WorldWideScience

Sample records for atm networks pc

  1. Functional and nonfunctional testing of ATM networks

    Science.gov (United States)

    Ricardo, Manuel; Ferreira, M. E. P.; Guimaraes, Francisco E.; Mamede, J.; Henriques, M.; da Silva, Jorge A.; Carrapatoso, E.

    1995-02-01

    ATM network will support new multimedia services that will require new protocols, those services and protocols will need different test strategies and tools. In this paper, the concepts of functional and non-functional testers of ATM networks are discussed, a multimedia service and its requirements are presented and finally, a summary description of an ATM network and of the test tool that will be used to validate it are presented.

  2. 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

  3. Flow enforcement algorithms for ATM networks

    DEFF Research Database (Denmark)

    Dittmann, Lars; Jacobsen, Søren B.; Moth, Klaus

    1991-01-01

    Four measurement algorithms for flow enforcement in asynchronous transfer mode (ATM) networks are presented. The algorithms are the leaky bucket, the rectangular sliding window, the triangular sliding window, and the exponentially weighted moving average. A comparison, based partly on teletraffic...

  4. 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

  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. Teleoperation system using Asynchronous transfer mode, ATM network

    International Nuclear Information System (INIS)

    Mohd Dani Baba; A Nasoruddin Mohamad

    1999-01-01

    This paper examines the application of Asynchronous Transfer Mode (ATM) in a distributed industrial environment such as in teleoperation, which performs real time control manipulation from a remote location. In our study, two models of teleoperation are proposed; the first model is a point to point connection and the second model is through an ATM network. The performance results are analysed as to determine whether the two models can support the teleoperation traffics via simulation using commercial software design tool. (Author)

  8. 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.

  9. The RETAIN project: DICOM teleradiology over an ATM-based network. Radiological Examinations Transfer on an ATM Integrated Network.

    Science.gov (United States)

    Heautot, J F; Eichelberg, M; Gibaud, B; Tréguier, C; Lemoine, D; Scarabin, J M; Piqueras, J; Carsin, M; Gandon, Y

    2000-01-01

    The RETAIN project (Radiological Examinations Transfer on an ATM Integrated Network) has aimed at testing videoconferencing and DICOM image transfers to get advice about difficult radiological cases over an asynchronous transfer mode (ATM)-based network, which affords a more comfortable interface than narrow-band networks and allows exchange of complete image series using the DICOM format of studies. For this purpose, an experimental ATM network was applied between six university hospitals in four different countries. An assessment of the functionalities of the system was performed by means of log-file analysis, video recording of the sessions and forms filled out by the participants at the end of each session. Questionnaires were answered by the users at the end of the project to bring out perspectives of utilisation and added value. We discussed 43 cases during 20 sessions. For technical or organisational problems, only 20 of the 36 planned sessions took place. The throughput over ATM (10.5 Mbit/s, 20 times faster than six ISDN B-channels) was adequate. Despite the experimental configuration of the network, the system was considered as satisfactory by all the physicians. In 72 % of the sessions, the expected result (answer to the question) was gained. By common consent, videoconferencing was unanimously regarded as a prominent tool in improving the interaction quality. Asynchronous transfer mode is an efficient method for fast transferring of radiologic examinations in DICOM format and for discussing them through high-quality videoconferencing.

  10. Networked ATM for Efficient Routing, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — We developed a EFB Data Communication Network (EDCN) concept that offers a more capable air-ground communications architecture. The solution takes full advantage of...

  11. The Design and Analysis of Virtual Network Configuration for a Wireless Mobile ATM Network

    OpenAIRE

    Bush, Stephen F.

    1999-01-01

    This research concentrates on the design and analysis of an algorithm referred to as Virtual Network Configuration (VNC) which uses predicted future states of a system for faster network configuration and management. VNC is applied to the configuration of a wireless mobile ATM network. VNC is built on techniques from parallel discrete event simulation merged with constraints from real-time systems and applied to mobile ATM configuration and handoff. Configuration in a mobile network is a dyna...

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

    DEFF Research Database (Denmark)

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

    1999-01-01

    In this paper, we propose a knowledge-based multiple access protocol for the extension of wireline ATM to wireless networks. The objective is to enable effecient transmission of all kinds of ATM traffic in the wireless channel with guaranteed QoS.The proposed protocol utilixes knowledge of the main...... guaranteed QoS requirements to a variety of ATM applications....

  13. 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.

  14. Video transmission on ATM networks. Ph.D. Thesis

    Science.gov (United States)

    Chen, Yun-Chung

    1993-01-01

    The broadband integrated services digital network (B-ISDN) is expected to provide high-speed and flexible multimedia applications. Multimedia includes data, graphics, image, voice, and video. Asynchronous transfer mode (ATM) is the adopted transport techniques for B-ISDN and has the potential for providing a more efficient and integrated environment for multimedia. It is believed that most broadband applications will make heavy use of visual information. The prospect of wide spread use of image and video communication has led to interest in coding algorithms for reducing bandwidth requirements and improving image quality. The major results of a study on the bridging of network transmission performance and video coding are: Using two representative video sequences, several video source models are developed. The fitness of these models are validated through the use of statistical tests and network queuing performance. A dual leaky bucket algorithm is proposed as an effective network policing function. The concept of the dual leaky bucket algorithm can be applied to a prioritized coding approach to achieve transmission efficiency. A mapping of the performance/control parameters at the network level into equivalent parameters at the video coding level is developed. Based on that, a complete set of principles for the design of video codecs for network transmission is proposed.

  15. Investment and Usage of New Technologies : Evidence from a Shared ATM Network

    NARCIS (Netherlands)

    Ferrari, S.; Verboven, F.L.; Degryse, H.A.

    2007-01-01

    When new technologies become available, it is not only essential that firms have the correct investment incentives, but often also that consumers make the proper usage decisions. This paper studies investment and usage in a shared ATM network. Be- cause all banks coordinate their ATM investment

  16. Investment and Usage of New Technologies : Evidence from a Shared ATM Network

    NARCIS (Netherlands)

    Ferrari, S.; Verboven, F.L.; Degryse, H.A.

    2008-01-01

    When new technologies become available, it is not only essential that firms have the correct investment incentives, but often also that consumers make the proper usage decisions. This paper studies investment and usage in a shared ATM network. Be- cause all banks coordinate their ATM investment

  17. 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...

  18. 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)

  19. 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)

  20. Telemedicine with integrated data security in ATM-based networks

    Science.gov (United States)

    Thiel, Andreas; Bernarding, Johannes; Kurth, Ralf; Wenzel, Rudiger; Villringer, Arno; Tolxdorff, Thomas

    1997-05-01

    Telemedical services rely on the digital transfer of large amounts of data in a short time. The acceptance of these services requires therefore new hard- and software concepts. The fast exchange of data is well performed within a high- speed ATM-based network. The fast access to the data from different platforms imposes more difficult problems, which may be divided into those relating to standardized data formats and those relating to different levels of data security across nations. For a standardized access to the formats and those relating to different levels of data security across nations. For a standardized access to the image data, a DICOM 3.0 server was implemented.IMages were converted into the DICOM 3.0 standard if necessary. The access to the server is provided by an implementation of DICOM in JAVA allowing access to the data from different platforms. Data protection measures to ensure the secure transfer of sensitive patient data are not yet solved within the DICOM concept. We investigated different schemes to protect data using the DICOM/JAVA modality with as little impact on data transfer speed as possible.

  1. 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.

  2. 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...

  3. Experience with PACS in an ATM/Ethernet switched network environment.

    Science.gov (United States)

    Pelikan, E; Ganser, A; Kotter, E; Schrader, U; Timmermann, U

    1998-03-01

    Legacy local area network (LAN) technologies based on shared media concepts are not adequate for the growth of a large-scale picture archiving and communication system (PACS) in a client-server architecture. First, an asymmetric network load, due to the requests of a large number of PACS clients for only a few main servers, should be compensated by communication links to the servers with a higher bandwidth compared to the clients. Secondly, as the number of PACS nodes increases, the network throughout should not measurably cut production. These requirements can easily be fulfilled using switching technologies. Here asynchronous transfer mode (ATM) is clearly one of the hottest topics in networking because the ATM architecture provides integrated support for a variety of communication services, and it supports virtual networking. On the other hand, most of the imaging modalities are not yet ready for integration into a native ATM network. For a lot of nodes already joining an Ethernet, a cost-effective and pragmatic way to benefit from the switching concept would be a combined ATM/Ethernet switching environment. This incorporates an incremental migration strategy with the immediate benefits of high-speed, high-capacity ATM (for servers and high-sophisticated display workstations), while preserving elements of the existing network technologies. In addition, Ethernet switching instead of shared media Ethernet improves the performance considerably. The LAN emulation (LANE) specification by the ATM forum defines mechanisms that allow ATM networks to coexist with legacy systems using any data networking protocol. This paper points out the suitability of this network architecture in accordance with an appropriate system design.

  4. The ATM signaling network in development and disease

    Science.gov (United States)

    Stracker, Travis H.; Roig, Ignasi; Knobel, Philip A.; Marjanović, Marko

    2013-01-01

    The DNA damage response (DDR) rapidly recognizes DNA lesions and initiates the appropriate cellular programs to maintain genome integrity. This includes the coordination of cell cycle checkpoints, transcription, translation, DNA repair, metabolism, and cell fate decisions, such as apoptosis or senescence (Jackson and Bartek, 2009). DNA double-strand breaks (DSBs) represent one of the most cytotoxic DNA lesions and defects in their metabolism underlie many human hereditary diseases characterized by genomic instability (Stracker and Petrini, 2011; McKinnon, 2012). Patients with hereditary defects in the DDR display defects in development, particularly affecting the central nervous system, the immune system and the germline, as well as aberrant metabolic regulation and cancer predisposition. Central to the DDR to DSBs is the ataxia-telangiectasia mutated (ATM) kinase, a master controller of signal transduction. Understanding how ATM signaling regulates various aspects of the DDR and its roles in vivo is critical for our understanding of human disease, its diagnosis and its treatment. This review will describe the general roles of ATM signaling and highlight some recent advances that have shed light on the diverse roles of ATM and related proteins in human disease. PMID:23532176

  5. The ATM signaling network in development and disease

    Directory of Open Access Journals (Sweden)

    Travis H. Stracker

    2013-03-01

    Full Text Available The DNA damage response (DDR rapidly recognizes DNA lesions and initiates the appropriate cellular programs to maintain genome integrity. This includes the coordination of cell cycle checkpoints, transcription, translation, DNA repair, metabolism and cell fate decisions, such as apoptosis or senescence(Jackson and Bartek, 2009. DNA double-strand breaks (DSBs represent one of the most cytotoxic DNA lesions and defects in their metabolism underlie many human hereditary diseases characterized by genomic instability(Stracker and Petrini, 2011;McKinnon, 2012. Patients with hereditary defects in the DDR display defects in development, particularly affecting the central nervous system (CNS, the immune system and the germline, as well as aberrant metabolic regulation and cancer predisposition. Central to the DDR to DSBs is the ATM kinase, a master controller of signal transduction. Understanding how ATM signaling regulates various aspects of the DDR and its roles in vivo is critical for our understanding of human disease, its diagnosis and its treatment. This review will describe the general roles of ATM signaling and highlight some recent advances that have shed light on the diverse roles of ATM and related proteins in human disease.

  6. The Design and Analysis of Virtual Network Configuration for a Wireless Mobile ATM Network

    Science.gov (United States)

    Bush, Stephen F.

    1999-05-01

    This research concentrates on the design and analysis of an algorithm referred to as Virtual Network Configuration (VNC) which uses predicted future states of a system for faster network configuration and management. VNC is applied to the configuration of a wireless mobile ATM network. VNC is built on techniques from parallel discrete event simulation merged with constraints from real-time systems and applied to mobile ATM configuration and handoff. Configuration in a mobile network is a dynamic and continuous process. Factors such as load, distance, capacity and topology are all constantly changing in a mobile environment. The VNC algorithm anticipates configuration changes and speeds the reconfiguration process by pre-computing and caching results. VNC propagates local prediction results throughout the VNC enhanced system. The Global Positioning System is an enabling technology for the use of VNC in mobile networks because it provides location information and accurate time for each node. This research has resulted in well defined structures for the encapsulation of physical processes within Logical Processes and a generic library for enhancing a system with VNC. Enhancing an existing system with VNC is straight forward assuming the existing physical processes do not have side effects. The benefit of prediction is gained at the cost of additional traffic and processing. This research includes an analysis of VNC and suggestions for optimization of the VNC algorithm and its parameters.

  7. A hybrid medium access control for convergence of broadband wireless and wireline ATM networks

    DEFF Research Database (Denmark)

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

    2000-01-01

    In this paper, we propose a hybrid medium access control protocol for supporting broadband integrated services in the wireless ATM networks. The integrated services include CBR, VBR and ABR traffic varying from low bit-rate to very high bit-rate. The proposed protocol is an excellent compromise...

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. Effect and Analysis of Sustainable Cell Rate using MPEG video Traffic in ATM Networks

    Directory of Open Access Journals (Sweden)

    Sakshi Kaushal

    2006-04-01

    Full Text Available The broadband networks inhibit the capability to carry multiple types of traffic – voice, video and data, but these services need to be controlled according to the traffic contract negotiated at the time of the connection to maintain desired Quality of service. Such control techniques use traffic descriptors to evaluate its performance and effectiveness. In case of Variable Bit Rate (VBR services, Peak Cell Rate (PCR and its Cell Delay Variation Tolerance (CDVTPCR are mandatory descriptors. In addition to these, ATM Forum proposed Sustainable Cell Rate (SCR and its Cell delay variation tolerance (CDVTSCR. In this paper, we evaluated the impact of specific SCR and CDVTSCR values on the Usage Parameter Control (UPC performance in case of measured MPEG traffic for improving the efficiency

  13. Web Based ATM PVC Management

    NARCIS (Netherlands)

    van der Waaij, B.D.; Sprenkels, Ron; van Beijnum, Bernhard J.F.; Pras, Aiko

    1998-01-01

    This paper discusses the design of a public domain web based ATM PVC Management tool for the Dutch SURFnet research ATM network. The aim of this tool is to assists in the creation and deletion of PVCs through local and remote ATM network domains. The tool includes security mechanisms to restrict the

  14. Construction of binary status information system using PC network

    International Nuclear Information System (INIS)

    Kurnianto, K.; Azriani, A.; Teddy, S.

    1998-01-01

    Binary status information system is a part of establishing reactor parameter with Pc that function as MPR-30 Process Computer. Binary Alarm system, consist of interface hardware and input binary module terminal, prepare the information that be displayed in text message and graphical form. Monitor software give facilities that binary status of RSG-GAS components can be monitored using computer network (LAN). This program consist of two part : reside in server computer and reside in user computer. Program in server acquire data from interface and than store it in data base (Access file). Than, user computer read this file and display it in Dynamic Process and Instrumentation Diagram. The number of user computer can be more then one because data base was designed for multi-user operation

  15. Wireless Connectivity to ATM Communication Grid

    National Research Council Canada - National Science Library

    Rajaravivarma, Veeramuthu

    1998-01-01

    The AFOSR funds were used to purchase a 12 port Fore ATM switch, ATM network interface cards, a SUN UltraSPARC workstation, Lucent WavePoint wireless bridge, and Lucent WaveLAN wireless network interface cards...

  16. 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

    protocol, the influence of SDMA on a contention based access protocol is investigated under collision resolution schemes derived from classical splitting algorithms. Although this work is embedded in the framework of wireless ATM and HIPERLAN/2 systems, the ideas are generally applicable....

  17. THESEUS: A wavelength division multiplexed/microwave subcarrier multiplexed optical network, its ATM switch applications and device requirements

    Science.gov (United States)

    Xin, Wei

    1997-10-01

    A Terabit Hybrid Electro-optical /underline[Se]lf- routing Ultrafast Switch (THESEUS) has been proposed. It is a self-routing wavelength division multiplexed (WDM) / microwave subcarrier multiplexed (SCM) asynchronous transfer mode (ATM) switch for the multirate ATM networks. It has potential to be extended to a large ATM switch as 1000 x 1000 without internal blocking. Among the advantages of the hybrid implementation are flexibility in service upgrade, relaxed tolerances on optical filtering, protocol simplification and less processing overhead. For a small ATM switch, the subcarrier can be used as output buffers to solve output contention. A mathematical analysis was conducted to evaluate different buffer configurations. A testbed has been successfully constructed. Multirate binary data streams have been switched through the testbed and error free reception ([<]10-9 bit error rate) has been achieved. A simple, intuitive theoretical model has been developed to describe the heterodyne optical beat interference. A new concept of interference time and interference length has been introduced. An experimental confirmation has been conducted. The experimental results match the model very well. It shows that a large portion of optical bandwidth is wasted due to the beat interference. Based on the model, several improvement approaches have been proposed. The photo-generated carrier lifetime of silicon germanium has been measured using time-resolved reflectivity measurement. Via oxygen ion implantation, the carrier lifetime has been reduced to as short as 1 ps, corresponding to 1 THz of photodetector bandwidth. It has also been shown that copper dopants act as recombination centers in the silicon germanium.

  18. 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...

  19. Performance of asynchronous transfer mode (ATM) local area and wide area networks for medical imaging transmission in clinical environment.

    Science.gov (United States)

    Huang, H K; Wong, A W; Zhu, X

    1997-01-01

    Asynchronous transfer mode (ATM) technology emerges as a leading candidate for medical image transmission in both local area network (LAN) and wide area network (WAN) applications. This paper describes the performance of an ATM LAN and WAN network at the University of California, San Francisco. The measurements were obtained using an intensive care unit (ICU) server connecting to four image workstations (WS) at four different locations of a hospital-integrated picture archiving and communication system (HI-PACS) in a daily regular clinical environment. Four types of performance were evaluated: magnetic disk-to-disk, disk-to-redundant array of inexpensive disks (RAID), RAID-to-memory, and memory-to-memory. Results demonstrate that the transmission rate between two workstations can reach 5-6 Mbytes/s from RAID-to-memory, and 8-10 Mbytes/s from memory-to-memory. When the server has to send images to all four workstations simultaneously, the transmission rate to each WS is about 4 Mbytes/s. Both situations are adequate for radiologic image communications for picture archiving and communication systems (PACS) and teleradiology applications.

  20. 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.

  1. Performance Analysis of Quality-of-Service Controls in a Cell-Cluster-Based Wireless ATM Network

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Young Jong [Ajou University, Suwon (Korea, Republic of)

    1997-04-01

    In this paper, an efficient cell-cluster-based call control scheme with guaranteed quality-of-service(QoS) provision ing is presented for next generation wireless ATM networks and its performance is mathematically analyzed using the open queuing network. With the cell-cluster-based call control, at the time a mobile connection is admitted to the network, a virtual cell is constructed by choosing a group of neighboring base stations to which the call may probabilistic ally hand over and by assigning to the call a collection of virtual paths between the base stations. Within a micro cell/pico cell environment, it is seen that the cell-cluster-based call control can support effectively a very high rate of handovers, provides very high system capacity, and guarantees a high degree of frequency reuse over the same geographical region without requiring the intervention of the network call control processor each time a handover occurs. But since mobiles, once admitted, are free to roam within the virtual cell, congestion condition occurs in which the number of calls to be handled by one base station exceeds the cell sites` capacity of radio channel and consequently a predefined QoS provision cannot be guaranteed. So, there must be a call admission control function to limit the number of calls existing in a cell-cluster such that required QoS objectives are met. As call acceptance criteria for constant-bit-rate or realtime variable-bit-rate ATM connections, we define four mobile QoS metrics: new-call blocking probability, wireless channel utilization efficiency, congestion probability and normalized average congestion duration. In addition, for QoS provision ing to available-bit-rate, unspecified-bit-rate or non-realtime variable-bit-rate connections, we further define another QoS metric, the minimum threshold breaking probability. By using the open network queuing model, we derive closed form expressions for the five QoS metrics defined above and show that they can be

  2. ATM security via "Stargate" solution

    OpenAIRE

    Hensley, Katrina; Ludden, Fredrick

    1999-01-01

    Approved for public release, distribution unlimited. In today's world of integrating voice, video and data into a single network, Asynchronous Transfer Mode (ATM) networks have become prevalent in the Department of Defense. The Department of Defense's critical data will have to pass through public networks, which causes concern for security. This study presents an efficient solution aimed at authenticating communications over public ATM networks. The authenticating device, Stargate, utiliz...

  3. 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

  4. The ENSDF radioactivity data base for IBM-PC and computer network access

    International Nuclear Information System (INIS)

    Ekstroem, P.; Spanier, L.

    1989-08-01

    A data base system for radioactivity gamma rays is described. A base with approximately 15000 gamma rays from 2777 decays is available for installation on the hard disk of a PC, and a complete system with approximately 73000 gamma rays is available for on-line access via the NORDic University computer NETwork (NORDUNET) and the Swedish University computer NETwork (SUNET)

  5. An ME-PC Enhanced HDMR Method for Efficient Statistical Analysis of Multiconductor Transmission Line Networks

    KAUST Repository

    Yucel, Abdulkadir C.

    2015-05-05

    An efficient method for statistically characterizing multiconductor transmission line (MTL) networks subject to a large number of manufacturing uncertainties is presented. The proposed method achieves its efficiency by leveraging a high-dimensional model representation (HDMR) technique that approximates observables (quantities of interest in MTL networks, such as voltages/currents on mission-critical circuits) in terms of iteratively constructed component functions of only the most significant random variables (parameters that characterize the uncertainties in MTL networks, such as conductor locations and widths, and lumped element values). The efficiency of the proposed scheme is further increased using a multielement probabilistic collocation (ME-PC) method to compute the component functions of the HDMR. The ME-PC method makes use of generalized polynomial chaos (gPC) expansions to approximate the component functions, where the expansion coefficients are expressed in terms of integrals of the observable over the random domain. These integrals are numerically evaluated and the observable values at the quadrature/collocation points are computed using a fast deterministic simulator. The proposed method is capable of producing accurate statistical information pertinent to an observable that is rapidly varying across a high-dimensional random domain at a computational cost that is significantly lower than that of gPC or Monte Carlo methods. The applicability, efficiency, and accuracy of the method are demonstrated via statistical characterization of frequency-domain voltages in parallel wire, interconnect, and antenna corporate feed networks.

  6. Generic Traffic Descriptors in Managing Service Quality in BISDN/ATM Network

    Directory of Open Access Journals (Sweden)

    Ivan Bošnjak

    2002-03-01

    Full Text Available Traffic models for multiservice broadband networks differsignificantly regarding simple analytic models applicable intelephone traffic and circuit-switch network. The paper presentsa clear analysis of standardised traffic descriptors andquality parameters of the main services in BISDNIATM. Trafficdescriptors have been associated with the basic values andconcepts developed within generic traffic theory. Part systematisationof traffic parameters has been performed as basis for formalisedgeneralised description of parameters and effectivequality management of A TM services.

  7. Distributed Large Data-Object Environments: End-to-End Performance Analysis of High Speed Distributed Storage Systems in Wide Area ATM Networks

    Science.gov (United States)

    Johnston, William; Tierney, Brian; Lee, Jason; Hoo, Gary; Thompson, Mary

    1996-01-01

    We have developed and deployed a distributed-parallel storage system (DPSS) in several high speed asynchronous transfer mode (ATM) wide area networks (WAN) testbeds to support several different types of data-intensive applications. Architecturally, the DPSS is a network striped disk array, but is fairly unique in that its implementation allows applications complete freedom to determine optimal data layout, replication and/or coding redundancy strategy, security policy, and dynamic reconfiguration. In conjunction with the DPSS, we have developed a 'top-to-bottom, end-to-end' performance monitoring and analysis methodology that has allowed us to characterize all aspects of the DPSS operating in high speed ATM networks. In particular, we have run a variety of performance monitoring experiments involving the DPSS in the MAGIC testbed, which is a large scale, high speed, ATM network and we describe our experience using the monitoring methodology to identify and correct problems that limit the performance of high speed distributed applications. Finally, the DPSS is part of an overall architecture for using high speed, WAN's for enabling the routine, location independent use of large data-objects. Since this is part of the motivation for a distributed storage system, we describe this architecture.

  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. Implementation of virtual LANs over ATM WANs

    Science.gov (United States)

    Braun, Torsten; Maehler, Martin

    1998-09-01

    Virtual LANs (VLANs) allow to interconnect users over campus or wide area networks and gives the users the impression as they would be connected to the same local area network (LAN). The implementation of VLANs is based on ATM Forum's LAN Emulation and LAN/ATM switches providing interconnection of emulated LANs over ATM and the LAN ports to which the user's end systems are attached to. The paper discusses possible implementation architectures and describes advanced features such as ATM short-cuts, QoS, and redundancy concepts.

  10. 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…

  11. Regulation of ATM induction

    International Nuclear Information System (INIS)

    Clarke, R.A.; Fang, Z.M.; Kearsley, J.H.; Lee, C.S.; Sarris, M.; De Murrell, D.

    2000-01-01

    Full text: ATM, the tumour suppressor protein mutated in ataxia-telangiectasia, is of pivotal importance in controlling the cells primary response to ionising radiation (IR) induced DNA damage. Mutations in ATM which reduce the level of the ATM protein and/or compromise ATM functions are known to give rise to radiosensitivity and defective cell cycle checkpoint control. In response to DNA damage ATM kinase is rapidly activated and initiates downstream signalling to cell cycle control molecules including p53. To investigate additional mechanisms of ATM control we have employed ATM antisense expression in cultured cells, western analyses and immunohistochemistry in situ. We report that ATM can be up-regulated up to 10-fold following exposure to low levels of ionising radiation. ATM radiation-induction was radiation dose dependent while the rapidity of the response indicates a post translational pathway. The concurrent time frames for the radiation-induction of ATM levels and the activation of ATM kinase activity appear to be complimentary in boosting ATM's protective response to IR induced DNA damage, especially in ATM 'low expressing' systems. We also provide the first report of ATM misregulation in 2 cancer patients, indicating that ATM is not only radio-protective but has possible implications in cancer, particularly breast cancer. These results have particular importance in defining the regulation of the ATM protein as an: adaptive radio-response; radio-prognostic market in tumours and normal tissue, and breast cancer marker

  12. 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...

  13. 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…

  14. Automated transportation management system (ATMS) software project management plan (SPMP)

    Energy Technology Data Exchange (ETDEWEB)

    Weidert, R.S., Westinghouse Hanford

    1996-05-20

    The Automated Transportation Management System (ATMS) Software Project Management plan (SPMP) is the lead planning document governing the life cycle of the ATMS and its integration into the Transportation Information Network (TIN). This SPMP defines the project tasks, deliverables, and high level schedules involved in developing the client/server ATMS software.

  15. A perspective on how ATM lost Control

    NARCIS (Netherlands)

    Crosby, S.; Rooney, S.; Isaacs, R.; Bos, H.J.

    2002-01-01

    Contrary to the initial high expectations, ATM failed to become the universal network technology covering all services and running from the desktop to the back-bone. This paper tries to identify the technological problems that contributed to this failure.

  16. A survey of IP over ATM architectures

    Energy Technology Data Exchange (ETDEWEB)

    Chen, H.; Tsang, R.; Brandt, J.; Hutchins, J.

    1997-07-01

    Over the past decade, the Internet has burgeoned into a worldwide information highway consisting of approximately 5 million hosts on over 45,000 interconnected networks. This unprecedented growth, together with the introduction of multimedia workstations, has spurred the development of innovative applications that require high speed, low latency, and real-time transport. Today`s Internet can neither scale in its bandwidth nor guarantee the Quality of Services (QoS) necessary to meet these performance requirements. Many network researchers propose to use the Asynchronous Transfer Mode (ATM) technology as the underlying infrastructure for the next generation of workgroup, campus, and enterprise IP networks. Since ATM is significantly different from today`s legacy network technologies, efficient implementation of IP over ATM is especially challenging. This tutorial paper covers several existing proposals that integrate IP over ATM.

  17. Gigabit ATM: another technical mistake?

    Science.gov (United States)

    Christ, Paul

    1998-09-01

    Once upon a time, or more precisely during February 1988 at the CCITT Seoul plenary, and definitely arriving as a revolution, ATM hit the hard-core B-ISDN circuit-switching gang. Initiated by the Telecoms' camp, but, surprisingly, soon to be pushed by computer minded people, ATM's generic technological history is somewhat richer than single-sided stories. Here are two classical elements of that history: Firstly, together with X.25, ATM suffers from the connection versus datagram dichotomy, well known for more than twenty years. Secondly, and lesser known, ATM's use of cells in support of the 'I' of B-ISDN was questioned from the very beginning by the packet switching camp. Furthermore, in this context, there are two other essential elements to be considered: Firstly, the exponential growth of the Internet and later intranets, using Internet technology, sparked by the success of the Web and the WINTEL alliance, resulted in a corresponding demand for both aggregate and end-system network bandwidth. Secondly, servers, historically restricted to the exclusive club of HIPPI-equipped supercomputers, suddenly become ordinary high-end PCs with 64-bit wide PCI busses -- definitely aiming at the Gigabit. Here, if your aim is for Gigabit ATM with 5000-transactions per second classical supercomputers, a 65K ATM MTU -- as implemented by Cray -- might be okay. Following Clark and others, another part of the story is the adoption and redefinition, by the IETF, of the Telecoms' notion of 'Integrated Services' and QoS mechanisms. The quest for low-delay IP packet forwarding, perhaps possible over ATM cut-throughs, has resulted in the switching versus/or integrated-with-routing movement. However, a blow for ATM may be the recent results concerning fast routing table lookup algorithms. This, by making Gigabit routing possible using ordinary Pentium processors may eventually render the much prophesized ATM switching performance unnecessary. Recently, with the rise of Gigabit Ethernet

  18. 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

  19. Simplified management of ATM traffic

    Science.gov (United States)

    Luoma, Marko; Ilvesmaeki, Mika

    1997-10-01

    ATM has been under a thorough standardization process for more than ten years. Looking at it now, what have we achieved during this time period? Originally ATM was meant to be an easy and efficient protocol enabling varying services over a single network. What it is turning to be it `yet another ISDN'--network full of hopes and promises but too difficult to implement and expensive to market. The fact is that more and more `nice features' are implemented on the cost of overloading network with hard management procedures. Therefore we need to adopt a new approach. This approach keeps a strong reminder on `what is necessary.' This paper presents starting points for an alternative approach to the traffic management. We refer to this approach as `the minimum management principle.' Choosing of the suitable service classes for the ATM network is made difficult by the fact that the more services one implements the more management he needs. This is especially true for the variable bit rate connections that are usually treated based on the stochastic models. Stochastic model, at its best, can only reveal momentary characteristics in the traffic stream not the long range behavior of it. Our assumption is that ATM will move towards Internet in the sense that strict values for quality make little or no sense in the future. Therefore stochastic modeling of variable bit rate connections seems to be useless. Nevertheless we see that some traffic needs to have strict guarantees and that the only economic way of doing so is to use PCR allocation.

  20. ATM supports gammaherpesvirus replication by attenuating type I interferon pathway.

    Science.gov (United States)

    Darrah, Eric J; Stoltz, Kyle P; Ledwith, Mitchell; Tarakanova, Vera L

    2017-10-01

    Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages. Using a mouse model that combines ATM and type I IFN receptor deficiencies we show that increased type I IFN response in the absence of ATM fully accounts for the proviral role of ATM during gammaherpesvirus replication. Further, increased type I IFN response rendered ATM deficient macrophages more susceptible to antiviral effects of type II IFN. This study identifies attenuation of type I IFN responses as the primary mechanism underlying proviral function of ATM during gammaherpesvirus infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Enhancing the Current Automated Teller Machine (ATM) in Nigerian ...

    African Journals Online (AJOL)

    This is going to be achieved by creating another input device that collects the money into the ATM system, reads its denomination and either saves it or transfers it the required customer ... Keywords: Automated Teller Machine (ATM), Interswitch, Local Area Network (LAN), Wide Area Network (WAN), Telecommunication.

  2. Will available bit rate (ABR) services give us the capability to offer virtual LANs over wide-area ATM networks?

    Science.gov (United States)

    Ferrandiz, Ana; Scallan, Gavin

    1995-10-01

    The available bit rate (ABR) service allows connections to exceed their negotiated data rates during the life of the connections when excess capacity is available in the network. These connections are subject to flow control from the network in the event of network congestion. The ability to dynamically adjust the data rate of the connection can provide improved utilization of the network and be a valuable service to end users. ABR type service is therefore appropriate for the transmission of bursty LAN traffic over a wide area network in a manner that is more efficient and cost effective than allocating bandwdith at the peak cell rate. This paper describes the ABR service and discusses if it is realistic to operate a LAN like service over a wide area using ABR.

  3. The over expression of long non-coding RNA ANRIL promotes epithelial-mesenchymal transition by activating the ATM-E2F1 signaling pathway in pancreatic cancer: An in vivo and in vitro study.

    Science.gov (United States)

    Chen, Shi; Zhang, Jia-Qiang; Chen, Jiang-Zhi; Chen, Hui-Xing; Qiu, Fu-Nan; Yan, Mao-Lin; Chen, Yan-Ling; Peng, Cheng-Hong; Tian, Yi-Feng; Wang, Yao-Dong

    2017-09-01

    This study aims to investigate the roles of lncRNA ANRIL in epithelial-mesenchymal transition (EMT) by regulating the ATM-E2F1 signaling pathway in pancreatic cancer (PC). PC rat models were established and ANRIL overexpression and interference plasmids were transfected. The expression of ANRIL, EMT markers (E-cadherin, N-cadherin and Vimentin) and ATM-E2F1 signaling pathway-related proteins (ATM, E2F1, INK4A, INK4B and ARF) were detected. Small molecule drugs were applied to activate and inhibit the ATM-E2F1 signaling pathway. Transwell assay and the scratch test were adopted to detect cell invasion and migration abilities. ANRIL expression in the PC cells was higher than in normal pancreatic duct epithelial cells. In the PC rat models and PC cells, ANRIL interference promoted the expressions of INK4B, INK4A, ARF and E-cadherin, while reduced N-cadherin and Vimentin expression. Over-expressed ANRIL decreased the expression of INK4B, INK4A, ARF and E-cadherin, but raised N-cadherin and Vimentin expressions. By inhibiting the ATM-E2F1 signaling pathway in PC cells, E-cadherin expression increased but N-cadherin and Vimentin expressions decreased. After ANRIL was silenced or the ATM-E2F1 signaling pathway inhibited, PC cell migration and invasion abilities were decreased. In conclusion, over-expression of lncRNA ANRIL can promote EMT of PC cells by activating the ATM-E2F1 signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Introducing an Adaptive Method to Tune Initial Backoff Window ( -ATM in IEEE 802.11 Wireless Networks

    Directory of Open Access Journals (Sweden)

    Tadayon Navid

    2010-01-01

    Full Text Available IEEE802.11 access protocol uses CSMA/CA in its Medium Access control layer as the main access function, which carries several deficiencies. In these networks, as the number of active stations increases, delay and throughput degrade severely. As far as throughput and service delay are vital elements in Quality of Service (QoS determination, such degradation could lead to intolerable situations and reduce the efficiency of WLANs. Networks (WLANs. Studies proved this problem arises due to constant initial backoff windows size ( , which is an important parameter in determination of network behavior. In this paper, we introduce a new method to tune this parameter adaptively according to changes in channel load. In this method, we do tune this parameter after every transmission using a feedback from transmission channel. Later it will be proven that applying this method in MAC layer enhances network stability; delay trend in all traffic classes exhibits a considerable reduction when compared with simple Enhanced Distributed Coordination Access (EDCA scenarios. Also throughput exhibits a salient improvement in level. In other word, QoS improves. Especially, with the aid of this method, delay variations in all decrease considerably and more smoothen delay trends are achieved.

  5. 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.

  6. The ENSDF radioactivity data base for IBM-PC and computer network access

    International Nuclear Information System (INIS)

    Ekstroem, P.; Spanier, L.

    1989-08-01

    A database for about 15000 gamma rays from 2777 radioactive nuclides derived from the international Evaluated Nuclear Structure Data File (ENSDF) is described together with supporting computer codes. The database is available on a PC diskette, costfree, from the IAEA Nuclear Data Section. (author)

  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. 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…

  9. Introduction to multiprotocol over ATM (MPOA)

    Science.gov (United States)

    Fredette, Andre N.

    1997-10-01

    Multiprotocol over ATM (MPOA) is a new protocol specified by the ATM Forum. MPOA provides a framework for effectively synthesizing bridging and routing with ATM in an environment of diverse protocols and network technologies. The primary goal of MPOA is the efficient transfer of inter-subnet unicast data in a LAN Emulation (LANE) environment. MPOA integrates LANE and the next hop resolution protocol (NHRP) to preserve the benefits of LAN Emulation, while allowing inter-subnet, internetwork layer protocol communication over ATM VCCs without requiring routers in the data path. It reduces latency and the internetwork layer forwarding load on backbone routers by enabling direct connectivity between ATM-attached edge devices (i.e., shortcuts). To establish these shortcuts, MPOA uses both routing and bridging information to locate the edge device closest to the addressed end station. By integrating LANE and NHRP, MPOA allows the physical separation of internetwork layer route calculation and forwarding, a technique known as virtual routing. This separation provides a number of key benefits including enhanced manageability and reduced complexity of internetwork layer capable edge devices. This paper provides an overview of MPOA that summarizes the goals, architecture, and key attributes of the protocol. In presenting this overview, the salient attributes of LANE and NHRP are described as well.

  10. PC communication

    International Nuclear Information System (INIS)

    Oh, Jae Cheol

    1992-03-01

    This text book is comprised of five charters, which is about PC communication for beginners who need to learn manners and how to use Ketel and PC serve. So it introduces first, conception of PC and precautions on using PC communication, second, preparation for PC communication with Modem, its program, install, kinds of protocol and how to use protocol, third directions of emulator of PC communication and super session, fourth, instruction of Ketel with join and access, basic command of Ketel, list of Ketel's menu, Ketel editor, service guide, directions of News service, Stock and bond service business and economic figures, exchange rate and interest rate, tax culture and leisure, Ketel BBS service and posting. The last part has a instruction of PC-serve about join, basic command of PC-serve, service guide and practical guideline.

  11. PC communication

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jae Cheol

    1992-03-15

    This text book is comprised of five charters, which is about PC communication for beginners who need to learn manners and how to use Ketel and PC serve. So it introduces first, conception of PC and precautions on using PC communication, second, preparation for PC communication with Modem, its program, install, kinds of protocol and how to use protocol, third directions of emulator of PC communication and super session, fourth, instruction of Ketel with join and access, basic command of Ketel, list of Ketel's menu, Ketel editor, service guide, directions of News service, Stock and bond service business and economic figures, exchange rate and interest rate, tax culture and leisure, Ketel BBS service and posting. The last part has a instruction of PC-serve about join, basic command of PC-serve, service guide and practical guideline.

  12. An ME-PC Enhanced HDMR Method for Efficient Statistical Analysis of Multiconductor Transmission Line Networks

    KAUST Repository

    Yucel, Abdulkadir C.; Bagci, Hakan; Michielssen, Eric

    2015-01-01

    An efficient method for statistically characterizing multiconductor transmission line (MTL) networks subject to a large number of manufacturing uncertainties is presented. The proposed method achieves its efficiency by leveraging a high

  13. Design of a QoS-controlled ATM-based communications system in chorus

    Science.gov (United States)

    Coulson, Geoff; Campbell, Andrew; Robin, Philippe; Blair, Gordon; Papathomas, Michael; Shepherd, Doug

    1995-05-01

    We describe the design of an application platform able to run distributed real-time and multimedia applications alongside conventional UNIX programs. The platform is embedded in a microkernel/PC environment and supported by an ATM-based, QoS-driven communications stack. In particular, we focus on resource-management aspects of the design and deal with CPU scheduling, network resource-management and memory-management issues. An architecture is presented that guarantees QoS levels of both communications and processing with varying degrees of commitment as specified by user-level QoS parameters. The architecture uses admission tests to determine whether or not new activities can be accepted and includes modules to translate user-level QoS parameters into representations usable by the scheduling, network, and memory-management subsystems.

  14. IT Career JumpStart An Introduction to PC Hardware, Software, and Networking

    CERN Document Server

    Alpern, Naomi J; Muller, Randy

    2011-01-01

    A practical approach for anyone looking to enter the IT workforce Before candidates can begin to prepare for any kind of certification, they need a basic understanding of the various hardware and software components used in a computer network. Aimed at aspiring IT professionals, this invaluable book strips down a network to its bare basics, and discusses this complex topic in a clear and concise manner so that IT beginners can confidently gain an understanding of fundamental IT concepts. In addition, a base knowledge has been established so that more advanced topics and technologies can be lea

  15. A survey on the status of ATM based LAN

    International Nuclear Information System (INIS)

    Yang, Sung Woon; Kang, Soon Ju

    1996-03-01

    This report presents the technical status of the ATM(Asynchronous Transfer Mode) as a new high speed data communication method. Since the FDDI(Fiber optic Distributed Data Interchange) backbone has been installed in september 1995, it has been used as a main network structure of KAERI. However, recently high speed and multimedia data communication environment is being required to accommodate the recent trend of the network usage in KAERI. For example, the rapid growth of Internet usage and increased activities of information retrieval systems on KAERI-Net demand more effective network system. Chapter 1 discusses the status of KAERI-Net and the selection criteria of a network model according to the national plan of super high speed network structure. In Chapter 2, the basic concept of ATM such as communication method and communication structure is studied, and Chapter 3 presents the overall concepts of standard model of ATM. In Chapter 4, we survey the recent trend of technical development of ATM and analyze the status of ATM technology. As a concluding remark, Chapter 5 discusses the criteria and check points for optimal design of KAERI-Net backbone. This report will be used as a technical reference for the installation of ATM in KAERI-Net. 10 tabs., 32 figs., 11 refs. (Author)

  16. 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 ...... to the bus, it is shown that consecutive service times of the local access queue are correlated. Two models, one of which includes the correlation, are presented. The correlation effect is illustrated and the models are evaluated by means of a number of simulation cases......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...

  17. A performance analysis of advanced I/O architectures for PC-based network file servers

    Science.gov (United States)

    Huynh, K. D.; Khoshgoftaar, T. M.

    1994-12-01

    In the personal computing and workstation environments, more and more I/O adapters are becoming complete functional subsystems that are intelligent enough to handle I/O operations on their own without much intervention from the host processor. The IBM Subsystem Control Block (SCB) architecture has been defined to enhance the potential of these intelligent adapters by defining services and conventions that deliver command information and data to and from the adapters. In recent years, a new storage architecture, the Redundant Array of Independent Disks (RAID), has been quickly gaining acceptance in the world of computing. In this paper, we would like to discuss critical system design issues that are important to the performance of a network file server. We then present a performance analysis of the SCB architecture and disk array technology in typical network file server environments based on personal computers (PCs). One of the key issues investigated in this paper is whether a disk array can outperform a group of disks (of same type, same data capacity, and same cost) operating independently, not in parallel as in a disk array.

  18. Remote CT reading using an ultramobile PC and web-based remote viewing over a wireless network.

    Science.gov (United States)

    Choi, Hyuk Joong; Lee, Jeong Hun; Kang, Bo Seung

    2012-01-01

    We developed a new type of mobile teleradiology system using an ultramobile PC (UMPC) for web-based remote viewing over a wireless network. We assessed the diagnostic performance of this system for abdominal CT interpretation. Performance was compared with an emergency department clinical monitor using a DICOM viewer. A total of 100 abdominal CT examinations were presented to four observers. There were 56 examinations showing appendicitis and 44 which were normal. The observers viewed the images using a UMPC display and an LCD monitor and rated each examination on a five-point scale. Receiver operating characteristics (ROC) analysis was used to test for differences. The sensitivity and specificities of all observers were similarly high. The average area under the ROC curve for readings performed on the UMPC and the LCD monitor was 0.959 and 0.976, respectively. There were no significant differences between the two display systems for interpreting abdominal CTs. The web-based mobile teleradiology system appears to be feasible for reading abdominal CTs for diagnosing appendicitis and may be valuable in emergency teleconsultation. Copyright © 2012 by the Royal Society of Medicine Press Ltd

  19. Studies of ATM Kinase Activity Using Engineered ATM Sensitive to ATP Analogues (ATM-AS).

    Science.gov (United States)

    Enari, Masato; Matsushima-Hibiya, Yuko; Miyazaki, Makoto; Otomo, Ryo

    2017-01-01

    Ataxia-telangiectasia mutated (ATM) protein is a member of the phosphatidylinositol 3-phosphate kinase (PI3-K)-related protein kinase (PIKK) family and is implicated in the initiation of signaling pathways following DNA double strand breaks (DSBs) elicited by exposure to ionizing irradiation (IR) or radiomimetic compounds. Loss of function of the ATM gene product results in the human genetic disorder ataxia-telangiectasia (A-T) characterized by neurodegeneration, immunodeficiency, genomic instability, and cancer predisposition. In response to DSBs, ATM is activated and phosphorylates Ser/Thr-Gln (S/T-Q) sequences on numerous proteins participating in DNA-damage responses. Among these proteins, phosphorylation of the tumor suppressor p53 at Ser15 is known as a target for ATM, which leads to the dissociation of MDM2, an E3 ubiquitin ligase, from p53 to prevent MDM2-dependent p53 degradation. Ser46 on p53 is phosphorylated in response to DSBs and contributes to the preferential transactivation of pro-apoptotic genes, such as p53AIP1, Noxa, and PUMA, to prevent tumor formation. Our group have shown that not only ATM preferentially phosphorylates S/T-Q sequences, but also Ser46, which is a noncanonical site with an S-P sequence for ATM. Ser46 on p53 is directly phosphorylated by ATM in a p53 conformation-dependent manner using the ATP analogue-accepting ATM mutant (ATM-AS) system. This protocol summarizes an approach to identify direct numerous targets for ATM kinase and is used to elucidate ATM signaling pathways in the DNA damage responses.

