to evaluate by operational criteria and removal efficiency, the performance of a Anaerobic Baffled Reactor (ABR, working as a biological pre-treatment of swine culture effluents. The physical-chemical analyses carried out were: total COD, BOD5, total solids (TS, fix (TFS and volatiles (TVS, temperature, pH, total Kjeldahl nitrogen, phosphorus, total acidity and alkalinity. The ABR unit worked with an average efficiency of 65.2 and 76.2%, respectively, concerning total COD and BOD5, with a hydraulic retention time (HRT about 15 hours. The results for volumetric organic loading rate (VOLR, organic loading rate (OLR and hydraulic loading rate (HLR were: 4.46 kg BOD m-3 day-1; 1.81 kg BOD5 kg TVS-1 day-1 and 1.57 m3 m-3 day-1, respectively. The average efficiency of the whole treatment system for total COD and BOD5 removal were 66.5 and 77.8%, showing an adequate performance in removing the organic matter from swine wastewater.

  11. The effects of polarity of click stimulation on auditory brainstem responses (ABR in patients with cochlear and retro-cochlear disorders in Amiralam and Resalat Hospitals 1995-97

    Directory of Open Access Journals (Sweden)

    Soltani AH

    2002-08-01

    Full Text Available Background: Auditory brainstem response (A.B.R is one of the most important electrophysiological tests in evaluating of auditory system, especially for diagnosing of auditory nerve and brainstem disorders. It is a non-invasive test and has reliability and validity characteristic. There is no contra-indication for this test. One of the most important of stimulation parameters of A.B.R is click polarity (rarefaction, condensation and alternative. Some of the investigators believed that different polarities have no effects on A.B.R are affected by different polarities. Materials and Methods: In this study, the results of ABR of 148 patients (296 ears were compared with three different polarities of rarefaction, condensation and alternative half click stimuli. The cases were categorized in three groups of normal (60 cases, cochlear (62 cases and retro-cochlear (17 cases. This classification were done according to the hearing level in pure tone audiometry results in three frequencies of 1000, 2000, 4000 Hz and to the site of the their disorders. The mean absolute latencies of waves I, III and V were obtained for each polarity. Inter-peak latency (I.P.L of wave also measured in three groups (normal, cochlear and retro-cochlear. Results: The results were showed a significant difference between absolute latency of wave I among different polarities on three above mentioned groups (P0.05. Conclusion: It was concluded that rarefaction polarity has better and more stable results of ABR tests.

  12. Enhanced decolorization of azo dye in a small pilot-scale anaerobic baffled reactor coupled with biocatalyzed electrolysis system (ABR-BES): a design suitable for scaling-up.

    Science.gov (United States)

    Cui, Dan; Guo, Yu-Qi; Lee, Hyung-Sool; Wu, Wei-Min; Liang, Bin; Wang, Ai-Jie; Cheng, Hao-Yi

    2014-07-01

    A four-compartment anaerobic baffled reactor (ABR) incorporated with membrane-less biocatalyzed electrolysis system (BES) was tested for the treatment of azo dye (alizarin yellow R, AYR) wastewater (AYR, 200 mg L(-1); glucose, 1000 mg L(-1)). The ABR-BES was operated without and with external power supply to examine AYR reduction process and reductive intermediates with different external voltages (0.3, 0.5 and 0.7 V) and hydraulic retention times (HRT: 8, 6 and 4h). The decolorization efficiency in the ABR-BES (8h HRT, 0.5 V) was higher than that in ABR-BES without electrolysis, i.e. 95.1 ± 1.5% versus 86.9 ± 6.3%. Incorporation of BES with ABR accelerated the consumption of VFAs (mainly acetate) and attenuated biogas (methane) production. Higher power supply (0.7 V) enhanced AYR decolorization efficiency (96.4 ± 1.8%), VFAs removal, and current density (24.1 Am(-3) TCV). Shorter HRT increased volumetric AYR decolorization rates, but decreased AYR decolorization efficiency.

  13. Characteristics of ABR waveforms in Senile Presbycusis Patients%90岁以上老年性聋患者的听性脑干反应

    Institute of Scientific and Technical Information of China (English)

    张锐宁; 马龙; 霍云峰; 张奋龙; 冀飞

    2014-01-01

    Objective To obtain the characteristics of auditory brainstem response (ABR) in senile patietns elder than 90 years. Methods Fourteen presbycusis patietns elder than 90 years (91.1±1.3 years, 26 ears) and 9 normal-hearing adults ( 22.7±1.2 years, 18 ears) were included in the study. ABRs were recorded in both groups by alternative clicks. The peak laten-cy (PL) of wave Ⅰ, Ⅲ, and Ⅴ, and the inter-peak latency (IPL) of Ⅰ-Ⅲ, Ⅲ-Ⅴ, and Ⅰ-Ⅴ were compared between groups. Results In 76.9%(20/26) of senile ears, wave I of ABRs were present, in 76.9%(20/26) of them, wave I of ABRs were present, and in 84.6%(22/26) of them, waveⅤwere present. For the senile group, the peak latencies ofⅠ,Ⅲ,Ⅴwere statistically longer than those of control group. There was no statistical difference between groups in the IPL of waveⅠ-Ⅲ, waveⅢ-Ⅴand waveⅠ-Ⅴ. Conclusion Worse ABR wave differentiation were found in senile patients over 90 years.%目的:分析90岁以上老年性聋患者听性脑干反应(ABR)的特征。方法对14例90岁以上老年性聋患者(平均年龄91.1.4±1.3岁,26耳)进行交替短声ABR测试。听力正常人9例(平均年龄22.7±1.2岁,18耳)作为对照组。观测Ⅰ、Ⅲ、Ⅴ波的峰潜伏期(Peak Latency,PL)和Ⅰ-Ⅲ、Ⅲ-Ⅴ、Ⅰ-Ⅴ波间期(Inter-Peak Latency,IPL),并分别与对照组总体均数进行比较。结果总体的I波引出率和III波引出率均为76.9%(20/26),V波引出率为84.6%(22/26)。高龄老年性聋组各波PL较对照组延长。Ⅰ-Ⅲ波IPL、Ⅲ-Ⅴ波IPL、Ⅰ-Ⅴ波IPL无组间统计学差异。结论90岁以上高龄老年性聋患者ABR波形分化较差。

  14. An ABRE-binding factor, OSBZ8, is highly expressed in salt tolerant cultivars than in salt sensitive cultivars of indica rice

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    Gupta Sudhiranjan

    2006-08-01

    Full Text Available Abstract Background The bZIP class Abscisic acid Responsive Element (ABRE-binding factor, OSBZ8 (38.5 kD has been considered to regulate ABA-mediated transcription in the suspension cultured cells of japonica rice. Still, nothing is known about the expression of OSBZ8 at protein level in vegetative tissue of salt sensitive and salt tolerant rice plants. In our previous study, Electrophoretic Mobility Shift Assay (EMSA of [32P]ABRE-DNA and nuclear extracts prepared from the lamina of Pokkali rice plants has detected the presence of an ABRE-binding factor. Northern analysis has also detected salinity stress induced accumulation of transcripts for bZIP class of factor. Therefore, OSBZ8 was considered to play an important role in the regulation of transcription in the vegetative tissue of rice. The aim of this study is to find out whether OSBZ8 has any role in regulating the NaCl-stress induced gene expression in vegetative tissue and whether the expression of OSBZ8 factor directly correlates with the stress tolerance of different varieties of indica type rice. Results Northern analysis of total RNA from roots and lamina of salt-sensitive M-I-48 and salt-tolerant Nonabokra, when probed with the N-terminal unique region of OSBZ8 (OSBZ8p, without the highly conserved basic region, a transcript of 1.3 kb hybridized and its level was much higher in tolerant cultivar. EMSA with Em1a, the strongest ABA Responsive Element till reported from the upstream of EmBP1, and the nuclear extracts from laminar tissue of untreated and salt-treated seedlings of three salt sensitive, one moderately sensitive and two salt tolerant indica rice cultivars showed specific binding of nuclear factor to ABRE element. Intensity of binding was low and inducible in salt sensitive rice cultivars while high and constitutive in salt tolerant cultivars. EMSA with 300 bp 5'upstream region of Rab16A gene, a well known salt stress and ABA-inducible gene of rice, showed formation of two

  15. 基于Smith原则的ATM网络拥塞控制%The Congestion Control of ATM Networks Based on the Smith Principle

    Institute of Scientific and Technical Information of China (English)

    关新平; 刘志新; 龙承念

    2003-01-01

    In this paper, the prediction of available bandwidth and Smith principle are applied into the congestion control based on the ATM model of single bottleneck node. The method can realize that the queue length in the switch traces the given desired value without error. And it also restrains the effect under the existence of wave of available bandwidth. In the simulation, we can see that the queue length keeps in a certain bound. The phenomenon of congestion is avoided and guarantees the quality of service at the same time. It verifies the effectivity and feasibility of the scheme.

  16. Analysis of CrIS-ATMS Data Using an AIRS Science Team Version 6 - Like Retrieval Algorithm

    Science.gov (United States)

    Susskind, Joel; Kouvaris, Louis C.

    2013-01-01

    CrIS/ATMS is flying on NPP and is scheduled to fly on JPSS-1. CrIS/ATMS has roughly equivalent capabilities to AIRS/AMSU. The AIRS Science Team Version 6 retrieval algorithm is currently producing very high quality level-3 Climate Data Records (CDR's) that will be critical for understanding climate processes AIRS CDRs should eventually cover the period September 2002 through at least 2020. CrIS/ATMS is the only scheduled follow on to AIRS AMSU. I have been asked by Ramesh Kakar if CrIS/ATMS can be counted on to adequately continue the AIRS/AMSU CDRs beyond 2020, or is something better needed? This research is being done to answer that question. A minimum requirement to obtain a yes answer is that CrIS/ATMS be analyzed using an AIRS Version 6 - like algorithm. NOAA is currently generating CrIS/ATMS products using 2 algorithms: IDPS and NUCAPS

  17. Existing and Required Modeling Capabilities for Evaluating ATM Systems and Concepts

    Science.gov (United States)

    Odoni, Amedeo R.; Bowman, Jeremy; Delahaye, Daniel; Deyst, John J.; Feron, Eric; Hansman, R. John; Khan, Kashif; Kuchar, James K.; Pujet, Nicolas; Simpson, Robert W.

    1997-01-01

    ATM systems throughout the world are entering a period of major transition and change. The combination of important technological developments and of the globalization of the air transportation industry has necessitated a reexamination of some of the fundamental premises of existing Air Traffic Management (ATM) concepts. New ATM concepts have to be examined, concepts that may place more emphasis on: strategic traffic management; planning and control; partial decentralization of decision-making; and added reliance on the aircraft to carry out strategic ATM plans, with ground controllers confined primarily to a monitoring and supervisory role. 'Free Flight' is a case in point. In order to study, evaluate and validate such new concepts, the ATM community will have to rely heavily on models and computer-based tools/utilities, covering a wide range of issues and metrics related to safety, capacity and efficiency. The state of the art in such modeling support is adequate in some respects, but clearly deficient in others. It is the objective of this study to assist in: (1) assessing the strengths and weaknesses of existing fast-time models and tools for the study of ATM systems and concepts and (2) identifying and prioritizing the requirements for the development of additional modeling capabilities in the near future. A three-stage process has been followed to this purpose: 1. Through the analysis of two case studies involving future ATM system scenarios, as well as through expert assessment, modeling capabilities and supporting tools needed for testing and validating future ATM systems and concepts were identified and described. 2. Existing fast-time ATM models and support tools were reviewed and assessed with regard to the degree to which they offer the capabilities identified under Step 1. 3 . The findings of 1 and 2 were combined to draw conclusions about (1) the best capabilities currently existing, (2) the types of concept testing and validation that can be carried

  18. BMI1 attenuates etoposide-induced G2/M checkpoints via reducing ATM activation.

    Science.gov (United States)

    Wei, F; Ojo, D; Lin, X; Wong, N; He, L; Yan, J; Xu, S; Major, P; Tang, D

    2015-06-04

    The BMI1 protein contributes to stem cell pluripotency and oncogenesis via multiple functions, including its newly identified role in DNA damage response (DDR). Although evidence clearly demonstrates that BMI1 facilitates the repair of double-stranded breaks via homologous recombination (HR), it remains unclear how BMI1 regulates checkpoint activation during DDR. We report here that BMI1 has a role in G2/M checkpoint activation in response to etoposide (ETOP) treatment. Ectopic expression of BMI1 in MCF7 breast cancer and DU145 prostate cancer cells significantly reduced ETOP-induced G2/M arrest. Conversely, knockdown of BMI1 in both lines enhanced the arrest. Consistent with ETOP-induced activation of the G2/M checkpoints via the ATM pathway, overexpression and knockdown of BMI1, respectively, reduced and enhanced ETOP-induced phosphorylation of ATM at serine 1981 (ATM pS1981). Furthermore, the phosphorylation of ATM targets, including γH2AX, threonine 68 (T68) on CHK2 (CHK2 pT68) and serine 15 (S15) on p53 were decreased in overexpression and increased in knockdown BMI1 cells in response to ETOP. In line with the requirement of NBS1 in ATM activation, we were able to show that BMI1 associates with NBS1 and that this interaction altered the binding of NBS1 with ATM. BMI1 consists of a ring finger (RF), helix-turn-helix-turn-helix-turn (HT), proline/serine (PS) domain and two nuclear localization signals (NLS). Although deletion of either RF or HT did not affect the association of BMI1 with NBS1, the individual deletions of PS and one NLS (KRMK) robustly reduced the interaction. Stable expression of these BMI1 mutants decreased ETOP-induced ATM pS1981 and CHK2 pT68, but not ETOP-elicited γH2AX in MCF7 cells. Furthermore, ectopic expression of BMI1 in non-transformed breast epithelial MCF10A cells also compromised ETOP-initiated ATM pS1981 and γH2AX. Taken together, we provide compelling evidence that BMI1 decreases ETOP-induced G2/M checkpoint activation via

  19. Performance Evaluation of Adaptive Rate Control (ARC for Burst Traffic over ATM Network

    Directory of Open Access Journals (Sweden)

    V.Ramesh

    2010-01-01

    Full Text Available Many research works have already been done for congestion control and resource management in ATM networks using static and dynamic algorithms. However, no comprehensive scheme has been suggested, which can claim optimized the resource allocations fulfilling the requirements of quality of services (QoS for existing and incoming sources. The paper suggests a new approach, which would make the dynamic allocation of resources by controlling the input rate (l, output/server rate (m and buffer size (c individually or in conjunction. The newly proposed approach with dynamical allocation of resources is much more comprehensive in nature and claims a shorter convergence time than the other previously suggested schemes based on similar dynamic allocation principle. In this paper we describe an Adaptive Rate Control (ARC implemented to improve the performance of high-speed network to handle burst traffic by guaranteeing the cell loss ratio (CLR for all cell streams. First, the cases in which a Tahoe, Reno, New Reno, SACK and Plain schemes are applicable in peak-cell-rate (PCR are discussed. The ARC improves the performance by regulating the increment (up and the decrease (down of window size (flow control. Incoming traffic rate, number of cell drop, preset size of the window and estimated delay time are taken into account for this regulation. Simulations are used to investigate how Tahoe, Reno, New Reno, SACK and Plain can conduct, as congestion existed. Then we compare these results from four schemes to the “Plain” scheme (no flow control application and to the proposed ARC. By altering windows size for the mentioned six schemes, we can obtain the supportive results.

  20. S-NPP ATMS Instrument Prelaunch and On-Orbit Performance Evaluation

    Science.gov (United States)

    Kim, Edward; Lyu, Cheng-Hsuan; Anderson, Kent; Leslie, Vincent R.; Blackwell, William J.

    2014-01-01

    The first of a new generation of microwave sounders was launched aboard the Suomi-National Polar-Orbiting Partnership satellite in October 2011. The Advanced Technology Microwave Sounder (ATMS) combines the capabilities and channel sets of three predecessor sounders into a single package to provide information on the atmospheric vertical temperature and moisture profiles that are the most critical observations needed for numerical weather forecast models. Enhancements include size/mass/power approximately one third of the previous total, three new sounding channels, the first space-based, Nyquist-sampled cross-track microwave temperature soundings for improved fusion with infrared soundings, plus improved temperature control and reliability. This paper describes the ATMS characteristics versus its predecessor, the advanced microwave sounding unit (AMSU), and presents the first comprehensive evaluation of key prelaunch and on-orbit performance parameters. Two-year on-orbit performance shows that the ATMS has maintained very stable radiometric sensitivity, in agreement with prelaunch data, meeting requirements for all channels (with margins of 40% for channels 1-15), and improvements over AMSU-A when processed for equivalent spatial resolution. The radiometric accuracy, determined by analysis from ground test measurements, and using on-orbit instrument temperatures, also shows large margins relative to requirements (specified as ATMS is especially important for this first proto-flight model unit of what will eventually be a series of ATMS sensors providing operational sounding capability for the U.S. and its international partners well into the next decade.

  1. Inactivation of the ATMIN/ATM pathway protects against glioblastoma formation.

    Science.gov (United States)

    Blake, Sophia M; Stricker, Stefan H; Halavach, Hanna; Poetsch, Anna R; Cresswell, George; Kelly, Gavin; Kanu, Nnennaya; Marino, Silvia; Luscombe, Nicholas M; Pollard, Steven M; Behrens, Axel

    2016-03-17

    Glioblastoma multiforme (GBM) is the most aggressive human primary brain cancer. Using a Trp53-deficient mouse model of GBM, we show that genetic inactivation of the Atm cofactor Atmin, which is dispensable for embryonic and adult neural development, strongly suppresses GBM formation. Mechanistically, expression of several GBM-associated genes, including Pdgfra, was normalized by Atmin deletion in the Trp53-null background. Pharmacological ATM inhibition also reduced Pdgfra expression, and reduced the proliferation of Trp53-deficient primary glioma cells from murine and human tumors, while normal neural stem cells were unaffected. Analysis of GBM datasets showed that PDGFRA expression is also significantly increased in human TP53-mutant compared with TP53-wild-type tumors. Moreover, combined treatment with ATM and PDGFRA inhibitors efficiently killed TP53-mutant primary human GBM cells, but not untransformed neural stem cells. These results reveal a new requirement for ATMIN-dependent ATM signaling in TP53-deficient GBM, indicating a pro-tumorigenic role for ATM in the context of these tumors.

  2. Activation and Inhibition of ATM by Phytochemicals: Awakening and Sleeping the Guardian Angel Naturally.

    Science.gov (United States)

    Farooqi, Ammad Ahmad; Wu, Shyh-Jong; Chang, Yung-Ting; Tang, Jen-Yang; Li, Kun-Tzu; Ismail, Muhammad; Liaw, Chih-Chuang; Li, Ruei-Nian; Chang, Hsueh-Wei

    2015-10-01

    Double-stranded breaks (DSBs) are cytotoxic DNA lesions caused by oxygen radicals, ionizing radiation, and radiomimetic chemicals. Increasing understanding of DNA damage signaling has provided an ever-expanding list of modulators reported to orchestrate DNA damage repair and ataxia telangiectasia mutated (ATM) is the master regulator and main transducer of the DSB response. Increasingly, it is being realized that DNA damage response is a synchronized and branched network that functionalizes different molecular cascades to activate special checkpoints, thus temporarily arresting progression of the cell cycle while damage is being assessed and processed. It is noteworthy that both nutrigenetics and nutrigenomics have revolutionized the field of molecular biology and rapidly accumulating experimental evidence has started to shed light on biological activities of a wide range of phytochemicals reported to modulate cell cycle, DNA repair, cell growth, differentiation and apoptosis as evidenced by cell-based studies. In this review, we have attempted to provide an overview of DNA damage signaling, how ATM signaling regulates tumor necrosis factors-related apoptosis inducing ligand (TRAIL)-induced intracellular network. We also illuminate on how resveratrol, epigallocatechin gallate, curcumin, jaceosidin, cucurbitacin, apigenin, genistein, and others trigger activation of ATM in different cancer cells as well as agents for ATM inactivation. Understanding the interplay of TRAIL-induced intracellular signaling and ATM modulation of downstream effectors is very important. This holds particularly for a reconceptualization of the apparently paradoxical roles and therapeutically targetable for enhancing the response to DNA damage-inducing therapy.

  3. The risk for developing cancer in Israeli ATM, BLM, and FANCC heterozygous mutation carriers.

    Science.gov (United States)

    Laitman, Yael; Boker-Keinan, Lital; Berkenstadt, Michal; Liphsitz, Irena; Weissglas-Volkov, Daphna; Ries-Levavi, Liat; Sarouk, Ifat; Pras, Elon; Friedman, Eitan

    2016-03-01

    Cancer risks in heterozygous mutation carriers of the ATM, BLM, and FANCC genes are controversial. To shed light on this issue, cancer rates were evaluated by cross referencing asymptomatic Israeli heterozygous mutation carriers in the ATM, BLM, and FANCC genes with cancer diagnoses registered at the Israeli National Cancer Registry (INCR). Comparison of observed to expected Standardized Incidence Rates (SIR) was performed. Overall, 474 individuals participated in the study: 378 females; 25 Arab and 31 Jewish ATM carriers, 152 BLM carriers, and 170 FANCC carriers (all Ashkenazim). Age range at genotyping was 19-53 years (mean + SD 30.6 + 5 years). In addition, 96 males were included; 5, 34, and 57 ATM, BLM, and FANCC mutation carriers, respectively. Over 5-16 years from genotyping (4721 person/years), 15 new cancers were diagnosed in mutation carriers: 5 breast, 4 cervical, 3 melanomas, and one each bone sarcoma, pancreatic, and colorectal cancer. No single cancer diagnosis was more prevalent then expected in all groups combined or per gene analyzed. Specifically breast cancer SIR was 0.02-0.77. We conclude that Israeli ATM, BLM, and FANCC heterozygous mutation carriers are not at an increased risk for developing cancer.

  4. Activation of the ATM-Snail pathway promotes breast cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Mianen Sun; David A. Engler; Ming Zhan; Stephen T.C. Wong; Li Fu; Bo Xu; Xiaojing Guo; Xiaolong Qian; Haibo Wang; Chunying Yang; Kathryn L. Brinkman; Monica Serrano-Gonzalez; Richard S. Jope; Binhua Zhou

    2012-01-01

    The DNA damage response (DDR) is critical for the maintenance of genetic stability and serves as an anti-cancer barrier during early tumorigenesis.However,the role of the DDR in tumor progression and metastasis is less known.Here,we demonstrate that the ATM kinase,one of the critical DDR elements,is hyperactive in late stage breast tumor tissues with lymph-node metastasis and this hyperactivity correlates with elevated expression of the epitheliai-mesenchymal transition marker,Snail.At the molecular level,we demonstrate that ATM regulates Snail stabilization by phosphorylation on Serine-100.Using mass spectrometry,we identified HSP90 as a critical binding protein of Snail in response to DNA damage.HsP9o binds to and stabilizes phosphorylated Snail.We further provide in vitro and in vivo evidence that activation of ATM-mediated Snail phosphorylation promotes tumor invasion and metastasis.Finally,we demonstrate that Snail Serine-100 phosphorylation is elevated in breast cancer tissues with lymph-node metastasis,indicating clinical significance of the ATM-Snail pathway.Together,our findings provide strong evidence that the ATM-Snail pathway promotes tumor metastasis,highlighting a previously undescribed role of the DDR in tumor invasion and metastasis.

  5. Limited Role of Murine ATM in Oncogene-Induced Senescence and p53-Dependent Tumor Suppression

    Science.gov (United States)

    Martinez-Pastor, Barbara; Ortega-Molina, Ana; Soria, Rebeca; Collado, Manuel; Fernandez-Capetillo, Oscar; Serrano, Manuel

    2009-01-01

    Recent studies in human fibroblasts have provided a new general paradigm of tumor suppression according to which oncogenic signaling produces DNA damage and this, in turn, results in ATM/p53-dependent cellular senescence. Here, we have tested this model in a variety of murine experimental systems. Overexpression of oncogenic Ras in murine fibroblasts efficiently induced senescence but this occurred in the absence of detectable DNA damage signaling, thus suggesting a fundamental difference between human and murine cells. Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling. Accordingly, K-Ras-driven adenomas were also senescent in Atm-null mice, and the tumorigenic progression of these lesions was only modestly accelerated by Atm-deficiency. Finally, we have examined chemically-induced fibrosarcomas, which possess a persistently activated DNA damage response and are highly sensitive to the activity of p53. We found that the absence of Atm favored genomic instability in the resulting tumors, but did not affect the persistent DNA damage response and did not impair p53-dependent tumor suppression. All together, we conclude that oncogene-induced senescence in mice may occur in the absence of a detectable DNA damage response. Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability. PMID:19421407

  6. Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression.

    Directory of Open Access Journals (Sweden)

    Alejo Efeyan

    Full Text Available Recent studies in human fibroblasts have provided a new general paradigm of tumor suppression according to which oncogenic signaling produces DNA damage and this, in turn, results in ATM/p53-dependent cellular senescence. Here, we have tested this model in a variety of murine experimental systems. Overexpression of oncogenic Ras in murine fibroblasts efficiently induced senescence but this occurred in the absence of detectable DNA damage signaling, thus suggesting a fundamental difference between human and murine cells. Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling. Accordingly, K-Ras-driven adenomas were also senescent in Atm-null mice, and the tumorigenic progression of these lesions was only modestly accelerated by Atm-deficiency. Finally, we have examined chemically-induced fibrosarcomas, which possess a persistently activated DNA damage response and are highly sensitive to the activity of p53. We found that the absence of Atm favored genomic instability in the resulting tumors, but did not affect the persistent DNA damage response and did not impair p53-dependent tumor suppression. All together, we conclude that oncogene-induced senescence in mice may occur in the absence of a detectable DNA damage response. Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability.

  7. Involvement of ATM/ATR-p38 MAPK cascade in MNNG induced G1-S arrest

    Institute of Scientific and Technical Information of China (English)

    Ke-Qing Zhu; Suo-Jiang Zhang

    2003-01-01

    AIM: To understand the effect of low concentration of Nmethyl-N′-nitro-nitrosoguanidine (MNNG), which is a widely distributed environmental mutagen and carcinogen especially for human gastric cancer, on DNA damage and to study its possible pathway in regulating cell cycle arrest.METHODS: The DNA damage effect was measured by Comet assay. A specific phospho-(Ser/Thr) ATM/ATR substrate antibody was used to detect the damage sensor by Western blot. p38 kinase activity was measured by direct kinase assay,and immunoprecipitation for the possible connection between ATM/ATR and p38 MAPK. Flow cytometry analysis and p38MAPK specific inhibitor SB203580 were combined to detect the possible cell cycle arrest by p38 MAPK.RESULTS: With the same low concentration MNNG exposure (0.2μM 2.5 h), Comet assays indicated that strand breaks accumulated, Western blot and kinase assay showed ATM/ATR and p38 kinase activated, immunoprecipitation showed phospho-ATM/ATR substrate antibody combined with both p38 MAPK antibody and phospho-p38 MAPK antibody, p38MAPK pathway was involved in the G1-S arrest.CONCLUSION: Activation of ATM/ATR by MNNG induced DNA damage leads to activation of p38 MAPK, which involves in the G1 checkpoint in mammalian cells.

  8. Mechanistic Rationale to Target PTEN-Deficient Tumor Cells with Inhibitors of the DNA Damage Response Kinase ATM.

    Science.gov (United States)

    McCabe, Nuala; Hanna, Conor; Walker, Steven M; Gonda, David; Li, Jie; Wikstrom, Katarina; Savage, Kienan I; Butterworth, Karl T; Chen, Clark; Harkin, D Paul; Prise, Kevin M; Kennedy, Richard D

    2015-06-01

    Ataxia telangiectasia mutated (ATM) is an important signaling molecule in the DNA damage response (DDR). ATM loss of function can produce a synthetic lethal phenotype in combination with tumor-associated mutations in FA/BRCA pathway components. In this study, we took an siRNA screening strategy to identify other tumor suppressors that, when inhibited, similarly sensitized cells to ATM inhibition. In this manner, we determined that PTEN and ATM were synthetically lethal when jointly inhibited. PTEN-deficient cells exhibited elevated levels of reactive oxygen species, increased endogenous DNA damage, and constitutive ATM activation. ATM inhibition caused catastrophic DNA damage, mitotic cell cycle arrest, and apoptosis specifically in PTEN-deficient cells in comparison with wild-type cells. Antioxidants abrogated the increase in DNA damage and ATM activation in PTEN-deficient cells, suggesting a requirement for oxidative DNA damage in the mechanism of cell death. Lastly, the ATM inhibitor KU-60019 was specifically toxic to PTEN mutant cancer cells in tumor xenografts and reversible by reintroduction of wild-type PTEN. Together, our results offer a mechanistic rationale for clinical evaluation of ATM inhibitors in PTEN-deficient tumors.

  9. Squalene Inhibits ATM-Dependent Signaling in γIR-Induced DNA Damage Response through Induction of Wip1 Phosphatase.

    Science.gov (United States)

    Tatewaki, Naoto; Konishi, Tetsuya; Nakajima, Yuki; Nishida, Miyako; Saito, Masafumi; Eitsuka, Takahiro; Sakamaki, Toshiyuki; Ikekawa, Nobuo; Nishida, Hiroshi

    2016-01-01

    Ataxia telangiectasia mutated (ATM) kinase plays a crucial role as a master controller in the cellular DNA damage response. Inhibition of ATM leads to inhibition of the checkpoint signaling pathway. Hence, addition of checkpoint inhibitors to anticancer therapies may be an effective targeting strategy. A recent study reported that Wip1, a protein phosphatase, de-phosphorylates serine 1981 of ATM during the DNA damage response. Squalene has been proposed to complement anticancer therapies such as chemotherapy and radiotherapy; however, there is little mechanistic information supporting this idea. Here, we report the inhibitory effect of squalene on ATM-dependent DNA damage signals. Squalene itself did not affect cell viability and the cell cycle of A549 cells, but it enhanced the cytotoxicity of gamma-irradiation (γIR). The in vitro kinase activity of ATM was not altered by squalene. However, squalene increased Wip1 expression in cells and suppressed ATM activation in γIR-treated cells. Consistent with the potential inhibition of ATM by squalene, IR-induced phosphorylation of ATM effectors such as p53 (Ser15) and Chk1 (Ser317) was inhibited by cell treatment with squalene. Thus, squalene inhibits the ATM-dependent signaling pathway following DNA damage through intracellular induction of Wip1 expression.

  10. An Integrated Broadband Switching System with Narrowband Service Support

    Institute of Scientific and Technical Information of China (English)

    GONG Xiangyang; ZHANG Peng; CHENG Shiduan

    2001-01-01

    It is considered that ATM is not suitable for traditional narrowband services such as voice because of large adapting delay. In this paper,we present an ATM-based broadband switching system, which is capable of supporting narrowband services. A composite cell adapting method is adopted in this system to reduce adapting delay and guarantee QoS (Quality of Service). In the realized system, several key parameters have been measured. The results prove that it can guarantee perfect QoS and relative high bandwidth efficiency.

  11. Fast collision resolution for real time services in SDMA based wireless ATM networks

    DEFF Research Database (Denmark)

    Vornefeld, U.; Schieimer, D.; Walke, B.

    1999-01-01

    This paper considers random access and collision resolution algorithms in the context of spatial division multiple access (SDMA). We focus on the random access phase of HIPERLAN/2 systems currently under standardization at ETSI-BRAN. Based on the dynamic slot assignment, DSA++ medium access contr...

  12. ROS-activated ATM-dependent phosphorylation of cytoplasmic substrates identified by large scale phosphoproteomics screen

    DEFF Research Database (Denmark)

    Kozlov, Sergei V; Waardenberg, Ashley J; Engholm-Keller, Kasper

    2016-01-01

    ATM (ataxia-telangiectasia, mutated) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signalling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoi......ATM (ataxia-telangiectasia, mutated) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signalling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle...... to identify cytoplasmic proteins altered in their phosphorylation state in control and A-T (ataxia-telangiectasia) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites...

  13. An ATM-independent S-phase checkpoint response involves CHK1 pathway

    Science.gov (United States)

    Zhou, Xiang-Yang; Wang, Xiang; Hu, Baocheng; Guan, Jun; Iliakis, George; Wang, Ya

    2002-01-01

    After exposure to genotoxic stress, proliferating cells actively slow down the DNA replication through a S-phase checkpoint to provide time for repair. We report that in addition to the ataxia-telangiectasia mutated (ATM)-dependent pathway that controls the fast response, there is an ATM-independent pathway that controls the slow response to regulate the S-phase checkpoint after ionizing radiation in mammalian cells. The slow response of S-phase checkpoint, which is resistant to wortmannin, sensitive to caffeine and UCN-01, and related to cyclin-dependent kinase phosphorylation, is much stronger in CHK1 overexpressed cells, and it could be abolished by Chk1 antisense oligonucleotides. These results provide evidence that the ATM-independent slow response of S-phase checkpoint involves CHK1 pathway.

  14. Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches off transcription for DSB repair.

    Science.gov (United States)

    Ui, Ayako; Nagaura, Yuko; Yasui, Akira

    2015-05-07

    Transcription is repressed if a DNA double-strand break (DSB) is introduced in close proximity to a transcriptional activation site at least in part by H2A-ubiquitination. While ATM signaling is involved, how it controls H2A-ubiquitination remains unclear. Here, we identify that, in response to DSBs, a transcriptional elongation factor, ENL (MLLT1), is phosphorylated by ATM at conserved SQ sites. This phosphorylation increases the interaction between ENL and the E3-ubiquitin-ligase complex of Polycomb Repressive Complex 1 (PRC1) via BMI1. This interaction promotes enrichment of PRC1 at transcription elongation sites near DSBs to ubiquitinate H2A leading to transcriptional repression. ENL SQ sites and BMI1 are necessary for KU70 accumulation at DSBs near active transcription sites and cellular resistance to DSBs. Our data suggest that ATM-dependent phosphorylation of ENL functions as switch from elongation to Polycomb-mediated repression to preserve genome integrity.

  15. The combined status of ATM and p53 link tumor development with therapeutic response

    DEFF Research Database (Denmark)

    Jiang, Hai; Reinhardt, H Christian; Bartkova, Jirina;

    2009-01-01

    commonly used by tumors to bypass early neoplastic checkpoints ultimately determine chemotherapeutic response and generate tumor-specific vulnerabilities that can be exploited with targeted therapies. Specifically, evaluation of the combined status of ATM and p53, two commonly mutated tumor suppressor...... genes, can help to predict the clinical response to genotoxic chemotherapies. We show that in p53-deficient settings, suppression of ATM dramatically sensitizes tumors to DNA-damaging chemotherapy, whereas, conversely, in the presence of functional p53, suppression of ATM or its downstream target Chk2......While the contribution of specific tumor suppressor networks to cancer development has been the subject of considerable recent study, it remains unclear how alterations in these networks are integrated to influence the response of tumors to anti-cancer treatments. Here, we show that mechanisms...

  16. An experimental study of VBR video over various ATM switch architectures

    Energy Technology Data Exchange (ETDEWEB)

    Tsang, R.P. [Sandia National Labs., Livermore, CA (United States); Hsieh, J.; Du, D.H.C. [Univ. of Minnesota, Minneapolis, MN (United States)

    1997-12-31

    One of the most important components of an Asynchronous Transfer Mode (ATM) network is the switch. Switch design is not a part of the ATM standards so vendors use a wide variety of techniques to build their switches. In this paper, the authors present experimental results of switching and multiplexing real-time Variable Bit Rate (VBR) video traffic (JPEG, MPEG-1, and MPEG-2) through two different ATM switch architectures. Real-time VBR traffic, such as digital video, is particularly interesting due to its high demands in terms of bandwidth, real-time delivery and processing requirements. The experiments show that the fastest switches, i.e., lowest latencies, do not necessarily perform better when transmitting VBR video. The impact of the high speed network components; characteristics, such as switch fabric architecture, buffering strategies, and higher layer transport protocols (i.e., UDP, TCP/IP), are illustrated through the experimental results.

  17. ATM Dependent Silencing Links Nucleolar Chromatin Reorganization to DNA Damage Recognition.

    Science.gov (United States)

    Harding, Shane M; Boiarsky, Jonathan A; Greenberg, Roger A

    2015-10-13

    Resolution of DNA double-strand breaks (DSBs) is essential for the suppression of genome instability. DSB repair in transcriptionally active genomic regions represents a unique challenge that is associated with ataxia telangiectasia mutated (ATM) kinase-mediated transcriptional silencing. Despite emerging insights into the underlying mechanisms, how DSB silencing connects to DNA repair remains undefined. We observe that silencing within the rDNA depends on persistent DSBs. Non-homologous end-joining was the predominant mode of DSB repair allowing transcription to resume. ATM-dependent rDNA silencing in the presence of persistent DSBs led to the large-scale reorganization of nucleolar architecture, with movement of damaged chromatin to nucleolar cap regions. These findings identify ATM-dependent temporal and spatial control of DNA repair and provide insights into how communication between DSB signaling and ongoing transcription promotes genome integrity.

  18. ATM Dependent Silencing Links Nucleolar Chromatin Reorganization to DNA Damage Recognition

    Directory of Open Access Journals (Sweden)

    Shane M. Harding

    2015-10-01

    Full Text Available Resolution of DNA double-strand breaks (DSBs is essential for the suppression of genome instability. DSB repair in transcriptionally active genomic regions represents a unique challenge that is associated with ataxia telangiectasia mutated (ATM kinase-mediated transcriptional silencing. Despite emerging insights into the underlying mechanisms, how DSB silencing connects to DNA repair remains undefined. We observe that silencing within the rDNA depends on persistent DSBs. Non-homologous end-joining was the predominant mode of DSB repair allowing transcription to resume. ATM-dependent rDNA silencing in the presence of persistent DSBs led to the large-scale reorganization of nucleolar architecture, with movement of damaged chromatin to nucleolar cap regions. These findings identify ATM-dependent temporal and spatial control of DNA repair and provide insights into how communication between DSB signaling and ongoing transcription promotes genome integrity.

  19. Queueing model for an ATM multiplexer with unequal input/output link capacities

    Science.gov (United States)

    Long, Y. H.; Ho, T. K.; Rad, A. B.; Lam, S. P. S.

    1998-10-01

    We present a queuing model for an ATM multiplexer with unequal input/output link capacities in this paper. This model can be used to analyze the buffer behaviors of an ATM multiplexer which multiplexes low speed input links into a high speed output link. For this queuing mode, we assume that the input and output slot times are not equal, this is quite different from most analysis of discrete-time queues for ATM multiplexer/switch. In the queuing analysis, we adopt a correlated arrival process represented by the Discrete-time Batch Markovian Arrival Process. The analysis is based upon M/G/1 type queue technique which enables easy numerical computation. Queue length distributions observed at different epochs and queue length distribution seen by an arbitrary arrival cell when it enters the buffer are given.

  20. Inter-calibration and validation of observations from SAPHIR and ATMS instruments

    Science.gov (United States)

    Moradi, I.; Ferraro, R. R.