  20. The new Passive microwave Neural network Precipitation Retrieval (PNPR algorithm for the cross-track scanning ATMS radiometer: description and verification study over Europe and Africa using GPM and TRMM spaceborne radars

    Directory of Open Access Journals (Sweden)

    P. Sanò

    2016-11-01

    Full Text Available The objective of this paper is to describe the development and evaluate the performance of a completely new version of the Passive microwave Neural network Precipitation Retrieval (PNPR v2, an algorithm based on a neural network approach, designed to retrieve the instantaneous surface precipitation rate using the cross-track Advanced Technology Microwave Sounder (ATMS radiometer measurements. This algorithm, developed within the EUMETSAT H-SAF program, represents an evolution of the previous version (PNPR v1, developed for AMSU/MHS radiometers (and used and distributed operationally within H-SAF, with improvements aimed at exploiting the new precipitation-sensing capabilities of ATMS with respect to AMSU/MHS. In the design of the neural network the new ATMS channels compared to AMSU/MHS, and their combinations, including the brightness temperature differences in the water vapor absorption band, around 183 GHz, are considered. The algorithm is based on a single neural network, for all types of surface background, trained using a large database based on 94 cloud-resolving model simulations over the European and the African areas. The performance of PNPR v2 has been evaluated through an intercomparison of the instantaneous precipitation estimates with co-located estimates from the TRMM Precipitation Radar (TRMM-PR and from the GPM Core Observatory Ku-band Precipitation Radar (GPM-KuPR. In the comparison with TRMM-PR, over the African area the statistical analysis was carried out for a 2-year (2013–2014 dataset of coincident observations over a regular grid at 0.5°  ×  0.5° resolution. The results have shown a good agreement between PNPR v2 and TRMM-PR for the different surface types. The correlation coefficient (CC was equal to 0.69 over ocean and 0.71 over vegetated land (lower values were obtained over arid land and coast, and the root mean squared error (RMSE was equal to 1.30 mm h−1 over ocean and 1.11 mm h−1 over

  1. PC Pricer

    Data.gov (United States)

    U.S. Department of Health & Human Services — The PC Pricer is a tool used to estimate Medicare PPS payments. The final payment may not be precise to how payments are determined in the Medicare claims processing...

  2. Fabrication and characterization of MCC [Materials Characterization Center] approved testing material---ATM-2, ATM-3, and ATM-4 glasses

    International Nuclear Information System (INIS)

    Wald, J.W.

    1988-03-01

    Materials Characterization Center glasses ATM-2, ATM-3, and ATM-4 are designed to simulate high-level waste glasses that are likely to result from the reprocessing of commercial nuclear reactor fuels. The three Approved Testing Materials (ATMs) are borosilicate glasses based upon the MCC-76-68 glass composition. One radioisotope was added to form each ATM. The radioisotopes added to form ATM-2, ATM-3, and ATM-4 were 241 Am, 237 Np, and 239 Pu, respectively. Each of the ATM lots was produced in a nominal lot size of 450 g from feed stock melted in a nitrogen-atmosphere glove box at 1200/degree/C in a platinum crucible. Each ATM was then cast into bars. Analyzed compositions of these glasses are listed. The nonradioactive elements were analyzed by inductively coupled argon plasma atomic emission spectroscopy (ICP), and the radioisotope analyses were done by alpha energy analysis. Results are discussed. 7 refs., 3 figs., 5 tabs

  3. Tug of War between Survival and Death: Exploring ATM Function in Cancer

    Directory of Open Access Journals (Sweden)

    Venturina Stagni

    2014-03-01

    Full Text Available Ataxia-telangiectasia mutated (ATM kinase is a one of the main guardian of genome stability and plays a central role in the DNA damage response (DDR. The deregulation of these pathways is strongly linked to cancer initiation and progression as well as to the development of therapeutic approaches. These observations, along with reports that identify ATM loss of function as an event that may promote tumor initiation and progression, point to ATM as a bona fide tumor suppressor. The identification of ATM as a positive modulator of several signalling networks that sustain tumorigenesis, including oxidative stress, hypoxia, receptor tyrosine kinase and AKT serine-threonine kinase activation, raise the question of whether ATM function in cancer may be more complex. This review aims to give a complete overview on the work of several labs that links ATM to the control of the balance between cell survival, proliferation and death in cancer.

  4. Tug of War between Survival and Death: Exploring ATM Function in Cancer

    Science.gov (United States)

    Stagni, Venturina; Oropallo, Veronica; Fianco, Giulia; Antonelli, Martina; Cinà, Irene; Barilà, Daniela

    2014-01-01

    Ataxia-telangiectasia mutated (ATM) kinase is a one of the main guardian of genome stability and plays a central role in the DNA damage response (DDR). The deregulation of these pathways is strongly linked to cancer initiation and progression as well as to the development of therapeutic approaches. These observations, along with reports that identify ATM loss of function as an event that may promote tumor initiation and progression, point to ATM as a bona fide tumor suppressor. The identification of ATM as a positive modulator of several signalling networks that sustain tumorigenesis, including oxidative stress, hypoxia, receptor tyrosine kinase and AKT serine-threonine kinase activation, raise the question of whether ATM function in cancer may be more complex. This review aims to give a complete overview on the work of several labs that links ATM to the control of the balance between cell survival, proliferation and death in cancer. PMID:24681585

  5. Supervisory control system based on PC applied to substations automatization of and to regional operation centers of distribution networks; Sistema de control supervisorio basado en PC aplicado en automatizacion de subestaciones y centros de operacion regional de redes de distribucion

    Energy Technology Data Exchange (ETDEWEB)

    Picasso B, Cuitlahuac [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico); Astorga Q, Clemente [Luz y Fuerza del Centro (Mexico)

    2003-07-01

    In order to increase the services quality in the electrical energy, to improve the process of identification of energy losses, to increase the equipment efficiency, to count on more complete statistics of profiles of load consumptions, among other applications, the Compania de Luz y Fuerza del Centro (LyFC) carries out the modernization in automatization of substations and regional operation centers of distribution networks. The technological base to make these programs requires automating the operative schemes of the substation and distribution centers that supervise the events of the electrical process. In this article the main results of the development and integration of master stations based on PC, that were made in the Instituto de Investigaciones Electricas (IIE) and that have been integrated in the electrical company LyFC are presented. [Spanish] Con el proposito de incrementar la calidad de los servicios en la energia electrica, mejorar el proceso de identificacion de perdidas de energia, aumentar la eficiencia de los equipos, contar con estadisticas mas completas de perfiles de consumos de carga, entre otras aplicaciones, la Compania de Luz y Fuerza del Centro (LyFC) lleva a cabo la modernizacion en automatizacion de subestaciones y centros de operacion regional de redes electricas de distribucion. La base tecnologica para realizar estos programas, requiere de automatizar los esquemas operativos de la subestacion y centros de distribucion que supervisan los eventos del proceso electrico. En este articulo se presentan los principales resultados del desarrollo e integracion de estaciones maestras basadas en PC, que se realizaron en el Instituto de Investigaciones Electricas (IIE) y que se han integrado en la compania electrica LyFC.

  6. Optimization of wide-area ATM and local-area ethernet/FDDI network configurations for high-speed telemedicine communications employing NASA's ACTS.

    Science.gov (United States)

    McDermott, W R; Tri, J L; Mitchell, M P; Levens, S P; Wondrow, M A; Huie, L M; Khandheria, B K; Gilbert, B K

    1999-01-01

    A high data rate terrestrial and satellite network was implemented to transfer medical images and data. This article describes the a optimization of the workstations and switching equipment incorporated into the network. Topics discussed in this article include tuning of the network software, the configuration of the Sun Microsystems workstations, the FORE Systems asynchronous transfer mode switches, as well as the throughput results of two telemedicine experiments undertaken by Mayo's physician staff. The technical staff was successful in achieving the data throughput needed by the telemedicine software; particularly important was the proper determination of peak throughput and TCP window sizes to ensure optimum use of the resources available on the Sun Microsystems and Hewlett Packard workstations.

  7. A TAD closer to ATM.

    Science.gov (United States)

    Aymard, Francois; Legube, Gaëlle

    2016-05-01

    Ataxia telangiectasia mutated (ATM) has been known for decades as the main kinase mediating the DNA double-strand break response. Our recent findings suggest that its major role at the sites of breaks likely resides in its ability to modify both the local chromatin landscape and the global chromosome organization in order to promote repair accuracy.

  8. 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.

  9. 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.

  10. CaC in ATM – the Diffuse Method

    OpenAIRE

    I. Baroňák; M. Vozňák

    2006-01-01

    Connection Admission Control is an element in the of preclusive mechanisms of ATM management. Its main task is to prevent overloading of the network and to ensure the required quality of service. This means that it has to predict the service of the network and according to its state it can manage both existing and new connections. This paper deals with the diffuse method, a CAC method that enables us to obtain the required results. 

  11. ATM in Europe: analysis of current status

    DEFF Research Database (Denmark)

    1999-01-01

    This deliverable provides an overview of the current status of the European market for ATM services. The offer of ATM services by principal operators in Belgium, Denmark, Finland, France, Germany, Greece, Italy, Norway, Portugal, Spain, Sweden and United Kingdom is described. In addition, a number...... of international providers of ATM in Europe are presented....

  12. Transition to Asynchronous Transfer Mode (ATM) an Implementation Model for NPS Software Metrics Lab

    National Research Council Canada - National Science Library

    Carney, Cameron

    1999-01-01

    With Asynchronous Transfer Mode (ATM), we are experiencing the emergence of a network technology that has the potential of satisfying the requirement for a worldwide standard to allow interoperability of information, regardless...

  13. Redes Atm de Alto Desempenho

    Directory of Open Access Journals (Sweden)

    Flávia Oliveira Santos de Sá Lisboa

    2015-12-01

    Full Text Available A tendência atual de integração de serviços de dados, voz e vídeo, estimulada pelo pleno sucesso da Internet, aumentou a demanda por maior banda e melhor desempenho nas redes de comunicação de dados. Neste contexto, a tecnologia ATM (Asynchronous Transfer Mode vem sendo utilizada na implementação de backbone de LANs e WANs, justamente por oferecer a possibilidade de integração de serviços com qualidade, alta escalabilidade e altas taxas de transferência em banda larga. Neste artigo serão abordados os principais conceitos relacionados à tecnologia ATM, suas vantagens e desvantagens em face de outras tecnologias (como Fast e Gigabit Ethernet, além de casos de sua utilização em empresas e instituições de ensino.

  14. Models for setting ATM parameter values

    DEFF Research Database (Denmark)

    Blaabjerg, Søren; Gravey, A.; Romæuf, L.

    1996-01-01

    essential to set traffic characteristic values that are relevant to the considered cell stream, and that ensure that the amount of non-conforming traffic is small. Using a queueing model representation for the GCRA formalism, several methods are available for choosing the traffic characteristics. This paper......In ATM networks, a user should negotiate at connection set-up a traffic contract which includes traffic characteristics and requested QoS. The traffic characteristics currently considered are the Peak Cell Rate, the Sustainable Cell Rate, the Intrinsic Burst Tolerance and the Cell Delay Variation...... (CDV) tolerance(s). The values taken by these traffic parameters characterize the so-called ''Worst Case Traffic'' that is used by CAC procedures for accepting a new connection and allocating resources to it. Conformance to the negotiated traffic characteristics is defined, at the ingress User...

  15. ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses.

    Science.gov (United States)

    Berger, N Daniel; Stanley, Fintan K T; Moore, Shaun; Goodarzi, Aaron A

    2017-10-05

    Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase with a master regulatory function in the DNA damage response. In this role, ATM commands a complex biochemical network that signals the presence of oxidative DNA damage, including the dangerous DNA double-strand break, and facilitates subsequent repair. Here, we review the current state of knowledge regarding ATM-dependent chromatin remodelling and epigenomic alterations that are required to maintain genomic integrity in the presence of DNA double-strand breaks and/or oxidative stress. We will focus particularly on the roles of ATM in adjusting nucleosome spacing at sites of unresolved DNA double-strand breaks within complex chromatin environments, and the impact of ATM on preserving the health of cells within the mammalian central nervous system.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'. © 2017 The Author(s).

  16. Defining ATM-Independent Functions of the Mre11 Complex with a Novel Mouse Model.

    Science.gov (United States)

    Balestrini, Alessia; Nicolas, Laura; Yang-Lott, Katherine; Guryanova, Olga A; Levine, Ross L; Bassing, Craig H; Chaudhuri, Jayanta; Petrini, John H J

    2016-02-01

    The Mre11 complex (Mre11, Rad50, and Nbs1) occupies a central node of the DNA damage response (DDR) network and is required for ATM activation in response to DNA damage. Hypomorphic alleles of MRE11 and NBS1 confer embryonic lethality in ATM-deficient mice, indicating that the complex exerts ATM-independent functions that are essential when ATM is absent. To delineate those functions, a conditional ATM allele (ATM(flox)) was crossed to hypomorphic NBS1 mutants (Nbs1(ΔB/ΔB) mice). Nbs1(ΔB/ΔB) Atm(-/-) hematopoietic cells derived by crossing to vav(cre) were viable in vivo. Nbs1(ΔB/ΔB) Atm(-/-) (VAV) mice exhibited a pronounced defect in double-strand break repair and completely penetrant early onset lymphomagenesis. In addition to repair defects observed, fragile site instability was noted, indicating that the Mre11 complex promotes genome stability upon replication stress in vivo. The data suggest combined influences of the Mre11 complex on DNA repair, as well as the responses to DNA damage and DNA replication stress. A novel mouse model was developed, by combining a vav(cre)-inducible ATM knockout mouse with an NBS1 hypomorphic mutation, to analyze ATM-independent functions of the Mre11 complex in vivo. These data show that the DNA repair, rather than DDR signaling functions of the complex, is acutely required in the context of ATM deficiency to suppress genome instability and lymphomagenesis. ©2015 American Association for Cancer Research.

  17. 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...

  18. Novel targets for ATM-deficient malignancies

    Science.gov (United States)

    Winkler, Johannes; Hofmann, Kay; Chen, Shuhua

    2014-01-01

    Conventional chemo- and radiotherapies for the treatment of cancer target rapidly dividing cells in both tumor and non-tumor tissues and can exhibit severe cytotoxicity in normal tissue and impair the patient's immune system. Novel targeted strategies aim for higher efficacy and tumor specificity. The role of ATM protein in the DNA damage response is well known and ATM deficiency frequently plays a role in tumorigenesis and development of malignancy. In addition to contributing to disease development, ATM deficiency also renders malignant cells heavily dependent on other pathways that cooperate with the ATM-mediated DNA damage response to ensure tumor cell survival. Disturbing those cooperative pathways by inhibiting critical protein components allows specific targeting of tumors while sparing healthy cells with normal ATM status. We review druggable candidate targets for the treatment of ATM-deficient malignancies and the mechanisms underlying such targeted therapies. PMID:27308314

  19. Synchronous and Asynchronous ATM Multiplexor Properties Comparsion

    OpenAIRE

    Jan Zabka

    2006-01-01

    The article is aimed to ATM multiplexor computer model utilisation. Based on simulation runs we try to review aspects of use a synchronous and asynchronous ATM multiplexors. ATM multiplexor is the input queuing model with three inputs. Synchronous multiplexor works without an input priority. Multiplexor inputs are served periodically. Asynchronous multiplexor model supports several queuing and priority mechanisms. CLR and CTD are basic performance parameters. Input cell flows are genera...

  20. Development of a queue warning system utilizing ATM infrastructure system development and field-testing : final report.

    Science.gov (United States)

    2017-06-13

    MnDOT has already deployed an extensive infrastructure for Active Traffic Management (ATM) on I-35W and I-94 with plans to expand on other segments of the Twin Cities freeway network. The ATM system includes intelligent lane control signals (ILCS) sp...

  1. ATM signaling and 53BP1

    International Nuclear Information System (INIS)

    Zgheib, Omar; Huyen, Yentram; DiTullio, Richard A.; Snyder, Andrew; Venere, Monica; Stavridi, Elena S.; Halazonetis, Thanos D.

    2005-01-01

    The ATM (mutated in Ataxia-Telangiectasia) protein kinase is an important player in signaling the presence of DNA double strand breaks (DSBs) in higher eukaryotes. Recent studies suggest that ATM monitors the presence of DNA DSBs indirectly, through DNA DSB-induced changes in chromatin structure. One of the proteins that sense these chromatin structure changes is 53BP1, a DNA damage checkpoint protein conserved in all eukaryotes and the putative ortholog of the S. cerevisiae RAD9 protein. We review here the mechanisms by which ATM is activated in response to DNA DSBs, as well as key ATM substrates that control cell cycle progression, apoptosis and DNA repair

  2. 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...

  3. Functional Characterization of ATM Kinase Using Acetylation-Specific Antibodies.

    Science.gov (United States)

    Sun, Yingli; Du, Fengxia

    2017-01-01

    The activation of ATM is critical in the DNA double strand breaks repair pathway. Acetylation of ATM by Tip60 histone acetyltransferase (HAT) plays a key role in the activation of ATM kinase activity in response to DNA damage. ATM forms a stable complex with Tip60 through the FATC domain of ATM. Tip60 acetylates lysine3016 of ATM, and this acetylation induces the activation of ATM. Several techniques are included in the study of ATM acetylation by Tip60, such as in vitro kinase assay, systematic mutagenesis, western blots. Here, we describe how to study the acetylation of ATM using acetylation-specific antibodies.

  4. Networked ATM for Efficient Routing, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Uncertainties in weather forecasts and traffic congestion sometimes result in inefficient planned flight paths for aircraft operating in the National Airspace System...

  5. Hyper-Spectral Communications, Networking and ATM as Foundation for Safe and Efficient Future Flight: Transcending Aviation Operational Limitations with Diverse and Secure Multi-Band, Multi-Mode, and mmWave Wireless Links: Project Overview, Aviation Communications and New Signaling

    Science.gov (United States)

    Matolak, David W.

    2017-01-01

    NASA's Aeronautics Research Mission Directorate (ARMD) has recently solicited proposals and awarded funds for research and development to achieve and exceed the goals envisioned in the ARMD Strategic Implementation Plan (SIP). The Hyper-Spectral Communications and Networking for Air Traffic Management (ATM) (HSCNA) project is the only University Leadership Initiative (ULI) program to address communications and networking (and to a degree, navigation and surveillance). This paper will provide an overview of the HSCNA project, and specifically describe two of the project's technical challenges: comprehensive aviation communications and networking assessment, and proposed multi-band and multimode communications and networking. The primary goals will be described, as will be research and development aimed to achieve and exceed these goals. Some example initial results are also provided.

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

    International Nuclear Information System (INIS)

    Wang, Jufang; Su, Fengtao; Smilenov, Lubomir B; Zhou, Libin; Hu, Wentao; Ding, Nan; Zhou, Guangming

    2011-01-01

    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. 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. 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. 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

  7. 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.

  8. An asynchronous data-driven event-building scheme based on ATM switching fabrics

    International Nuclear Information System (INIS)

    Letheren, M.; Christiansen, J.; Mandjavidze, I.; Verhille, H.; De Prycker, M.; Pauwels, B.; Petit, G.; Wright, S.; Lumley, J.

    1994-01-01

    The very high data rates expected in experiments at the next generation of high luminosity hadron colliders will be handled by pipelined front-end readout electronics and multiple levels (2 or 3) of triggering. A variety of data acquisition architectures have been proposed for use downstream of the first level trigger. Depending on the architecture, the aggregate bandwidths required for event building are expected to be of the order 10--100 Gbit/s. Here, an Asynchronous Transfer Mode (ATM) packet-switching network technology is proposed as the interconnect for building high-performance, scalable data acquisition architectures. This paper introduces the relevant characteristics of ATM and describes components for the construction of an ATM-based event builder: (1) a multi-path, self-routing, scalable ATM switching fabric, (2) an experimental high performance workstation ATM-interface, and (3) a VMEbus ATM-interface. The requirement for traffic shaping in ATM-based event-builders is discussed and an analysis of the performance of several such schemes is presented

  9. 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 ...

  10. Activation of ATM by DNA Damaging Agents

    National Research Council Canada - National Science Library

    Kurz, Ebba U; Lees-Miller, Susan P

    2004-01-01

    Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase that acts as a master switch controlling the cell cycle in response to ionizing radiation-induced DNA double-strand breaks (DSBs...

  11. Activation of ATM by DNA Damaging Agents

    National Research Council Canada - National Science Library

    Kurz, Ebba U; Lees-Miller, Susan P

    2005-01-01

    Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase that acts as a master switch controlling the cell cycle in response to ionizing radiation-induced DNA double-strand breaks (DSBs...

  12. ATM Card Cloning and Ethical Considerations.

    Science.gov (United States)

    Kaur, Paramjit; Krishan, Kewal; Sharma, Suresh K; Kanchan, Tanuj

    2018-05-01

    With the advent of modern technology, the way society handles and performs monetary transactions has changed tremendously. The world is moving swiftly towards the digital arena. The use of Automated Teller Machine (ATM) cards (credit and debit) has led to a "cash-less society" and has fostered digital payments and purchases. In addition to this, the trust and reliance of the society upon these small pieces of plastic, having numbers engraved upon them, has increased immensely over the last two decades. In the past few years, the number of ATM fraud cases has increased exponentially. With the money of the people shifting towards the digital platform, ATM skimming has become a problem that has eventually led to a global outcry. The present review discusses the serious repercussions of ATM card cloning and the associated privacy, ethical and legal concerns. The preventive measures which need to be taken and adopted by the government authorities to mitigate the problem have also been discussed.

  13. 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.

  14. Biomimicry 1: PC.

    Science.gov (United States)

    Cumberland, D C; Gunn, J; Malik, N; Holt, C M

    1998-01-01

    The surface properties of stents can be modified by coating them, for example with a polymer. Phosphorylcoline (PC) is the major component of the outer layer of the cell membrane. The haemo- and biocompatibility of a PC-containing polymer is thus based on biomimicry, and has been confirmed by several experiments showing much reduced thrombogenicity of PC-coated surfaces, and porcine coronary artery implants showing no sign of adverse effect. Clinical experience with the PC-coated BiodivYsio appears favourable. The PC coating can be tailored for take up and controlled elution of various drugs for stent-based local delivery, a property which is being actively explored.

  15. Ataxia-telangiectasia gene (ATM) mutation heterozygosity in breast cancer: a narrative review.

    Science.gov (United States)

    Jerzak, K J; Mancuso, T; Eisen, A

    2018-04-01

    Despite the fact that heterozygosity for a pathogenic ATM variant is present in 1%-2% of the adult population, clinical guidelines to inform physicians and genetic counsellors about optimal management in that population are lacking. In this narrative review, we describe the challenges and controversies in the management of women who are heterozygous for a pathogenic ATM variant with respect to screening for breast and other malignancies, to choices for systemic therapy, and to decisions about radiation therapy. Given that the lifetime risk for breast cancer in women who are heterozygous for a pathogenic ATM variant is likely greater than 25%, those women should undergo annual mammographic screening starting at least by 40 years of age. For women in this group who have a strong family history of breast cancer, earlier screening with both magnetic resonance imaging and mammography should be considered. High-quality data to inform the management of established breast cancer in carriers of pathogenic ATM variants are lacking. Although deficiency in the ATM gene product might confer sensitivity to dna-damaging pharmaceuticals such as inhibitors of poly (adp-ribose) polymerase or platinum agents, prospective clinical trials have not been conducted in the relevant patient population. Furthermore, the evidence with respect to radiation therapy is mixed; some data suggest increased toxicity, and other data suggest improved clinical benefit from radiation in women who are carriers of a pathogenic ATM variant. As in the 2017 U.S. National Comprehensive Cancer Network guidelines, we recommend high-risk imaging for women in Ontario who are heterozygous for a pathogenic ATM variant. Currently, ATM carrier status should not influence decisions about systemic or radiation therapy in the setting of an established breast cancer diagnosis.

  16. Aurora-B Mediated ATM Serine 1403 Phosphorylation Is Required For Mitotic ATM Activation and the Spindle Checkpoint

    OpenAIRE

    Yang, Chunying; Tang, Xi; Guo, Xiaojing; Niikura, Yohei; Kitagawa, Katsumi; Cui, Kemi; Wong, Stephen T.C.; Fu, Li; Xu, Bo

    2011-01-01

    The ATM kinase plays a critical role in the maintenance of genetic stability. ATM is activated in response to DNA damage and is essential for cell cycle checkpoints. Here, we report that ATM is activated in mitosis in the absence of DNA damage. We demonstrate that mitotic ATM activation is dependent on the Aurora-B kinase and that Aurora-B phosphorylates ATM on serine 1403. This phosphorylation event is required for mitotic ATM activation. Further, we show that loss of ATM function results in...

  17. 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...... 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 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...

  18. Health ATMs in Saudi Arabia: A Perspective.

    Science.gov (United States)

    Aldosari, Bakheet

    2017-06-01

    Health ATMs are terminals which are connected to a centrally located database storing patients' electronic healthcare records (EHR). These machines are capable of collecting information in a far superior fashion than humans and are also able to rectify obsolete data in a manner that humans are generally not inclined to. The main goal of this study is to assess the importance of adopting health ATMs in the Kingdom of Saudi Arabia (KSA), which can improve the confidence of patients, reward health self-management, and achieve positive health outcomes through their easy-to-use applications that are secure and accessible through various devices. Strength, Weakness, Opportunity, and Threat (SWOT) analysis was used to assess the efficiency of adopting health ATMs in KSA and reveal the said characteristics. Three focus groups assembled in the cities of Riyadh, Jeddah and Dammam during the period 2013-2014. The groups consisted of individuals experienced in the function of health ATMs. It was found that the sector possessed a number of strengths that would help it in reaching the goals outlined therein, thereby achieving successful outcomes. Health ATMs could be a promising new advancement in the field of health if the project were to be planned and implemented correctly. Their benefits would consequently reach organizational and national levels. It is, therefore, crucial to educate the project managers about the benefits of learning from others as well as educating them about the needs and the requirements of the concerned organization.

  19. Recent studies on the ATM gene

    International Nuclear Information System (INIS)

    Lavin, M.F.; Khanna, K.K.; Waters, D.

    1996-01-01

    Full text: Radiosensitivity is a universal characteristic of ataxia-telangiectasia (A-T), observed after exposure of patients and of cells in culture to radiation. This sensitivity is manifested as higher levels of radiation-induced chromosomal aberrations and reduced survival compared to controls. The gene for A-T was mapped to chromosome 11q 22-23 seven years ago and more recently we have been involved in the cloning of a single gene, ATM (ataxia-telangiectasia mutated), mutated in this syndrome. ATM is a large gene, approximately 150 kb in size, composed of 66 exons and codes for a major mRNA of 13 kb with a predicted open reading frame of 9.135 kb. It is not yet known what activity the ATM gene product possesses, but the ralatedness of this gene sequence to the phosphatidylinositol 3-kinase gene family supports a role for ATM in intracellular signalling. Considerable information is already available on defective signalling through the p53 damage-inducible pathway in A-T. This includes failure to arrest at either the G1/S or G2/M checkpoints as well as radioresistant DNA synthesis. A reduced and/or delayed response in the induction of p53 after exposure of A-T cells to ionizing radiation can account for the defective G1/S checkpoint. More recently we have demonstrated that the ATM gene product is involved in the control of multiple cell cycle checkpoints. Antibodies prepared against ATM peptides demonstrate the presence of a protein 350 kDa in size, which is the predicted size for this protein based on open reading frame of 9 kb. This protein is present both in the nucleus and in the cytoplasm where it is present in vesicular structures. As expected from mutation data the ATM protein is absent in cells from some patients with A-T. The cloning of the ATM gene will allow for screening of radiosensitive patients for mutations in this gene and will provide a means of identifying interacting proteins and thus an understanding of how it functions

  20. 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..

  1. Comparison of performance between TCP/IP over ATM e ATM nativo

    OpenAIRE

    Marcelo Silva Freitas

    2001-01-01

    Com o recente desenvolvimento de tecnologias de redes de altas taxas de transmissão, tais como Asynchronous Transfer Mode (ATM), o problema da carência por largura de banda foi solucionado. A questão atual é a implementação de sistemas que suportem os protocolos ATM de forma nativa e integral. Atualmente tem-se utilizado aplicativos tradicionais baseados nos protocolos TCP(UDP)/IP no topo da pilha de protocolos ATM. Tal modelo traz redundâncias que implicam diretamente em aumento de overhead ...

  2. IBM PC/IX operating system evaluation plan

    Science.gov (United States)

    Dominick, Wayne D. (Editor); Granier, Martin; Hall, Philip P.; Triantafyllopoulos, Spiros

    1984-01-01

    An evaluation plan for the IBM PC/IX Operating System designed for IBM PC/XT computers is discussed. The evaluation plan covers the areas of performance measurement and evaluation, software facilities available, man-machine interface considerations, networking, and the suitability of PC/IX as a development environment within the University of Southwestern Louisiana NASA PC Research and Development project. In order to compare and evaluate the PC/IX system, comparisons with other available UNIX-based systems are also included.

  3. Automated Transportation Management System (ATMS) Configuration Management Plan. Revision 1

    International Nuclear Information System (INIS)

    Weidert, R.S.

    1994-01-01

    This document describes the Software Configuration Management (SCM) approach and procedures to be utilized in developing and maintaining the Automated Transportation Management System (ATMS). The configuration management procedures are necessary to ensure that any changes made to software and related documentation are consistent with ATMS goals and contained securely in a central library. This plan applies to all software and associated documentation used in producing ATMS V1.0 and ATMS V2.0 system

  4. PC-BLAS, PC Linear Algebra Subroutines

    International Nuclear Information System (INIS)

    Hanson, R.J.

    1989-01-01

    1 - Description of program or function: PC-BLAS is a highly optimized version of the Basic Linear Algebra Subprograms (BLAS), a standardized set of 38 routines that perform low-level operations on vectors of numbers in single- and double-precision real and complex arithmetic. Routines are included to find the index of the largest component of a vector, apply a Givens or modified Givens rotation, multiply a vector by a constant, determine the Euclidean length, perform a dot product, swap and copy vectors, and find the norm of a vector. 2 - Restrictions on the complexity of the problem: The number of components in any vector and the spacing or stride between their entries must not exceed 32,767 (2 15 -1). PC-BLAS will not work with an 80286 CPU operating in 'protected' mode

  5. Implementasi Penggunaan Smartphone Android untuk Control PC (Personal Computer

    Directory of Open Access Journals (Sweden)

    Imam Solikin

    2018-05-01

    Full Text Available The purpose of this research is to simplify the control of personal computer (PC such as control pointer, keyboard control and make it easier to do the presentation by controlling the slide remotely using smartphone through wifi connections facility. The smartphone is a multimedia phone that combines PC functionality with microprocessor, memory, and built-in modem to produce smart smartphone gadgets. Problems that occur when performing a presentation such as PC control, control pointer and keyboard control for input should be close to the PC so it is less than optimal in explaining the material. The model used in implementing the use of Android Smartphone for PC control is a conceptual model consisting of several stages: potential and problems, data collection, system testing, test results, and system implementation or implementation. From the results of PC control research can be done by connecting the Smartphone with a PC via wifi network so that PC can be controlled remotely. PC control application is an application that can control PC remotely connected via wifi network connection. Benefits derived from this research make it easy to mengedalikan PC remotely such as facilitate in the percentage and control pointer and control Keyboard for input process.

  6. 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.

  7. PC clusters at CERN's PC farm

    CERN Multimedia

    Patrice Loïez

    2001-01-01

    These Linux-based PC clusters are mainly used for batch and interactive data processing. When the LHC starts operation in 2008, it will produce enough data every year to fill a stack of CDS 20 km tall, so high quality processing is required. To further facilitate this the LHC Computing Grid (LCG) has been set up to share processing power between facilities around the world.

  8. The PC graphics handbook

    CERN Document Server

    Sanchez, Julio

    2003-01-01

    Part I - Graphics Fundamentals PC GRAPHICS OVERVIEW History and Evolution Short History of PC Video PS/2 Video Systems SuperVGA Graphics Coprocessors and Accelerators Graphics Applications State-of-the-Art in PC Graphics 3D Application Programming Interfaces POLYGONAL MODELING Vector and Raster Data Coordinate Systems Modeling with Polygons IMAGE TRANSFORMATIONS Matrix-based Representations Matrix Arithmetic 3D Transformations PROGRAMMING MATRIX TRANSFORMATIONS Numeric Data in Matrix Form Array Processing PROJECTIONS AND RENDERING Perspective The Rendering Pipeline LIGHTING AND SHADING Lightin

  9. Leo II PC

    Data.gov (United States)

    Kansas Data Access and Support Center — LEO II is a second-generation software system developed for use on the PC, which is designed to convert location references accurately between legal descriptions and...

  10. 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

    2016-01-01

    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

  11. Atm reactivation reverses ataxia telangiectasia phenotypes in vivo.

    Science.gov (United States)

    Di Siena, Sara; Campolo, Federica; Gimmelli, Roberto; Di Pietro, Chiara; Marazziti, Daniela; Dolci, Susanna; Lenzi, Andrea; Nussenzweig, Andre; Pellegrini, Manuela

    2018-02-22

    Hereditary deficiencies in DNA damage signaling are invariably associated with cancer predisposition, immunodeficiency, radiation sensitivity, gonadal abnormalities, premature aging, and tissue degeneration. ATM kinase has been established as a central player in DNA double-strand break repair and its deficiency causes ataxia telangiectasia, a rare, multi-system disease with no cure. So ATM represents a highly attractive target for the development of novel types of gene therapy or transplantation strategies. Atm tamoxifen-inducible mouse models were generated to explore whether Atm reconstitution is able to restore Atm function in an Atm-deficient background. Body weight, immunodeficiency, spermatogenesis, and radioresistance were recovered in transgenic mice within 1 month from Atm induction. Notably, life span was doubled after Atm restoration, mice were protected from thymoma and no cerebellar defects were observed. Atm signaling was functional after DNA damage in vivo and in vitro. In summary, we propose a new Atm mouse model to investigate novel therapeutic strategies for ATM activation in ataxia telangiectasia disease.

  12. ATM induction insufficiency in a radiosensitive breast-cancer patient

    International Nuclear Information System (INIS)

    Clarke, R.A.; Fang, Z.H.; Marr, P.J.; Kearsley, J.H.; Papadatos, G.; Lee, C.S.; University of Sydney, Camperdown, NSW

    2002-01-01

    ATM induction insufficiency in a radiosensitive breast-cancer patient The ataxia telangiectasia (A-T) gene (ATM) is a dominant breast cancer gene with tumour suppressor activity. ATM also regulates cellular sensitivity to ionising radiation (IR) presumably through its role as a facilitator of DNA repair. In normal cells and tissues the ATM protein is rapidly induced by IR to threshold/maximum levels. The kinase function of the ATM protein is also rapidly activated in response to IR. The fact that women carriers of ATM mutations can have an increased risk of developing breast cancer and that many sporadic breast tumours have reduced levels of the ATM protein broadens the scope of ATM's tumour suppressor within the breast. This report describes the downregulation of ATM protein levels in a radiosensitive breast cancer patient. Postinduction ATM levels were up to tenfold lower in the patient's fresh tissues compared to normal controls. These results might indicate a much broader role for ATM anomalies in breast cancer aetiology. Copyright (2002) Blackwell Science Pty Ltd

  13. Tyrosine 370 phosphorylation of ATM positively regulates DNA damage response

    Science.gov (United States)

    Lee, Hong-Jen; Lan, Li; Peng, Guang; Chang, Wei-Chao; Hsu, Ming-Chuan; Wang, Ying-Nai; Cheng, Chien-Chia; Wei, Leizhen; Nakajima, Satoshi; Chang, Shih-Shin; Liao, Hsin-Wei; Chen, Chung-Hsuan; Lavin, Martin; Ang, K Kian; Lin, Shiaw-Yih; Hung, Mien-Chie

    2015-01-01

    Ataxia telangiectasia mutated (ATM) mediates DNA damage response by controling irradiation-induced foci formation, cell cycle checkpoint, and apoptosis. However, how upstream signaling regulates ATM is not completely understood. Here, we show that upon irradiation stimulation, ATM associates with and is phosphorylated by epidermal growth factor receptor (EGFR) at Tyr370 (Y370) at the site of DNA double-strand breaks. Depletion of endogenous EGFR impairs ATM-mediated foci formation, homologous recombination, and DNA repair. Moreover, pretreatment with an EGFR kinase inhibitor, gefitinib, blocks EGFR and ATM association, hinders CHK2 activation and subsequent foci formation, and increases radiosensitivity. Thus, we reveal a critical mechanism by which EGFR directly regulates ATM activation in DNA damage response, and our results suggest that the status of ATM Y370 phosphorylation has the potential to serve as a biomarker to stratify patients for either radiotherapy alone or in combination with EGFR inhibition. PMID:25601159

  14. Study of ATM Phosphorylation by Cdk5 in Neuronal Cells.

    Science.gov (United States)

    She, Hua; Mao, Zixu

    2017-01-01

    The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) plays a central role in coordinating the DNA damage responses including cell cycle checkpoint control, DNA repair, and apoptosis. Mutations of ATM cause a spectrum of defects ranging from neurodegeneration to cancer predisposition. We previously showed that Cdk5 (cyclin-dependent kinase 5) is activated by DNA damage and directly phosphorylates ATM at serine 794 in postmitotic neurons. Phosphorylation at serine 794 precedes and is required for ATM autophosphorylation at serine 1981, and activates ATM kinase activity. Cdk5-ATM pathway plays a crucial role in DNA damage-induced neuronal injury. This chapter describes protocols used in analyzing ATM phosphorylation by Cdk5 in CGNs (cerebellar granule neurons) and its effects on neuronal survival.

  15. 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.

  16. Preventive Methods for ATM Mode Control

    OpenAIRE

    Ivan Baronak; Robert Trska

    2004-01-01

    Broadband transfer mode ATM represent one of alternative solutions for growing requirements on transfer capabilities. Its advantage is an effort for provisions of guaranteed quality of transport services with preservations of high transfer rate. This property is covered by several mechanisms, which role is to control not only the traffic of existing connections, but also the admission of new ones and prevent the violation of requirements on transport quality of existing and new connections.

  17. 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

  18. 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

  19. Test and evaluation of the Malicious Activity Simulation Tool (MAST) in a Local Area Network (LAN) running the Common PC Operating System Environment (COMPOSE)

    OpenAIRE

    Littlejohn, Aaron M.; Makhlouf, Ehab

    2013-01-01

    APPLIED CYBER OPERATIONS CAPSTONE PROJECT REPORT Approved for public release; distribution is unlimited In the Department of the Navys layered defense approach to protecting a computer network, it is the networks administrators who provide the last layer of defense before the end user. Training network administrators is a rather expensive and time consuming process. However, this training needs to be provided on a regular basis in order to refresh their readiness and to train them to re...

  20. OPTIMIZATION OF ATM AND BRANCH CASH OPERATIONS USING AN INTEGRATED CASH REQUIREMENT FORECASTING AND CASH OPTIMIZATION MODEL

    Directory of Open Access Journals (Sweden)

    Canser BİLİR

    2018-04-01

    Full Text Available In this study, an integrated cash requirement forecasting and cash inventory optimization model is implemented in both the branch and automated teller machine (ATM networks of a mid-sized bank in Turkey to optimize the bank’s cash supply chain. The implemented model’s objective is to minimize the idle cash levels at both branches and ATMs without decreasing the customer service level (CSL by providing the correct amount of cash at the correct location and time. To the best of our knowledge, the model is the first integrated model in the literature to be applied to both ATMs and branches simultaneously. The results demonstrated that the integrated model dramatically decreased the idle cash levels at both branches and ATMs without degrading the availability of cash and hence customer satisfaction. An in-depth analysis of the results also indicated that the results were more remarkable for branches. The results also demonstrated that the utilization of various seasonal indices plays a very critical role in the forecasting of cash requirements for a bank. Another unique feature of the study is that the model is the first to include the recycling feature of ATMs. The results demonstrated that as a result of the inclusion of the deliberate seasonal indices in the forecasting model, the integrated cash optimization models can be used to estimate the cash requirements of recycling ATMs.

  1. Transforming PC Power Supplies into Smart Car Battery Conditioners

    Science.gov (United States)

    Rodriguez-Ascariz, J. M.; Boquete-Vazquez, L.

    2011-01-01

    This paper describes a laboratory project consisting of a PC power supply modification into an intelligent car-battery conditioner with both wireless and wired networking capabilities. Adding a microcontroller to an average PC power supply transforms it into a flexible, intelligent device that can be configured and that is suitable to keep car…

  2. 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 G 2 /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. The DNA damage response (DDR) is essential for prevention of a broad spectrum of different human neurologic diseases. However, a detailed understanding of the DDR at a physiological level is lacking. In contrast to many in

  3. 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.

  4. Building the perfect PC

    CERN Document Server

    Thompson, Robert Bruce

    2006-01-01

    This popular Build-It-Yourself (BIY) PC book covers everything you want to know about building your own system: Planning and picking out the right components, step-by-step instructions for assembling your perfect PC, and an insightful discussion of why you'd want to do it in the first place. Most big brand computers from HP, Dell and others use lower-quality components so they can meet their aggressive pricing targets. But component manufacturers also make high-quality parts that you can either purchase directly, or obtain through distributors and resellers. Consumers and corporations

  5. Dancing on damaged chromatin. Functions of ATM and the RAD50/MRE11/NBS1 complex in cellular responses to DNA damage

    International Nuclear Information System (INIS)

    Iijima, Kenta; Ohara, Maki; Seki, Ryota; Tauchi, Hiroshi

    2008-01-01

    In order to preserve and protect genetic information, eukaryotic cells have developed a signaling or communications network to help the cell respond to DNA damage, and ATM and NBS1 are key players in this network. ATM is a protein kinase which is activated immediately after a DNA double strand break (DSB) is formed, and the resulting signal cascade generated in response to cellular DSBs is regulated by post-translational protein modifications such as phosphorylation and acetylation. In addition, to ensure the efficient functioning of DNA repair and cell cycle checkpoints, the highly ordered structure of eukaryotic chromatin must be appropriately altered to permit access of repair-related factors to DNA. These alterations are termed chromatin remodeling, and are executed by a specific remodeling complex in conjunction with histone modifications. Current advances in the molecular analysis of DNA damage responses have shown that the auto-phosphorylation of ATM and the interaction between ATM and NBS1 are key steps for ATM activation, and that the association of ATM and NBS1 is involved in chromatin remodeling. Identification of novel factors which function in ubiquitination (RNF8, Ubc13, Rap80, etc.) has also enabled us to understand more details of the early stages in DNA repair pathways which respond to DSBs. In this review, the focus is on the role of ATM and the RAD50/MRE11/NBS1 complex in DSB response pathways, and their role in DSB repair and in the regulation of chromatin remodeling. (author)

  6. Susceptibility of ATM-deficient pancreatic cancer cells to radiation.

    Science.gov (United States)

    Ayars, Michael; Eshleman, James; Goggins, Michael

    2017-05-19

    Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay. We find that while rendering pancreatic cancer cells ATM-deficient did not significantly change their sensitivity to several chemotherapeutics, it did render them exquisitely sensitized to radiation. Pancreatic cancer ATM status may help predict response to radiotherapy.

  7. Identification of ATM Protein Kinase Phosphorylation Sites by Mass Spectrometry.

    Science.gov (United States)

    Graham, Mark E; Lavin, Martin F; Kozlov, Sergei V

    2017-01-01

    ATM (ataxia-telangiectasia mutated) protein kinase is a key regulator of cellular responses to DNA damage and oxidative stress. DNA damage triggers complex cascade of signaling events leading to numerous posttranslational modification on multitude of proteins. Understanding the regulation of ATM kinase is therefore critical not only for understanding the human genetic disorder ataxia-telangiectasia and potential treatment strategies, but essential for deciphering physiological responses of cells to stress. These responses play an important role in carcinogenesis, neurodegeneration, and aging. We focus here on the identification of DNA damage inducible ATM phosphorylation sites to understand the importance of autophosphorylation in the mechanism of ATM kinase activation. We demonstrate the utility of using immunoprecipitated ATM in quantitative LC-MS/MS workflow with stable isotope dimethyl labeling of ATM peptides for identification of phosphorylation sites.

  8. 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.

  9. MPLS y ATM como tecnologías backbone para la transferencia de videoconferencia

    Directory of Open Access Journals (Sweden)

    Danilo López

    2012-09-01

    Full Text Available This article presents the results obtained by modeling the performance of a core IP/ATM network compared to a CRLDP/IP/MPLS network when carrying delay sensitive traffic (videoconferencing with minimum resource reservation guarantees and optimal interaction between user and applications. In order conduct the experiments, OPNET-modeler simulation software (educational version was used, which encouraged alternative implementation features that help decide which of the two technologies represents a suitable solution for current networking problems, where large volumes of information need to be transmitted and the QoS offered to average users is pretty poor.

  10. ATM-induced radiosensitization in vitro and in vivo

    International Nuclear Information System (INIS)

    Choi, E. K.; Ahn, S. D.; Rhee, Y. H.; Chung, H. S.; Ha, S. W; Song, C. W.; Griffin, R. J.; Park, H. J.

    2003-01-01

    It has been known that ATM plays a central role in response of cells to ionizing radiation by enhancing DNA repair. We have investigated the feasibility of increasing radiosensitivity of tumor cells with the use of ATM inhibitors such as caffeine, pentoxifylline and wortmannin. Human colorectal cancer RKO.C cells and RKO-ATM cells (RKO cells overexpressing ATM) were used in the present study. The clonogenic cell survival in vitro indicated that RKO-ATM cells were markedly radioresistant than RKO.C cells. Treatment with 3 mM of caffeine significantly increased the radiosensitivity of cells, particulary the RKO-ATM cells, so that the radiosensitivity of RKO.C cells and RKO-ATM cells were almost similar. The radiation induced G2/M arrest in RKO-ATM cells was noticeably longer than that in RKO.C cells and caffeine treatment significantly reduced the length of the radiation induced G2/M arrest in both RKO.C and RKO-ATM cells. Pentoxifylline and wortmannin were also less effective than caffeine to radiosensitize RKO.C or RKO-ATM cells. However, wortmannin was more effective than caffeine against human lung adenocarcinoma A549 cells indicating the efficacy of ATM inhibitor to increase radiosensitivity is cell line dependent. For in vivo study, RKO.C cells were injected s.c. into the hind-leg of BALB/c-nuslc nude mice, and allowed to grow to 130mm3 tumor. The mice were i.p. injected with caffeine solution or saline and the tumors irradiated with 10 Gy of X-rays. The radiation induced growth delay was markedly increased by 1-2 mg/g of caffeine. It was concluded that caffeine increases radiosensitivity of tumor cells by inhibiting ATM kinase function, thereby inhibiting DNA repair, that occurs during the G2/M arrest after radiation

  11. 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.

  12. Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

    DEFF Research Database (Denmark)

    Munk, Stephanie; Sigurðsson, Jón Otti; Xiao, Zhenyu

    2017-01-01

    The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM)-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essentia....... They analyze changes in the SUMO and phosphoproteome after MMC and hydroxyurea treatments and find that the DNA damage response kinases ATR and ATM globally regulate SUMOylation upon replication stress and fork breakage....

  13. The mammalian mid-pachytene checkpoint: meiotic arrest in spermatocytes with a mutation in Atm alone or in combination with a Trp53 (p53) or Cdkn1a (p21/cip1) mutation

    NARCIS (Netherlands)

    Ashley, T.; Westphal, C.; Plug-de Maggio, A.; de rooij, D. G.

    2004-01-01

    ATM, the protein product of the gene mutated in the human autosomal recessive disorder ataxia telangiectasia, is involved in detection of double strand breaks (DSBs) and is a key component of the damage surveillance network of cell cycle proteins. In somatic cells ATM phosphorylates many other

  14. 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. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  15. 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

    2016-01-01

    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. PMID:26420831

  16. ATM (ataxia-telangiectasia mutated) abnormality and diseases

    International Nuclear Information System (INIS)

    Takagi, Masatoshi; Nakata, Shinichiro; Mizutani, Shuki

    2007-01-01

    Ataxia-Telangiectasia (A-T) is an autosomal recessive inherited disease due to mutation of ATM gene on chromosome 11q22.3, with major symptoms of ataxia, telangiectasia, immunodeficiency and frequent complication of cancer, and the cells have characters of chromosomal break, high sensitivity to radiation and inappropriate continuation of DNA synthesis after radiation. This review describes past and present studies of ATM functions with clinical features in the following order: Clinical symptoms and epidemiology; ATM gene mutation in A-T patients, mainly by frame-shift (80-90%); ATM, whose gene consisted from 66 exons (150 kb), functions in phosphoinositide-3-kinase related kinase family which protecting cells from stress and integrating their system, at response to DNA double strand break, and in the cell cycle checkpoints at G1/S, S and G2/M phases; ATM nonsense/missense mutations in embryonic cells leading to carcinogenesis and role of ATM in the suppression of carcinogenesis in somatic cells; Chromosomal translocation which relating to carcinogenesis, by functional defect of ATM; and Other functions of ATM in neuronal growth, immunodeficiency, carbohydrate and lipid metabolism, early senescence, and virus infection. ATM is thus an essential molecule to maintain growth and homeostasis. (T.I.)

  17. OPTIMIZATION OF ATM AND BRANCH CASH OPERATIONS USING AN INTEGRATED CASH REQUIREMENT FORECASTING AND CASH OPTIMIZATION MODEL

    OpenAIRE

    Canser BİLİR

    2018-01-01

    In this study, an integrated cash requirement forecasting and cash inventory optimization model is implemented in both the branch and automated teller machine (ATM) networks of a mid-sized bank in Turkey to optimize the bank’s cash supply chain. The implemented model’s objective is to minimize the idle cash levels at both branches and ATMs without decreasing the customer service level (CSL) by providing the correct amount of cash at the correct location and time. To the best of our knowledge,...

  18. ATM, radiation, and the risk of second primary breast cancer.

    Science.gov (United States)

    Bernstein, Jonine L; Concannon, Patrick

    2017-10-01

    It was first suggested more than 40 years ago that heterozygous carriers for the human autosomal recessive disorder Ataxia-Telangiectasia (A-T) might also be at increased risk for cancer. Subsequent studies have identified the responsible gene, Ataxia-Telangiectasia Mutated (ATM), characterized genetic variation at this locus in A-T and a variety of different cancers, and described the functions of the ATM protein with regard to cellular DNA damage responses. However, an overall model of how ATM contributes to cancer risk, and in particular, the role of DNA damage in this process, remains lacking. This review considers these questions in the context of contralateral breast cancer (CBC). Heterozygous carriers of loss of function mutations in ATM that are A-T causing, are at increased risk of breast cancer. However, examination of a range of genetic variants, both rare and common, across multiple cancers, suggests that ATM may have additional effects on cancer risk that are allele-dependent. In the case of CBC, selected common alleles at ATM are associated with a reduced incidence of CBC, while other rare and predicted deleterious variants may act jointly with radiation exposure to increase risk. Further studies that characterize germline and somatic ATM mutations in breast cancer and relate the detected genetic changes to functional outcomes, particularly with regard to radiation responses, are needed to gain a complete picture of the complex relationship between ATM, radiation and breast cancer.

  19. Parametric analysis of ATM solar array.

    Science.gov (United States)

    Singh, B. K.; Adkisson, W. B.

    1973-01-01

    The paper discusses the methods used for the calculation of ATM solar array performance characteristics and provides the parametric analysis of solar panels used in SKYLAB. To predict the solar array performance under conditions other than test conditions, a mathematical model has been developed. Four computer programs have been used to convert the solar simulator test data to the parametric curves. The first performs module summations, the second determines average solar cell characteristics which will cause a mathematical model to generate a curve matching the test data, the third is a polynomial fit program which determines the polynomial equations for the solar cell characteristics versus temperature, and the fourth program uses the polynomial coefficients generated by the polynomial curve fit program to generate the parametric data.

  20. ATM-induced radiosensitization in vitro and in vivo

    International Nuclear Information System (INIS)

    Song, C. W.; Griffin, R. J.; Park, H. J.; Chung, H. S.; Choi, E. K.; Ahn, S. D.; Rhee, Y. H.; Ha, S. W.

    2002-01-01

    It has been known that ATM plays a central role in response of cells to ionizing radiation by enhancing DNA repair. Based in large part on studies of the homologous proteins in yeast, it is predicted that ATM function as proximal signal transducers in G1, S, and G2 checkpoint pathways. With the exception of p53, the downstream components of these pathways remain largely undefined. We have investigated the feasibility of increasing radiosensitivity of tumor cells with the use of ATM inhibitors such as caffeine, pentoxifylline, and wortmannin. Also in an effort to examine and understand the molecular mechanism by which ATM might exert its cellular effects, we have expressed the full length wild type ATM in RKO cells

  1. PC Scene Generation

    Science.gov (United States)

    Buford, James A., Jr.; Cosby, David; Bunfield, Dennis H.; Mayhall, Anthony J.; Trimble, Darian E.

    2007-04-01

    AMRDEC has successfully tested hardware and software for Real-Time Scene Generation for IR and SAL Sensors on COTS PC based hardware and video cards. AMRDEC personnel worked with nVidia and Concurrent Computer Corporation to develop a Scene Generation system capable of frame rates of at least 120Hz while frame locked to an external source (such as a missile seeker) with no dropped frames. Latency measurements and image validation were performed using COTS and in-house developed hardware and software. Software for the Scene Generation system was developed using OpenSceneGraph.

  2. ORPLOT.PC: a graphic utility for ORMGEN.PC and ORVIRT.PC

    International Nuclear Information System (INIS)

    Inversini, C.; Bryson, J.W.

    1986-06-01

    ORPLOT.PC is an interactive graphic utility for ORMGEN.PC and ORVIRT.PC. It executes on an IBM PC/XT or PC/AT equipped with hard disk, graphic card, and 512K minimum memory. The program is capable of: (1) displaying finite-element meshes generated by ORMGEN.PC complete with node numbers, element numbers, and boundary conditions; and (2) generating deformed mesh plots, contour plots, line (X-Y) plots, and developed surface plots of ORVIRT.PC output. A zooming feature allows detailed inspection of any subregion. Because simplicity and ease of use were important objectives during program development, all commands are entered interactively using free format. The option of automatic or user-defined scaling for most plots is another convenience. Plot files may be created and written to hard disk for subsequent hardcopy to printer or plotter. 2 refs., 7 figs

  3. Scenarios for control and data flows in multiprotocol over ATM

    Science.gov (United States)

    Kujoory, Ali

    1997-10-01

    The multiprotocol over ATM (MPOA), specified by the ATM Forum, provides an architecture for transfer of Internetwork layer packets (Layer 3 datagram such as IP, IPX) over ATM subnets or across the emulated LANs. MPOA provides shortcuts that bypass routers to avoid router bottlenecks. It is a grand union of some of the existing standards such as LANE by the ATM Forum, NHRP by the IETF, and the Q.2931 by ITU. The intent of this paper is to clarify the data flows between pairs of source and destination hosts in an MPOA system. It includes scenarios for both the intra- and inter-subnet flows between different pairs of MPOA end-systems. The intrasubnet flows simply use LANE for address resolution or data transfer. The inter-subnet flows may use a default path for short-lived flows or a shortcut for long-lived flows. The default path uses the LANE and router capabilities. The shortcut path uses LANE plus NHRP for ATM address resoluton. An ATM virtual circuit is established before the data transfer. This allows efficient transfer of internetwork layer packets over ATM for real-time applications.

  4. 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

    2016-05-01

    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.

  5. Investigasi Serangan Malware Njrat Pada PC

    Directory of Open Access Journals (Sweden)

    Devi Rizky Septiani

    2016-12-01

    Full Text Available Malware merupakan salah satu bentuk dari kejahatan komputer yang terjadi pada sebuah sistem jaringan komputer, malware Njrat termasuk jenis Trojan horse. Trojan adalah salah satu jenis malware yang ikut berkembang di dalamnya, yang memungkinkan attacker masuk ke dalam sistem tanpa diketahui oleh pemilik. Penggunaan trojan saat ini lebih ke arah kejahatan dunia maya (cyber crime, salah satu dari malware yang sangat berbahaya karena besarnya dampak kerugian yang ditimbulkan, mulai dari pencurian data penting sampai mengubah hak akses pada PC korban. Sasaran terbanyak penybaran trojan adalah pengguna sistem operasi windows. Penyebaran trojan ini dilakukan dengan metode social engineering, yaitu teknik yang menggunakan kelemahan manusia, sehingga user tanpa curiga langsung mengeksekusi sebuah program yang tidak dikenal.  Aktivitas malware berkaitan erat dengan  performa PC dan juga aktifitas network pada system computer. Penelitian ini bertujuan untuk mengetahui cara kerja malware Njrat dan melakukan investigasi terhadap performa pada system computer. Metodologi yang digunakan dynamic analysis dengan melakukan analisa malware pada suatu sistem dan melihat aktivitas atau proses yang diaktifkan oleh malware tersebut. Dampak perubahan yang terjadi pada PC Target terlihat pada performa masing-masing PC yang telah disisipkan malware. Kata kunci            Malware, Njrat, System computer

  6. Methylation of the ATM promoter in glioma cells alters ionizing radiation sensitivity

    International Nuclear Information System (INIS)

    Roy, Kanaklata; Wang, Lilin; Makrigiorgos, G. Mike; Price, Brendan D.

    2006-01-01

    Glioblastomas are among the malignancies most resistant to radiation therapy. In contrast, cells lacking the ATM protein are highly sensitive to ionizing radiation. The relationship between ATM protein expression and radiosensitivity in 3 glioma cell lines was examined. T98G cells exhibited normal levels of ATM protein, whereas U118 and U87 cells had significantly lower levels of ATM and increased (>2-fold) sensitivity to ionizing radiation compared to T98G cells. The ATM promoter was methylated in U87 cells. Demethylation by azacytidine treatment increased ATM protein levels in the U87 cells and decreased their radiosensitivity. In contrast, the ATM promoter in U118 cells was not methylated. Further, expression of exogenous ATM did not significantly alter the radiosensitivity of U118 cells. ATM expression is therefore heterogeneous in the glioma cells examined. In conclusion, methylation of the ATM promoter may account for the variable radiosensitivity and heterogeneous ATM expression in a fraction of glioma cells

  7. 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.

  8. ATM localization and gene expression in the adult mouse eye.

    Science.gov (United States)

    Leemput, Julia; Masson, Christel; Bigot, Karine; Errachid, Abdelmounaim; Dansault, Anouk; Provost, Alexandra; Gadin, Stéphanie; Aoufouchi, Said; Menasche, Maurice; Abitbol, Marc

    2009-01-01

    High levels of metabolism and oxygen consumption in most adult murine ocular compartments, combined with exposure to light and ultraviolet (UV) radiation, are major sources of oxidative stress, causing DNA damage in ocular cells. Of all mammalian body cells, photoreceptor cells consume the largest amount of oxygen and generate the highest levels of oxidative damage. The accumulation of such damage throughout life is a major factor of aging tissues. Several multiprotein complexes have recently been identified as the major sensors and mediators involved in the maintenance of DNA integrity. The activity of these complexes initially seemed to be restricted to dividing cells, given their ultimate role in major cell cycle checkpoints. However, it was later established that they are also active in post-mitotic cells. Recent findings demonstrate that the DNA damage response (DDR) is essential for the development, maintenance, and normal functioning of the adult central nervous system. One major molecular factor in the DDR is the protein, ataxia telangiectasia mutated (ATM). It is required for the rapid induction of cellular responses to DNA double-strand breaks. These cytotoxic DNA lesions may be caused by oxidative damage. To understand how ATM prevents oxidative stress and participates in the maintenance of genomic integrity and cell viability of the adult retina, we determined the ATM expression patterns and studied its localization in the adult mouse eye. Atm gene expression was analyzed by RT-PCR experiments and its localization by in situ hybridization on adult mouse ocular and cerebellar tissue sections. ATM protein expression was determined by western blot analysis of proteins homogenates extracted from several mouse tissues and its localization by immunohistochemistry experiments performed on adult mouse ocular and cerebellar tissue sections. In addition, subcellular localization was realized by confocal microscopy imaging of ocular tissue sections, with a special

  9. 76 FR 5467 - Airworthiness Directives; Pilatus Aircraft Ltd. Models PC-6, PC-6-H1, PC-6-H2, PC-6/350, PC-6/350...

    Science.gov (United States)

    2011-02-01

    ...;Prices of new books are listed in the first FEDERAL REGISTER issue of each #0;week. #0; #0; #0; #0;#0..., Fairchild Heli Porter PC-6 airplanes, or Fairchild-Hiller Corporation PC-6 airplanes. Discussion Section... [[Page 5469

  10. Repairing and Upgrading Your PC

    CERN Document Server

    Thompson, Robert

    2009-01-01

    Repairing and Upgrading Your PC delivers start-to-finish instructions, simple enough for even the most inexperienced PC owner, for troubleshooting, repairing, and upgrading your computer. Written by hardware experts Robert Bruce Thompson and Barbara Fritchman Thompson, this book covers it all: how to troubleshoot a troublesome PC, how to identify which components make sense for an upgrade, and how to tear it all down and put it back together. This book shows how to repair and upgrade all of your PC's essential components.

  11. 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.

  12. Recent Greenland Thinning from Operation IceBridge ATM and LVIS Data

    Science.gov (United States)

    Sutterley, T. C.; Velicogna, I.

    2015-12-01

    We investigate regional thinning rates in Greenland using two Operation IceBridge lidar instruments, the Airborne Topographic Mapper (ATM) and the Land, Vegetation and Ice Sensor (LVIS). IceBridge and Pre-IceBridge ATM data are available from 1993 to present and IceBridge and Pre-Icebridge LVIS data are available from 2007 to present. We compare different techniques for combining the two datasets: overlapping footprints, triangulated irregular network meshing and radial basis functions. We validate the combination for periods with near term overlap of the two instruments. By combining the two lidar datasets, we are able to investigate intra-annual, annual, interannual surface elevation change. We investigate both the high melt season of 2012 and the low melt season of 2013. In addition, the major 2015 IceBridge Arctic campaign provides new crucial data for determining seasonal ice sheet thinning rates. We compare our LVIS/ATM results with surface mass balance outputs from two regional climate models: the Regional Atmospheric Climate Model (RACMO) and the Modèle Atmosphérique Régional (MAR). We also investigate the thinning rates of major outlet glaciers.

  13. Virtual C Machine and Integrated Development Environment for ATMS Controllers.

    Science.gov (United States)

    2000-04-01

    The overall objective of this project is to develop a prototype virtual machine that fits on current Advanced Traffic Management Systems (ATMS) controllers and provides functionality for complex traffic operations.;Prepared in cooperation with Utah S...

  14. An HTRF® Assay for the Protein Kinase ATM.

    Science.gov (United States)

    Adams, Phillip; Clark, Jonathan; Hawdon, Simon; Hill, Jennifer; Plater, Andrew

    2017-01-01

    Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase that plays a key role in the regulation of DNA damage pathways and checkpoint arrest. In recent years, there has been growing interest in ATM as a therapeutic target due to its association with cancer cell survival following genotoxic stress such as radio- and chemotherapy. Large-scale targeted drug screening campaigns have been hampered, however, by technical issues associated with the production of sufficient quantities of purified ATM and the availability of a suitable high-throughput assay. Using a purified, functionally active recombinant ATM and one of its physiological substrates, p53, we have developed an in vitro FRET-based activity assay that is suitable for high-throughput drug screening.

  15. Cost-benefit analysis of the ATM automatic deposit service

    Directory of Open Access Journals (Sweden)

    Ivica Županović

    2015-03-01

    Full Text Available Bankers and other financial experts have analyzed the value of automated teller machines (ATM in terms of growing consumer demand, rising costs of technology development, decreasing profitability and market share. This paper presents a step-by-step cost-benefit analysis of the ATM automatic deposit service. The first step is to determine user attitudes towards using ATM automatic deposit service by using the Technology Acceptance Model (TAM. The second step is to determine location priorities for ATMs that provide automatic deposit services using the Analytic Hierarchy Process (AHP model. The results of the previous steps enable a highly efficient application of cost-benefit analysis for evaluating costs and benefits of automatic deposit services. To understand fully the proposed procedure outside of theoretical terms, a real-world application of a case study is conducted.

  16. Automated Transportation Management System (ATMS) user's manual. Revision 1

    International Nuclear Information System (INIS)

    Smith, P.D.

    1994-01-01

    The Automated Transportation Management System (ATMS) Software User Guide (SUG) constitutes the user procedures for the ATMS System. Information in this document will be used by the user to operate the automated system. It is intended to be used as a reference manual to guide and direct the user(s) through the ATMS software product and its environment. The objectives of ATMS are as follows: to better support the Procurement function with freight rate information; to free Transportation Logistics personnel from routine activities such as the auditing and input of freight billing information; to comply with Headquarters Department of Energy-Inspector General (DOE-IG) audit findings to automate transportation management functions; to reduce the keying of data into the Shipment Mobility Accountability Collection (SMAC) database; and to provide automation for the preparing of Bill of Lading, Declaration of Dangerous Goods, Emergency Response Guide and shipping Labels using HM181 Retrieval of hazardous material table text information

  17. Method of ATMS operators in the formalism of Faddeev equations

    International Nuclear Information System (INIS)

    Zubarev, D.A.

    1991-01-01

    The method of ATMS operators is generalized for the case of Faddeev equations. The method to construct effective equations for both elastic scattering and scattering with rearrangement is presented. Properties to obtained equations are considered

  18. 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. .

  19. Statistical multiplexing of identical bursty sources in an ATM network

    DEFF Research Database (Denmark)

    Dittmann, Lars; Jacobsen, Søren B

    1988-01-01

    The authors study the performance of a statistical multiplexer with a common buffer and bursty sources. A uniform arrival and service model has been used to calculate the loss probability as a function of several parameters. It is shown that the ratio of the number of cells in an average burst to...

  20. Quantitative and Dynamic Imaging of ATM Kinase Activity.

    Science.gov (United States)

    Nyati, Shyam; Young, Grant; Ross, Brian Dale; Rehemtulla, Alnawaz

    2017-01-01

    Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase critical to the cellular DNA-damage response, including DNA double-strand breaks (DSBs). ATM activation results in the initiation of a complex cascade of events facilitating DNA damage repair, cell cycle checkpoint control, and survival. Traditionally, protein kinases have been analyzed in vitro using biochemical methods (kinase assays using purified proteins or immunological assays) requiring a large number of cells and cell lysis. Genetically encoded biosensors based on optical molecular imaging such as fluorescence or bioluminescence have been developed to enable interrogation of kinase activities in live cells with a high signal to background. We have genetically engineered a hybrid protein whose bioluminescent activity is dependent on the ATM-mediated phosphorylation of a substrate. The engineered protein consists of the split luciferase-based protein complementation pair with a CHK2 (a substrate for ATM kinase activity) target sequence and a phospho-serine/threonine-binding domain, FHA2, derived from yeast Rad53. Phosphorylation of the serine residue within the target sequence by ATM would lead to its interaction with the phospho-serine-binding domain, thereby preventing complementation of the split luciferase pair and loss of reporter activity. Bioluminescence imaging of reporter expressing cells in cultured plates or as mouse xenografts provides a quantitative surrogate for ATM kinase activity and therefore the cellular DNA damage response in a noninvasive, dynamic fashion.

  1. ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity

    International Nuclear Information System (INIS)

    Boohaker, Rebecca J.; Cui, Xiaoli; Stackhouse, Murray; Xu, Bo

    2013-01-01

    Purpose: Activation of the DNA damage responsive protein kinase ATM is a critical step for cellular survival in response to ionizing irradiation (IR). Direct targets of ATM regulating radiosensitivity remain to be fully investigated. We have recently reported that ATM phosphorylates the transcriptional repressor Snail on Serine 100. We aimed to further study the functional significance of ATM-mediated Snail phosphorylation in response to IR. Material and methods: We transfected vector-only, wild-type, the Serine 100 to alanine (S100A) or to glutamic acid (S100E) substitution of Snail into various cell lines. We assessed colony formation, γ-H2AX focus formation and the invasion index in the cells treated with or without IR. Results: We found that over-expression of the S100A mutant Snail in HeLa cells significantly increased radiosensitivity. Meanwhile the expression of S100E, a phospho-mimicking mutation, resulted in enhanced radio-resistance. Interestingly, S100E could rescue the radiosensitive phenotype in ATM-deficient cells. We also found that expression of S100E increased γ-H2AX focus formation and compromised inhibition of invasion in response to IR independent of cell survival. Conclusion: ATM-mediated Snail Serine 100 phosphorylation in response to IR plays an important part in the regulation of radiosensitivity

  2. ELIPGRID-PC: Upgraded version

    International Nuclear Information System (INIS)

    Davidson, J.R.

    1995-12-01

    Evaluating the need for and the effectiveness of remedial cleanup at waste sites often includes finding average contaminant concentrations and identifying pockets of contamination called hot spots. The standard tool for calculating the probability of detecting pockets of contamination called hot spots has been the ELIPGRID code of singer and Wickman. The ELIPGRID-PC program has recently made this algorithm available for an IBM reg-sign personal computer (PC) or compatible. A new version of ELIPGRID-PC, incorporating Monte Carlo test results and simple graphics, is herein described. Various examples of how to use the program for both single and multiple hot spot cases are given. The code for an American National Standards Institute C version of the ELIPGRID algorithm is provided, and limitations and further work are noted. This version of ELIPGRID-PC reliably meets the goal of moving Singer's ELIPGRID algorithm to the PC

  3. Troubleshooting and Maintaining Your PC All-in-One Desk Reference For Dummies

    CERN Document Server

    Gookin, Dan

    2009-01-01

    Maintaining a PC is important, and troubleshooting a PC can be a challenge. Dan Gookin is great at explaining how to handle common PC problems, and he's provided a complete, plain-English manual in Troubleshooting & Maintaining Your PC All-in-One For Dummies. Liberally laced with Dan's famous humor and clear instructions, Troubleshooting & Maintaining Your PC All-in-One For Dummies is divided into six minibooks covering hardware, software, laptops, Internet, networking, and maintenance. Each one gives you some background on what causes common problems, to help you understand what's wrong as we

  4. COMMUNICA TION NETWORK FOR TELEMEDICINE Debretsion G ...

    African Journals Online (AJOL)

    (3) continuing medical education and (4) Training the medical ... Telemedicine system consists of at least five major subsystems. [l,4]. ... and wire-line (optical network) telecommunication facilities .... An ATM network needs certain traffic control.

  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. Performance Evaluation of a Multipurpose Bare PC Gateway

    DEFF Research Database (Denmark)

    Tsetse, Anthony; Appiah-Kubi, Patrick; Loukili, Alae

    2015-01-01

    . Different solutions (6to4 tunneling, IVI translation, NAT64, DNS64 etc.), have being proposed but these are all standalone systems. In this paper we discuss the design,implementation and performance evaluation of a multipurpose Bare PC Gateway which incorporates Network Address translation (NAT), 6to4...... results indicate a relatively better performance (18%-45%) of the Bare PC gateway compared to a Linux gateway (running the functionalities as standalone systems). We believe the proposed solution could easily scale to wide area networks and also provide a cost efficient solution...

  7. PC-based car license plate reader

    Science.gov (United States)

    Hwang, Chung-Mu; Shu, Shyh-Yeong; Chen, Wen-Yu; Chen, Yie-Wern; Wen, Kuang-Pu

    1992-11-01

    A car license plate reader (CLPR) using fuzzy inference and neural network algorithm has been developed in Industrial Technology Research Institute (ITRI) and installed in highway toll stations to identify stolen cars. It takes an average of 0.7 seconds to recognize a car license plate by using a PC with 80486-50 CPU. The recognition rate of the system is about 97%. The techniques of CLPR include vehicle sensing, image grab control, optic pre- processing, lighting, and optic character recognition (OCR). The CLPR can be used in vehicle flow statistics, the checking of stolen vehicles, automatic charging systems in parking lots or garage management, and so on.

  8. ATM and checkpoint responses to DNA double strand breaks

    International Nuclear Information System (INIS)

    Khanna, K.K.

    2003-01-01

    DNA damage checkpoints can be classified into G1/S, intra-S and G2/M checkpoints, so named according to the cell cycle transitions that they regulate. DNA damage incurred during the G1 or G2 phase of the cell cycle leads to growth arrest at the G1/S and G2/M phase boundaries, respectively, whereas genotoxic stress during S phase results in the transient suppression of DNA synthesis. In mammals, ATM (ataxia-telangiectasia mutated) is a protein kinase that controls all checkpoint responses to DNA damage. ATM is a versatile kinase which uses various means to regulate a given checkpoint pathway. It has been shown to act upon several proteins within the same pathway, many times controlling several different modifications of the same protein or using several different targets to arrive at the same end point. Some of the ATM targets act as adaptors by recruiting additional substrates for ATM. ATM controls two types of responses in G1. The p53-dependent responses inhibit Cyclin/Cdk activity by transcriptional induction of p21, whereas p53-independent responses inhibit CDKs through degradation of Cdc25A to maintain CdK2 inhibitory phosphorylation. In regulating p53, ATM directly phosphorylates p53 on Ser15, which likely causes p53 transcriptional activation, concurrently activating other kinases that phosphorylate p53 at other sites such as Ser20, which reduces the ability of MDM2 to bind p53, thus promoting its stability. ATM further ensures p53 stability by phosphorylating MDM2. At least six ATM targets, namely CHK2, CHK1, NBS1, BRCA1, SMC1 and FANCD2, have been implicated in the control of S-phase checkpoint. Cdc25A is the downstream effector of CHK1 and CHK2, though the underlying mechanism for control of intra S-phase checkpoint by other targets remain obscure. G2 checkpoint prevents mitotic entry solely through inhibitory phosphorylation of Cdc2/Cdk1. Several ATM targets including CHK1, CHK2, BRCA1, MDC1 and p53BP1 have been implicated in the control of G2/M

  9. Structures of closed and open conformations of dimeric human ATM

    Science.gov (United States)

    Baretić, Domagoj; Pollard, Hannah K.; Fisher, David I.; Johnson, Christopher M.; Santhanam, Balaji; Truman, Caroline M.; Kouba, Tomas; Fersht, Alan R.; Phillips, Christopher; Williams, Roger L.

    2017-01-01

    ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase–related protein kinase (PIKK) best known for its role in DNA damage response. ATM also functions in oxidative stress response, insulin signaling, and neurogenesis. Our electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic equilibrium between closed and open dimers. In the closed state, the PIKK regulatory domain blocks the peptide substrate–binding site, suggesting that this conformation may represent an inactive or basally active enzyme. The active site is held in this closed conformation by interaction with a long helical hairpin in the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related molecule. The open dimer has two protomers with only a limited contact interface, and it lacks the intermolecular interactions that block the peptide-binding site in the closed dimer. This suggests that the open conformation may be more active. The ATM structure shows the detailed topology of the regulator-interacting N-terminal helical solenoid. The ATM conformational dynamics shown by the structures represent an important step in understanding the enzyme regulation. PMID:28508083

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    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

  11. 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.

  12. The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response.

    Directory of Open Access Journals (Sweden)

    Jan Karlseder

    2004-08-01

    Full Text Available The telomeric protein TRF2 is required to prevent mammalian telomeres from activating DNA damage checkpoints. Here we show that overexpression of TRF2 affects the response of the ATM kinase to DNA damage. Overexpression of TRF2 abrogated the cell cycle arrest after ionizing radiation and diminished several other readouts of the DNA damage response, including phosphorylation of Nbs1, induction of p53, and upregulation of p53 targets. TRF2 inhibited autophosphorylation of ATM on S1981, an early step in the activation of this kinase. A region of ATM containing S1981 was found to directly interact with TRF2 in vitro, and ATM immunoprecipitates contained TRF2. We propose that TRF2 has the ability to inhibit ATM activation at telomeres. Because TRF2 is abundant at chromosome ends but not elsewhere in the nucleus, this mechanism of checkpoint control could specifically block a DNA damage response at telomeres without affecting the surveillance of chromosome internal damage.

  13. ATM signaling and genomic stability in response to DNA damage

    International Nuclear Information System (INIS)

    Lavin, Martin F.; Birrell, Geoff; Chen, Philip; Kozlov, Sergei; Scott, Shaun; Gueven, Nuri

    2005-01-01

    DNA double strand breaks represent the most threatening lesion to the integrity of the genome in cells exposed to ionizing radiation and radiomimetic chemicals. Those breaks are recognized, signaled to cell cycle checkpoints and repaired by protein complexes. The product of the gene (ATM) mutated in the human genetic disorder ataxia-telangiectasia (A-T) plays a central role in the recognition and signaling of DNA damage. ATM is one of an ever growing number of proteins which when mutated compromise the stability of the genome and predispose to tumour development. Mechanisms for recognising double strand breaks in DNA, maintaining genome stability and minimizing risk of cancer are discussed

  14. VIDEO-PC, SVGA Routines for FORTRAN on PC

    International Nuclear Information System (INIS)

    1994-01-01

    1 - Description of program or function: These primitives are the lowest level routines needed to perform super VGA graphics on a PC. A sample main program is included that exercises the primitives. Both Lahey and Microsoft FORTRAN's have graphics libraries. However, the libraries do not support 256 color graphics at resolutions greater than 320x200. The primitives bypass these libraries while still conforming to standard usage of BIOS. The supported graphics modes depend upon the PC graphics card and its memory. Super VGA resolutions of 640x480 and 800x600 have been tested on an ATI VGA Wonder card with 512 K memory and on several 80486 PC's (unknown manufacturers) at retail stores. 2 - Method of solution: Both Lahey and Microsoft primitives depend upon sending the correct parameters to the PC BIOS (basic input output system) as discussed in the references. 3 - Restrictions on the complexity of the problem: The primitives were developed for 256 color VGA applications. It is known, for instance, that some CGA and 16 color VGA video modes will not operate correctly using these primitives. Potential users should try the test program on their PC/video card combination to determine applicability

  15. ATM regulates Cdt1 stability during the unperturbed S phase to prevent re-replication

    Science.gov (United States)

    Iwahori, Satoko; Kohmon, Daisuke; Kobayashi, Junya; Tani, Yuhei; Yugawa, Takashi; Komatsu, Kenshi; Kiyono, Tohru; Sugimoto, Nozomi; Fujita, Masatoshi

    2014-01-01

    Ataxia-telangiectasia mutated (ATM) plays crucial roles in DNA damage responses, especially with regard to DNA double-strand breaks (DSBs). However, it appears that ATM can be activated not only by DSB, but also by some changes in chromatin architecture, suggesting potential ATM function in cell cycle control. Here, we found that ATM is involved in timely degradation of Cdt1, a critical replication licensing factor, during the unperturbed S phase. At least in certain cell types, degradation of p27Kip1 was also impaired by ATM inhibition. The novel ATM function for Cdt1 regulation was dependent on its kinase activity and NBS1. Indeed, we found that ATM is moderately phosphorylated at Ser1981 during the S phase. ATM silencing induced partial reduction in levels of Skp2, a component of SCFSkp2 ubiquitin ligase that controls Cdt1 degradation. Furthermore, Skp2 silencing resulted in Cdt1 stabilization like ATM inhibition. In addition, as reported previously, ATM silencing partially prevented Akt phosphorylation at Ser473, indicative of its activation, and Akt inhibition led to modest stabilization of Cdt1. Therefore, the ATM-Akt-SCFSkp2 pathway may partly contribute to the novel ATM function. Finally, ATM inhibition rendered cells hypersensitive to induction of re-replication, indicating importance for maintenance of genome stability. PMID:24280901

  16. Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

    Directory of Open Access Journals (Sweden)

    Stephanie Munk

    2017-10-01

    Full Text Available The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essential role for SUMOs (small ubiquitin-like modifiers has also been established. Here, we investigate the global interplay between phosphorylation and SUMOylation in response to replication stress. Using SUMO and phosphoproteomic technologies, we identify thousands of regulated modification sites. We find co-regulation of central DNA damage and replication stress responders, of which the ATR-activating factor TOPBP1 is the most highly regulated. Using pharmacological inhibition of the DNA damage response kinases ATR and ATM, we find that these factors regulate global protein SUMOylation in the protein networks that protect DNA upon replication stress and fork breakage, pointing to integration between phosphorylation and SUMOylation in the cellular systems that protect DNA integrity.

  17. Convective transport in ATM simulations and its relation to the atmospheric stability conditions

    Science.gov (United States)

    Kusmierczyk-Michulec, Jolanta

    2017-04-01

    The International Monitoring System (IMS) developed by the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) is a global system of monitoring stations, using four complementary technologies: seismic, hydroacoustic, infrasound and radionuclide. Data from all stations, belonging to IMS, are collected and transmitted to the International Data Centre (IDC) in Vienna, Austria. The radionuclide network comprises 80 stations, of which more than 60 are certified. The aim of radionuclide stations is a global monitoring of radioactive aerosols and radioactive noble gases, in particular xenon isotopes, supported by the atmospheric transport modeling (ATM). One of the important noble gases, monitored on a daily basis, is radioxenon. It can be produced either during a nuclear explosion with a high fission yield, and thus be considered as an important tracer to prove the nuclear character of an explosion, or be emitted from nuclear power plants (NPPs) or from isotope production facilities (IPFs). To investigate the transport of xenon emissions, the Provisional Technical Secretariat (PTS) operates an Atmospheric Transport Modelling (ATM) system based on the Lagrangian Particle Dispersion Model FLEXPART. To address the question whether including the convective transport in ATM simulations will change the results significantly, the differences between the outputs with the convective transport turned off and turned on, were computed and further investigated taking into account the atmospheric stability conditions. For that purpose series of 14 days forward simulations, with convective transport and without it, released daily in the period January 2011 to February 2012, were analysed. The release point was at the ANSTO facility in Australia. The unique opportunity of having access to both daily emission values for ANSTO as well as measured Xe-133 activity concentration (AC) values at the IMS stations, gave a chance to validate the simulations.

  18. Adaptive Restoration of Airborne Daedalus AADS1268 ATM Thermal Data

    International Nuclear Information System (INIS)

    D. Yuan; E. Doak; P. Guss; A. Will

    2002-01-01

    To incorporate the georegistration and restoration processes into airborne data processing in support of U.S. Department of Energy's nuclear emergency response task, we developed an adaptive restoration filter for airborne Daedalus AADS1268 ATM thermal data based on the Wiener filtering theory. Preliminary assessment shows that this filter enhances the detectability of small weak thermal anomalies in AADS1268 thermal images

  19. Characterization of spent fuel approved testing material: ATM-106

    International Nuclear Information System (INIS)

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

    1988-10-01

    The characterization data obtained to date are described for Approved Testing Material (ATM)-106 spent fuel from Assembly BT03 of pressurized-water reactor Calvert Cliffs No. 1. This report is one in a series being prepared by the Materials Characterization Center at Pacific Northwest Laboratory 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 (OCWRM) program. ATM-106 consists of 20 full-length irradiated fuel rods with rod-average burnups of about 3700 GJ/kgM (43 MWd/kgM) and expected fission gas release of /approximately/10%. Characterization data include (1) 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) calculated nuclide inventories and radioactivities in the fuel and cladding; and (6) radiochemical analyses of the fuel and cladding. Additional analyses of the fuel rod are being conducted and will be included in planned revisions of this report. 12 refs., 110 figs., 81 tabs

  20. The ATM gene and the radiobiology of ataxia-telangiectasia

    International Nuclear Information System (INIS)

    Jorgensen, T.J.; Shiloh, Y.

    1996-01-01

    Ataxia-telangiectasia (A-T) is the classic human genetic disease involving severe ionizing radiation sensitivity and as such has been intensely studied by radiation biologists over the years. Unlike its counterpart for UV light sensitivity -xeroderma pigmentosum - A-T has no obvious DNA repair defect; and there has been much speculation as to the mechanism underlying the altered radioresponses associated with this disease. The gene defective in A-T (ATM) has recently been cloned, and its primary coding sequence determined. The primary sequence of the ATM protein suggests that it has some regulatory functions related to cellular radioresponse and maintenance of genomic stability, and shares these functions with a growing family of other proteins in various organisms. At this juncture it is appropriate to review our current knowledge about the radiobiology of A-T and reflect on the possible radiobiological mechanisms that are suggested by the ATM gene itself. This article will attempt briefly to review current knowledge about the radiobiology of A-T and to introduce new speculations about underlying radiobiological mechanisms that are suggested by the primary amino acid sequence of the predicted ATM gene product. (Author)

  1. Utilisation des modules ATM pour le projet FP420

    CERN Document Server

    Renaglia, T

    2006-01-01

    Le but de cette note est de résumer les premières caractéristiques de l'intégration de 2 modules ATM pour le projet FP420 (voir note technique EDMS n° 743628) ainsi que la liste des problèmes découverts à ce jour sur l

  2. Germline variants in the ATM gene and breast cancer susceptibility ...

    African Journals Online (AJOL)

    Chaymaa Marouf

    2017-03-06

    Mar 6, 2017 ... Results: We did not detect the ATM c.7271T > G and c.1066–6T > G (IVS10–6T > G) ..... [8] Lavin MF, Shiloh Y. The genetic defect in ataxia-telangiectasia. .... [36] Inskip HM, Kinlen LJ, Taylor AM, Woods CG, Arlett CF. Risk of ...

  3. 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.

  4. 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

    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...... 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 ATM...

  5. The Kaleidoscope switch-a new concept for implementation of a large and fault tolerant ATM switch system

    DEFF Research Database (Denmark)

    Dittmann, Lars

    1997-01-01

    This paper describes a new concept for implementing a large switch network based on smaller modules. The concept is based an an alternative self-routing structure that due to a point symmetry allows the bit in the routing tag to be processed in a random order. Among others this property provides ...... an inherent fault protection and allows a simple implementation of broadcast and multicast. The concept has been implemented as a small prototype, that currently is used in a national experimental ATM network in Denmark...

  6. A pharmacological screen for compounds that rescue the developmental lethality of a Drosophila ATM mutant.

    Science.gov (United States)

    Rimkus, Stacey A; Wassarman, David A

    2018-01-01

    Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. As an example, conditional loss-of-function ATM alleles in flies cause progressive neurodegeneration through activation of the innate immune response. However, unlike in mammals, null alleles of ATM in flies cause lethality during development. With the goals of understanding biological and molecular roles of ATM in a whole animal and identifying candidate therapeutics for A-T, we performed a screen of 2400 compounds, including FDA-approved drugs, natural products, and bioactive compounds, for modifiers of the developmental lethality caused by a temperature-sensitive ATM allele (ATM8) that has reduced kinase activity at non-permissive temperatures. Ten compounds reproducibly suppressed the developmental lethality of ATM8 flies, including Ronnel, which is an organophosphate. Ronnel and other suppressor compounds are known to cause mitochondrial dysfunction or to inhibit the enzyme acetylcholinesterase, which controls the levels of the neurotransmitter acetylcholine, suggesting that detrimental consequences of reduced ATM kinase activity can be rescued by inhibiting the function of mitochondria or increasing acetylcholine levels. We carried out further studies of Ronnel because, unlike the other compounds that suppressed the developmental lethality of homozygous ATM8 flies, Ronnel was toxic to the development of heterozygous ATM8 flies. Ronnel did not affect the innate immune response of ATM8 flies, and it further increased the already high levels of DNA damage in brains of ATM8 flies, but its effects were not harmful to the lifespan of rescued ATM8 flies. These results provide

  7. Port virtual addressing for PC

    International Nuclear Information System (INIS)

    Bolanos, L.; Arista, E.; Osorio Deliz, J.F.

    1997-01-01

    Instruments for nuclear signal measurements based on add-on card for a personal computer (PC) are designed often. Then one faces the problem of the addressing of data input/output devices which show an integration level or intelligence that makes the use of several port address indispensable, and these are limited in the PC. The virtual addressing offers the advantage of the occupation of few addresses to accede to many of these devices. The principles of this technique and the appliances of a solution in radiometric in a radiometric card based on programmed logic are discussed in this paper

  8. ATM Technology and Banking System in West African Sub-Region ...

    African Journals Online (AJOL)

    User

    2011-04-19

    Apr 19, 2011 ... At this point in time, it is pertinent to ask, what is ATM? ATM is Automated .... can be installed on ATMs running Microsoft Windows XP operating system that records sensitive ... almost real time bank services. The citizens of ...

  9. A 2.5 gb/s GaAs ATM Mux Demux ASIC

    DEFF Research Database (Denmark)

    Madsen, Jens Kargaard; Lassen, Peter Stuhr

    1995-01-01

    This paper describes the design and implementation of a high speed GaAs ATM Mux Demur ASIC (AMDA) which is the key element in a high speed ATM Add-Drop unit. This unit is used in a new distributed ATM multiplexing-demultiplexing architecture for broadband switching systems. The Add-Drop unit...

  10. ATM Technology and Banking System in West African Sub-Region ...

    African Journals Online (AJOL)

    Automated Teller Machine (ATM) technology has had its significant impact in banking system in Nigeria and some other West African Countries. The most significant impact of ATM technology is the customer's ability to withdraw money outside banking hours. But this feat achieved by ATM technology is not without ...

  11. Junior PC-Kørekort

    DEFF Research Database (Denmark)

    Hansbøl, Mikala; Mathiasen, Helle

    udviklingsprojekt med forsøg med DANSK IT's Junior PC-kørekort® som metode og redskab til at evaluere og dokumentere elevernes IT-kompetencer. Projektet blev gennemført i perioden fra 2002-2003 og afsluttet i foråret 2003. Rapporten er baseret på kvalitative case studier af elever og læreres arbejde med Junior PC......-kørekort® prøverne. DANSK IT's Junior PC-kørekort® kan betragtes som et forsøg på at etablere en bestemt fælleskulturel tilgang til elevernes IT-kompetencer i folkeskolen. Ud fra et situeret læringsperspektiv problematiserer rapporten anvendelsen af de standardiserede prøver som metode til at dokumentere og evaluere...... elevernes IT-kompetencer. Rapporten (2MB) fylder 80 sider ekskl. bilag. Bemærk, at forskningsrapporten handler om Dansk IT's Junior PC-kørekort - ikke at forveksle med det IT-bevis for folkeskolens elever, som Undevisningsministeriet har udviklet. Dette IT-bevis koncept skiftede navn i januar 2004, hvor...

  12. Multi-satellite study of the excitation of Pc3 and Pc4-5 ULF waves and their penetration across the plasmapause during the 2003 Halloween superstorm

    Science.gov (United States)

    Balasis, G.; Daglis, I. A.; Mann, I. R.; Papadimitriou, C.; Zesta, E.; Georgiou, M.; Haagmans, R.; Tsinganos, K.

    2015-10-01

    We use multi-satellite and ground-based magnetic data to investigate the concurrent characteristics of Pc3 (22-100 mHz) and Pc4-5 (1-22 mHz) ultra-low-frequency (ULF) waves on the 31 October 2003 during the Halloween magnetic superstorm. ULF waves are seen in the Earth's magnetosphere, topside ionosphere, and Earth's surface, enabling an examination of their propagation characteristics. We employ a time-frequency analysis technique and examine data from when the Cluster and CHAMP spacecraft were in good local time (LT) conjunction near the dayside noon-midnight meridian. We find clear evidence of the excitation of both Pc3 and Pc4-5 waves, but more significantly we find a clear separation in the L shell of occurrence of the Pc4-5 and Pc3 waves in the equatorial inner magnetosphere, separated by the density gradients at the plasmapause boundary layer. A key finding of the wavelet spectral analysis of data collected from the Geotail, Cluster, and CHAMP spacecraft and the CARISMA and GIMA magnetometer networks was a remarkably clear transition of the waves' frequency into dominance in a higher-frequency regime within the Pc3 range. Analysis of the local field line resonance frequency suggests that the separation of the Pc4-5 and Pc3 emissions across the plasmapause is consistent with the structure of the inhomogeneous field line resonance Alfvén continuum. The Pc4-5 waves are consistent with direct excitation by the solar wind in the plasma trough, as well as Pc3 wave absorption in the plasmasphere following excitation by upstream waves originating at the bow shock in the local noon sector. However, despite good solar wind coverage, our study was not able to unambiguously identify a clear explanation for the sharp universal time (UT) onset of the discrete frequency and large-amplitude Pc3 wave power.

  13. Multi-satellite study of the excitation of Pc3 and Pc4-5 ULF waves and their penetration across the plasmapause during the 2003 Halloween superstorm

    Directory of Open Access Journals (Sweden)

    G. Balasis

    2015-10-01

    Full Text Available We use multi-satellite and ground-based magnetic data to investigate the concurrent characteristics of Pc3 (22–100 mHz and Pc4-5 (1–22 mHz ultra-low-frequency (ULF waves on the 31 October 2003 during the Halloween magnetic superstorm. ULF waves are seen in the Earth's magnetosphere, topside ionosphere, and Earth's surface, enabling an examination of their propagation characteristics. We employ a time–frequency analysis technique and examine data from when the Cluster and CHAMP spacecraft were in good local time (LT conjunction near the dayside noon–midnight meridian. We find clear evidence of the excitation of both Pc3 and Pc4-5 waves, but more significantly we find a clear separation in the L shell of occurrence of the Pc4-5 and Pc3 waves in the equatorial inner magnetosphere, separated by the density gradients at the plasmapause boundary layer. A key finding of the wavelet spectral analysis of data collected from the Geotail, Cluster, and CHAMP spacecraft and the CARISMA and GIMA magnetometer networks was a remarkably clear transition of the waves' frequency into dominance in a higher-frequency regime within the Pc3 range. Analysis of the local field line resonance frequency suggests that the separation of the Pc4-5 and Pc3 emissions across the plasmapause is consistent with the structure of the inhomogeneous field line resonance Alfvén continuum. The Pc4-5 waves are consistent with direct excitation by the solar wind in the plasma trough, as well as Pc3 wave absorption in the plasmasphere following excitation by upstream waves originating at the bow shock in the local noon sector. However, despite good solar wind coverage, our study was not able to unambiguously identify a clear explanation for the sharp universal time (UT onset of the discrete frequency and large-amplitude Pc3 wave power.