    2015-12-01

    We present the results of evaluating observations from microwave instruments aboard the Suomi National Polar-orbiting Partnership (NPP, ATMS instrument) and Megha-Tropiques (SAPHIR instrument) satellites. The study includes inter-comparison and inter-calibration of observations of similar channels from the two instruments, evaluation of the satellite data using high-quality radiosonde data from Atmospheric Radiation Measurement Program and GPS Radio Occultaion Observations from COSMIC mission, as well as geolocation error correction. The results of this study are valuable for generating climate data records from these instruments as well as for extending current climate data records from similar instruments such as AMSU-B and MHS to the ATMS and SAPHIR instruments. Reference: Moradi et al., Intercalibration and Validation of Observations From ATMS and SAPHIR Microwave Sounders. IEEE Transactions on Geoscience and Remote Sensing. 01/2015; DOI: 10.1109/TGRS.2015.2427165

  1. Role of ATM in bystander signaling between human monocytes and lung adenocarcinoma cells.

    Science.gov (United States)

    Ghosh, Somnath; Ghosh, Anu; Krishna, Malini

    2015-12-01

    The response of a cell or tissue to ionizing radiation is mediated by direct damage to cellular components and indirect damage mediated by radiolysis of water. Radiation affects both irradiated cells and the surrounding cells and tissues. The radiation-induced bystander effect is defined by the presence of biological effects in cells that were not themselves in the field of irradiation. To establish the contribution of the bystander effect in the survival of the neighboring cells, lung carcinoma A549 cells were exposed to gamma-irradiation, 2Gy. The medium from the irradiated cells was transferred to non-irradiated A549 cells. Irradiated A549 cells as well as non-irradiated A549 cells cultured in the presence of medium from irradiated cells showed decrease in survival and increase in γ-H2AX and p-ATM foci, indicating a bystander effect. Bystander signaling was also observed between different cell types. Phorbol-12-myristate-13-acetate (PMA)-stimulated and gamma-irradiated U937 (human monocyte) cells induced a bystander response in non-irradiated A549 (lung carcinoma) cells as shown by decreased survival and increased γ-H2AX and p-ATM foci. Non-stimulated and/or irradiated U937 cells did not induce such effects in non-irradiated A549 cells. Since ATM protein was activated in irradiated cells as well as bystander cells, it was of interest to understand its role in bystander effect. Suppression of ATM with siRNA in A549 cells completely inhibited bystander effect in bystander A549 cells. On the other hand suppression of ATM with siRNA in PMA stimulated U937 cells caused only a partial inhibition of bystander effect in bystander A549 cells. These results indicate that apart from ATM, some additional factor may be involved in bystander effect between different cell types.

  2. DNA double-strand breaks activate ATM independent of mitochondrial dysfunction in A549 cells.

    Science.gov (United States)

    Kalifa, Lidza; Gewandter, Jennifer S; Staversky, Rhonda J; Sia, Elaine A; Brookes, Paul S; O'Reilly, Michael A

    2014-10-01

    Excessive nuclear or mitochondrial DNA damage can lead to mitochondrial dysfunction, decreased energy production, and increased generation of reactive oxygen species (ROS). Although numerous cell signaling pathways are activated when cells are injured, the ataxia telangiectasia mutant (ATM) protein has emerged as a major regulator of the response to both mitochondrial dysfunction and nuclear DNA double-strand breaks (DSBs). Because mitochondrial dysfunction is often a response to excessive DNA damage, it has been difficult to determine whether nuclear and/or mitochondrial DNA DSBs activate ATM independent of mitochondrial dysfunction. In this study, mitochondrial and nuclear DNA DSBs were generated in the A549 human lung adenocarcinoma cell line by infecting with retroviruses expressing the restriction endonuclease PstI fused to a mitochondrial targeting sequence (MTS) or nuclear localization sequence (NLS) and a hemagglutinin antigen epitope tag (HA). Expression of MTS-PstI-HA or NLS-PstI-HA activated the DNA damage response defined by phosphorylation of ATM, the tumor suppressor protein p53 (TP53), KRAB-associated protein (KAP)-1, and structural maintenance of chromosomes (SMC)-1. Phosphorylated ATM and SMC1 were detected in nuclear fractions, whereas phosphorylated TP53 and KAP1 were detected in both mitochondrial and nuclear fractions. PstI also enhanced expression of the cyclin-dependent kinase inhibitor p21 and inhibited cell growth. This response to DNA damage occurred in the absence of detectable mitochondrial dysfunction and excess production of ROS. These findings reveal that DNA DSBs are sufficient to activate ATM independent of mitochondrial dysfunction and suggest that the activated form of ATM and some of its substrates are restricted to the nuclear compartment, regardless of the site of DNA damage.

  3. DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis.

    Science.gov (United States)

    Enriquez-Rios, Vanessa; Dumitrache, Lavinia C; Downing, Susanna M; Li, Yang; Brown, Eric J; Russell, Helen R; McKinnon, Peter J

    2017-01-25

    The DNA damage response (DDR) orchestrates a network of cellular processes that integrates cell-cycle control and DNA repair or apoptosis, which serves to maintain genome stability. DNA-PKcs (the catalytic subunit of the DNA-dependent kinase, encoded by PRKDC), ATM (ataxia telangiectasia, mutated), and ATR (ATM and Rad3-related) are related PI3K-like protein kinases and central regulators of the DDR. Defects in these kinases have been linked to neurodegenerative or neurodevelopmental syndromes. In all cases, the key neuroprotective function of these kinases is uncertain. It also remains unclear how interactions between the three DNA damage-responsive kinases coordinate genome stability, particularly in a physiological context. Here, we used a genetic approach to identify the neural function of DNA-PKcs and the interplay between ATM and ATR during neurogenesis. We found that DNA-PKcs loss in the mouse sensitized neuronal progenitors to apoptosis after ionizing radiation because of excessive DNA damage. DNA-PKcs was also required to prevent endogenous DNA damage accumulation throughout the adult brain. In contrast, ATR coordinated the DDR during neurogenesis to direct apoptosis in cycling neural progenitors, whereas ATM regulated apoptosis in both proliferative and noncycling cells. We also found that ATR controls a DNA damage-induced G2/M checkpoint in cortical progenitors, independent of ATM and DNA-PKcs. These nonoverlapping roles were further confirmed via sustained murine embryonic or cortical development after all three kinases were simultaneously inactivated. Thus, our results illustrate how DNA-PKcs, ATM, and ATR have unique and essential roles during the DDR, collectively ensuring comprehensive genome maintenance in the nervous system.

  4. ATM limits incorrect end utilization during non-homologous end joining of multiple chromosome breaks.

    Science.gov (United States)

    Bennardo, Nicole; Stark, Jeremy M

    2010-11-04

    Chromosome rearrangements can form when incorrect ends are matched during end joining (EJ) repair of multiple chromosomal double-strand breaks (DSBs). We tested whether the ATM kinase limits chromosome rearrangements via suppressing incorrect end utilization during EJ repair of multiple DSBs. For this, we developed a system for monitoring EJ of two tandem DSBs that can be repaired using correct ends (Proximal-EJ) or incorrect ends (Distal-EJ, which causes loss of the DNA between the DSBs). In this system, two DSBs are induced in a chromosomal reporter by the meganuclease I-SceI. These DSBs are processed into non-cohesive ends by the exonuclease Trex2, which leads to the formation of I-SceI-resistant EJ products during both Proximal-EJ and Distal-EJ. Using this method, we find that genetic or chemical disruption of ATM causes a substantial increase in Distal-EJ, but not Proximal-EJ. We also find that the increase in Distal-EJ caused by ATM disruption is dependent on classical non-homologous end joining (c-NHEJ) factors, specifically DNA-PKcs, Xrcc4, and XLF. We present evidence that Nbs1-deficiency also causes elevated Distal-EJ, but not Proximal-EJ, to a similar degree as ATM-deficiency. In addition, to evaluate the roles of these factors on end processing, we examined Distal-EJ repair junctions. We found that ATM and Xrcc4 limit the length of deletions, whereas Nbs1 and DNA-PKcs promote short deletions. Thus, the regulation of end processing appears distinct from that of end utilization. In summary, we suggest that ATM is important to limit incorrect end utilization during c-NHEJ.

  5. ATM limits incorrect end utilization during non-homologous end joining of multiple chromosome breaks.

    Directory of Open Access Journals (Sweden)

    Nicole Bennardo

    2010-11-01

    Full Text Available Chromosome rearrangements can form when incorrect ends are matched during end joining (EJ repair of multiple chromosomal double-strand breaks (DSBs. We tested whether the ATM kinase limits chromosome rearrangements via suppressing incorrect end utilization during EJ repair of multiple DSBs. For this, we developed a system for monitoring EJ of two tandem DSBs that can be repaired using correct ends (Proximal-EJ or incorrect ends (Distal-EJ, which causes loss of the DNA between the DSBs. In this system, two DSBs are induced in a chromosomal reporter by the meganuclease I-SceI. These DSBs are processed into non-cohesive ends by the exonuclease Trex2, which leads to the formation of I-SceI-resistant EJ products during both Proximal-EJ and Distal-EJ. Using this method, we find that genetic or chemical disruption of ATM causes a substantial increase in Distal-EJ, but not Proximal-EJ. We also find that the increase in Distal-EJ caused by ATM disruption is dependent on classical non-homologous end joining (c-NHEJ factors, specifically DNA-PKcs, Xrcc4, and XLF. We present evidence that Nbs1-deficiency also causes elevated Distal-EJ, but not Proximal-EJ, to a similar degree as ATM-deficiency. In addition, to evaluate the roles of these factors on end processing, we examined Distal-EJ repair junctions. We found that ATM and Xrcc4 limit the length of deletions, whereas Nbs1 and DNA-PKcs promote short deletions. Thus, the regulation of end processing appears distinct from that of end utilization. In summary, we suggest that ATM is important to limit incorrect end utilization during c-NHEJ.

  6. Evidence for long isolation among populations of a pacific cycad: genetic diversity and differentiation in Cycas seemannii A.Br. (Cycadaceae).

    Science.gov (United States)

    Keppel, G; Lee, S-W; Hodgskiss, P D

    2002-01-01

    The genetic structure of Cycas seemannii A.Br. (Cycadaceae), sampled throughout its range in Vanuatu, New Caledonia, Fiji, and Tonga, was studied using starch-gel electrophoresis. Twenty enzyme loci in 13 enzyme systems were examined. Low genetic diversity within populations (A = 1.2, P = 21.3, Ho = 0.047, and He = 0.057) and a high degree of differentiation among populations (F(ST) = 0.594) were found. This, together with low gene flow estimates, suggests genetic drift by isolation to have been most critical to the current genetic structure of the species. Inbreeding may occur to some extent (F(IS) = 0.165). The decline in abundance of C. seemannii, coupled with the low level of genetic diversity, suggest that conservation strategies are urgently needed.

  7. 异步传输技术(ATM)综述%Asynchronous Transfer Mode

    Institute of Scientific and Technical Information of China (English)

    徐华中; 徐捷

    2005-01-01

    概述了异步传输模式(ATM)的产生、概念,并分析了ATM交换原理,在此基础上简单的介绍了ATM的应用.中心议题是异步传输的研究方向,因而又介绍了ATM的走向、ATM与IP的相互结合技术及MPLS、IPOA、ATM+MPEG2等等ATM的最新研究进展.

  8. A Methodology to Integrate Security and Cost-effectiveness in ATM

    Directory of Open Access Journals (Sweden)

    Francesca Matarese

    2014-01-01

    prioritizing the threats and proposing cost-effective countermeasures for the weaknesses found. ATM security is concerned with securing ATM assets in order to prevent threats and limit their effects on the overall aviation network. This effect limitation can be achieved by removing the vulnerability from the system and/or increasing the tolerance in case of component failures due to attacks. The security risk assessment methodology proposed is based on what is currently being done by the industry (the International Civil Aviation Organization (ICAO and the International Standard Organization (ISO, etc..

  9. APPLICATION OF GRAY EVALUATION MODEL BASED ON AHP IN ATM SYSTEM

    Institute of Scientific and Technical Information of China (English)

    Wu Zhijun; Pan Wen

    2008-01-01

    This paper presents a hierarchy model of Air Traffic Management (ATM) according to the security requirements in ATM system, analyzes it by grey assessment and Analytic Hierarchy Process(AHP), and evaluates it in details. It also provides theoretical support for building an effective evaluation system. The basic idea is to use AHP and Grey Assessment to obtain the weights of the indicators, and count grey evaluation coefficients with whitening function. The compositive clustering coefficients are obtained by combining the weights and the grey evaluation coefficients. Evaluation result can be gotten from the compositive clustering coefficients.

  10. A Virtual Private Local PCN Ring Network Based on ATM VP Cross—Connection

    Institute of Scientific and Technical Information of China (English)

    LinBin; MaYingjun; 等

    1995-01-01

    Avirtual private local PCNring network (VPLPR)is proposed .VPLPR is a virtual logic ring seuved for digital cordless telephone system and it works on ATM VP cross-connection mechanism.Full-distributed data bases are organized for visitor location registers(VLR)and home location register(HLR).The signaling protocols are compatible upward to B-ISDN. The architecture and some of the main characteristics of VPLPR are given.How to configure the ATM VP cross-connection ring is described.And then a protocol conversion between STM frames and ATMcells in base station controller(BSC)is presented.

  11. Towards Designing a Biometric Measure for Enhancing ATM Security in Nigeria E-Banking System

    CERN Document Server

    Ibidapo,; Omogbadegun, Zaccheous O; Oyelami, Olufemi M

    2011-01-01

    Security measures at banks can play a critical, contributory role in preventing attacks on customers. These measures are of paramount importance when considering vulnerabilities and causation in civil litigation. Banks must meet certain standards in order to ensure a safe and secure banking environment for their customers. This paper focuses on vulnerabilities and the increasing wave of criminal activities occurring at Automated Teller Machines (ATMs) where quick cash is the prime target for criminals rather than at banks themselves. A biometric measure as a means of enhancing the security has emerged from the discourse. Keywords-Security, ATM, Biometric, Crime.

  12. ATM, ATR and DNA-PKcs expressions correlate to adverse clinical outcomes in epithelial ovarian cancers

    Science.gov (United States)

    Abdel-Fatah, Tarek M.A.; Arora, Arvind; Moseley, Paul; Coveney, Clare; Perry, Christina; Johnson, Kerstie; Kent, Christopher; Ball, Graham; Chan, Stephen; Madhusudan, Srinivasan

    2014-01-01

    Background Ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia mutated and rad3 related (ATR) and DNA-dependent protein kinase catalytic sub-unit (DNA-PKcs) play critical roles in DNA damage response (DDR) by linking DNA damage sensing to DDR effectors that regulate cell cycle progression and DNA repair. Our objective was to evaluate if ATM, ATR and DNA-PKcs expressions could predict response to therapy and clinical outcome in epithelial ovarian cancers. Methods We investigated ATM, ATR, and DNA-PKcs expressions in ovarian epithelial cancers [protein expression (n = 194 patients), mRNA expression (n = 156 patients)] and correlated to clinicopathological outcomes as well as expression of X-ray repair cross-complementing protein 1 (XRCC1), cell division cycle-45 (CDC45), cyclin-dependent kinase 1(CDK1) and Ki-67 in tumours. Results High ATM protein expression was associated with serous cystadenocarcinomas (p = 0.021) and platinum resistance (p = 0.017). High DNA-PKcs protein expression was associated with serous cystadenocarcinomas (p = 0.006) and advanced stage tumours (p = 0.018). High ATM protein (p = 0.001), high ATM mRNA (p = 0.018), high DNA-PKcs protein (p = 0.002), high DNA-PKcs mRNA (p = 0.044) and high ATR protein (p = 0.001) expressions are correlated with poor ovarian cancer specific survival (OCSS). In multivariate Cox model, high DNA-PKcs (p = 0.006) and high ATR (p = 0.043) protein expressions remain independently associated with poor OCSS. Conclusions ATM, ATR and DNA-PKcs expressions may have prognostic and predictive significances in epithelial ovarian cancer. General significance The data presented here provides evidence that ATM, ATR and DNA-PKcs involved in DDR are not only promising biomarkers but are also rational targets for personalized therapy in ovarian cancer. PMID:26674120

  13. Inactivation of ATM/ATR DNA damage checkpoint promotes androgen induced chromosomal instability in prostate epithelial cells.

    Directory of Open Access Journals (Sweden)

    Yung-Tuen Chiu

    Full Text Available The ATM/ATR DNA damage checkpoint functions in the maintenance of genetic stability and some missense variants of the ATM gene have been shown to confer a moderate increased risk of prostate cancer. However, whether inactivation of this checkpoint contributes directly to prostate specific cancer predisposition is still unknown. Here, we show that exposure of non-malignant prostate epithelial cells (HPr-1AR to androgen led to activation of the ATM/ATR DNA damage response and induction of cellular senescence. Notably, knockdown of the ATM gene expression in HPr-1AR cells can promote androgen-induced TMPRSS2: ERG rearrangement, a prostate-specific chromosome translocation frequently found in prostate cancer cells. Intriguingly, unlike the non-malignant prostate epithelial cells, the ATM/ATR DNA damage checkpoint appears to be defective in prostate cancer cells, since androgen treatment only induced a partial activation of the DNA damage response. This mechanism appears to preserve androgen induced autophosphorylation of ATM and phosphorylation of H2AX, lesion processing and repair pathway yet restrain ATM/CHK1/CHK2 and p53 signaling pathway. Our findings demonstrate that ATM/ATR inactivation is a crucial step in promoting androgen-induced genomic instability and prostate carcinogenesis.

  14. AZD6738, a novel oral inhibitor of ATR, induces synthetic lethality with ATM-deficiency in gastric cancer cells.

    Science.gov (United States)

    Min, Ahrum; Im, Seock-Ah; Jang, Hyemin; Kim, Seongyeong; Lee, Miso; Kim, Debora Keunyoung; Yang, Yaewon; Kim, Hee-Jun; Lee, Kyung-Hun; Kim, Jin Won; Kim, Tae-Yong; Oh, Do-Youn; Brown, Jeff; Lau, Alan; O Connor, Mark J; Bang, Yung-Jue

    2017-01-30

    Ataxia telangiectasia and Rad3-related (ATR) can be considered an attractive target for cancer treatment due to its deleterious effect on cancer cells harboring a homologous recombination defect (HRD). The aim of this study was to investigate the potential use of the ATR inhibitor, AZD6738, to treat gastric cancer. In SNU-601 cells with dysfunctional ATM, AZD6738 treatment led to an accumulation of DNA damage due to dysfunctional RAD51 foci formation, S phase arrest, and caspase 3-dependent apoptosis. In contrast, SNU-484 cells with functional ATM were not sensitive to AZD6738. Inhibition of ATM in SNU-484 cells enhanced AZD6738 sensitivity to a level comparable with that observed in SNU-601 cells, showing that activation of the ATM-Chk2 signaling pathway attenuates AZD6738 sensitivity. In addition, decreased HDAC1 expression was found to be associated with ATM inactivation in SNU-601 cells, demonstrating the interaction between HDAC1 and ATM can affect sensitivity to AZD6738. Furthermore, in an in vivo tumor xenograft mouse model, AZD6738 significantly suppressed tumor growth and increased apoptosis. These findings suggest synthetic lethality between ATR inhibition and ATM-deficiency in gastric cancer cells. Further clinical studies on the interaction between AZD 6738 and ATM-deficiency are warranted to develop novel treatment strategies for gastric cancer.

  15. Congestion Control for ATM Networks Based on Diagonal Recurrent Neural Networks

    Institute of Scientific and Technical Information of China (English)

    HuangYunxian; YanWei

    1997-01-01

    An adaptive control model and its algorithms based on simple diagonal recurrent neural networks are presented for the dynamic congestion control in broadband ATM networks.Two simple dynamic queuing models of real networks are used to test the performance of the suggested control scheme.

  16. Evaluating ATM Technology for Distance Education in Library and Information Science.

    Science.gov (United States)

    Stanford, Serena W.

    1997-01-01

    Investigates the impact of asynchronous transfer mode (ATM) technology in an interactive environment providing distance education in library and information science at two San Jose State University (California) sites. The main purpose of the study was to develop a reliable and valid evaluation instrument. Contains 6 tables. (Author/AEF)

  17. Designing a Strategic Plan through an Emerging Knowledge Generation Process: The ATM Experience

    Science.gov (United States)

    Zanotti, Francesco

    2012-01-01

    Purpose: The aim of this contribution is to describe a new methodology for designing strategic plans and how it was implemented by ATM, a public transportation agency based in Milan, Italy. Design/methodology/approach: This methodology is founded on a new system theory, called "quantum systemics". It is based on models and metaphors both…

  18. Risk of cancer by ATM missense mutations in the general population

    DEFF Research Database (Denmark)

    Dombernowsky, Sarah Louise; Weischer, Maren; Allin, Kristine Højgaard;

    2008-01-01

    PURPOSE: Truncating and missense mutations in the ATM gene, which cause insufficient DNA damage surveillance, allow damaged cells to proceed into mitosis, which eventually results in increased cancer susceptibility. We tested the hypotheses that ATM Ser49Cys and ATM Ser707Pro heterozygosity......: Multifactorially adjusted hazard ratios for ATM Ser49Cys heterozygotes versus noncarriers were 1.2 (95% CI, 0.9 to 1.5) for cancer overall, 0.8 (95% CI, 0.3 to 2.0) for breast cancer, 4.8 (95% CI, 2.2 to 11) for melanoma, 2.3 (95% CI, 1.1 to 5.0) for prostate cancer, and 3.4 (95% CI, 1.1 to 11) for cancer...... increase the risk of cancer overall, of breast cancer, and of 26 other cancer subtypes in the general population. PATIENTS AND METHODS: We genotyped 10,324 individuals from the Danish general population who were observed prospectively for 36 years, during which 2,056 developed cancer. RESULTS...

  19. PALB2, CHEK2 and ATM rare variants and cancer risk: Data from COGS

    NARCIS (Netherlands)

    M.C. Southey (Melissa); D. Goldgar (David); R. Winqvist (Robert); K. Pykäs (Katri); F.J. Couch (Fergus); M. Tischkowitz (Marc); W.D. Foulkes (William); J. Dennis (Joe); K. Michailidou (Kyriaki); E.J. van Rensburg (Elizabeth); T. Heikkinen (Tuomas); H. Nevanlinna (Heli); J.L. Hopper (John); T. Dörk (Thilo); K.B.M. Claes (Kathleen B.M.); J.S. Reis-Filho (Jorge); Teo, Z.L. (Zhi Ling); P. Radice (Paolo); Catucci, I. (Irene); P. Peterlongo (Paolo); H. Tsimiklis (Helen); F. Odefrey (Fabrice); J.G. Dowty (James); M.K. Schmidt (Marjanka); A. Broeks (Annegien); F.B.L. Hogervorst (Frans); S. Verhoef; T.A. Carpenter (Adrian); C. Clarke (Christine); R.J. Scott (Rodney); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias); J. Peto (Julian); I. dos Santos Silva (Isabel); O. Fletcher (Olivia); Johnson, N. (Nichola); M.K. Bolla (Manjeet K.); Sawyer, E.J. (Elinor J.); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); Marme, F. (Federik); B. Burwinkel (Barbara); R. Yang (Rongxi); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); Sanchez, M. (Marie); S.E. Bojesen (Stig); S.F. Nielsen (Sune); H. Flyger (Henrik); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); P. Menéndez (Primitiva); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); A. Ziogas (Argyrios); C.A. Clarke (Christina); H. Brenner (Hermann); Arndt, V. (Volker); C. Stegmaier (Christa); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); Muranen, T.A. (Taru A.); K. Aittomäki (Kristiina); C. Blomqvist (Carl); N.V. Bogdanova (Natalia); Antonenkova, N.N. (Natalia N.); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); A.B. Spurdle (Amanda); E. Wauters (Erwin); D. Smeets (Dominiek); B. Beuselinck (B.); O.A.M. Floris; J. Chang-Claude (Jenny); Rudolph, A. (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); J.E. Olson (Janet); C. Vachon (Celine); V.S. Pankratz (Shane); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher A.); B.E. Henderson (Brian); F.R. Schumacher (Fredrick R); L. Le Marchand (Loic); V. Kristensen (Vessela); Alnæs, G.G. (Grethe Grenaker); W. Zheng (Wei); D. Hunter (David); S. Lindstrom (Stephen); Hankinson, S.E. (Susan E.); P. Kraft (Peter); I.L. Andrulis (Irene); J.A. Knight (Julia); Glendon, G. (Gord); A.-M. Mulligan (Anna-Marie); A. Jukkola-Vuorinen (Arja); Grip, M. (Mervi); S. Kauppila (Saila); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); A. Hollestelle (Antoinette); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); J. Lissowska (Jolanta); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mats); D. Eccles (Diana); M. Rafiq (Meena); W. Tapper (William); S.M. Gerty (Sue); M.J. Hooning (Maartje); J.W.M. Martens (John); J.M. Collée; M.M.A. Tilanus-Linthorst (Madeleine); P. Hall (Per); J. Li (Jingmei); J.S. Brand (Judith S.); K. Humphreys (Keith); A. Cox (Angela); M.W.R. Reed (Malcolm); C. Luccarini (Craig); Baynes, C. (Caroline); A.M. Dunning (Alison); U. Hamann (Ute); D. Torres (Diana); H.U. Ulmer (Hans); T. Rud̈iger (Thomas); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); Durda, K. (Katarzyna); S. Slager (Susan); A.E. Toland (Amanda); C.B. Ambrosone (Christine); Yannoukakos, D. (Drakoulis); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Jones (Michael); A. González-Neira (Anna); G. Pita (G.); M.R. Alonso (M Rosario); N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); J. Simard (Jacques); M. Dumont (Martine); Soucy, P. (Penny); R. Eeles (Rosalind); K.R. Muir (K.); F. Wiklund (Fredrik); H. Grönberg (Henrik); Schleutker, J. (Johanna); B.G. Nordestgaard (Børge); M. Weischer (Maren); S.P.L. Travis (Simon); D. Neal (David); J. Donovan (Jenny); F. Hamdy (Freddie); K.T. Khaw; Stanford, J.L. (Janet L.); W.J. Blot (William); S.N. Thibodeau (Stephen); D.J. Schaid (D.); Kelley, J.L. (Joseph L.); Maier, C. (Christiane); A. Kibel (Adam); C. Cybulski (Cezary); L.A. Cannon-Albright (Lisa); K. Butterbach (Katja); Park, J. (Jong); R. Kaneva (Radka); Batra, J. (Jyotsna); P.J. Teixeira; Z. Kote-Jarai; A.A. Al Olama (Ali Amin); S. Benlloch (Sara); S.P. Renner (S.); A. Hartmann; Hein, A. (Alexander); Ruebner, M. (Matthias); Lambrechts, D. (Diether); E. Van Nieuwenhuysen (Els); I. Vergote (Ignace); Lambretchs, S. (Sandrina); J.A. Doherty (Jennifer A.); M.A. Rossing (Mary Anne); Nickels, S. (Stefan); U. Eilber (Ursula); S. Wang-Gohrke (Shan); K. Odunsi (Kunle); Sucheston-Campbell, L.E. (Lara E.); G. Friel (Grace); G. Lurie (Galina); Killeen, J.L. (Jeffrey L.); L.R. Wilkens (Lynne R.); M.T. Goodman (Marc); I.B. Runnebaum (Ingo); P. Hillemanns (Peter); L.M. Pelttari (Liisa); R. Butzow (Ralf); F. Modugno (Francesmary); R. Edwards (Robert); R.B. Ness (Roberta); K.B. Moysich (Kirsten); Bois, A. (Andreas du); P.U. Heitz; P. Harter (Philipp); Kommoss, S. (Stefan); Karlan, B.Y. (Beth Y.); C.S. Walsh (Christine); K.J. Lester (Kathryn); A. Jensen (Allan); M. Kjaer (Michael); E. Høgdall (Estrid); B. Peissel (Bernard); B. Bonnani (Bernardo); L. Bernard (Loris); E.L. Goode (Ellen); B.L. Fridley (Brooke); R.A. Vierkant (Robert); J.M. Cunningham (Julie); M.C. Larson (Melissa); Fogarty, Z.C. (Zachary C.); Kalli, K.R. (Kimberly R.); D. Liang (Dong); K.H. Lu (Karen); M.A.T. Hildebrandt (Michelle A.T.); X. Wu (Xifeng); D.A. Levine (Douglas); Dao, F. (Fanny); M. Bisogna (Maria); A. Berchuck (Andrew); E. Iversen (Erik); J.R. Marks (Jeffrey); Akushevich, L. (Lucy); D.W. Cramer (Daniel); J.M. Schildkraut (Joellen); K.L. Terry (Kathryn); E.M. Poole (Elizabeth); M.J. Stampfer (Meir J.); Tworoger, S.S. (Shelley S.); E.V. Bandera (Elisa); I. Orlow (Irene); S.H. Olson (Sara); L. Bjorge (Line); H.B. Salvesen (Helga); A.M. van Altena (Anne); K.K.H. Aben (Katja); L.A.L.M. Kiemeney (Bart); L.F. Massuger (Leon); T. Pejovic (Tanja); Y. Bean (Yukie); A. Brooks-Wilson (Angela); L.E. Kelemen (Linda); L.S. Cook (Linda S.); N.D. Le (Nhu D.); B. Górski (Bohdan); J. Gronwald (Jacek); J. Menkiszak (Janusz); C.K. Høgdall (Claus); L. Lundvall (Lene); L. Nedergaard (Lotte); S.A. Engelholm (Svend Aage); E. Dicks (Ed); J.P. Tyrer (Jonathan); I. Campbell (Ian); I. McNeish (Iain); J. Paul (James); N. Siddiqui (Nadeem); R. Glasspool (Rosalind); A.S. Whittemore (Alice); J.H. Rothstein (Joseph H.); W.P. McGuire; W. Sieh (Weiva); H. Cai (Hui); X.-O. Shu (Xiao-Ou); Teten, R.T. (Rachel T.); Sutphen, R. (Rebecca); J. McLaughlin (John); S.A. Narod (Steven A.); C. Phelan (Catherine); A.N.A. Monteiro (Alvaro N.); Fenstermacher, D. (David); Lin, H.-Y. (Hui-Yi); Permuth, J.B. (Jennifer B.); T.A. Sellers (Thomas A.); Chen, Y.A. (Y Ann); Tsai, Y.-Y. (Ya-Yu); Chen, Z. (Zhihua); A. Gentry-Maharaj (Aleksandra); S.A. Gayther (Simon); S.J. Ramus (Susan); U. Menon (Usha); A.H. Wu (Anna); C.L. Pearce (Celeste); D. Van Den Berg (David); M.C. Pike (Malcolm C.); A. Dansonka-Mieszkowska (Agnieszka); J. Plisiecka-Halasa (Joanna); J. Moes-Sosnowska (Joanna); J. Kupryjanczyk (Jolanta); P.D.P. Pharoah (Paul); H. Song (Honglin); I.M. Winship (Ingrid); G. Chenevix-Trench (Georgia); Giles, G.G. (Graham G.); S.V. Tavtigian (Sean); D.F. Easton (Douglas F.); R.L. Milne (Roger)

    2016-01-01

    textabstractBackground The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with

  20. ATM prevents DSB formation by coordinating SSB repair and cell cycle progression.

    Science.gov (United States)

    Khoronenkova, Svetlana V; Dianov, Grigory L

    2015-03-31

    DNA single-strand breaks (SSBs) arise as a consequence of spontaneous DNA instability and are also formed as DNA repair intermediates. Their repair is critical because they otherwise terminate gene transcription and generate toxic DNA double-strand breaks (DSBs) on replication. To prevent the formation of DSBs, SSB repair must be completed before DNA replication. To accomplish this, cells should be able to detect unrepaired SSBs, and then delay cell cycle progression to allow more time for repair; however, to date there is no evidence supporting the coordination of SSB repair and replication in human cells. Here we report that ataxia-telangiectasia mutated kinase (ATM) plays a major role in restricting the replication of SSB-containing DNA and thus prevents DSB formation. We show that ATM is activated by SSBs and coordinates their repair with DNA replication. SSB-mediated ATM activation is followed by a G1 cell cycle delay that allows more time for repair and thus prevents the replication of damaged DNA and DSB accrual. These findings establish an unanticipated role for ATM in the signaling of DNA SSBs and provide important insight into the molecular defects leading to genetic instability in patients with ataxia-telangiectasia.

  1. PALB2, CHEK2 and ATM rare variants and cancer risk

    DEFF Research Database (Denmark)

    Southey, Melissa C; Goldgar, David E; Winqvist, Robert

    2016-01-01

    BACKGROUND: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BR...

  2. Inhibition of TGFbeta1 Signaling Attenutates ATM Activity inResponse to Genotoxic Stress

    Energy Technology Data Exchange (ETDEWEB)

    Kirshner, Julia; Jobling, Michael F.; Pajares, Maria Jose; Ravani, Shraddha A.; Glick, Adam B.; Lavin, Martin J.; Koslov, Sergei; Shiloh, Yosef; Barcellos-Hoff, Mary Helen

    2006-09-15

    Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor {beta}1 (TGF{beta}), which is activated by radiation, is a potent and pleiotropic mediator of physiological and pathological processes. Here we show that TGF{beta} inhibition impedes the canonical cellular DNA damage stress response. Irradiated Tgf{beta}1 null murine epithelial cells or human epithelial cells treated with a small molecule inhibitor of TGF{beta} type I receptor kinase exhibit decreased phosphorylation of Chk2, Rad17 and p53, reduced {gamma}H2AX radiation-induced foci, and increased radiosensitivity compared to TGF{beta} competent cells. We determined that loss of TGF{beta} signaling in epithelial cells truncated ATM autophosphorylation and significantly reduced its kinase activity, without affecting protein abundance. Addition of TGF{beta} restored functional ATM and downstream DNA damage responses. These data reveal a heretofore undetected critical link between the microenvironment and ATM that directs epithelial cell stress responses, cell fate and tissue integrity. Thus, TGF{beta}1, in addition to its role in homoeostatic growth control, plays a complex role in regulating responses to genotoxic stress, the failure of which would contribute to the development of cancer; conversely, inhibiting TGF{beta} may be used to advantage in cancer therapy.

  3. ABR处理大豆蛋白废水产氢效能的研究%Performance of hydrogen production in anaerobic baffled reactor (ABR) treating soy protein wastewater

    Institute of Scientific and Technical Information of China (English)

    王帅; 李博; 赵倩; 姜力行; 曹莉; 李永峰

    2011-01-01

    Anaerobic Baffled Reactor (ABR) is a class derived from multi-phase anaerobic reactor stages (Staged Multi -Phase Anaerobic Reactor, SMPA) theory of the third generation of a new anaerobic reactor. To study of anaerobic baffled reactor (ABR) soy protein wastewater treatment efficiency and operating characteristics of the 4 cell room operation of the system of ABR control measures were studied using the effective volume of 42 L four -room frame ABR, MLVSS in the sludge inoculum for the 18.0 g/ L, influent COD concentration of 2 000 mg/L , HRT 48 h, (35 ± 1) ℃ and other conditions (ie OLR1. 0 kg/( m3 · d) ) , running through a period of 80 d of the study based on the influent COD concentration was increased organic load ( OLR) to change the impact of its processing power, can successfully started in 31 d and reached the initial ABR and stable operation. In addition, rate of 96% , studied different organic load, ABR reactor COD removal efficiency and gas production. On this basis, for the efficient development of ABR equipment, and successfully applied to fermentation technology and bio-hydrogen production of soy protein wastewater treatment under study was provided.%厌氧折流板反应器(ABR)是一类源于分阶段多相厌氧反应器(Staged Multi -Phase Anaerobic Reactor,SMPA)理论的第三代新型厌氧反应器.为考察厌氧折流板反应器(ABR)处理大豆蛋白生产废水的效能及其运行特征,对4格室ABR反应系统的运行控制对策进行了研究,采用有效容积为42L的四格室ABR,在污泥接种量MLVSS为18.0 g/L、进水COD质量浓度2 000 mg/L、HRT 48 h、(35±1)℃等条件下(即OLR 1.0 kg/(m3·d)),通过为期80 d的运行,研究了基于进水COD质量浓度提高的有机负荷(OLR)改变对其处理效能的影响,可在31 d内成功启动ABR并达到初步稳定运行,研究不同有机负荷下,ABR反应器的COD去除效率及产气量.为在此基础上研发高效的ABR反应设备,并成功将其应用到发

  4. ATR inhibition induces synthetic lethality and overcomes chemoresistance in TP53- or ATM-defective chronic lymphocytic leukemia cells.

    Science.gov (United States)

    Kwok, Marwan; Davies, Nicholas; Agathanggelou, Angelo; Smith, Edward; Oldreive, Ceri; Petermann, Eva; Stewart, Grant; Brown, Jeff; Lau, Alan; Pratt, Guy; Parry, Helen; Taylor, Malcolm; Moss, Paul; Hillmen, Peter; Stankovic, Tatjana

    2016-02-04

    TP53 and ataxia telangiectasia mutated (ATM) defects are associated with genomic instability, clonal evolution, and chemoresistance in chronic lymphocytic leukemia (CLL). Currently, therapies capable of providing durable remissions in relapsed/refractory TP53- or ATM-defective CLL are lacking. Ataxia telangiectasia and Rad3-related (ATR) mediates response to replication stress, the absence of which leads to collapse of stalled replication forks into chromatid fragments that require resolution through the ATM/p53 pathway. Here, using AZD6738, a novel ATR kinase inhibitor, we investigated ATR inhibition as a synthetically lethal strategy to target CLL cells with TP53 or ATM defects. Irrespective of TP53 or ATM status, induction of CLL cell proliferation upregulated ATR protein, which then became activated in response to replication stress. In TP53- or ATM-defective CLL cells, inhibition of ATR signaling by AZD6738 led to an accumulation of unrepaired DNA damage, which was carried through into mitosis because of defective cell cycle checkpoints, resulting in cell death by mitotic catastrophe. Consequently, AZD6738 was selectively cytotoxic to both TP53- and ATM-defective CLL cell lines and primary cells. This was confirmed in vivo using primary xenograft models of TP53- or ATM-defective CLL, where treatment with AZD6738 resulted in decreased tumor load and reduction in the proportion of CLL cells with such defects. Moreover, AZD6738 sensitized TP53- or ATM-defective primary CLL cells to chemotherapy and ibrutinib. Our findings suggest that ATR is a promising therapeutic target for TP53- or ATM-defective CLL that warrants clinical investigation.