  14. 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

    2017-04-01

    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. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Absence of Wip1 partially rescues Atm deficiency phenotypes in mice

    Science.gov (United States)

    Darlington, Yolanda; Nguyen, Thuy-Ai; Moon, Sung-Hwan; Herron, Alan; Rao, Pulivarthi; Zhu, Chengming; Lu, Xiongbin; Donehower, Lawrence A.

    2011-01-01

    Wildtype p53-Induced Phosphatase 1 (WIP1) is a serine/threonine phosphatase that dephosphorylates proteins in the ataxia telangiectasia mutated (ATM)-initiated DNA damage response pathway. WIP1 may play a homeostatic role in ATM signaling by returning the cell to a normal pre-stress state following completion of DNA repair. To better understand the effects of WIP1 on ATM signaling, we crossed Atm-deficient mice to Wip1-deficient mice and characterized phenotypes of the double knockout progeny. We hypothesized that the absence of Wip1 might rescue Atm deficiency phenotypes. Atm null mice, like ATM-deficient humans with the inherited syndrome ataxia telangiectasia, exhibit radiation sensitivity, fertility defects, and are T-cell lymphoma prone. Most double knockout mice were largely protected from lymphoma development and had a greatly extended lifespan compared to Atm null mice. Double knockout mice had increased p53 and H2AX phosphorylation and p21 expression compared to their Atm null counterparts, indicating enhanced p53 and DNA damage responses. Additionally, double knockout splenocytes displayed reduced chromosomal instability compared to Atm null mice. Finally, doubly null mice were partially rescued from infertility defects observed in Atm null mice. These results indicate that inhibition of WIP1 may represent a useful strategy for cancer treatment in general and A-T patients in particular. PMID:21765465

  16. 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.

  17. Participation of ATM in cellular response to DNA damage induced by ionizing radiation

    International Nuclear Information System (INIS)

    Meng Xiangbing; Song Yi; Mao Jianping; Gong Bo; Dong Yan; Liu Bin; Sun Zhixian

    2000-01-01

    Objective: To clone ATM full length cDNA and cDNA fragments containing some functional domains and to identify proteins that interact with ATM and mediate DNA damage signal transduction in cellular response to DNA damage. Methods: ATM cDNA was amplified from MarthomTM-Ready cDNA kit of human leukocytes by LD-PCR. ATM-interacting proteins were screened by yeast two hybrid system. Results: ATM full-length cDNA and cDNA fragments containing PI3K kinase domain, leucine zipper and proline rich region were amplified from human cDNAs. Several candidate clones that interacted with ATM PI3K domain were identified. Conclusion: ATM mediates DNA damage signal transduction by interacting with many proteins

  18. 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.

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

    International Nuclear Information System (INIS)

    Jang, Eun Ryoung; Choi, Jae Duk; Jeong, Gajin; Lee, Jong-Soo

    2010-01-01

    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 γ-irradiation in ATM + cells but not ATM - 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.

  20. Analysis of expected ATM processes changes in Central Europe

    Directory of Open Access Journals (Sweden)

    Tomislav MIHETEC

    2012-01-01

    Full Text Available This paper evaluates feasibility of the new Air Traffic Management (ATM organisation in Functional Airspace Block Central Europe (FAB CE and specifies the implementation scenarios that are proposed by Central European Air Traffic Services Coordination Group (CEATS CG. The paper elaborates elements of required Functional Airspace Block Central Europe implementation and identifies and assesses the implementation blockers. Provision of air navigation services in European Civil Aviation Conference (ECAC area is diversely regulated and highly fragmented.

  1. 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.

  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. 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

  4. 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

  5. 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

  6. Wireless ATM: A Technologi cal Framework to m-banking

    OpenAIRE

    Susmi Routray; A. M. Sherry; B. V. R. Reddy

    2008-01-01

    Mobile and Wireless communication devices are becoming enablers for organizations to conduct business more effectively and efficiently. One of the most effective applications is mobile banking (m-banking). For any application to gain recognition technological advancements play a vital role. To make m-banking application a success bandwidth management is an important issue. The incr eased flexibility and mobility feature of wireless ATM and its bandwidth on demand fu...

  7. Sterigmatocystin-induced DNA damage triggers G2 arrest via an ATM/p53-related pathway in human gastric epithelium GES-1 cells in vitro.

    Directory of Open Access Journals (Sweden)

    Donghui Zhang

    Full Text Available Sterigmatocystin (ST, which is commonly detected in food and feed commodities, is a mutagenic and carcinogenic mycotoxin that has been recognized as a possible human carcinogen. Our previous study showed that ST can induce G2 phase arrest in GES-1 cells in vitro and that the MAPK and PI3K signaling pathways are involved in the ST-induced G2 arrest. It is now widely accepted that DNA damage plays a critical role in the regulation of cell cycle arrest and apoptosis. In response to DNA damage, a complex signaling network is activated in eukaryotic cells to trigger cell cycle arrest and facilitate DNA repair. To further explore the molecular mechanism through which ST induces G2 arrest, the current study was designed to precisely dissect the role of DNA damage and the DNA damage sensor ataxia telangiectasia-mutated (ATM/p53-dependent pathway in the ST-induced G2 arrest in GES-1 cells. Using the comet assay, we determined that ST induces DNA damage, as evidenced by the formation of DNA comet tails, in GES-1 cells. We also found that ST induces the activation of ATM and its downstream molecules, Chk2 and p53, in GES-1 cells. The ATM pharmacological inhibitor caffeine was found to effectively inhibit the activation of the ATM-dependent pathways and to rescue the ST-induced G2 arrest in GES-1 cells, which indicating its ATM-dependent characteristic. Moreover, the silencing of the p53 expression with siRNA effectively attenuated the ST-induced G2 arrest in GES-1 cells. We also found that ST induces apoptosis in GES-1 cells. Thus, our results show that the ST-induced DNA damage activates the ATM/53-dependent signaling pathway, which contributes to the induction of G2 arrest in GES-1 cells.

  8. ATM is required for SOD2 expression and homeostasis within the mammary gland.

    Science.gov (United States)

    Dyer, Lisa M; Kepple, Jessica D; Ai, Lingbao; Kim, Wan-Ju; Stanton, Virginia L; Reinhard, Mary K; Backman, Lindsey R F; Streitfeld, W Scott; Babu, Nivetha Ramesh; Treiber, Nicolai; Scharffetter-Kochanek, Karin; McKinnon, Peter J; Brown, Kevin D

    2017-12-01

    ATM activates the NF-κB transcriptional complex in response to genotoxic and oxidative stress. The purpose of this study was to examine if the NF-κB target gene and critical antioxidant SOD2 (MnSOD) in cultured mammary epithelium is also ATM-dependent, and what phenotypes arise from deletion of ATM and SOD2 within the mammary gland. SOD2 expression was studied in human mammary epithelial cells and MCF10A using RNAi to knockdown ATM or the NF-κB subunit RelA. To study ATM and SOD2 function in mammary glands, mouse lines containing Atm or Sod2 genes containing LoxP sites were mated with mice harboring Cre recombinase under the control of the whey acidic protein promoter. Quantitative PCR was used to measure gene expression, and mammary gland structure was studied using histology. SOD2 expression is ATM- and RelA-dependent, ATM knockdown renders cells sensitive to pro-oxidant exposure, and SOD mimetics partially rescue this sensitivity. Mice with germline deletion of Atm fail to develop mature mammary glands, but using a conditional knockout approach, we determined that Atm deletion significantly diminished the expression of Sod2. We also observed that these mice (termed Atm Δ/Δ ) displayed a progressive lactation defect as judged by reduced pup growth rate, aberrant lobulo-alveolar structure, diminished milk protein gene expression, and increased apoptosis within lactating glands. This phenotype appears to be linked to dysregulated Sod2 expression as mammary gland-specific deletion of Sod2 phenocopies defects observed in Atm Δ/Δ dams. We conclude that ATM is required to promote expression of SOD2 within the mammary epithelium, and that both ATM and SOD2 play a crucial role in mammary gland homeostasis.

  9. ATM Protein Physically and Functionally Interacts with Proliferating Cell Nuclear Antigen to Regulate DNA Synthesis*

    Science.gov (United States)

    Gamper, Armin M.; Choi, Serah; Matsumoto, Yoshihiro; Banerjee, Dibyendu; Tomkinson, Alan E.; Bakkenist, Christopher J.

    2012-01-01

    Ataxia telangiectasia (A-T) is a pleiotropic disease, with a characteristic hypersensitivity to ionizing radiation that is caused by biallelic mutations in A-T mutated (ATM), a gene encoding a protein kinase critical for the induction of cellular responses to DNA damage, particularly to DNA double strand breaks. A long known characteristic of A-T cells is their ability to synthesize DNA even in the presence of ionizing radiation-induced DNA damage, a phenomenon termed radioresistant DNA synthesis. We previously reported that ATM kinase inhibition, but not ATM protein disruption, blocks sister chromatid exchange following DNA damage. We now show that ATM kinase inhibition, but not ATM protein disruption, also inhibits DNA synthesis. Investigating a potential physical interaction of ATM with the DNA replication machinery, we found that ATM co-precipitates with proliferating cell nuclear antigen (PCNA) from cellular extracts. Using bacterially purified ATM truncation mutants and in vitro translated PCNA, we showed that the interaction is direct and mediated by the C terminus of ATM. Indeed, a 20-amino acid region close to the kinase domain is sufficient for strong binding to PCNA. This binding is specific to ATM, because the homologous regions of other PIKK members, including the closely related kinase A-T and Rad3-related (ATR), did not bind PCNA. ATM was found to bind two regions in PCNA. To examine the functional significance of the interaction between ATM and PCNA, we tested the ability of ATM to stimulate DNA synthesis by DNA polymerase δ, which is implicated in both DNA replication and DNA repair processes. ATM was observed to stimulate DNA polymerase activity in a PCNA-dependent manner. PMID:22362778

  10. Poster session ELIPGRID-PC

    International Nuclear Information System (INIS)

    Davidson, J.R.

    1995-01-01

    ELIPGRID-PC, a new personal computer program, has been developed to provide easy access to Singer's ELIPGRID algorithm for hot-spot detection probabilities. Three features of the program are the ability to determine: (1) the grid size required for specified conditions, (2) the smallest hot spot that can be sampled with a given probability, and (3) the approximate grid size resulting from specified conditions and sampling cost. ELIPGRID-PC also provides probability of detection versus cost data for graphing with spreadsheets or graphics software. The program has been successfully tested using Singer's published ELIPGRID results. An apparent error in the published ELIPGRID code has been uncovered and an appropriate modification incorporated into the new program

  11. PC based uranium enrichment analyser

    International Nuclear Information System (INIS)

    Madan, V.K.; Gopalakrishana, K.R.; Bairi, B.R.

    1991-01-01

    It is important to measure enrichment of unirradiated nuclear fuel elements during production as a quality control measure. An IBM PC based system has recently been tested for enrichment measurements for Nuclear Fuel Complex (NFC), Hyderabad. As required by NFC, the system has ease of calibration. It is easy to switch the system from measuring enrichment of fuel elements to pellets and also automatically store the data and the results. The system uses an IBM PC plug in card to acquire data. The card incorporates programmable interval timers (8253-5). The counter/timer devices are executed by I/O mapped I/O's. A novel algorithm has been incorporated to make the system more reliable. The application software has been written in BASIC. (author). 9 refs., 1 fig

  12. El blindaje de una PC

    Directory of Open Access Journals (Sweden)

    Revista Chasqui

    2015-01-01

    Full Text Available La navegación en Internet y la consiguiente conexión a una red expone a una computadora a un sinfín de riesgos y peligros. Una PC que no sea utilizada para navegar en Internet o que no esté conectada a una red puede,incluso, ser también afectada por virus, por la utilización de disquetes contaminados que la contaminen con un virus. Para enfrentar esos problemas, la industria informática ha previsto una serie de protecciones y recaudos, de cuyo uso y utilización deben estar plenamente informados los usuarios de una PC.

  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. 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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Fabrication and characterization of MCC approved testing material - ATM-1 glass

    International Nuclear Information System (INIS)

    Wald, J.W.

    1985-10-01

    The Materials Characterization Center Approved Testing Material ATM-1 is a borosilicate glass that incorporates nonradioactive constituents and uranium to represent high-level waste (HLW) resulting from the reprocessing of commercial nuclear reactor fuel. Its composition is based upon the simulated HLW glass type 76-68 to which depleted uranium has been added as UO 2 . Three separate lots of ATM-1 glass have been fabricated, designated ATM-1a, ATM-1b, and ATM-1c. Limited analyses and microstructural evaluations were conducted on each type. Each lot of ATM-1 glass was produced from a feedstock melted in an air atmosphere at between 1150 to 1200 0 C and cast into stress annealed rectangular bars. Bars of ATM-1a were nominally 1.3 x 1.3 x 7.6 cm (approx.36 g each), bars of ATM-1b were nominally 2 x 2.5 x 17.5 cm (approx.190 g each) and bars of ATM-1c were nominally 1.9 x 1.9 x 15 cm (approx.170 g each). Thirteen bars of ATM-1a, 14 bars of ATM-1b, and 6 bars of ATM-1c were produced. Twelve random samples from each of lots ATM-1a, ATM-1b, and ATM-1c were analyzed. The concentrations (except for U and Cs) were obtained by Inductively-Coupled Argon Plasma Atomic Emission Spectroscopy analysis. Cesium analysis was performed by Atomic Absorption Spectroscopy, while uranium was analyzed by Pulsed Laser Fluorometry. X-ray diffraction analysis of four samples indicated that lot ATM-1a had no detectable crystalline phases (<3 wt %), while ATM-1b and ATM-1c contained approx.3 to 5 wt % iron-chrome spinel crystals. These concentrations of secondary spinel component are not considered uncommon. Scanning electron microscopy examination of fracture surfaces revealed only a random, apparently crystalline, second phase (1-10 μm diam) and a random distribution of small voids or bubbles (approx.1 μm nominal diam)

  16. Empirically modelled Pc3 activity based on solar wind parameters

    Directory of Open Access Journals (Sweden)

    B. Heilig

    2010-09-01

    Full Text Available It is known that under certain solar wind (SW/interplanetary magnetic field (IMF conditions (e.g. high SW speed, low cone angle the occurrence of ground-level Pc3–4 pulsations is more likely. In this paper we demonstrate that in the event of anomalously low SW particle density, Pc3 activity is extremely low regardless of otherwise favourable SW speed and cone angle. We re-investigate the SW control of Pc3 pulsation activity through a statistical analysis and two empirical models with emphasis on the influence of SW density on Pc3 activity. We utilise SW and IMF measurements from the OMNI project and ground-based magnetometer measurements from the MM100 array to relate SW and IMF measurements to the occurrence of Pc3 activity. Multiple linear regression and artificial neural network models are used in iterative processes in order to identify sets of SW-based input parameters, which optimally reproduce a set of Pc3 activity data. The inclusion of SW density in the parameter set significantly improves the models. Not only the density itself, but other density related parameters, such as the dynamic pressure of the SW, or the standoff distance of the magnetopause work equally well in the model. The disappearance of Pc3s during low-density events can have at least four reasons according to the existing upstream wave theory: 1. Pausing the ion-cyclotron resonance that generates the upstream ultra low frequency waves in the absence of protons, 2. Weakening of the bow shock that implies less efficient reflection, 3. The SW becomes sub-Alfvénic and hence it is not able to sweep back the waves propagating upstream with the Alfvén-speed, and 4. The increase of the standoff distance of the magnetopause (and of the bow shock. Although the models cannot account for the lack of Pc3s during intervals when the SW density is extremely low, the resulting sets of optimal model inputs support the generation of mid latitude Pc3 activity predominantly through

  17. ATM-deficiency increases genomic instability and metastatic potential in a mouse model of pancreatic cancer.

    Science.gov (United States)

    Drosos, Yiannis; Escobar, David; Chiang, Ming-Yi; Roys, Kathryn; Valentine, Virginia; Valentine, Marc B; Rehg, Jerold E; Sahai, Vaibhav; Begley, Lesa A; Ye, Jianming; Paul, Leena; McKinnon, Peter J; Sosa-Pineda, Beatriz

    2017-09-11

    Germline mutations in ATM (encoding the DNA-damage signaling kinase, ataxia-telangiectasia-mutated) increase Familial Pancreatic Cancer (FPC) susceptibility, and ATM somatic mutations have been identified in resected human pancreatic tumors. Here we investigated how Atm contributes to pancreatic cancer by deleting this gene in a murine model of the disease expressing oncogenic Kras (Kras G12D ). We show that partial or total ATM deficiency cooperates with Kras G12D to promote highly metastatic pancreatic cancer. We also reveal that ATM is activated in pancreatic precancerous lesions in the context of DNA damage and cell proliferation, and demonstrate that ATM deficiency leads to persistent DNA damage in both precancerous lesions and primary tumors. Using low passage cultures from primary tumors and liver metastases we show that ATM loss accelerates Kras-induced carcinogenesis without conferring a specific phenotype to pancreatic tumors or changing the status of the tumor suppressors p53, p16 Ink4a and p19 Arf . However, ATM deficiency markedly increases the proportion of chromosomal alterations in pancreatic primary tumors and liver metastases. More importantly, ATM deficiency also renders murine pancreatic tumors highly sensitive to radiation. These and other findings in our study conclusively establish that ATM activity poses a major barrier to oncogenic transformation in the pancreas via maintaining genomic stability.

  18. 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. © The Author(s) 2016.

  19. Neurodegeneration in ataxia-telangiectasia: Multiple roles of ATM kinase in cellular homeostasis.

    Science.gov (United States)

    Choy, Kay Rui; Watters, Dianne J

    2018-01-01

    Ataxia-telangiectasia (A-T) is characterized by neuronal degeneration, cancer, diabetes, immune deficiency, and increased sensitivity to ionizing radiation. A-T is attributed to the deficiency of the protein kinase coded by the ATM (ataxia-telangiectasia mutated) gene. ATM is a sensor of DNA double-strand breaks (DSBs) and signals to cell cycle checkpoints and the DNA repair machinery. ATM phosphorylates numerous substrates and activates many cell-signaling pathways. There has been considerable debate about whether a defective DNA damage response is causative of the neurological aspects of the disease. In proliferating cells, ATM is localized mainly in the nucleus; however, in postmitotic cells such as neurons, ATM is mostly cytoplasmic. Recent studies reveal an increasing number of roles for ATM in the cytoplasm, including activation by oxidative stress. ATM associates with organelles including mitochondria and peroxisomes, both sources of reactive oxygen species (ROS), which have been implicated in neurodegenerative diseases and aging. ATM is also associated with synaptic vesicles and has a role in regulating cellular homeostasis and autophagy. The cytoplasmic roles of ATM provide a new perspective on the neurodegenerative process in A-T. This review will examine the expanding roles of ATM in cellular homeostasis and relate these functions to the complex A-T phenotype. Developmental Dynamics 247:33-46, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. 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. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Molecular and functional characterization of a human ATM gene analogue at Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Garcia, V.

    2001-12-01

    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)

  2. 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.

  3. Data acquisition techniques using PC

    CERN Document Server

    Austerlitz, Howard

    1991-01-01

    Data Acquisition Techniques Using Personal Computers contains all the information required by a technical professional (engineer, scientist, technician) to implement a PC-based acquisition system. Including both basic tutorial information as well as some advanced topics, this work is suitable as a reference book for engineers or as a supplemental text for engineering students. It gives the reader enough understanding of the topics to implement a data acquisition system based on commercial products. A reader can alternatively learn how to custom build hardware or write his or her own software.

  4. Development of the Advanced Technology Microwave Sounder (ATMS) for NPOESS C1

    Science.gov (United States)

    Brann, C.; Kunkee, D.

    2008-12-01

    The National Polar-orbiting Operational Environmental Satellite System's Advanced Technology Microwave Sounder (ATMS) is planned for flight on the first NPOESS mission (C1) in 2013. The C1 ATMS will be the second instrument of the ATMS series and will provide along with the companion Cross-track Infrared Sounder (CrIS), atmospheric temperature and moisture profiles for NPOESS. The first flight of the ATMS is scheduled in 2010 on the NPOESS Preparatory Project (NPP) satellite, which is an early instrument risk reduction component of the NPOESS mission. This poster will focus on the development of the ATMS for C1 including aspects of the sensor calibration, antenna beam and RF characteristics and scanning. New design aspects of the C1 ATMS, required primarily by parts obsolescence, will also be addressed in this poster.

  5. HealthATM: personal health cyberinfrastructure for underserved populations.

    Science.gov (United States)

    Botts, Nathan E; Horan, Thomas A; Thoms, Brian P

    2011-05-01

    There is an opportunity for personal health record (PHR) systems to play a vital role in fostering health self-management within underserved populations. If properly designed and promoted, it is possible that patients will use PHRs to become more empowered in taking an active role toward managing their health needs. This research examines the potential of a cyberinfrastructure-based PHR to encourage patient activation in health care, while also having population health implications. A multi-phased, iterative research approach was used to design and evaluate a PHR system called HealthATM, which utilizes services from a cloud computing environment. These services were integrated into an ATM-style interface aimed at providing a broad range of health consumers with the ability to manage health conditions and encourage accomplishment of health goals. Evaluation of the PHR included 115 patients who were clients of several free clinics in Los Angeles County. The majority of patients perceived ease of use (74%) and confidence (73%) in using the HealthATM system, and thought they would like to use it frequently (73%). Patients also indicated a belief in being responsible for their own health. However, fewer felt as though they were able to maintain necessary life changes to improve their health. Findings from the field tests suggest that PHRs can be a beneficial health management tool for underserved populations. In order for these types of tools to be effective within safety-net communities, they must be technically accessible and provide meaningful opportunities to increase patient engagement in their health care. Copyright © 2011. Published by Elsevier Inc.

  6. Distributed medical services within the ATM-based Berlin regional test bed

    Science.gov (United States)

    Thiel, Andreas; Bernarding, Johannes; Krauss, Manfred; Schulz, Sandra; Tolxdorff, Thomas

    1996-05-01

    The ATM-based Metropolitan Area Network (MAN) of Berlin connects two university hospitals (Benjamin Franklin University Hospital and Charite) with the computer resources of the Technical University of Berlin (TUB). Distributed new medical services have been implemented and will be evaluated within the highspeed MAN of Berlin. The network with its data transmission rates of up to 155 Mbit/s renders these medical services externally available to practicing physicians. Resource and application sharing is demonstrated by the use of two software systems. The first software system is an interactive 3D reconstruction tool (3D- Medbild), based on a client-server mechanism. This structure allows the use of high- performance computers at the TUB from the low-level workstations in the hospitals. A second software system, RAMSES, utilizes a tissue database of Magnetic Resonance Images. For the remote control of the software, the developed applications use standards such as DICOM 3.0 and features of the World Wide Web. Data security concepts are being tested and integrated for the needs of the sensitive medical data. The highspeed network is the necessary prerequisite for the clinical evaluation of data in a joint teleconference. The transmission of digitized real-time sequences such as video and ultrasound and the interactive manipulation of data are made possible by Multi Media tools.

  7. Characterization of Early and Late Adopters of ATM Card in Indian Banking Industry

    Directory of Open Access Journals (Sweden)

    Kamalpreet Kaur

    2012-11-01

    Full Text Available Normal 0 false false false IN X-NONE AR-SA MicrosoftInternetExplorer4 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. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso

  8. KONTROLÖR ALAN AĞI ESASLI BİR ATM ALAN TAŞITININ TASARLANMASI

    Directory of Open Access Journals (Sweden)

    Mahmut TENRUH

    2006-03-01

    Full Text Available Kontrolör Alan Ağı (KAA taşıtı başlangıçta otomotiv uygulamaları için önerilmiş fakat düşük maliyeti yüksek hızı ve güvenilirliği sayesinde endüstriyel dağılımlı gerçek zamanlı kontrol uygulamalarında da bir standart haline gelmiştir. ATM veri, ses ve görüntü gibi tüm haberleşme türlerini bir network yapısı içerisinde birleştirmeyi hedefleyen hızlı bir ağ teknolojisidir. Ethernet ve Token Ring gibi mevcut ağ türlerinin ATM ile bağlanması için çeşitli çalışmalar sürdürülmüştür. Kontrol Taşıtı haberleşmesinin de bu çerçevede ele alınması önem taşımaktadır. Bu çalışma ATM teknolojisinin Kontrol Taşıtı haberleşmesi ile birlikte kullanılmasını amaçlamaktadır. Bu kapsamda KAA esaslı ATM Taşıt yapısı sunulmaktadır. Bu yapı aynı zamanda Kontrol Taşıt ağlarının ATM ağları ile doğrudan bağlanabilmesi için de bir imkan sunmaktadır. Önerilen modelin geçerliliğini görmek amacıyla simülasyon çalışmaları yürütülmüş ve sonuçlar sistemin ek avantajlarla uygulanabilir olduğunu göstermiştir.

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

    OpenAIRE

    Matarese, Francesca; Montefusco, Patrizia; Neves, José; Rocha, André

    2014-01-01

    The objective of this paper is the definition of a new methodology for carrying out security risk assessment in the air traffic management (ATM) domain so as to enhance security awareness and integrate secure and cost-effective design objectives. This process is carried out by modelling the system, identifying the assets, threats and vulnerabilities, prioritizing the threats and proposing cost-effective countermeasures for the weaknesses found. ATM security is concerned with securing ATM a...

  10. Automated Biometric Voice-Based Access Control in Automatic Teller Machine (ATM)

    OpenAIRE

    Yekini N.A.; Itegboje A.O.; Oyeyinka I.K.; Akinwole A.K.

    2012-01-01

    An automatic teller machine requires a user to pass an identity test before any transaction can be granted. The current method available for access control in ATM is based on smartcard. Efforts were made to conduct an interview with structured questions among the ATM users and the result proofed that a lot of problems was associated with ATM smartcard for access control. Among the problems are; it is very difficult to prevent another person from attaining and using a legitimate persons card, ...

  11. APPLICATION OF QUEUING THEORY TO AUTOMATED TELLER MACHINE (ATM) FACILITIES USING MONTE CARLO SIMULATION

    OpenAIRE

    UDOANYA RAYMOND MANUEL; ANIEKAN OFFIONG

    2014-01-01

    This paper presents the importance of applying queuing theory to the Automated Teller Machine (ATM) using Monte Carlo Simulation in order to determine, control and manage the level of queuing congestion found within the Automated Teller Machine (ATM) centre in Nigeria and also it contains the empirical data analysis of the queuing systems obtained at the Automated Teller Machine (ATM) located within the Bank premises for a period of three (3) months. Monte Carlo Simulation is applied to th...

  12. PC based vibration monitoring system

    International Nuclear Information System (INIS)

    Jain, Sanjay K.; Roy, D.A.; Pithawa, C.K.; Patil, R.K.

    2004-01-01

    Health of large rotating machinery gets reflected in the vibration signature of the rotor and supporting structures and proper recording of these signals and their analysis can give a clear picture of the health of the machine. Using these data and their trending, it is possible to predict an impending trouble in the machine so that preventive action can be taken in time and catastrophic failure can be avoided. Continuous monitoring and analysis can give quick warning and enable operator to take preventive measures. Reactor Control Division, BARC is developing a PC based Vibration monitoring system for turbo generator machinery. The System can acquire 20 vibration signals at a rate of 5000 samples per second and also 15 process signals at a rate of 100 samples/ sec. The software for vibration monitoring system includes acquisition modules, analysis modules and Graphical User Interface module. The acquisition module involves initialization, setting of required parameters and acquiring the data from PC-based data acquisition cards. The acquired raw vibration data is then stored for analysis using various software packages. The display and analysis of acquired data is done in LabVIEW 7.0 where the data is displayed in time as well as frequency domain along with the RMS value of the signal. (author)

  13. PC driven integrated vacuum system

    International Nuclear Information System (INIS)

    Curuia, Marian; Culcer, Mihai; Brandea, Iulian; Anghel, Mihai

    2001-01-01

    The monitoring of industrial plants by virtual instrumentation represents the most modern trend in the domain of electronic equipment. The integrated vacuum system presented here has several facilities, including the automated data storing of measurement results on hard disk and providing warning messages for operators when the measured parameters are lower or higher upper than the fixed values. The system can also work stand-alone, receiving the commands from the keyboards placed on his front panel but, when it is included in a automation complex system, a remote control from PC is necessary . Both parts of the system, power supply unit for turbo-molecular pump and the vacuum gage, are controlled by an 80C31 microcontroller. Because this microcontroller has a built-in circuitry for a serial communication, we established a serial communication between the PC and the power supply unit for turbo-molecular pump and the vacuum gage, according to the RS-232 hardware standard. As software, after careful evaluation of several options, we chose to develop a hybrid software packing using two different software development tools: LabVIEW, and assembly language. We chose LabVIEW because it is dedicated to data acquisition and communications, containing libraries for data collection, analysis, display and storage. (authors)

  14. PC/104 Embedded IOCs at Jefferson Lab

    International Nuclear Information System (INIS)

    Yan, Jianxun; Allison, Trent; Witherspoon, Sue; Cuffe, Anthony

    2009-01-01

    Jefferson Lab has developed embedded IOCs based on PC/104 single board computers (SBC) for low level control systems. The PC/104 IOCs run EPICS on top of the RTEMS operating system. Two types of control system configurations are used in different applications, PC/104 SBC with commercial PC/104 I/O cards and PC/104 SBC with custom designed FPGA-based boards. RTEMS was built with CEXP shell to run on the PC/104 SBC. CEXP shell provides the function of dynamic object loading, which is similar to the widely used VxWorks operating system. Standard software configurations were setup for PC/104 IOC application development to provide a familiar format for new projects as well as ease the conversion of applications from VME based IOCs to PC/104 IOCs. Many new projects at Jefferson Lab are going to employ PC/104 SBCs as IOCs and some applications have already been running them for accelerator operations. The PC/104 - RTEMS IOC provides a free open source Real-Time Operating System (RTOS), low cost/maintenance, easily installed/ configured, flexible, and reliable solution for accelerator control and 12GeV Upgrade projects.

  15. The Landscape of Somatic Genetic Alterations in Breast Cancers From ATM Germline Mutation Carriers.

    Science.gov (United States)

    Weigelt, Britta; Bi, Rui; Kumar, Rahul; Blecua, Pedro; Mandelker, Diana L; Geyer, Felipe C; Pareja, Fresia; James, Paul A; Couch, Fergus J; Eccles, Diana M; Blows, Fiona; Pharoah, Paul; Li, Anqi; Selenica, Pier; Lim, Raymond S; Jayakumaran, Gowtham; Waddell, Nic; Shen, Ronglai; Norton, Larry; Wen, Hannah Y; Powell, Simon N; Riaz, Nadeem; Robson, Mark E; Reis-Filho, Jorge S; Chenevix-Trench, Georgia

    2018-02-28

    Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53 mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATM variants and TP53 somatic mutations are mutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-related mutational signatures, and that TP53 and ATM genetic alterations are likely epistatic.

  16. 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.

  17. ATM directs DNA damage responses and proteostasis via genetically separable pathways.

    Science.gov (United States)

    Lee, Ji-Hoon; Mand, Michael R; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W; Richards, Alicia L; Coon, Joshua J; Paull, Tanya T

    2018-01-09

    The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated the activation of ATM by DNA damage from that by oxidative stress using separation-of-function mutations. We found that deficient activation of ATM by the Mre11-Rad50-Nbs1 complex and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of a variant ATM incapable of activation by oxidative stress resulted in widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicate ATM in the control of protein homeostasis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  18. 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

    whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice......, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate...

  19. Premeiotic germ cell defect in seminiferous tubules of Atm-null testis

    International Nuclear Information System (INIS)

    Takubo, Keiyo; Hirao, Atsushi; Ohmura, Masako; Azuma, Masaki; Arai, Fumio; Nagamatsu, Go; Suda, Toshio

    2006-01-01

    Lifelong spermatogenesis is maintained by coordinated sequential processes including self-renewal of stem cells, proliferation of spermatogonial cells, meiotic division, and spermiogenesis. It has been shown that ataxia telangiectasia-mutated (ATM) is required for meiotic division of the seminiferous tubules. Here, we show that, in addition to its role in meiosis, ATM has a pivotal role in premeiotic germ cell maintenance. ATM is activated in premeiotic spermatogonial cells and the Atm-null testis shows progressive degeneration. In Atm-null testicular cells, differing from bone marrow cells of Atm-null mice, reactive oxygen species-mediated p16 Ink4a activation does not occur in Atm-null premeiotic germ cells, which suggests the involvement of different signaling pathways from bone marrow defects. Although Atm-null bone marrow undergoes p16 Ink4a -mediated cellular senescence program, Atm-null premeiotic germ cells exhibited cell cycle arrest and apoptotic elimination of premeiotic germ cells, which is different from p16 Ink4a -mediated senescence

  20. Parallel computing and networking; Heiretsu keisanki to network

    Energy Technology Data Exchange (ETDEWEB)

    Asakawa, E; Tsuru, T [Japan National Oil Corp., Tokyo (Japan); Matsuoka, T [Japan Petroleum Exploration Co. Ltd., Tokyo (Japan)

    1996-05-01

    This paper describes the trend of parallel computers used in geophysical exploration. Around 1993 was the early days when the parallel computers began to be used for geophysical exploration. Classification of these computers those days was mainly MIMD (multiple instruction stream, multiple data stream), SIMD (single instruction stream, multiple data stream) and the like. Parallel computers were publicized in the 1994 meeting of the Geophysical Exploration Society as a `high precision imaging technology`. Concerning the library of parallel computers, there was a shift to PVM (parallel virtual machine) in 1993 and to MPI (message passing interface) in 1995. In addition, the compiler of FORTRAN90 was released with support implemented for data parallel and vector computers. In 1993, networks used were Ethernet, FDDI, CDDI and HIPPI. In 1995, the OC-3 products under ATM began to propagate. However, ATM remains to be an interoffice high speed network because the ATM service has not spread yet for the public network. 1 ref.

  1. Future ATM Concepts Evaluation Tool (FACET) Interface Control Document

    Science.gov (United States)

    Grabbe, Shon R.

    2017-01-01

    This Interface Control Document (ICD) documents the airspace adaptation and air traffic inputs of NASA's Future ATM Concepts and Evaluation Tool (FACET). Its intended audience is the project manager, project team, development team, and stakeholders interested in interfacing with the system. FACET equips Air Traffic Management (ATM) researchers and service providers with a way to explore, develop and evaluate advanced air transportation concepts before they are field-tested and eventually deployed. FACET is a flexible software tool that is capable of quickly generating and analyzing thousands of aircraft trajectories. It provides researchers with a simulation environment for preliminary testing of advanced ATM concepts. Using aircraft performance profiles, airspace models, weather data, and flight schedules, the tool models trajectories for the climb, cruise, and descent phases of flight for each type of aircraft. An advanced graphical interface displays traffic patterns in two and three dimensions, under various current and projected conditions for specific airspace regions or over the entire continental United States. The system is able to simulate a full day's dynamic national airspace system (NAS) operations, model system uncertainty, measure the impact of different decision-makers in the NAS, and provide analysis of the results in graphical form, including sector, airport, fix, and airway usage statistics. NASA researchers test and analyze the system-wide impact of new traffic flow management algorithms under anticipated air traffic growth projections on the nation's air traffic system. In addition to modeling the airspace system for NASA research, FACET has also successfully transitioned into a valuable tool for operational use. Federal Aviation Administration (FAA) traffic flow managers and commercial airline dispatchers have used FACET technology for real-time operations planning. FACET integrates live air traffic data from FAA radar systems and weather data

  2. A mathematical model for the detection mechanism of DNA double-strand breaks depending on autophosphorylation of ATM.

    Science.gov (United States)

    Mouri, Kazunari; Nacher, Jose C; Akutsu, Tatsuya

    2009-01-01

    After IR stress, DNA double-strand breaks (DSBs) occur and repair proteins (RPs) bind to them, generating DSB-RP complexes (DSBCs), which results in repaired DSBs (RDSBs). In recent experimental studies, it is suggested that the ATM proteins detect these DNA lesions depending on the autophosphorylation of ATM which exists as a dimer before phosphorylation. Interestingly, the ATM proteins can work as a sensor for a small number of DSBs (approximately 18 DSBs in a cell after exposure to IR). Thus the ATM proteins amplify the small input signals based on the phosphorylation of the ATM dimer proteins. The true DSB-detection mechanism depending on ATM autophosphorylation has yet to be clarified. We propose a mathematical model for the detection mechanism of DSBs by ATM. Our model includes both a DSB-repair mechanism and an ATM-phosphorylation mechanism. We model the former mechanism as a stochastic process, and obtain theoretical mean values of DSBs and DSBCs. In the latter mechanism, it is known that ATM autophosphorylates itself, and we find that the autophosphorylation induces bifurcation of the phosphorylated ATM (ATM*). The bifurcation diagram depends on the total concentration of ATM, which makes three types of steady state diagrams of ATM*: monostable, reversible bistable, and irreversible bistable. Bistability exists depending on the Hill coefficient in the equation of ATM autophosphorylation, and it emerges as the total concentration of ATM increases. Combining these two mechanisms, we find that ATM* exhibits switch-like behaviour in the presence of bistability, and the detection time after DNA damage decreases when the total concentration of ATM increases. This work provides a mathematical model that explains the DSB-detection mechanism depending on ATM autophosphorylation. These results indicate that positive auto-regulation works both as a sensor and amplifier of small input signals.

  3. Asynchronous transfer mode and Local Area Network emulation standards, protocols, and security implications

    OpenAIRE

    Kirwin, John P.

    1999-01-01

    A complex networking technology called Asynchronous Transfer Mode (ATM) and a networking protocol called Local Area Network Emulation (LANE) are being integrated into many naval networks without any security-driven naval configuration guidelines. No single publication is available that describes security issues of data delivery and signaling relating to the transition of Ethernet to LANE and ATM. The thesis' focus is to provide: (1) an overview and security analysis of standardized protocols ...

  4. Tele-ultrasound using ATM over a T-1 satellite connection

    Science.gov (United States)

    Williamson, Morgan P.; Suitor, Charles T.; de Treville, Robert E.; Freckleton, Michael W.; Kinsey, Van; Goeringer, Fred; Lyche, David K.; Hunter, Bruce; Jennings, Neal E.; Shelton, Philip D.; Marcy, Jon; Poore, Tom; North, Jack

    1996-04-01

    In September 1995 the United States military conducted a demonstration project to provide live ultrasound video and diagnostic DICOM still images using GTE's asynchronous transfer mode (ATM) technologies over an Orion T-1 satellite link. Still images were frame-grabbed from a Diasonics ultrasound and sent to the ALI Wide Area Network system. A group of diagnostic images was then sent in DICOM 3.0 format over a virtual ethernet satellite link from Chantilly, Virginia to Dayton, Ohio. These images came across a DICOM gateway into the Medical Diagnostic Imaging Support (MDIS) System. Live video from the ultrasound was also routed through a CLI Radiance VTC over the satellite to a VTC in Ohio. The video bandwidth was progressively narrowed with two radiologists determining the minimal acceptable bandwidth for detecting test objects in a phantom. The radiologists accepted live video ultrasound at bandwidths as low as 384 kbps from the hands of an experienced ultrasonographer located hundreds of miles away. DICOM still images were sent uncompressed and were of acceptable image quality when viewed on the MDIS system. The technology demonstrated holds great promise for both deployed U.S. Military Forces and civil uses of remote radiology. Detailed network drawings and videotapes of the ultrasound examinations at the remote site are provided.

  5. A PC based control system for the CERN ISOLDE separators

    International Nuclear Information System (INIS)

    Billinge, R.; Bret, A.; Deloose, I.; Pace, A.; Shering, G.

    1992-01-01

    The control system of the two isotope separators of CERN, named ISOLDE, is being completely redesigned with the goal of having a flexible, high performance and inexpensive system. A new architecture that makes heavy use of the commercial software and hardware available for the huge Personal Computer (PC) market is being implemented on the 1700 geographically distributed control channels of the separators. 8 MS-DOS TM i386-based PCs with about 80 acquisition/control boards are used to access the equipments while 3 other PCs running Microsoft Windows TM and Microsoft Excel TM are used as consoles, the whole through a Novell TM Local Area Network with a PC Disk Server used as a database. This paper describes the interesting solutions found and discusses the reduced programming work load and costs that are expected to build the system before the start of the separators in March 1992. (author)

  6. Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC.

    Science.gov (United States)

    Petersen, Lars F; Klimowicz, Alexander C; Otsuka, Shannon; Elegbede, Anifat A; Petrillo, Stephanie K; Williamson, Tyler; Williamson, Chris T; Konno, Mie; Lees-Miller, Susan P; Hao, Desiree; Morris, Don; Magliocco, Anthony M; Bebb, D Gwyn

    2017-06-13

    Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients.

  7. 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

    present both a predicted and observed crustal upliftfor the Jakobshavn glacier using ATM data (Airborne Topographic Mapper) from NASA ATM flights during 1997, 2005 and 2010 supplemented with data provided from continuous Global Positioning System (GPS), measurements made on bedrock between 2005...

  8. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. 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.

  10. 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.

  11. 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. Copyright © 2016 the American Physiological Society.

  12. 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 Ida Antoinette; 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

  13. ATM haplotypes and cellular response to DNA damage: association with breast cancer risk and clinical radiosensitivity.

    NARCIS (Netherlands)

    Angele, S.; Romestaing, P.; Moullan, N.; Vuillaume, M.; Chapot, B.; Friesen, M.; Jongmans, W.; Cox, D.G.; Pisani, P.; Gerard, J.P.; Hall, J.

    2003-01-01

    The ATM gene, mutated in the cancer-prone and radiation-sensitive syndrome ataxia-telangiectasia (AT), could predispose to breast cancer (BC) development and adverse radiotherapy responses. Sixteen ATM variants were genotyped in 254 BC cases, 70 of whom were adverse radiotherapy responders (RS-BC),

  14. Analisis Tingkat Kepentingan Dan Kinerja Layanan Automated Teller Machine (Atm) Bank Mandiri

    OpenAIRE

    Setiawati, Lenny; Sugiharto, Toto

    2008-01-01

    Penelitian ini ditujukan untuk menganalisis tingkat kepentingan dan kinerja layananATM Bank Mandiri. Analisis Servqual yang terdiri atas dimensi tangible, realibility,responsiveness, assurance,dan empathy digunakan untuk menganalisis kinerjalayanan ATM. Sementara itu, Customer Satisfaction Index dan ImportancePerformance Analysis yang terdiri atas analisis kuadran dan analisis kesenjangandigunakan untuk menginvestigasi kepuasan pelanggan dan untuk mengidentifikasikandimensi layanan yang kiner...

  15. Materials of 13. conference: ATM'92 - Advanced materials and technologies

    International Nuclear Information System (INIS)

    1992-01-01

    13th conference on metal science, modern materials and technologies (ATM'92) has been held in Popowo near Warsaw, Poland in September 1992. The conference has been divided into 9 sections. There are: Plenary section (7 lectures); Functional materials (12 lectures); Methods of material microstructure shaping (5 lectures and 14 posters); Surface engineering (5 lectures and 27 posters); Composites (5 lectures and 9 posters); Iron alloys A (7 lectures and 8 posters); Iron alloys B (7 lectures and 18 posters); Non-ferrous metal alloys (7 lectures and 11 posters) and Methods for materials research (5 lectures and 23 posters). The new materials preparation, their properties and structure as well as a methods for obtaining a desirable properties of material or their surface have been broadly referred and discussed

  16. Analysis of components from drip tests with ATM-10 glass

    International Nuclear Information System (INIS)

    Fortner, J.A.; Bates, J.K.; Gerding, T.J.

    1996-09-01

    Waste package assemblies consisting of actinide-doped West Valley ATM-10 reference glass and sensitized 304L stainless steel have been reacted with simulated repository groundwater using the Unsaturated Test Method. Analyses of surface corrosion and reaction products resulting from tests that were terminated at scheduled intervals between 13 and 52 weeks are reported. Analyses reveal complex interactions between the groundwater, the sensitized stainless steel waste form holder, and the glass. Alteration phases form that consist mainly of smectite clay, brockite, and an amorphous thorium iron titanium silicate, the latter two incorporating thorium, uranium, and possibly transuranics. The results from the terminated tests, combined with data from tests that are still ongoing, will help determine the suitability of glass waste forms in the proposed high-level repository at the Yucca Mountain Site

  17. 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...... actually protects tumors from being killed by genotoxic agents. Furthermore, ATM-deficient cancer cells display strong nononcogene addiction to DNA-PKcs for survival after DNA damage, such that suppression of DNA-PKcs in vivo resensitizes inherently chemoresistant ATM-deficient tumors to genotoxic...

  18. ARF and ATM/ATR cooperate in p53-mediated apoptosis upon oncogenic stress

    International Nuclear Information System (INIS)

    Pauklin, Siim; Kristjuhan, Arnold; Maimets, Toivo; Jaks, Viljar

    2005-01-01

    Induction of apoptosis is pivotal for eliminating cells with damaged DNA or deregulated proliferation. We show that tumor suppressor ARF and ATM/ATR kinase pathways cooperate in the induction of apoptosis in response to elevated expression of c-myc, β-catenin or human papilloma virus E7 oncogenes. Overexpression of oncogenes leads to the formation of phosphorylated H2AX foci, induction of Rad51 protein levels and ATM/ATR-dependent phosphorylation of p53. Inhibition of ATM/ATR kinases abolishes both induction of Rad51 and phosphorylation of p53, and remarkably reduces the level of apoptosis induced by co-expression of oncogenes and ARF. However, the induction of apoptosis is downregulated in p53-/- cells and does not depend on activities of ATM/ATR kinases, indicating that efficient induction of apoptosis by oncogene activation depends on coordinated action of ARF and ATM/ATR pathways in the regulation of p53

  19. Experiences with ATM in a multivendor pilot system at Forschungszentrum Julich

    Science.gov (United States)

    Kleines, H.; Ziemons, K.; Zwoll, K.

    1998-08-01

    The ATM technology for high speed serial transmission provides a new quality of communication by introducing novel features in a LAN environment, especially support of real time communication, of both LAN and WAN communication and of multimedia streams. In order to evaluate ATM for future DAQ systems and remote control systems as well as for a high speed picture archiving and communications system for medical images, Forschungszentrum Julich has build up a pilot system for the evaluation of ATM and standard low cost multimedia systems. It is a heterogeneous multivendor system containing a variety of switches and desktop solutions, employing different protocol options of ATM. The tests conducted in the pilot system revealed major difficulties regarding stability, interoperability and performance. The paper presents motivations, layout and results of the pilot system. Discussion of results concentrates on performance issues relevant for realistic applications, e.g., connection to a RAID system via NFS over ATM.

  20. ASCIZ/ATMIN is dispensable for ATM signaling in response to replication stress.

    Science.gov (United States)

    Liu, Rui; King, Ashleigh; Hoch, Nicolas C; Chang, Catherine; Kelly, Gemma L; Deans, Andrew J; Heierhorst, Jörg

    2017-09-01

    The ATM kinase plays critical roles in the response to DNA double-strand breaks, and can also be activated by prolonged DNA replication blocks. It has recently been proposed that replication stress-dependent ATM activation is mediated by ASCIZ (also known as ATMIN, ZNF822), an essential developmental transcription factor. In contrast, we show here that ATM activation, and phosphorylation of its substrates KAP1, p53 and H2AX in response to the replication blocking agent aphidicolin was unaffected in both immortalized and primary ASCIZ/ATMIN-deficient murine embryonic fibroblasts compared to control cells. Similar results were also obtained in human ASCIZ/ATMIN-deleted lymphoma cells. The results demonstrate that ASCIZ/ATMIN is dispensable for ATM activation, and contradict the previously reported dependence of ATM on ASCIZ/ATMIN. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. 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.

  2. ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations.

    Science.gov (United States)

    Cheng, Aifang; Zhao, Teng; Tse, Kai-Hei; Chow, Hei-Man; Cui, Yong; Jiang, Liwen; Du, Shengwang; Loy, Michael M T; Herrup, Karl

    2018-01-09

    ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) are large PI3 kinases whose human mutations result in complex syndromes that include a compromised DNA damage response (DDR) and prominent nervous system phenotypes. Both proteins are nuclear-localized in keeping with their DDR functions, yet both are also found in cytoplasm, including on neuronal synaptic vesicles. In ATM- or ATR-deficient neurons, spontaneous vesicle release is reduced, but a drop in ATM or ATR level also slows FM4-64 dye uptake. In keeping with this, both proteins bind to AP-2 complex components as well as to clathrin, suggesting roles in endocytosis and vesicle recycling. The two proteins play complementary roles in the DDR; ATM is engaged in the repair of double-strand breaks, while ATR deals mainly with single-strand damage. Unexpectedly, this complementarity extends to these proteins' synaptic function as well. Superresolution microscopy and coimmunoprecipitation reveal that ATM associates exclusively with excitatory (VGLUT1 + ) vesicles, while ATR associates only with inhibitory (VGAT + ) vesicles. The levels of ATM and ATR respond to each other; when ATM is deficient, ATR levels rise, and vice versa. Finally, blocking NMDA, but not GABA, receptors causes ATM levels to rise while ATR levels respond to GABA, but not NMDA, receptor blockade. Taken together, our data suggest that ATM and ATR are part of the cellular "infrastructure" that maintains the excitatory/inhibitory balance of the nervous system. This idea has important implications for the human diseases resulting from their genetic deficiency.

  3. ATM-Dependent Hyper-Radiosensitivity in Mammalian Cells Irradiated by Heavy Ions

    International Nuclear Information System (INIS)

    Xue Lian; Yu Dong; Furusawa, Yoshiya; Cao Jianping; Okayasu, Ryuichi; Fan Saijun

    2009-01-01

    Purpose: Low-dose hyper-radiosensitivity (HRS) and the later appearing radioresistance (termed induced radioresistance [IRR]) was mainly studied in low linear energy transfer (LET) radiation with survival observation. The aim of this study was to find out whether equivalent hypersensitivity occurred in high LET radiation, and the roles of ataxia telangiectasia mutated (ATM) kinase. Methods and Materials: Survival and mutation were measured by clonogenic assay and HPRT mutation assay. ATM Ser1981 activation was detected by Western blotting and immunofluorescent staining. Pretreatment of specific ATM inhibitor (10 μM KU55933) and activator (20 μg/mL chloroquine) before carbon radiation were adopted to explore the involvement of ATM. The roles of ATM were also investigated in its G2/M checkpoint function with histone H3 phosphorylation analysis and flow cytometric assay, and DNA double strand break (DSB) repair function measured using γ-H2AX foci assay. Results: HRS/IRR was observed with survival and mutation in normal human skin fibroblast cells by carbon ions, while impaired in cells with intrinsic ATM deficiency or normal cells modified with specific ATM activator or inhibitor before irradiation. The dose-response pattern of ATM kinase activation was concordant with the transition from HRS to IRR. The ATM-dependent 'early' G2 checkpoint arrest and DNA DSB repair efficiency could explain the difference between HRS and IRR. Conclusions: These data demonstrate that the HRS/IRR by carbon ion radiation is an ATM-dependent phenomenon in the cellular response to DNA damage.

  4. Asociación entre manifestaciones respiratorias atópicas y contaminantes primarios de la atmósfera

    Directory of Open Access Journals (Sweden)

    Roberto Álvarez Sintes

    1997-06-01

    Full Text Available Se realizó un estudio prospectivo en 94 pacientes asmáticos atendidos en el consultorio del médico de la familia No. 43 perteneciente al Policlínico Docente "Antonio Maceo" del municipio Cerro de Ciudad de La Habana. Durante un año (12 meses consecutivos relacionamos las eventualidades diarias de su estado de salud con los siguientes contaminantes primarios de la atmósfera: dióxido de nitrógeno, dióxido de azufre y hollín. Las muestras fueron analizadas en el Laboratorio de Higiene del Aire del Instituto Nacional de Higiene y Epidemiología del Ministerio de Salud Pública de Cuba. El análisis estadístico se realizó utilizando el entrecruzamiento de variables, regresión múltiple, el método de paso a paso del paquete estadístico SPSS/PC Plus. Se realizó la matriz de correlación lineal paramétrica. Se obtuvo una correlación directa significativa entre la coriza, la tos, las crisis de asma y los contaminantes primarios de la atmósfera.A prospective study of 94 asthmatic patients receiving attention at the family physician's office No. 43 from the "Antonio Maceo" Teaching Polyclinic in Cerro municipality, Havana City, was conducted. During a year (12 months in a row we related their daily health status to the following primary air pollutants: nitrogen dioxide, sulphur dioxide, and soot. The samples were analyzed at the Air Hygiene Laboratory of the National Institute of Hygiene and Epidemiology, Ministry of Public Health. The statistical analysis was made by using the intercrossing of variables, the multiple regression, and the step by step method of the SPSS/PC Plus statistical package. The parametric lineal correlation matrix was also calculated. There was a significant direct correlation among coryza, cough, asthma crises, and the primary air pollutants.

  5. Functional analyses of ATM, ATR and Fanconi anemia proteins in lung carcinoma

    International Nuclear Information System (INIS)

    Beumer, Jan H.; Fu, Katherine Y.; Anyang, Bean N.; Siegfried, Jill M.; Bakkenist, Christopher J.

    2015-01-01

    ATM and ATR are kinases implicated in a myriad of DNA-damage responses. ATM kinase inhibition radiosensitizes cells and selectively kills cells with Fanconi anemia (FA) gene mutations. ATR kinase inhibition sensitizes cells to agents that induce replication stress and selectively kills cells with ATM and TP53 mutations. ATM mutations and FANCF promoter-methylation are reported in lung carcinomas. We undertook functional analyses of ATM, ATR, Chk1 and FA proteins in lung cancer cell lines. We included Calu6 that is reported to be FANCL-deficient. In addition, the cancer genome atlas (TCGA) database was interrogated for alterations in: 1) ATM, MRE11A, RAD50 and NBN; 2) ATR, ATRIP and TOPBP1; and 3) 15 FA genes. No defects in ATM, ATR or Chk1 kinase activation, or FANCD2 monoubiquitination were identified in the lung cancer cell lines examined, including Calu6, and major alterations in these pathways were not identified in the TCGA database. Cell lines were radiosensitized by ATM kinase inhibitor KU60019, but no cell killing by ATM kinase inhibitor alone was observed. While no synergy between gemcitabine or carboplatin and ATR kinase inhibitor ETP-46464 was observed, synergy between gemcitabine and Chk1 kinase inhibitor UCN-01 was observed in 54 T, 201 T and H460, and synergy between carboplatin and Chk1 kinase inhibitor was identified in 201 T and 239 T. No interactions between ATM, ATR and FA activation were observed by either ATM or ATR kinase inhibition in the lung cancer cell lines. Analyses of ATM serine 1981 and Chk1 serine 345 phosphorylation, and FANCD2 monoubiquitination revealed that ATM and ATR kinase activation and FA pathway signaling are intact in the lung cancer cell lines examined. As such, these posttranslational modifications may have utility as biomarkers for the integrity of DNA damage signaling pathways in lung cancer. Different sensitization profiles between gemcitabine and carboplatin and ATR kinase inhibitor ETP-46464 and Chk1 kinase inhibitor

  6. Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers.

    Science.gov (United States)

    Renault, Anne-Laure; Mebirouk, Noura; Fuhrmann, Laetitia; Bataillon, Guillaume; Cavaciuti, Eve; Le Gal, Dorothée; Girard, Elodie; Popova, Tatiana; La Rosa, Philippe; Beauvallet, Juana; Eon-Marchais, Séverine; Dondon, Marie-Gabrielle; d'Enghien, Catherine Dubois; Laugé, Anthony; Chemlali, Walid; Raynal, Virginie; Labbé, Martine; Bièche, Ivan; Baulande, Sylvain; Bay, Jacques-Olivier; Berthet, Pascaline; Caron, Olivier; Buecher, Bruno; Faivre, Laurence; Fresnay, Marc; Gauthier-Villars, Marion; Gesta, Paul; Janin, Nicolas; Lejeune, Sophie; Maugard, Christine; Moutton, Sébastien; Venat-Bouvet, Laurence; Zattara, Hélène; Fricker, Jean-Pierre; Gladieff, Laurence; Coupier, Isabelle; Chenevix-Trench, Georgia; Hall, Janet; Vincent-Salomon, Anne; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Lesueur, Fabienne

    2018-04-17

    The ataxia telangiectasia mutated (ATM) gene is a moderate-risk breast cancer susceptibility gene; germline loss-of-function variants are found in up to 3% of hereditary breast and ovarian cancer (HBOC) families who undergo genetic testing. So far, no clear histopathological and molecular features of breast tumours occurring in ATM deleterious variant carriers have been described, but identification of an ATM-associated tumour signature may help in patient management. To characterise hallmarks of ATM-associated tumours, we performed systematic pathology review of tumours from 21 participants from ataxia-telangiectasia families and 18 participants from HBOC families, as well as copy number profiling on a subset of 23 tumours. Morphology of ATM-associated tumours was compared with that of 599 patients with no BRCA1 and BRCA2 mutations from a hospital-based series, as well as with data from The Cancer Genome Atlas. Absolute copy number and loss of heterozygosity (LOH) profiles were obtained from the OncoScan SNP array. In addition, we performed whole-genome sequencing on four tumours from ATM loss-of-function variant carriers with available frozen material. We found that ATM-associated tumours belong mostly to the luminal B subtype, are tetraploid and show LOH at the ATM locus at 11q22-23. Unlike tumours in which BRCA1 or BRCA2 is inactivated, tumours arising in ATM deleterious variant carriers are not associated with increased large-scale genomic instability as measured by the large-scale state transitions signature. Losses at 13q14.11-q14.3, 17p13.2-p12, 21p11.2-p11.1 and 22q11.23 were observed. Somatic alterations at these loci may therefore represent biomarkers for ATM testing and harbour driver mutations in potentially 'druggable' genes that would allow patients to be directed towards tailored therapeutic strategies. Although ATM is involved in the DNA damage response, ATM-associated tumours are distinct from BRCA1-associated tumours in terms of morphological

  7. Identification of p32 as a novel substrate for ATM in heart

    International Nuclear Information System (INIS)

    Kato, Hisakazu; Takashima, Seiji; Asano, Yoshihiro; Shintani, Yasunori; Yamazaki, Satoru; Seguchi, Osamu; Yamamoto, Hiroyuki; Nakano, Atsushi; Higo, Shuichiro; Ogai, Akiko; Minamino, Tetsuo; Kitakaze, Masafumi; Hori, Masatsugu

    2008-01-01

    Chemotherapeutic agents to induce DNA damage have been limited to use due to severe side effects of cardiotoxicity. ATM (Ataxia-telangiectasia mutated) is an essential protein kinase in triggering DNA damage responses. However, it is unclear how the ATM-mediated DNA damage responses are involved in the cardiac cell damage. To elucidate these functions in heart, we searched for specific substrates of ATM from mouse heart homogenate. Combining an in vitro phosphorylation following anion-exchange chromatography with purification by reverse-phase high-performance liquid chromatography (HPLC), we successfully identified p32, an ASF/SF2-associated protein, as a novel substrate for ATM. An in vitro kinase assay using recombinant p32 revealed that ATM directly phosphorylated p32. Furthermore, we determined Ser 148 of p32 as an ATM phosphorylation site. Since p32 is known to regulate mRNA splicing and transcription, p32 phosphorylation by ATM might be a new transcriptional regulatory pathway for specific DNA damage responses in heart

  8. 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. © 2015 International Federation for Cell Biology.

  9. Lead (Pb) induced ATM-dependent mitophagy via PINK1/Parkin pathway.

    Science.gov (United States)

    Gu, Xueyan; Qi, Yongmei; Feng, Zengxiu; Ma, Lin; Gao, Ke; Zhang, Yingmei

    2018-07-01

    Lead (Pb), a widely distributed environmental pollutant, is known to induce mitochondrial damage as well as autophagy in vitro and in vivo. In this study, we found that Pb could trigger mitophagy in both HEK293 cells and the kidney cortex of male Kunming mice. However, whether ataxia telangiectasis mutated (ATM) which is reported to be linked with PTEN-induced putative kinase 1 (PINK1)/Parkin pathway (a well-characterized mitophagic pathway) participates in the regulation of Pb-induced mitophagy and its exact role remains enigmatic. Our results indicated that Pb activated ATM in vitro and in vivo, and further in vitro studies showed that ATM could co-localize with PINK1 and Parkin in cytosol and interact with PINK1. Knockdown of ATM by siRNA blocked Pb-induced mitophagy even under the circumstance of enhanced accumulation of PINK1 and mitochondrial Parkin. Intriguingly, elevation instead of reduction in phosphorylation level of PINK1 and Parkin was observed in response to ATM knockdown and Pb did not contribute to the further increase of their phosphorylation level, implying that ATM indirectly regulated PINK1/Parkin pathway. These findings reveal a novel mechanism for Pb toxicity and suggest the regulatory importance of ATM in PINK1/Parkin-mediated mitophagy. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Ataxia-telangiectasia mutated (ATM) silencing promotes neuroblastoma progression through a MYCN independent mechanism

    Science.gov (United States)

    Mandriota, Stefano J.; Valentijn, Linda J.; Lesne, Laurence; Betts, David R.; Marino, Denis; Boudal-Khoshbeen, Mary; London, Wendy B.; Rougemont, Anne-Laure; Attiyeh, Edward F.; Maris, John M.; Hogarty, Michael D.; Koster, Jan; Molenaar, Jan J.; Versteeg, Rogier

    2015-01-01

    Neuroblastoma, a childhood cancer with highly heterogeneous biology and clinical behavior, is characterized by genomic aberrations including amplification of MYCN. Hemizygous deletion of chromosome 11q is a well-established, independent marker of poor prognosis. While 11q22-q23 is the most frequently deleted region, the neuroblastoma tumor suppressor in this region remains to be identified. Chromosome bands 11q22-q23 contain ATM, a cell cycle checkpoint kinase and tumor suppressor playing a pivotal role in the DNA damage response. Here, we report that haploinsufficiency of ATM in neuroblastoma correlates with lower ATM expression, event-free survival, and overall survival. ATM loss occurs in high stage neuroblastoma without MYCN amplification. In SK-N-SH, CLB-Ga and GI-ME-N human neuroblastoma cells, stable ATM silencing promotes neuroblastoma progression in soft agar assays, and in subcutaneous xenografts in nude mice. This effect is dependent on the extent of ATM silencing and does not appear to involve MYCN. Our findings identify ATM as a potential haploinsufficient neuroblastoma tumor suppressor, whose inactivation mirrors the increased aggressiveness associated with 11q deletion in neuroblastoma. PMID:26053094

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

    Science.gov (United States)

    Daniel, Jeremy A; Pellegrini, Manuela; Lee, Baeck-Seung; Guo, Zhi; Filsuf, Darius; Belkina, Natalya V; You, Zhongsheng; Paull, Tanya T; Sleckman, Barry P; Feigenbaum, Lionel; Nussenzweig, André

    2012-08-06

    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 whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate-ribose) polymerase inhibition and increased genomic instability. These results may explain why missense mutations with no detectable kinase activity are rarely found in patients with classical A-T. We propose that ATM kinase-inactive missense mutations, unless otherwise compensated for, interfere with HR during embryogenesis.

  12. Function of the ATR N-terminal domain revealed by an ATM/ATR chimera

    International Nuclear Information System (INIS)

    Chen Xinping; Zhao Runxiang; Glick, Gloria G.; Cortez, David

    2007-01-01

    The ATM and ATR kinases function at the apex of checkpoint signaling pathways. These kinases share significant sequence similarity, phosphorylate many of the same substrates, and have overlapping roles in initiating cell cycle checkpoints. However, they sense DNA damage through distinct mechanisms. ATR primarily senses single stranded DNA (ssDNA) through its interaction with ATRIP, and ATM senses double strand breaks through its interaction with Nbs1. We determined that the N-terminus of ATR contains a domain that binds ATRIP. Attaching this domain to ATM allowed the fusion protein (ATM*) to bind ATRIP and associate with RPA-coated ssDNA. ATM* also gained the ability to localize efficiently to stalled replication forks as well as double strand breaks. Despite having normal kinase activity when tested in vitro and being phosphorylated on S1981 in vivo, ATM* is defective in checkpoint signaling and does not complement cellular deficiencies in either ATM or ATR. These data indicate that the N-terminus of ATR is sufficient to bind ATRIP and to promote localization to sites of replication stress

  13. Human lymphocyte damage and phosphorylation of H2AX and ATM induced by γ-rays

    International Nuclear Information System (INIS)

    Tian Mei; Pan Yan; Liu Jianxiang; Ruan Jianlei; Su Xu

    2011-01-01

    Objective: To investigate 60 Co γ-ray induced damage in lymphocytes and the relationship between doses of 60 Co γ-ray irradiation and the levels of phosphorylated H2AX and ATM. Methods: Cells were irradiated with 60 Co γ-rays in the range of 0-8 Gy. The levels of phosphorylated H2AX and ATM were detected by Western blot and FACScan,respectively. The micronucleus(MN)was analyzed by CB method to evaluate DNA damage. Results: FACScan results showed the dose-effect relationship of γ-H2AX expression were linear.square at 0.5 h post-irradiation to different doses, and the fitting curve was shown as Y=3.96+11.29D-0.45D 2 . The level of phosphorylated ATM (p-ATM) was not changed significantly by using the same method. Western blot showed that p-ATM protein expression was significantly increased after irradiation compared with sham, irradiated group. The MN assay which represented DNA damage was sensitive to different doses. Conclusions: γ-ray irradiation could induce the phosphorylation of H2AX and ATM, which may play an important role in indicating DNA damage. Both of H2AX and ATM have the potential as sensitive biomarker and biodosimeter for radiation damage. (authors)

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

    International Nuclear Information System (INIS)

    Kuang, Xianghong; Shen, Jianjun; Wong, Paul K.Y.; Yan, Mingshan

    2009-01-01

    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.

  15. 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.

  16. Promoter Hypermethylation of the ATM Gene as a Novel Biomarker for Breast Cancer

    Science.gov (United States)

    Begam, Nasrin; Jamil, Kaiser; Raju, Suryanarayana G

    2017-11-26

    Background: Breast cancer may be induced by activation of protooncogenes to oncogenes and in many cases inactivation of tumor suppressor genes. Ataxia telangiectasia mutated (ATM) is an important tumor suppressor gene which plays central roles in the maintenance of genomic integrity by activating cell cycle checkpoints and promoting repair of double-strand breaks of DNA. In breast cancer, decrease ATM expression correlates with a poor outcome; however, the molecular mechanisms underlying downregulation are still unclear. Promoter hypermethylation may contribute in downregulation. Hence the present investigation was designed to evaluate promoter methylation and expression of the ATM gene in breast cancer cases, and to determine links with clinical and demographic manifestations, in a South Indian population. Methods: Tumor biopsy samples were collected from 50 pathologically confirmed sporadic breast cancer cases. DNA was isolated from tumor and adjacent non-tumorous regions, and sodium bisulfite conversion and methylation-specific PCR were performed using MS-PCR primers for the ATM promoter region. In addition, ATM mRNA expression was also analyzed for all samples using real-time PCR. Results: Fifty eight percent (58%) of cancer tissue samples showed promoter hypermethylation for the ATM gene, in contrast to only 4.44% of normal tissues (p= 0.0001). Furthermore, ATM promoter methylation was positively associated with age (p = 0.01), tumor size (p=0.045) and advanced stage of disease i.e. stages III and IV (p =0.019). An association between promoter hypermethylation and lower expression of ATM mRNA was also found (p=0.035). Conclusion: We report for the first time that promoter hypermethylation of ATM gene may be useful as a potential new biomarker for breast cancer, especially in the relatively young patients. Creative Commons Attribution License

  17. ATM and p53 combined analysis predicts survival in glioblastoma multiforme patients: A clinicopathologic study.

    Science.gov (United States)

    Romano, Francesco Jacopo; Guadagno, Elia; Solari, Domenico; Borrelli, Giorgio; Pignatiello, Sara; Cappabianca, Paolo; Del Basso De Caro, Marialaura

    2018-06-01

    Glioblastoma is one of the most malignant cancers, with a distinguishing dismal prognosis: surgery followed by chemo- and radiotherapy represents the current standard of care, and chemo- and radioresistance underlie disease recurrence and short overall survival of patients suffering from this malignancy. ATM is a kinase activated by autophosphorylation upon DNA doublestrand breaks arising from errors during replication, byproducts of metabolism, chemotherapy or ionizing radiations; TP53 is one of the most popular tumor suppressor, with a preeminent role in DNA damage response and repair. To study the effects of the immunohistochemical expression of p-ATM and p53 in glioblastoma patients, 21 cases were retrospectively examined. In normal brain tissue, p-ATM was expressed only in neurons; conversely, in tumors cells, the protein showed a variable cytoplasmic expression (score: +,++,+++), with being completely undetectable in three cases. Statistical analysis revealed that high p-ATM score (++/+++) strongly correlated to shorter survival (P = 0.022). No difference in overall survival was registered between p53 normally expressed (NE) and overexpressed (OE) glioblastoma patients (P = 0.669). Survival analysis performed on the results from combined assessment of the two proteins showed that patients with NE p53 /low pATM score had longer overall survival than the NE p53/ high pATM score counterpart. Cox-regression analysis confirmed this finding (HR = 0.025; CI 95% = 0.002-0.284; P = 0.003). Our study outlined the immunohistochemical expression of p-ATM/p53 in glioblastomas and provided data on their possible prognostic/predictive of response role. A "non-oncogene addiction" to ATM for NEp53 glioblastoma could be postulated, strengthening the rationale for development of ATM inhibiting drugs. © 2018 Wiley Periodicals, Inc.

  18. 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....

  19. PC-Reactor-core transient simulation code

    International Nuclear Information System (INIS)

    Nakata, H.

    1989-10-01

    PC-REATOR, a reactor core transient simulation code has been developed for the real-time operator training on a IBM-PC microcomputer. The program presents capabilities for on-line exchange of the operating parameters during the transient simulation, by friendly keyboard instructions. The model is based on the point-kinetics approximation, with 2 delayed neutron percursors and up to 11 decay power generating groups. (author) [pt

  20. Pc Card Sony Ericsson: Semiotik Dan Iklan

    OpenAIRE

    Mutmainnah, Yulia

    2014-01-01

    Through advertisement, producers send messages for their product strength to consumers. Those messages are conveyed through various kinds of signs either in the form of language, picture, caption, icon, index, or symbol. There is communicative exchange on GC79 PC Card Sony Ericsson advertisement between sender and receiver. Sender (advertisement maker) of this advertisement makes good use of reward polluter style, which is, persuading comsumers to use PC Card Sony Ericsson product.

  1. PC 11: Symbiotic star or planetary nebulae?

    International Nuclear Information System (INIS)

    Gutierrez-Moreno, A.; Moreno, H.; Cortes, G.

    1987-01-01

    PC 11 is an object listed in Perek and Kohoutek (1967) Catalogue of Galactic Planetary Nebulae as PK 331 -5 0 1. Some authors suggest that it is not a planetary nebula, but that it has some characteristics (though not all) of symbiotic stars. We have made photographic, spectrophotometric and spectroscopic observations of PC 11. The analysis of the results suggests that it is a young planetary nebula. (Author)

  2. 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.

  3. MPLS for metropolitan area networks

    CERN Document Server

    Tan, Nam-Kee

    2004-01-01

    METROPOLITAN AREA NETWORKS AND MPLSRequirements of Metropolitan Area Network ServicesMetropolitan Area Network OverviewThe Bandwidth DemandThe Metro Service Provider's Business ApproachesThe Emerging Metro Customer Expectations and NeedsSome Prevailing Metro Service OpportunitiesService Aspects and RequirementsRoles of MPLS in Metropolitan Area NetworksMPLS PrimerMPLS ApplicationsTRAFFIC ENGINEERING ASPECTS OF METROPOLITAN AREA NETWORKSTraffic Engineering ConceptsNetwork CongestionHyper Aggregation ProblemEasing CongestionNetwork ControlTactical versus Strategic Traffic EngineeringIP/ATM Overl

  4. Gender, academic achievement, and ownership of ATM as predictors of accounting students’ financial literacy

    Science.gov (United States)

    Susanti; Hardini, H. T.

    2018-01-01

    This study examined the relationships between GPA, gender, and ownership of ATM on accounting students’ financial literacy (n = 184). Financial literacy was assessed using a paper-and-pencil objective (multiple choice) test measuring general knowledge of finance, income, money management savings, loans, and investment. Gender and GPA data were obtained from the university records. Regression analysis found that GPA and ownership of ATM were associated with financial literacy, but gender was not. Female students with an ownership of ATM and those with a high GPA were found to be superior to males. The implication of this research is that students are expected to increase their GPA and utilize financial facilities in the form of ownership ATM and other financial instruments so as to increase financial literacy. In addition, the need for financial literacy training from related parties to improve financial literacy for students who have low financial literacy.

  5. Pre-IceBridge ATM L2 Icessn Elevation, Slope, and Roughness

    Data.gov (United States)

    National Aeronautics and Space Administration — The NASA Pre-IceBridge ATM Level-2 Icessn Elevation, Slope, and Roughness (BLATM2) data set contains resampled and smoothed elevation measurements of Arctic and...

  6. Four-Hour Dives with Exercise While Breathing Oxygen Partial Pressure of 1.3 ATM

    National Research Council Canada - National Science Library

    Shykoff, B

    2006-01-01

    ...) or less but does not address the possible accumulation of effects over multiple days. We have conducted experimental four-hour dives with oxygen partial pressure (Po2) of approximately 1.4 atmospheres (atm...

  7. Three-Hour Dives with Exercise While Breathing Oxygen Partial Pressure of 1.3 ATM

    National Research Council Canada - National Science Library

    Shykoff, B

    2007-01-01

    ...) or less but does not address the possible accumulation of effects over multiple days. When we conducted experimental four-hour dives with oxygen partial pressure (Po2) of approximately 1.4 atmospheres (atm...

  8. A Novel Method to Screen for Dominant Negative ATM Mutations in Familial Breast Cancer

    National Research Council Canada - National Science Library

    Khanna, Kum K; Chenevix-Trench, Georgia; Grimmond, Sean

    2005-01-01

    The aim of this proposal is to identify families carrying potentially pathogenic A TM mutations by assaying for ATM kinase activity in cell lines derived from individuals with multiple cases of breast...

  9. ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

    National Research Council Canada - National Science Library

    Rosenstein, Barry S

    2005-01-01

    The hypothesis being tested in this project is that a greater proportion of patients who develop radiation-induced subcutaneous late tissue morbidity possess a variant allele in the ATM gene compared...

  10. ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

    National Research Council Canada - National Science Library

    Rosenstein, Barry S

    2006-01-01

    The hypothesis being tested in this project is that a greater proportion of patients who develop radiation-induced subcutaneous late tissue morbidity possess a variant allele in the ATM gene compared...

  11. Gene mutation in ATM/PI3K region of nasopharyngeal carcinoma cell lines

    International Nuclear Information System (INIS)

    Wang Hongmei; Wu Xinyao; Xia Yunfei

    2002-01-01

    Objective: To define the correlation between nasopharyngeal carcinoma (NPC) cell radiosensitivity and gene mutation in the ATM/PI3K coding region. Methods: The gene mutation in the ATM/PI3K region of nasopharyngeal carcinoma cell lines which vary in radiosensitivity, was monitored by reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence-marked ddNTP cycle sequencing technique. Results: No gene mutation was detected in the ATM/PI3K region of either CNE1 or CNE2. Conclusion: Disparity in intrinsic radiosensitivity between different NPC cell lines depends on some other factors and mechanism without being related to ATM/PI3K mutations

  12. Phenotypic Analysis of ATM Protein Kinase in DNA Double-Strand Break Formation and Repair.

    Science.gov (United States)

    Mian, Elisabeth; Wiesmüller, Lisa

    2017-01-01

    Ataxia telangiectasia mutated (ATM) encodes a serine/threonine protein kinase, which is involved in various regulatory processes in mammalian cells. Its best-known role is apical activation of the DNA damage response following generation of DNA double-strand breaks (DSBs). When DSBs appear, sensor and mediator proteins are recruited, activating transducers such as ATM, which in turn relay a widespread signal to a multitude of downstream effectors. ATM mutation causes Ataxia telangiectasia (AT), whereby the disease phenotype shows differing characteristics depending on the underlying ATM mutation. However, all phenotypes share progressive neurodegeneration and marked predisposition to malignancies at the organismal level and sensitivity to ionizing radiation and chromosome aberrations at the cellular level. Expression and localization of the ATM protein can be determined via western blotting and immunofluorescence microscopy; however, detection of subtle alterations such as resulting from amino acid exchanges rather than truncating mutations requires functional testing. Previous studies on the role of ATM in DSB repair, which connects with radiosensitivity and chromosomal stability, gave at first sight contradictory results. To systematically explore the effects of clinically relevant ATM mutations on DSB repair, we engaged a series of lymphoblastoid cell lines (LCLs) derived from AT patients and controls. To examine DSB repair both in a quantitative and qualitative manners, we used an EGFP-based assay comprising different substrates for distinct DSB repair mechanisms. In this way, we demonstrated that particular signaling defects caused by individual ATM mutations led to specific DSB repair phenotypes. To explore the impact of ATM on carcinogenic chromosomal aberrations, we monitored chromosomal breakage at a breakpoint cluster region hotspot within the MLL gene that has been associated with therapy-related leukemia. PCR-based MLL-breakage analysis of HeLa cells

  13. ATM Polymorphisms Are Associated With Risk of Radiation-Induced Pneumonitis

    International Nuclear Information System (INIS)

    Zhang Li; Yang Ming; Bi Nan; Fang Mingjing; Sun Tong; Ji Wei; Tan Wen; Zhao Lujun; Yu Dianke; Lin Dongxin; Wang Luhua

    2010-01-01

    Purpose: Since the ataxia telangiectasia mutated (ATM) protein plays crucial roles in repair of double-stranded DNA breaks, control of cell cycle checkpoints, and radiosensitivity, we hypothesized that variations in this gene might be associated with radiation-induced pneumonitis (RP). Methods and Materials: A total of 253 lung cancer patients receiving thoracic irradiation between 2004 and 2006 were included in this study. Common Terminology Criteria for Adverse Events version 3.0 was used to grade RP. Five haplotype-tagging single nucleotide polymorphisms (SNPs) in the ATM gene were genotyped using DNA from blood lymphocytes. Hazard ratios (HRs) and 95% confidence intervals (CIs) of RP for genotypes were computed by the Cox model, adjusted for clinical factors. The function of the ATM SNP associated with RP was examined by biochemical assays. Results: During the median 22-month follow-up, 44 (17.4%) patients developed grade ≥ 2 RP. In multivariate Cox regression models adjusted for other clinical predictors, we found two ATM variants were independently associated with increased RP risk. They were an 111G > A) polymorphism (HR, 2.49; 95% CI, 1.07-5.80) and an ATM 126713G > A polymorphism (HR, 2.47; 95% CI, 1.16-5.28). Furthermore, genotype-dependent differences in ATM expression were demonstrated both in cell lines (p < 0.001) and in individual lung tissue samples (p = 0.003), which supported the results of the association study. Conclusions: Genetic polymorphisms of ATM are significantly associated with RP risk. These variants might exert their effect through regulation of ATM expression and serve as independent biomarkers for prediction of RP in patients treated with thoracic radiotherapy.

  14. Factors affecting on customers’ satisfaction an empirical investigation of ATM service

    OpenAIRE

    Kumbhar, Vijay

    2011-01-01

    The present empirical study focuses on identifying key factors that have influences customers satisfaction in ATM service provided by public and private sector banks. For the purpose of the study primary data were collected using schedule and collected data from March to November 2010. Results of factor analysis, correlation and regression analysis show that a cost effectiveness, easy to use and security and responsiveness in ATM service were most important factors in customer satisfaction.

  15. Ataxia telangiectasia mutated (ATM) interacts with p400 ATPase for an efficient DNA damage response.

    Science.gov (United States)

    Smith, Rebecca J; Savoian, Matthew S; Weber, Lauren E; Park, Jeong Hyeon

    2016-11-04

    Ataxia telangiectasia mutated (ATM) and TRRAP proteins belong to the phosphatidylinositol 3-kinase-related kinase family and are involved in DNA damage repair and chromatin remodeling. ATM is a checkpoint kinase that is recruited to sites of DNA double-strand breaks where it phosphorylates a diverse range of proteins that are part of the chromatin and DNA repair machinery. As an integral subunit of the TRRAP-TIP60 complexes, p400 ATPase is a chromatin remodeler that is also targeted to DNA double-strand break sites. While it is understood that DNA binding transcriptional activators recruit p400 ATPase into a regulatory region of the promoter, how p400 recognises and moves to DNA double-strand break sites is far less clear. Here we investigate a possibility whether ATM serves as a shuttle to deliver p400 to break sites. Our data indicate that p400 co-immunoprecipitates with ATM independently of DNA damage state and that the N-terminal domain of p400 is vital for this interaction. Heterologous expression studies using Sf9 cells revealed that the ATM-p400 complex can be reconstituted without other mammalian bridging proteins. Overexpression of ATM-interacting p400 regions in U2OS cells induced dominant negative effects including the inhibition of both DNA damage repair and cell proliferation. Consistent with the dominant negative effect, the stable expression of an N-terminal p400 fragment showed a decrease in the association of p400 with ATM, but did not alter the association of p400 with TRRAP. Taken together, our findings suggest that a protein-protein interaction between ATM and p400 ATPase occurs independently of DNA damage and contributes to efficient DNA damage response and repair.

  16. ATM/RB1 mutations predict shorter overall survival in urothelial cancer.

    Science.gov (United States)

    Yin, Ming; Grivas, Petros; Emamekhoo, Hamid; Mendiratta, Prateek; Ali, Siraj; Hsu, JoAnn; Vasekar, Monali; Drabick, Joseph J; Pal, Sumanta; Joshi, Monika

    2018-03-30

    Mutations of DNA repair genes, e.g. ATM/RB1 , are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of ATM/RB1 mutations in UC can inform clinical decision making and trial designs. In the discovery dataset, ATM/RB1 mutations were present in 24% of patients and were associated with shorter OS (adjusted HR 2.67, 95% CI, 1.45-4.92, p = 0.002). There was a higher mutation load in patients carrying ATM/RB1 mutations (median mutation load: 6.7 versus 5.5 per Mb, p = 0.072). In the validation dataset, ATM/RB1 mutations were present in 22.2% of patients and were non-significantly associated with shorter OS (adjusted HR 1.87, 95% CI, 0.97-3.59, p = 0.06) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, p = 0.126). Exome sequencing data of 130 bladder UC patients from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of ATM/RB1 mutations. Results were validated in an independent cohort of 81 advanced UC patients. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) to compare overall survival (OS). ATM/RB1 mutations may be a biomarker of poor prognosis in unselected UC patients and may correlate with higher mutational load. Further studies are required to determine factors that can further stratify prognosis and evaluate predictive role of ATM/RB1 mutation status to immunotherapy and platinum-based chemotherapy.

  17. Expression and clinical significance of ATM and PUMA gene in patients with colorectal cancer.

    Science.gov (United States)

    Xiong, Hui; Zhang, Jiangnan

    2017-12-01

    The expression of ataxia-telangiectasia mutated (ATM) and p53 upregulated modulator of apoptosis (PUMA) genes in patients with colorectal cancer were investigated, to explore the correlation between the expression of ATM and PUMA and tumor development, to evaluate the clinical significance of ATM and PUMA in the treatment of colorectal cancer. Quantitative real-time PCR was used to detect the expression of ATM and PUMA in tumor tissue and adjacent healthy tissue of 67 patients with colorectal cancer and in normal colorectal tissue of 33 patients with colorectal polyps at mRNA level. The expression level of ATM mRNA in colorectal cancer tissues was significantly higher than that in normal mucosa tissues and adjacent non-cancerous tissue (P≤0.05), while no significant differences in expression level of ATM mRNA were found between normal mucosa tissues and adjacent noncancerous tissue (P=0.07). There was a negative correlation between the expression of ATM mRNA and the degree of differentiation of colorectal cancer (r= -0.312, P=0.013), while expression level of ATM mRNA was not significantly correlated with the age, sex, tumor invasion, lymph node metastasis or clinical stage (P>0.05). Expression levels of PUMA mRNA in colorectal cancer tissues, adjacent noncancerous tissue and normal tissues were 0.68±0.07, 0.88±0.04 and 1.76±0.06, respectively. Expression level of PUMA mRNA in colorectal cancer tissues and adjacent noncancerous tissue was significantly lower than that in normal colorectal tissues (PATM mRNA is expressed abnormally in colorectal cancer tissues. Expression of PUMA gene in colorectal carcinoma is downregulated, and is negatively correlated with the occurrence of cancer.

  18. 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.

  19. Complex control of ATM in response to radiation damage to DNA

    International Nuclear Information System (INIS)

    Lavin, M.F.; Beamish, H.; Chen, P.; Keating, K.; Scott, S.; Spring, K.; Kozlov, S.; Walters, D.

    2000-01-01

    Full text: The human genetic disorder ataxia-telangiectasia is characterized by neurodegeneration, immunodeficiency, extreme sensitivity to ionizing radiation, abnormalities in cell cycle checkpoints and a predisposition to develop leukemias and lymphomas. It appears likely that the basis of the hypersensitivity to ionizing radiation is due to defective sensing of double strand breaks in DNA and as a consequence a failure to repair all of these breaks. After exposure of cells to radiation the kinase activity of pre-existing ATM protein is rapidly activated leading to the radiation-induced phosphoylation of a number of important substrates including p53, c-Abl, BRCA1, NBS1 and chk2. Defective phosphorylation of BRCA1 and NBS1 is associated with increased sensitivity to ionizing radiation. We have also demonstrated that a reduction in the amount of ATM protein using antisense ATM cDNA transfection prior to exposure to radiation also sensitizes cells. This was further confirmed by treating human lymphoblastoid cells with EGF prior to radiation exposure. Furthermore radiation reverses the downregulation of ATM by EGF over a 3 hour period. Under these conditions cells are still sensitized to radiation since the restoration of ATM kinase activity is slower than that arising from activation of existing protein. Alterations in the amount of ATM protein are also observed in response to mitogenic agents. Thus it is evident that ATM protein and kinase activity are regulated in a complex fashion and this appears to vary in different tissues. The implications for altering ATM for therapeutic benefit will be discussed

  20. Fabrication and characterization of MCC [Materials Characterization Center] approved testing material: ATM-10 glass

    International Nuclear Information System (INIS)

    Maupin, G.D.; Bowen, W.M.; Daniel, J.L.

    1988-04-01

    The Materials Characterization Center ATM-10 glass represents a reference commercial high-level waste form similar to that which will be produced by the West Valley Nuclear Service Co. Inc., West Valley, New York. The target composition and acceptable range of composition were defined by the sponsor, West Valley Nuclear Service. The ATM-10 glass was produced in accordance with the Pacific Northwest Laboratory QA Manual for License-Related Programs, MCC technical procedures, and MCC QA Plan that were in effect during the course of the work. The method and procedure to be used in the fabrication and characterization of the ATM-10 glass were specified in two run plans for glass preparation and a characterization plan. All of the ATM-10 glass was produced in the form of bars 1.9 /times/ 1.9 /times/ 10 cm nominal size, and 93 g nominal mass. A total of 15 bars of ATM-10 glass weighing 1394 g was produced. The production bars were characterized to determine the mean composition, oxidation state, and microstructure of the ATM-10 product. Table A summarizes the characterization results. The ATM-10 glass meets all specifications. The elemental composition and oxidation state of the glass are within the specifications of the client. Visually, the ATM-10 glass bars appear uniformly glassy and generally without exterior features. Microscopic examination revealed low (less than 2 wt %) concentractions of 3-μm iron-chrome (suspected spinel) crystals and /approximately/0.5-μm ruthenium inclusions scattered randomly throughout the glassy matrix. Closed porosity, with pores ranging in diameter from 5 to 250 μm, was observed in all samples. 4 refs., 10 figs., 21 tabs

  1. A PC-PCL-based control system for the high-voltage pulsed-power operation of the Intense Diagnostic Neutral Beam (IDNB) Experiment

    International Nuclear Information System (INIS)

    Gribble, R.

    1993-06-01

    A stand-alone, semiautomated control system for the high-voltage pulsed-power energy sources on the Intense Diagnostic Neutral Beam Experiment at Los Alamos National Laboratory using personal computer (PC) and programmable logic controller (PLC) technology has been developed and implemented. The control system, consisting of a PC with the graphic operator interface, the network connecting the PC to the PLC, the PLC, the PLC I/O modules, fiber-optic interfaces and software, is described

  2. ATM regulates 3-methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents.

    Science.gov (United States)

    Agnihotri, Sameer; Burrell, Kelly; Buczkowicz, Pawel; Remke, Marc; Golbourn, Brian; Chornenkyy, Yevgen; Gajadhar, Aaron; Fernandez, Nestor A; Clarke, Ian D; Barszczyk, Mark S; Pajovic, Sanja; Ternamian, Christian; Head, Renee; Sabha, Nesrin; Sobol, Robert W; Taylor, Michael D; Rutka, James T; Jones, Chris; Dirks, Peter B; Zadeh, Gelareh; Hawkins, Cynthia

    2014-10-01

    Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular, the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM), were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors. Inhibition of ATM and MPG-mediated BER cooperate to sensitize tumor cells to alkylating agents, impairing tumor growth in vitro and in vivo with no toxicity to normal cells, providing an ideal therapeutic window. ©2014 American Association for Cancer Research.

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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.

  5. 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

    2014-01-01

    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. PMID:24672010

  6. Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria.

    Science.gov (United States)

    Qian, Minxian; Liu, Zuojun; Peng, Linyuan; Tang, Xiaolong; Meng, Fanbiao; Ao, Ying; Zhou, Mingyan; Wang, Ming; Cao, Xinyue; Qin, Baoming; Wang, Zimei; Zhou, Zhongjun; Wang, Guangming; Gao, Zhengliang; Xu, Jun; Liu, Baohua

    2018-05-02

    DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 extend lifespan in Atm-/- mice, with restored metabolic homeostasis. Moreover, the treatment with CQ remarkably extends lifespan of Caenorhabditis elegans , but not the ATM-1 mutants. In a progeria mouse model with low DNA repair capacity, long-term administration of CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases. © 2018, Qian et al.

  7. ATM phosphorylation in HepG2 cells following continuous low dose-rate irradiation

    International Nuclear Information System (INIS)

    Mei Quelin; Du Duanming; Chen Zaizhong; Liu Pengcheng; Yang Jianyong; Li Yanhao

    2008-01-01

    Objective: To investigate the change of ATM phosphorylation in HepG2 cells following a continuous low dose-rate irradiation. Methods: Cells were persistently exposed to low dose-rate (8.28 cGy/h) irradiation. Indirect immunofluorescence and Western blot were used to detect the expression of ATM phosphorylated proteins. Colony forming assay was used to observe the effect of a low dose-rate irradiation on HepG2 cell survival. Results: After 30 min of low dose-rate irradiation, the phosphorylation of ATM occurred. After 6 h persistent irradiation, the expression of ATM phosphorylated protein reached the peak value, then gradually decreased. After ATM phosphorylation was inhibited with Wortmannin, the surviving fraction of HepG2 cells was lower than that of the irradiation alone group at each time point (P<0.05). Conclusions: Continuous low dose-rate irradiation attenuated ATM phosphorylation, suggesting that continuous low dose-rate irradiation has a potential effect for increasing the radiosensitivity of HepG2 cells. (authors)

  8. Upgrading of analogue gamma cameras with PC based computer system

    International Nuclear Information System (INIS)

    Fidler, V.; Prepadnik, M.