  5. Clinicopathological Significance of ATM-Chk2 Expression in Sporadic Breast Cancers: a Comprehensive Analysis in Large Cohorts1

    Science.gov (United States)

    Abdel-Fatah, Tarek M.A.; Arora, Arvind; Alsubhi, Nouf; Agarwal, Devika; Moseley, Paul M.; Perry, Christina; Doherty, Rachel; Chan, Stephen Y.T.; Green, Andrew R.; Rakha, Emad; Ball, Graham; Ellis, Ian O.; Madhusudan, Srinivasan

    2014-01-01

    ATM-Chk2 network is critical for genomic stability, and its deregulation may influence breast cancer pathogenesis. We investigated ATM and Chk2 protein levels in two cohorts [cohort 1 (n = 1650) and cohort 2 (n = 252)]. ATM and Chk2 mRNA expression was evaluated in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n = 1950). Low nuclear ATM protein level was significantly associated with aggressive breast cancer including larger tumors, higher tumor grade, higher mitotic index, pleomorphism, tumor type, lymphovascular invasion, estrogen receptor (ER)−, PR −, AR −, triple-negative, and basal-like phenotypes (Ps < .05). Breast cancer 1, early onset negative, low XRCC1, low SMUG1, high FEN1, high MIB1, p53 mutants, low MDM2, low Bcl-2, low p21, low Bax, high CDK1, and low Chk2 were also more frequent in tumors with low nuclear ATM level (Ps < .05). Low ATM protein level was significantly associated with poor survival including in patients with ER-negative tumors who received adjuvant anthracycline or cyclophosphamide, methotrexate, and 5-fluorouracil–based adjuvant chemotherapy (Ps < .05). Low nuclear Chk2 protein was likely in ER −/PR −/AR −; HER-2 positive; breast cancer 1, early onset negative; low XRCC1; low SMUG1; low APE1; low polβ; low DNA-PKcs; low ATM; low Bcl-2; and low TOPO2A tumors (P < .05). In patients with ER + tumors who received endocrine therapy or ER-negative tumors who received chemotherapy, nuclear Chk2 levels did not significantly influence survival. In p53 mutant tumors, low ATM (P < .000001) or high Chk2 (P < .01) was associated with poor survival. When investigated together, low-ATM/high-Chk2 tumors have the worst survival (P = .0033). Our data suggest that ATM-Chk2 levels in sporadic breast cancer may have prognostic and predictive significance. PMID:25425972

  6. TINJAUAN YURIDIS PARA PIHAK DALAM TRANSAKSI PENGAMBILAN ATAU TRANSFER DANA MELALUI MESIN ANJUNGAN TUNAI MANDIRI (ATM

    Directory of Open Access Journals (Sweden)

    Augustinus Simanjuntak

    2007-01-01

    Full Text Available According to civil code or Burgerlijk Wetboek (BW, article 1320, there are four legal conditions of business contract must be fulfilled by parties. One of condition is agreement. Based on this condition, the position of each parties must be equal at the same level. Besides, each parties must be exist and make effective communication before get in to that agreement. Commonly, every subjects in business transaction need dealing process first between one to another party, and than the parties goes to delivering or transfering the object of transaction. At least they have to know each other first if transaction will be implemented. But, this legal term is not fully found in one of banking transaction facilities that is automatic teller machine as we called Anjungan Tunai Mandiri (ATM. The legal issue which come out from this transaction system is particularly regarding to the subjects or parties. Every time the customer goes to ATM, she or he will not find another party existing there. It means that customer do transaction without presence of bank party. So, if ATM has broken and the balance in costumer account has decreased for debit, bank does not always liable for the costumer loss. Abstract in Bahasa Indonesia : Menurut pasal 1320 Kitab Undang-undang Hukum Perdata atau Burgerlijk Wetboek (BW, ada empat syarat sahnya suatu kontrak bisnis yang harus dipenuhi oleh para pihak. Salah satunya ialah kesepakatan. Berdasarkan syarat ini, posisi para pihak harus sejajar pada tingkat yang sama. Selain itu, masing-masing pihak harus eksis dan melakukan komunikasi yang efektif sebelum mencapai kesepakatan. Lazimnya, setiap subjek dalam transaksi bisnis membutuhkan proses persetujuan terlebih dahulu antara pihak yang satu dengan pihak lainnya, dan kemudian para pihak menuju pada penyerahan atau pemindahan objek transaksi. Paling tidak, mereka harus saling mengetahui bila transaksi akan dilaksanakan. Tetapi, syarat hukum ini tidak sepenuhnya ditemukan di salah

  7. Mudanças nos parâmetros do clique durante a captação do BERA Changes in click characteristics during ABR recording

    Directory of Open Access Journals (Sweden)

    Mariana Lopes Fávero

    2007-02-01

    Full Text Available Mudanças no estímulo auditivo afetam os potenciais evocados do BERA e ajudam no diagnóstico, principalmente em indivíduos com neuropatia auditiva. Alguns pacientes com neuropatia auditiva perdem as emissões otoacústicas evocadas e, nestes casos, a comparação das respostas obtidas com cliques rarefeitos e condensados e a redução da freqüência de apresentação deste clique podem mostrar um microfonismo coclear alargado ou uma melhor captação do potencial elétrico. OBJETIVO: Analisar o efeito destas mudanças sobre os potenciais captados em pacientes com deficiência auditiva, como forma de melhorar o diagnóstico. FORMA DO ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: 59 pacientes com deficiência auditiva foram submetidos à captação do BERA usando cliques rarefeitos e condensados apresentados a uma freqüência de 27,7/seg. e cliques rarefeitos apresentados a uma freqüência de 3,3/seg. Os resultados foram comparados com as emissões otoacústicas evocadas. RESULTADOS: Oito (13,53% pacientes apresentaram alterações nos resultados do BERA com as mudanças nas características do clique, como microfonismo coclear alargado, ou uma melhora no traçado. Cinco não apresentavam emissões otoacústicas evocadas. CONCLUSÃO: Mudanças nas características do clique podem melhorar o diagnóstico topográfico de perda auditiva, principalmente no grupo de indivíduos com neuropatia auditiva e ausência de emissões otoacústicas, onde muitas vezes somente desta forma é possível o diagnóstico.Manipulation of auditory stimuli affect the ABR evoked potentials and aid the diagnosis, particularly in auditory neuropathy patients. Some patients with auditory neuropathy lose evoked otoacoustic emissions over time; in these cases, comparing responses to rarefaction and condensation clicks, and decreasing the stimulus rate can show an extended cochlear microphonism or yield an improved electric potential record. AIM: To analyze the effect

  8. Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation

    DEFF Research Database (Denmark)

    Gatei, Magtouf; Sloper, Katie; Sørensen, Claus Storgaard

    2003-01-01

    In mammals, the ATM (ataxia-telangiectasia-mutated) and ATR (ATM and Rad3-related) protein kinases function as critical regulators of the cellular DNA damage response. The checkpoint functions of ATR and ATM are mediated, in part, by a pair of checkpoint effector kinases termed Chk1 and Chk2...

  9. EGb 761 protects cardiac microvascular endothelial cells against hypoxia/reoxygenation injury and exerts inhibitory effect on ATM pathway.

    Science.gov (United States)

    Zhang, Chao; Wang, Deng-Feng; Zhang, Zhuang; Han, Dong; Yang, Kan

    2016-12-14

    Ginkgo biloba extract (EGb 761) has been widely clinically used to reduce myocardial ischemia reperfusion injury (MIRI). Microvascular endothelial cells (MVECs) may be a proper cellular model in vitro for the effect and mechanism study against MIRI. However, the effect of EGb 761 on MVECs resisting hypoxia/reoxygenation (H/R) injury is little reported. In this study, H/R-injuried MVECs were treated with EGb 761, then cell viability, apoptosis, ROS production, SOD activity, caspase-3 activity, and the protein level of ATM, γ-H2AX, p53, Bax were measured. ATM siRNA was transfected to study the changes of protein in ATM pathway. EGb 761 presented protective effect on H/R-injuried MVECs with decreasing cell death, apoptosis and ROS, and elevated SOD activity. Next, EGb 761 could inhibit H/R-induced ATM, γ-H2AX, p53, Bax in a dose-dependent manner. Moreover, ATM siRNA also could inhibit H/R-induced ATM, γ-H2AX, p53, Bax. Overall, these findings verify EGb 761 protects cardiac MVECs from H/R injury, and for the first time, illustrate the influence on ATM pathway and apoptosis of EGb 761 via dampening ROS.

  10. Tetraploidization or autophagy: The ultimate fate of senescent human endometrial stem cells under ATM or p53 inhibition.

    Science.gov (United States)

    Borodkina, Aleksandra V; Shatrova, Alla N; Deryabin, Pavel I; Grukova, Anastasiya A; Nikolsky, Nikolay N; Burova, Elena B

    2016-01-01

    Previously we demonstrated that endometrium-derived human mesenchymal stem cells (hMESCs) via activation of the ATM/p53/p21/Rb pathway enter the premature senescence in response to oxidative stress. Down regulation effects of the key components of this signaling pathway, particularly ATM and p53, on a fate of stressed hMESCs have not yet been investigated. In the present study by using the specific inhibitors Ku55933 and Pifithrin-α, we confirmed implication of both ATM and p53 in H(2)O(2)-induced senescence of hMESCs. ATM or p53 down regulation was shown to modulate differently the cellular fate of H(2)O(2)-treated hMESCs. ATM inhibition allowed H(2)O(2)-stimulated hMESCs to escape the permanent cell cycle arrest due to loss of the functional ATM/p53/p21/Rb pathway, and induced bypass of mitosis and re-entry into S phase, resulting in tetraploid cells. On the contrary, suppression of the p53 transcriptional activity caused a pronounced cell death of H(2)O(2)-treated hMESCs via autophagy induction. The obtained data clearly demonstrate that down regulation of ATM or p53 shifts senescence of human endometrial stem cells toward tetraploidization or autophagy.

  11. A novel ATM-dependent checkpoint defect distinct from loss of function mutation promotes genomic instability in melanoma.

    Science.gov (United States)

    Spoerri, Loredana; Brooks, Kelly; Chia, KeeMing; Grossman, Gavriel; Ellis, Jonathan J; Dahmer-Heath, Mareike; Škalamera, Dubravka; Pavey, Sandra; Burmeister, Bryan; Gabrielli, Brian

    2016-05-01

    Melanomas have high levels of genomic instability that can contribute to poor disease prognosis. Here, we report a novel defect of the ATM-dependent cell cycle checkpoint in melanoma cell lines that promotes genomic instability. In defective cells, ATM signalling to CHK2 is intact, but the cells are unable to maintain the cell cycle arrest due to elevated PLK1 driving recovery from the arrest. Reducing PLK1 activity recovered the ATM-dependent checkpoint arrest, and over-expressing PLK1 was sufficient to overcome the checkpoint arrest and increase genomic instability. Loss of the ATM-dependent checkpoint did not affect sensitivity to ionizing radiation demonstrating that this defect is distinct from ATM loss of function mutations. The checkpoint defective melanoma cell lines over-express PLK1, and a significant proportion of melanomas have high levels of PLK1 over-expression suggesting this defect is a common feature of melanomas. The inability of ATM to impose a cell cycle arrest in response to DNA damage increases genomic instability. This work also suggests that the ATM-dependent checkpoint arrest is likely to be defective in a higher proportion of cancers than previously expected.

  12. The ATM- and ATR-related SCD domain is over-represented in proteins involved in nervous system development.

    Science.gov (United States)

    Cara, Lukas; Baitemirova, Medina; Follis, Jack; Larios-Sanz, Maia; Ribes-Zamora, Albert

    2016-01-08

    ATM and ATR are cellular kinases with a well-characterized role in the DNA-damage response. Although the complete set of ATM/ATR targets is unknown, they often contain clusters of S/TQ motifs that constitute an SCD domain. In this study, we identified putative ATM/ATR targets that have a conserved SCD domain across vertebrates. Using this approach, we have identified novel putative ATM/ATR targets in pathways known to be under direct control of these kinases. Our analysis has also unveiled significant enrichment of SCD-containing proteins in cellular pathways, such as vesicle trafficking and actin cytoskeleton, where a regulating role for ATM/ATR is either unknown or poorly understood, hinting at a much broader and overarching role for these kinases in the cell. Of particular note is the overrepresentation of conserved SCD-containing proteins involved in pathways related to neural development. This finding suggests that ATM/ATR could be directly involved in controlling this process, which may be linked to the adverse neurological effects observed in patients with mutations in ATM.

  13. Regulation of ATM-Dependent DNA Damage Responses in Breast Cancer by the RhoGEF Net1

    Science.gov (United States)

    2015-05-01

    Award Number: W81XWH-12-1-0014 TITLE: Regulation of ATM -Dependent DNA Damage Responses in Breast Cancer by the RhoGEF Net1 PRINCIPAL INVESTIGATOR...signaling in breast cancer. Body Task 1: Determine the role of Net1 in ATM -mediated DNA repair (Months 24-27). In the previous reporting period of...the fellowship, we observed that knockdown of Net1A dramatically decreased activation of ATM and its downstream targets Chk2 and H2AX in MCF7 cells

  14. Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen.

    Science.gov (United States)

    Kozlov, Sergei V; Waardenberg, Ashley J; Engholm-Keller, Kasper; Arthur, Jonathan W; Graham, Mark E; Lavin, Martin

    2016-03-01

    Ataxia-telangiectasia, mutated (ATM) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signaling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoints, initiating DNA repair, and regulating gene expression. ATM kinase can be activated by a variety of stimuli, including oxidative stress. Here, we confirmed activation of cytoplasmic ATM by autophosphorylation at multiple sites. Then we employed a global quantitative phosphoproteomics approach to identify cytoplasmic proteins altered in their phosphorylation state in control and ataxia-telangiectasia (A-T) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites, including 6,686 high-confidence sites mapping to 2,536 unique proteins. A total of 62 differentially phosphorylated peptides were identified; of these, 43 were phosphorylated in control but not in A-T cells, and 19 varied in their level of phosphorylation. Motif enrichment analysis of phosphopeptides revealed that consensus ATM serine glutamine sites were overrepresented. When considering phosphorylation events, only observed in control cells (not observed in A-T cells), with predicted ATM sites phosphoSerine/phosphoThreonine glutamine, we narrowed this list to 11 candidate ATM-dependent cytoplasmic proteins. Two of these 11 were previously described as ATM substrates (HMGA1 and UIMCI/RAP80), another five were identified in a whole cell extract phosphoproteomic screens, and the remaining four proteins had not been identified previously in DNA damage response screens. We validated the phosphorylation of three of these proteins (oxidative stress responsive 1 (OSR1), HDGF, and ccdc82) as ATM dependent after H2O2 exposure, and another protein (S100A11) demonstrated ATM

  15. Regulation of ATM-Dependent DNA Damage Responses in Breast Cancer by the RhoGEF Net1

    Science.gov (United States)

    2014-04-01

    DSBs (Months 19-21). MDC1 is an ATM substrate and mediates the accumulation of many DDR factors at the sites of DSBs, including the ATM, the MRN...to IR. Task 2b: Determine the role of Net1 in ATM-mediated DNA repair (Months 13-24). The DNA damage response ( DDR ) is a signal transduction...pathway leading to transient cell cycle arrest, DNA repair, and elimination of damaged cells by apoptosis (12). DDR is primarily mediated by the

  16. ATM-dependent phosphorylation of MRE11 controls extent of resection during homology directed repair by signalling through Exonuclease 1

    OpenAIRE

    Kijas, Amanda W.; Lim, Yi Chieh; Bolderson, Emma; Cerosaletti, Karen; Gatei, Magtouf; Jakob, Burkhard; Tobias, Frank; Taucher-Scholz, Gisela; Gueven, Nuri; Oakley, Greg; Concannon, Patrick; Wolvetang, Ernst; Khanna, Kum Kum; Wiesmüller, Lisa; Lavin, Martin F.

    2015-01-01

    The MRE11/RAD50/NBS1 (MRN) complex plays a central role as a sensor of DNA double strand breaks (DSB) and is responsible for the efficient activation of ataxia-telangiectasia mutated (ATM) kinase. Once activated ATM in turn phosphorylates RAD50 and NBS1, important for cell cycle control, DNA repair and cell survival. We report here that MRE11 is also phosphorylated by ATM at S676 and S678 in response to agents that induce DNA DSB, is dependent on the presence of NBS1, and does not affect the ...

  17. Defective ATM-Kap-1-mediated chromatin remodeling impairs DNA repair and accelerates senescence in progeria mouse model.

    Science.gov (United States)

    Liu, Baohua; Wang, Zimei; Ghosh, Shrestha; Zhou, Zhongjun

    2013-04-01

    ATM-mediated phosphorylation of KAP-1 triggers chromatin remodeling and facilitates the loading and retention of repair proteins at DNA lesions. Mouse embryonic fibroblasts (MEFs) derived from Zmpste24(-/-) mice undergo early senescence, attributable to delayed recruitment of DNA repair proteins. Here, we show that ATM-Kap-1 signaling is compromised in Zmpste24(-/-) MEFs, leading to defective DNA damage-induced chromatin remodeling. Knocking down Kap-1 rescues impaired chromatin remodeling, defective DNA repair and early senescence in Zmpste24(-/-) MEFs. Thus, ATM-Kap-1-mediated chromatin remodeling plays a critical role in premature aging, carrying significant implications for progeria therapy.

  18. Reduction of COD and Turbidity of Effluent in the Swine Productions Unit Employing Anaerobic Baffled Reactor (ABR Followed by Biological Filters and Sand Filter

    Directory of Open Access Journals (Sweden)

    Euzebio Beli

    2010-04-01

    Full Text Available The growing swine production is constantly in conflict with the environment due to the lack of environmental management directed to the cycle of animal production and the industrial sector, mainly due to the mishandling of slurry produced. In association with large concentrations of confined animals appear huge dumps of organic matter, inorganic nutrients and gaseous emissions, which require special care for its disposal to the environment. The aim of this study was to evaluate the use of an anaerobic baffled reactor (ABR in series with two downflow biological filters, followed by a sand filter as a polishing treatment. It were analyzed the reduction of COD and turbidity, and the behavior of pH in all phases of treatment. The removal of COD in the conjugated system, which occurred during treatment ranged from 74.55% to 94.41% with an average removal of 84.24%. In turn, the removal of turbidity from the period ranged from 53.07% to 96.11% with an average removal of 85.49%. In the studied period the pH changed from 5,6 to 8,4. This system was efficient in the removal of COD and turbidity of swine wastewater.

  19. ATM-WPCC技术的开发应用及前景展望%Application and prospects of ATM-WPCC technology

    Institute of Scientific and Technical Information of China (English)

    俞正千; 胡楠; 王桂林

    2013-01-01

    阐述了碱回收苛化及白泥回收传统生产模式和工业碳酸钙生产原理与方法,比较分析了工业碳酸钙的大型工业生产方法与传统碱回收的苛化及白泥回收的异同,通过介绍ATM-WPCC技术(新型苛化及白泥资源化技术)生产WPCC(晶体白泥碳酸钙),阐明了实现碱回收苛化白泥处置与工业沉淀碳酸钙生产行业整合的技术可行性和整合的效益。%The traditional production process of causticizing and lime mud recovery in alkali recovery systems and industrial calcium carbonate production principle and method were explained, and comparative analysis on large scale industrial production method of industrial calcium carbonate with the similarities and differences of the traditional alkali recovery causticizing and lime mud recovery was conducted in this paper. The feasibility and integrated beneifts of integration of disposal of lime mud from alkali recovery causticizing and industrial precipitated calcium carbonate production technology were illustrated with introducing ATM-WPCC new causticizing process and the comprehensive utilization technology of lime mud to be used to produce calcium carbonate.

  20. Real-time services in IP network architectures

    Science.gov (United States)

    Gilardi, Antonella

    1996-12-01

    The worldwide internet system seems to be the success key for the provision of real time multimedia services to both residential and business users and someone says that in such a way broadband networks will have a reason to exist. This new class of applications that use multiple media (voice, video and data) impose constraints to the global network nowadays consisting of subnets with various data links. The attention will be focused on the interconnection of IP non ATM and ATM networks. IETF and ATM forum are currently involved in the developing specifications suited to adapt the connectionless IP protocol to the connection oriented ATM protocol. First of all the link between the ATM and the IP service model has to be set in order to match the QoS and traffic requirements defined in the relative environment. A further significant topic is represented by the mapping of IP resource reservation model onto the ATM signalling and in the end it is necessary to define how the routing works when there are QoS parameters associated. This paper, considering only unicast applications, will examine the above issues taking as a starting point the situation where an host launches as call set up request with the relevant QoS and traffic descriptor and at some point a router at the edge of the ATM network has to decide how forwarding and request in order to establish an end to end link with the right capabilities. The aim is to compare the proposals emerging from different standard bodies to point out convergency or incompatibility.

  1. Results from CrIS-ATMS Obtained Using the AIRS Science Team Retrieval Methodology

    Science.gov (United States)

    Susskind, Joel; Kouvaris, Louis C.; Iredell, Lena

    2013-01-01

    AIRS was launched on EOS Aqua in May 2002, together with AMSU-A and HSB (which subsequently failed early in the mission), to form a next generation polar orbiting infrared and microwave atmospheric sounding system. AIRS/AMSU had two primary objectives. The first objective was to provide real-time data products available for use by the operational Numerical Weather Prediction Centers in a data assimilation mode to improve the skill of their subsequent forecasts. The second objective was to provide accurate unbiased sounding products with good spatial coverage that are used to generate stable multi-year climate data sets to study the earth's interannual variability, climate processes, and possibly long-term trends. AIRS/AMSU data for all time periods are now being processed using the state of the art AIRS Science Team Version-6 retrieval methodology. The Suomi-NPP mission was launched in October 2011 as part of a sequence of Low Earth Orbiting satellite missions under the "Joint Polar Satellite System" (JPSS). NPP carries CrIS and ATMS, which are advanced infra-red and microwave atmospheric sounders that were designed as follow-ons to the AIRS and AMSU instruments. The main objective of this work is to assess whether CrIS/ATMS will be an adequate replacement for AIRS/AMSU from the perspective of the generation of accurate and consistent long term climate data records, or if improved instruments should be developed for future flight. It is critical for CrIS/ATMS to be processed using an algorithm similar to, or at least comparable to, AIRS Version-6 before such an assessment can be made. We have been conducting research to optimize products derived from CrIS/ATMS observations using a scientific approach analogous to the AIRS Version-6 retrieval algorithm. Our latest research uses Version-5.70 of the CrIS/ATMS retrieval algorithm, which is otherwise analogous to AIRS Version-6, but does not yet contain the benefit of use of a Neural-Net first guess start-up system

  2. Issues in ATM Support of High-Performance, Geographically Distributed Computing

    Science.gov (United States)

    Claus, Russell W.; Dowd, Patrick W.; Srinidhi, Saragur M.; Blade, Eric D.G

    1995-01-01

    This report experimentally assesses the effect of the underlying network in a cluster-based computing environment. The assessment is quantified by application-level benchmarking, process-level communication, and network file input/output. Two testbeds were considered, one small cluster of Sun workstations and another large cluster composed of 32 high-end IBM RS/6000 platforms. The clusters had Ethernet, fiber distributed data interface (FDDI), Fibre Channel, and asynchronous transfer mode (ATM) network interface cards installed, providing the same processors and operating system for the entire suite of experiments. The primary goal of this report is to assess the suitability of an ATM-based, local-area network to support interprocess communication and remote file input/output systems for distributed computing.

  3. Results from CrIS/ATMS Obtained Using an "AIRS Version-6 Like" Retrieval Algorithm

    Science.gov (United States)

    Susskind, Joel; Kouvaris, Louis; Iredell, Lena; Blaisdell, John

    2015-01-01

    AIRS and CrIS Version-6.22 O3(p) and q(p) products are both superior to those of AIRS Version-6.Monthly mean August 2014 Version-6.22 AIRS and CrIS products agree reasonably well with OMPS, CERES, and witheach other. JPL plans to process AIRS and CrIS for many months and compare interannual differences. Updates to thecalibration of both CrIS and ATMS are still being finalized. We are also working with JPL to develop a joint AIRS/CrISlevel-1 to level-3 processing system using a still to be finalized Version-7 retrieval algorithm. The NASA Goddard DISCwill eventually use this system to reprocess all AIRS and recalibrated CrIS/ATMS. .

  4. Analysis of CrIS ATMS and AIRS AMSU Data Using Scientifically Equivalent Retrieval Algorithms

    Science.gov (United States)

    Susskind, Joel; Kouvaris, Louis; Iredell, Lena; Blaisdell, John

    2016-01-01

    Monthly mean August 2014 Version-6.28 AIRS and CrIS products agree well with OMPS and CERES, and reasonably well with each other. Version-6.28 CrIS total precipitable water is biased dry compared to AIRS. AIRS and CrIS Version-6.36 water vapor products are both improved compared to Version-6.28. Version-6.36 AIRS and CrIS total precipitable water also shows improved agreement with each other. AIRS Version-6.36 total ozone agrees even better with OMPS than does AIRS Version-6.28, and gives reasonable results during polar winter where OMPS does not generate products. CrIS and ATMS are high spectral resolution IR and Microwave atmospheric sounders currently flying on the SNPP satellite, and are also scheduled for flight on future NPOESS satellites. CrIS/ATMS have similar sounding capabilities to those of the AIRS/AMSU sounder suite flying on EOS Aqua. The objective of this research is to develop and implement scientifically equivalent AIRS/AMSU and CrIS/ATMS retrieval algorithms with the goal of generating a continuous data record of AIRS/AMSU and CrIS/ATMS level-3 data products with a seamless transition between them in time. To achieve this, monthly mean AIRS/AMSU and CrIS/ATMS retrieved products, and more importantly their interannual differences, should show excellent agreement with each other. The currently operational AIRS Science Team Version-6 retrieval algorithm has generated 14 years of level-3 data products. A scientifically improved AIRS Version-7 retrieval algorithm is expected to become operational in 2017. We see significant improvements in water vapor and ozone in Version-7 retrieval methodology compared to Version-6.We are working toward finalization and implementation of scientifically equivalent AIRS/AMSU and CrIS/ATMS Version-7 retrieval algorithms to be used for the eventual processing of all AIRS/AMSU and CrIS/ATMS data. The latest version of our retrieval algorithm is Verison-6.36, which includes almost all the improvements we want in Version-7

  5. The depletion of ATM inhibits colon cancer proliferation and migration via B56γ2-mediated Chk1/p53/CD44 cascades.

    Science.gov (United States)

    Liu, Rui; Tang, Jiajia; Ding, Chaodong; Liang, Weicheng; Zhang, Li; Chen, Tianke; Xiong, Yan; Dai, Xiaowei; Li, Wenfeng; Xu, Yunsheng; Hu, Jin; Lu, Liting; Liao, Wanqin; Lu, Xincheng

    2017-04-01

    Ataxia-telangiectasia mutated (ATM) protein kinase is a major guardian of genomic stability, and its well-established function in cancer is tumor suppression. Here, we report an oncogenic role of ATM. Using two isogenic sets of human colon cancer cell lines that differed only in their ATM status, we demonstrated that ATM deficiency significantly inhibits cancer cell proliferation, migration, and invasion. The tumor-suppressive function of ATM depletion is not modulated by the compensatory activation of ATR, but it is associated with B56γ2-mediated Chk1/p53/CD44 signaling pathways. Under normal growth conditions, the depletion of ATM prevents B56γ2 ubiquitination and degradation, which activates PP2A-mediated Chk1/p53/p21 signaling pathways, leading to senescence and cell cycle arrest. CD44 was validated as a novel ATM target based on its ability to rescue cell migration and invasion defects in ATM-depleted cells. The activation of p53 induced by ATM depletion suppresses CD44 transcription, thus resulting in epithelial-mesenchymal transition (EMT) and cell migration suppression. Our study suggests that ATM has tumorigenic potential in post-formed colon neoplasia, and it supports ATM as an appealing target for improving cancer therapy.

  6. A Formal Integrity Framework with Application to a Secure Information ATM (SIATM)

    Science.gov (United States)

    2012-10-01

    biometric factor in addition to an RFID card swipe. For simplicity in this example model, this is assumed to be constant across all users. ATM files : FFile...between SIATMs, printing of RFID - tagged documents and downgrade of documents between classification levels. With regards to RFID -tagging of documents...tamperResistanceValue : ContextValueProb; userIdentificationValue : ContextValueProb; [user does simple RFID swipe] userAuthenticationValue

  7. ATM protects against oxidative stress induced by oxidized low-density lipoprotein

    OpenAIRE

    2011-01-01

    Chronic oxidative stress is involved in the pathogenesis of multiple inflammatory diseases, including cardiovascular disease and atherosclerosis. The rare autosomal recessive disorder Ataxia-telangiectasia (A-T) is characterized by progressive cerebellar ataxia secondary to Purkinje cell death, immunodeficiency, and increased cancer incidence. ATM, the protein mutated in A-T, plays a key role in cellular DNA-damage responses. A-T cells show poor cellular anti-oxidant defences and increased ox...

  8. ATM Coastal Topography - Louisiana, 2001: UTM Zone 16 (Part 2 of 2)

    Science.gov (United States)

    Yates, Xan; Nayegandhi, Amar; Brock, John C.; Sallenger, Asbury H.; Klipp, Emily S.; Wright, C. Wayne

    2009-01-01

    These remotely sensed, geographically referenced elevation measurements of lidar-derived first-surface (FS) topography were produced collaboratively by the U.S. Geological Survey (USGS), Florida Integrated Science Center (FISC), St. Petersburg, FL, and the National Aeronautics and Space Administration (NASA), Wallops Flight Facility, VA. This project provides highly detailed and accurate datasets of a portion of the Louisiana coastline beach face within UTM Zone 16, from Grand Isle to the Chandeleur Islands, acquired September 7 and 9, 2001. The datasets are made available for use as a management tool to research scientists and natural-resource managers. An innovative scanning lidar instrument originally developed by NASA, and known as the Airborne Topographic Mapper (ATM), was used during data acquisition. The ATM system is a scanning lidar system that measures high-resolution topography of the land surface and incorporates a green-wavelength laser operating at pulse rates of 2 to 10 kilohertz. Measurements from the laser-ranging device are coupled with data acquired from inertial navigation system (INS) attitude sensors and differentially corrected global positioning system (GPS) receivers to measure topography of the surface at accuracies of +/-15 centimeters. The nominal ATM platform is a Twin Otter or P-3 Orion aircraft, but the instrument may be deployed on a range of light aircraft. Elevation measurements were collected over the survey area using the ATM system, and the resulting data were then processed using the Airborne Lidar Processing System (ALPS), a custom-built processing system developed in a NASA-USGS collaboration. ALPS supports the exploration and processing of lidar data in an interactive or batch mode. Modules for presurvey flight-line definition, flight-path plotting, lidar raster and waveform investigation, and digital camera image playback have been developed. Processing algorithms have been developed to extract the range to the first and

  9. ATM Coastal Topography-Louisiana, 2001: UTM Zone 15 (Part 1 of 2)

    Science.gov (United States)

    Yates, Xan; Nayegandhi, Amar; Brock, John C.; Sallenger, A.H.; Klipp, Emily S.; Wright, C. Wayne

    2010-01-01

    These remotely sensed, geographically referenced elevation measurements of lidar-derived first-surface (FS) topography were produced collaboratively by the U.S. Geological Survey (USGS), Florida Integrated Science Center (FISC), St. Petersburg, FL, and the National Aeronautics and Space Administration (NASA), Wallops Flight Facility, VA. This project provides highly detailed and accurate datasets of a portion of the Louisiana coastline beach face within UTM Zone 15, from Isles Dernieres to Grand Isle, acquired September 7 and 10, 2001. The datasets are made available for use as a management tool to research scientists and natural-resource managers. An innovative scanning lidar instrument originally developed by NASA, and known as the Airborne Topographic Mapper (ATM), was used during data acquisition. The ATM system is a scanning lidar system that measures high-resolution topography of the land surface and incorporates a green-wavelength laser operating at pulse rates of 2 to 10 kilohertz. Measurements from the laser-ranging device are coupled with data acquired from inertial navigation system (INS) attitude sensors and differentially corrected global positioning system (GPS) receivers to measure topography of the surface at accuracies of +/-15 centimeters. The nominal ATM platform is a Twin Otter or P-3 Orion aircraft, but the instrument may be deployed on a range of light aircraft. Elevation measurements were collected over the survey area using the ATM system, and the resulting data were then processed using the Airborne Lidar Processing System (ALPS), a custom-built processing system developed in a NASA-USGS collaboration. ALPS supports the exploration and processing of lidar data in an interactive or batch mode. Modules for presurvey flight-line definition, flight-path plotting, lidar raster and waveform investigation, and digital camera image playback have been developed. Processing algorithms have been developed to extract the range to the first and last

  10. Sistem Pemrosesan Transaksi (SPT) Anjungan Tunai Mandiri (ATM) Pada PT. Bank CIMB Niaga Medan

    OpenAIRE

    Maya, Dewi

    2010-01-01

    Penelitian ini bertujuan untuk mengetahui Bagaimana Sistem Pemrosesan Transaksi ATM yang digunakan oleh Bank CIMB Niaga. Penelitian ini merupakan penelitian deskriptif. Jenis data dan sumber data yang dipakai adalah data primer dan data sekunder. Penelitian ini dilakukan pada PT. Bank Cimb Niaga Medan yang beralamat di jalan Bukit Barisan No. 5 Medan. Jadwal penelitian dimulai dari bulan Juli 2009 sampai bulan Oktober 2009. Teknik pengumpulan data adalah wawancara dan teknik kepustakaan. M...

  11. ENTORNOS MPLS Y ATM PARA EL TRANSPORTE DE VOZ SOBRE INTERNET

    Directory of Open Access Journals (Sweden)

    Nancy Yaneth Gelvez García

    2012-08-01

    Full Text Available Este artículo presenta los resultados obtenidos en el estudio de la calidad de servicio sobre redes IP en tráficos sensibles al retardo como la VoIP sobre la tecnología ATM y MPLS. Se analizaran diferentes topologías con características propias que permitirán evaluar valores tales como el retardo y el ancho de banda.

  12. THE TRANSITION PROBABILITY MATRIX OF A MARKOV CHAIN MODEL IN AN ATM NETWORK

    Institute of Scientific and Technical Information of China (English)

    YUE Dequan; ZHANG Huachen; TU Fengsheng

    2003-01-01

    In this paper we consider a Markov chain model in an ATM network, which has been studied by Dag and Stavrakakis. On the basis of the iterative formulas obtained by Dag and Stavrakakis, we obtain the explicit analytical expression of the transition probability matrix. It is very simple to calculate the transition probabilities of the Markov chain by these expressions. In addition, we obtain some results about the structure of the transition probability matrix, which are helpful in numerical calculation and theoretical analysis.

  13. Fielded ATM network for the Air National Guard Global Yankee Fort Drum exercise

    Science.gov (United States)

    Kaminski, Robert L.; Hague, Daniel; Maciag, Chester

    1996-06-01

    This paper will review the deployment, demonstration, and test of an Asynchronous Transfer Mode (ATM) network to support the Air National Guard `Global Yankee' field exercise held at Fort Drum, New York. The network provided forty five (45) megabit per second (mbps) ATM connections between the Air Operations Center (AOC) and Forward Operating Location (FOL) located at Fort Drum, the State University of New York (SUNY) Health Science Center located in Syracuse, New York and Rome Laboratory located in Rome, New York. Connections were made with both fiber and free space equipment. The fiber connections used were part of the existing ATM New York Network (NYNet) between Rome Lab, SUNY Health Science Center and NYNEX Corporation. This network was extended to Watertown, New York by NYNEX to provide connectivity to Fort Drum. The free space links were provided by commercial DS-3 (45 mbps) radios, and 2 to 6 mbps Troposcatter Satellite Support Radios (TSSRs). This paper will also discuss significant digital Command, Control, Communications and Intelligence enhancements to the battlefield provided by the deployed ATM network. For example, videoconferencing and shared workspace capability was demonstrated over the AOC-to-FOL TSSR link, enabling remote intelligence briefings, pilot Battle Damage Assessment, and Search and Rescue coordination. Remote Medical Diagnostics videoconferencing with MRI high resolution digital imagery was demonstrated between the FOL, AOC, and SUNY Health Science Center. Finally, the network provided connectivity between the AOC and the Joint Surveillance System (JSS) radar's located at Griffiss Air Force BAse. The JSS data combined with the Rome Lab developed Radar Analysis Program provided AOC personnel with air picture areas of interest.

  14. Nitric oxide induces ataxia telangiectasia mutated (ATM) protein-dependent γH2AX protein formation in pancreatic β cells.

    Science.gov (United States)

    Oleson, Bryndon J; Broniowska, Katarzyna A; Schreiber, Katherine H; Tarakanova, Vera L; Corbett, John A

    2014-04-18

    In this study, the effects of cytokines on the activation of the DNA double strand break repair factors histone H2AX (H2AX) and ataxia telangiectasia mutated (ATM) were examined in pancreatic β cells. We show that cytokines stimulate H2AX phosphorylation (γH2AX formation) in rat islets and insulinoma cells in a nitric oxide- and ATM-dependent manner. In contrast to the well documented role of ATM in DNA repair, ATM does not appear to participate in the repair of nitric oxide-induced DNA damage. Instead, nitric oxide-induced γH2AX formation correlates temporally with the onset of irreversible DNA damage and the induction of apoptosis. Furthermore, inhibition of ATM attenuates cytokine-induced caspase activation. These findings show that the formation of DNA double strand breaks correlates with ATM activation, irreversible DNA damage, and ATM-dependent induction of apoptosis in cytokine-treated β cells.

  15. Challenges of Automated Teller Machine (ATM Usage and Fraud Occurrences in Nigeria – A Case Study of Selected Banks in Minna Metropolis

    Directory of Open Access Journals (Sweden)

    Adelowo Solomon Adepoju

    2010-08-01

    Full Text Available Over time, consumers have come to depend on and trust the Automatic Teller Machine (ATM to conveniently meet their banking needs. But in recent time there have been a proliferation of ATM frauds in the country even and across the globe. Managing the risk associated with ATM fraud as well as diminishing its impact is an important issue that face financial institutions as fraud techniques have become more advanced with increased occurrences. The ATM is only one of many Electronic Funds Transfer (EFT devices that are vulnerable to fraud attacks. This paper carried out an empirical research to analyse the cases of ATM usage and fraud occurrences within some banks in Minna. The research identifies the common ATM fraud, how, where and when these frauds are perpetuated and then proffer security recommendation that should be adhered to by both the banks as financial institutions and the ATM users in order to eliminate or reduce it to the barest minimum

  16. MOF phosphorylation by ATM regulates 53BP1-mediated DSB repair pathway choice

    Science.gov (United States)

    Gupta, Arun; Hunt, Clayton R.; Hegdec, Muralidhar L.; Chakraborty, Sharmistha; Udayakumar, Durga; Horikoshi, Nobuo; Singh1, Mayank; Ramnarain, Deepti B.; Hittelman, Walter N.; Namjoshi, Sarita; Asaithamby, Aroumougame; Hazra, Tapas K.; Ludwig, Thomas; Pandita, Raj K.; Tyler, Jessica K.; Pandita, Tej K.

    2014-01-01

    Cell cycle phase is a critical determinant of the choice between DNA damage repair by non-homologous end joining (NHEJ) or homologous recombination (HR). Here we report that DSBs induce ATM-dependent MOF (a histone H4 acetyl-transferase) phosphorylation (p-T392-MOF) and that phosphorylated MOF co-localizes with γ-H2AX, ATM, and 53BP1 foci. Mutation of the phosphorylation site (MOF-T392A) impedes DNA repair in S- and G2-phase but not G1-phase cells. Expression of MOF-T392A also reverses the reduction in DSB associated 53BP1 seen in wild type S/G2-phase cells, resulting in enhanced 53BP1 and reduced BRCA1 association. Decreased BRCA1 levels at DSB sites correlates with defective repairosome formation, reduced HR repair and decreased cell survival following irradiation. These data support a model whereby ATM mediated MOF-T392 phosphorylation modulates 53BP1 function to facilitate the subsequent recruitment of HR repair proteins, uncovering a regulatory role for MOF in DSB repair pathway choice during S/G2-phase. PMID:24953651

  17. ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage.

    Science.gov (United States)

    Chen, Lihong; Gilkes, Daniele M; Pan, Yu; Lane, William S; Chen, Jiandong

    2005-10-05

    The p53 tumor suppressor is activated after DNA damage to maintain genomic stability and prevent transformation. Rapid activation of p53 by ionizing radiation is dependent on signaling by the ATM kinase. MDM2 and MDMX are important p53 regulators and logical targets for stress signals. We found that DNA damage induces ATM-dependent phosphorylation and degradation of MDMX. Phosphorylated MDMX is selectively bound and degraded by MDM2 preceding p53 accumulation and activation. Reduction of MDMX level by RNAi enhances p53 response to DNA damage. Loss of ATM prevents MDMX degradation and p53 stabilization after DNA damage. Phosphorylation of MDMX on S342, S367, and S403 were detected by mass spectrometric analysis, with the first two sites confirmed by phosphopeptide-specific antibodies. Mutation of MDMX on S342, S367, and S403 each confers partial resistance to MDM2-mediated ubiquitination and degradation. Phosphorylation of S342 and S367 in vivo require the Chk2 kinase. Chk2 also stimulates MDMX ubiquitination and degradation by MDM2. Therefore, the E3 ligase activity of MDM2 is redirected to MDMX after DNA damage and contributes to p53 activation.

  18. MOF Phosphorylation by ATM Regulates 53BP1-Mediated Double-Strand Break Repair Pathway Choice

    Directory of Open Access Journals (Sweden)

    Arun Gupta

    2014-07-01

    Full Text Available Cell-cycle phase is a critical determinant of the choice between DNA damage repair by nonhomologous end-joining (NHEJ or homologous recombination (HR. Here, we report that double-strand breaks (DSBs induce ATM-dependent MOF (a histone H4 acetyl-transferase phosphorylation (p-T392-MOF and that phosphorylated MOF colocalizes with γ-H2AX, ATM, and 53BP1 foci. Mutation of the phosphorylation site (MOF-T392A impedes DNA repair in S and G2 phase but not G1 phase cells. Expression of MOF-T392A also blocks the reduction in DSB-associated 53BP1 seen in wild-type S/G2 phase cells, resulting in enhanced 53BP1 and reduced BRCA1 association. Decreased BRCA1 levels at DSB sites correlates with defective repairosome formation, reduced HR repair, and decreased cell survival following irradiation. These data support a model whereby ATM-mediated MOF-T392 phosphorylation modulates 53BP1 function to facilitate the subsequent recruitment of HR repair proteins, uncovering a regulatory role for MOF in DSB repair pathway choice during S/G2 phase.

  19. Human tumor cells segregate into radiosensitivity groups that associate with ATM and TP53 status

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Jerry R.; Yonggang Zhang; Russell, James [Radiobiology Laboratory, Johns Hopkins Oncology Center. Baltimore, MD (United States); Koch, Cameron [Dept. of Radiation Oncology, Univ. of Pennsylvania, Philadelphia, PA (United States); Little, John B. [John B. Little Center, Harvard School of Public Health. Boston, MA (United States)

    2007-07-15

    We seek to determine whether cellular radiosensitivity in nineteen human colorectal tumor cell lines and three human glioblastoma tumor cell lines segregate into statistically distinct groups and whether such groups correlate with gene expression. We measure clonogenic survival in 22 cell lines that vary in radiosensitivity and in expression of selected genes: ATM, TP53, CDKN1A, 14-3-3{sigma}, Ki-ras and DNA mismatch repair genes. We describe and compare radiosensitivity in these cell lines by one-parameter or two parameter analysis. Radiosensitivity varies among and between colorectal tumor cell lines and glioblastoma cell lines. When compared directly using survival, or using two-parameter analysis of radiosensitivity, cell lines distribute into four statistically-significant radiosensitivity groups. These groups associate strongly with the status of two genes, ATM and TP53, but do not associate with CDKN1A, 14-3-3{sigma}, Ki-ras and DNA mismatch repair genes. Intrinsic cellular radiosensitivity of 22 colorectal and glioblastoma cell lines fall into four radiosensitivity groups that associate with expression of ATM and TP53. These analyses suggest multiple mechanisms underlay intrinsic cellular radiosensitivity.

  20. Characterization of Early and Late Adopters of ATM Card in Indian Banking Industry

    Directory of Open Access Journals (Sweden)

    Kamalpreet Kaur

    2012-10-01

    Full Text Available The present study deals with affect of adoption pattern of the ATMs by banks on its characteristics. With the exploration of various characteristics of the banks like Size, Profi tability, Efficiency, Cost of Operations, Asset quality and Credit risk, Financing Pattern, Diversifi cation and Age etc.; the study has tried to differentiate between the early and late adopter category of the banks regarding ATM cards. The banks have been categorized into early and late adopters on the basis of their adoption period. For this purpose, 50 scheduled commercial banks consisting of 27 Public Sector Banks and 23 Private Sector Banks have been taken as sample to investigate the various aspects of and early adopter banks in comparison to late adopter banks. The time period of the study is 20 years i.e. from 1991 to 2010. It can be concluded that the initiators and fi rst movers take advantage over the late adopters and laggards. They have found to perform better in terms of various parameters. Overall, the early adopter banks are larger in size, more diversifi ed, having lesser branches, more market share and wide ATM network as compared to late adopter ones. Thus, the empirical results evidently reveal that the both the groups have their own different characteristics.

  1. MOF phosphorylation by ATM regulates 53BP1-mediated double-strand break repair pathway choice.

    Science.gov (United States)

    Gupta, Arun; Hunt, Clayton R; Hegde, Muralidhar L; Chakraborty, Sharmistha; Chakraborty, Sharmistha; Udayakumar, Durga; Horikoshi, Nobuo; Singh, Mayank; Ramnarain, Deepti B; Hittelman, Walter N; Namjoshi, Sarita; Asaithamby, Aroumougame; Hazra, Tapas K; Ludwig, Thomas; Pandita, Raj K; Tyler, Jessica K; Pandita, Tej K

    2014-07-10

    Cell-cycle phase is a critical determinant of the choice between DNA damage repair by nonhomologous end-joining (NHEJ) or homologous recombination (HR). Here, we report that double-strand breaks (DSBs) induce ATM-dependent MOF (a histone H4 acetyl-transferase) phosphorylation (p-T392-MOF) and that phosphorylated MOF colocalizes with γ-H2AX, ATM, and 53BP1 foci. Mutation of the phosphorylation site (MOF-T392A) impedes DNA repair in S and G2 phase but not G1 phase cells. Expression of MOF-T392A also blocks the reduction in DSB-associated 53BP1 seen in wild-type S/G2 phase cells, resulting in enhanced 53BP1 and reduced BRCA1 association. Decreased BRCA1 levels at DSB sites correlates with defective repairosome formation, reduced HR repair, and decreased cell survival following irradiation. These data support a model whereby ATM-mediated MOF-T392 phosphorylation modulates 53BP1 function to facilitate the subsequent recruitment of HR repair proteins, uncovering a regulatory role for MOF in DSB repair pathway choice during S/G2 phase.

  2. ATM induces MacroD2 nuclear export upon DNA damage

    Science.gov (United States)

    Golia, Barbara; Moeller, Giuliana Katharina; Jankevicius, Gytis; Schmidt, Andreas; Hegele, Anna; Preißer, Julia; Tran, Mai Ly; Imhof, Axel; Timinszky, Gyula

    2017-01-01

    ADP-ribosylation is a dynamic post-translation modification that regulates the early phase of various DNA repair pathways by recruiting repair factors to chromatin. ADP-ribosylation levels are defined by the activities of specific transferases and hydrolases. However, except for the transferase PARP1/ARDT1 little is known about regulation of these enzymes. We found that MacroD2, a mono-ADP-ribosylhydrolase, is exported from the nucleus upon DNA damage, and that this nuclear export is induced by ATM activity. We show that the export is dependent on the phosphorylation of two SQ/TQ motifs, suggesting a novel direct interaction between ATM and ADP-ribosylation. Lastly, we show that MacroD2 nuclear export temporally restricts its recruitment to DNA lesions, which may decrease the net ADP-ribosylhydrolase activity at the site of DNA damage. Together, our results identify a novel feedback regulation between two crucial DNA damage-induced signaling pathways: ADP-ribosylation and ATM activation. PMID:28069995

  3. ATM release at resected double-strand breaks provides heterochromatin reconstitution to facilitate homologous recombination.

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    Verena Geuting

    Full Text Available Non-homologous end-joining (NHEJ and homologous recombination (HR represent the two main pathways for repairing DNA double-strand breaks (DSBs. During the G2 phase of the mammalian cell cycle, both processes can operate and chromatin structure is one important factor which determines DSB repair pathway choice. ATM facilitates the repair of heterochromatic DSBs by phosphorylating and inactivating the heterochromatin building factor KAP-1, leading to local chromatin relaxation. Here, we show that ATM accumulation and activity is strongly diminished at DSBs undergoing end-resection during HR. Such DSBs remain unrepaired in cells devoid of the HR factors BRCA2, XRCC3 or RAD51. Strikingly, depletion of KAP-1 or expression of phospho-mimic KAP-1 allows repair of resected DSBs in the absence of BRCA2, XRCC3 or RAD51 by an erroneous PARP-dependent alt-NHEJ process. We suggest that DSBs in heterochromatin elicit initial local heterochromatin relaxation which is reversed during HR due to the release of ATM from resection break ends. The restored heterochromatic structure facilitates HR and prevents usage of error-prone alternative processes.

  4. ATP-driven Rad50 conformations regulate DNA tethering, end resection, and ATM checkpoint signaling.

    Science.gov (United States)

    Deshpande, Rajashree A; Williams, Gareth J; Limbo, Oliver; Williams, R Scott; Kuhnlein, Jeff; Lee, Ji-Hoon; Classen, Scott; Guenther, Grant; Russell, Paul; Tainer, John A; Paull, Tanya T

    2014-03-03

    The Mre11-Rad50 complex is highly conserved, yet the mechanisms by which Rad50 ATP-driven states regulate the sensing, processing and signaling of DNA double-strand breaks are largely unknown. Here we design structure-based mutations in Pyrococcus furiosus Rad50 to alter protein core plasticity and residues undergoing ATP-driven movements within the catalytic domains. With this strategy we identify Rad50 separation-of-function mutants that either promote or destabilize the ATP-bound state. Crystal structures, X-ray scattering, biochemical assays, and functional analyses of mutant PfRad50 complexes show that the ATP-induced 'closed' conformation promotes DNA end binding and end tethering, while hydrolysis-induced opening is essential for DNA resection. Reducing the stability of the ATP-bound state impairs DNA repair and Tel1 (ATM) checkpoint signaling in Schizosaccharomyces pombe, double-strand break resection in Saccharomyces cerevisiae, and ATM activation by human Mre11-Rad50-Nbs1 in vitro, supporting the generality of the P. furiosus Rad50 structure-based mutational analyses. These collective results suggest that ATP-dependent Rad50 conformations switch the Mre11-Rad50 complex between DNA tethering, ATM signaling, and 5' strand resection, revealing molecular mechanisms regulating responses to DNA double-strand breaks.

  5. The ATM-related domain of TRRAP is required for histone acetyltransferase recruitment and Myc-dependent oncogenesis

    Science.gov (United States)

    Park, Jeonghyeon; Kunjibettu, Sudeesha; McMahon, Steven B.; Cole, Michael D.

    2001-01-01

    The ATM-related TRRAP protein is a component of several different histone acetyltransferase (HAT) complexes but lacks the kinase activity characteristic of other ATM family members. We identified a novel function for this evolutionarily conserved domain in its requirement for the assembly of a functional HAT complex. Ectopic expression of TRRAP protein with a mutation in the ATM-related domain inhibits Myc-mediated oncogenic transformation. The Myc-binding region of TRRAP maps to a separable domain, and ectopic expression of this domain inhibits cell growth. These findings demonstrate that the ATM-related domain of TRRAP forms a structural core for the assembly and recruitment of HAT complexes by transcriptional activators. PMID:11445536

  6. Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage

    OpenAIRE

    Pereg, Yaron; Shkedy, Dganit; de Graaf, Petra; Meulmeester, Erik; Edelson-Averbukh, Marina; Salek, Mogjiborahman; Biton, Sharon; Teunisse, Amina F.A.S.; Lehmann, Wolf D.; Jochemsen, Aart G.; Shiloh, Yosef

    2005-01-01

    Maintenance of genomic stability depends on the DNA damage response, an extensive signaling network that is activated by DNA lesions such as double-strand breaks (DSBs). The primary activator of the mammalian DSB response is the nuclear protein kinase ataxia–telangiectasia, mutated (ATM), which phosphorylates key players in various arms of this network. The activation and stabilization of the p53 protein play a major role in the DNA damage response and are mediated by ATM-dependent posttransl...

  7. Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts

    Science.gov (United States)

    Worgul, Basil V.; Smilenov, Lubomir; Brenner, David J.; Junk, Anna; Zhou, Wei; Hall, Eric J.

    2002-01-01

    It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM(+/-) cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.

  8. Induction of ATM/ATR pathway combined with Vγ2Vδ2 T cells enhances cytotoxicity of ovarian cancer cells.

    Science.gov (United States)

    Lu, Jingwei; Das, Manjusri; Kanji, Suman; Aggarwal, Reeva; Joseph, Matthew; Ray, Alo; Shapiro, Charles L; Pompili, Vincent J; Das, Hiranmoy

    2014-07-01

    Many ovarian cancer cells express stress-related molecule MICA/B on their surface that is recognized by Vγ2Vδ2 T cells through their NKG2D receptor, which is transmitted to downstream stress-signaling pathway. However, it is yet to be established how Vγ2Vδ2 T cell-mediated recognition of MICA/B signal is transmitted to downstream stress-related molecules. Identifying targeted molecules would be critical to develop a better therapy for ovarian cancer cells. It is well established that ATM/ATR signal transduction pathways, which is modulated by DNA damage, replication stress, and oxidative stress play central role in stress signaling pathway regulating cell cycle checkpoint and apoptosis. We investigated whether ATM/ATR and its down stream molecules affect Vγ2Vδ2 T cell-mediated cytotoxicity. Herein, we show that ATM/ATR pathway is modulated in ovarian cancer cells in the presence of Vγ2Vδ2 T cells. Furthermore, downregulation of ATM pathway resulted downregulation of MICA, and reduced Vγ2Vδ2 T cell-mediated cytotoxicity. Alternately, stimulating ATM pathway enhanced expression of MICA, and sensitized ovarian cancer cells for cytotoxic lysis by Vγ2Vδ2 T cells. We further show that combining currently approved chemotherapeutic drugs, which induced ATM signal transduction, along with Vγ2Vδ2 T cells enhanced cytotoxicity of resistant ovarian cancer cells. These findings indicate that ATM/ATR pathway plays an important role in tumor recognition, and drugs promoting ATM signaling pathway might be considered as a combination therapy together with Vγ2Vδ2 T cells for effectively treating resistant ovarian cancer cells.

  9. Relationship of HepG2 cell sensitivity to continuous low dose-rate irradiation with ATM phosphorylation

    Institute of Scientific and Technical Information of China (English)

    Quelin Mei; Jianyong Yang; Duanming Du; Zaizhong Cheng; Pengcheng liu

    2008-01-01

    Objective: To investigate the change of ATM phosphorylation in HepG2 cells and its effect on HepG2 cell survival under a continuous low dose-rate irradiation.Methods: HepG2 cells were exposed to equivalent doses of irradiation delivered at either a continuous low dose-rate (7.76 cGy/h) or a high dose-rate (4500 cGy/h).The ATM phosphorylated proteins and surviving fraction of HepG2 cell after low dose-rate irradiation were compared with that after equivalent doses of high dose-rate irradiation.Results: The phosphorylation of ATM protein was maximal at 0.5 Gy irradiation delivered at either a high dose-rate or a continuous low dose-rate.As the radiation dose increased, the phosphorylation of ATM protein decreased under continuous low dose-rate irradiation.However, the phosphorylation of ATM protein was remained stable under high dose-rate irradiation.When the phosphorylation of ATM protein under continuous low dose-rate irradiation was equal to that under high dose-rate irradiation, there was no significant difference in the surviving fraction of HepG2 cells between two ir-radiation methods (P>0.05).When the phosphorylation of ATM protein significantly decreased after continuous low dose-rate irradiation compared with that after high dose-rate irradiation, increased amounts of cell killing was found in low dose-rate irradiation (P<0.01).Conclusion: Continuous low dose-rate irradiation increases HepG2 cells radiosensitivity compared with high dose-rate irradiation.The increased amounts of cell killing following continuous low dose-rate exposures are associated with reduced ATM phosphorylated protein.

  10. The ATM signaling cascade promotes recombination-dependent pachytene arrest in mouse spermatocytes.

    Directory of Open Access Journals (Sweden)

    Sarai Pacheco

    2015-03-01

    Full Text Available Most mutations that compromise meiotic recombination or synapsis in mouse spermatocytes result in arrest and apoptosis at the pachytene stage of the first meiotic prophase. Two main mechanisms are thought to trigger arrest: one independent of the double-strand breaks (DSBs that initiate meiotic recombination, and another activated by persistent recombination intermediates. Mechanisms underlying the recombination-dependent arrest response are not well understood, so we sought to identify factors involved by examining mutants deficient for TRIP13, a conserved AAA+ ATPase required for the completion of meiotic DSB repair. We find that spermatocytes with a hypomorphic Trip13 mutation (Trip13mod/mod arrest with features characteristic of early pachynema in wild type, namely, fully synapsed chromosomes without incorporation of the histone variant H1t into chromatin. These cells then undergo apoptosis, possibly in response to the arrest or in response to a defect in sex body formation. However, TRIP13-deficient cells that additionally lack the DSB-responsive kinase ATM progress further, reaching an H1t-positive stage (i.e., similar to mid/late pachynema in wild type despite the presence of unrepaired DSBs. TRIP13-deficient spermatocytes also progress to an H1t-positive stage if ATM activity is attenuated by hypomorphic mutations in Mre11 or Nbs1 or by elimination of the ATM-effector kinase CHK2. These mutant backgrounds nonetheless experience an apoptotic block to further spermatogenic progression, most likely caused by failure to form a sex body. DSB numbers are elevated in Mre11 and Nbs1 hypomorphs but not Chk2 mutants, thus delineating genetic requirements for the ATM-dependent negative feedback loop that regulates DSB numbers. The findings demonstrate for the first time that ATM-dependent signaling enforces the normal pachytene response to persistent recombination intermediates. Our work supports the conclusion that recombination defects trigger

  11. The association between ATM IVS 22-77 T>C and cancer risk: a meta-analysis.

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    Lin Zhao

    Full Text Available BACKGROUND AND OBJECTIVES: It has become increasingly clear that ATM (ataxia-telangiectasia-mutated safeguards genome stability, which is a cornerstone of cellular homeostasis, and ATM IVS 22-77 T>C affects the normal activity of ATM proteins. However, the association between the ATM IVS 22-77 T>C genetic variant and cancer risk is controversial. Therefore, we conducted a systematic meta-analysis to estimate the overall cancer risk associated with the polymorphism and to quantify any potential between-study heterogeneity. METHODS: A total of nine studies including 4,470 cases and 4,862 controls were analyzed for ATM IVS 22-77 T>C association with cancer risk in this meta-analysis. Heterogeneity among articles and their publication bias were also tested. RESULTS: Our results showed that no association reached the level of statistical significance in the overall risk. Interestingly, in the stratified analyses, we observed an inverse relationship in lung and breast cancer. CONCLUSION: Further functional research on the ATM mechanism should be performed to explain the inconsistent results in different cancer types.

  12. Temporally distinct roles of ATM and ROS in genotoxic-stress-dependent induction and maintenance of cellular senescence.

    Science.gov (United States)

    Nair, Raji R; Bagheri, Meisam; Saini, Deepak Kumar

    2015-01-15

    Cells exposed to genotoxic stress induce cellular senescence through a DNA damage response (DDR) pathway regulated by ATM kinase and reactive oxygen species (ROS). Here, we show that the regulatory roles for ATM kinase and ROS differ during induction and maintenance of cellular senescence. Cells treated with different genotoxic agents were analyzed using specific pathway markers and inhibitors to determine that ATM kinase activation is directly proportional to the dose of the genotoxic stress and that senescence initiation is not dependent on ROS or the p53 status of cells. Cells in which ROS was quenched still activated ATM and initiated the DDR when insulted, and progressed normally to senescence. By contrast, maintenance of a viable senescent state required the presence of ROS as well as activated ATM. Inhibition or removal of either of the components caused cell death in senescent cells, through a deregulated ATM-ROS axis. Overall, our work demonstrates existence of an intricate temporal hierarchy between genotoxic stress, DDR and ROS in cellular senescence. Our model reports the existence of different stages of cellular senescence with distinct regulatory networks.

  13. ATM-dependent phosphorylation of MRE11 controls extent of resection during homology directed repair by signalling through Exonuclease 1.

    Science.gov (United States)

    Kijas, Amanda W; Lim, Yi Chieh; Bolderson, Emma; Cerosaletti, Karen; Gatei, Magtouf; Jakob, Burkhard; Tobias, Frank; Taucher-Scholz, Gisela; Gueven, Nuri; Oakley, Greg; Concannon, Patrick; Wolvetang, Ernst; Khanna, Kum Kum; Wiesmüller, Lisa; Lavin, Martin F

    2015-09-30

    The MRE11/RAD50/NBS1 (MRN) complex plays a central role as a sensor of DNA double strand breaks (DSB) and is responsible for the efficient activation of ataxia-telangiectasia mutated (ATM) kinase. Once activated ATM in turn phosphorylates RAD50 and NBS1, important for cell cycle control, DNA repair and cell survival. We report here that MRE11 is also phosphorylated by ATM at S676 and S678 in response to agents that induce DNA DSB, is dependent on the presence of NBS1, and does not affect the association of members of the complex or ATM activation. A phosphosite mutant (MRE11S676AS678A) cell line showed decreased cell survival and increased chromosomal aberrations after radiation exposure indicating a defect in DNA repair. Use of GFP-based DNA repair reporter substrates in MRE11S676AS678A cells revealed a defect in homology directed repair (HDR) but single strand annealing was not affected. More detailed investigation revealed that MRE11S676AS678A cells resected DNA ends to a greater extent at sites undergoing HDR. Furthermore, while ATM-dependent phosphorylation of Kap1 and SMC1 was normal in MRE11S676AS678A cells, there was no phosphorylation of Exonuclease 1 consistent with the defect in HDR. These results describe a novel role for ATM-dependent phosphorylation of MRE11 in limiting the extent of resection mediated through Exonuclease 1.

  14. Application of jingsongling and ketamine for ABR test of guinea pigs%氯胺酮静松灵联合麻醉在豚鼠ABR测试中的应用

    Institute of Scientific and Technical Information of China (English)

    曹华; 董明敏

    2000-01-01

    目的:开发慢性动物实验的理想麻醉剂。方法:以传统麻醉剂戊巴比妥钠为对照,应用静松灵氯胺酮合剂对32只豚鼠进行听脑干反应(auditory brainstem response,ABR)测试。结果与结论:与戊巴比妥钠相比,氯胺酮静松灵合剂具有起效迅速、ABR测试完毕后苏醒快、死亡率低等优点。所测得的ABR诸参数与应用戊巴比妥钠一致。%Aim: To look for a satisfying anesthetic for chronic animal experiment. Methods:Experimental group and controlgroup were anesthetized by jingsongling-ketamine mixture and pentobartitone respectively and all the guinea pigs were tested of au-ditory brainstem response (ABR). Festlts and Conclusion: The results revealed that jingsongling-ketamine mixture workedfaster, and had a shorter awaking duration after the test and a lower death rate than pentobartitone did while ABR testing resultswere consistent between the 2 groups.

  15. Production of bioenergy in anaerobic baffled reactor (ABR) and sludge blanket (UASB) in the treatment os swine waste water; Producao de bioenergia em reatores anaerobios compartimentado (RAC) e de manta de lodo (UASB) no tratamento de efluentes de suinocultura

    Energy Technology Data Exchange (ETDEWEB)

    Moterani, Fabricio; Pereira, Erlon Lopes; Campos, Claudio M.M. [Universidade Federal de Lavras (DEG/UFLA), MG (Brazil). Dept. de Engenharia], email: fabricio_moterani@yahoo.com.br

    2011-07-01

    The biogas is obtained in the processes of degradation of organic matter by the action of bacterial consortium in the environment. The aim of this study was to evaluate the biogas production in anaerobic UASB and ABR in swine wastewater treatment. For this we used the theoretical estimated and actual production of biogas measured by anaerobic gasometers installed in the units. Methane was determined by gas chromatography (GC) and its theoretical output was 66 LCH4 kgSVT d{sup -1} and 11.9 LCH4 kgSVT d{sup -1} and 24.7 m{sup 3} d{sup -1} and 5.4 m{sup 3} d{sup -1} to ABR and UASB, respectively. Regarding the actual production of biogas in the reactor provided by the gas tank, found the values of 1,166.4 m{sup 3}; 0.1 m{sup 3}; 27.4 m{sup 3} and 12,598.5 m{sup 3} of biogas for compartments 1, 2 and 3 and ABR for the UASB reactor, respectively, totaling, production of 13,792.4 m{sup 3} in the units together, with an average of 113 m{sup 3} of biogas per day. But, it concludes with this research that the use of effluent from produce energy through biogas in swine farming is effective, which can be used in rural productive system itself. (author)

  16. Tasquinimod (ABR-215050, a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors

    Directory of Open Access Journals (Sweden)

    Isaacs John T

    2010-05-01

    Full Text Available Abstract Background The orally active quinoline-3-carboxamide tasquinimod [ABR-215050; CAS number 254964-60-8, which currently is in a phase II-clinical trial in patients against metastatic prostate cancer, exhibits anti-tumor activity via inhibition of tumor angiogenesis in human and rodent tumors. To further explore the mode of action of tasquinimod, in vitro and in vivo experiments with gene microarray analysis were performed using LNCaP prostate tumor cells. The array data were validated by real-time semiquantitative reversed transcriptase polymerase chain reaction (sqRT-PCR and protein expression techniques. Results One of the most significant differentially expressed genes both in vitro and in vivo after exposure to tasquinimod, was thrombospondin-1 (TSP1. The up-regulation of TSP1 mRNA in LNCaP tumor cells both in vitro and in vivo correlated with an increased expression and extra cellular secretion of TSP1 protein. When nude mice bearing CWR-22RH human prostate tumors were treated with oral tasquinimod, there was a profound growth inhibition, associated with an up-regulation of TSP1 and a down- regulation of HIF-1 alpha protein, androgen receptor protein (AR and glucose transporter-1 protein within the tumor tissue. Changes in TSP1 expression were paralleled by an anti-angiogenic response, as documented by decreased or unchanged tumor tissue levels of VEGF (a HIF-1 alpha down stream target in the tumors from tasquinimod treated mice. Conclusions We conclude that tasquinimod-induced up-regulation of TSP1 is part of a mechanism involving down-regulation of HIF1α and VEGF, which in turn leads to reduced angiogenesis via inhibition of the "angiogenic switch", that could explain tasquinimods therapeutic potential.

  17. Effect of ATM heterozygosity on heritable DNA damage in mice following paternal F{sub 0} germline irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Baulch, Janet E. [University of Maryland, Baltimore, Radiation Oncology Research Laboratory, BRB 7-002, 655 West Baltimore Street, Baltimore, MD 21201 (United States)]. E-mail: jbaulch@som.umaryland.edu; Li, M.-W. [Center for Health and the Environment, University of California Davis, CA 95616 (United States); Raabe, Otto G. [Center for Health and the Environment, University of California Davis, CA 95616 (United States)

    2007-03-01

    The ataxia telangiectasia mutated (ATM) gene product maintains genome integrity and initiates cellular DNA repair pathways following exposures to genotoxic agents. ATM also plays a significant role in meiotic recombination during spermatogenesis. Fertilization with sperm carrying damaged DNA could lead to adverse effects in offspring including developmental defects or increased cancer susceptibility. Currently, there is little information regarding the effect of ATM heterozygosity on germline DNA repair and heritable effects of paternal germline-ionizing irradiation. We used neutral pH comet assays to evaluate spermatozoa 45 days after acute whole-body irradiation of male mice (0.1 Gy, attenuated {sup 137}Cs {gamma} rays) to determine the effect of ATM heterozygosity on delayed DNA damage effects of Type A/B spermatogonial irradiation. Using the neutral pH sperm comet assay, significant irradiation-related differences were found in comet tail length, percent tail DNA and tail extent moment, but there were no observed differences in effect between wild-type and ATM +/- mice. However, evaluation of spermatozoa from third generation descendants of irradiated male mice for heritable chromatin effects revealed significant differences in DNA electrophoretic mobility in the F{sub 3} descendants that were based upon the irradiated F{sub 0} sire's genotype. In this study, radiation-induced chromatin alterations to Type A/B spermatogonia, detected in mature sperm 45 days post-irradiation, led to chromatin effects in mature sperm three generations later. The early cellular response to and repair of DNA damage is critical and appears to be affected by ATM zygosity. Our results indicate that there is potential for heritable genetic or epigenetic changes following Type A/B spermatogonial irradiation and that ATM heterozygosity increases this effect00.

  18. SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products.

    Science.gov (United States)

    Sowd, Gregory A; Mody, Dviti; Eggold, Joshua; Cortez, David; Friedman, Katherine L; Fanning, Ellen

    2014-12-01

    Simian virus 40 (SV40) and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PK(cs) kinase activity, facilitates some aspects of double strand break (DSB) repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR) and do not colocalize with non-homologous end joining (NHEJ) factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PK(cs) and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5' to 3' end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication.

  19. SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products.

    Directory of Open Access Journals (Sweden)

    Gregory A Sowd

    2014-12-01

    Full Text Available Simian virus 40 (SV40 and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PK(cs kinase activity, facilitates some aspects of double strand break (DSB repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR and do not colocalize with non-homologous end joining (NHEJ factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PK(cs and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5' to 3' end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication.

  20. ATM suppresses SATB1-induced malignant progression in breast epithelial cells.

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    Ellen Ordinario

    Full Text Available SATB1 drives metastasis when expressed in breast tumor cells by radically reprogramming gene expression. Here, we show that SATB1 also has an oncogenic activity to transform certain non-malignant breast epithelial cell lines. We studied the non-malignant MCF10A cell line, which is used widely in the literature. We obtained aliquots from two different sources (here we refer to them as MCF10A-1 and MCF10A-2, but found them to be surprisingly dissimilar in their responses to oncogenic activity of SATB1. Ectopic expression of SATB1 in MCF10A-1 induced tumor-like morphology in three-dimensional cultures, led to tumor formation in immunocompromised mice, and when injected into tail veins, led to lung metastasis. The number of metastases correlated positively with the level of SATB1 expression. In contrast, SATB1 expression in MCF10A-2 did not lead to any of these outcomes. Yet DNA copy-number analysis revealed that MCF10A-1 is indistinguishable genetically from MCF10A-2. However, gene expression profiling analysis revealed that these cell lines have significantly divergent signatures for the expression of genes involved in oncogenesis, including cell cycle regulation and signal transduction. Above all, the early DNA damage-response kinase, ATM, was greatly reduced in MCF10A-1 cells compared to MCF10A-2 cells. We found the reason for reduction to be phenotypic drift due to long-term cultivation of MCF10A. ATM knockdown in MCF10A-2 and two other non-malignant breast epithelial cell lines, 184A1 and 184B4, enabled SATB1 to induce malignant phenotypes similar to that observed for MCF10A-1. These data indicate a novel role for ATM as a suppressor of SATB1-induced malignancy in breast epithelial cells, but also raise a cautionary note that phenotypic drift could lead to dramatically different functional outcomes.

  1. ATM suppresses SATB1-induced malignant progression in breast epithelial cells.

    Science.gov (United States)

    Ordinario, Ellen; Han, Hye-Jung; Furuta, Saori; Heiser, Laura M; Jakkula, Lakshmi R; Rodier, Francis; Spellman, Paul T; Campisi, Judith; Gray, Joe W; Bissell, Mina J; Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi

    2012-01-01

    SATB1 drives metastasis when expressed in breast tumor cells by radically reprogramming gene expression. Here, we show that SATB1 also has an oncogenic activity to transform certain non-malignant breast epithelial cell lines. We studied the non-malignant MCF10A cell line, which is used widely in the literature. We obtained aliquots from two different sources (here we refer to them as MCF10A-1 and MCF10A-2), but found them to be surprisingly dissimilar in their responses to oncogenic activity of SATB1. Ectopic expression of SATB1 in MCF10A-1 induced tumor-like morphology in three-dimensional cultures, led to tumor formation in immunocompromised mice, and when injected into tail veins, led to lung metastasis. The number of metastases correlated positively with the level of SATB1 expression. In contrast, SATB1 expression in MCF10A-2 did not lead to any of these outcomes. Yet DNA copy-number analysis revealed that MCF10A-1 is indistinguishable genetically from MCF10A-2. However, gene expression profiling analysis revealed that these cell lines have significantly divergent signatures for the expression of genes involved in oncogenesis, including cell cycle regulation and signal transduction. Above all, the early DNA damage-response kinase, ATM, was greatly reduced in MCF10A-1 cells compared to MCF10A-2 cells. We found the reason for reduction to be phenotypic drift due to long-term cultivation of MCF10A. ATM knockdown in MCF10A-2 and two other non-malignant breast epithelial cell lines, 184A1 and 184B4, enabled SATB1 to induce malignant phenotypes similar to that observed for MCF10A-1. These data indicate a novel role for ATM as a suppressor of SATB1-induced malignancy in breast epithelial cells, but also raise a cautionary note that phenotypic drift could lead to dramatically different functional outcomes.

  2. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Du, Zhongli [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Wencheng [Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Xiao, Zefen, E-mail: xiaozefen@sina.com [Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Tan, Wen, E-mail: tanwen@cicams.ac.cn [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); and others

    2015-09-01

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy.

  3. Silicon Monoxide at 1 atm and Elevated Pressures: Crystalline or Amorphous?

    KAUST Repository

    AlKaabi, Khalid

    2014-03-05

    The absence of a crystalline SiO phase under ordinary conditions is an anomaly in the sequence of group 14 monoxides. We explore theoretically ordered ground-state and amorphous structures for SiO at P = 1 atm, and crystalline phases also at pressures up to 200 GPa. Several competitive ground-state P = 1 atm structures are found, perforce with Si-Si bonds, and possessing Si-O-Si bridges similar to those in silica (SiO2) polymorphs. The most stable of these static structures is enthalpically just a little more stable than a calculated random bond model of amorphous SiO. In that model we find no segregation into regions of amorphous Si and amorphous SiO2. The P = 1 atm structures are all semiconducting. As the pressure is increased, intriguing new crystalline structures evolve, incorporating Si triangular nets or strips and stishovite-like regions. A heat of formation of crystalline SiO is computed; it is found to be the most negative of all the group 14 monoxides. Yet, given the stability of SiO2, the disproportionation 2SiO (s) → Si(s)+SiO2(s) is exothermic, falling right into the series of group 14 monoxides, and ranging from a highly negative ΔH of disproportionation for CO to highly positive for PbO. There is no major change in the heat of disproportionation with pressure, i.e., no range of stability of SiO with respect to SiO2. The high-pressure SiO phases are metallic. © 2014 American Chemical Society.

  4. Efficient Cycloaddition Reaction of Carbon Dioxide with Epoxide by Rhodamine Based Catalyst Under 1 atm Pressure

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Qing; Luo, Huadong; Cao, Di; Zhang, Haibo; Wang, Wenjing; Zhou, Xiaohai [Wuhan University, Wuhan (China)

    2012-06-15

    Rhodamine B (RhB) and rhodamine 6G (Rh6G) were employed as catalysts for the synthesis of cyclic carbonate from carbon dioxide and epoxide. It turned out that the catalytic activity of Rh6G was nearly 29 times higher than that of RhB at 1 atm pressure, 90 .deg. C. Furthermore, the catalytic efficiency of RhB and Rh6G was greatly enhanced with triethylamine as co-catalyst. Under the optimized conditions, the best isolated yield (93%) of cyclic carbonate was achieved without organic solvent and metal component

  5. Estudio de los principales procesos que originan emisiones de gases a la atmósfera.

    OpenAIRE

    2011-01-01

    Se abordaron los diferentes procesos que originaron emisiones de gases a la atmósfera y principalmente los ocasionados por la combustión de los motores diesel estacionarios y del efecto que estos causan al medio ambiente y sus consecuencias. Por otra parte se muestran los distintos procedimientos empleados para el control y la prevención de la contaminación ambiental originada por la actividad del hombre y los diferentes métodos de control. Se brindan datos de planes de control para la calida...

  6. Alternaría y Cladosporium: aeroalergenos en la atmósfera de Huelva

    OpenAIRE

    1995-01-01

    [ES] Este trabajo forma parte de un proyecto más amplio que pretende conocer la aeromicoflora de la ciudad de Huelva. Destacamos la incidencia de las esporas de Alternaría y Cladosporium en la atmósfera de la ciudad para el periodo 1989-91, debido a que ambos géneros son los principales responsables de las crisis asmáticas de origen fúngico. [EN] This work is part of a broader study which aims to know the aeromycoflora in the atmosphere of Huelva during 1989-91. The incidence of Alternaría...

  7. Ankles back in randomized controlled trial (ABrCt: braces versus neuromuscular exercises for the secondary prevention of ankle sprains. Design of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Verhagen Evert ALM

    2011-09-01

    Full Text Available Abstract Background Ankle sprains are the most common sports and physical activity related injury. There is extensive evidence that there is a twofold increased risk for injury recurrence for at least one year post injury. In up to 50% of all cases recurrences result in disability and lead to chronic pain or instability, requiring prolonged medical care. Therefore ankle sprain recurrence prevention in athletes is essential. This RCT evaluates the effect of the combined use of braces and neuromuscular training (e.g. proprioceptive training/sensorimotor training/balance training against the individual use of either braces or neuromuscular training alone on ankle sprain recurrences, when applied to individual athletes after usual care. Methods/Design This study was designed as three way randomized controlled trial with one year follow-up. Healthy individuals between 12 and 70 years of age, who were actively participating in sports and who had sustained a lateral ankle sprain in the two months prior to inclusion, were eligible for inclusion. After subjects had finished ankle sprain treatment by means of usual care, they were randomised to any of the three study groups. Subjects in group 1 received an eight week neuromuscular training program, subjects in group 2 received a sports brace to be worn during all sports activities for the duration of one year, and group 3 received a combination of the neuromuscular training program and a sports brace to be worn during all sports activities for the duration of eight weeks. Outcomes were assessed at baseline and every month for 12 months therafter. The primary outcome measure was incidence of ankle sprain recurrences. Secondary outcome measures included the direct and indirect costs of recurrent injury, the severity of recurrent injury, and the residual complaints during and after the intervention. Discussion The ABrCt is the first randomized controlled trial to directly compare the secondary preventive

  8. Analysis of Chromosomal Aberrations after Low and High Dose Rate Gamma Irradiation in ATM or NBS Suppressed Human Fibroblast Cells

    Science.gov (United States)

    Hada, M.; Huff, J. L.; Patel, Z.; Pluth, J. M.; George, K. A.; Cucinotta, F. A.