    2002-01-01

    Full text: Dedicated nuclear medicine computers for acquisition and processing of images from analogue gamma cameras in developing countries are in many cases faulty and technologically obsolete. The aim of the upgrading project of International Atomic Energy Agency (IAEA) was to support the development of the PC based computer system which would cost 5.000 $ in total. Several research institutions from different countries (China, Cuba, India and Slovenia) were financially supported in this development. The basic demands for the system were: one acquisition card an ISA bus, image resolution up to 256x256, SVGA graphics, low count loss at high count rates, standard acquisition and clinical protocols incorporated in PIP (Portable Image Processing), on-line energy and uniformity correction, graphic printing and networking. The most functionally stable acquisition system tested on several international workshops and university clinics was the Slovenian one with a complete set of acquisition and clinical protocols, transfer of scintigraphic data from acquisition card to PC through PORT, count loss less than 1 % at count rate of 120 kc/s, improvement of integral uniformity index by a factor of 3-5 times, reporting, networking and archiving solutions for simple MS network or server oriented network systems (NT server, etc). More than 300 gamma cameras in 52 countries were digitized and put in the routine work. The project of upgrading the analogue gamma cameras yielded a high promotion of nuclear medicine in the developing countries by replacing the old computer systems, improving the technological knowledge of end users on workshops and training courses and lowering the maintenance cost of the departments. (author)

  9. 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)

  10. Networking

    OpenAIRE

    Rauno Lindholm, Daniel; Boisen Devantier, Lykke; Nyborg, Karoline Lykke; Høgsbro, Andreas; Fries, de; Skovlund, Louise

    2016-01-01

    The purpose of this project was to examine what influencing factor that has had an impact on the presumed increasement of the use of networking among academics on the labour market and how it is expressed. On the basis of the influence from globalization on the labour market it can be concluded that the globalization has transformed the labour market into a market based on the organization of networks. In this new organization there is a greater emphasis on employees having social qualificati...

  11. Internet2-based 3D PET image reconstruction using a PC cluster

    International Nuclear Information System (INIS)

    Shattuck, D.W.; Rapela, J.; Asma, E.; Leahy, R.M.; Chatzioannou, A.; Qi, J.

    2002-01-01

    We describe an approach to fast iterative reconstruction from fully three-dimensional (3D) PET data using a network of PentiumIII PCs configured as a Beowulf cluster. To facilitate the use of this system, we have developed a browser-based interface using Java. The system compresses PET data on the user's machine, sends these data over a network, and instructs the PC cluster to reconstruct the image. The cluster implements a parallelized version of our preconditioned conjugate gradient method for fully 3D MAP image reconstruction. We report on the speed-up factors using the Beowulf approach and the impacts of communication latencies in the local cluster network and the network connection between the user's machine and our PC cluster. (author)

  12. Compartment-Specific Biosensors Reveal a Complementary Subcellular Distribution of Bioactive Furin and PC7

    Directory of Open Access Journals (Sweden)

    Pierpaolo Ginefra

    2018-02-01

    Full Text Available Furin trafficking, and that of related proprotein convertases (PCs, may regulate which substrates are accessible for endoproteolysis, but tools to directly test this hypothesis have been lacking. Here, we develop targeted biosensors that indicate Furin activity in endosomes is 10-fold less inhibited by decanoyl-RVKR-chloromethylketone and enriched >3-fold in endosomes compared to the trans-Golgi network (TGN. Endogenous PC7, which resists this inhibitor, was active in distinct vesicles. Only overexpressed PC7 activity reached the cell surface, endosomes, and the TGN. A PLC motif in the cytosolic tail of PC7 was dispensable for endosomal activity, but it was specifically required for TGN recycling and to rescue proActivin-A cleavage in Furin-depleted B16F1 melanoma cells. In sharp contrast, PC7 complemented Furin in cleaving Notch1 independently of PLC-mediated TGN access. Our study provides a proof in principle that compartment-specific biosensors can be used to gain insight into the regulation of PC trafficking and to map the tropism of PC-specific inhibitors.

  13. Multimedia information processing in the SWAN mobile networked computing system

    Science.gov (United States)

    Agrawal, Prathima; Hyden, Eoin; Krzyzanowsji, Paul; Srivastava, Mani B.; Trotter, John

    1996-03-01

    Anytime anywhere wireless access to databases, such as medical and inventory records, can simplify workflow management in a business, and reduce or even eliminate the cost of moving paper documents. Moreover, continual progress in wireless access technology promises to provide per-user bandwidths of the order of a few Mbps, at least in indoor environments. When combined with the emerging high-speed integrated service wired networks, it enables ubiquitous and tetherless access to and processing of multimedia information by mobile users. To leverage on this synergy an indoor wireless network based on room-sized cells and multimedia mobile end-points is being developed at AT&T Bell Laboratories. This research network, called SWAN (Seamless Wireless ATM Networking), allows users carrying multimedia end-points such as PDAs, laptops, and portable multimedia terminals, to seamlessly roam while accessing multimedia data streams from the wired backbone network. A distinguishing feature of the SWAN network is its use of end-to-end ATM connectivity as opposed to the connectionless mobile-IP connectivity used by present day wireless data LANs. This choice allows the wireless resource in a cell to be intelligently allocated amongst various ATM virtual circuits according to their quality of service requirements. But an efficient implementation of ATM in a wireless environment requires a proper mobile network architecture. In particular, the wireless link and medium-access layers need to be cognizant of the ATM traffic, while the ATM layers need to be cognizant of the mobility enabled by the wireless layers. This paper presents an overview of SWAN's network architecture, briefly discusses the issues in making ATM mobile and wireless, and describes initial multimedia applications for SWAN.

  14. VLSI implementation of a fairness ATM buffer system

    DEFF Research Database (Denmark)

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

    1996-01-01

    that can provide a resource allocation policy and enforcement of this policy. It can be used in networks in order to provide defined allocation policies (fairness) and improve network robustness. The presented design illustrates how the theoretical weighted fair queueing model can be approximated...

  15. 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

  16. PC based 8-parameter data acquisition system

    International Nuclear Information System (INIS)

    Gupta, J.D.; Naik, K.V.; Jain, S.K.; Pathak, R.V.; Suman, B.

    1989-01-01

    Multiparameter data acquisition (MPA) systems which analyse nuclear events with respect to more than one property of the event are essential tools for the study of some complex nuclear phenomena requiring analysis of time coincident spectra. For better throughput and accuracy each parameter is digitized by its own ADC. A stand alone low cost IBM PC based 8-parameter data acquisition system developed by the authors makes use of Address Recording technique for acquiring data from eight 12 bit ADC's in the PC Memory. Two memory buffers in the PC memory are used in ping-pong fashion so that data acquisition in one bank and dumping of data onto PC disk from the other bank can proceed simultaneously. Data is acquired in the PC memory through DMA mode for realising high throughput and hardware interrupt is used for switching banks for data acquisition. A comprehensive software package developed in Turbo-Pascal offers a set of menu-driven interactive commands to the user for setting-up system parameters and control of the system. The system is to be used with pelletron accelerator. (author). 5 figs

  17. Critical involvement of the ATM-dependent DNA damage response in the apoptotic demise of HIV-1-elicited syncytia.

    Directory of Open Access Journals (Sweden)

    Jean-Luc Perfettini

    Full Text Available DNA damage can activate the oncosuppressor protein ataxia telangiectasia mutated (ATM, which phosphorylates the histone H2AX within characteristic DNA damage foci. Here, we show that ATM undergoes an activating phosphorylation in syncytia elicited by the envelope glycoprotein complex (Env of human immunodeficiency virus-1 (HIV-1 in vitro. This was accompanied by aggregation of ATM in discrete nuclear foci that also contained phospho-histone H2AX. DNA damage foci containing phosphorylated ATM and H2AX were detectable in syncytia present in the brain or lymph nodes from patients with HIV-1 infection, as well as in a fraction of blood leukocytes, correlating with viral status. Knockdown of ATM or of its obligate activating factor NBS1 (Nijmegen breakage syndrome 1 protein, as well as pharmacological inhibition of ATM with KU-55933, inhibited H2AX phosphorylation and prevented Env-elicited syncytia from undergoing apoptosis. ATM was found indispensable for the activation of MAP kinase p38, which catalyzes the activating phosphorylation of p53 on serine 46, thereby causing p53 dependent apoptosis. Both wild type HIV-1 and an HIV-1 mutant lacking integrase activity induced syncytial apoptosis, which could be suppressed by inhibiting ATM. HIV-1-infected T lymphoblasts from patients with inactivating ATM or NBS1 mutations also exhibited reduced syncytial apoptosis. Altogether these results indicate that apoptosis induced by a fusogenic HIV-1 Env follows a pro-apoptotic pathway involving the sequential activation of ATM, p38MAPK and p53.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after DNA repair. - Abstract: 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

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

    International Nuclear Information System (INIS)

    Fukumoto, Yasunori; Kuki, Kazumasa; Morii, Mariko; Miura, Takahito; Honda, Takuya; Ishibashi, Kenichi; Hasegawa, Hitomi; Kubota, Sho; Ide, Yudai; Yamaguchi, Noritaka; Nakayama, Yuji; Yamaguchi, Naoto

    2014-01-01

    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

  20. PC'eren på arbejde. 3. udgave

    DEFF Research Database (Denmark)

    Andersen, Povl Erik Rostgård

    En generel og ikke-programspecifik introduktion til edb-området med speciel fokus på pc'er og pc-programmel.......En generel og ikke-programspecifik introduktion til edb-området med speciel fokus på pc'er og pc-programmel....

  1. 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.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

    Highlights: → iPS cells were induced with a fluorescence monitoring system. → ATM-deficient tail-tip fibroblasts exhibited quite a low reprogramming efficiency. → iPS cells obtained from ATM-deficient cells had pluripotent cell characteristics. → 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.

  3. Functional link between DNA damage responses and transcriptional regulation by ATM in response to a histone deacetylase inhibitor TSA.

    Science.gov (United States)

    Lee, Jong-Soo

    2007-09-01

    Mutations in the ATM (ataxia-telangiectasia mutated) gene, which encodes a 370 kd protein with a kinase catalytic domain, predisposes people to cancers, and these mutations are also linked to ataxia-telangiectasia (A-T). The histone acetylaion/deacetylation- dependent chromatin remodeling can activate the ATM kinase-mediated DNA damage signal pathway (in an accompanying work, Lee, 2007). This has led us to study whether this modification can impinge on the ATM-mediated DNA damage response via transcriptional modulation in order to understand the function of ATM in the regulation of gene transcription. To identify the genes whose expression is regulated by ATM in response to histone deaceylase (HDAC) inhibition, we performed an analysis of oligonucleotide microarrays with using the appropriate cell lines, isogenic A-T (ATM(-)) and control (ATM(+)) cells, following treatment with a HDAC inhibitor TSA. Treatment with TSA reprograms the differential gene expression profile in response to HDAC inhibition in ATM(-) cells and ATM(+) cells. We analyzed the genes that are regulated by TSA in the ATM-dependent manner, and we classified these genes into different functional categories, including those involved in cell cycle/DNA replication, DNA repair, apoptosis, growth/differentiation, cell- cell adhesion, signal transduction, metabolism and transcription. We found that while some genes are regulated by TSA without regard to ATM, the patterns of gene regulation are differentially regulated in an ATM-dependent manner. Taken together, these finding indicate that ATM can regulate the transcription of genes that play critical roles in the molecular response to DNA damage, and this response is modulated through an altered HDAC inhibition-mediated gene expression.

  4. Constitutive phosphorylation of ATM in lymphoblastoid cell lines from patients with ICF syndrome without downstream kinase activity.

    Science.gov (United States)

    Goldstine, Jimena V; Nahas, Shareef; Gamo, Kristin; Gartler, Stanley M; Hansen, R Scott; Roelfsema, Jeroen H; Gatti, Richard A; Marahrens, York

    2006-04-08

    Double strand DNA breaks in the genome lead to the activation of the ataxia-telangiectasia mutated (ATM) kinase in a process that requires ATM autophosphorylation at serine-1981. ATM autophosphorylation only occurs if ATM is previously acetylated by Tip60. The activated ATM kinase phosphorylates proteins involved in arresting the cell cycle, including p53, and in repairing the DNA breaks. Chloroquine treatment and other manipulations that produce chromatin defects in the absence of detectable double strand breaks also trigger ATM phosphorylation and the phosphorylation of p53 in primary human fibroblasts, while other downstream substrates of ATM that are involved in the repair of DNA double strand breaks remain unphosphorylated. This raises the issue of whether ATM is constitutively activated in patients with genetic diseases that display chromatin defects. We examined lymphoblastoid cell lines (LCLs) generated from patients with different types of chromatin disorders: Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome, Coffin Lowry syndrome, Rubinstein Taybi syndrome and Fascioscapulohumeral Muscular Dystrophy. We show that ATM is phosphorylated on serine-1981 in LCLs derived from ICF patients but not from the other syndromes. The phosphorylated ATM in ICF cells did not phosphorylate the downstream targets NBS1, SMC1 and H2AX, all of which require the presence of double strand breaks. We demonstrate that ICF cells respond normally to ionizing radiation, ruling out the possibility that genetic deficiency in ICF cells renders activated ATM incapable of phosphorylating its downstream substrates. Surprisingly, p53 was also not phosphorylated in ICF cells or in chloroquine-treated wild type LCLs. In this regard the response to chromatin-altering agents differs between primary fibroblasts and LCLs. Our findings indicate that although phosphorylation at serine-1981 is essential in the activation of the ATM kinase, serine-1981 phosphorylation is

  5. 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

  6. Peak Pc Prediction in Conjunction Analysis: Conjunction Assessment Risk Analysis. Pc Behavior Prediction Models

    Science.gov (United States)

    Vallejo, J.J.; Hejduk, M.D.; Stamey, J. D.

    2015-01-01

    Satellite conjunction risk typically evaluated through the probability of collision (Pc). Considers both conjunction geometry and uncertainties in both state estimates. Conjunction events initially discovered through Joint Space Operations Center (JSpOC) screenings, usually seven days before Time of Closest Approach (TCA). However, JSpOC continues to track objects and issue conjunction updates. Changes in state estimate and reduced propagation time cause Pc to change as event develops. These changes a combination of potentially predictable development and unpredictable changes in state estimate covariance. Operationally useful datum: the peak Pc. If it can reasonably be inferred that the peak Pc value has passed, then risk assessment can be conducted against this peak value. If this value is below remediation level, then event intensity can be relaxed. Can the peak Pc location be reasonably predicted?

  7. Population dose assessment: characteristics of PC CREAM

    International Nuclear Information System (INIS)

    Alonso, Maria T.; Curti, Adriana R.

    2000-01-01

    This paper presents the main features of the PC CREAM, a program for performing radiological impact assessments due to radioactive discharges into the environment during the operation of radioactive and nuclear facilities. PC CREAM is a suite of six programs that can be used to estimate individual and collective radiation doses. The methodology of PC CREAM is based on updated environmental and dosimetric models, including ICRP 60 recommendations. The models include several exposure pathways and the input files are easy to access. The ergonomics of the program improves the user interaction and makes easier the input of local data. This program is useful for performing sensitivity analysis, siting studies and validation of model comparing the activity concentration output data with environmental monitoring data. The methodology of each module is described as well as the output data. (author)

  8. Simultaneous targeting of ATM and Mcl-1 increases cisplatin sensitivity of cisplatin-resistant non-small cell lung cancer.

    Science.gov (United States)

    Zhang, Fuquan; Shen, Mingjing; Yang, Li; Yang, Xiaodong; Tsai, Ying; Keng, Peter C; Chen, Yongbing; Lee, Soo Ok; Chen, Yuhchyau

    2017-08-03

    Development of cisplatin-resistance is an obstacle in non-small cell lung cancer (NSCLC) therapeutics. To investigate which molecules are associated with cisplatin-resistance, we analyzed expression profiles of several DNA repair and anti-apoptosis associated molecules in parental (A549P and H157P) and cisplatin-resistant (A549CisR and H157CisR) NSCLC cells. We detected constitutively upregulated nuclear ATM and cytosolic Mcl-1 molcules in cisplatin-resistant cells compared with parental cells. Increased levels of phosphorylated ATM (p-ATM) and its downstream molecules, CHK2, p-CHK2, p-53, and p-p53 were also detected in cisplatin-resistant cells, suggesting an activation of ATM signaling in these cells. Upon inhibition of ATM and Mcl-1 expression/activity using specific inhibitors of ATM and/or Mcl-1, we found significantly enhanced cisplatin-cytotoxicity and increased apoptosis of A549CisR cells after cisplatin treatment. Several A549CisR-derived cell lines, including ATM knocked down (A549CisR-siATM), Mcl-1 knocked down (A549CisR-shMcl1), ATM/Mcl-1 double knocked down (A549CisR-siATM/shMcl1) as well as scramble control (A549CisR-sc), were then developed. Higher cisplatin-cytotoxicity and increased apoptosis were observed in A549CisR-siATM, A549CisR-shMcl1, and A549CisR-siATM/shMcl1 cells compared with A549CisR-sc cells, and the most significant effect was shown in A549CisR-siATM/shMcl1 cells. In in vivo mice studies using subcutaneous xenograft mouse models developed with A549CisR-sc and A549CisR-siATM/shMcl1 cells, significant tumor regression in A549CisR-siATM/shMcl1 cells-derived xenografts was observed after cisplatin injection, but not in A549CisR-sc cells-derived xenografts. Finally, inhibitor studies revealed activation of Erk signaling pathway was most important in upregulation of ATM and Mcl-1 molcules in cisplatin-resistant cells. These studies suggest that simultaneous blocking of ATM/Mcl-1 molcules or downstream Erk signaling may recover the

  9. MicroRNA203a suppresses glioma tumorigenesis through an ATM-dependent interferon response pathway.

    Science.gov (United States)

    Yang, Chuan He; Wang, Yinan; Sims, Michelle; Cai, Chun; He, Ping; Häcker, Hans; Yue, Junming; Cheng, Jinjun; Boop, Frederick A; Pfeffer, Lawrence M

    2017-12-22

    Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We previously showed that miR-203a is expressed at relatively low levels in GBM patients, and ectopic miR-203a expression in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon (IFN) or temozolomide in vitro , and inhibited GBM tumorigenesis in vivo . Here we show that ectopic expression of miR-203a in GBM cell lines promotes the IFN response pathway as evidenced by increased IFN production and IFN-stimulated gene (ISG) expression, and high basal tyrosine phosphorylation of multiple STAT proteins. Importantly, we identified that miR-203a directly suppressed the protein levels of ataxia-telangiectasia mutated (ATM) kinase that negatively regulates IFN production. We found that high ATM expression in GBM correlates with poor patient survival and that ATM expression is inversely correlated with miR-203a expression. Knockout of ATM expression and inhibition of ATM function in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by therapeutic agents in vitro , and markedly suppressed GBM tumor growth and promoted animal survival. In contrast, restoring ATM levels in GBM cells ectopically expressing miR-203a increased tumorigenicity and decreased animal survival. Our study suggests that low miR-203a expression in GBM suppresses the interferon response through an ATM-dependent pathway.

  10. Breast cancer in female carriers of ATM gene alterations: outcome of adjuvant radiotherapy

    International Nuclear Information System (INIS)

    Meyer, Andreas; John, Esther; Doerk, Thilo; Sohn, Christof; Karstens, Johann H.; Bremer, Michael

    2004-01-01

    Background and purpose: We analyzed the clinical outcome of breast cancer patients carrying sequence variants in the ATM gene who received postoperative radiotherapy after breast conservative surgery to test whether an increased cellular radiosensitivity may translate into enhanced tumor cell killing and thereby result in an improvement of the therapeutic ratio. Patients and methods: We investigated a cohort of 138 breast cancer patients who received adjuvant radiotherapy following breast conservative surgery for T1 and T2 tumors. Genomic DNA samples of these patients had previously been scanned for mutations in the ATM gene. Follow-up data were available in 135 patients, with a median follow-up of 87 months. Local relapse-free, metastasis-free and overall survival were compared between carriers and non-carriers of a sequence variant in the ATM gene. Results: Twenty patients were found to carry a sequence variant in the ATM gene (truncating, 7; missense, 13). The actuarial 7-year local relapse-free survival of carriers vs. non-carriers were 88 vs. 94% (P=0.34). Actuarial metastasis-free and overall survival after 7 years were 63 vs. 85% (P=0.01) and 73 vs. 89% (P=0.055), respectively. However, the presence of a variant in the ATM gene did not remain a significant discriminator for metastasis-free survival in a multivariate Cox regression analysis (P=0.068). Conclusions: Our results do not support the hypothesis that breast cancer patients carrying a sequence variant in the ATM gene differentially benefit from postoperative radiotherapy. These findings have to be verified using larger number of cases to clarify the clinical consequences of sequence variants in the ATM gene

  11. Effect of ATM heterozygosity on heritable DNA damage in mice following paternal F0 germline irradiation

    International Nuclear Information System (INIS)

    Baulch, Janet E.; Li, M.-W.; Raabe, Otto G.

    2007-01-01

    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 137 Cs γ 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 3 descendants that were based upon the irradiated F 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 effect

  12. Tablet PC Support of Students' Learning Styles

    Directory of Open Access Journals (Sweden)

    Shreya Kothaneth

    2012-12-01

    Full Text Available In the context of rapid technology development, it comes as no surprise that technology continues to impact the educational domain, challenging traditional teaching and learning styles. This study focuses on how students with different learning styles use instructional technology, and in particular, the tablet PC, to enhance their learning experience. The VARK model was chosen as our theoretical framework as we analyzed responses of an online survey, both from a quantitative and qualitative standpoint. Results indicate that if used correctly, the tablet PC can be used across different learning styles to enrich the educational experience.

  13. PHAST- a spectrum stabilising PC-MCA

    International Nuclear Information System (INIS)

    Mukhopadhyay, P.K.; Satish, P.; Shrivastava, V.D.

    2001-01-01

    Model PHAST, a PC-card with programmable features, incorporates a 100 MHz Wilkinson ADC with conversion gain of 8K. It also provides SCA mode MCS operation. The card caters to the needs of precision nuclear spectroscopy at low to moderate count rates. Spectrum drift may be eliminated by spectrum stabilisation. Proper dead time correction is achieved by Gedcke-Hale or pulse generator based schemes. Multiple cards may be operated together in a single PC in independent operating modes. These cards have onboard histogram memory and updating mechanism. Hence they will usually continue to acquire data in the event of a system crash. (author)

  14. Installation and implementation of PC COSYMA

    International Nuclear Information System (INIS)

    Rossi, J.

    1995-12-01

    COSYMA is a probabilistic reactor accident consequence assessment model developed in the 1980's by the research institutes of the EC countries, primarily by NRPB and KfK. In 1993 a simplified version of the program was released to be implemented on a PC. In the study the PC COSYMA program was applied to calculate as the end points nuclide concentrations, doses received, numbers of health effects, areas affected by countermeasures and other results related to countermeasure strategies. Some results are compared with the results obtained by the ARANO program developed by VTT Energy (Technical Research Centre of Finland) to quarantee proper interpretation of the application. (15 refs.)

  15. Nedd4 family interacting protein 1 (Ndfip1) is required for ubiquitination and nuclear trafficking of BRCA1-associated ATM activator 1 (BRAT1) during the DNA damage response.

    Science.gov (United States)

    Low, Ley-Hian; Chow, Yuh-Lit; Li, Yijia; Goh, Choo-Peng; Putz, Ulrich; Silke, John; Ouchi, Toru; Howitt, Jason; Tan, Seong-Seng

    2015-03-13

    During injury, cells are vulnerable to apoptosis from a variety of stress conditions including DNA damage causing double-stranded breaks. Without repair, these breaks lead to aberrations in DNA replication and transcription, leading to apoptosis. A major response to DNA damage is provided by the protein kinase ATM (ataxia telangiectasia mutated) that is capable of commanding a plethora of signaling networks for DNA repair, cell cycle arrest, and even apoptosis. A key element in the DNA damage response is the mobilization of activating proteins into the cell nucleus to repair damaged DNA. BRAT1 is one of these proteins, and it functions as an activator of ATM by maintaining its phosphorylated status while also keeping other phosphatases at bay. However, it is unknown how BRAT1 is trafficked into the cell nucleus to maintain ATM phosphorylation. Here we demonstrate that Ndfip1-mediated ubiquitination of BRAT1 leads to BRAT1 trafficking into the cell nucleus. Without Ndfip1, BRAT1 failed to translocate to the nucleus. Under genotoxic stress, cells showed increased expression of both Ndfip1 and phosphorylated ATM. Following brain injury, neurons show increased expression of Ndfip1 and nuclear translocation of BRAT1. These results point to Ndfip1 as a sensor protein during cell injury and Ndfip1 up-regulation as a cue for BRAT1 ubiquitination by Nedd4 E3 ligases, followed by nuclear translocation of BRAT1. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Noncanonical ATM Activation and Signaling in Response to Transcription-Blocking DNA Damage.

    Science.gov (United States)

    Marteijn, Jurgen A; Vermeulen, Wim; Tresini, Maria

    2017-01-01

    Environmental genotoxins and metabolic byproducts generate DNA lesions that can cause genomic instability and disrupt tissue homeostasis. To ensure genomic integrity, cells employ mechanisms that convert signals generated by stochastic DNA damage into organized responses, including activation of repair systems, cell cycle checkpoints, and apoptotic mechanisms. DNA damage response (DDR) signaling pathways coordinate these responses and determine cellular fates in part, by transducing signals that modulate RNA metabolism. One of the master DDR coordinators, the Ataxia Telangiectasia Mutated (ATM) kinase, has a fundamental role in mediating DNA damage-induced changes in mRNA synthesis. ATM acts by modulating a variety of RNA metabolic pathways including nascent RNA splicing, a process catalyzed by the spliceosome. Interestingly, ATM and the spliceosome influence each other's activity in a reciprocal manner by a pathway that initiates when transcribing RNA polymerase II (RNAPII) encounters DNA lesions that prohibit forward translocation. In response to stalling of RNAPII assembly of late-stage spliceosomes is disrupted resulting in increased splicing factor mobility. Displacement of spliceosomes from lesion-arrested RNA polymerases facilitates formation of R-loops between the nascent RNA and DNA adjacent to the transcription bubble. R-loops signal for noncanonical ATM activation which in quiescent cells occurs in absence of detectable dsDNA breaks. In turn, activated ATM signals to regulate spliceosome dynamics and AS genome wide.This chapter describes the use of fluorescence microscopy methods that can be used to evaluate noncanonical ATM activation by transcription-blocking DNA damage. First, we present an immunofluorescence-detection method that can be used to evaluate ATM activation by autophosphorylation, in fixed cells. Second, we present a protocol for Fluorescence Recovery After Photobleaching (FRAP) of GFP-tagged splicing factors, a highly sensitive and

  17. ATM deficiency results in accumulation of DNA-topoisomerase I covalent intermediates in neural cells.

    Directory of Open Access Journals (Sweden)

    Meryem Alagoz

    Full Text Available Accumulation of peptide-linked DNA breaks contributes to neurodegeration in humans. This is typified by defects in tyrosyl DNA phosphodiesterase 1 (TDP1 and human hereditary ataxia. TDP1 primarily operates at single-strand breaks (SSBs created by oxidative stress or by collision of transcription machinery with topoisomerase I intermediates (Top1-CCs. Cellular and cell-free studies have shown that Top1 at stalled Top1-CCs is first degraded to a small peptide resulting in Top1-SSBs, which are the primary substrates for TDP1. Here we established an assay to directly compare Top1-SSBs and Top1-CCs. We subsequently employed this assay to reveal an increased steady state level of Top1-CCs in neural cells lacking Atm; the protein mutated in ataxia telangiectasia. Our data suggest that the accumulation of endogenous Top1-CCs in Atm-/- neural cells is primarily due to elevated levels of reactive oxygen species. Biochemical purification of Top1-CCs from neural cell extract and the use of Top1 poisons further confirmed a role for Atm during the formation/resolution of Top1-CCs. Finally, we report that global transcription is reduced in Atm-/- neural cells and fails to recover to normal levels following Top1-mediated DNA damage. Together, these data identify a distinct role for ATM during the formation/resolution of neural Top1-CCs and suggest that their accumulation contributes to the neuropathology of ataxia telangiectasia.

  18. Poly(ADP-ribose) polymerase-1 inhibits ATM kinase activity in DNA damage response

    International Nuclear Information System (INIS)

    Watanabe, Fumiaki; Fukazawa, Hidesuke; Masutani, Mitsuko; Suzuki, Hiroshi; Teraoka, Hirobumi; Mizutani, Shuki; Uehara, Yoshimasa

    2004-01-01

    DNA double-strand breaks (DSB) mobilize DNA-repair machinery and cell cycle checkpoint by activating the ataxia-telangiectasia (A-T) mutated (ATM). Here we show that ATM kinase activity is inhibited by poly(ADP-ribose) polymerase-1 (PARP-1) in vitro. It was shown by biochemical fractionation procedure that PARP-1 as well as ATM increases at chromatin level after induction of DSB with neocarzinostatin (NCS). Phosphorylation of histone H2AX on serine 139 and p53 on serine 15 in Parp-1 knockout (Parp-1 -/- ) mouse embryonic fibroblasts (MEF) was significantly induced by NCS treatment compared with MEF derived from wild-type (Parp-1 +/+ ) mouse. NCS-induced phosphorylation of histone H2AX on serine 139 in Parp-1 -/- embryonic stem cell (ES) clones was also higher than that in Parp-1 +/+ ES clone. Furthermore, in vitro, PARP-1 inhibited phosphorylation of p53 on serine 15 and 32 P-incorporation into p53 by ATM in a DNA-dependent manner. These results suggest that PARP-1 negatively regulates ATM kinase activity in response to DSB

  19. Association of ATM and BMI-1 genetic variation with breast cancer risk in Han Chinese.

    Science.gov (United States)

    Yue, Li-Ling; Wang, Fu-Chao; Zhang, Ming-Long; Liu, Dan; Chen, Ping; Mei, Qing-Bu; Li, Peng-Hui; Pan, Hong-Ming; Zheng, Li-Hong

    2018-04-24

    We tested the hypothesis that genetic variation in ATM and BMI-1 genes can alter the risk of breast cancer through genotyping 6 variants among 524 breast cancer cases and 518 cancer-free controls of Han nationality. This was an observational, hospital-based, case-control association study. Analyses of single variant, linkage, haplotype, interaction and nomogram were performed. Risk was expressed as odds ratio (OR) and 95% confidence interval (CI). All studied variants were in the Hardy-Weinberg equilibrium and were not linked. The mutant allele frequencies of rs1890637, rs3092856 and rs1801516 in ATM gene were significantly higher in cases than in controls (P = .005, ATM gene were significantly associated with 1.98-fold and 6.04-fold increased risk of breast cancer (95% CI: 1.36-2.90 and 1.65-22.08, respectively). Nomogram analysis estimated that the cumulative proportion of 3 significant variants in ATM gene was about 12.5%. Our findings collectively indicated that ATM gene was a candidate gene in susceptibility to breast cancer in Han Chinese. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  20. ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage.

    Science.gov (United States)

    Perkhofer, Lukas; Schmitt, Anna; Romero Carrasco, Maria Carolina; Ihle, Michaela; Hampp, Stephanie; Ruess, Dietrich Alexander; Hessmann, Elisabeth; Russell, Ronan; Lechel, André; Azoitei, Ninel; Lin, Qiong; Liebau, Stefan; Hohwieler, Meike; Bohnenberger, Hanibal; Lesina, Marina; Algül, Hana; Gieldon, Laura; Schröck, Evelin; Gaedcke, Jochen; Wagner, Martin; Wiesmüller, Lisa; Sipos, Bence; Seufferlein, Thomas; Reinhardt, Hans Christian; Frappart, Pierre-Olivier; Kleger, Alexander

    2017-10-15

    Pancreatic ductal adenocarcinomas (PDAC) harbor recurrent functional mutations of the master DNA damage response kinase ATM, which has been shown to accelerate tumorigenesis and epithelial-mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated the molecular and functional effects of conditional Atm deletion in a mouse model of PDAC. ATM deficiency was associated with increased mitotic defects, recurrent genomic rearrangements, and deregulated DNA integrity checkpoints, reminiscent of human PDAC. We hypothesized that altered genome integrity might allow synthetic lethality-based options for targeted therapeutic intervention. Supporting this possibility, we found that the PARP inhibitor olaparib or ATR inhibitors reduced the viability of PDAC cells in vitro and in vivo associated with a genotype-selective increase in apoptosis. Overall, our results offered a preclinical mechanistic rationale for the use of PARP and ATR inhibitors to improve treatment of ATM-mutant PDAC. Cancer Res; 77(20); 5576-90. ©2017 AACR . ©2017 American Association for Cancer Research.

  1. 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.

  2. 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...... of the oral cavity/pharynx. Multifactorially adjusted hazard ratios for ATM Ser707Pro heterozygotes versus noncarriers were 0.8 (95% CI, 0.6 to 1.2) for cancer overall, 0.6 (95% CI, 0.2 to 1.6) for breast cancer, 10 (95% CI, 1.1 to 93) for thyroid/other endocrine tumors, and 2.7 (95% CI, 1.0 to 7...

  3. Authenticated tracking and monitoring system (ATMS) tracking shipments from an Australian uranium mine

    International Nuclear Information System (INIS)

    Schoeneman, J.L.

    1998-01-01

    The Authenticated Tracking and Monitoring System (ATMS) answers the need for global monitoring of the status and location of sensitive items on a worldwide basis, 24 hours a day. ATMS uses wireless sensor packs to monitor the status of the items and environmental conditions. A receiver and processing unit collect a variety of sensor event data. The collected data are transmitted to the INMARSAT satellite communication system, which then sends the data to appropriate ground stations. Authentication and encryption algorithms secure the data during communication activities. A typical ATMS application would be to track and monitor the safety and security of a number of items in transit along a scheduled shipping route. The resulting tracking, timing, and status information could then be processed to ensure compliance with various agreements. Following discussions between the Australian Safeguards Office (ASO), the US Department of Energy (DOE), and Sandia National Laboratories (SNL) in early 1995, the parties mutually agreed to conduct and evaluate a field trial prototype ATMS to track and monitor shipments of uranium ore concentrate (UOC) from an operating uranium mine in Australia to a final destination in Rotterdam, the Netherlands, with numerous stops along the way. During the months of February and March 1998, the trial was conducted on a worldwide basis, with tracking and monitoring stations located at sites in both Australia and the US. This paper describes ATMS and the trial

  4. 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.

  5. Requirement of the ATM/p53 tumor suppressor pathway for glucose homeostasis.

    Science.gov (United States)

    Armata, Heather L; Golebiowski, Diane; Jung, Dae Young; Ko, Hwi Jin; Kim, Jason K; Sluss, Hayla K

    2010-12-01

    Ataxia telangiectasia (A-T) patients can develop multiple clinical pathologies, including neuronal degeneration, an elevated risk of cancer, telangiectasias, and growth retardation. Patients with A-T can also exhibit an increased risk of insulin resistance and type 2 diabetes. The ATM protein kinase, the product of the gene mutated in A-T patients (Atm), has been implicated in metabolic disease, which is characterized by insulin resistance and increased cholesterol and lipid levels, blood pressure, and atherosclerosis. ATM phosphorylates the p53 tumor suppressor on a site (Ser15) that regulates transcription activity. To test whether the ATM pathway that regulates insulin resistance is mediated by p53 phosphorylation, we examined insulin sensitivity in mice with a germ line mutation that replaces the p53 phosphorylation site with alanine. The loss of p53 Ser18 (murine Ser15) led to increased metabolic stress, including severe defects in glucose homeostasis. The mice developed glucose intolerance and insulin resistance. The insulin resistance correlated with the loss of antioxidant gene expression and decreased insulin signaling. N-Acetyl cysteine (NAC) treatment restored insulin signaling in late-passage primary fibroblasts. The addition of an antioxidant in the diet rendered the p53 Ser18-deficient mice glucose tolerant. This analysis demonstrates that p53 phosphorylation on an ATM site is an important mechanism in the physiological regulation of glucose homeostasis.

  6. Experience using EPICS on PC platforms

    International Nuclear Information System (INIS)

    Hill, J.O.; Kasemire, K.U.

    1997-03-01

    The Experimental Physics and Industrial Control System (EPICS) has been widely adopted in the accelerator community. Although EPICS is available on many platforms, the majority of implementations have used UNIX workstations as clients, and VME- or VXI-based processors for distributed input output controllers. Recently, a significant portion of EPICS has been ported to personal computer (PC) hardware platforms running Microsoft's operating systems, and also Wind River System's real time vxWorks operating system. This development should significantly reduce the cost of deploying EPICS systems, and the prospect of using EPICS together with the many high quality commercial components available for PC platforms is also encouraging. A hybrid system using both PC and traditional platforms is currently being implemented at LANL for LEDA, the low energy demonstration accelerator under construction as part of the Accelerator Production of Tritium (APT) project. To illustrate these developments the authors compare their recent experience deploying a PC-based EPICS system with experience deploying similar systems based on traditional (UNIX-hosted) EPICS hardware and software platforms

  7. An Introduction To PC-TRIM.

    Science.gov (United States)

    John R. Mills

    1989-01-01

    The timber resource inventory model (TRIM) has been adapted to run on person al computers. The personal computer version of TRIM (PC-TRIM) is more widely used than its mainframe parent. Errors that existed in previous versions of TRIM have been corrected. Information is presented to help users with program input and output management in the DOS environment, to...

  8. An Automation Interface for Kappa PC

    DEFF Research Database (Denmark)

    Hartvig, Susanne C

    1999-01-01

    The reports documents an automation interface for Kappa PC. The automation interface can be used to embed Kappa applications in 32-bit Windowsapplications.The interface includes functions for initialising Kappa, for loading an application, for settingvalues, for getting values, and for stopping...

  9. A PC based thin film dosimeter system

    DEFF Research Database (Denmark)

    Miller, A.; Hargittai, P.; Kovacs, A.

    2000-01-01

    A dosimeter system based on the Riso B3 dosimeter film, an office scanner for use with PC and the associated software is presented. The scanned image is analyzed either with standard software (Paint Shop Pro 5 or Excel) functions or with the computer code "Scanalizer" that allows presentation...

  10. Brugervejledning til pc-programmet STLRAMME

    DEFF Research Database (Denmark)

    Buhelt, M.

    Pc-programmet STLRAMME supplerer SBI-anvisning 187, 'Simple stålrammebygninger. Dimensionering og udførelse'. Programmet kan anvendes til dimensionering af stålrammebygninger med andre mål end dem, der er medtaget i anvisningens tabeller; men det erstatter kun stålramme- og åsetabellerne, ikke an...

  11. ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression and autophagy.

    Science.gov (United States)

    Antonelli, Martina; Strappazzon, Flavie; Arisi, Ivan; Brandi, Rossella; D'Onofrio, Mara; Sambucci, Manolo; Manic, Gwenola; Vitale, Ilio; Barilà, Daniela; Stagni, Venturina

    2017-03-28

    The efficacy of Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition in cancer therapy is tempered by the identification of new emerging functions of ATM, which suggests that the role of this protein in cancer progression is complex. We recently demonstrated that this tumor suppressor gene could act as tumor promoting factor in HER2 (Human Epidermal Growth Factor Receptor 2) positive breast cancer. Herein we put in evidence that ATM expression sustains the proportion of cells with a stem-like phenotype, measured as the capability to form mammospheres, independently of HER2 expression levels. Transcriptomic analyses revealed that, in mammospheres, ATM modulates the expression of cell cycle-, DNA repair- and autophagy-related genes. Among these, the silencing of the autophagic gene, autophagy related 4C cysteine peptidase (ATG4C), impairs mammosphere formation similarly to ATM depletion. Conversely, ATG4C ectopic expression in cells silenced for ATM expression, rescues mammospheres growth. Finally, tumor array analyses, performed using public data, identify a significant correlation between ATM and ATG4C expression levels in all human breast cancer subtypes, except for the basal-like one.Overall, we uncover a new connection between ATM kinase and autophagy regulation in breast cancer. We demonstrate that, in breast cancer cells, ATM and ATG4C are essential drivers of mammosphere formation, suggesting that their targeting may improve current approaches to eradicate breast cancer cells with a stem-like phenotype.

  12. Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1.

    Science.gov (United States)

    Kobayashi, Junya; Tauchi, Hiroshi; Chen, Benjamin; Burma, Sandeep; Bruma, Sandeep; Tashiro, Satoshi; Matsuura, Shinya; Tanimoto, Keiji; Chen, David J; Komatsu, Kenshi

    2009-03-20

    Phosphorylated histone H2AX (gamma-H2AX) functions in the recruitment of DNA damage response proteins to DNA double-strand breaks (DSBs) and facilitates DSB repair. ATM also co-localizes with gamma-H2AX at DSB sites following its auto-phosphorylation. However, it is unclear whether gamma-H2AX has a role in activation of ATM-dependent cell cycle checkpoints. Here, we show that ATM as well as NBS1 is recruited to damaged-chromatin in a gamma-H2AX-dependent manner. Foci formation of phosphorylated ATM and ATM-dependent phosphorylation is repressed in H2AX-knockdown cells. Furthermore, anti-gamma-H2AX antibody co-immunoprecipitates an ATM-like protein kinase activity in vitro and recombinant H2AX increases in vitro kinase activity of ATM from un-irradiated cells. Moreover, H2AX-deficient cells exhibited a defect in ATM-dependent cell cycle checkpoints. Taken together, gamma-H2AX has important role for effective DSB-dependent activation of ATM-related damage responses via NBS1.

  13. Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1

    International Nuclear Information System (INIS)

    Kobayashi, Junya; Tauchi, Hiroshi; Chen, Benjamin; Bruma, Sandeep; Tashiro, Satoshi; Matsuura, Shinya; Tanimoto, Keiji; Chen, David J.; Komatsu, Kenshi

    2009-01-01

    Phosphorylated histone H2AX (γ-H2AX) functions in the recruitment of DNA damage response proteins to DNA double-strand breaks (DSBs) and facilitates DSB repair. ATM also co-localizes with γ-H2AX at DSB sites following its auto-phosphorylation. However, it is unclear whether γ-H2AX has a role in activation of ATM-dependent cell cycle checkpoints. Here, we show that ATM as well as NBS1 is recruited to damaged-chromatin in a γ-H2AX-dependent manner. Foci formation of phosphorylated ATM and ATM-dependent phosphorylation is repressed in H2AX-knockdown cells. Furthermore, anti-γ-H2AX antibody co-immunoprecipitates an ATM-like protein kinase activity in vitro and recombinant H2AX increases in vitro kinase activity of ATM from un-irradiated cells. Moreover, H2AX-deficient cells exhibited a defect in ATM-dependent cell cycle checkpoints. Taken together, γ-H2AX has important role for effective DSB-dependent activation of ATM-related damage responses via NBS1.

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

    Directory of Open Access Journals (Sweden)

    Naoto Tatewaki

    Full Text Available 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.

  15. Fuzzy Based PC-PUSH in CR-MANETs

    Directory of Open Access Journals (Sweden)

    S. Nejatian

    2014-01-01

    Full Text Available In cognitive radio (CR, the secondary user (SU needs to hand off its ongoing communication to an idle channel in order to avoid interference to the primary user (PU. Spectrum hand off issue becomes challenging in CR mobile ad hoc networks (CR-MANETs because of the uncertainty in spectrum availability, broad range of spectrum bands and lack of central entity. The purpose of this study is to design a unified spectrum handoff (USH scheme for CR-MANETs that considers the spectrum heterogeneity and its availability over time and space. A local flow hand off is performed when spectrum hand off cannot be carried out due to the SUs mobility. To improve further USH, preemptive unified spectrum handoff (PUSH algorithm is proposed in which two different preemptive hand off threshold regions are defined. The PUSH algorithm also predicts the cognitive link availability considering the PU interference boundary. Although the PUSH scheme improves the hand off performance, the number of spectrum hand offs due to the PU activity should be reduced in this scheme. Therefore, the PC-PUSH (Power Controller-PUSH scheme is proposed in which the fuzzy logic is used to improve the PUSH in terms of the number of spectrum handoffs because of the PU activity. The PC-PUSH decreases the interference to the PUs, while reducing the number of spectrum handoffs. The results show that the proposed scheme improves the link maintenance probability, decreases the hand off delay, and reduces the number of spectrum handoffs.

  16. Preparation of heterogeneous networks for ambient intelligence

    NARCIS (Netherlands)

    Stok, van der P.D.V.; Basten, A.A.; Geilen, M.C.W.; Groot, de H.W.H.

    2003-01-01

    Ambient Intelligence assumes the existence of ubiquitous networked computing. Networking is supported in the home by a so-called home network. Currently, the home network emerges from the purchase of a second PC in the home. Extending the home network confronts the prospective buyer with a multitude

  17. WIPP Transparency Project - container tracking and monitoring demonstration using the Authenticated Tracking and Monitoring System (ATMS)

    International Nuclear Information System (INIS)

    SCHOENEMAN, J. LEE; SMARTT, HEIDI ANNE; HOFER, DENNIS

    2000-01-01

    The Authenticated Tracking and Monitoring System (ATMS) is designed to answer the need for global monitoring of the status and location of proliferation-sensitive items on a worldwide basis, 24 hours a day. ATMS uses wireless sensor packs to monitor the status of the items within the shipment and surrounding environmental conditions. Receiver and processing units collect a variety of sensor event data that is integrated with GPS tracking data. The collected data are transmitted to the International Maritime Satellite (INMARSAT) communication system, which then sends the data to mobile ground stations. Authentication and encryption algorithms secure the data during communication activities. A typical ATMS application would be to track and monitor the stiety and security of a number of items in transit along a scheduled shipping route. The resulting tracking, timing, and status information could then be processed to ensure compliance with various agreements

  18. 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, F...... for any of the SNPs with an overall trend OR of 1.06 (P-trend = 0.04). The trend OR among bilateral and familial cases was 1.12 (95% confidence interval, 1.02-1.23; P-trend = 0.02). Conclusions: In this large combined analysis, these five missense ATM SNPs were associated with a small increased risk...

  19. 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.

  20. CLIPS - C LANGUAGE INTEGRATED PRODUCTION SYSTEM (IBM PC VERSION)

    Science.gov (United States)

    Riley, G.

    1994-01-01

    The C Language Integrated Production System, CLIPS, is a shell for developing expert systems. It is designed to allow artificial intelligence research, development, and delivery on conventional computers. The primary design goals for CLIPS are portability, efficiency, and functionality. For these reasons, the program is written in C. CLIPS meets or outperforms most micro- and minicomputer based artificial intelligence tools. CLIPS is a forward chaining rule-based language. The program contains an inference engine and a language syntax that provide a framework for the construction of an expert system. It also includes tools for debugging an application. CLIPS is based on the Rete algorithm, which enables very efficient pattern matching. The collection of conditions and actions to be taken if the conditions are met is constructed into a rule network. As facts are asserted either prior to or during a session, CLIPS pattern-matches the number of fields. Wildcards and variables are supported for both single and multiple fields. CLIPS syntax allows the inclusion of externally defined functions (outside functions which are written in a language other than CLIPS). CLIPS itself can be embedded in a program such that the expert system is available as a simple subroutine call. Advanced features found in CLIPS version 4.3 include an integrated microEMACS editor, the ability to generate C source code from a CLIPS rule base to produce a dedicated executable, binary load and save capabilities for CLIPS rule bases, and the utility program CRSV (Cross-Reference, Style, and Verification) designed to facilitate the development and maintenance of large rule bases. Five machine versions are available. Each machine version includes the source and the executable for that machine. The UNIX version includes the source and binaries for IBM RS/6000, Sun3 series, and Sun4 series computers. The UNIX, DEC VAX, and DEC RISC Workstation versions are line oriented. The PC version and the Macintosh

  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. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Fabrication and characterization of MCC approved testing material - ATM-12 glass

    International Nuclear Information System (INIS)

    Wald, J.W.

    1985-10-01

    The Materials Characterization Center (MCC) Approved Testing Material ATM-12 is a borosilicate glass that incorporates elements typical of high-level waste (HLW) resulting from the reprocessing of commercial nuclear reactor fuels. The composition has been adjusted to match that predicted for HLW type 76-68 glass at an age of 300 y. Radioactive constituents contained in this glass include depleted uranium, 99 Tc, 237 Np, 239 Pu, and 241 Am. The glass was produced by the MCC at the Pacific Northwest Laboratory (PNL). ATM-12 glass ws produced from July to November of 1984 at the request of the Nevada Nuclear Waste Site Investigations (NNWSI) Program and is the third in a series of glasses produced for NNWSI. Most of the glass produced was in the form of cast bars; special castings and crushed material were also produced. Three kilograms of ATM-12 glass were produced from a feedstock melted in a nitrogen-atmosphere glove box at 1150 0 C in a platinum crucible, and formed into stress-annealed rectangular bars and the special casting shapes requested by NNWSI. Bars of ATM-12 were nominally 1.9 x 1.9 x 10 cm, with an average mass of 111 g each. Nineteen bars and 37 special castings were made. ATM-12 glass has been provided to the NNWSI Program, in the form of bars, crushed powder and special castings. As of August 1985 approximately 590 g of ATM-12 is available for distribution. Requests for materials or services related to this glass should be directed to the Materials Characterization Center Program Office, PNL

  3. Experiments at SRT Using the NOAA CrIS/ATMS Proxy Data Set

    Science.gov (United States)

    Susskind, Joel; Kouvaris, Louis; Iredell, Lena

    2011-01-01

    The objectives of the talk are: (1) Assess the performance of NGAS Version-1.5.03.00 CrIS/ATMS retrieval algorithm as delivered by LaRC, modified to include the MW and IR tuning coefficients and new CrIS noise model (a) Percent acceptance (b) RMS and mean differences of T(p) vs. ECMWF truth as a function of % yield (2) Compare performance of NGAS retrieval algorithm with an AIRS Science Team Version-6 like retrieval algorithm modified at Sounder Research Team (SRT) for CrIS/ATMS

  4. ATM/ATR-mediated phosphorylation of PALB2 promotes RAD51 function

    DEFF Research Database (Denmark)

    Ahlskog, Johanna K; Larsen, Brian D; Achanta, Kavya

    2016-01-01

    DNA damage activates the ATM and ATR kinases that coordinate checkpoint and DNA repair pathways. An essential step in homology-directed repair (HDR) of DNA breaks is the formation of RAD51 nucleofilaments mediated by PALB2-BRCA2; however, roles of ATM and ATR in this critical step of HDR are poor...... function, as the PALB2-dependent checkpoint response is normal in cells expressing the phospho-deficient PALB2 mutant. Collectively, our findings highlight a critical importance of PALB2 phosphorylation as a novel regulatory step in genome maintenance after genotoxic stress....

  5. Reconstrucción de Atmósferas Sonoras Tridimensionales

    Directory of Open Access Journals (Sweden)

    Jhosimar Aguacía Fisco

    2014-03-01

    Full Text Available El propósito de este proyecto es la reconstrucción de atmósferas sonoras tridimensionales, por medio de la tecnología Ambisonics, implementando un sistema de captura Native B-Format, codificación de fuentes puntuales y el uso de algunos audios grabados con micrófonos Soundfield, para crear así atmósferas sonoras naturales y artificiales, que serán reproducidas en un sistema 10.2, con el fin de generar un envolvimiento total, incluyendo alturas.

  6. 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.

  7. PC12 polarity on biopolymer nanogratings

    International Nuclear Information System (INIS)

    Cecchini, M; Ferrari, A; Beltram, F

    2008-01-01

    Cell differentiation properties are strongly entangled with the morphology and physical properties of the extracellular environment. A complete understanding of this interaction needs artificial scaffolds with controlled nano-/micro-topography. We induced specific topographies by nanoimprint lithography (NIL) on tissue culture polystyrene (TCPS) dishes substrates and, using light microscopy and high-magnification scanning-electron-microscopy, quantitatively compared the changes in PC12 differentiation phenotype induced by the periodicity of the nanopatterns. This analysis revealed that nanogratings reduce the number of neurites produced by PC12 cells upon treatment with NGF and that neuronal bipolarity correlated with an increased stretching of the cell body and a reduced length of the cell neuronal protrusions

  8. IBM PC enhances the world's future

    Science.gov (United States)

    Cox, Jozelle

    1988-01-01

    Although the purpose of this research is to illustrate the importance of computers to the public, particularly the IBM PC, present examinations will include computers developed before the IBM PC was brought into use. IBM, as well as other computing facilities, began serving the public years ago, and is continuing to find ways to enhance the existence of man. With new developments in supercomputers like the Cray-2, and the recent advances in artificial intelligence programming, the human race is gaining knowledge at a rapid pace. All have benefited from the development of computers in the world; not only have they brought new assets to life, but have made life more and more of a challenge everyday.

  9. PC imaging system for reactor NDE

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    PC-based systems have been given recent attention by EPRI to organize and manage inspection data (RP-2405-15, TestPro system); integrate with larger, mainframe computers to maintain dialogue for on-site and remote applications; and, in this project, to aid the operator in providing guidance to render decisions on the data. The PC system configuration for this project consisted of a central processing unit (CPU), a hard disk and a floppy disk, 640K bytes of system memory, a high-resolution graphics card and compatible color monitor, and a mouse for operator interaction with software. The software package was written in FORTRAN under the PC Disk Operating System (PC-DOS) and utilized a graphics package for image display. Application of this package to crack-counterbore discrimination in piping welds was investigated. Present automatic techniques utilize signal features from single, A-scan data to render a decision on whether the reflector is benign (i.e., counterbore, weld root) or a crack. However, experienced manual operators in the field make reliable decisions based on the integrated response from the reflector as the transducer is scanned past the suspicious region. Since this software package could display and manipulate ensemble A-scans, spatial features - similar to those used by experts - were developed as discriminants. Ultrasonic responses from intergranular stress corrosion cracks (IGSCCs) were discovered to vary both in time-of-flight and in their amplitude, whereas counterbore responses were more consistent. The software package contains methods for viewing and quantifying these spatial features

  10. PC 386-based version of DORT

    International Nuclear Information System (INIS)

    Tanker, E.

    1992-01-01

    Problems encountered during the adaptation of DORT on a personal computer using a Fortran77 compiler are described, modifications done to solve these are explained. Three test cases were run with the modified version and results are compared with those obtained on an IBM 3090/200. Numerical differences were observed in the last three decimal digits of the computations at most. The running times on the PC were found to be satisfactory for these test cases

  11. Low ATM protein expression and depletion of p53 correlates with olaparib sensitivity in gastric cancer cell lines

    Science.gov (United States)

    Kubota, Eiji; Williamson, Christopher T; Ye, Ruiqiong; Elegbede, Anifat; Peterson, Lars; Lees-Miller, Susan P; Bebb, D Gwyn

    2014-01-01

    Small-molecule inhibitors of poly (ADP-ribose) polymerase (PARP) have shown considerable promise in the treatment of homologous recombination (HR)-defective tumors, such as BRCA1- and BRCA2-deficient breast and ovarian cancers. We previously reported that mantle cell lymphoma cells with deficiency in ataxia telangiectasia mutated (ATM) are sensitive to PARP-1 inhibitors in vitro and in vivo. Here, we report that PARP inhibitors can potentially target ATM deficiency arising in a solid malignancy. We show that ATM protein expression varies between gastric cancer cell lines, with NUGC4 having significantly reduced protein levels. Significant correlation was found between ATM protein expression and sensitivity to the PARP inhibitor olaparib, with NUGC4 being the most sensitive. Moreover, reducing ATM kinase activity using a small-molecule inhibitor (KU55933) or shRNA-mediated depletion of ATM protein enhanced olaparib sensitivity in gastric cancer cell lines with depletion or inactivation of p53. Our results demonstrate that ATM is a potential predictive biomarker for PARP-1 inhibitor activity in gastric cancer harboring disruption of p53, and that combined inhibition of ATM and PARP-1 is a rational strategy for expanding the utility of PARP-1 inhibitors to gastric cancer with p53 disruption. PMID:24841718

  12. Glycosaminoglycan composition of PC12 pheochromocytoma cells: a comparison with PC12D cells, a new subline of PC12 cells

    Energy Technology Data Exchange (ETDEWEB)

    Katoh-Semba, R.; Oohira, A.; Sano, M.; Watanabe, K.; Kitajima, S.; Kashiwamata, S.

    1989-03-01

    PC12D cells, a new subline of conventional PC12 cells, respond not only to nerve growth factor but also to cyclic AMP by extending their neurites. These cells are flat in shape and are similar in appearance to PC12 cells that have been treated with nerve growth factor for a few days. In both cell lines, we have characterized the glycosaminoglycans, the polysaccharide moieties of proteoglycans, which are believed to play an important role in cell adhesion and in cell morphology. Under the present culture conditions, only chondroitin sulfate was detected in the media from PC12 and PC12D cells, whereas both chondroitin sulfate and heparan sulfate were found in the cell layers. The levels of cell-associated heparan sulfate and chondroitin sulfate were about twofold and fourfold higher in PC12D cells than in PC12 cells, respectively. Compared to PC12 cells, the amounts of (/sup 35/S)sulfate incorporated for 48 h into chondroitin sulfate were twofold lower but those into heparan sulfate were 35% higher in PC12D cells. The amount of chondroitin sulfate released by PC12D cells into the medium was about a half of that released by PC12 cells. The ratio of (/sup 35/S)sulfate-labeled heparan sulfate to chondroitin sulfate was 6.2 in PC12D cells and 2.2 in PC12 cells. These results suggest that there may be some correlation between the increase in content of glycosaminoglycans and the change in cell morphology, which is followed by neurite outgrowth.

  13. Pc-based car license plate reading

    Science.gov (United States)

    Tanabe, Katsuyoshi; Marubayashi, Eisaku; Kawashima, Harumi; Nakanishi, Tadashi; Shio, Akio

    1994-03-01

    A PC-based car license plate recognition system has been developed. The system recognizes Chinese characters and Japanese phonetic hiragana characters as well as six digits on Japanese license plates. The system consists of a CCD camera, vehicle sensors, a strobe unit, a monitoring center, and an i486-based PC. The PC includes in its extension slots: a vehicle detector board, a strobe emitter board, and an image grabber board. When a passing vehicle is detected by the vehicle sensors, the strobe emits a pulse of light. The light pulse is synchronized with the time the vehicle image is frozen on an image grabber board. The recognition process is composed of three steps: image thresholding, character region extraction, and matching-based character recognition. The recognition software can handle obscured characters. Experimental results for hundreds of outdoor images showed high recognition performance within relatively short performance times. The results confirmed that the system is applicable to a wide variety of applications such as automatic vehicle identification and travel time measurement.

  14. Phosphatidylcholine (PC) biosynthesis in pancreatic islets of Langerhans

    International Nuclear Information System (INIS)

    Hoffman, J.M.; Laychock, S.G.

    1986-01-01

    Islets of Langerhans isolated from rat pancreata were incubated with [ 14 C]choline to determine the biosynthesis of PC by the CDP choline to determine the biosynthesis of PC by the CDPcholine pathway. Recovery of [ 14 C]PC in islet membranes was time-related, and stimulated by glucose (17mM) during 60 min. The rate of PC synthesis was constant during 60 min with glucose stimulation. In contrast, the sulfonylurea tolbutamide (2 mM) reduced the recovery of [ 14 C]choline in PC, and 8-bromo-cyclic AMP (5 mM) did not significantly affect [ 14 C]PC recovery. Incubation of islets in Ca 2+ -free medium enhanced glucose-stimulated recovery of [ 14 C]choline-labeled PC due to the inhibition of phospholipase and phospholipid hydrolysis. Inhibition of CTP:phosphocholine cytidylyltransferase with 5-deoxy-5'-isobutylthioadenosine (SIBA) reduced [ 14 C]PC levels and insulin release in a concentration dependent manner. Treatment with SIBA also reduced Mg 2+ -dependent Ca 2+ -ATPase activity in islet microsomes. Quantitation of membrane PC showed that glucose stimulation did not alter islet P levels. Thus, islet PC biosynthesis is linked to glucose stimulation and contributes to the maintenance of PC levels in membranes undergoing exocytosis and phospholipid hydrolysis. Adequate PC levels support Ca 2+ pump activity and secretory mechanisms

  15. The USL NASA PC R and D development environment standards

    Science.gov (United States)

    Dominick, Wayne D. (Editor); Moreau, Dennis R.

    1984-01-01

    The development environment standards which have been established in order to control usage of the IBM PC/XT development systems and to prevent interference between projects being currently developed on the PC's are discussed. The standards address the following areas: scheduling PC resources; login/logout procedures; training; file naming conventions; hard disk organization; diskette care; backup procedures; and copying policies.

  16. Multifunctional Role of ATM/Tel1 Kinase in Genome Stability: From the DNA Damage Response to Telomere Maintenance

    Science.gov (United States)

    2014-01-01

    The mammalian protein kinase ataxia telangiectasia mutated (ATM) is a key regulator of the DNA double-strand-break response and belongs to the evolutionary conserved phosphatidylinositol-3-kinase-related protein kinases. ATM deficiency causes ataxia telangiectasia (AT), a genetic disorder that is characterized by premature aging, cerebellar neuropathy, immunodeficiency, and predisposition to cancer. AT cells show defects in the DNA damage-response pathway, cell-cycle control, and telomere maintenance and length regulation. Likewise, in Saccharomyces cerevisiae, haploid strains defective in the TEL1 gene, the ATM ortholog, show chromosomal aberrations and short telomeres. In this review, we outline the complex role of ATM/Tel1 in maintaining genomic stability through its control of numerous aspects of cellular survival. In particular, we describe how ATM/Tel1 participates in the signal transduction pathways elicited by DNA damage and in telomere homeostasis and its importance as a barrier to cancer development. PMID:25247188

  17. Calcium dysregulation and Cdk5-ATM pathway involved in a mouse model of fragile X-associated tremor/ataxia syndrome.

    Science.gov (United States)

    Robin, Gaëlle; López, José R; Espinal, Glenda M; Hulsizer, Susan; Hagerman, Paul J; Pessah, Isaac N

    2017-07-15

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurological disorder that affects premutation carriers with 55-200 CGG-expansion repeats (preCGG) in FMR1, presenting with early alterations in neuronal network formation and function that precede neurodegeneration. Whether intranuclear inclusions containing DNA damage response (DDR) proteins are causally linked to abnormal synaptic function, neuronal growth and survival are unknown. In a mouse that harbors a premutation CGG expansion (preCGG), cortical and hippocampal FMRP expression is moderately reduced from birth through adulthood, with greater FMRP reductions in the soma than in the neurite, despite several-fold elevation of Fmr1 mRNA levels. Resting cytoplasmic calcium concentration ([Ca2+]i) in cultured preCGG hippocampal neurons is chronically elevated, 3-fold compared to Wt; elevated ROS and abnormal glutamatergic responses are detected at 14 DIV. Elevated µ-calpain activity and a higher p25/p35 ratio in the cortex of preCGG young adult mice indicate abnormal Cdk5 regulation. In support, the Cdk5 substrate, ATM, is upregulated by 1.5- to 2-fold at P0 and 6 months in preCGG brain, as is p-Ser1981-ATM. Bax:Bcl-2 is 30% higher in preCGG brain, indicating a greater vulnerability to apoptotic activation. Elevated [Ca2+]i, ROS, and DDR signals are normalized with dantrolene. Chronic [Ca2+]i dysregulation amplifies Cdk5-ATM signaling, possibly linking impaired glutamatergic signaling and DDR to neurodegeneration in preCGG brain. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Allocating resources between network nodes for providing a network node function

    NARCIS (Netherlands)

    Strijkers, R.J.; Meulenhoff, P.J.

    2014-01-01

    The invention provides a method wherein a first network node advertises available resources that a second network node may use to offload network node functions transparently to the first network node. Examples of the first network node are a client device (e.g. PC, notebook, tablet, smart phone), a

  19. DNA damage-induced regulatory interplay between DAXX, p53, ATM kinase and Wip1 phosphatase

    Czech Academy of Sciences Publication Activity Database

    Bražina, Jan; Švadlenka, Jan; Macůrek, Libor; Anděra, Ladislav; Hodný, Zdeněk; Bartek, Jiří; Hanzlíková, Hana

    2015-01-01

    Roč. 14, č. 3 (2015), s. 375-387 ISSN 1538-4101 R&D Projects: GA ČR GPP305/11/P683 Institutional support: RVO:68378050 Keywords : ATM * DAXX * DNA damage * p53 * Wip1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.952, year: 2015

  20. EUV observations of the active Sun from the Havard experiment on ATM

    International Nuclear Information System (INIS)

    Noyes, R.W.; Foukal, P.V.; Huber, M.C.E.; Reeves, E.M.; Schmahl, E.J.; Timothy, J.G.; Vernazza, J.E.; Withbroe, G.L.

    1975-01-01

    The authors review some preliminary results from the Harvard College Observatory Extreme Ultraviolet Spectroheliometer on ATM that pertain to solar activity. The results reviewed are described in more detail in other papers referred to in the text. They first describe the instrument and its capabilities, and then turm to results on active regions, sunspots, flares, EUV bright points, coronal holes, and prominences. (Auth.)

  1. 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.

  2. Melting diagram of hydrogen-deuterium solutions for pressures up to 100 atm

    International Nuclear Information System (INIS)

    Bereznyak, N.G.; Sheinina, A.A.

    1985-01-01

    Curves of the onset of melting of hydrogen-deuterium solutions of three different concentrations versus the vapor pressure up to ∼140 atm are measured. The topology of the melting diagram of H 2 --D 2 solutions at elevated pressures is determined. The isotope separation coefficients between the liquid and solid phases are calculated

  3. WSB1 overcomes oncogene-induced senescence by targeting ATM for degradation

    Science.gov (United States)

    Kim, Jung Jin; Lee, Seung Baek; Yi, Sang-Yeop; Han, Sang-Ah; Kim, Sun-Hyun; Lee, Jong-Min; Tong, Seo-Yun; Yin, Ping; Gao, Bowen; Zhang, Jun; Lou, Zhenkun

    2017-01-01

    Oncogene-induced senescence (OIS) or apoptosis through the DNA-damage response is an important barrier of tumorigenesis. Overcoming this barrier leads to abnormal cell proliferation, genomic instability, and cellular transformation, and finally allows cancers to develop. However, it remains unclear how the OIS barrier is overcome. Here, we show that the E3 ubiquitin ligase WD repeat and SOCS box-containing protein 1 (WSB1) plays a role in overcoming OIS. WSB1 expression in primary cells helps the bypass of OIS, leading to abnormal proliferation and cellular transformation. Mechanistically, WSB1 promotes ATM ubiquitination, resulting in ATM degradation and the escape from OIS. Furthermore, we identify CDKs as the upstream kinase of WSB1. CDK-mediated phosphorylation activates WSB1 by promoting its monomerization. In human cancer tissue and in vitro models, WSB1-induced ATM degradation is an early event during tumorigenic progression. We suggest that WSB1 is one of the key players of early oncogenic events through ATM degradation and destruction of the tumorigenesis barrier. Our work establishes an important mechanism of cancer development and progression in premalignant lesions. PMID:27958289

  4. 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…

  5. ATM Technology and Banking System in West African Sub-Region ...

    African Journals Online (AJOL)

    User

    2011-04-19

    Apr 19, 2011 ... bank account makes financial transactions a breeze by eliminating the waste of writing cheques or the dangers of carrying large sums of cash. The debit cards benefit both the card holders and the banks. Some of the benefits of ATM technology is bank decongestion, reduced cost of transactions for both ...

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

    International Nuclear Information System (INIS)

    Vismari, Lucio Flavio; Batista Camargo Junior, Joao

    2011-01-01

    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.

  7. 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.

  8. 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 (Margriet); 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 (Guillermo); M.R. Alonso (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 (Arndt); 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

  9. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

    NARCIS (Netherlands)

    Southey, M.C.; Goldgar, D.E.; Winqvist, R.; Pylkas, K.; Couch, F.; Tischkowitz, M.; Foulkes, W.D.; Dennis, J.; Michailidou, K.; Rensburg, E.J. van; Heikkinen, T.; Nevanlinna, H.; Hopper, J.L.; Dork, T.; Claes, K.B.; Reis-Filho, J.; Teo, Z.L.; Radice, P.; Catucci, I.; Peterlongo, P.; Tsimiklis, H.; Odefrey, F.A.; Dowty, J.G.; Schmidt, M.K.; Broeks, A.; Hogervorst, F.B.; Verhoef, S.; Carpenter, J.; Clarke, C.; Scott, R.J.; Fasching, P.A.; Haeberle, L.; Ekici, A.B.; Beckmann, M.W.; Peto, J.; Dos-Santos-Silva, I.; Fletcher, O.; Johnson, N.; Bolla, M.K.; Sawyer, E.J.; Tomlinson, I.; Kerin, M.J.; Miller, N.; Marme, F.; Burwinkel, B.; Yang, R.; Guenel, P.; Truong, T.; Menegaux, F.; Sanchez, M.; Bojesen, S.; Nielsen, S.F.; Flyger, H.; Benitez, J.; Zamora, M.P.; Perez, J.I.; Menendez, P.; Anton-Culver, H.; Neuhausen, S.; Ziogas, A.; Clarke, C.A.; Brenner, H.; Arndt, V.; Stegmaier, C.; Brauch, H.; Bruning, T.; Ko, Y.D.; Muranen, T.A.; Aittomaki, K.; Blomqvist, C.; Bogdanova, N.V.; Antonenkova, N.N.; Lindblom, A.; Margolin, S.; Mannermaa, A.; Kataja, V.; Kosma, V.M.; Hartikainen, J.M.; Spurdle, A.B.; Wauters, E.; Smeets, D.; Beuselinck, B.; Floris, G.; Chang-Claude, J.; Rudolph, A.; Seibold, P.; Flesch-Janys, D.; Olson, J.E.; Vachon, C.; Pankratz, V.S.; McLean, C.; Haiman, C.A.; Henderson, B.E.; Schumacher, F.; Marchand, L. Le; Kristensen, V.; Alnaes, G.G.; Zheng, W.; Hunter, D.J.; Altena, A.M. van; Aben, K.K.H.; Kiemeney, L.A.L.M.; Massuger, L.F.A.G.; et al.,

    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

  10. Fabrication and characterization of MCC approved testing material: ATM-WV/205 glass

    International Nuclear Information System (INIS)

    Maupin, G.D.; Bowen, W.M.; Daniel, J.L.

    1988-08-01

    The ATM-WV/205 glass was produced in accordance with PNL's QA Manual for License-Related Programs, MCC technical procedures, and MCC QA Plan that were in effect during the course of this work. The method and procedure to be used in the fabrication and characterization of the ATM-WV/205 glass were specified in two run plans for glass preparation and a characterization plan. The ATM-WV/205 glass meets all specifications. The elemental composition and oxidation state of the glass are within the sponsor's specifications. Visually, the ATM-WV/205 glass bars appear uniformly glassy and generally without exterior features. Microscopic examination and x-ray diffraction revealed low (about 0.5 wt %) concentrations of 3-μm iron chrome spinel crystals and 1-μm ruthenium inclusions scattered randomly throughout the glassy matrix. Closed porosity, with pores ranging in diameter from 20 to 135 μm, was observed in all samples. 3 refs., 10 figs., 21 tabs

  11. 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).

  12. Cisplatin-mediated radiosensitization of non-small cell lung cancer cells is stimulated by ATM inhibition

    International Nuclear Information System (INIS)

    Toulany, Mahmoud; Mihatsch, Julia; Holler, Marina; Chaachouay, Hassan; Rodemann, H. Peter

    2014-01-01

    Background and purpose: Cisplatin activates ataxia-telangiectasia-mutated (ATM), a protein with roles in DNA repair, cell cycle progression and autophagy. We investigated the radiosensitizing effect of cisplatin with respect to its effect on ATM pathway activation. Material and methods: Non-small cell lung cancer cells (NSCLC) cell lines (A549, H460) and human fibroblast (ATM-deficient AT5, ATM-proficient 1BR3) cells were used. The effects of cisplatin combined with irradiation on ATM pathway activity, clonogenicity, DNA double-strand break (DNA-DSB) repair and cell cycle progression were analyzed with Western blotting, colony formation and γ-H2AX foci assays as well as FACS analysis, respectively. Results: Cisplatin radiosensitized H460 cells, but not A549 cells. Radiosensitization of H460 cells was not due to impaired DNA-DSB repair, increased apoptosis or cell cycle dysregulation. The lack of radiosensitization demonstrated for A549 cells was associated with cisplatin-mediated stimulation of ATM (S1981) and AMPKα (T172) phosphorylation and autophagy. However, in both cell lines inhibition of ATM and autophagy by KU-55933 and chloroquine diphosphate (CQ) respectively resulted in a significant radiosensitization. Combined treatment with the AMPK inhibitor compound-C led to radiosensitization of A549 but not of H460 cells. As compared to the treatment with KU-55933 alone, radiosensitivity of A549 cells was markedly stimulated by the combination of KU-55933 and cisplatin. However, the combination of CQ and cisplatin did not modulate the pattern of radiation sensitivity of A549 or H460 cells. In accordance with the results that cisplatin via stimulation of ATM activity can abrogate its radiosensitizing effect, ATM deficient cells were significantly sensitized to ionizing radiation by cisplatin. Conclusion: The results obtained indicate that ATM targeting can potentiate cisplatin-induced radiosensitization

  13. ATM variants and cancer risk in breast cancer patients from Southern Finland

    Directory of Open Access Journals (Sweden)

    Aittomäki Kristiina

    2006-08-01

    Full Text Available Abstract Background Individuals heterozygous for germline ATM mutations have been reported to have an increased risk for breast cancer but the role for ATM genetic variants for breast cancer risk has remained unclear. Recently, a common ATM variant, ATMivs38 -8T>C in cis with the ATMex39 5557G>A (D1853N variant, was suggested to associate with bilateral breast cancer among familial breast cancer patients from Northern Finland. We have here evaluated the 5557G>A and ivs38-8T>C variants in an extensive case-control association analysis. We also aimed to investigate whether there are other ATM mutations or variants contributing to breast cancer risk in our population. Methods Two common ATM variants, 5557G>A and ivs38-8T>C, previously suggested to associate with bilateral breast cancer, were genotyped in an extensive set of 786 familial and 884 unselected breast cancer cases as well as 708 healthy controls. We also screened the entire coding region and exon-intron boundaries of the ATM gene in 47 familial breast cancer patients and constructed haplotypes of the patients. The identified variants were also evaluated for increased breast cancer risk among additional breast cancer cases and controls. Results Neither of the two common variants, 5557G>A and ivs38-8T>C, nor any haplotype containing them, was significantly associated with breast cancer risk, bilateral breast cancer or multiple primary cancers in any of the patient groups or subgoups. Three rare missense alterations and one intronic change were each found in only one patient of over 250 familial patients studied and not among controls. The fourth missense alteration studied further was found with closely similar frequencies in over 600 familial cases and controls. Conclusion Altogether, our results suggest very minor effect, if any, of ATM genetic variants on familial breast cancer in Southern Finland. Our results do not support association of the 5557G>A or ivs38-8T>C variant with

  14. Telomere length, ATM mutation status and cancer risk in Ataxia-Telangiectasia families.

    Science.gov (United States)

    Renault, Anne-Laure; Mebirouk, Noura; Cavaciuti, Eve; Le Gal, Dorothée; Lecarpentier, Julie; d'Enghien, Catherine Dubois; Laugé, Anthony; Dondon, Marie-Gabrielle; Labbé, Martine; Lesca, Gaetan; Leroux, Dominique; Gladieff, Laurence; Adenis, Claude; Faivre, Laurence; Gilbert-Dussardier, Brigitte; Lortholary, Alain; Fricker, Jean-Pierre; Dahan, Karin; Bay, Jacques-Olivier; Longy, Michel; Buecher, Bruno; Janin, Nicolas; Zattara, Hélène; Berthet, Pascaline; Combès, Audrey; Coupier, Isabelle; Hall, Janet; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Lesueur, Fabienne

    2017-10-01

    Recent studies have linked constitutive telomere length (TL) to aging-related diseases including cancer at different sites. ATM participates in the signaling of telomere erosion, and inherited mutations in ATM have been associated with increased risk of cancer, particularly breast cancer. The goal of this study was to investigate whether carriage of an ATM mutation and TL interplay to modify cancer risk in ataxia-telangiectasia (A-T) families.The study population consisted of 284 heterozygous ATM mutation carriers (HetAT) and 174 non-carriers (non-HetAT) from 103 A-T families. Forty-eight HetAT and 14 non-HetAT individuals had cancer, among them 25 HetAT and 6 non-HetAT were diagnosed after blood sample collection. We measured mean TL using a quantitative PCR assay and genotyped seven single-nucleotide polymorphisms (SNPs) recurrently associated with TL in large population-based studies.HetAT individuals were at increased risk of cancer (OR = 2.3, 95%CI = 1.2-4.4, P = 0.01), and particularly of breast cancer for women (OR = 2.9, 95%CI = 1.2-7.1, P = 0.02), in comparison to their non-HetAT relatives. HetAT individuals had longer telomeres than non-HetAT individuals (P = 0.0008) but TL was not associated with cancer risk, and no significant interaction was observed between ATM mutation status and TL. Furthermore, rs9257445 (ZNF311) was associated with TL in HetAT subjects and rs6060627 (BCL2L1) modified cancer risk in HetAT and non-HetAT women.Our findings suggest that carriage of an ATM mutation impacts on the age-related TL shortening and that TL per se is not related to cancer risk in ATM carriers. TL measurement alone is not a good marker for predicting cancer risk in A-T families. © The Author 2017. Published by Oxford University Press.

  15. 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

  16. 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.

  17. Clinical applications of an ATM/Ethernet network in departments of neuroradiology and radiotherapy.

    Science.gov (United States)

    Cimino, C; Pizzi, R; Fusca, M; Bruzzone, M G; Casolino, D; Sicurello, F

    1997-01-01

    An integrated system for the multimedia management of images and clinical information has been developed at the Isituto Nazionale Neurologico C. Besta in Milan. The Institute physicians have the daily need of consulting images coming from various modalities. The high volume of archived material and the need of retrieving and displaying new and past images and clinical information has motivated the development of a Picture Archiving and Communication System (PACS) for the automatic management of images and clinical data, related not only to the Radiology Department, but also to the Radiotherapy Department for 3D virtual simulation, to remote teleconsulting, and in the following to all the wards, ambulatories and labs.

  18. 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.

  19. 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

  20. ATM splicing variants as biomarkers for low dose dexamethasone treatment of A-T.

    Science.gov (United States)

    Menotta, Michele; Biagiotti, Sara; Spapperi, Chiara; Orazi, Sara; Rossi, Luigia; Chessa, Luciana; Leuzzi, Vincenzo; D'Agnano, Daniela; Soresina, Annarosa; Micheli, Roberto; Magnani, Mauro

    2017-07-05

    Ataxia Telangiectasia (AT) is a rare incurable genetic disease, caused by biallelic mutations in the Ataxia Telangiectasia-Mutated (ATM) gene. Treatment with glucocorticoid analogues has been shown to improve the neurological symptoms that characterize this syndrome. Nevertheless, the molecular mechanism underlying the glucocorticoid action in AT patients is not yet understood. Recently, we have demonstrated that Dexamethasone treatment may partly restore ATM activity in AT lymphoblastoid cells by a new ATM transcript, namely ATMdexa1. In the present study, the new ATMdexa1 transcript was also identified in vivo, specifically in the PMBCs of AT patients treated with intra-erythrocyte Dexamethasone (EryDex). In these patients it was also possible to isolate new "ATMdexa1 variants" originating from canonical and non-canonical splicing, each containing the coding sequence for the ATM kinase domain. The expression of the ATMdexa1 transcript family was directly related to treatment and higher expression levels of the transcript in patients' blood correlated with a positive response to Dexamethasone therapy. Neither untreated AT patients nor untreated healthy volunteers possessed detectable levels of the transcripts. ATMdexa1 transcript expression was found to be elevated 8 days after the drug infusion, while it decreased 21 days after treatment. For the first time, the expression of ATM splicing variants, similar to those previously observed in vitro, has been found in the PBMCs of patients treated with EryDex. These findings show a correlation between the expression of ATMdexa1 transcripts and the clinical response to low dose dexamethasone administration.

  1. Hour-Glass Neural Network Based Daily Money Flow Estimation for Automatic Teller Machines

    Science.gov (United States)

    Karungaru, Stephen; Akashi, Takuya; Nakano, Miyoko; Fukumi, Minoru

    Monetary transactions using Automated Teller Machines (ATMs) have become a normal part of our daily lives. At ATMs, one can withdraw, send or debit money and even update passbooks among many other possible functions. ATMs are turning the banking sector into a ubiquitous service. However, while the advantages for the ATM users (financial institution customers) are many, the financial institution side faces an uphill task in management and maintaining the cash flow in the ATMs. On one hand, too much money in a rarely used ATM is wasteful, while on the other, insufficient amounts would adversely affect the customers and may result in a lost business opportunity for the financial institution. Therefore, in this paper, we propose a daily cash flow estimation system using neural networks that enables better daily forecasting of the money required at the ATMs. The neural network used in this work is a five layered hour glass shaped structure that achieves fast learning, even for the time series data for which seasonality and trend feature extraction is difficult. Feature extraction is carried out using the Akamatsu Integral and Differential transforms. This work achieves an average estimation accuracy of 92.6%.

  2. PC Software for Artificial Intelligence Applications.

    Science.gov (United States)

    Epp, H; Kalin, M; Miller, D

    1988-05-06

    Our review has emphasized that AI tools are programming languages inspired by some problem-solving paradigm. We want to underscore their status as programming languages; even if an AI tool seems to fit a problem perfectly, its proficient use still requires the training and practice associated with any programming language. The programming manuals for PC-Plus, Smalltalk/ V, and Nexpert Object are all tutorial in nature, and the corresponding software packages come with sample applications. We find the manuals to be uniformly good introductions that try to anticipate the problems of a user who is new to the technology. All three vendors offer free technical support by telephone to licensed users. AI tools are sometimes oversold as a way to make programming easy or to avoid it altogether. The truth is that AI tools demand programming-but programming that allows you to concentrate on the essentials of the problem. If we had to implement a diagnostic system, we would look first to a product such as PC-Plus rather than BASIC or C, because PC-Plus is designed specifically for such a problem, whereas these conventional languages are not. If we had to implement a system that required graphical interfaces and could benefit from inheritance, we would look first to an object-oriented system such as Smalltalk/V that provides built-in mechanisms for both. If we had to implement an expert system that called for some mix of AI and conventional techniques, we would look first to a product such as Nexpert Object that integrates various problem-solving technologies. Finally, we might use FORTRAN if we were concerned primarily with programming a well-defined numerical algorithm. AI tools are a valuable complement to traditional languages.

  3. Installation and implementation of PC COSYMA; PC COSYMAn kaeyttoeoenotto ja soveltaminen

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, J [VTT Energy, Espoo (Finland). Nuclear Energy

    1995-12-01

    COSYMA is a probabilistic reactor accident consequence assessment model developed in the 1980`s by the research institutes of the EC countries, primarily by NRPB and KfK. In 1993 a simplified version of the program was released to be implemented on a PC. In the study the PC COSYMA program was applied to calculate as the end points nuclide concentrations, doses received, numbers of health effects, areas affected by countermeasures and other results related to countermeasure strategies. Some results are compared with the results obtained by the ARANO program developed by VTT Energy (Technical Research Centre of Finland) to quarantee proper interpretation of the application. (15 refs.).

  4. Captor of Iodine coupled to PC

    International Nuclear Information System (INIS)

    Arista Romeu, Eduardo; Alonso Abad Dolores; Arteche Diaz, Raul

    2005-01-01

    A measurement - detection system (DETEC -PC) is presented to be used in Iodine Thyroid Uptake Studies. It consists of three elements: the detector with its collimator, a blind measurement module and the application software. The measurement module communicates trough a RS-232 serial interface to the Personal Computer where the application software (DETEC ) resides. The software was designed according to the principles of Object oriented programming using C++ language. It automatically fixes spectrometric measurement parameters and besides patient measurement also performs statistical analysis of a batch of samples. It possesses a PARADOX database with all information of measured patients and an 'on line' help with the system options

  5. PC-assisted translation of photogrammetric papers

    Science.gov (United States)

    Güthner, Karlheinz; Peipe, Jürgen

    A PC-based system for machine translation of photogrammetric papers from the English into the German language and vice versa is described. The computer-assisted translating process is not intended to create a perfect interpretation of a text but to produce a rough rendering of the content of a paper. Starting with the original text, a continuous data flow is effected into the translated version by means of hardware (scanner, personal computer, printer) and software (OCR, translation, word processing, DTP). An essential component of the system is a photogrammetric microdictionary which is being established at present. It is based on several sources, including e.g. the ISPRS Multilingual Dictionary.

  6. Repair genes expression profile of MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers.

    Science.gov (United States)

    Alves, Mônica Ghislaine Oliveira; Carta, Celina Faig Lima; de Barros, Patrícia Pimentel; Issa, Jaqueline Scholz; Nunes, Fábio Daumas; Almeida, Janete Dias

    2017-01-01

    The aim of this study was to evaluate the effect of chronic smoking on the expression profile of the repair genes MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers and never smokers. The sample consisted of thirty exfoliative cytology smears per group obtained from Smokers and Never Smokers. Total RNA was extracted and expression of the MLH1, MSH2 and ATM genes were evaluated by quantitative real-time and immunocytochemistry. The gene and protein expression data were correlated to the clinical data. Gene expression was analyzed statistically using the Student t-test and Pearson's correlation coefficient, with pMLH1, MSH2 and ATM genes were downregulated in the smoking group compared to the control with significant values for MLH1 (p=0.006), MSH2 (p=0.0001) and ATM (p=0.0001). Immunocytochemical staining for anti-MLH1, anti-MSH2 and anti-ATM was negative in Never Smokers; in Smokers it was rarely positive. No significant correlation was observed among the expression of MLH1, MSH2, ATM and age, number of cigarettes consumed per day, time of smoking during life, smoking history or levels of CO in expired air. The expression of genes and proteins related to DNA repair mechanism MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers was reduced. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect.

    Science.gov (United States)

    Oikemus, Sarah R; McGinnis, Nadine; Queiroz-Machado, Joana; Tukachinsky, Hanna; Takada, Saeko; Sunkel, Claudio E; Brodsky, Michael H

    2004-08-01

    Terminal deletions of Drosophila chromosomes can be stably protected from end-to-end fusion despite the absence of all telomere-associated sequences. The sequence-independent protection of these telomeres suggests that recognition of chromosome ends might contribute to the epigenetic protection of telomeres. In mammals, Ataxia Telangiectasia Mutated (ATM) is activated by DNA damage and acts through an unknown, telomerase-independent mechanism to regulate telomere length and protection. We demonstrate that the Drosophila homolog of ATM is encoded by the telomere fusion (tefu) gene. In the absence of ATM, telomere fusions occur even though telomere-specific Het-A sequences are still present. High levels of spontaneous apoptosis are observed in ATM-deficient tissues, indicating that telomere dysfunction induces apoptosis in Drosophila. Suppression of this apoptosis by p53 mutations suggests that loss of ATM activates apoptosis through a DNA damage-response mechanism. Loss of ATM reduces the levels of heterochromatin protein 1 (HP1) at telomeres and suppresses telomere position effect. We propose that recognition of chromosome ends by ATM prevents telomere fusion and apoptosis by recruiting chromatin-modifying complexes to telomeres.

  8. 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. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Evidence for the Deregulation of Protein Turnover Pathways in Atm-Deficient Mouse Cerebellum: An Organotypic Study.

    Science.gov (United States)

    Kim, Catherine D; Reed, Ryan E; Juncker, Meredith A; Fang, Zhide; Desai, Shyamal D

    2017-07-01

    Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells. In the current study, we show that, as in A-T cells, ISG15 protein expression is elevated in cerebellums and various other tissues obtained from Atm-compromised mice in an Atm-allele-dependent manner (Atm+/+ Atm+/- Atm-/-). Notably, in cerebellums, the brain part primarily affected in A-T, levels of ISG15 were significantly greater (3-fold higher) than cerebrums obtained from the same set of mice. Moreover, as in A-T cell culture, UV induces aberrant degradation of ubiquitylated proteins and autophagy in Atm-deficient, but not in Atm-proficient, cerebellar brain slices grown in culture. Thus, the ex vivo organotypic A-T mouse brain culture model mimics that of an A-T human cell culture model and could be useful for studying the role of ISG15-dependent proteinopathy in cerebellar neurodegeneration, a hallmark of A-T in humans. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  10. Modulation of proteostasis counteracts oxidative stress and affects DNA base excision repair capacity in ATM-deficient cells.

    Science.gov (United States)

    Poletto, Mattia; Yang, Di; Fletcher, Sally C; Vendrell, Iolanda; Fischer, Roman; Legrand, Arnaud J; Dianov, Grigory L

    2017-09-29

    Ataxia telangiectasia (A-T) is a syndrome associated with loss of ATM protein function. Neurodegeneration and cancer predisposition, both hallmarks of A-T, are likely to emerge as a consequence of the persistent oxidative stress and DNA damage observed in this disease. Surprisingly however, despite these severe features, a lack of functional ATM is still compatible with early life, suggesting that adaptation mechanisms contributing to cell survival must be in place. Here we address this gap in our knowledge by analysing the process of human fibroblast adaptation to the lack of ATM. We identify profound rearrangement in cellular proteostasis occurring very early on after loss of ATM in order to counter protein damage originating from oxidative stress. Change in proteostasis, however, is not without repercussions. Modulating protein turnover in ATM-depleted cells also has an adverse effect on the DNA base excision repair pathway, the major DNA repair system that deals with oxidative DNA damage. As a consequence, the burden of unrepaired endogenous DNA lesions intensifies, progressively leading to genomic instability. Our study provides a glimpse at the cellular consequences of loss of ATM and highlights a previously overlooked role for proteostasis in maintaining cell survival in the absence of ATM function. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. EGb 761 Protects Cardiac Microvascular Endothelial Cells against Hypoxia/Reoxygenation Injury and Exerts Inhibitory Effect on the ATM Pathway.

    Science.gov (United States)

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

    2017-03-28

    Ginkgo bilob a extract (EGb 761) has been widely used clinically 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 protective effect of EGb 761 on MVECs resisting hypoxia/reoxygenation (H/R) injury is little reported. In this study, H/R-injured MVECs were treated with EGb 761, and then the cell viability, apoptosis, ROS production, SOD activity, caspase-3 activity, and protein level of ATM, γ-H2AX, p53, and Bax were measured. ATM siRNA was transfected to study the changes of protein in the ATM pathway. EGb 761 presented protective effect on H/R-injured MVECs, with decreasing cell death, apoptosis, and ROS, and elevated SOD activity. Next, EGb 761 could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax in a dose-dependent manner. Moreover, ATM siRNA also could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax. Overall, these findings verify that EGb 761 protects cardiac MVECs from H/R injury, and for the first time, illustrate the influence on the ATM pathway and apoptosis by EGb 761 via dampening ROS.

  12. 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.

  13. Almost 2% of Spanish breast cancer families are associated to germline pathogenic mutations in the ATM gene.

    Science.gov (United States)

    Tavera-Tapia, A; Pérez-Cabornero, L; Macías, J A; Ceballos, M I; Roncador, G; de la Hoya, M; Barroso, A; Felipe-Ponce, V; Serrano-Blanch, R; Hinojo, C; Miramar-Gallart, M D; Urioste, M; Caldés, T; Santillan-Garzón, S; Benitez, J; Osorio, A

    2017-02-01

    There is still a considerable percentage of hereditary breast and ovarian cancer (HBOC) cases not explained by BRCA1 and BRCA2 genes. In this report, next-generation sequencing (NGS) techniques were applied to identify novel variants and/or genes involved in HBOC susceptibility. Using whole exome sequencing, we identified a novel germline mutation in the moderate-risk gene ATM (c.5441delT; p.Leu1814Trpfs*14) in a family negative for mutations in BRCA1/2 (BRCAX). A case-control association study was performed to establish its prevalence in Spanish population, in a series of 1477 BRCAX families and 589 controls further screened, and NGS panels were used for ATM mutational screening in a cohort of 392 HBOC Spanish BRCAX families and 350 patients affected with diseases not related to breast cancer. Although the interrogated mutation was not prevalent in case-control association study, a comprehensive mutational analysis of the ATM gene revealed 1.78% prevalence of mutations in the ATM gene in HBOC and 1.94% in breast cancer-only BRCAX families in Spanish population, where data about ATM mutations were very limited. ATM mutation prevalence in Spanish population highlights the importance of considering ATM pathogenic variants linked to breast cancer susceptibility.

  14. Versatile PC-logger for radioisotope measurements

    International Nuclear Information System (INIS)

    Furman, L.; Petryka, L.; Przewlocki, K.; Stegowski, Z.; Wierzbicki, A.

    1998-01-01

    The logger, a personal computer and software is all to set up a radioisotope measuring system. It may find numerous applications in a wide range of disciplines: kinetics description of flow process in industry, slip velocity measurements in hydrotransport, flow rates evaluation in waste water treatment plants, nucleonic gauges in industry, ect. Readings from up to 4 scintillation detectors, the user has set to log, are stored in regular intervals. The user can set the logger to start and stop logging manually, with keyboard or from a program running on a connected PC. Stored data can be transferred to any computer with RS232 serial interface. The logger works equally well together with conventional PC's and 'lap-tops' for field work. Its internal program is stored in nonvolatile RAM. This makes it possible to upgrade or change the code by just down loading a new one. The logger is internal rechargeable batteries for measuring off-line; they remain as a back-up in case the external supply is disconnected or fails. (author)

  15. p27Kip1 Is Required to Mediate a G1 Cell Cycle Arrest Downstream of ATM following Genotoxic Stress.