    2009-01-01

    A detailed understanding of the biological effects of heavy nuclei is needed for space radiation protection and for cancer therapy. High-LET radiation produces more complex DNA lesions that may be non-repairable or that may require additional processing steps compared to endogenous DSBs, increasing the possibility of misrepair. Interplay between radiation sensitivity, dose, and radiation quality has not been studied extensively. Previously we studied chromosome aberrations induced by low- and high- LET radiation in several cell lines deficient in ATM (ataxia telangactasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. We found that the yields of both simple and complex chromosomal aberrations were significantly increased in the DSB repair defective cells compared to normal cells. The increased aberrations observed for the ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex aberrations, while the linear dose-response term was significantly higher in NBS cells only for simple exchanges. These results point to the importance of the functions of ATM and NBS in chromatin modifications that function to facilitate correct DSB repair and minimize aberration formation. To further understand the sensitivity differences that were observed in ATM and NBS deficient cells, in this study, chromosomal aberration analysis was performed in normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, or Mirin, an MRN complex inhibitor involved in activation of ATM. We are also testing siRNA knockdown of these proteins. Normal and ATM or NBS suppressed cells were irradiated with gamma-rays and chromosomes were collected with a premature chromosome

  9. ATR- and ATM-Mediated DNA Damage Response Is Dependent on Excision Repair Assembly during G1 but Not in S Phase of Cell Cycle.

    Science.gov (United States)

    Ray, Alo; Blevins, Chessica; Wani, Gulzar; Wani, Altaf A

    2016-01-01

    Cell cycle checkpoint is mediated by ATR and ATM kinases, as a prompt early response to a variety of DNA insults, and culminates in a highly orchestrated signal transduction cascade. Previously, we defined the regulatory role of nucleotide excision repair (NER) factors, DDB2 and XPC, in checkpoint and ATR/ATM-dependent repair pathway via ATR and ATM phosphorylation and recruitment to ultraviolet radiation (UVR)-induced damage sites. Here, we have dissected the molecular mechanisms of DDB2- and XPC- mediated regulation of ATR and ATM recruitment and activation upon UVR exposures. We show that the ATR and ATM activation and accumulation to UVR-induced damage not only depends on DDB2 and XPC, but also on the NER protein XPA, suggesting that the assembly of an active NER complex is essential for ATR and ATM recruitment. ATR and ATM localization and H2AX phosphorylation at the lesion sites occur as early as ten minutes in asynchronous as well as G1 arrested cells, showing that repair and checkpoint-mediated by ATR and ATM starts early upon UV irradiation. Moreover, our results demonstrated that ATR and ATM recruitment and H2AX phosphorylation are dependent on NER proteins in G1 phase, but not in S phase. We reasoned that in G1 the UVR-induced ssDNA gaps or processed ssDNA, and the bound NER complex promote ATR and ATM recruitment. In S phase, when the UV lesions result in stalled replication forks with long single-stranded DNA, ATR and ATM recruitment to these sites is regulated by different sets of proteins. Taken together, these results provide evidence that UVR-induced ATR and ATM recruitment and activation differ in G1 and S phases due to the existence of distinct types of DNA lesions, which promote assembly of different proteins involved in the process of DNA repair and checkpoint activation.

  10. Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage.

    Science.gov (United States)

    Pereg, Yaron; Shkedy, Dganit; de Graaf, Petra; Meulmeester, Erik; Edelson-Averbukh, Marina; Salek, Mogjiborahman; Biton, Sharon; Teunisse, Amina F A S; Lehmann, Wolf D; Jochemsen, Aart G; Shiloh, Yosef

    2005-04-05

    Maintenance of genomic stability depends on the DNA damage response, an extensive signaling network that is activated by DNA lesions such as double-strand breaks (DSBs). The primary activator of the mammalian DSB response is the nuclear protein kinase ataxia-telangiectasia, mutated (ATM), which phosphorylates key players in various arms of this network. The activation and stabilization of the p53 protein play a major role in the DNA damage response and are mediated by ATM-dependent posttranslational modifications of p53 and Mdm2, a ubiquitin ligase of p53. p53's response to DNA damage also depends on Mdm2-dependent proteolysis of Mdmx, a homologue of Mdm2 that represses p53's transactivation function. Here we show that efficient damage-induced degradation of human Hdmx depends on functional ATM and at least three sites on the Hdmx that are phosphorylated in response to DSBs. One of these sites, S403, is a direct ATM target. Accordingly, each of these sites is important for Hdm2-mediated ubiquitination of Hdmx after DSB induction. These results demonstrate a sophisticated mechanism whereby ATM fine-tunes the optimal activation of p53 by simultaneously modifying each player in the process.

  11. ATM-dependent MiR-335 targets CtIP and modulates the DNA damage response.

    Directory of Open Access Journals (Sweden)

    Nathan T Martin

    2013-05-01

    Full Text Available ATM plays a critical role in cellular responses to DNA double-strand breaks (DSBs. We describe a new ATM-mediated DSB-induced DNA damage response pathway involving microRNA (miRNA: irradiation (IR-induced DSBs activate ATM, which leads to the downregulation of miR-335, a miRNA that targets CtIP, which is an important trigger of DNA end resection in homologous recombination repair (HRR. We demonstrate that CREB is responsible for a large portion of miR-335 expression by binding to the promoter region of miR-335. CREB binding is greatly reduced after IR, corroborating with previous studies that IR-activated ATM phosphorylates CREB to reduce its transcription activity. Overexpression of miR-335 in HeLa cells resulted in reduced CtIP levels and post-IR colony survival and BRCA1 foci formation. Further, in two patient-derived lymphoblastoid cell lines with decreased post-IR colony survival, a "radiosensitive" phenotype, we demonstrated elevated miR-335 expression, reduced CtIP levels, and reduced BRCA1 foci formation. Colony survival, BRCA1 foci, and CtIP levels were partially rescued by miRNA antisense AMO-miR-335 treatment. Taken together, these findings strongly suggest that an ATM-dependent CREB-miR-335-CtIP axis influences the selection of HRR for repair of certain DSB lesions.

  12. Induction of G2/M arrest by pseudolaric acid B is mediated by activation of the ATM signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Ai-guo MENG; Ling-lingJIANG

    2009-01-01

    Aim: The aim of this study was to investigate the mechanism of pseudolaric acid B (PLAB)-induced cell cycle arrest in human melanoma SK-28 cells. Methods: Cell growth inhibition was detected by MTT assay, the cell cycle was analyzed by flow cytometry, and protein expression was examined by Western blot analysis.Results: PLAB inhibited the growth of human melanoma ceils and induced G2/M arrest in SK-28 cells, accompanied by an up-regulation of Cdc2 phosphorylation and a subsequent down-regulation of Cdc2 expression. Furthermore, PLAB decreased the expression of Cdc25C phosphatase and increased the expression of Wee1 kinase. Meanwhile, a reduction in Cdc2 activity was party due to induction of the expression of p21wsaf1/cip1 in a p53-dependent manner. In addition, PLAB activated the checkpoint kinase, Chk2, and increased the expression of p53, two major targets of ATM kinase. These effects were inhibited by caffeine, an ATM kinase inhibitor. We also found that PLAB significantly enhanced ATM kinase activity. Conclusion: Taken together, these results suggest that PLAB induced G2/M arrest in human melanoma cells via a mechanism involving the activation of ATM, and the effect of PLAB on Cdc2 activity was mediated via interactions with the Chk2-Cdc25C and p53 signalling pathways, two distinct downstream pathways of ATM. PLAB may be a promising chemopreventive agent for treating human melanoma.

  13. Evidence toward an expanded international civil aviation organization (ICAO) concept of a single unified global communication navigation surveillance air traffic management (CNS/ATM) system: A quantitative analysis of ADS-B technology within a CNS/ATM system

    Science.gov (United States)

    Gardner, Gregory S.

    This research dissertation summarizes research done on the topic of global air traffic control, to include technology, controlling world organizations and economic considerations. The International Civil Aviation Organization (ICAO) proposed communication, navigation, surveillance, air traffic management system (CNS/ATM) plan is the basis for the development of a single global CNS/ATM system concept as it is discussed within this study. Research will be evaluated on the efficacy of a single technology, Automatic Dependent Surveillance-Broadcast (ADS-B) within the scope of a single global CNS/ATM system concept. ADS-B has been used within the Federal Aviation Administration's (FAA) Capstone program for evaluation since the year 2000. The efficacy of ADS-B was measured solely by using National Transportation Safety Board (NTSB) data relating to accident and incident rates within the Alaskan airspace (AK) and that of the national airspace system (NAS).

  14. Functional intersection of ATM and DNA-dependent protein kinase catalytic subunit in coding end joining during V(D)J recombination

    DEFF Research Database (Denmark)

    Lee, Baeck-Seung; Gapud, Eric J; Zhang, Shichuan

    2013-01-01

    -PKcs deficiency leads to a nearly complete block in coding join formation, as DNA-PKcs is required to activate Artemis, the endonuclease that opens hairpin-sealed coding ends. In contrast to loss of DNA-PKcs protein, here we show that inhibition of DNA-PKcs kinase activity has no effect on coding join formation...... when ATM is present and its kinase activity is intact. The ability of ATM to compensate for DNA-PKcs kinase activity depends on the integrity of three threonines in DNA-PKcs that are phosphorylation targets of ATM, suggesting that ATM can modulate DNA-PKcs activity through direct phosphorylation of DNA...

  15. Adoption of Biometric Fingerprint Identification as an Accessible, Secured form of ATM Transaction Authentication

    Directory of Open Access Journals (Sweden)

    Michael Mireku Kwakye

    2015-10-01

    Full Text Available Security is continuously an important concern for most Information Technology-related industries, especially the banking industry. The banking industry is concerned with protecting and securing the privacy and data of their customers, as well as their transactions. The adoption of biometric technology as a means of identifying and authenticating individuals has been proposed as one of the varied solutions to many of the security challenges faced by the banking industry. In this paper, the authors address the ATM transaction authentication problem of banking transactions using fingerprint identification as one form of biometric authentication. The novel methodology adopted proposes the use of an online off-card fingerprint verification, which involves the matching of live fingerprint (templates with pre-stored templates read from the ATM smart card. The experimental evaluation of the proposed methodology presents a system that offers a faster and relatively better security of authentication, as compared to previous and existing methodologies. Moreover, the use of BioHASH templates ensures an irreversible cryptographic hash function, facilitates a faster authentication, and enables an efficient framework of detecting potential duplicates of banking account holders.

  16. DBC1 phosphorylation by ATM/ATR inhibits SIRT1 deacetylase in response to DNA damage

    Institute of Scientific and Technical Information of China (English)

    Laura Zannini; Giacomo Buscemi; Ja-Eun Kim; Enrico Fontanella; Domenico Delia

    2012-01-01

    Human DBC1 (deleted in breast cancer-1; KIAA1967) is a nuclear protein that,in response to DNA damage,competitively inhibits the NAD+-dependent deacetylase SIRT1,a regulator of p53 apoptotic functions in response to genotoxic stress.DBC1 depletion in human cells increases SIRT1 activity,resulting in the deacetylation of p53 and protection from apoptosis.However,the mechanisms regulating this process have not yet been determined.Here,we report that,in human cell lines,DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related)kinases.Phosphorylated DBC1 bound to and inhibited SIRT1,resulting in the dissociation of the SIRT1-p53 complex and stimulating p53 acetylation and p53-dependent cell death.Indeed,DBC1-mediated genotoxicity,which was shown in knockdown experiments to be dependent on SIRT1 and p53 expression,was defective in cells expressing the phospho-mutant DBC1T454A.This study describes the first post-translational modification of DBC1 and provides new mechanistic insight linking ATM/ATR to the DBC1-SIRT1-p53 apoptotic axis triggered by DNA damage.

  17. AES Cardless Automatic Teller Machine (ATM) Biometric Security System Design Using FPGA Implementation

    Science.gov (United States)

    Ahmad, Nabihah; Rifen, A. Aminurdin M.; Helmy Abd Wahab, Mohd

    2016-11-01

    Automated Teller Machine (ATM) is an electronic banking outlet that allows bank customers to complete a banking transactions without the aid of any bank official or teller. Several problems are associated with the use of ATM card such card cloning, card damaging, card expiring, cast skimming, cost of issuance and maintenance and accessing customer account by third parties. The aim of this project is to give a freedom to the user by changing the card to biometric security system to access the bank account using Advanced Encryption Standard (AES) algorithm. The project is implemented using Field Programmable Gate Array (FPGA) DE2-115 board with Cyclone IV device, fingerprint scanner, and Multi-Touch Liquid Crystal Display (LCD) Second Edition (MTL2) using Very High Speed Integrated Circuit Hardware (VHSIC) Description Language (VHDL). This project used 128-bits AES for recommend the device with the throughput around 19.016Gbps and utilized around 520 slices. This design offers a secure banking transaction with a low rea and high performance and very suited for restricted space environments for small amounts of RAM or ROM where either encryption or decryption is performed.

  18. Estudio de los principales procesos que originan emisiones de gases a la atmósfera.

    Directory of Open Access Journals (Sweden)

    María Elvira Font Pérez

    2011-01-01

    Full Text Available Se abordaron los diferentes procesos que originaron emisiones de gases a la atmósfera y principalmente los ocasionados por la combustión de los motores diesel estacionarios y del efecto que estos causan al medio ambiente y sus consecuencias. Por otra parte se muestran los distintos procedimientos empleados para el control y la prevención de la contaminación ambiental originada por la actividad del hombre y los diferentes métodos de control. Se brindan datos de planes de control para la calidad de aire aplicados en algunos países y las características del equipamiento necesario para estos fines. Se presenta como objetivo fundamental la realización de un estudio teórico de los procesos que provocan la contaminación atmosférica durante la explotación prolongada de los motores diesel estacionarios y el objetivo fue describir los métodos utilizados para el control y la prevención de la contaminación ambiental. Se abordaron los principios básicos aplicados para eliminar los impactos negativos sobre la calidad del agua, la atmósfera y el suelo; se consideró cómo la atención se ha desviado del control a la prevención y por último se analizaron las limitaciones de las soluciones propuestas para un medio en particular.

  19. PERLINDUNGAN HUKUM TERHADAP NASABAH KORBAN KEJAHATAN PENGGANDAAN KARTU ATM PADA BANK SWASTA NASIONAL DI DENPASAR

    Directory of Open Access Journals (Sweden)

    Komang Juniawan

    2013-07-01

    Full Text Available Responsibility of the bank to refund customers money that became victims of ATMcard duplication is the bank have responsibility to refund the customer money, so that theloss of customer funds was caused by his own negligence, then the bank is not haveresponsibility to refund losses suffered by customers. Legal efforts taken by the bank torefund customers money that became victims of ATM card duplication such as :Clarification of customer complaints by checking the data to determine the customer'saccount transactions that cause a reduction in the customer's account balance, thendeliver customer transactions was conducted customer; Checking customer transactionsallegedly clumsy, one of which is checking the CCTV at the cash machine withdrawalsare not recognized by the customer, checking and known whether the transaction isconcluded that the transaction is correct or odd transactions; Returns missing customerfunds, if it is concluded that the clients do not make transactions recorded in thecustomer's account, and making a crime report in the ATM card duplication police to dothe investigation against the perpetrators

  20. Clinical significance of ABR results in unilateral tinnitus with normal hearing%听力正常单侧耳鸣的双侧ABR结果比较及临床意义

    Institute of Scientific and Technical Information of China (English)

    杨海弟; 彭解人; 区永康; 黄夏茵

    2012-01-01

    目的 听力正常单侧耳鸣患者的双侧听性脑干反应(ABR)的结果比较及临床意义进行探讨,阐明听力正常耳鸣的可能发病机制.方法 对20例听力正常的单侧耳鸣患者,常规进行耳专科检查及声导抗检查,排除外中耳病变.分别记录双侧纯音测听、耳声发射(DPOAE)及ABR,将耳鸣侧与非耳鸣侧的ABR结果进行对比分析.结果 耳鸣侧与非耳鸣侧在纯音听阈、声导抗、DPOAE及ABR阈值上均表现正常,无统计学差异,但耳鸣侧ABR的I波幅度0.19uV,V波幅度0.24uV,V/I比值为1.31;非耳鸣侧ABR的I波幅度0.14uV,V波幅度0.26uV,V/I比值为2.19.结论 虽然单侧耳鸣患者耳鸣侧未发现听阈提高,但其V/I比值明显较非耳鸣侧下降(V/I比值为1.31vs2.19),提示在中脑传入信号减少,在听觉中枢维持内环境神经平衡的机制作用下导致听觉皮层神经元兴奋性增强,可能是耳鸣产生的原因之一.%Objective Comparison the bilateral auditory brainstem response ( ABR ) results of unilateral tinnitus patients with normal hearing and analysis clinical significance,discussed the possible mechanism of tinnitus with normal hearing. Methods 20 cases of unilateral tinnitus patients with normal hearing were documented bilateral audiometry, otoacoustic emission ( DPOAE ) and ABR, comparative analysis the ABR results of the side with the tinnitus and non-tinnitus side.Results The pure tone audiometry, DPOAE and ABR threshold showed normal, no statistical difference, but the tinnitus side I wave amplitude is 0.19uV,V wave amplitude is 0.24uV, V/I ratio is 1.31; but the non-tinnitus side I wave amplitude is 0.14uV, V wave amplitude is 0.26uV,V/I ratio is 2.19. Conclusion Although unilateral tinnitus patients with tinnitus side did not found threshold increase, but the V/I ratio was significantly decreased than the non-tinnitus side (V/I is 1.31vs 2.19), prompting in the midbrain afferent signal is reduced, in the central auditory system of

  1. 银行ATM智能发卡管理系统设计%Bank ATM smart card management system design

    Institute of Scientific and Technical Information of China (English)

    陈俊; 邓绍涛

    2013-01-01

    In order to address the growing demand for the non-cash business directly through a bank ATM,component-based application development model is adopted to design a bank ATM smart card management system,the software reusability and new business it carry comparing to the traditional ATM are obviously the advantages.%为了解决直接通过银行ATM办理非现金业务的日益增长的需求,本文基于组件的应用程序开发模型,设计了一个由软件组件的银行ATM智能发卡管理系统,具有软件复用性及相比于传统ATM的一系列崭新业务优势.

  2. PTEN enhances G2/M arrest in etoposide-treated MCF‑7 cells through activation of the ATM pathway.

    Science.gov (United States)

    Zhang, Ruopeng; Zhu, Li; Zhang, Lirong; Xu, Anli; Li, Zhengwei; Xu, Yijuan; He, Pei; Wu, Maoqing; Wei, Fengxiang; Wang, Chenhong

    2016-05-01

    As an effective tumor suppressor, phosphatase and tensin homolog (PTEN) has attracted the increased attention of scientists. Recent studies have shown that PTEN plays unique roles in the DNA damage response (DDR) and can interact with the Chk1 pathway. However, little is known about how PTEN contributes to DDR through the ATM-Chk2 pathway. It is well-known that etoposide induces G2/M arrest in a variety of cell lines, including MCF-7 cells. The DNA damage-induced G2/M arrest results from the activation of protein kinase ataxia telangiectasia mutated (ATM), followed by the activation of Chk2 that subsequently inactivates CDC25C, resulting in G2/M arrest. In the present study, we assessed the contribution of PTEN to the etoposide-induced G2/M cell cycle arrest. PTEN was knocked down in MCF-7 cells by specific shRNA, and the effects of PTEN on the ATM-Chk2 pathway were investigated through various approaches. The results showed that knockdown of PTEN strongly antagonized ATM activation in response to etoposide treatment, and thereby reduced the phosphorylation level of ATM substrates, including H2AX, P53 and Chk2. Furthermore, depletion of PTEN reduced the etoposide-induced phosphorylation of CDC25C and strikingly compromised etoposide-induced G2/M arrest in the MCF-7 cells. Altogether, we demonstrated that PTEN plays a unique role in etoposide-induced G2/M arrest by facilitating the activation of the ATM pathway, and PTEN was required for the proper activation of checkpoints in response to DNA damage in MCF-7 cells.

  3. Aurora-A controls cancer cell radio- and chemoresistance via ATM/Chk2-mediated DNA repair networks.

    Science.gov (United States)

    Sun, Huizhen; Wang, Yan; Wang, Ziliang; Meng, Jiao; Qi, Zihao; Yang, Gong

    2014-05-01

    High expression of Aurora kinase A (Aurora-A) has been found to confer cancer cell radio- and chemoresistance, however, the underlying mechanism is unclear. In this study, by using Aurora-A cDNA/shRNA or the specific inhibitor VX680, we show that Aurora-A upregulates cell proliferation, cell cycle progression, and anchorage-independent growth to enhance cell resistance to cisplatin and X-ray irradiation through dysregulation of DNA damage repair networks. Mechanistic studies showed that Aurora-A promoted the expression of ATM/Chk2, but suppressed the expression of BRCA1/2, ATR/Chk1, p53, pp53 (Ser15), H2AX, γH2AX (Ser319), and RAD51. Aurora-A inhibited the focus formation of γH2AX in response to ionizing irradiation. Treatment of cells overexpressing Aurora-A and ATM/Chk2 with the ATM specific inhibitor KU-55933 increased the cell sensitivity to cisplatin and irradiation through increasing the phosphorylation of p53 at Ser15 and inhibiting the expression of Chk2, γH2AX (Ser319), and RAD51. Further study revealed that BRCA1/2 counteracted the function of Aurora-A to suppress the expression of ATM/Chk2, but to activate the expression of ATR/Chk1, pp53, γH2AX, and RAD51, leading to the enhanced cell sensitivity to irradiation and cisplatin, which was also supported by the results from animal assays. Thus, our data provide strong evidences that Aurora-A and BRCA1/2 inversely control the sensitivity of cancer cells to radio- and chemotherapy through the ATM/Chk2-mediated DNA repair networks, indicating that the DNA repair molecules including ATM/Chk2 may be considered for the targeted therapy against cancers with overexpression of Aurora-A.

  4. Naphthalimides Induce G2 Arrest Through the ATM-Activated Chk2-Executed Pathway in HCT116 Cells

    Directory of Open Access Journals (Sweden)

    Hong Zhu

    2009-11-01

    Full Text Available Naphthalimides, particularly amonafide and 2-(2-dimethylamino-6-thia-2-aza-benzo[def]chrysene-1,3-diones (R16, have been identified to possess anticancer activities and to induce G2-M arrest through inhibiting topoisomerase II accompanied by Chk1 degradation. The current study was designed to precisely dissect the signaling pathway(s responsible for the naphthalimide-induced cell cycle arrest in human colon carcinoma HCT116 cells. Using phosphorylated histone H3 and mitotic protein monoclonal 2 as mitosis markers, we first specified the G2 arrest elicited by the R16 and amonafide. Then, R16 and amonafide were revealed to induce phosphorylation of the DNA damage sensor ataxia telangiectasia-mutated (ATM responding to DNA double-strand breaks (DSBs. Inhibition of ATM by both the pharmacological inhibitor caffeine and the specific small interference RNA (siRNA rescued the G2 arrest elicited by R16, indicating its ATM-dependent characteristic. Furthermore, depletion of Chk2, but not Chk1 with their corresponding siRNA, statistically significantly reversed the R16- and amonafide-triggered G2 arrest. Moreover, the naphthalimides phosphorylated Chk2 in an ATM-dependent manner but induced Chk1 degradation. These data indicate that R16 and amonafide preferentially used Chk2 as evidenced by the differential ATM-executed phosphorylation of Chk1 and Chk2. Thus, a clear signaling pathway can be established, in which ATM relays the DNA DSBs signaling triggered by the naphthalimides to the checkpoint kinases, predominantly to Chk2,which finally elicits G2 arrest. The mechanistic elucidation not only favors the development of the naphthalimides as anticancer agents but also provides an alternative strategy of Chk2 inhibition to potentiate the anticancer activities of these agents.

  5. Start-up of Packed Cage ABR for Brewery Wastewater Treatment%笼状填料式ABR反应器处理啤酒废水启动试验

    Institute of Scientific and Technical Information of China (English)

    范荣桂; 李贤; 高海娟; 王会川

    2013-01-01

    Contrast experiments were used to investigate the start-up of packed cage ABR for brewery wastewater treatment at constant temperature of (25 ±2) ℃ and variable temperature of 10 to 20℃. The variation in COD and influence factors in the start-up stage were analyzed. The relationship of variation in pH to the microbial populations and their functions in each room of the ABR was discussed. The results showed that the start-up time of ABR was shorter at constant temperature, and was longer at variable temperature due to an adaptation period. The variation of pH value in each room of ABR met the needs of distribution of the microbial populations in each room and the gradual conversion of pollutants in wastewater under the anaerobic conditions. The objectives of the packed cage were increasing the contact area, improving the hydraulic condition and intercepting the pollutants effectively. The volume load should be gradually increased in the start-up stage.%采用对比试验,分别考察了恒温[(25±2)℃]和变温(10~20℃)条件下自主设计的笼状填料式ABR反应器处理啤酒废水的启动情况,分析了启动阶段COD的变化及其影响因素,并探讨了ABR反应器各隔室pH值的变化与微生物种群及其功能的关系.结果表明,恒温条件下ABR的启动更快;变温条件下ABR有一定的适应期,启动时间相对较长;ABR内pH值的变化规律满足厌氧条件下微生物种群逐室变化及废水中污染物逐级转化的需求;笼状填料具有增加接触面积、改善水力条件和有效截污的作用;启动阶段的容积负荷宜逐步提高.

  6. Comparative Results of AIRS/AMSU and CrIS/ATMS Retrievals Using a Scientifically Equivalent Retrieval Algorithm

    Science.gov (United States)

    Susskind, Joel; Kouvaris, Louis; Iredell, Lena

    2016-01-01

    The AIRS Science Team Version-6 retrieval algorithm is currently producing high quality level-3 Climate Data Records (CDRs) from AIRS/AMSU which are critical for understanding climate processes. The AIRS Science Team is finalizing an improved Version-7 retrieval algorithm to reprocess all old and future AIRS data. AIRS CDRs should eventually cover the period September 2002 through at least 2020. CrIS/ATMS is the only scheduled follow on to AIRS/AMSU. The objective of this research is to prepare for generation of long term CrIS/ATMS CDRs using a retrieval algorithm that is scientifically equivalent to AIRS/AMSU Version-7.

  7. Association of common ATM variants with familial breast cancer in a South American population

    Directory of Open Access Journals (Sweden)

    Peralta Octavio

    2008-04-01

    Full Text Available Abstract Background The ATM gene has been frequently involved in hereditary breast cancer as a low-penetrance susceptibility gene but evidence regarding the role of ATM as a breast cancer susceptibility gene has been contradictory. Methods In this study, a full mutation analysis of the ATM gene was carried out in patients from 137 Chilean breast cancer families, of which 126 were BRCA1/2 negatives and 11 BRCA1/2 positives. We further perform a case-control study between the subgroup of 126 cases BRCA1/2 negatives and 200 controls for the 5557G>A missense variant and the IVS38-8T>C and the IVS24-9delT polymorphisms. Results In the full mutation analysis we detected two missense variants and eight intronic polymorphisms. Carriers of the variant IVS24-9delT, or IVS38-8T>C, or 5557G>A showed an increase in breast cancer risk. The higher significance was observed in the carriers of IVS38-8T>C (OR = 3.09 [95%CI 1.11–8.59], p = 0.024. The IVS24-9 T/(-T, IVS38-8 T/C, 5557 G/A composite genotype confered a 3.19 fold increase in breast cancer risk (OR = 3.19 [95%CI 1.16–8.89], p = 0.021. The haplotype estimation suggested a strong linkage disequilibrium between the three markers (D' = 1. We detected only three haplotypes in the cases and control samples, some of these may be founder haplotypes in the Chilean population. Conclusion The IVS24-9 T/(-T, IVS38-8 T/C, 5557 G/A composite genotype alone or in combination with certain genetic background and/or environmental factors, could modify the cancer risk by increasing genetic inestability or by altering the effect of the normal DNA damage response.

  8. Installation and maintenance of SDH/SONET, ATM, Xdsl, and synchronization networks

    CERN Document Server

    Caballero, Jose; Sequra, Roger; Guimera, Andreu

    2003-01-01

    Service level agreements guaranteeing quality of service have helped your organization to keep old customers and win new ones over. Although it may be easy for the sales department to ink a service level agreement, you have to handle the constant problems of phase fluctuations, jitter, and wander, that threaten the quality of service spelled out in these service level agreements.

  9. Early B-cell Specific Inactivation of ATM Synergizes with Ectopic CyclinD1 Expression to Promote Pre-germinal center B-cell Lymphomas in Mice

    Science.gov (United States)

    Yamamoto, Kenta; Lee, Brian J.; Li, Chen; Dubois, Richard L.; Hobeika, Elias; Bhagat, Govind; Zha, Shan

    2017-01-01

    Ataxia Telangiectasia Mutated (ATM) kinase is a master regulator of the DNA damage response. ATM is frequently inactivated in human B-cell non-Hodgkin Lymphomas (B-NHL), including ~50% of mantle cell lymphomas (MCLs) characterized by ectopic expression of CyclinD1. Here we report that early and robust deletion of ATM in precursor/progenitor B-cells causes cell-autonomous, clonal mature B cell lymphomas of both pre- and post-germinal center (GC) origins. Unexpectedly naïve B cell specific deletion of ATM is not sufficient to induce lymphomas in mice, highlighting the important tumor suppressor function of ATM in immature B cells. While EμCyclinD1 is not sufficient to induce lymphomas, EμCyclinD1 accelerates the kinetics and increased the incidence of clonal lymphomas in ATM-deficient B-cells and skews the lymphomas towards pre-GC derived small lymphocytic neoplasms sharing morphological features of human MCL. This is in part due to CyclinD1-driven expansion of ATM-deficient naïve B cells with genomic instability, which promotes the deletions of additional tumor suppressor genes (i.g. Trp53, Mll2, Rb1 and Cdkn2a). Together these findings define a synergistic function of ATM and CyclinD1 in pre-germinal center B-cell proliferation and lymphomagenesis and provide a prototypic animal model to study the pathogenesis of human MCL. PMID:25676421

  10. Ataxia Telangiectasia-Mutated (ATM) kinase activity is regulated by ATP-driven conformational changes in the Mre11/Rad50/Nbs1 (MRN) complex

    NARCIS (Netherlands)

    J.-H. Lee (Ji-Hoon); M.R. Mand (Michael); R.A. Deshpande (Rajashree); E. Kinoshita (Eri); S.-H. Yang (Soo-Hyun); C. Wyman (Claire); T.T. Paull

    2013-01-01

    textabstractThe Ataxia Telangiectasia-Mutated (ATM) protein kinase is recruited to sites of double-strand DNA breaks by the Mre11/Rad50/Nbs1 (MRN) complex, which also facilitates ATM monomerization and activation. MRN exists in at least two distinct conformational states, dependent on ATP binding an

  11. Early B-cell-specific inactivation of ATM synergizes with ectopic CyclinD1 expression to promote pre-germinal center B-cell lymphomas in mice.

    Science.gov (United States)

    Yamamoto, K; Lee, B J; Li, C; Dubois, R L; Hobeika, E; Bhagat, G; Zha, S

    2015-06-01

    Ataxia telangiectasia-mutated (ATM) kinase is a master regulator of the DNA damage response. ATM is frequently inactivated in human B-cell non-Hodgkin lymphomas, including ~50% of mantle cell lymphomas (MCLs) characterized by ectopic expression of CyclinD1. Here we report that early and robust deletion of ATM in precursor/progenitor B cells causes cell autonomous, clonal mature B-cell lymphomas of both pre- and post-germinal center (GC) origins. Unexpectedly, naive B-cell-specific deletion of ATM is not sufficient to induce lymphomas in mice, highlighting the important tumor suppressor function of ATM in immature B cells. Although EμCyclinD1 is not sufficient to induce lymphomas, EμCyclinD1 accelerates the kinetics and increases the incidence of clonal lymphomas in ATM-deficient B-cells and skews the lymphomas toward pre-GC-derived small lymphocytic neoplasms, sharing morphological features of human MCL. This is in part due to CyclinD1-driven expansion of ATM-deficient naive B cells with genomic instability, which promotes the deletions of additional tumor suppressor genes (i.e. Trp53, Mll2, Rb1 and Cdkn2a). Together these findings define a synergistic function of ATM and CyclinD1 in pre-GC B-cell proliferation and lymphomagenesis and provide a prototypic animal model to study the pathogenesis of human MCL.

  12. Antennas Designed for Advanced Communications for Air Traffic Management (AC/ATM) Project

    Science.gov (United States)

    Zakrajsek, Robert J.

    2000-01-01

    The goal of the Advanced Communications for Air Traffic Management (AC/ATM) Project at the NASA Glenn Research Center at Lewis Field is to enable a communications infrastructure that provides the capacity, efficiency, and flexibility necessary to realize a mature free-flight environment. The technical thrust of the AC/ATM Project is targeted at the design, development, integration, test, and demonstration of enabling technologies for global broadband aeronautical communications. Since Ku-band facilities and equipment are readily available, one of the near-term demonstrations involves a link through a Kuband communications satellite. Two conformally mounted antennas will support the initial AC/ATM communications links. Both of these are steered electronically through monolithic microwave integrated circuit (MMIC) amplifiers and phase shifters. This link will be asymmetrical with the downlink to the aircraft (mobile vehicle) at a throughput rate of greater than 1.5 megabits per second (Mbps), whereas the throughput rate of the uplink from the aircraft will be greater than 100 kilobits per second (kbps). The data on the downlink can be narrow-band, wide-band, or a combination of both, depending on the requirements of the experiment. The AC/ATM project is purchasing a phased-array Ku-band transmitting antenna for the uplink from the test vehicle. Many Ku-band receiving antennas have been built, and one will be borrowed for a short time to perform the initial experiments at the NASA Glenn Research Center at Lewis Field. The Ku-band transmitting antenna is a 254-element MMIC phased-array antenna being built by Boeing Phantom Works. Each element can radiate 100 mW. The antenna is approximately 43-cm high by 24-cm wide by 3.3-cm thick. It can be steered beyond 60 from broadside. The beamwidth varies from 6 at broadside to 12 degrees at 60 degrees, which is typical of phased-array antennas. When the antenna is steered to 60 degrees, the beamwidth will illuminate

  13. Fenómenos solares que afectan la atmósfera terrestre

    Science.gov (United States)

    Rovira, M.

    Se describen los principales fenómenos solares como fulguraciones, prominencias eruptivas, viento solar y eyecciones de masa coronal (CME) que tienen consecuencias en la atmósfera terrestre. En algunos casos el material es eyectado a velocidades superiores a los 900 km/seg y tarda menos de 48 horas en llegar a la Tierra. En general, estos CME no son peligrosos ya que el campo magnético terrestre actúa como protector siendo un aislante efectivo. Si el viento solar es muy intenso puede comprimir la magnetósfera y producir una tormenta geomagnética. En casos extremos, puede interferir la transmisión de potencia eléctrica, perturbar los satélites y producir auroras polares.

  14. Millimeter and sub-millimeter atmospheric performance at Dome C combining radiosoundings and ATM synthetic spectra

    CERN Document Server

    De Gregori, S; Decina, B; Lamagna, L; Pardo, J R; Petkov, B; Tomasi, C; Valenziano, L

    2012-01-01

    The reliability of astronomical observations at millimeter and sub-millimeter wavelengths closely depends on a low vertical content of water vapor as well as on high atmospheric emission stability. Although Concordia station at Dome C (Antarctica) enjoys good observing conditions in this atmospheric spectral windows, as shown by preliminary site-testing campaigns at different bands and in, not always, time overlapped periods, a dedicated instrument able to continuously determine atmospheric performance for a wide spectral range is not yet planned. In the absence of such measurements, in this paper we suggest a semi-empirical approach to perform an analysis of atmospheric transmission and emission at Dome C to compare the performance for 7 photometric bands ranging from 100 GHz to 2 THz. Radiosoundings data provided by the Routine Meteorological Observations (RMO) Research Project at Concordia station are corrected by temperature and humidity errors and dry biases and then employed to feed ATM (Atmospheric Tra...

  15. Study on Cell Error Rate of a Satellite ATM System Based on CDMA

    Institute of Scientific and Technical Information of China (English)

    赵彤宇; 张乃通

    2003-01-01

    In this paper, the cell error rate (CER) of a CDMA-based satellite ATM system is analyzed. Two fading models, i.e. the partial fading model and the total fading model are presented according to multi-path propagation fading and shadow effect. Based on the total shadow model, the relation of CER vs. the number of subscribers at various elevations under 2D-RAKE receiving and non-diversity receiving is got. The impact on cell error rate with pseudo noise (PN) code length is also considered. The result that the maximum likelihood combination of multi-path signal would not improve the system performance when multiple access interference (MAI) is small, on the contrary the performance may be even worse is abtained.

  16. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

    Science.gov (United States)

    Southey, Melissa C; Goldgar, David E; Winqvist, Robert; Pylkäs, Katri; Couch, Fergus; Tischkowitz, Marc; Foulkes, William D; Dennis, Joe; Michailidou, Kyriaki; van Rensburg, Elizabeth J; Heikkinen, Tuomas; Nevanlinna, Heli; Hopper, John L; Dörk, Thilo; Claes, Kathleen BM; Reis-Filho, Jorge; Teo, Zhi Ling; Radice, Paolo; Catucci, Irene; Peterlongo, Paolo; Tsimiklis, Helen; Odefrey, Fabrice A; Dowty, James G; Schmidt, Marjanka K; Broeks, Annegien; Hogervorst, Frans B; Verhoef, Senno; Carpenter, Jane; Clarke, Christine; Scott, Rodney J; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Peto, Julian; dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federik; Burwinkel, Barbara; Yang, Rongxi; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig; Nielsen, Sune F; Flyger, Henrik; Benitez, Javier; Zamora, M Pilar; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan; Ziogas, Argyrios; Clarke, Christina A; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V; Antonenkova, Natalia N; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Spurdle, Amanda B; Investigators, kConFab; Wauters, Els; Smeets, Dominiek; Beuselinck, Benoit; Floris, Giuseppe; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Olson, Janet E; Vachon, Celine; Pankratz, Vernon S; McLean, Catriona; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Kristensen, Vessela; Alnæs, Grethe Grenaker; Zheng, Wei; Hunter, David J; Lindstrom, Sara; Hankinson, Susan E; Kraft, Peter; Andrulis, Irene; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Jukkola-Vuorinen, Arja; Grip, Mervi; Kauppila, Saila; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Hollestelle, Antoinette; Garcia-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Eccles, Diana M; Rafiq, Sajjad; Tapper, William J; Gerty, Sue M; Hooning, Maartje J; Martens, John W M; Collée, J Margriet; Tilanus-Linthorst, Madeleine; Hall, Per; Li, Jingmei; Brand, Judith S; Humphreys, Keith; Cox, Angela; Reed, Malcolm W R; Luccarini, Craig; Baynes, Caroline; Dunning, Alison M; Hamann, Ute; Torres, Diana; Ulmer, Hans Ulrich; Rüdiger, Thomas; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Simard, Jacques; Dumont, Martine; Soucy, Penny; Eeles, Rosalind; Muir, Kenneth; Wiklund, Fredrik; Gronberg, Henrik; Schleutker, Johanna; Nordestgaard, Børge G; Weischer, Maren; Travis, Ruth C; Neal, David; Donovan, Jenny L; Hamdy, Freddie C; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Schaid, Daniel J; Kelley, Joseph L; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Butterbach, Katja; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Benlloch, Sara; Renner, Stefan P; Hartmann, Arndt; Hein, Alexander; Ruebner, Matthias; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Lambretchs, Sandrina; Doherty, Jennifer A; Rossing, Mary Anne; Nickels, Stefan; Eilber, Ursula; Wang-Gohrke, Shan; Odunsi, Kunle; Sucheston-Campbell, Lara E; Friel, Grace; Lurie, Galina; Killeen, Jeffrey L; Wilkens, Lynne R; Goodman, Marc T; Runnebaum, Ingo; Hillemanns, Peter A; Pelttari, Liisa M; Butzow, Ralf; Modugno, Francesmary; Edwards, Robert P; Ness, Roberta B; Moysich, Kirsten B; du Bois, Andreas; Heitz, Florian; Harter, Philipp; Kommoss, Stefan; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Jensen, Allan; Kjaer, Susanne Krüger; Høgdall, Estrid; Peissel, Bernard; Bonanni, Bernardo; Bernard, Loris; Goode, Ellen L; Fridley, Brooke L; Vierkant, Robert A; Cunningham, Julie M; Larson, Melissa C; Fogarty, Zachary C; Kalli, Kimberly R; Liang, Dong; Lu, Karen H; Hildebrandt, Michelle A T; Wu, Xifeng; Levine, Douglas A; Dao, Fanny; Bisogna, Maria; Berchuck, Andrew; Iversen, Edwin S; Marks, Jeffrey R; Akushevich, Lucy; Cramer, Daniel W; Schildkraut, Joellen; Terry, Kathryn L; Poole, Elizabeth M; Stampfer, Meir; Tworoger, Shelley S; Bandera, Elisa V; Orlow, Irene; Olson, Sara H; Bjorge, Line; Salvesen, Helga B; van Altena, Anne M; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Pejovic, Tanja; Bean, Yukie; Brooks-Wilson, Angela; Kelemen, Linda E; Cook, Linda S; Le, Nhu D; Górski, Bohdan; Gronwald, Jacek; Menkiszak, Janusz; Høgdall, Claus K; Lundvall, Lene; Nedergaard, Lotte; Engelholm, Svend Aage; Dicks, Ed; Tyrer, Jonathan; Campbell, Ian; McNeish, Iain; Paul, James; Siddiqui, Nadeem; Glasspool, Rosalind; Whittemore, Alice S; Rothstein, Joseph H; McGuire, Valerie; Sieh, Weiva; Cai, Hui; Shu, Xiao-Ou; Teten, Rachel T; Sutphen, Rebecca; McLaughlin, John R; Narod, Steven A; Phelan, Catherine M; Monteiro, Alvaro N; Fenstermacher, David; Lin, Hui-Yi; Permuth, Jennifer B; Sellers, Thomas A; Chen, Y Ann; Tsai, Ya-Yu; Chen, Zhihua; Gentry-Maharaj, Aleksandra; Gayther, Simon A; Ramus, Susan J; Menon, Usha; Wu, Anna H; Pearce, Celeste L; Van Den Berg, David; Pike, Malcolm C; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Moes-Sosnowska, Joanna; Kupryjanczyk, Jolanta; Pharoah, Paul DP; Song, Honglin; Winship, Ingrid; Chenevix-Trench, Georgia; Giles, Graham G; Tavtigian, Sean V; Easton, Doug F; Milne, Roger L

    2016-01-01

    Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important. PMID:27595995

  17. Modular and Stochastic Approaches to Molecular Pathway Models of ATM, TGF beta, and WNT Signaling

    Science.gov (United States)

    Cucinotta, Francis A.; O'Neill, Peter; Ponomarev, Artem; Carra, Claudio; Whalen, Mary; Pluth, Janice M.

    2009-01-01

    Deterministic pathway models that describe the biochemical interactions of a group of related proteins, their complexes, activation through kinase, etc. are often the basis for many systems biology models. Low dose radiation effects present a unique set of challenges to these models including the importance of stochastic effects due to the nature of radiation tracks and small number of molecules activated, and the search for infrequent events that contribute to cancer risks. We have been studying models of the ATM, TGF -Smad and WNT signaling pathways with the goal of applying pathway models to the investigation of low dose radiation cancer risks. Modeling challenges include introduction of stochastic models of radiation tracks, their relationships to more than one substrate species that perturb pathways, and the identification of a representative set of enzymes that act on the dominant substrates. Because several pathways are activated concurrently by radiation the development of modular pathway approach is of interest.

  18. A NEW BUSINESS MODEL FOR ATM TRANSACTION SECURITY USING FINGERPRINT RECOGNITION

    Directory of Open Access Journals (Sweden)

    SOWMYA RAVIKUMAR

    2013-06-01

    Full Text Available Money transactions play a vital role in the nature of trade. Today, ATMs and Credit cards are used for this purpose, the authentication of these transactions are unsecure. To overcome this shortcoming of piracy in money transactions, the author proposes the idea of using fingerprints of customers as password in place of traditional pin number. Here, if the fingerprint is recognized, then it allows transaction. This model has an additional feature i.e., a reference fingerprint of the nominee or a close family member of the customer can be used if the customer is not available in case of emergencies. This proposed business model helps the society, mainly the rural people, by enhancing the security using Fingerprint recognition in Digital image processing. As the fingerprint of every person is unique and unchangeable, this biometric feature is used over the others.

  19. Desenvolvimento da ATM e prevalência de desordens temporomandibulares em crianças

    OpenAIRE

    Pereira, Nicole

    2011-01-01

    Trabalho apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária. Introdução: O estudo da oclusão humana e de cada uma das suas partes constituintes assume-se como uma das áreas de maior complexidade na Medicina Dentária. Para que este estudo seja possível é necessária a análise do desenvolvimento das estruturas que constituem a ATM, desde o período intra-uterino até à sua fase madura. Recentemente, o estudo das Desordens te...

  20. Autoprotección del aluminio anodizado sin sellar expuesto a la atmósfera

    Directory of Open Access Journals (Sweden)

    Escudero, E.

    2005-04-01

    Full Text Available To confirm or refute the widely held idea that the sealing operation is vital to guarantee the good resistance of anodised aluminium to atmospheric corrosion, unsealed anodised specimens with three different film thicknesses were exposed in 9 atmospheres in Iberoamérica with salinity values of between 3.9 and 684 mg m sup>-2 day-1 of chlorides. Using a wide variety of techniques, from scanning and transmission electron microscopy to direct measurements by gravimetry, and including indirect measurements by electrochemical techniques as well as standard sealing quality control tests, the self-sealing capacity of unsealed anodic coatings during atmospheric exposure is demonstrated. Surprisingly, unlike other types of protective coatings, the quality of anodic films improves with ageing. Keywords

    Para confirmar o rebatir la idea, muy difundida, de que la operación de sellado es imprescindible para garantizar una buena resistencia del aluminio anodizado a la corrosión atmosférica, se expusieron muestras de anodizados sin sellar, de tres espesores diferentes, en 9 atmósferas de Iberoamérica, con salinidades comprendidas entre 3,9 y 684 mg m-2 d-1 de cloruros. Por las más variadas técnicas, desde la microscopía electrónica de barrido o transmisión a la medida directa por gravimetría, pasando por los ensayos normalizados de control de calidad del sellado y la medida indirecta por técnicas electroquímicas, se demuestra la capacidad de autosellado, durante la exposición a la atmósfera, de los recubrimientos anódicos sin sellar. Sorprendentemente, a diferencia de lo que ocurre en recubrimientos protectores de otra naturaleza, la calidad de los anodizados mejora con el envejecimiento.

  1. Collaboration of MLLT1/ENL, Polycomb and ATM for transcription and genome integrity.

    Science.gov (United States)

    Ui, Ayako; Yasui, Akira

    2016-04-25

    Polycomb group (PcG) repress, whereas Trithorax group (TrxG) activate transcription for tissue development and cellular proliferation, and misregulation of these factors is often associated with cancer. ENL (MLLT1) and AF9 (MLLT3) are fusion partners of Mixed Lineage Leukemia (MLL), TrxG proteins, and are factors in Super Elongation Complex (SEC). SEC controls transcriptional elongation to release RNA polymerase II, paused around transcription start site. In MLL rearranged leukemia, several components of SEC have been found as MLL-fusion partners and the control of transcriptional elongation is misregulated leading to tumorigenesis in MLL-SEC fused Leukemia. It has been suggested that unexpected collaboration of ENL/AF9-MLL and PcG are involved in tumorigenesis in leukemia. Recently, we found that the collaboration of ENL/AF9 and PcG led to a novel mechanism of transcriptional switch from elongation to repression under ATM-signaling for genome integrity. Activated ATM phosphorylates ENL/AF9 in SEC, and the phosphorylated ENL/AF9 binds BMI1 and RING1B, a heterodimeric E3-ubiquitin-ligase complex in Polycomb Repressive complex 1 (PRC1), and recruits PRC1 at transcriptional elongation sites to rapidly repress transcription. The ENL/AF9 in SEC- and PcG-mediated transcriptional repression promotes DSB repair near transcription sites. The implication of this is that the collaboration of ENL/AF9 in SEC and PcG ensures a rapid response of transcriptional switching from elongation to repression to neighboring genotoxic stresses for DSB repair. Therefore, these results suggested that the collaboration of ENL/AF9 and PcG in transcriptional control is required to maintain genome integrity and may be link to the MLL-ENL/AF9 leukemia.

  2. FY1995 next generation highly parallel database / dataminig server using 100 PC's and ATM switch; 1995 nendo tasudai no pasokon wo ATM ketsugoshita jisedai choheiretsu database mining server no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The objective of the research is first to build a highly parallel processing system using 100 personal computers and an ATM switch. The former is a commodity for computer, while the latter can be regarded as a commodity for future communication systems. Second is to implement parallel relational database management system and parallel data mining system over the 100-PC cluster system. Third is to run decision-support queries typicalto data warehouses, to run association rule mining, and to prove the effectiveness of the proposed architecture as a next generation parallel database/datamining server. Performance/cost ratio of PC is significantly improved compared with workstations and proprietry systems due to its mass production. The cost of ATM switch is also considerably decreasing since ATM is being widely accepted as a communication-on infrastructure. By combining 100 PCs as computing commodities and ATM switch as a communication commodity, we built large sca-le parallel processing system inexpensively. Each mode employs the Pentium Pro CPU and the communication badwidth between PC's is more than 120Mbits/sec. A new parallel relational DBMS is design-ed and implemented. TPC-D, which is a standard benchmark for decision support applicants (100GBytes) is executed. Our system attained much higher performance than current commercial systems which are also much more expensive than ours. In addition, we developed a novel parallel data mining algorithm to extract associate rules. We implemented it in our system and succeeded toattain high performance. Thus it is verified that ATM connected PC cluster is very promising as a next generation platform for large scale database/dataminig server. (NEDO)

  3. Training of Evaluators in the Third World: Implementation of the Action Training Model (ATM) in Kenya and Botswana.

    Science.gov (United States)

    Bhola, H. S.

    The Action Training Model (ATM) was developed for the delivery of evaluation training to development workers in Kenya and Botswana and implemented under the aegis of the German Foundation for International Development. Training of evaluators is a challenge in any context, but in the Third World environment, evaluation training offers special…

  4. Base station MAC with APRMA protocol for broadband multimedia ATM in micro/pico-cellular mobile networks

    DEFF Research Database (Denmark)

    Le, Khanh Hoang; Nielsen, Søren Nørskov; Dittmann, Lars

    1998-01-01

    The concept for a wireless ATM access system that enables seamless mobile connectivity to the B-ISDN is presented. It is based on small, low cost and intelligent base stations running a medium access control (MAC) protocol using adaptive packet reservation multiple access (APRMA). Both the princi...

  5. Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks

    Directory of Open Access Journals (Sweden)

    Pierre Caron

    2015-11-01

    Full Text Available DNA double-strand breaks (DSBs elicit the so-called DNA damage response (DDR, largely relying on ataxia telangiectasia mutated (ATM and DNA-dependent protein kinase (DNA-PKcs, two members of the PI3K-like kinase family, whose respective functions during the sequential steps of the DDR remains controversial. Using the DIvA system (DSB inducible via AsiSI combined with high-resolution mapping and advanced microscopy, we uncovered that both ATM and DNA-PKcs spread in cis on a confined region surrounding DSBs, independently of the pathway used for repair. However, once recruited, these kinases exhibit non-overlapping functions on end joining and γH2AX domain establishment. More specifically, we found that ATM is required to ensure the association of multiple DSBs within “repair foci.” Our results suggest that ATM acts not only on chromatin marks but also on higher-order chromatin organization to ensure repair accuracy and survival.

  6. Mre11 ATLD17/18 mutation retains Tel1/ATM activity but blocks DNA double-strand break repair

    NARCIS (Netherlands)

    O. Limbo (Oliver); D. Moiani (Davide); A. Kertokalio (Aryandi); C. Wyman (Claire); J.A. Tainer (John); P. Russell (Paul)

    2012-01-01

    textabstractThe Mre11 complex (Mre11-Rad50-Nbs1 or MRN) binds double-strand breaks where it interacts with CtIP/Ctp1/Sae2 and ATM/Tel1 to preserve genome stability through its functions in homology-directed repair, checkpoint signaling and telomere maintenance. Here, we combine biochemical, structur

  7. Novel Smad proteins localize to IR-induced double-strand breaks: interplay between TGFβ and ATM pathways

    Science.gov (United States)

    Wang, Minli; Saha, Janapriya; Hada, Megumi; Anderson, Jennifer A.; Pluth, Janice M.; O’Neill, Peter; Cucinotta, Francis A.

    2013-01-01

    Cellular damage from ionizing radiation (IR) is in part due to DNA damage and reactive oxygen species, which activate DNA damage response (DDR) and cytokine signaling pathways, including the ataxia telangiectasia mutated (ATM) and transforming growth factor (TGF)β/Smad pathways. Using classic double-strand breaks (DSBs) markers, we studied the roles of Smad proteins in DDR and the crosstalk between TGFβ and ATM pathways. We observed co-localization of phospho-Smad2 (pSmad2) and Smad7 with DSB repair proteins following low and high linear energy transfer (LET) radiation in human fibroblasts and epithelial cells. The decays of both foci were similar to that of γH2AX foci. Irradiation with high LET particles induced pSmad2 and Smad7 foci tracks indicating the particle trajectory through cells. pSmad2 foci were absent in S phase cells, while Smad7 foci were present in all phases of cell cycle. pSmad2 (but not Smad7) foci were completely abolished when ATM was depleted or inactivated. In contrast, a TGFβ receptor 1 (TGFβR1) inhibitor abrogated Smad7, but not pSmad2 foci at DSBs sites. In summary, we suggest that Smad2 and Smad7 contribute to IR-induced DSB signaling in an ATM or TGFβR1-dependent manner, respectively. PMID:23221633

  8. Regulation of ATM in DNA double strand break repair accounts for the radiosensitivity in human cells exposed to high linear energy transfer ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Xue Lian, E-mail: xuelian@suda.edu.cn [School of Radiation Medicine and Public Health, Medical College of Soochow University, No. 199, Ren' ai Road, Suzhou 215123 (China); Yu Dong, E-mail: ydong@ncc.go.jp [Tumor Endocrinology Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Furusawa, Yoshiya; Okayasu, Ryuichi [Heavy-Ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-shi 263-8555 (Japan); Tong Jian; Cao Jianping; Fan Saijun [School of Radiation Medicine and Public Health, Medical College of Soochow University, No. 199, Ren' ai Road, Suzhou 215123 (China)

    2009-11-02

    High linear energy transfer (LET) radiation shows different biological effects from low-LET radiation. The complex nature of high LET radiation-induced damage, especially the clustered DNA damage, brings about slow repair of DNA double strand breaks (DSBs), which finally lead to higher lethality and chromosome aberration. Ionizing radiation (IR) induced DNA DSBs are repaired by both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR) pathways in mammalian cells. The novel function of ataxia telangiectasia-mutated (ATM) protein is its involvement in the DSB repair of slow kinetics for 'dirty' breaks rejoining by NHEJ, this suggests that ATM may play a more important role in high LET radiation-induced DNA damage. We show here that KU55933, an ATM inhibitor could distinctly lower the clonogenic survival in normal human skin fibroblast cells exposed to carbon ion radiation and dramatically impair the normal process for DSB repair. We also implicated the involvement of ATM in the two pathways of DNA DSB repair, with DNA-PKcs and Rad51 as the representative proteins. The phosphorylation of DNA-PKcs at Thr-2609 with both immunoblotting and immunofluorescent staining indicated an ATM-dependent change, while for Rad51, KU55933 pretreatment could postpone the formation of nuclear Rad51 foci. Interestingly, we also found that pretreatment with chloroquine, an ATM stimulator could protect cells from carbon ion radiation only at lower doses. For doses over 1 Gy, protection was no longer observed. There was a dose-dependent increase for ATM kinase activity, with saturation at about 1 Gy. Chloroquine pretreatment prior to 1 Gy of carbon ion radiation did not enhance the autophosphorylation of ATM at serine 1981. The function of ATM in G2/M checkpoint arrest facilitated DSB repair in high-LET irradiation. Our results provide a possible mechanism for the direct involvement of ATM in DSB repair by high-LET irradiation.

  9. A novel manganese-dependent ATM-p53 signaling pathway is selectively impaired in patient-based neuroprogenitor and murine striatal models of Huntington's disease.

    Science.gov (United States)

    Tidball, Andrew M; Bryan, Miles R; Uhouse, Michael A; Kumar, Kevin K; Aboud, Asad A; Feist, Jack E; Ess, Kevin C; Neely, M Diana; Aschner, Michael; Bowman, Aaron B

    2015-04-01

    The essential micronutrient manganese is enriched in brain, especially in the basal ganglia. We sought to identify neuronal signaling pathways responsive to neurologically relevant manganese levels, as previous data suggested that alterations in striatal manganese handling occur in Huntington's disease (HD) models. We found that p53 phosphorylation at serine 15 is the most responsive cell signaling event to manganese exposure (of 18 tested) in human neuroprogenitors and a mouse striatal cell line. Manganese-dependent activation of p53 was severely diminished in HD cells. Inhibitors of ataxia telangiectasia mutated (ATM) kinase decreased manganese-dependent phosphorylation of p53. Likewise, analysis of ATM autophosphorylation and additional ATM kinase targets, H2AX and CHK2, support a role for ATM in the activation of p53 by manganese and that a defect in this process occurs in HD. Furthermore, the deficit in Mn-dependent activation of ATM kinase in HD neuroprogenitors was highly selective, as DNA damage and oxidative injury, canonical activators of ATM, did not show similar deficits. We assessed cellular manganese handling to test for correlations with the ATM-p53 pathway, and we observed reduced Mn accumulation in HD human neuroprogenitors and HD mouse striatal cells at manganese exposures associated with altered p53 activation. To determine if this phenotype contributes to the deficit in manganese-dependent ATM activation, we used pharmacological manipulation to equalize manganese levels between HD and control mouse striatal cells and rescued the ATM-p53 signaling deficit. Collectively, our data demonstrate selective alterations in manganese biology in cellular models of HD manifest in ATM-p53 signaling.

  10. Differential Processing of Low and High LET Radiation Induced DNA Damage: Investigation of Switch from ATM to ATR Signaling

    Science.gov (United States)

    Saha, Janapriya; Wang, Minli; Hada, Megumi; Cucinotta, Francis A.

    2011-01-01

    The members of the phosphatidylinositol kinase-like kinase family of proteins namely ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are directly responsible for the maintenance of genomic integrity by mounting DDR through signaling and facilitating the recruitment of repair factors at the sites of DNA damage along with coordinating the deployment of cell cycle checkpoints to permit repair by phosphorylating Checkpoint kinase Chk1, Chk2 and p53. High LET radiation from GCR (Galactic Cosmic Rays) consisting mainly of protons and high energy and charged (HZE) particles from SPE (Solar Particle Event) pose a major health risk for astronauts on their space flight missions. The determination of these risks and the design of potential safeguards require sound knowledge of the biological consequences of lesion induction and the capability of the cells to counter them. We here strive to determine the coordination of ATM and ATR kinases at the break sites directly affecting checkpoint signaling and DNA repair and whether differential processing of breaks induced by low and high LET radiation leads to possible augmentation of swap of these damage sensors at the sites of DNA damage. Exposure of cells to IR triggers rapid autophosphorylation of serine-1981 that causes dimer dissociation and initiates monomer formation of ATM. ATM kinase activity depends on the disruption of the dimer, which allows access and phosphorylation of downstream ATM substrates like Chk2. Evidence suggests that ATM is activated by the alterations in higher-order chromatin structure although direct binding of ATM to DSB ends may be a crucial step in its activation. On the other hand, in case of ATR, RPA (replication protein A)-coated ssDNA (single-stranded DNA) generated as a result of stalled DNA replication or during processing of chromosomal lesions is crucial for the localization of ATR to sites of DNA damage in association with ATR-interacting protein (ATRIP). Although the

  11. ATM Polymorphisms Predict Severe Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Huihua [Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan (China); Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Zhensheng [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Xu, Ting [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Qiming; Liu, Hongliang [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko; Gomez, Daniel [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Li-E [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Qingyi, E-mail: qwei@mdanderson.org [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-03-15

    Purpose: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP). Methods and Materials: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered. Results: Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites. Conclusions: ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.

  12. Genome stability of Arabidopsis atm, ku80 and rad51b mutants: somatic and transgenerational responses to stress.

    Science.gov (United States)

    Yao, Youli; Bilichak, Andriy; Titov, Viktor; Golubov, Andrey; Kovalchuk, Igor

    2013-06-01

    DNA double-strand breaks (DSBs) can be repaired via two main mechanisms: non-homologous end joining (NHEJ) and homologous recombination (HR). Our previous work showed that exposure to abiotic stresses resulted in an increase in point mutation frequency (PMF) and homologous recombination frequency (HRF), and these changes were heritable. We hypothesized that mutants impaired in DSB recognition and repair would also be deficient in somatic and transgenerational changes in PMF and HRF. To test this hypothesis, we analyzed the genome stability of the Arabidopsis thaliana mutants deficient in ATM (communication between DNA strand break recognition and the repair machinery), KU80 (deficient in NHEJ) and RAD51B (deficient in HR repair) genes. We found that all three mutants exhibited higher levels of DSBs. Plants impaired in ATM had a lower spontaneous PMF and HRF, whereas ku80 plants had higher frequencies. Plants impaired in RAD51B had a lower HRF. HRF in wild-type, atm and rad51b plants increased in response to several abiotic stressors, whereas it did not increase in ku80 plants. The progeny of stressed wild-type and ku80 plants exhibited an increase in HRF in response to all stresses, and the increase was higher in ku80 plants. The progeny of atm plants showed an increase in HRF only when the parental generation was exposed to cold or flood, whereas the progeny of rad51b plants completely lacked a transgenerational increase in HRF. Our experiments showed that mutants impaired in the recognition and repair of DSBs exhibited changes in the efficiency of DNA repair as reflected by changes in strand breaks, point mutation and HRF. They also showed that the HR RAD51B protein and the protein ATM that recognized damaged DNA might play an important role in transgenerational changes in HRF.

  13. A quasi-quantitative dual multiplexed immunoblot method to simultaneously analyze ATM and H2AX Phosphorylation in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Bakkenist, Christopher J; Czambel, R Kenneth; Hershberger, Pamela A; Tawbi, Hussein; Beumer, Jan H; Schmitz, John C

    2015-01-01

    Pharmacologic inhibition of DNA repair may increase the efficacy of many cytotoxic cancer agents. Inhibitors of DNA repair enzymes including APE1, ATM, ATR, DNA-PK and PARP have been developed and the PARP inhibitor olaparib is the first-in-class approved in Europe and the USA for the treatment of advanced BRCA-mutated ovarian cancer. Sensitive pharmacodynamic (PD) biomarkers are needed to further evaluate the efficacy of inhibitors of DNA repair enzymes in clinical trials. ATM is a protein kinase that mediates cell-cycle checkpoint activation and DNA double-strand break repair. ATM kinase activation at DNA double-strand breaks (DSBs) is associated with intermolecular autophosphorylation on serine-1981. Exquisite sensitivity and high stoichiometry as well as facile extraction suggest that ATM serine-1981 phosphorylation may be a highly dynamic PD biomarker for both ATM kinase inhibitors and radiation- and chemotherapy-induced DSBs. Here we report the pre-clinical analytical validation and fit-for-purpose biomarker method validation of a quasi-quantitative dual multiplexed immunoblot method to simultaneously analyze ATM and H2AX phosphorylation in human peripheral blood mononuclear cells (PBMCs). We explore the dynamics of these phosphorylations in PBMCs exposed to chemotherapeutic agents and DNA repair inhibitors in vitro, and show that ATM serine-1981 phosphorylation is increased in PBMCs in sarcoma patients treated with DNA damaging chemotherapy.

  14. Dual inhibition of ATR and ATM potentiates the activity of trabectedin and lurbinectedin by perturbing the DNA damage response and homologous recombination repair.

    Science.gov (United States)

    Lima, Michelle; Bouzid, Hana; Soares, Daniele G; Selle, Frédéric; Morel, Claire; Galmarini, Carlos M; Henriques, João A P; Larsen, Annette K; Escargueil, Alexandre E

    2016-05-03

    Trabectedin (Yondelis®, ecteinascidin-743, ET-743) is a marine-derived natural product approved for treatment of advanced soft tissue sarcoma and relapsed platinum-sensitive ovarian cancer. Lurbinectedin is a novel anticancer agent structurally related to trabectedin. Both ecteinascidins generate DNA double-strand breaks that are processed through homologous recombination repair (HRR), thereby rendering HRR-deficient cells particularly sensitive. We here characterize the DNA damage response (DDR) to trabectedin and lurbinectedin in HeLa cells. Our results show that both compounds activate the ATM/Chk2 (ataxia-telangiectasia mutated/checkpoint kinase 2) and ATR/Chk1 (ATM and RAD3-related/checkpoint kinase 1) pathways. Interestingly, pharmacological inhibition of Chk1/2, ATR or ATM is not accompanied by any significant improvement of the cytotoxic activity of the ecteinascidins while dual inhibition of ATM and ATR strongly potentiates it. Accordingly, concomitant inhibition of both ATR and ATM is an absolute requirement to efficiently block the formation of γ-H2AX, MDC1, BRCA1 and Rad51 foci following exposure to the ecteinascidins. These results are not restricted to HeLa cells, but are shared by cisplatin-sensitive and -resistant ovarian carcinoma cells. Together, our data identify ATR and ATM as central coordinators of the DDR to ecteinascidins and provide a mechanistic rationale for combining these compounds with ATR and ATM inhibitors.

  15. ATM Expression Predicts Veliparib and Irinotecan Sensitivity in Gastric Cancer by Mediating P53-Independent Regulation of Cell Cycle and Apoptosis.

    Science.gov (United States)

    Subhash, Vinod Vijay; Tan, Shi Hui; Yeo, Mei Shi; Yan, Fui Leng; Peethala, Praveen C; Liem, Natalia; Krishnan, Vaidehi; Yong, Wei Peng

    2016-12-01

    Identification of synthetically lethal cellular targets and synergistic drug combinations is important in cancer chemotherapy as they help to overcome treatment resistance and increase efficacy. The Ataxia Telangiectasia Mutated (ATM) kinase is a nuclear protein that plays a major role in the initiation of DNA repair signaling and cell-cycle check points during DNA damage. Although ATM was shown to be associated with poor prognosis in gastric cancer, its implications as a predictive biomarker for cancer chemotherapy remain unexplored. The present study evaluated ATM-induced synthetic lethality and its role in sensitization of gastric cancer cells to PARP and TOP1 inhibitors, veliparib (ABT-888) and irinotecan (CPT-11), respectively. ATM expression was detected in a panel of gastric cell lines, and the IC50 against each inhibitors was determined. The combinatorial effect of ABT-888 and CPT-11 in gastric cancer cells was also determined both in vitro and in vivo ATM deficiency was found to be associated with enhanced sensitivity to ABT-888 and CPT-11 monotherapy, hence suggesting a mechanism of synthetic lethality. Cells with high ATM expression showed reduced sensitivity to monotherapy; however, they showed a higher therapeutic effect with ABT-888 and CPT-11 combinatorial therapy. Furthermore, ATM expression was shown to play a major role in cellular homeostasis by regulating cell-cycle progression and apoptosis in a P53-independent manner. The present study highlights the clinical utility of ATM expression as a predictive marker for sensitivity of gastric cancer cells to PARP and TOP1 inhibition and provides a deeper mechanistic insight into ATM-dependent regulation of cellular processes. Mol Cancer Ther; 15(12); 3087-96. ©2016 AACR.

  16. Analysis of a generic model for a bottleneck link in an integrated services communications network

    NARCIS (Netherlands)

    Al-Begain, K.; Heindl, A.; Telek, M.; Litjens, R.; Boucherie, R.J.

    2007-01-01

    We develop and analyse a generic model for performance evaluation, parameter optimisation and dimensioning of a bottleneck link in an integrated services communications network. Possible application areas include ip, atm and gsm/gprs networks. The model enables analytical evaluation for a scenario o

  17. 网络接入设备的ATM UTOPIA接口设计与实现%The Design and Implement of ATM UTOPIA Interface in Network Access Device

    Institute of Scientific and Technical Information of China (English)

    刘雅娟; 田素芬; 冉茂儒

    2003-01-01

    本文针对网络接入设备为用户端提供ATM支持,主要探讨了基于MPC850研制的网络接入设备设计中如何设计ATM UTOPIA接口,并探讨了在物理层上信元传输的时序与传输过程.

  18. Reality of LOG analytical tool of ATM teller machines movement actions%ATM取款机机芯动作LOG文件解析工具的实现

    Institute of Scientific and Technical Information of China (English)

    何惠英; 李纪红; 俞妍; 沈虹

    2013-01-01

    To reduce the demands to general maintenance personnels for bank self-service teller machines, it provides a log files analytical tool of ATM teller machine in Chinese based on Python language. By analyzing data in nearly 20,000 machines of 500G capacity with the analytical tool based on the method mentioned in this article, it can concluded that by using this method , the operating performance of the machines can be obtained fastly, accurately and detailedly, and machine failures can be excluded easily.%文中基于降低对银行自助取款机一般维护人员要求的目的,采用Python编程语言编写了取款机机芯运行记录文件的中文解析工具.通过近两万台500G容量的生产环境下机器运行数据分析,得出采用本文所述方法编写的解析工具可以快速、准确、详细地获得机器的运行性能并能据此排除机器故障的结论.

  19. Congestion control for ATM multiplexers using neural networks:multiple sources/single buffer scenario

    Institute of Scientific and Technical Information of China (English)

    杜树新; 袁石勇

    2004-01-01

    A new neural network based method for solving the problem of congestion control arising at the user network interface (UNI) of ATM networks is proposed in this paper. Unlike the previous methods where the coding rate for all traffic sources as controller output signals is tuned in a body, the proposed method adjusts the coding rate for only a part of the traffic sources while the remainder sources send the cells in the previous coding rate in case of occurrence of congestion. The controller output signals include the source coding rate and the percentage of the sources that send cells at the corresponding coding rate. The control methods not only minimize the cell loss rate but also guarantee the quality of information (such as voice sources) fed into the multiplexer buffer. Simulations with 150 ADPCM voice sources fed into the multiplexer buffer showed that the proposed methods have advantage over the previous methods in the aspect of the performance indices such as cell loss rate (CLR) and voice quality.

  20. Congestion control for ATM multiplexers using neural networks:multiple sources/single buffer scenario

    Institute of Scientific and Technical Information of China (English)

    杜树新; 袁石勇

    2004-01-01

    A new neural network based method for solving the problem of congestion control arising at the user network interface (UNI) of ATM networks is proposed in this paper. Unlike the previous methods where the coding rate for all traffic sources as controller output signals is tuned in a body, the proposed method adjusts the coding rate for only a part of the traffic sources while the remainder sources send the cells in the previous coding rate in case of occurrence of congestion. The controller output signals include the source coding rate and the percentage of the sources that send cells at the corresponding coding rate. The control methods not only minimize the cell loss rate but also guarantee the quality of information (such as voice sources) fed into the multiplexer buffer. Simulations with 150 ADPCM voice sources fed into the multiplexer buffer showed that the proposed methods have advantage over the previous methods in the aspect of the performance indices such as cell loss rate (CLR) and voice quality.

  1. Reduction of NO by propane in a JSR at 1 atm: experimental and kinetic modeling

    Energy Technology Data Exchange (ETDEWEB)

    Dagaut, P.; Luche, J.; Cathonnet, M. [CNRS, Laboratoire de Combustin et Systemes Reactifs, Orleans (France)

    2001-05-01

    The reduction of nitric oxide( NO) by propane in simulated conditions of the reburning zone has been studied in a fused silica jets-stirred reactor operating at 1 atm. The temperatures were in the range from 1150 to 1400 K. In the present experiments, the initial mole fraction of NO was 1000 ppm, that of propane was 2490-2930 ppm. The equivalence ratio has been varied fro 0.6 to 2. It was demonstrated that the reduction of NO varies with the temperature and that for a given temperature, a maximum O-reduction occurs slightly above stoichiometric conditions. The present results generally follow those obtained in previous studies involving simple hydrocarbons or natural gas as reburn fuel. The neat oxidation of propane was also studied in the same conditions of temperature, pressure and residence time. A detailed chemical kinetic modeling of the present experiments was performed using an updated and improved kinetic scheme (89 reversible reactions and 113 species). An overall reasonable agreement between the present data and the modeling was obtained. Also, the proposed kinetic mechanism can be successfully used to model the reduction of NO by ethane, ethylene, a natural gas blend (methane-ethane 10:1). According to this study, the main route to NO-reduction by propane involves the ketenyl radical. 17 refs., 6 figs.

  2. Buffer allocation in an ATM switch with output buffer and speed constraints

    Science.gov (United States)

    Gupta, Anil K.; Georganas, N. D.

    A synchronous nonblocking N times N switch for asynchronous transfer mode (ATM) networks or high speed packet switching networks transporting fixed length packets called cells is considered. Such a switch with output queuing achieves the optimal performance, however it requires the switch fabric to work at the speed of N. In practice the switch may operate L times faster than the input/output trunk. It is assumed that queues at each output port have a limited buffer space and whenever an output queue is full, the back-pressure is applied and the packets are retained at the head of the input queues. The upper bound on the packet loss probability at the input queues in such a switch are computed. To achieve a given packet loss rate, the switch with L equals 2 requires almost the same amount of input and output buffers as with L equals 4 up to 70 percent input load, but as the load increases beyond 70 percent the switch with L equals 4 would require more output buffers and less input buffers in comparison with a switch operating at L equals 2. The performance of a switch with L equals 3 is very similar to that for L equals 4 and is not considered.

  3. Results from CrIS/ATMS Obtained Using an AIRS "Version-6 like" Retrieval Algorithm

    Science.gov (United States)

    Susskind, Joel; Kouvaris, Louis; Iredell, Lena

    2015-01-01

    We tested and evaluated Version-6.22 AIRS and Version-6.22 CrIS products on a single day, December 4, 2013, and compared results to those derived using AIRS Version-6. AIRS and CrIS Version-6.22 O3(p) and q(p) products are both superior to those of AIRS Version-6All AIRS and CrIS products agree reasonably well with each other. CrIS Version-6.22 T(p) and q(p) results are slightly poorer than AIRS over land, especially under very cloudy conditions. Both AIRS and CrIS Version-6.22 run now at JPL. Our short term plans are to analyze many common months at JPL in the near future using Version-6.22 or a further improved algorithm to assess the compatibility of AIRS and CrIS monthly mean products and their interannual differences. Updates to the calibration of both CrIS and ATMS are still being finalized. JPL plans, in collaboration with the Goddard DISC, to reprocess all AIRS data using a still to be finalized Version-7 retrieval algorithm, and to reprocess all recalibrated CrISATMS data using Version-7 as well.

  4. ATM participates in the regulation of viability and cell cycle via ellipticine in bladder cancer

    Science.gov (United States)

    Tao, Shuixiang; Meng, Shuai; Zheng, Xiangyi; Xie, Liping

    2017-01-01

    Ellipticine, an alkaloid isolated from Apocyanaceae plants, has been demonstrated to exhibit antitumor activity in several cancers. However, the effect and the mechanisms underlying its action have not been investigated in human bladder cancer cells. The aim of the present study was to investigate the effect and mechanism of ellipticine on the behavior of T-24 bladder cancer cells. T-24 cells were treated with varying concentrations and durations of ellipticine. Cell viability was evaluated by Cell Counting Kit-8 assay. Cell motility was analyzed by Transwell migration assay. Flow cytometry, reverse transcription-quantitative polymerase chain reaction and western blot analyses were performed to detect the cell cycle and signaling pathways involved. The results demonstrated that ellipticine suppressed proliferation and inhibited the migration ability of T-24 bladder cancer cells in a dose- and time-dependent manner, and resulted in G2/M cell cycle arrest. The mechanism of this action was demonstrated to be due to ellipticine-triggered activation of the ATM serine/threonine kinase pathway. These data therefore suggest that ellipticine may be effective towards treating human bladder cancer. PMID:28138703

  5. The crustal uplift determined at the Jakobshavn glacier (West Greenland) using ATM and GPS data

    DEFF Research Database (Denmark)

    Muresan, Ioana Stefania; Frumosu, Flavia Dalia; Khan, Shfaqat Abbas

    The Greenland ice sheet has experienced record melting in recent years. In order to estimate the ice loss we can make use of the earth’s natural elasticity to weigh the ice. Ice bends down the bedrock so when the ice melts away, the bedrock rises measurably in response. Throughout this abstract we....... The total ice mass loss inkm3 of water predicted from the ATM dataconcerning the Jakobshavn area is -88.815between 2010 and 2005 and -83.599between 2005 and 1997. It seems fair to state that this differences, between the predicted and observed rates, mayalso be due to the fact that not all the errors have......-2010. In order to compute the crustal uplift in response to the ice mass loss of the Jakobshavnarea from the GPS stations, the convolution of the gridded thinning rates has been computed with the vertical-displacement Green’s function as described in [1]. Several manipulations of data were required in order...

  6. Redox regulation of SUMO enzymes is required for ATM activity and survival in oxidative stress.

    Science.gov (United States)

    Stankovic-Valentin, Nicolas; Drzewicka, Katarzyna; König, Cornelia; Schiebel, Elmar; Melchior, Frauke

    2016-06-15

    To sense and defend against oxidative stress, cells depend on signal transduction cascades involving redox-sensitive proteins. We previously identified SUMO (small ubiquitin-related modifier) enzymes as downstream effectors of reactive oxygen species (ROS). Hydrogen peroxide transiently inactivates SUMO E1 and E2 enzymes by inducing a disulfide bond between their catalytic cysteines. How important their oxidation is in light of many other redox-regulated proteins has however been unclear. To selectively disrupt this redox switch, we identified a catalytically fully active SUMO E2 enzyme variant (Ubc9 D100A) with strongly reduced propensity to maintain a disulfide with the E1 enzyme in vitro and in cells. Replacement of Ubc9 by this variant impairs cell survival both under acute and mild chronic oxidative stresses. Intriguingly, Ubc9 D100A cells fail to maintain activity of the ATM-Chk2 DNA damage response pathway that is induced by hydrogen peroxide. In line with this, these cells are also more sensitive to the ROS-producing chemotherapeutic drugs etoposide/Vp16 and Ara-C. These findings reveal that SUMO E1~E2 oxidation is an essential redox switch in oxidative stress.

  7. Nuclear initiated NF-κB signaling: NEMO and ATM take center stage

    Institute of Scientific and Technical Information of China (English)

    Shigeki Miyamoto

    2011-01-01

    A large body of literature describes elaborate NF-κB signaling networks induced by inflammatory and immune signals.Decades of research has revealed that transcriptionally functional NF-κB dimers are activated by two major pathways,canonical and non-canonical.Both pathways involve the release of NF-κB dimers from inactive cytoplasmic complexes to cause their nuclear translocation to modulate gene expression programs and biological responses.NF-κB is also responsive to genotoxic agents; however,signal communication networks that are initiated in the nucleus following DNA damage induction are less defined.Evidence in the literature supports the presence of such signaling pathways induced by multiple distinct genotoxic agents,resulting in the activation of cytoplasmic IKK complex.An example is a pathway that involves the DNA damage-responsive kinase ataxia telangiectasia mutated(ATM)and a series of post-translational modifications of NF-κB essential modulator(NEMO)in the nucleus of a genotoxinexposed cell.Recent evidence also suggests that this nuclear-initiated NF-κB signaling pathway plays significant physiological and pathological roles,particularly in lymphocyte development and human cancer progression.This review will summarize these new developments,while identifying significant unanswered questions and providing new hypotheses that may be addressed in future studies.

  8. Clock- and data-recovery IC with demultiplexer for a 2.5 Gb/s ATM physical layer controller

    DEFF Research Database (Denmark)

    Hansen, Flemming; Salama, C.A.T.

    1996-01-01

    A Clock- and Data-Recovery (CDR) IC for a Physical Layer Controller in an Asynchronous Transfer Mode (ATM) system operating at a bit rate of 2.488 Gb/s is presented. The circuit was designed and fabricated in a 0.8 μm BiCMOS process featuring 13 GHz fT bipolar transistors. Clock-recovery is accom......A Clock- and Data-Recovery (CDR) IC for a Physical Layer Controller in an Asynchronous Transfer Mode (ATM) system operating at a bit rate of 2.488 Gb/s is presented. The circuit was designed and fabricated in a 0.8 μm BiCMOS process featuring 13 GHz fT bipolar transistors. Clock...

  9. ATM sequence variants and risk of radiation-induced subcutaneous fibrosis after postmastectomy radiotherapy

    DEFF Research Database (Denmark)

    Andreassen, Christian Nicolaj; Overgaard, Jens; Alsner, Jan

    2006-01-01

    in 22 patients. The ED50 (95% confidence interval) of 60.2 (55.7-65.1) Gy calculated for patients without a sequence variation did not differ significantly from the ED50 of 58.4 (54.0-63.1) Gy for the group of patients with any ATM sequence abnormality. The ED50 of 53.7 (50.2-57.5) Gy for those patients...... alteration. This resulted in an enhancement ratio (ratio of the ED50 values) of 1.13 (1.05-1.22), which was significantly greater than unity. CONCLUSION: The results of this study suggest an association between the ATM codon 1853 Asn/Asp and Asn/Asn genotypes with the development of Grade 3 fibrosis...

  10. ATM在计算机通信网中的应用%Application of ATM in Computer Communication Network

    Institute of Scientific and Technical Information of China (English)

    范江波

    2005-01-01

    本文主要介绍了ATM(Asynchronous transfer mode)即异步传输模式的基本原理、特点、信元结构、交换原理、网络结构.以及它在计算机通信网中关于ATM局域网仿真和IP over ATM技术中的应用.

  11. Radiosensitivity to high energy iron ions is influenced by heterozygosity for Atm, Rad9 and Brca1

    Science.gov (United States)

    Zhou, G.; Smilenov, L. B.; Lieberman, H. B.; Ludwig, T.; Hall, E. J.

    2010-09-01

    Loss of function of DNA repair genes has been implicated in the development of many types of cancer. In the last several years, heterozygosity leading to haploinsufficiency for proteins involved in DNA repair was shown to play a role in genomic instability and carcinogenesis after DNA damage is induced, for example by ionizing radiation. Since the effect of heterozygosity for one gene is relatively small, we hypothesize that predisposition to cancer could be a result of the additive effect of heterozygosity for two or more genes critical to pathways that control DNA damage signaling, repair or apoptosis. We investigated the role of heterozygosity for Atm, Rad9 and Brca1 on cell oncogenic transformation and cell survival induced by 1 GeV/ n56Fe ions. Our results show that cells heterozygous for both Atm and Rad9 or Atm and Brca1 have high survival rates and are more sensitive to transformation by high energy iron ions when compared with wild-type controls or cells haploinsufficient for only one of these proteins. Since mutations or polymorphisms for similar genes exist in a small percentage of the human population, we have identified a radiosensitive sub-population. This finding has several implications. First, the existence of a radiosensitive sub-population may distort the shape of the dose-response relationship. Second, it would not be ethical to put exceptionally radiosensitive individuals into a setting where they may potentially be exposed to substantial doses of radiation.

  12. Alterations in cellular energy metabolism associated with the antiproliferative effects of the ATM inhibitor KU-55933 and with metformin.

    Directory of Open Access Journals (Sweden)

    Mahvash Zakikhani

    Full Text Available KU-55933 is a specific inhibitor of the kinase activity of the protein encoded by Ataxia telangiectasia mutated (ATM, an important tumor suppressor gene with key roles in DNA repair. Unexpectedly for an inhibitor of a tumor suppressor gene, KU-55933 reduces proliferation. In view of prior preliminary evidence suggesting defective mitochondrial function in cells of patients with Ataxia Telangiectasia (AT, we examined energy metabolism of cells treated with KU-55933. The compound increased AMPK activation, glucose uptake and lactate production while reducing mitochondrial membrane potential and coupled respiration. The stimulation of glycolysis by KU-55933 did not fully compensate for the reduction in mitochondrial functions, leading to decreased cellular ATP levels and energy stress. These actions are similar to those previously described for the biguanide metformin, a partial inhibitor of respiratory complex I. Both compounds decreased mitochondrial coupled respiration and reduced cellular concentrations of fumarate, malate, citrate, and alpha-ketogluterate. Succinate levels were increased by KU-55933 levels and decreased by metformin, indicating that the effects of ATM inhibition and metformin are not identical. These observations suggest a role for ATM in mitochondrial function and show that both KU-55933 and metformin perturb the TCA cycle as well as oxidative phosphorylation.

  13. Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation.

    Science.gov (United States)

    Vendetti, Frank P; Leibowitz, Brian J; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O'Connor, Mark J; Yu, Jian; Beumer, Jan H; Bakkenist, Christopher J

    2017-02-01

    We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21(CIP/WAF1))-/- mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21(CIP/WAF1))-/- mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21(CIP/WAF1))-/-, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21(CIP/WAF1))-/- mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI.

  14. Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage.

    Science.gov (United States)

    Quek, Hazel; Luff, John; Cheung, KaGeen; Kozlov, Sergei; Gatei, Magtouf; Lee, C Soon; Bellingham, Mark C; Noakes, Peter G; Lim, Yi Chieh; Barnett, Nigel L; Dingwall, Steven; Wolvetang, Ernst; Mashimo, Tomoji; Roberts, Tara L; Lavin, Martin F

    2016-11-28

    Mutations in the ataxia-telangiectasia (A-T)-mutated (ATM) gene give rise to the human genetic disorder A-T, characterized by immunodeficiency, cancer predisposition, and neurodegeneration. Whereas a series of animal models recapitulate much of the A-T phenotype, they fail to present with ataxia or neurodegeneration. We describe here the generation of an Atm missense mutant [amino acid change of leucine (L) to proline (P) at position 2262 (L2262P)] rat by intracytoplasmic injection (ICSI) of mutant sperm into oocytes. Atm-mutant rats (Atm(L2262P/L2262P)) expressed low levels of ATM protein, suggesting a destabilizing effect of the mutation, and had a significantly reduced lifespan compared with Atm(+/+) Whereas these rats did not show cerebellar atrophy, they succumbed to hind-limb paralysis (45%), and the remainder developed tumors. Closer examination revealed the presence of both dsDNA and ssDNA in the cytoplasm of cells in the hippocampus, cerebellum, and spinal cord of Atm(L2262P/L2262P) rats. Significantly increased levels of IFN-β and IL-1β in all 3 tissues were indicative of DNA damage induction of the type 1 IFN response. This was further supported by NF-κB activation, as evidenced by p65 phosphorylation (P65) and translocation to the nucleus in the spinal cord and parahippocampus. Other evidence of neuroinflammation in the brain and spinal cord was the loss of motor neurons and the presence of increased activation of microglia. These data provide support for a proinflammatory phenotype that is manifested in the Atm mutant rat as hind-limb paralysis. This mutant represents a useful model to investigate the importance of neuroinflammation in A-T .

  15. p38 MAPK-Mediated Bmi-1 down-regulation and defective proliferation in ATM-deficient neural stem cells can be restored by Akt activation.

    Directory of Open Access Journals (Sweden)

    Jeesun Kim

    Full Text Available A-T (ataxia telangiectasia is a genetic disease caused by a mutation in the Atm (A-T mutated gene that leads to neurodegeneration. Despite an increase in the numbers of studies in this area in recent years, the mechanisms underlying neurodegeneration in human A-T are still poorly understood. Previous studies demonstrated that neural stem cells (NSCs isolated from the subventricular zone (SVZ of Atm(-/- mouse brains show defective self-renewal and proliferation, which is accompanied by activation of chronic p38 mitogen-activated protein kinase (MAPK and a lower level of the polycomb protein Bmi-1. However, the mechanism underlying Bmi-1 down-regulation and its relevance to defective proliferation in Atm(-/- NSCs remained unclear. Here, we show that over-expression of Bmi-1 increases self-renewal and proliferation of Atm(-/- NSCs to normal, indicating that defective proliferation in Atm(-/- NSCs is a consequence of down-regulation of Bmi-1. We also demonstrate that epidermal growth factor (EGF-induced Akt phosphorylation renders Bmi-1 resistant to the proteasomal degradation, leading to its stabilization and accumulation in the nucleus. However, inhibition of the Akt-dependent Bmi-1 stabilizing process by p38 MAPK signaling reduces the levels of Bmi-1. Treatment of the Atm(-/- NSCs with a specific p38 MAPK inhibitor SB203580 extended Bmi-1 posttranscriptional turnover and H2A ubiquitination in Atm(-/- NSCs. Our observations demonstrate the molecular basis underlying the impairment of self-renewal and proliferation in Atm(-/- NSCs through the p38 MAPK-Akt-Bmi-1-p21 signaling pathway.

  16. Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation

    Science.gov (United States)

    Vendetti, Frank P.; Leibowitz, Brian J.; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F.; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O’Connor, Mark J.; Yu, Jian; Beumer, Jan H.; Bakkenist, Christopher J.

    2017-01-01

    We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21CIP/WAF1)−/− mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21CIP/WAF1)−/− mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21CIP/WAF1)−/−, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21CIP/WAF1)−/− mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI. PMID:28145510

  17. High LET Radiation Can Enhance TGF(Beta) Induced EMT and Cross-Talk with ATM Pathways

    Science.gov (United States)

    Wang, Minli; Hada, Megumi; Huff, Janice; Pluth, Janice M.; Anderson, Janniffer; ONeill, Peter; Cucinotta, Francis A.

    2010-01-01

    The TGF(Beta) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation in mammary epithelial cells. We investigated possible interactions between the TGF(Beta) and ATM pathways following simulated space radiation using hTERT immortalized human esophageal epithelial cells (EPC-hTERT), mink lung epithelial cells (Mv1lu), and several human fibroblast cell lines. TGF(Beta) is a key modulator of the Epithelial-Mesenchymal Transition (EMT), important in cancer progression and metastasis. The implication of EMT by radiation also has several lines of developing evidence, however is poorly understood. The identification of TGF(Beta) induced EMT can be shown in changes to morphology, related gene over expression or down regulation, which can be detected by RT-PCR, and immunostaining and western blotting. In this study, we have observed morphologic and molecular alternations consistent with EMT after Mv1lu cells were treated with TGF(Beta) High LET radiation enhanced TGF(Beta) mediated EMT with a dose as low as 0.1Gy. In order to consider the TGF(Beta) interaction with ATM we used a potent ATM inhibitor Ku55933 and investigated gene expression changes and Smad signaling kinetics. Ku559933 was observed to reverse TGF(Beta) induced EMT, while this was not observed in dual treated cells (radiation+TGF(Beta)). In EPC-hTERT cells, TGF(Beta) alone was not able to induce EMT after 3 days of application. A combined treatment with high LET, however, significantly caused the alteration of EMT markers. To study the function of p53 in the process of EMT, we knocked down P53 through RNA interference. Morphology changes associated with EMT were observed in epithelial cells with silenced p53. Our study indicates: high LET radiation can enhance TGF(Beta) induced EMT; while ATM is triggering the process of TGF(Beta)-induced EMT, p53 might be an essential repressor for EMT phenotypes.

  18. Concordance of ATM (ataxia telangiectasia mutated) immunohistochemistry between biopsy or metastatic tumor samples and primary tumors in gastric cancer patients.

    Science.gov (United States)

    Kim, Hee Sung; Kim, Min A; Hodgson, Darren; Harbron, Christopher; Wellings, Robert; O'Connor, Mark J; Womack, Christopher; Yin, Xiaolu; Bang, Yung-Jue; Im, Seok-Ah; Lee, Byung Lan; Kim, Woo Ho

    2013-01-01

    ATM (ataxia telangiectasia mutated) is one of several DNA repair proteins that are suggested to sensitize tumor cells to the poly(ADP-ribose) polymerase inhibitor olaparib when deficient. The aim of this study was to assess the spatiotemporal concordance of ATM immunohistochemistry (IHC) in gastric cancer in order to determine if measurements made at the level of various sample types and times could be inferred as having the potential to be relevant to treatment decisions made at the patient level. Two independent cohorts composed of 591 gastric cancer patients divided into a gastrectomy cohort (n = 450) and a metastasis cohort (n = 141) were used in this study. A total of 2,705 ATM IHC samples were examined, including 450 whole tissue, 3 sets of 450 tissue microarray (TMA), 301 biopsy, 222 metastatic tumor and 2 additional whole tissue samples of 50 cases from the gastrectomy cohort, and 141 pairs of primary and metastatic tumors from the metastasis cohort. The prevalence of ATM negativity was 13.1% in biopsies, 13.9, 15.1, and 16.0% in TMAs and 15.9% in whole tissue samples of the gastrectomy cohort, and 21.4% in primary tumor and 21.5% in metastatic tumor samples of the metastasis cohort. coefficients were 0.341 for biopsy, 0.572 as the average of 3 TMAs and 0.415 for the largely synchronous metastatic tumors of the gastrectomy cohort, and 0.153 for the largely asynchronous metastatic tumors of the metastasis cohort. Using whole tissue sections from tumor resections or primary tumor, respectively, as the reference standards, specificity and sensitivity were 91.6 and 41.0% for biopsy, 93.9 and 61.9% as the average of 3 TMAs, and 86.6 and 58.8% for metastatic tumors of the gastrectomy cohort and 81.7 and 33.3% for metastatic tumors of the metastasis cohort, respectively. Although we have demonstrated that the IHC assay for ATM was robust and reproducible in gastric tumor samples, we have also found that measurements were subject to significant discordance across

  19. Activation of H2AX and ATM in varicella-zoster virus (VZV)-infected cells is associated with expression of specific VZV genes.

    Science.gov (United States)

    Yamamoto, Takenobu; Ali, Mir A; Liu, XueQiao; Cohen, Jeffrey I

    2014-03-01

    Mammalian cells activate DNA damage response pathways in response to virus infections. Activation of these pathways can enhance replication of many viruses, including herpesviruses. Activation of cellular ATM results in phosphorylation of H2AX and recruits proteins to sites of DNA damage. We found that varicella-zoster (VZV) infected cells had elevated levels of phosphorylated H2AX and phosphorylated ATM and that these levels increased in cells infected with VZV deleted for ORF61 or ORF63, but not deleted for ORF67. Expression of VZV ORF61, ORF62, or ORF63 alone did not result in phosphorylation of H2AX. While BGLF4, the Epstein-Barr virus homolog of VZV ORF47 protein kinase, phosphorylates H2AX and ATM, neither VZV ORF47 nor ORF66 protein kinase phosphorylated H2AX or ATM. Cells lacking ATM had no reduction in VZV replication. Thus, VZV induces phosphorylation of H2AX and ATM and this effect is associated with the presence of specific VZV genes in virus-infected cells.

  20. Nbn and atm cooperate in a tissue and developmental stage-specific manner to prevent double strand breaks and apoptosis in developing brain and eye.

    Directory of Open Access Journals (Sweden)

    Paulo M G Rodrigues

    Full Text Available Nibrin (NBN or NBS1 and ATM are key factors for DNA Double Strand Break (DSB signaling and repair. Mutations in NBN or ATM result in Nijmegen Breakage Syndrome and Ataxia telangiectasia. These syndromes share common features such as radiosensitivity, neurological developmental defects and cancer predisposition. However, the functional synergy of Nbn and Atm in different tissues and developmental stages is not yet understood. Here, we show in vivo consequences of conditional inactivation of both genes in neural stem/progenitor cells using Nestin-Cre mice. Genetic inactivation of Atm in the central nervous system of Nbn-deficient mice led to reduced life span and increased DSBs, resulting in increased apoptosis during neural development. Surprisingly, the increase of DSBs and apoptosis was found only in few tissues including cerebellum, ganglionic eminences and lens. In sharp contrast, we showed that apoptosis associated with Nbn deletion was prevented by simultaneous inactivation of Atm in developing retina. Therefore, we propose that Nbn and Atm collaborate to prevent DSB accumulation and apoptosis during development in a tissue- and developmental stage-specific manner.

  1. Enzymological Characterization of Atm, the First Laccase from Agrobacterium sp. S5-1, with the Ability to Enhance In Vitro digestibility of Maize Straw.

    Directory of Open Access Journals (Sweden)

    Wei Si

    Full Text Available Laccase is an enzyme that catalyzes oxidation of phenolic compounds, diamines and aromatic amines. In this study, a novel laccase-like gene (atm in a ligninolyitic isolate Agrobacterium sp. S5-1 from soil humus was identified and heterologously expressed in Escherichia coli. Atm exhibited its maximal activity at pH 4.5 and at 50°C. This enzyme was tolerant to high temperature, a broad range of pH, heavy metal ions (Co3+, Mn2+, Cu2+ and Ni2+, 20 mM and all tested organic solvents. Furthermore, Atm significantly (p<0.05 increased dry matter digestibility of maize straw from 23.44% to 27.96% and from 29.53% to 37.10% after 8 or 24 h of digestion and improved acid detergent fiber digestibility from 5.81% to 10.33% and from 12.80% to 19.07% after 8 or 24 h of digestion, respectively. The combination of Atm and fibrolytic enzymes significantly (p<0.05 enhanced neutral detergent fiber digestibility from 19.02% to 24.55% after 24 h of digestion respectively. Results showed treatment with Atm effectively improved in vitro digestibility of maize straw, thus suggesting that Atm has an application potential for bioconversion of lignin rich agricultural byproducts into animal feed and cellulosic ethanol.

  2. Enzymological Characterization of Atm, the First Laccase from Agrobacterium sp. S5-1, with the Ability to Enhance In Vitro digestibility of Maize Straw.

    Science.gov (United States)

    Si, Wei; Wu, ZhaoWei; Wang, LiangLiang; Yang, MingMing; Zhao, Xin

    2015-01-01

    Laccase is an enzyme that catalyzes oxidation of phenolic compounds, diamines and aromatic amines. In this study, a novel laccase-like gene (atm) in a ligninolyitic isolate Agrobacterium sp. S5-1 from soil humus was identified and heterologously expressed in Escherichia coli. Atm exhibited its maximal activity at pH 4.5 and at 50°C. This enzyme was tolerant to high temperature, a broad range of pH, heavy metal ions (Co3+, Mn2+, Cu2+ and Ni2+, 20 mM) and all tested organic solvents. Furthermore, Atm significantly (p<0.05) increased dry matter digestibility of maize straw from 23.44% to 27.96% and from 29.53% to 37.10% after 8 or 24 h of digestion and improved acid detergent fiber digestibility from 5.81% to 10.33% and from 12.80% to 19.07% after 8 or 24 h of digestion, respectively. The combination of Atm and fibrolytic enzymes significantly (p<0.05) enhanced neutral detergent fiber digestibility from 19.02% to 24.55% after 24 h of digestion respectively. Results showed treatment with Atm effectively improved in vitro digestibility of maize straw, thus suggesting that Atm has an application potential for bioconversion of lignin rich agricultural byproducts into animal feed and cellulosic ethanol.

  3. Down-regulation of EBV-LMP1 radio-sensitizes nasal pharyngeal carcinoma cells via NF-κB regulated ATM expression.

    Directory of Open Access Journals (Sweden)

    Xiaoqian Ma

    Full Text Available BACKGROUND: The latent membrane protein 1 (LMP1 encoded by EBV is expressed in the majority of EBV-associated human malignancies and has been suggested to be one of the major oncogenic factors in EBV-mediated carcinogenesis. In previous studies we experimentally demonstrated that down-regulation of LMP1 expression by DNAzymes could increase radiosensitivity both in cells and in a xenograft NPC model in mice. RESULTS: In this study we explored the molecular mechanisms underlying the radiosensitization caused by the down-regulation of LMP1 in nasopharyngeal carcinoma. It was confirmed that LMP1 could up-regulate ATM expression in NPCs. Bioinformatic analysis of the ATM ptomoter region revealed three tentative binding sites for NF-κB. By using a specific inhibitor of NF-κB signaling and the dominant negative mutant of IkappaB, it was shown that the ATM expression in CNE1-LMP1 cells could be efficiently suppressed. Inhibition of LMP1 expression by the DNAzyme led to attenuation of the NF-κB DNA binding activity. We further showed that the silence of ATM expression by ATM-targeted siRNA could enhance the radiosensitivity in LMP1 positive NPC cells. CONCLUSIONS: Together, our results indicate that ATM expression can be regulated by LMP1 via the NF-κB pathways through direct promoter binding, which resulted in the change of radiosensitivity in NPCs.

  4. Characterization of Torin2, an ATP-competitive inhibitor of mTOR, ATM and ATR

    Science.gov (United States)

    Liu, Qingsong; Xu, Chunxiao; Kirubakaran, Sivapriya; Zhang, Xin; Hur, Wooyoung; Liu, Yan; Kwiatkowski, Nicholas P.; Wang, Jinhua; Westover, Kenneth D.; Gao, Peng; Ercan, Dalia; Niepel, Mario; Thoreen, Carson C.; Kang, Seong A.; Patricelli, Matthew P.; Wang, Yuchuan; Tupper, Tanya; Altabef, Abigail; Kawamura, Hidemasa; Held, Kathryn D.; Chou, Danny M.; Elledge, Stephen J.; Janne, Pasi A.; Wong, Kwok-Kin; Sabatini, David M.; Gray, Nathanael S.

    2013-01-01

    mTOR is a highly conserved serine/threonine protein kinase that serves as a central regulator of cell growth, survival and autophagy. Deregulation of the PI3K/Akt/mTOR signaling pathway occurs commonly in cancer and numerous inhibitors targeting the ATP-binding site of these kinases are currently undergoing clinical evaluation. Here we report the characterization of Torin2, a second generation ATP-competitive inhibitor that is potent and selective for mTOR with a superior pharmacokinetic profile to previous inhibitors. Torin2 inhibited mTORC1-dependent T389 phosphorylation on S6K (RPS6KB1) with an EC50 of 250 pM with approximately 800-fold selectivity for cellular mTOR versus PI3K. Torin2 also exhibited potent biochemical and cellular activity against PIKK family kinases including ATM (EC50 28 nM), ATR (EC50 35 nM) and DNA-PK (EC50 118 nM) (PRKDC), the inhibition of which sensitized cells to Irradiation. Similar to the earlier generation compound Torin1 and in contrast to other reported mTOR inhibitors, Torin2 inhibited mTOR kinase and mTORC1 signaling activities in a sustained manner suggestive of a slow dissociation from the kinase. Cancer cell treatment with Torin2 for 24 hours resulted in a prolonged block in negative feedback and consequent T308 phosphorylation on Akt. These effects were associated with strong growth inhibition in vitro. Single agent treatment with Torin2 in vivo did not yield significant efficacy against KRAS-driven lung tumors, but the combination of Torin2 with MEK inhibitor AZD6244 yielded a significant growth inhibition. Taken together, our findings establish Torin2 as a strong candidate for clinical evaluation in a broad number of oncological settings where mTOR signaling has a pathogenic role. PMID:23436801

  5. Arecoline-induced phosphorylated p53 and p21(WAF1) protein expression is dependent on ATM/ATR and phosphatidylinositol-3-kinase in clone-9 cells.

    Science.gov (United States)

    Chou, Wen-Wen; Guh, Jinn-Yuh; Tsai, Jung-Fa; Hwang, Chi-Ching; Chiou, Shean-Jaw; Chuang, Lea-Yea

    2009-06-01

    Betel-quid use is associated with liver cancer whereas its constituent arecoline is cytotoxic, genotoxic, and induces p53-dependent p21(WAF1) protein expression in Clone-9 cells (rat hepatocytes). The ataxia telangiectasia mutated (ATM)/rad3-related (ATR)-p53-p21(WAF1) and the phosphatidylinositol-3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathways are involved in the DNA damage response and the pathogenesis of cancers. Thus, we studied the role of ATM/ATR and PI3K in arecoline-induced p53 and p21(WAF1) protein expression in Clone-9 cells. We found that arecoline (0.5 mM) activated the ATM/ATR kinase at 30 min. The arecoline-activated ATM/ATR substrate contained p-p53Ser15. Moreover, arecoline only increased the levels of the p-p53Ser6, p-p53Ser15, and p-p53Ser392 phosphorylated p53 isoforms among the known isoforms. ATM shRNA attenuated arecoline-induced p-p53Ser15 and p21(WAF1) at 24 h. Arecoline (0.5 mM) increased phosphorylation levels of p-AktSer473 and p-mTORSer2448 at 30-60 min. Dominant-negative PI3K plasmids attenuated arecoline-induced p21(WAF1), but not p-p53Ser15, at 24 h. Rapamycin attenuated arecoline-induced phosphrylated p-p53Ser15, but not p21(WAF1), at 24 h. ATM shRNA, but not dominant-negative PI3K plasmids, attenuated arecoline-induced p21(WAF1) gene transcription. We conclude that arecoline activates the ATM/ATR-p53-p21(WAF1) and the PI3K/Akt-mTOR-p53 pathways in Clone-9 cells. Arecoline-induced phosphorylated p-p53Ser15 expression is dependent on ATM whereas arecoline-induced p21(WAF1) protein expression is dependent on ATM and PI3K. Moreover, p21(WAF1) gene is transcriptionally induced by arecoline-activated ATM.

  6. 年龄对言语诱发 ABR 的频率跟随反应影响%The Effects of Aging on Frequency Following Response in Speech Evoked Auditory Brainstem Response

    Institute of Scientific and Technical Information of China (English)

    郝文洋; 商莹莹; 倪道凤; 姜鸿; 徐春晓; 高志强; 王素菊; 李奉蓉; 赵翠霞

    2016-01-01

    Objective This study was to record the speech evoked auditory brainstem response (s-ABR) of normal hearing young and aged people ,then compared the frequency following responses (FFR) of s-ABR between the two groups ,in order to explore the contribution of FFR on revealing possible aging mechanisms of central audi‐tory system .Methods Twelve normal hearing young adults and aged people respectively (24 ears) were enrolled and s-ABRs (syllable/da/) were recorded using a SmartEP auditory evoked potential system .Results The comparison of waveforms between the two groups showed that the wave latencies of transient responses in the aged group was longer than that of young group ,while the wave latencies of the sustained response ,FFR ,were of no significant differences .The amplitudes of FFR waves in the aged group were lower than those of in the young group .The FFR spectrum analysis showed that the relative energy of each formant for the aged group was lower than that of in the young group and for some formants .Moreover ,for the aged group ,formant frequency differences between FFR and stimulus signal were greater than the young group .Conclusion Compared with young people ,the FFR of aged peo‐ple showed lower amplitudes and less accuracy ,meaning that aging can lead to the weakness of the brainstem neurons'spectral encoding ability .It may be one of the mechanisms causing the reduction of speech recognition in presbycusis patients .%目的:分析听力正常青年人与老年人之间言语诱发听性脑干反应(speech evoked auditory brainstem response ,s-ABR)的频率跟随反应(frequency following response ,FFR)差异,探讨其在揭示听觉系统老化机制中的作用。方法应用SmartEP听觉诱发电位系统对听力正常青年人(18~25岁)与老年人(60~70岁)各12例(24耳)进行言语声信号/da/诱发的s-ABR检测,比较两组s -ABR波形图及频谱图、FFR各波潜伏期及共振峰等。结

  7. Avaliação da presença de receptores purinergicos P2X funcionais na região da ATM de ratos e do papel do ATP endogeno na sensibilização dos nociceptores da ATM

    OpenAIRE

    2004-01-01

    Muitos estudos evidenciam o papel do ATP no processo de desencadeamento da dor por agir em receptores P2X expressos nos terminais nervosos aferentes nociceptivos. Para investigar se esses receptores exercem uma função na dor da ATM, estudamos a presença de receptores P2X funcionais na ATM de ratos, examinando as conseqüências comportamentais da administração de um agonista seletivo para o receptor P2X α,β- metileno ATP (α,β-me ATP) na região da ATM em ratos conscientes. O ...

  8. ATM与肿瘤的关系研究进展%The research progress of the relevance of ATM with tumors

    Institute of Scientific and Technical Information of China (English)

    刘小群

    2011-01-01

    Ataxia-telangiectasia mutated gene (ATM gene), being a kind of DNA-repair gene, is mapped to the chromosomal region 1 lq22-23. The ATM genetic germline mutation or polymorphism results in individual susceptibility to some tumors, including lymphoid tumors and solid tumors. The ATM protein encoded by the ATM gene possesses a kind of autophosphorating character allowing it to play a critical role in the signal transduction of cell cycle checkpoint and the repair of DNA damage and the apoptosis. In vitro, the expression of the ATM protein or the abnormality of its activation is implicated in oncogenesis and oncotherapy, thus the ATM gene would be a novel potential target in cancer treatment.%共济失调毛细血管扩张征突变基因(ataxia-telangiectasia mutated gene,ATM gene)属于一种DNA修复基因,定位于染色体llq22-q23.ATM基因的胚系突变或基因多态性导致个体对多种肿瘤易感,包括淋巴样肿瘤和实体瘤.ATM基因编码产物——ATM蛋白属于一种自动磷酸化蛋白激酶,在DNA损伤修复、细胞周期阻滞和细胞凋亡过程中发挥着关键的调控作用.体外实验发现,许多肿瘤的发生和治疗过程涉及了ATM蛋白表达或活性的改变,提示ATM基因或许能成为肿瘤治疗过程中一个新的潜在作用靶点.

  9. Changes in the response of MCF-7 cells to ionizing radiation after the combination of ATM and DNA-PK inhibition.

    Science.gov (United States)

    Ćmielová, Jana; Havelek, Radim; Vávrová, Jiřina; Řezáčová, Martina

    2015-05-01

    The aim of the present study is to evaluate the role of ATM (KU55933) and DNA-PK (NU7441) inhibitors in the repair of double-strand breaks and downstream signaling of DNA damage introduced by ionizing radiation. The irradiation of MCF-7 cells alone increased the proportion of cells in the G1 phase in comparison with mock-treated cells. After ATM inhibitor pretreatment, the cells were more accumulated in the G2 phase, whereas DNA-PK inhibitor application increased the percentage of cells in the G1 phase. ATM and DNA-PK inhibitor application alone increased the sensitivity of MCF-7 cells to ionizing radiation; however, combining both inhibitors together resulted in a further enhancement of cell death. Unexpectedly, combining both inhibitors decreased the percentage of senescent cells and increased G2 cell cycle arrest 3 days after treatment. After irradiation, the p21 protein was increased and Chk1 and Chk2 were activated. These proteins were not increased in cells pretreated with the ATM inhibitor prior to ionizing radiation exposure, albeit DNA-PK inhibitor application did not affect the amount of proteins detected. Formation of γH2AX was found to be ATM and DNA-PK dependent, application of the ATM inhibitor suppressed incidence of γH2AX, whereas DNA-PK caused persistence of γH2AX. Our results suggest that the further investigation of the ATM inhibitor in combination with the DNA-PK inhibitor as sensitizers preventing cell senescence and promoting cell death in breast carcinoma MCF-7 cells is warranted.

  10. ALDH1A1 Deficiency in Gorlin Syndrome Suggests a Central Role for Retinoic Acid and ATM Deficits in Radiation Carcinogenesis.

    Science.gov (United States)

    Weber, Thomas J; Magnaldo, Thierry; Xiong, Yijia

    2014-09-11

    We hypothesize that aldehyde dehydrogenase 1A1 (ALDH1A1) deficiency will result in impaired ataxia-telangiectasia mutated (ATM) activation in a retinoic acid-sensitive fashion. Data supporting this hypothesis include (1) reduced ATM activation in irradiated primary dermal fibroblasts from ALDH1A1-deficient Gorlin syndrome patients (GDFs), relative to ALDH1A1-positive normal human dermal fibroblasts (NHDFs) and (2) increased ATM activation by X-radiation in GDFs pretreated with retinoic acid, however, the impact of donor variability on ATM activation in fibroblasts was not assessed and is a prudent consideration in future studies. Clonogenic survival of irradiated cells showed differential responses to retinoic acid as a function of treatment time. Long-term (5 Day) retinoic acid treatment functioned as a radiosensitizer and was associated with downregulation of ATM protein levels. Short-term (7 h) retinoic acid treatment showed a trend toward increased survival of irradiated cells and did not downregulate ATM protein levels. Using a newly developed IncubATR technology, which defines changes in bulk chemical bond patterns in live cells, we can discriminate between the NHDF and GDF phenotypes, but treatment of GDFs with retinoic acid does not induce reversion of bulk chemical bond patterns associated with GDFs toward the NHDF phenotype. Collectively, our preliminary investigation of the Gorlin phenotype has identified deficient ALDH1A1 expression associated with deficient ATM activation as a possible susceptibility factor that is consistent with the high incidence of spontaneous and radiation-induced carcinogenesis in these patients. The IncubATR technology exhibits sufficient sensitivity to detect phenotypic differences in live cells that may be relevant to radiation health effects.

  11. Low doses of X-rays induce prolonged and ATM-independent persistence of γH2AX foci in human gingival mesenchymal stem cells.

    Science.gov (United States)

    Osipov, Andreyan N; Pustovalova, Margarita; Grekhova, Anna; Eremin, Petr; Vorobyova, Natalia; Pulin, Andrey; Zhavoronkov, Alex; Roumiantsev, Sergey; Klokov, Dmitry Y; Eremin, Ilya

    2015-09-29

    Diagnostic imaging delivering low doses of radiation often accompany human mesenchymal stem cells (MSCs)-based therapies. However, effects of low dose radiation on MSCs are poorly characterized. Here we examine patterns of phosphorylated histone H2AX (γH2AX) and phospho-S1981 ATM (pATM) foci formation in human gingiva-derived MSCs exposed to X-rays in time-course and dose-response experiments. Both γH2AX and pATM foci accumulated linearly with dose early after irradiation (5-60 min), with a maximum induction observed at 30-60 min (37 ± 3 and 32 ± 3 foci/cell/Gy for γH2AX and pATM, respectively). The number of γH2AX foci produced by intermediate doses (160 and 250 mGy) significantly decreased (40-60%) between 60 and 240 min post-irradiation, indicating rejoining of DNA double-strand breaks. In contrast, γH2AX foci produced by low doses (20-80 mGy) did not change after 60 min. The number of pATM foci between 60 and 240 min decreased down to control values in a dose-independent manner. Similar kinetics was observed for pATM foci co-localized with γH2AX foci. Collectively, our results suggest differential DNA double-strand break signaling and processing in response to low vs. intermediate doses of X-rays in human MSCs. Furthermore, mechanisms governing the prolonged persistence of γH2AX foci in these cells appear to be ATM-independent.

  12. Real-time telemedicine using shared three-dimensional workspaces over ATM

    Science.gov (United States)

    Cahoon, Peter; Forsey, David R.; Hutchison, Susan

    1999-03-01

    During the past five years a high speed ATM network has been developed at UBC that provides a campus testbed, a local testbed to the hospitals, and a National testbed between here and the BADLAB in Ottawa. This testbed has been developed to combine a commercial shared audio/video/whiteboard environment coupled with a shared interactive 3-dimensional solid model. This solid model ranges from a skull reconstructed from a CT scan with muscles and an overlying skin, to a model of the ventricle system of the human brain. Typical interactions among surgeon, radiologist and modeler consist of having image slices of the original scan shared by all and the ability to adjust the surface of the model to conform to each individuals perception of what the final object should look like. The purpose of this interaction can range from forensic reconstruction from partial remains to pre-maxillofacial surgery. A joint project with the forensic unit of the R.C.M.P. in Ottawa using the BADLAB is now in the stages of testing this methodology on a real case beginning with a CT scan of partial remains. A second study underway with the department of Maxiofacial reconstruction at Dalhousie University in Halifax Nova Scotia and concerns a subject who is about to undergo orthognathic surgery, in particular a mandibular advancement. This subject has been MRI scanned, a solid model constructed of the mandible and the virtual surgery constructed on the model. This model and the procedure have been discussed and modified by the modeler and the maxillofacial specialist using these shared workspaces. The procedure will be repeated after the actual surgery to verify the modeled procedure. The advantage of this technique is that none of the specialists need be in the same room, or city. Given the scarcity of time and specialists this methodology shows great promise. In November of this last year a shared live demonstration of this facial modeler was done between Vancouver and Dalhousie University in

  13. Multi-objective optimisation of aircraft flight trajectories in the ATM and avionics context

    Science.gov (United States)

    Gardi, Alessandro; Sabatini, Roberto; Ramasamy, Subramanian

    2016-05-01

    The continuous increase of air transport demand worldwide and the push for a more economically viable and environmentally sustainable aviation are driving significant evolutions of aircraft, airspace and airport systems design and operations. Although extensive research has been performed on the optimisation of aircraft trajectories and very efficient algorithms were widely adopted for the optimisation of vertical flight profiles, it is only in the last few years that higher levels of automation were proposed for integrated flight planning and re-routing functionalities of innovative Communication Navigation and Surveillance/Air Traffic Management (CNS/ATM) and Avionics (CNS+A) systems. In this context, the implementation of additional environmental targets and of multiple operational constraints introduces the need to efficiently deal with multiple objectives as part of the trajectory optimisation algorithm. This article provides a comprehensive review of Multi-Objective Trajectory Optimisation (MOTO) techniques for transport aircraft flight operations, with a special focus on the recent advances introduced in the CNS+A research context. In the first section, a brief introduction is given, together with an overview of the main international research initiatives where this topic has been studied, and the problem statement is provided. The second section introduces the mathematical formulation and the third section reviews the numerical solution techniques, including discretisation and optimisation methods for the specific problem formulated. The fourth section summarises the strategies to articulate the preferences and to select optimal trajectories when multiple conflicting objectives are introduced. The fifth section introduces a number of models defining the optimality criteria and constraints typically adopted in MOTO studies, including fuel consumption, air pollutant and noise emissions, operational costs, condensation trails, airspace and airport operations

  14. Berberine, a genotoxic alkaloid, induces ATM-Chk1 mediated G2 arrest in prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yu; Liu Qiao; Liu Zhaojian; Li Boxuan; Sun Zhaoliang; Zhou Haibin; Zhang Xiyu; Gong Yaoqin [Ministry of Education Key Laboratory of Experimental Teratology and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan (China); Shao Changshun, E-mail: changshun.shao@gmail.com [Ministry of Education Key Laboratory of Experimental Teratology and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan (China)

    2012-06-01

    Berberine has been shown to possess anti-tumor activity against a wide spectrum of cancer cells. It inhibits cancer cell proliferation by inducing cell cycle arrest, at G1 and/or G2/M, and apoptosis. While it has been documented that berberine induces G1 arrest by activating the p53-p21 cascade, it remains unclear what mechanism underlies the berberine-induced G2/M arrest, which is p53-independent. In this study, we tested the anti-proliferative effect of berberine on murine prostate cancer cell line RM-1 and characterized the underlying mechanisms. Berberine dose-dependently induced DNA double-strand breaks and apoptosis. At low concentrations, berberine was observed to induce G1 arrest, concomitant with the activation of p53-p21 cascade. Upon exposure to berberine at a higher concentration (50 {mu}M) for 24 h, cells exhibited G2/M arrest. Pharmacological inhibition of ATM by KU55933, or Chk1 by UCN-01, could efficiently abrogate the G2/M arrest in berberine-treated cells. Downregulation of Chk1 by RNA interference also abolished the G2/M arrest caused by berberine, confirming the role of Chk1 in the pathway leading to G2/M arrest. Abrogation of G2/M arrest by ATM inhibition forced more cells to undergo apoptosis in response to berberine treatment. Chk1 inhibition by UCN-01, on the other hand, rendered cells more sensitive to berberine only when p53 was inhibited. Our results suggest that combined administration of berberine and caffeine, or other ATM inhibitor, may accelerate the killing of cancer cells.

  15. Kaempferol induces ATM/p53-mediated death receptor and mitochondrial apoptosis in human umbilical vein endothelial cells.

    Science.gov (United States)

    Lee, Chiu-Fang; Yang, Jai-Sing; Tsai, Fuu-Jen; Chiang, Ni-Na; Lu, Chi-Cheng; Huang, Yu-Syuan; Chen, Chun; Chen, Fu-An

    2016-05-01

    Kaempferol is a member of the flavonoid compounds found in vegetables and fruits. It is shown to exhibit biological impact and anticancer activity, but no report exists on the angiogenic effect of kaempferol and induction of cell apoptosis in vitro. In this study, we investigated the role of kaempferol on anti-angiogenic property and the apoptotic mechanism of human umbilical vein endothelial cells (HUVECs). Our results demonstrated that kaempferol decreased HUVEC viability in a time- and concentration-dependent manner. Kaempferol also induced morphological changes and sub-G1 phase cell population (apoptotic cells). Kaempferol triggered apoptosis of HUVECs as detecting by DNA fragmentation, comet assay and immunofluorescent staining for activated caspase-3. The caspase signals, including caspase-8, -9 and -3, were time-dependently activated in HUVECs after kaempferol exposure. Furthermore, pre-treatment with a specific inhibitor of caspase-8 (Z-IETD-FMK) significantly reduced the activity of caspase-8, -9 and -3, indicating that extrinsic pathway is a major signaling pathway in kaempferol-treated HUVECs. Importantly, kaempferol promoted reactive oxygen species (ROS) evaluated using flow cytometric assay in HUVECs. We further investigated the upstream extrinsic pathway and showed that kaempferol stimulated death receptor signals [Fas/CD95, death receptor 4 (DR4) and DR5] through increasing the levels of phosphorylated p53 and phosphorylated ATM pathways in HUVECs, which can be individually confirmed by N-acetylcysteine (NAC), ATM specific inhibitor (caffeine) and p53 siRNA. Based on these results, kaempferol-induced HUVEC apoptosis was involved in an ROS-mediated p53/ATM/death receptor signaling. Kaempferol might possess therapeutic effects on cancer treatment in anti-vascular targeting.

  16. Use of JPSS ATMS, CrIS, and VIIRS data to Improve Tropical Cyclone Track and Intensity Forecasting

    Science.gov (United States)

    Chirokova, G.; Demaria, M.; DeMaria, R.; Knaff, J. A.; Dostalek, J.; Musgrave, K. D.; Beven, J. L.

    2015-12-01

    JPSS data provide unique information that could be critical for the forecasting of tropical cyclone (TC) track and intensity and is currently underutilized. Preliminary results from several TC applications using data from the Advanced Technology Microwave Sounder (ATMS), the Cross-Track Infrared Sounder (CrIS), and the Visible Infrared Imaging Radiometer Suite (VIIRS), carried by the Suomi National Polar-Orbiting Partnership satellite (SNPP), will be discussed. The first group of applications, which includes applications for moisture flux and for eye-detection, aims to improve rapid intensification (RI) forecasts, which is one of the highest priorities within NOAA. The applications could be used by forecasters directly and will also provide additional input to the Rapid Intensification Index (RII), the statistical-dynamical tool for forecasting RI events that is operational at the National Hurricane Center. The moisture flux application uses bias-corrected ATMS-MIRS (Microwave Integrated Retrieval System) and NUCAPS (NOAA Unique CrIS ATMS Processing System), retrievals that provide very accurate temperature and humidity soundings in the TC environment to detect dry air intrusions. The objective automated eye-detection application uses geostationary and VIIRS data in combination with machine learning and computer vision techniques for determining the onset of eye formation which is very important for TC intensity forecast but is usually determined by subjective methods. First version of the algorithm showed very promising results with a 75% success rate. The second group of applications develops tools to better utilize VIIRS data, including day-night band (DNB) imagery, for tropical cyclone forecasting. Disclaimer: The views, opinions, and findings contained in this article are those of the authors and should not be construed as an official National Oceanic and Atmospheric Administration (NOAA) or U.S. Government position, policy, or decision.

  17. ATM alters the otherwise robust chromatin mobility at sites of DNA double-strand breaks (DSBs in human cells.

    Directory of Open Access Journals (Sweden)

    Annabelle Becker

    Full Text Available Ionizing radiation induces DNA double strand breaks (DSBs which can lead to the formation of chromosome rearrangements through error prone repair. In mammalian cells the positional stability of chromatin contributes to the maintenance of genome integrity. DSBs exhibit only a small, submicron scale diffusive mobility, but a slight increase in the mobility of chromatin domains by the induction of DSBs might influence repair fidelity and the formation of translocations. The radiation-induced local DNA decondensation in the vicinity of DSBs is one factor potentially enhancing the mobility of DSB-containing chromatin domains. Therefore in this study we focus on the influence of different chromatin modifying proteins, known to be activated by the DNA damage response, on the mobility of DSBs. IRIF (ionizing radiation induced foci in U2OS cells stably expressing 53BP1-GFP were used as a surrogate marker of DSBs. Low angle charged particle irradiation, known to trigger a pronounced DNA decondensation, was used for the defined induction of linear tracks of IRIF. Our results show that movement of IRIF is independent of the investigated chromatin modifying proteins like ACF1 or PARP1 and PARG. Also depletion of proteins that tether DNA strands like MRE11 and cohesin did not alter IRIF dynamics significantly. Inhibition of ATM, a key component of DNA damage response signaling, resulted in a pronounced confinement of DSB mobility, which might be attributed to a diminished radiation induced decondensation. This confinement following ATM inhibition was confirmed using X-rays, proving that this effect is not restricted to densely ionizing radiation. In conclusion, repair sites of DSBs exhibit a limited mobility on a small spatial scale that is mainly unaffected by depletion of single remodeling or DNA tethering proteins. However, it relies on functional ATM kinase which is considered to influence the chromatin structure after irradiation.

  18. Regiospecificities and Prenylation Mode Specificities of the Fungal Indole Diterpene Prenyltransferases AtmD and PaxD

    Science.gov (United States)

    Liu, Chengwei; Minami, Atsushi; Noike, Motoyoshi; Toshima, Hiroaki; Oikawa, Hideaki

    2013-01-01

    We recently reported the function of paxD, which is involved in the paxilline (compound 1) biosynthetic gene cluster in Penicillium paxilli. Recombinant PaxD catalyzed a stepwise regular-type diprenylation at the 21 and 22 positions of compound 1 with dimethylallyl diphosphate (DMAPP) as the prenyl donor. In this study, atmD, which is located in the aflatrem (compound 2) biosynthetic gene cluster in Aspergillus flavus and encodes an enzyme with 32% amino acid identity to PaxD, was characterized using recombinant enzyme. When compound 1 and DMAPP were used as substrates, two major products and a trace of minor product were formed. The structures of the two major products were determined to be reversely monoprenylated compound 1 at either the 20 or 21 position. Because compound 2 and β-aflatrem (compound 3), both of which are compound 1-related compounds produced by A. flavus, have the same prenyl moiety at the 20 and 21 position, respectively, AtmD should catalyze the prenylation in compound 2 and 3 biosynthesis. More importantly and surprisingly, AtmD accepted paspaline (compound 4), which is an intermediate of compound 1 biosynthesis that has a structure similar to that of compound 1, and catalyzed a regular monoprenylation of compound 4 at either the 21 or 22 position, though the reverse prenylation was observed with compound 1. This suggests that fungal indole diterpene prenyltransferases have the potential to alter their position and regular/reverse specificities for prenylation and could be applicable for the synthesis of industrially useful compounds. PMID:24038699

  19. Diseño de una planta de envasado de patatas en atmósfera modificada

    OpenAIRE

    Roldán Fernández, Rubén

    2012-01-01

    El proyecto pretende diseñar una planta de envasado de patatas, variedad Monalisa, para su comercialización y posterior distribución de este producto hortofrutícola. En dicha planta se realizarán las operaciones de lavado, pelado, selección, corte, secado y envasado en atmósfera modificada (CO2, O2 y N2). El producto envasado se almacenará en cámaras frigoríficas hasta su comercialización. Los españoles consumimos una media de 60,54 Kg de hortalizas frescas por persona y ...

  20. Almacenamiento refrigerado de frutos de mora de castilla (rubus glaucus benth.) en empaques con atmósfera modificada

    OpenAIRE

    Sora, Ángel Dayron; Fischer, Gerhard; Flórez, Rafael

    2010-01-01

    Con el objeto de aumentar la vida útil de la mora de Castilla en poscosecha, se colocaron frutos en el grado de madurez (GM) 3 y 5, según Icontec (Instituto Colombiano de Normas Técnicas y Certificación), en atmósferas modificadas activas con concentraciones de gases de 25% CO2, 5% O2, 70% N2 y 20% CO2, 10% O2, 70% N2, empleando empaques de polietileno de baja densidad (PEBD) y polipropileno (PP), calibre   (0,035 mm). La temperatura de almacenamiento fue 4 ºC, la humedad relativa varió entre...

  1. Origen del polen de "artemisia" en la atmósfera de Extremadura "so España"

    OpenAIRE

    2000-01-01

    Origen del polen de Artemisia en la atmósfera de Extremadura (SO España). Mediante tres captadores volumétricos de tipo Hirst se ha podido conocer la concentración de granos de polen de Artemisia en Extremadura entre 1993 y 1998 para Badajoz y entre 1996 y 1998 para Cáceres y Mérida. Su presencia es muy esporádica y la cantidad reducida, aparece centrada fundamentalmente entre agosto y noviembre, aunque se detectan también en menor cantidad entre enero y marzo, la cantidad encontrada nunca ll...

  2. Clasificación de emplazamientos peligrosos para atmósferas explosivas de gases y polvos combustibles

    OpenAIRE

    Pérez Carbonell, Carlos

    2005-01-01

    El proyecto surge de la necesidad establecida por la Directiva 1999/92/CE europea transpuesta al R.D. 681/2003 español de evaluar el riesgo de explosión en los lugares de trabajo. Dicha evaluación tiene una fase inicial de clasificación de los emplazamientos con riesgo a formar una atmósfera potencialmente explosiva de gases, vapores inflamables y sustancias pulverulentas. Las explosiones son fenómenos en los que se desarrolla en un sistema cerrado o abierto una sobrepresión...

  3. Assessing the potential number of ATMs in banks, financial and credit institutions using Analytic Network Process (ANP and Gray Clustering Analysis (GCA Case study: between Enghelab Sq and Ferdowsi Sq- Enghelab Street of Tehran

    Directory of Open Access Journals (Sweden)

    H.A. Faraji Sabokbar

    2012-01-01

    Full Text Available Extended abstracts1- IntroductionMost organizations and financial institutions are facing with spatial decision makings. Optimum decision making affects the institutes’ success, achievement to their objectives and attracting customers. Modern banking services have evolved by the development of modern technologies. The most sensible aspect of banking services evolution is based on using the modern technologies of ATMs. The rapid growth in application of these devices could have been caused by the increasing acceptance of them among customers (Foukerdi, 2005: 2. Because of the same reason, in spite of the high costs of purchase, initiation and maintenance, banks, financial and credit institutions are still interested in the development of ATMs. On the other hand, inattention and mismanagement in site selection and the number of such devices could be effective in failure of these systems. Selecting the optimum and most proper location to install the ATMs takes into account with respect to various factors that have different impact factors. Economical zoning of the cities for selecting potential and capable locations of such activities is assumed as the success agent of institutions and is a powerful method for future decisions. Therefore, the overall purpose of this research is to provide a model for economic zoning to install the services and facilities of banking system (ATMs. The research type is developmental- applied and the research method is descriptive-analytical. In the first step, effective economic factors in banking system were specified throughout library studies (previous studies with respect to research purposes, then it was supplemented by expert’s viewpoints, also, spatial data were obtained from area by surveying with respect to relevant criteria. Weight of each criterion was specified with Analytic Network Process (ANP after supplement of couple comparison circular by experts and it was used in Gray cluster analysis for

  4. High-frequency stimulation ABRs in patient with sudden hearing loss%高刺激速率ABR对突发性耳聋预后评估的价值

    Institute of Scientific and Technical Information of China (English)

    艾毛毛; 于锋; 周枫

    2016-01-01

    目的:探讨突发性耳聋患者高刺激听性脑干反应的特点及临床价值。方法对2014年1月至12月就诊于我院的43例(45耳)16~45岁青中年无眩晕、心脑血管疾病病史的突聋患者(病例组)及同龄听力正常人20例40耳(对照组)分别进行纯音测听和高(51.1次/秒)、低(11.1次/秒)刺激率听性脑干反应(auditory brainstem response,ABR)检测,以两种刺激率的ABRⅠ-Ⅴ波间期差值(interpeak latency,△IPL)>0.28为异常。比较突聋患者中ABR结果异常者(A组)与ABR结果正常者(B组)间的治疗有效率。采用SPSS13.0软件,以χ2检验比较两组间的差异。结果病例组患侧高刺激ABR引出率为75.56%(34例),其中异常率为79%(27例);对照组高刺激ABR引出率为100%,异常率为5%(2例),两组间高刺激ABR异常率差异有统计学意义(χ2=42.124,P<0.01)。A组与B组突聋患者的平均纯音听阈结果无明显差异;病例组中A组治疗有效率为40.74%(11例),B组的有效率为83.33%(15例),两组间比较差异有统计学意义(χ2=6.613,P=0.005)。结论突聋患者高刺激ABRⅠ-Ⅴ波间期差异常率明显增加,且高刺激ABR结果异常提示预后较差。%Objective To report characteristics of high-frequency stimulation Auditory Brainstem Responses in pa-tients with idiopathic sudden sensorineural hearing loss (ISSHL). Methods Forty three patients (45 ears) aged 16-45 years with ISSHL who were treated in Guangzhou Otolaryngology Head and Neck Surgery Hospital between January 2014 and December 2014 were included in the study group, while 20 normal volunteers (40 ears) were recruited as the control group. Subjects had no history of vertigo or cerebrocardiovascular diseases, and received pure tone audiometry (PTA) tests. Audito-ry brainstem responses (ABRs) were tested using clicks at a rate of 51.1/s or 11.1/s. A difference in I-V interpeak

  5. Phosphorylation of p65(RelA on Ser(547 by ATM represses NF-κB-dependent transcription of specific genes after genotoxic stress.

    Directory of Open Access Journals (Sweden)

    Hélène Sabatel

    Full Text Available The NF-κB pathway is involved in immune and inflammation responses, proliferation, differentiation and cell death or survival. It is activated by many external stimuli including genotoxic stress. DNA double-strand breaks activate NF-κB in an ATM-dependent manner. In this manuscript, a direct interaction between p65(RelA and the N-terminal extremity of ATM is reported. We also report that only one of the five potential ATM-(S/TQ target sites present in p65, namely Ser(547, is specifically phosphorylated by ATM in vitro. A comparative transcriptomic analysis performed in HEK-293 cells expressing either wild-type HA-p65 or a non-phosphorylatable mutant HA-p65(S547A identified several differentially transcribed genes after an etoposide treatment (e.g. IL8, A20, SELE. The transcription of these genes is increased in cells expressing the mutant. Substitution of Ser(547 to alanine does not affect p65 binding abilities on the κB site of the IL8 promoter but reduces p65 interaction with HDAC1. Cells expressing p65(S547A have a higher level of histone H3 acetylated on Lys(9 at the IL8 promoter, which is in agreement with the higher gene induction observed. These results indicate that ATM regulates a sub-set of NF-κB dependent genes after a genotoxic stress by direct phosphorylation of p65.

  6. The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo.

    Science.gov (United States)

    Vendetti, Frank P; Lau, Alan; Schamus, Sandra; Conrads, Thomas P; O'Connor, Mark J; Bakkenist, Christopher J

    2015-12-29

    ATR and ATM are DNA damage signaling kinases that phosphorylate several thousand substrates. ATR kinase activity is increased at damaged replication forks and resected DNA double-strand breaks (DSBs). ATM kinase activity is increased at DSBs. ATM has been widely studied since ataxia telangiectasia individuals who express no ATM protein are the most radiosensitive patients identified. Since ATM is not an essential protein, it is widely believed that ATM kinase inhibitors will be well-tolerated in the clinic. ATR has been widely studied, but advances have been complicated by the finding that ATR is an essential protein and it is widely believed that ATR kinase inhibitors will be toxic in the clinic. We describe AZD6738, an orally active and bioavailable ATR kinase inhibitor. AZD6738 induces cell death and senescence in non-small cell lung cancer (NSCLC) cell lines. AZD6738 potentiates the cytotoxicity of cisplatin and gemcitabine in NSCLC cell lines with intact ATM kinase signaling, and potently synergizes with cisplatin in ATM-deficient NSCLC cells. In contrast to expectations, daily administration of AZD6738 and ATR kinase inhibition for 14 consecutive days is tolerated in mice and enhances the therapeutic efficacy of cisplatin in xenograft models. Remarkably, the combination of cisplatin and AZD6738 resolves ATM-deficient lung cancer xenografts.

  7. Factors Affecting the Decisions of Tabung Haji Customers in Malaysia to Use ATM Banking: An Empirical Investigation

    Directory of Open Access Journals (Sweden)

    Hanudin Amin

    2010-08-01

    Full Text Available The aim of this paper is to provide a preliminary investigation of the factors that determine whether Malaysia’s Tabung Haji customers in Eastern Malaysia will use or not a new facility introduced by the institution, namely Automated Teller Machine or ATM banking. As such, this study introduces the concept Tabung Haji ATM Banking (TAB. In order to explain the factors, this paper extends the applicability of the technology acceptance model (TAM to TAB and includes “ perceived credibility (PC”, and “perceived religiosity (PR”, in addition to “perceived usefulness (PU” and “perceived ease of use (PEOU”. The results indicate that PU, PEOU, PC and PR are the key determinants to predicting the intentions to use TAB. In addition, PEOU is significantly associated with PU, which, in turn, affecting usage intention among Tabung Haji customers on TAB. This study suffers from two limitations, first is on its location of study and, second is on its limited number of measures suggested in the modified model for the study. Nevertheless, these limitations provide directions for the future study and also provide new information in a new introduced financial innovation at Tabung Haji. The results will be primarily of benefit to Tabung Ha ji since this study offers insights on the intentions of its customers to use TAB

  8. Comportamiento del aluminio desnudo y anodizado en atmósferas con grados de contaminación muy diferentes

    Directory of Open Access Journals (Sweden)

    Bautista, A.

    1998-05-01

    Full Text Available In the present research, the responses of unprotected and anodized aluminium specimens are compared after they have been exposed to 12 different atmospheres. The significance of the anodizing and the sealing on the atmospheric corrosion behaviour is analysed. The results show that the anodizing and sealing of aluminium exclude the risk of pitting corrosion in marine atmospheres and that the oxide thickness is not determining, at least during the first year of exposure.

    En la presente investigación, comparando las respuestas de muestras de aluminio desnudas y anodizadas, expuestas a 12 atmósferas diferentes, se analiza la repercusión del anodizado y sellado del aluminio en el comportamiento frente a la corrosión atmosférica. Se demuestra que la anodización y sellado del aluminio elimina el riesgo de corrosión por picaduras que afecta a estos materiales en atmósferas marinas, sin que el espesor del recubrimiento resulte determinante, al menos, en el primer año de exposición.

  9. Contribution of ATM and ATR kinase pathways to p53-mediated response in etoposide and methyl methanesulfonate induced DNA damage.

    Science.gov (United States)

    Sun, Bin; Ross, Susan M; Rowley, Sean; Adeleye, Yeyejide; Clewell, Rebecca A

    2017-03-01

    p53 is a key integrator of cellular response to DNA damage, supporting post-translational repair and driving transcription-mediated responses including cell cycle arrest, apoptosis, and repair. DNA damage sensing kinases recognize different types of DNA damage and initiate specific responses through various post-translational modifications of p53. This study evaluated chemical specificity of the p53 pathway response by manipulating p53 or its upstream kinases and assessing the effect on DNA damage and cellular responses to prototype chemicals: etoposide (ETP, topoisomerase II inhibitor) and methyl methane sulfonate (MMS, alkylating agent). p53-deficient cells demonstrated reduced accumulation of the p53 target proteins MDM2, p21, and Wip1; reduced apoptotic response; and increased DNA damage (p-H2AX and micronuclei) with both chemicals. However, p53 was not essential for cell cycle arrest in HT1080 or HCT116 cells. The two chemicals induced different patterns of kinase activation, particularly in terms of Chk 1, Chk 2, p38, and ERK 1/2. However, inhibition of the ATM pathway showed a greater effect on p53 activtation, apoptosis, and accumulation of DNA damage than ATR-Chk 1 or the MAP kinases regardless of the chemical used. These results indicate that ATM is the predominant upstream kinase responsible for activation of the p53-mediated DNA damage response for both MMS and ETP, though the downstream kinase response is markedly different. Environ. Mol. Mutagen. 58:72-83, 2017. © 2017 Wiley Periodicals, Inc.

  10. Galiellalactone induces cell cycle arrest and apoptosis through the ATM/ATR pathway in prostate cancer cells.

    Science.gov (United States)

    García, Víctor; Lara-Chica, Maribel; Cantarero, Irene; Sterner, Olov; Calzado, Marco A; Muñoz, Eduardo

    2016-01-26

    Galiellalactone (GL) is a fungal metabolite that presents antitumor activities on prostate cancer in vitro and in vivo. In this study we show that GL induced cell cycle arrest in G2/M phase, caspase-dependent apoptosis and also affected the microtubule organization and migration ability in DU145 cells. GL did not induce double strand DNA break but activated the ATR and ATM-mediated DNA damage response (DDR) inducing CHK1, H2AX phosphorylation (fH2AX) and CDC25C downregulation. Inhibition of the ATM/ATR activation with caffeine reverted GL-induced G2/M cell cycle arrest, apoptosis and DNA damage measured by fH2AX. In contrast, UCN-01, a CHK1 inhibitor, prevented GL-induced cell cycle arrest but enhanced apoptosis in DU145 cells. Furthermore, we found that GL did not increase the levels of intracellular ROS, but the antioxidant N-acetylcysteine (NAC) completely prevented the effects of GL on fH2AX, G2/M cell cycle arrest and apoptosis. In contrast to NAC, other antioxidants such as ambroxol and EGCG did not interfere with the activity of GL on cell cycle. GL significantly suppressed DU145 xenograft growth in vivo and induced the expression of fH2AX in the tumors. These findings identify for the first time that GL activates DDR in prostate cancer.

  11. Mapas de España de corrosividad del zinc en atmósferas rurales

    Directory of Open Access Journals (Sweden)

    Morcillo, M.

    2010-12-01

    Full Text Available Atmospheric corrosivity maps provide useful information on the extent of atmospheric corrosion phenomena in a given geographic scope. The preparation of such maps helps designers to select the most suitable metallic material in terms of corrosion resistance and economy and to define the right type of protection for a given durability. This is a difficult task, due to the numerous climate-related factors upon which atmospheric corrosion depends. This work summarizes a funded project by BP Solar to develop atmospheric corrosivity maps of Spain for zinc considering both annual corrosion and long term (15 years corrosion, which will determine the protection required for the metal structures used in photovoltaic systems, for practically pollution-free rural atmospheres. The method used has been to apply dose/response equations (damage functions to estimate the corrosion rate as a function of meteorological variables. These variables have been obtained from information of meteorological stations placed in mainland Spain.

    El interés en la elaboración de mapas de corrosividad atmosférica radica en su utilidad para disponer de información sobre el alcance del fenómeno de corrosión atmosférica en un determinado punto geográfico. Con ello se facilitaría la selección del material metálico más adecuado, tanto desde el punto de vista de resistencia a la corrosión como económicamente, y definir, asimismo, el tipo de protección idónea para una durabilidad determinada. En la práctica se trata de una tarea difícil, debido a los numerosos factores climáticos de los que depende la corrosión atmosférica. Este trabajo resume un proyecto financiado por BP Solar para el desarrollo de mapas de España para la corrosividad atmosférica del zinc, tanto de corrosión anual como de corrosión a largo plazo (15 años, que determinará el tipo de protección requerido en las estructuras metálicas utilizadas en sistemas fotovoltaicos para atm

  12. FUZZY REQUIREMENT BASED STRATEGY OF QoS SERVICE FOR BROADBAND TELECOMMUNICATION NETWORKS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A fuzzy requirement based strategy for QoS service in broadband networks was presented. With the analysis of QoS service in ATM networks and broadband IP networks, it gave a requirement-based strategy for QoS service application with Fuzzy language evaluation principles. The requirement parameters are chosen according to the WANT/COST rule, and a fuzzy set is constructed to realize the fuzzy determinant. The simulation results show that it is useful to evaluate the QoS service in broadband networks, and to effectively simplify the access protocols and solve the billing issues in broadband networks.

  13. The Passive Microwave Neural Network Precipitation Retrieval (PNPR) for AMSU/MHS and ATMS cross-track scanning radiometers

    Science.gov (United States)

    Sano', Paolo; Casella, Daniele; Panegrossi, Giulia; Cinzia Marra, Anna; Dietrich, Stefano

    2016-04-01

    Spaceborne microwave cross-track scanning radiometers, originally developed for temperature and humidity sounding, have shown great capabilities to provide a significant contribution in precipitation monitoring both in terms of measurement quality and spatial/temporal coverage. The Passive microwave Neural network Precipitation Retrieval (PNPR) algorithm for cross-track scanning radiometers, originally developed for the Advanced Microwave Sounding Unit/Microwave Humidity Sounder (AMSU-A/MHS) radiometers (on board the European MetOp and U.S. NOAA satellites), was recently newly designed to exploit the Advanced Technology Microwave Sounder (ATMS) on board the Suomi-NPP satellite and the future JPSS satellites. The PNPR algorithm is based on the Artificial Neural Network (ANN) approach. The main PNPR-ATMS algorithm changes with respect to PNPR-AMSU/MHS are the design and implementation of a new ANN able to manage the information derived from the additional ATMS channels (respect to the AMSU-A/MHS radiometer) and a new screening procedure for not-precipitating pixels. In order to achieve maximum consistency of the retrieved surface precipitation, both PNPR algorithms are based on the same physical foundation. The PNPR is optimized for the European and the African area. The neural network was trained using a cloud-radiation database built upon 94 cloud-resolving simulations over Europe and the Mediterranean and over the African area and radiative transfer model simulations of TB vectors consistent with the AMSU-A/MHS and ATMS channel frequencies, viewing angles, and view-angle dependent IFOV sizes along the scan projections. As opposed to other ANN precipitation retrieval algorithms, PNPR uses a unique ANN that retrieves the surface precipitation rate for all types of surface backgrounds represented in the training database, i.e., land (vegetated or arid), ocean, snow/ice or coast. This approach prevents different precipitation estimates from being inconsistent with one

  14. Functional switching of ATM: sensor of DNA damage in proliferating cells and mediator of Akt survival signal in post-mitotic human neuron-like cells

    Institute of Scientific and Technical Information of China (English)

    Yan Li; Hua Xiong; Da-Qing Yang

    2012-01-01

    Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by cerebellar ataxia and oculocutaneous telangiectasias.The gene mutated in this disease,ATM (A-T,mutated),encodes a 370-kDa Ser/Thr protein kinase.ATM not only mediates cellular response to DNA damage but also acts as an activator of Akt in response to insulin.However,despite intensive studies,the mechanism underlying the neuronal degeneration symptoms of human A-T is still poorly understood.We found that the topoisomerase inhibitors etoposide and camptothecin readily induced apoptosis in undifferentiated proliferating SH-SY5Y cells but could not induce apoptosis in neuronally differentiated SH-SY5Y cells.In addition,etoposide induced p53 phosphorylation and H2AX foci formation in proliferating SH-SY5Y cells but failed to do so in differentiated SH-SY5Y cells.Moreover,while inhibition of ATM in undifferentiated SH-SY5Y cells partially protected them from etoposide-induced apoptosis,the same treatment had no effect on cell viability in differentiated SH-SY5Y cells.These results suggest that DNA damage or defective response to DNA damage is not the cause of neuronal cell death in human A-T.In contrast,we discovered that Akt phosphorylation was inhibited when ATM activity was suppressed in differentiated SH-SY5Y cells.Furthermore,inhibition of ATM induced apoptosis following serum starvation in neuronally differentiated SH-SY5Y cells but could not trigger apoptosis under the same conditions in undifferentiated proliferating SH-SY5Y cells.These results demonstrate that ATM mediates the Akt signaling and promotes cell survival in neuron-like human SH-SY5Y cells,suggesting that impaired activation of Akt is the reason for neuronal degeneration in human A-T.

  15. The complexity of DNA double strand break is a crucial factor for activating ATR signaling pathway for G2/M checkpoint regulation regardless of ATM function.

    Science.gov (United States)

    Xue, Lian; Furusawa, Yoshiya; Okayasu, Ryuichi; Miura, Masahiko; Cui, Xing; Liu, Cuihua; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Yajima, Hirohiko; Yu, Dong

    2015-01-01

    DNA double strand break (DSB) repair pathway choice following ionizing radiation (IR) is currently an appealing research topic, which is still largely unclear. Our recent paper indicated that the complexity of DSBs is a critical factor that enhances DNA end resection. It has been well accepted that the RPA-coated single strand DNA produced by resection is a signaling structure for ATR activation. Therefore, taking advantage of high linear energy transfer (LET) radiation to effectively produce complex DSBs, we investigated how the complexity of DSB influences the function of ATR pathway on the G2/M checkpoint regulation. Human skin fibroblast cells with or without ATM were irradiated with X rays or heavy ion particles, and dual-parameter flow cytometry was used to quantitatively assess the mitotic entry at early period post radiation by detecting the cells positive for phosphor histone H3. In ATM-deficient cells, ATR pathway played a pivotal role and functioned in a dose- and LET-dependent way to regulate the early G2/M arrest even as low as 0.2Gy for heavy ion radiation, which indicated that ATR pathway could be rapidly activated and functioned in an ATM-independent, but DSB complexity-dependent manner following exposure to IR. Furthermore, ATR pathway also functioned more efficiently in ATM-proficient cells to block G2 to M transition at early period of particle radiation exposure. Accordingly, in contrast to ATM inhibitor, ATR inhibitor had a more effective radiosensitizing effect on survival fraction following heavy ion beams as compared with X ray radiation. Taken together, our results reveal that the complexity of DSBs is a crucial factor for the activation of ATR pathway for G2/M checkpoint regulation, and ATM-dependent end resection is not essential for the activation.

  16. Assessment of targeted and non-targeted responses in cells deficient in ATM function following exposure to low and high dose X-rays.

    Science.gov (United States)

    Kiuru, Anne; Kämäräinen, Meerit; Heinävaara, Sirpa; Pylkäs, Katri; Chapman, Kim; Koivistoinen, Armi; Parviainen, Teuvo; Winqvist, Robert; Kadhim, Munira; Launonen, Virpi; Lindholm, Carita

    2014-01-01

    Radiation sensitivity at low and high dose exposure to X-rays was investigated by means of chromosomal aberration (CA) analysis in heterozygous ATM mutation carrier and A-T patient (biallelic ATM mutation) lymphoblastoid cell lines (LCLs). Targeted and non-targeted responses to acutely delivered irradiation were examined by applying a co-culture system that enables study of both directly irradiated cells and medium-mediated bystander effects in the same experimental setting. No indication of radiation hypersensitivity was observed at doses of 0.01 Gy or 0.1 Gy for the ATM mutation carrier LCL. The A-T patient cells also did not show low-dose response. There was significant increase in unstable CA yields for both ATM mutation carrier and A-T LCLs at 1 and 2 Gy, the A-T cells displaying more distinct dose dependency. Both chromosome and chromatid type aberrations were induced at an increased rate in the irradiated A-T cells, whereas for ATM carrier cells, only unstable chromosomal aberrations were increased above the level observed in the wild type cell line. No bystander effect could be demonstrated in any of the cell lines or doses applied. Characteristics typical for the A-T cell line were detected, i.e., high baseline frequency of CA that increased with dose. In addition, dose-dependent loss of cell viability was observed. In conclusion, CA analysis did not demonstrate low-dose (≤100 mGy) radiosensitivity in ATM mutation carrier cells or A-T patient cells. However, both cell lines showed increased radiosensitivity at high dose exposure.

  17. Assessment of targeted and non-targeted responses in cells deficient in ATM function following exposure to low and high dose X-rays.

    Directory of Open Access Journals (Sweden)

    Anne Kiuru

    Full Text Available Radiation sensitivity at low and high dose exposure to X-rays was investigated by means of chromosomal aberration (CA analysis in heterozygous ATM mutation carrier and A-T patient (biallelic ATM mutation lymphoblastoid cell lines (LCLs. Targeted and non-targeted responses to acutely delivered irradiation were examined by applying a co-culture system that enables study of both directly irradiated cells and medium-mediated bystander effects in the same experimental setting. No indication of radiation hypersensitivity was observed at doses of 0.01 Gy or 0.1 Gy for the ATM mutation carrier LCL. The A-T patient cells also did not show low-dose response. There was significant increase in unstable CA yields for both ATM mutation carrier and A-T LCLs at 1 and 2 Gy, the A-T cells displaying more distinct dose dependency. Both chromosome and chromatid type aberrations were induced at an increased rate in the irradiated A-T cells, whereas for ATM carrier cells, only unstable chromosomal aberrations were increased above the level observed in the wild type cell line. No bystander effect could be demonstrated in any of the cell lines or doses applied. Characteristics typical for the A-T cell line were detected, i.e., high baseline frequency of CA that increased with dose. In addition, dose-dependent loss of cell viability was observed. In conclusion, CA analysis did not demonstrate low-dose (≤100 mGy radiosensitivity in ATM mutation carrier cells or A-T patient cells. However, both cell lines showed increased radiosensitivity at high dose exposure.

  18. Mechanical Service; Service Mechanique

    Energy Technology Data Exchange (ETDEWEB)

    Alliaume, T.; Benoit, A.; Bonin, H.; Ducimetiere, D.; Essertaize, D.; Gelin, G.; Guillot, G.; Lemoine, C.; Mabo, J.C.; Mounier, F.; Tissot, S.; Verdier, G. [Inst. de Physique Nucleaire, Lyon-1 Univ., 69 - Villeurbanne (France)

    1998-12-31

    The service studies the mechanical part of the experiment or detectors used by the physics groups in collaboration with the physicists, engineers and the technicians of the experiment assistance group as well as with other technical groups. The mechanical service was implied in the following projects: CMS, VIRGO (the IGISOL ion guide chamber), PIAFE, NA50 (reaction chamber, metallic cluster source), ORION, SICANE, EDELWEISS II 2 figs.

  19. Hallazgos artroscópicos en un caso de disco articular adherido de la ATM Arthroscopic findings in a fixed disc case of the TMJ

    OpenAIRE

    R. Martín-Granizo López; J. Giner Díaz; J.J. Sánchez Gutiérrez

    2005-01-01

    El síndrome de disco adherido (SDA) o stuck syndrome de la articulación temporomandibular (ATM) es un fenómeno que ha sido descrito recientemente y cuya fisiopatogenia es una alteración bioquímica que se produce en algunas ATMs con disfunción temporomandibular. En el presente artículo describimos un caso clínico y especialmente los interesantes hallazgos artroscópicos encontrados, que ayudarían a corroborar el mecanismo fisiopatogénico propuesto. Son de especial relevancia la correcta posició...

  20. Uso de películas poliméricas para el almacenamiento en atmósfera modificada de mora azul

    OpenAIRE

    García Torres, Rosalía

    2005-01-01

    Uno de los problemas que se presentan con los productos hortícolas, es que se dan muchas pérdidas por el rápido deterioro de los mismos debido a su proceso normal de maduración,sin embargo existen frutas con un alto valor nutrimental como las moras, que retan a la industria alimenticia a desarrollar tecnologías que permitan alargar la vida de estos productos, una de estas tecnologías es el empacado en atmósfera modificada que combina el cambio en composición de la atmósfe...