    Directory of Open Access Journals (Sweden)

    Erica K Cassimere

    Full Text Available The DNA damage response (DDR is a coordinated signaling network that ensures the maintenance of genome stability under DNA damaging stress. In response to DNA lesions, activation of the DDR leads to the establishment of cell cycle checkpoints that delay cell-cycle progression and allow repair of the defects. The tumor suppressor p27Kip1 is a cyclin-CDK inhibitor that plays an important role in regulating quiescence in a variety of tissues. Several studies have suggested that p27Kip1 also plays a role in the maintenance of genomic integrity. Here we demonstrate that p27Kip1 is essential for the establishment of a G1 checkpoint arrest after DNA damage. We also uncovered that ATM phosphorylates p27Kip1 on a previously uncharacterized residue (Ser-140, which leads to its stabilization after induction of DNA double-strand breaks. Inhibition of this stabilization by replacing endogenous p27Kip1 with a Ser-140 phospho-mutant (S140A significantly sensitized cells to IR treatments. Our findings reveal a novel role for p27Kip1 in the DNA damage response pathway and suggest that part of its tumor suppressing functions relies in its ability to mediate a G1 arrest after the induction of DNA double strand breaks.

  16. EBV-encoded miRNAs target ATM-mediated response in nasopharyngeal carcinoma.

    Science.gov (United States)

    Lung, Raymond W-M; Hau, Pok-Man; Yu, Ken H-O; Yip, Kevin Y; Tong, Joanna H-M; Chak, Wing-Po; Chan, Anthony W-H; Lam, Ka-Hei; Lo, Angela Kwok-Fung; Tin, Edith K-Y; Chau, Shuk-Ling; Pang, Jesse C-S; Kwan, Johnny S-H; Busson, Pierre; Young, Lawrence S; Yap, Lee-Fah; Tsao, Sai-Wah; To, Ka-Fai; Lo, Kwok-Wai

    2018-04-01

    Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignancy that is prevalent in southern China and Southeast Asia. It is consistently associated with latent Epstein-Barr virus (EBV) infection. In NPC, miR-BARTs, the EBV-encoded miRNAs derived from BamH1-A rightward transcripts, are abundantly expressed and contribute to cancer development by targeting various cellular and viral genes. In this study, we establish a comprehensive transcriptional profile of EBV-encoded miRNAs in a panel of NPC patient-derived xenografts and an EBV-positive NPC cell line by small RNA sequencing. Among the 40 miR-BARTs, predominant expression of 22 miRNAs was consistently detected in these tumors. Among the abundantly expressed EBV-miRNAs, BART5-5p, BART7-3p, BART9-3p, and BART14-3p could negatively regulate the expression of a key DNA double-strand break (DSB) repair gene, ataxia telangiectasia mutated (ATM), by binding to multiple sites on its 3'-UTR. Notably, the expression of these four miR-BARTs represented more than 10% of all EBV-encoded miRNAs in tumor cells, while downregulation of ATM expression was commonly detected in all of our tested sequenced samples. In addition, downregulation of ATM was also observed in primary NPC tissues in both qRT-PCR (16 NP and 45 NPC cases) and immunohistochemical staining (35 NP and 46 NPC cases) analysis. Modulation of ATM expression by BART5-5p, BART7-3p, BART9-3p, and BART14-3p was demonstrated in the transient transfection assays. These findings suggest that EBV uses miRNA machinery as a key mechanism to control the ATM signaling pathway in NPC cells. By suppressing these endogenous miR-BARTs in EBV-positive NPC cells, we further demonstrated the novel function of miR-BARTs in inhibiting Zta-induced lytic reactivation. These findings imply that the four viral miRNAs work co-operatively to modulate ATM activity in response to DNA damage and to maintain viral latency, contributing to the tumorigenesis of NPC. © 2017 The Authors

  17. PC-based Multiple Information System Interface (PC/MISI) detailed design and implementation plan

    Science.gov (United States)

    Dominick, Wayne D. (Editor); Hall, Philip P.

    1985-01-01

    The design plan for the personal computer multiple information system interface (PC/MISI) project is discussed. The document is intended to be used as a blueprint for the implementation of the system. Each component is described in the detail necessary to allow programmers to implement the system. A description of the system data flow and system file structures is given.

  18. Constraining lowermost mantle structure with PcP/P amplitude ratios from large aperture arrays

    Science.gov (United States)

    Ventosa, S.; Romanowicz, B. A.

    2015-12-01

    Observations of weak short-period teleseismic body waves help to resolve lowermost mantle structure at short wavelengths, which is essential for understanding mantle dynamics and the interactions between the mantle and core. Their limited amount and uneven distribution are however major obstacles to solve for volumetric structure of the D" region, topography of the core-mantle boundary (CMB) and D" discontinuity, and the trade-offs among them. While PcP-P differential travel times provide important information, there are trade-offs between velocity structure and core-mantle boundary topography, which PcP/P amplitude ratios can help resolve, as long as lateral variations in attenuation and biases due to focusing are small or can be corrected for. Dense broadband seismic networks help to improve signal-to-noise ratio (SNR) of the target phases and signal-to-interference ratio (SIR) of other mantle phases when the slowness difference is large enough. To improve SIR and SNR of teleseismic PcP data, we have introduced the slant-stacklet transform to define coherent-guided filters able to separate and enhance signals according to their slowness, time of arrival and frequency content. We thus obtain optimal PcP/P amplitude ratios in the least-square sense using two short sliding windows to match the P signal with a candidate PcP signal. This method allows us to dramatically increase the amount of high-quality observations of short-period PcP/P amplitude ratios by allowing for smaller events and wider epicentral distance and depth ranges.We present the results of measurement of PcP/P amplitude ratios, sampling regions around the Pacific using dense arrays in North America and Japan. We observe that short-period P waves traveling through slabs are strongly affected by focusing, in agreement with the bias we have observed and corrected for due to mantle heterogeneities on PcP-P travel time differences. In Central America, this bias is by far the stronger anomaly we observe

  19. Closing the loop; Production data management by PC's in the field

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, S. (Samedan Oil Corp. (US))

    1991-11-01

    This paper reports that accounting and engineering groups have long commanded a high level of expertise in the ability to manipulate oil well production data for the calculation of well performance trends, reserve estimations, and lease-hold accounting. Unfortunately, the data crucial to the accuracy of this work are often affected negatively by human error in the calculation of production volumes, the time available in performing paperwork-oriented tasks, and the timeliness with which computed data are made available to these groups. To correct this situation, the authors have developed a PC-based Production Acquisition Allocation and Reporting System (PAARS) for field and office personnel. With this system, all data entry and allocations are still assembled in the field, but all calculations are done by the PC. Additional tracked data include personnel costs and activities, regulatory compliance information, and marketing data. Whenever desired, data are transmitted to a central PC or mainframe data base, where they become immediately available for use by accounting, engineering, marketing, and management personnel. At the Offshore Div., for example, the office staff has current production and well test data available off the PC network, for every operated well, when they arrive at work in the morning.

  20. Adaptive MAC-layer protocol for multiservice digital access via tree and branch communication networks

    Science.gov (United States)

    Sriram, Kotikalapudi; Li, Chia-Chang; Magill, Peter; Whitaker, Norman A.; Dail, James E.; Dajer, Miguel A.; Siller, Curtis A.

    1995-11-01

    Described here is an adaptive MAC-layer protocol that supports multiservice (STM and ATM) applications in the context of subscriber access to tree and branch (e.g., fiber-coaxial cable) networks. The protocol adapts to changing demands for a mix of circuit and cell mode applications, and efficiently allocates upstream and downstream bandwidth to a variety of bursty and isochronous traffic sources. In the case of a hybrid fiber-coaxial (HFC) network the protocol resides in customer premises equipment and a common head-end controller. A medium-access control (MAC) processor provides for dividing the time domain for a given digital bitstream into successive frames, each with multiple STM and ATM time slots. Within the STM region of a frame, variable length time slots are allocated to calls (e.g., telephony, video telephony) requiring different amounts of bandwidth. A contention access signaling channel is also provided in this region for call control and set-up requests. Within the ATM region fixed-length time slots accommodate one individual ATM cell. These ATM time slots may be reserved for a user for the duration of a call or burst of successive ATM cells, or shared via a contention process. At least one contention time slot is available for signaling messages related to ATM call control and set-up requests. Further, the fixed-length ATM time slots may be reserved by a user for the duration of a call, or shared through a contention process. This paper describes the MAC-layer protocol, its relation to circuit- and ATM- amenable applications, and its performance with respect to signaling throughput and latency, and bandwidth efficiency for several service scenarios.

  1. 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. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 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. .

  3. 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

  4. D-ATM, a working example of health care interoperability: From dirt path to gravel road.

    Science.gov (United States)

    DeClaris, John-William

    2009-01-01

    For many years, there have been calls for interoperability within health care systems. The technology currently exists and is being used in business areas like banking and commerce, to name a few. Yet the question remains, why has interoperability not been achieved in health care? This paper examines issues encountered and success achieved with interoperability during the development of the Digital Access To Medication (D-ATM) project, sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA). D-ATM is the first government funded interoperable patient management system. The goal of this paper is to provide lessons learned and propose one possible road map for health care interoperability within private industry and how government can help.

  5. 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

  6. PC application in DIII-D neutral beam operation

    International Nuclear Information System (INIS)

    Gladd, A.S.

    1986-01-01

    An IBM PC/AT has been implemented to improve operation of the DIII-D neutral beams. The PC system provides centralization of all beam data with reasonable access for online shot-to-shot control and analysis. The PC hardware was configured to interface all four neutral beam host mini-computers, support multi-tasking, and provide storage for approximately one month's accumulation of beam data. The PC software is composed of commercial packages used for performance and statistical analysis (i.e. LOTUS 123, PC PLOT, etc.) host communications software (i.e. PCLINK, KERMIT, etc.) and applications developed software utilizing FORTRAN and BASIC. The objectives of this paper are to describe the implementation of the PC system, the methods of integrating the various software packages, and the scenario for online control and analysis

  7. Organic photovoltaic effects depending on CuPc layer thickness

    International Nuclear Information System (INIS)

    Hur, Sung Woo; Kim, Tae Wan; Chung, Dong Hoe; Oh, Hyun Seok; Kim, Chung Hyeok; Lee, Joon Ung; Park, Jong Wook

    2004-01-01

    Organic photovoltaic effects were studied in device structures of ITO/CuPc/Al and ITO/CuPc/C 60 /BCP/Al by varying the CuPc layer thickness. Since the exciton diffusion length is relatively short in organic semiconductors, a study on the thickness-dependent photovoltaic effects is important. The thickness of the CuPc layer was varied from 10 nm to 50 nm. We found that the optimum CuPc layer thickness was around 40 nm from the analysis of the current density-voltage characteristics in an ITO/CuPc/Al photovoltaic cell. The efficiency of the device shows that the multi-layered heterojunction structure is more appropriate for photovoltaic cells.

  8. 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.

  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. 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

  11. Arctic Sea Ice: Using Airborne Topographic Mapper Measurements (ATM) to Determine Sea Ice Thickness

    Science.gov (United States)

    2011-05-10

    Track Distance (Km) E le v a ti o n ( m ) ATM Elevation Profile Elevation 18 Figure 13: Geoid shape of earth’s equipotential surface , which is...inferred for the region between successive leads. Therefore, flying over a lead in the ice is very important for determining the exact sea surface elevation...inferred for the region between successive leads. Therefore, flying over a lead in the ice is very important for determining the exact sea surface

  12. Materials accounting system for an IBM PC

    International Nuclear Information System (INIS)

    Bearse, R.C.; Thomas, R.J.; Henslee, S.P.; Jackson, B.G.; Tracy, D.B.; Pace, D.M.

    1986-01-01

    We have adapted the Los Alamos MASS accounting system for use on an IBM PC/AT at the Fuels Manufacturing Facility (FMF) at Argonne National Laboratory-West (ANL-WEST) in Idaho Falls, Idaho. Cost of hardware and proprietary software was less than $10,000 per station. The system consists of three stations between which accounting information is transferred using floppy disks accompanying special nuclear material shipments. The programs were implemented in dBASEIII and were compiled using the proprietary software CLIPPER. Modifications to the inventory can be posted in just a few minutes, and operator/computer interaction is nearly instantaneous. After the records are built by the user, it takes 4 to 5 seconds to post the results to the database files. A version of this system was specially adapted and is currently in use at the FMF facility at Argonne National Laboratory in Idaho Falls. Initial satisfaction is adequate and software and hardware problems are minimal

  13. Graphics based PC analysis of alpha spectra

    International Nuclear Information System (INIS)

    Chapman, T.C.

    1991-01-01

    New personal computer (PC) software performs interactive analysis of alpha spectra using EGA graphics. Spectra are collected with a commercial MCA board and analyzed using the software described here. The operator is required to approve each peak integration area before analysis proceeds. Sample analysis can use detector efficiencies or spike yields or both. Background corrections are made and upper limit values are calculated when specified. Nuclide identification uses a library of up to 64 nuclides with up to 8 alpha lines for each nuclide. Any one of 32 subset libraries can be used in an analysis. Analysis time is short and is limited by interaction with the operator, not by calculation time. Utilities include nuclide library editing, library subset editing, energy calibration, efficiency calibration, and background update

  14. ATM Mediates pRB Function To Control DNMT1 Protein Stability and DNA Methylation

    Science.gov (United States)

    Suzuki, Misa; Hayashi, Naoyuki; Kobayashi, Masahiko; Sasaki, Nobunari; Nishiuchi, Takumi; Doki, Yuichiro; Okamoto, Takahiro; Kohno, Susumu; Muranaka, Hayato; Kitajima, Shunsuke; Yamamoto, Ken-ichi

    2013-01-01

    The retinoblastoma tumor suppressor gene (RB) product has been implicated in epigenetic control of gene expression owing to its ability to physically bind to many chromatin modifiers. However, the biological and clinical significance of this activity was not well elucidated. To address this, we performed genetic and epigenetic analyses in an Rb-deficient mouse thyroid C cell tumor model. Here we report that the genetic interaction of Rb and ATM regulates DNMT1 protein stability and hence controls the DNA methylation status in the promoters of at least the Ink4a, Shc2, FoxO6, and Noggin genes. Furthermore, we demonstrate that inactivation of pRB promotes Tip60 (acetyltransferase)-dependent ATM activation; allows activated ATM to physically bind to DNMT1, forming a complex with Tip60 and UHRF1 (E3 ligase); and consequently accelerates DNMT1 ubiquitination driven by Tip60-dependent acetylation. Our results indicate that inactivation of the pRB pathway in coordination with aberration in the DNA damage response deregulates DNMT1 stability, leading to an abnormal DNA methylation pattern and malignant progression. PMID:23754744

  15. Titanium dioxide nanoparticles activate the ATM-Chk2 DNA damage response in human dermal fibroblasts

    Science.gov (United States)

    Prasad, Raju Y.; Chastain, Paul D.; Nikolaishvili-Feinberg, Nana; Smeester, Lisa M.; Kaufmann, William K.; Fry, Rebecca C.

    2013-01-01

    The use of nanoparticles in consumer products increases their prevalence in the environment and the potential risk to human health. Although recent studies have shown in vivo and in vitro toxicity of titanium dioxide nanoparticles (nano-TiO2), a more detailed view of the underlying mechanisms of this response needs to be established. Here the effects of nano-TiO2 on the DNA damage response and DNA replication dynamics were investigated in human dermal fibroblasts. Specifically, the relationship between nano-TiO2 and the DNA damage response pathways regulated by ATM/Chk2 and ATR/Chk1 were examined. The results show increased phosphorylation of H2AX, ATM, and Chk2 after exposure. In addition, nano-TiO2 inhibited the overall rate of DNA synthesis and frequency of replicon initiation events in DNA combed fibers. Taken together, these results demonstrate that exposure to nano-TiO2 activates the ATM/Chk2 DNA damage response pathway. PMID:22770119

  16. Screening for ATM Mutations in an African-American Population to Identify a Predictor of Breast Cancer Susceptibility

    National Research Council Canada - National Science Library

    Rosenstein, Barry S

    2006-01-01

    The hypothesis being tested in this project is that a greater proportion of African-Americans with breast cancer harbor a specific germline genetic alteration in the ATM gene or possess a particular...

  17. ATM Heterozygosity and the Development of Radiation-Induced Erectile Dysfunction and Urinary Morbidity Following Radiotherapy for Prostate Cancer

    National Research Council Canada - National Science Library

    Cesaretti, Jamie A

    2006-01-01

    The goal of this training grant project is to determine whether the prevalence of ATM carriers among prostate cancer patients treated with radiotherapy that develop erectile dysfunction and urinary...

  18. ATM Heterozygosity and the Development of Radiation-Induced Erectile Dysfunction and Urinary Morbidity Following Radiotherapy for Prostate Cancer

    National Research Council Canada - National Science Library

    Cesaretti, Jamie A

    2007-01-01

    The goal of this training grant project is to determine whether the prevalence of ATM carriers among prostate cancer patients treated with radiotherapy that develop erectile dysfunction and urinary...

  19. ATM Heterozygosity and the Development of Radiation-Induced Erectile Dysfunction and Urinary Morbidity Following Radiotherapy for Prostate Cancer

    National Research Council Canada - National Science Library

    Cesaretti, Jamie A

    2008-01-01

    The goal of this training grant project is to determine whether the prevalence of ATM carriers among prostate cancer patients treated with radiotherapy that develop erectile dysfunction and urinary...

  20. Design of multichannel counting system for IBM PC and compatibles

    International Nuclear Information System (INIS)

    Majeed, B.; Ahmad, Z.; Osman, A.; Ysain, M.M.

    1995-07-01

    A Multichannel Counting System (MCCS), based on IBM-PC and compatible computer systems have been designed. The MCCS consists of a Multichannel Counting System plug-in interface card (MCCS-PC) for IBM PC and compatibles and a NIM-BIN module (MCCS-NB). The MCCS-PC provides simultaneous monitoring of upto seven independent SCA type inputs. An on board programmable timer provides elapsed time measurement. A menu-driven program for data acquisition and timer control has also been developed. (author) 8 figs

  1. The readout performance evaluation of PowerPC

    International Nuclear Information System (INIS)

    Chu Yuanping; Zhang Hongyu; Zhao Jingwei; Ye Mei; Tao Ning; Zhu Kejun; Tang Suqiu; Guo Yanan

    2003-01-01

    PowerPC, as a powerful low-cost embedded computer, is one of the very important research objects in recent years in the project of BESIII data acquisition system. The researches on the embedded system and embedded computer have achieved many important results in the field of High Energy Physics especially in the data acquisition system. The one of the key points to design an acquisition system using PowerPC is to evaluate the readout ability of PowerPC correctly. The paper introduce some tests for the PowerPC readout performance. (authors)

  2. Effect of silencing of ATM expression by siRNA on radiosensitivity of human lung adenocarcinoma A549 cells

    International Nuclear Information System (INIS)

    Liu Xiaoqun; Qiao Tiankui

    2014-01-01

    Objective: To investigate the effect of silencing of ataxia-telangiectasia mutated (ATM) expression by plasmid-mediated RNA interference on the radiosensitivity of human lung adenocarcinoma A 549 cells. Methods: Eukaryotic expression plasmid containing ATM small interfering RNA (siRNA) (pSilencer2.1-ATM), as well as pSilencer2.1-nonspecific, was constructed.Lung adenocarcinoma A 549 cells were divided into positive group, negative group,and control group to be transfected with pSilencer2.1-ATM, pSilencer2.1-nonspecific, and no plasmid, respectively. The mRNA and protein expression of ATM was measured by RT-PCR and Western blot, respectively. The change in cell radiosensitivity was observed by colony-forming assay. Cell cycle and cell apoptosis were analyzed by flow cytometry. Results: The eukaryotic expression plasmid containing ATM siRNA was successfully constructed. The RT-PCR and Western blot demonstrated that the expression of ATM was down-regulated in the positive group. The sensitization enhancement ratios (D 0 ratios) for the positive group and negative group were 1.50 and 1.01, respectively. The flow cytometry revealed that the proportions of A 549 cells in G 1 and G 2 /M phases were significantly lower in the positive group than in the control group (51.27% vs 61.85%, P = 0.012; 6.34% vs 10.91%, P = 0.008) and that the apoptosis rate was significantly higher in the positive group than in the control group and negative group (49.31% vs 13.58%, P = 0.000; 49.31% vs 13.17%, P = 0.000). Conclusions: Silencing of ATM expression may increase the radiosensitivity of human lung adenocarcinoma A 549 cells, probably by affecting the cell cycle and promoting cell apoptosis. (authors)

  3. 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.

  4. Barriers and Facilitators of Iranian Elderly in Use of ATM Machines: A Qualitative Research in the Way of Cultural Probes

    Directory of Open Access Journals (Sweden)

    Azade Mokhberi

    2013-10-01

    Full Text Available Objectives: Having considering to the rate of increasing of elder people population in Iran, is preadicted that in the next thirty years the number of elderly people who need to independently work with electronic devices such as ATMs machineswill be significantly increased while there is no sufficient studies in order to modification of these devices considering physical, mental and psychology abilities of the elder people. Methods & Materials: This article is part of a qualitative study with cultural Probes Methodology to explore the needs and barriers and facilitators in the work ATMs. This study collected data through observation, interview and documentation participants respectively. This qualitative study was conducted in two stages. In the first phase interviewed with 30 elderly people in Tehran.In the second Phase according to cultural probes method we designed a package to extract the needs and problems associated with ATM. purposive sample of 10 elderly people in Tehran, 6 participants were female and 4 males. Interviews continued until data saturation, data Were coded and categorized by content analysis method. Results: Six key factors required for the design of ATM data were extracted according to the Iranian people, that pleasant, unpleasant, wants and desires, problems and obstacles, banking and mishaps. that the classification of barriers and facilitating factors these factors were extracted for the elderly. The results showed a much higher barriers to Elderly people using ATMs in facilitating conditions are present. Conclusion: According to the Iranian people using ATMs barrier is recommended to attention to ATMs in the the environment, nature and location of the installation, ATMs appear particularly relevant in the context of software that can be tailored to the elderly should be done. Finally, it is suggested that future studies in different groups of people, especially older people with disabilities and low literacy are doing.

  5. An Exploratory Study of the Critical Factors Affecting the Acceptability of Automated Teller Machine (ATM) in Nigeria

    OpenAIRE

    Olusegun Folorunso; Oluwafunmilayo Ayobami Ateji; Gabriel Oludare Awe

    2010-01-01

    This paper uses the Technology Acceptance Model (TAM) as a basis for studying critical factors that affects the acceptability of Automated Teller Machine (ATM) in Nigeria. Questionnaire approach was used with the respondents predominantly between 20-29 years old. Factor analysis was used to test which of the factors are the main factors affecting the adoption of the technology in Nigeria. It was discovered that the major factors affecting people’s intention to accept ATM are the security issu...

  6. 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

  7. ATM is required for the repair of Topotecan-induced replication-associated double-strand breaks

    International Nuclear Information System (INIS)

    Köcher, Sabrina; Spies-Naumann, Anja; Kriegs, Malte; Dahm-Daphi, Jochen; Dornreiter, Irena

    2013-01-01

    Purpose: DNA replication is a promising target for anti-cancer therapies. Therefore, the understanding of replication-associated DNA repair mechanisms is of great interest. One key factor of DNA double-strand break (DSB) repair is the PIK kinase Ataxia-Telangiectasia Mutated (ATM) but it is still unclear whether ATM is involved in the repair of replication-associated DSBs. Here, we focused on the involvement of ATM in homology-directed repair (HDR) of indirect DSBs associated with replication. Material and methods: Experiments were performed using ATM-deficient and -proficient human cells. Replication-associated DSBs were induced with Topotecan (TPT) and compared with γ-irradiation (IR). Cell survival was measured by clonogenic assay. Overall DSB repair and HDR were evaluated by detecting residual γH2AX/53BP1 and Rad51 foci, respectively. Cell cycle distribution was analysed by flow cytometry and protein expression by Western blot. Results: ATM-deficiency leads to enhanced numbers of residual DSBs, resulting in a pronounced S/G2-block and decreased survival upon TPT-treatment. In common with IR, persisting Rad51 foci were detected following TPT-treatment. Conclusions: These results demonstrate that ATM is essentially required for the completion of HR-mediated repair of TPT-induced DSBs formed indirectly at replication forks

  8. The association between ATM IVS 22-77 T>C and cancer risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    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.

  9. Radiotherapy induces cell cycle arrest and cell apoptosis in nasopharyngeal carcinoma via the ATM and Smad pathways.

    Science.gov (United States)

    Li, Ming-Yi; Liu, Jin-Quan; Chen, Dong-Ping; Li, Zhou-Yu; Qi, Bin; He, Lu; Yu, Yi; Yin, Wen-Jin; Wang, Meng-Yao; Lin, Ling

    2017-09-02

    Nasopharyngeal carcinoma (NPC) is a common malignant neoplasm of the head and neck which is harmful to human's health. Radiotherapy is commonly used in the treatment of NPC and it induces immediate cell cycle arrest and cell apoptosis. However, the mechanism remains unknown. Evidences suggested the activation of Ataxia telangiectasia mutated (ATM) pathway and Smad pathway are 2 of the important crucial mediators in the function of radiotherapy. In this study, we performed in vitro assays with human nasopharyngeal carcinoma CNE-2 cells and in vivo assays with nude mice to investigate the role of the ATM and Smad pathways in the treatment of nasopharyngeal carcinoma with radiotherapy. The results suggested that radiation induced activation of ATM pathway by inducing expression of p-ATM, p-CHK1, p-CHK2, p15 and inhibiting expression of p-Smad3. In addition, Caspase3 expression was increased while CDC25A was decreased, leading to cell cycle arrest and cell apoptosis. On the other hand, activation of Smad3 can inhibited the ATM pathway and attenuated the efficacy of radiation. In summary, we suggest that both ATM and Smad pathways contribute to the cell cycle arrest and cell apoptosis during nasopharyngeal carcinoma cells treated with radiation.

  10. ATM inhibition induces synthetic lethality and enhances sensitivity of PTEN-deficient breast cancer cells to cisplatin.

    Science.gov (United States)

    Li, Ke; Yan, Huaying; Guo, Wenhao; Tang, Mei; Zhao, Xinyu; Tong, Aiping; Peng, Yong; Li, Qintong; Yuan, Zhu

    2018-05-01

    PTEN deficiency often causes defects in DNA damage repair. Currently, effective therapies for breast cancer are lacking. ATM is an attractive target for cancer treatment. Previous studies suggested a synthetic lethality between PTEN and PARP. However, the synthetically lethal interaction between PTEN and ATM in breast cancer has not been reported. Moreover, the mechanism remains elusive. Here, using KU-60019, an ATM kinase inhibitor, we investigated ATM inhibition as a synthetically lethal strategy to target breast cancer cells with PTEN defects. We found that KU-60019 preferentially sensitizes PTEN-deficient MDA-MB-468 breast cancer cells to cisplatin, though it also slightly enhances sensitivity of PTEN wild-type breast cancer cells. The increased cytotoxic sensitivity is associated with apoptosis, as evidenced by flow cytometry and PARP cleavage. Additionally, the increase of DNA damage accumulation due to the decreased capability of DNA repair, as indicated by γ-H2AX and Rad51 foci, also contributed to this selective cytotoxicity. Mechanistically, compared with PTEN wild-type MDA-MB-231 cells, PTEN-deficient MDA-MB-468 cells have lower level of Rad51, higher ATM kinase activity, and display the elevated level of DNA damage. Moreover, these differences could be further enlarged by cisplatin. Our findings suggest that ATM is a promising target for PTEN-defective breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Decreased expression of the ATM gene linked to poor prognosis for gastric cancer of different nationalities in Xinjiang.

    Science.gov (United States)

    Han, Mei; Ma, Lanying; Qu, Yanli; Tang, Yong

    2017-08-01

    To explore the clinicopathological significance of ATM gene in the occurrence and prognosis of gastric cancer (GC) from different nationalities in Xinjiang. The expression of ATM in 385 patients with GC (including 98 Uygurs, 231 Hans and 56 Kazaks) and its corresponding adjacent tissues were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry assay to, analyze its correlations with clinicopathological features and prognosis of GC. The ATM expression in GC tissues was significantly decreased when compared to that in adjacent normal tissues of Uygur, Han and Kazak patients in Xinjiang, while Uygurs and Kazaks were much lower than Hans in the ATM expression of GC tissues (all PATM-negative tumors had a markedly lower survival rate than patients in Hans (P=0.028), and GC patients with ATM negative expression presented more unfavorable overall survival rate than those with positive expression among the three different nationalities (all PATM expression, TNM staging, depth of invasion, and lymph node metastasis were independent factors affecting the prognosis of GC patients in Xinjiang (all PATM was downregulated in GC patients in Xinjiang, especially for Uygurs and Kazaks, which suggested ATM to be an independent indicator of prognosis for GC therapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. MiR-2964a-5p binding site SNP regulates ATM expression contributing to age-related cataract risk.

    Science.gov (United States)

    Rong, Han; Gu, Shanshan; Zhang, Guowei; Kang, Lihua; Yang, Mei; Zhang, Junfang; Shen, Xinyue; Guan, Huaijin

    2017-10-17

    This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated ( ATM ) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifically down-regulated luciferase reporter expression and ATM expression in the cell lines transfected with rs4585 T allele compared to rs4585 G allele. The molecular assay on human tissue samples discovered that ATM expression was down-regulated in majority of ARC tissues and correlated with ATM genotypes. In addition, the Comet assay of cellular DNA damage of peripheral lymphocytes indicated that individuals carrying the G allele (GG/GT) of ATM -rs4585 had lower DNA breaks compared to individuals with TT genotype. These findings suggested that the SNP rs4585 in ATM might affect ARC risk through modulating the regulatory affinity of miR-2964a-5p. The reduced DSBs repair might be involved in ARC pathogenesis.

  13. The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation

    International Nuclear Information System (INIS)

    Alao, John P; Sunnerhagen, Per

    2009-01-01

    The ataxia telangiectasia mutated (ATM) and the ATM- related (ATR) kinases play a central role in facilitating the resistance of cancer cells to genotoxic treatment regimens. The components of the ATM and ATR regulated signaling pathways thus provide attractive pharmacological targets, since their inhibition enhances cellular sensitivity to chemo- and radiotherapy. Caffeine as well as more specific inhibitors of ATM (KU55933) or ATM and ATR (CGK733) have recently been shown to induce cell death in drug-induced senescent tumor cells. Addition of these agents to cancer cells previously rendered senescent by exposure to genotoxins suppressed the ATM mediated p21 expression required for the survival of these cells. The precise molecular pharmacology of these agents however, is not well characterized. Herein, we report that caffeine, CGK733, and to a lesser extent KU55933, inhibit the proliferation of otherwise untreated human cancer and non-transformed mouse fibroblast cell lines. Exposure of human cancer cell lines to caffeine and CGK733 was associated with a rapid decline in cyclin D1 protein levels and a reduction in the levels of both phosphorylated and total retinoblastoma protein (RB). Our studies suggest that observations based on the effects of these compounds on cell proliferation and survival must be interpreted with caution. The differential effects of caffeine/CGK733 and KU55933 on cyclin D1 protein levels suggest that these agents will exhibit dissimilar molecular pharmacological profiles

  14. ELIPGRID-PC: A PC program for calculating hot spot probabilities

    International Nuclear Information System (INIS)

    Davidson, J.R.

    1994-10-01

    ELIPGRID-PC, a new personal computer program has been developed to provide easy access to Singer's 1972 ELIPGRID algorithm for hot-spot detection probabilities. Three features of the program are the ability to determine: (1) the grid size required for specified conditions, (2) the smallest hot spot that can be sampled with a given probability, and (3) the approximate grid size resulting from specified conditions and sampling cost. ELIPGRID-PC also provides probability of hit versus cost data for graphing with spread-sheets or graphics software. The program has been successfully tested using Singer's published ELIPGRID results. An apparent error in the original ELIPGRID code has been uncovered and an appropriate modification incorporated into the new program

  15. A Pc-interface module has been developed that provides an easy way to interface PC

    International Nuclear Information System (INIS)

    Rifai, Ahmad; Gunawan, Usep Setia

    2003-01-01

    A pc-interface module has been developed that provides an easy way to interface PC with I/O devices. This MSC51 micro controller based module accepts series of commands from a personal computer through a serial port. The commands are defined to easily control 24 I/O lines available on the module. These lines can be individually used as either input or output that make the module very verstile. A command is received by the module on ASCII string basis. Each character sent to the module will give an interrupt. The firmware's interrupt handler will store the character in a buffer until end of command character arrives. The firmware then parses and interpreters the command and responses accordingly

  16. Detection of ATM germline variants by the p53 mitotic centrosomal localization test in BRCA1/2-negative patients with early-onset breast cancer.

    Science.gov (United States)

    Prodosmo, Andrea; Buffone, Amelia; Mattioni, Manlio; Barnabei, Agnese; Persichetti, Agnese; De Leo, Aurora; Appetecchia, Marialuisa; Nicolussi, Arianna; Coppa, Anna; Sciacchitano, Salvatore; Giordano, Carolina; Pinnarò, Paola; Sanguineti, Giuseppe; Strigari, Lidia; Alessandrini, Gabriele; Facciolo, Francesco; Cosimelli, Maurizio; Grazi, Gian Luca; Corrado, Giacomo; Vizza, Enrico; Giannini, Giuseppe; Soddu, Silvia

    2016-09-06

    Variant ATM heterozygotes have an increased risk of developing cancer, cardiovascular diseases, and diabetes. Costs and time of sequencing and ATM variant complexity make large-scale, general population screenings not cost-effective yet. Recently, we developed a straightforward, rapid, and inexpensive test based on p53 mitotic centrosomal localization (p53-MCL) in peripheral blood mononuclear cells (PBMCs) that diagnoses mutant ATM zygosity and recognizes tumor-associated ATM polymorphisms. Fresh PBMCs from 496 cancer patients were analyzed by p53-MCL: 90 cases with familial BRCA1/2-positive and -negative breast and/or ovarian cancer, 337 with sporadic cancers (ovarian, lung, colon, and post-menopausal breast cancers), and 69 with breast/thyroid cancer. Variants were confirmed by ATM sequencing. A total of seven individuals with ATM variants were identified, 5/65 (7.7 %) in breast cancer cases of familial breast and/or ovarian cancer and 2/69 (2.9 %) in breast/thyroid cancer. No variant ATM carriers were found among the other cancer cases. Excluding a single case in which both BRCA1 and ATM were mutated, no p53-MCL alterations were observed in BRCA1/2-positive cases. These data validate p53-MCL as reliable and specific test for germline ATM variants, confirm ATM as breast cancer susceptibility gene, and highlight a possible association with breast/thyroid cancers.

  17. A NICE approach to managing large numbers of desktop PC's

    International Nuclear Information System (INIS)

    Foster, David

    1996-01-01

    The problems of managing desktop systems are far from resolved. As we deploy increasing numbers of systems, PC's Mackintoshes and UN*X Workstations. This paper will concentrate on the solution adopted at CERN for the management of the rapidly increasing numbers of desktop PC's in use in all parts of the laboratory. (author)

  18. Application of simplified PC-SAFT to glycol ethers

    DEFF Research Database (Denmark)

    Avlund, Ane Søgaard; Kontogeorgis, Georgios; Michelsen, Michael Locht

    2012-01-01

    The simplified PC-SAFT (sPC-SAFT) equation of state is applied for binary glycol ether-containing mixtures, and it is investigated how the results are influenced by inclusion of intramolecular association in the association theory. Three different glycol ethers are examined: 2-methoxyethanol, 2...

  19. PC Assisted Anatomical Measurements in 3D Using CT Data

    DEFF Research Database (Denmark)

    Hvidtfeldt, Mogens; Pedersen, Steen

    1999-01-01

    To assess facilities and applications of a programme for a PC based CT measurements in 3D of anatomical angelse in the skeleton.......To assess facilities and applications of a programme for a PC based CT measurements in 3D of anatomical angelse in the skeleton....

  20. PrPC from stem cells to cancer

    Directory of Open Access Journals (Sweden)

    Séverine eMartin-Lannerée

    2014-09-01

    Full Text Available The cellular prion protein PrPC was initially discovered as the normal counterpart of the pathological scrapie prion protein PrPSc, the main component of the infectious agent of Transmissible Spongiform Encephalopathies. While clues as to the physiological function of this ubiquitous protein were greatly anticipated from the development of knock-out animals, PrP-null mice turned out to be viable and to develop without major phenotypic abnormalities. Notwithstanding, the discovery that hematopoietic stem cells from PrP-null mice have impaired long-term repopulating potential has set the stage for investigating into the role of PrPC in stem cell biology. A wealth of data have now exemplified that PrPC is expressed in distinct types of stem cells and regulates their self-renewal as well as their differentiation potential. A role for PrPC in the fate restriction of embryonic stem cells has further been proposed. Paralleling these observations, an overexpression of PrPC has been documented in various types of tumours. In line with the contribution of PrPC to stemness and to the proliferation of cancer cells, PrPC was recently found to be enriched in subpopulations of tumour-initiating cells. In the present review, we summarize the current knowledge of the role played by PrPC in stem cell biology and discuss how the subversion of its function may contribute to cancer progression.

  1. Monte Carlo tests of the ELIPGRID-PC algorithm

    International Nuclear Information System (INIS)

    Davidson, J.R.

    1995-04-01

    The standard tool for calculating the probability of detecting pockets of contamination called hot spots has been the ELIPGRID computer code of Singer and Wickman. The ELIPGRID-PC program has recently made this algorithm available for an IBM reg-sign PC. However, no known independent validation of the ELIPGRID algorithm exists. This document describes a Monte Carlo simulation-based validation of a modified version of the ELIPGRID-PC code. The modified ELIPGRID-PC code is shown to match Monte Carlo-calculated hot-spot detection probabilities to within ±0.5% for 319 out of 320 test cases. The one exception, a very thin elliptical hot spot located within a rectangular sampling grid, differed from the Monte Carlo-calculated probability by about 1%. These results provide confidence in the ability of the modified ELIPGRID-PC code to accurately predict hot-spot detection probabilities within an acceptable range of error

  2. PcFKH1, a novel regulatory factor from the forkhead family, controls the biosynthesis of penicillin in Penicillium chrysogenum.

    Science.gov (United States)

    Domínguez-Santos, Rebeca; García-Estrada, Carlos; Kosalková, Katarina; Prieto, Carlos; Santamarta, Irene; Martín, Juan-Francisco

    2015-08-01

    Penicillin biosynthesis in Penicillium chrysogenum (re-identified as Penicillium rubens) is a good example of a biological process subjected to complex global regulatory networks and serves as a model to study fungal secondary metabolism. The winged-helix family of transcription factors recently described, which includes the forkhead type of proteins, is a key type of regulatory proteins involved in this process. In yeasts and humans, forkhead transcription factors are involved in different processes (cell cycle regulation, cell death control, pre-mRNA processing and morphogenesis); one member of this family of proteins has been identified in the P. chrysogenum genome (Pc18g00430). In this work, we have characterized this novel transcription factor (named PcFKH1) by generating knock-down mutants and overexpression strains. Results clearly indicate that PcFKH1 positively controls antibiotic biosynthesis through the specific interaction with the promoter region of the penDE gene, thus regulating penDE mRNA levels. PcFKH1 also binds to the pcbC promoter, but with low affinity. In addition, it also controls other ancillary genes of the penicillin biosynthetic process, such as phlA (encoding phenylacetyl CoA ligase) and ppt (encoding phosphopantetheinyl transferase). PcFKH1 also plays a role in conidiation and spore pigmentation, but it does not seem to be involved in hyphal morphology or cell division in the improved laboratory reference strain Wisconsin 54-1255. A genome-wide analysis of processes putatively coregulated by PcFKH1 and PcRFX1 (another winged-helix transcription factor) in P. chrysogenum provided evidence of the global effect of these transcription factors in P. chrysogenum metabolism. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  3. 100 pc renewable energies: the last obstacles

    International Nuclear Information System (INIS)

    Claustre, Raphael; Bringault, Anne; Mery, Jane; Regnier, Yannick; Leca, Christel; Jedliczka, Marc; Houssard, Pascal; Gaboriau, Denis

    2015-01-01

    As some countries or territories have set a target of 100 pc of renewable energies by 2015, a first article discusses the different components of a scenario corresponding to this objective: reduction of primary energy consumption, sobriety, efficiency, electricity and heat production, mobility, development of exchanges and solidarities between territories, new roles for the different actors. A second article briefly presents the situation of different cities and territories in terms of production of renewable energies and of energy savings (Vancouver, Costa Rica, Canaries Islands, the region of Thouars in France, Denmark, Frankfurt, and Bangladesh). Two persons belonging either to a company or to a public body, both committed in energy efficiency issues, give their opinion on issues of governance and innovation. The next article outlines that, despite the content of the law on energy transition, there is still much to be done to develop the empowerment of local communities or, in other words, to introduce an energetic decentralisation. A researcher then outlines the need to introduce a strong tax system in relationship with carbon emission to support the development of renewable energies. An article then describes the example of the Vendee district which has been developing since 2012 an infrastructure of charging points for electric vehicles. The last article outlines the role of training organisations which will have to adapt themselves to new professions in various sectors

  4. Pc-Based Floating Point Imaging Workstation

    Science.gov (United States)

    Guzak, Chris J.; Pier, Richard M.; Chinn, Patty; Kim, Yongmin

    1989-07-01

    The medical, military, scientific and industrial communities have come to rely on imaging and computer graphics for solutions to many types of problems. Systems based on imaging technology are used to acquire and process images, and analyze and extract data from images that would otherwise be of little use. Images can be transformed and enhanced to reveal detail and meaning that would go undetected without imaging techniques. The success of imaging has increased the demand for faster and less expensive imaging systems and as these systems become available, more and more applications are discovered and more demands are made. From the designer's perspective the challenge to meet these demands forces him to attack the problem of imaging from a different perspective. The computing demands of imaging algorithms must be balanced against the desire for affordability and flexibility. Systems must be flexible and easy to use, ready for current applications but at the same time anticipating new, unthought of uses. Here at the University of Washington Image Processing Systems Lab (IPSL) we are focusing our attention on imaging and graphics systems that implement imaging algorithms for use in an interactive environment. We have developed a PC-based imaging workstation with the goal to provide powerful and flexible, floating point processing capabilities, along with graphics functions in an affordable package suitable for diverse environments and many applications.

  5. Allocating resources between network nodes for providing a network node function

    OpenAIRE

    Strijkers, R.J.; Meulenhoff, P.J.

    2014-01-01

    The invention provides a method wherein a first network node advertises available resources that a second network node may use to offload network node functions transparently to the first network node. Examples of the first network node are a client device (e.g. PC, notebook, tablet, smart phone), a server (e.g. application server, a proxy server, cloud location, router). Examples of the second network node are an application server, a cloud location or a router. The available resources may b...

  6. Possession of ATM Sequence Variants as Predictor for Late Normal Tissue Responses in Breast Cancer Patients Treated With Radiotherapy

    International Nuclear Information System (INIS)

    Ho, Alice Y.; Fan, Grace; Atencio, David P.; Green, Sheryl; Formenti, Silvia C.; Haffty, Bruce G.; Iyengar, Preetha B.A.; Bernstein, Jonine L.; Stock, Richard G.; Cesaretti, Jamie A.; Rosenstein, Barry S.

    2007-01-01

    Purpose: The ATM gene product is a central component of cell cycle regulation and genomic surveillance. We hypothesized that DNA sequence alterations in ATM predict for adverse effects after external beam radiotherapy for early breast cancer. Methods and Materials: A total of 131 patients with a minimum of 2 years follow-up who had undergone breast-conserving surgery and adjuvant radiotherapy were screened for sequence alterations in ATM using DNA from blood lymphocytes. Genetic variants were identified using denaturing high performance liquid chromatography. The Radiation Therapy Oncology Group late morbidity scoring schemes for skin and subcutaneous tissues were applied to quantify the radiation-induced effects. Results: Of the 131 patients, 51 possessed ATM sequence alterations located within exons or in short intron regions flanking each exon that encompass putative splice site regions. Of these 51 patients, 21 (41%) exhibited a minimum of a Grade 2 late radiation response. In contrast, of the 80 patients without an ATM sequence variation, only 18 (23%) had radiation-induced adverse responses, for an odds ratio of 2.4 (95% confidence interval, 1.1-5.2). Fifteen patients were heterozygous for the G→A polymorphism at nucleotide 5557, which causes substitution of asparagine for aspartic acid at position 1853 of the ATM protein. Of these 15 patients, 8 (53%) exhibited a Grade 2-4 late response compared with 31 (27%) of the 116 patients without this alteration, for an odds ratio of 3.1 (95% confidence interval, 1.1-9.4). Conclusion: Sequence variants located in the ATM gene, in particular the 5557 G→A polymorphism, may predict for late adverse radiation responses in breast cancer patients

  7. 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.

  8. Germline variants in the ATM gene and breast cancer susceptibility in Moroccan women: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Chaymaa Marouf

    2017-10-01

    Full Text Available Background: The ATM gene encoding a large protein kinase is mutated in ataxia-telangiectasia (AT, an autosomale recessive disease characterized by neurological and immunological symptoms, and cancer predisposition. Previous studies suggest that heterozygous carriers of ATM mutations have an increased risk of breast cancer compared with non carriers, but the contribution of specific variants has been difficult to estimate. However, two functional ATM variants, c.7271T > G and c.1066–6T > G (IVS10–6T > G, are associated with increased risk for the development of breast cancer. Methods: To investigate the role of ATM in breast cancer susceptibility, we genotyped 163 case patients with breast cancer and 150 healthy control individuals for the c.7271T > G and c.1066–6T > G (IVS10–6T > G ATM variants using polymerase chain reaction (PCR-restriction fragment length polymorphism (RFLP analysis. Results: We did not detect the ATM c.7271T > G and c.1066–6T > G (IVS10–6T > G mutations in any of 150 healthy control individuals and 163 breast cancer patients, including 59 women diagnosed with breast cancer at an early age ( G (IVS10–6T > G mutation and the rare c.7271T > G variant are not a risk factor for developing breast cancer in the Moroccan population. Larger and/or combined association studies are needed to clarify this issue. Keywords: Breast cancers, ATM gene, Germline mutation, Genetic susceptibility, Moroccan population

  9. 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

    2014-01-01

    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-PKcs 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-PKcs 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. PMID:25474690

  10. Workshop on The Epidemiology of the ATM Gene: Impact on Breast Cancer Risk and Treatment, Present Status and Future Focus, Lillehammer, Norway, 29 June 2002

    International Nuclear Information System (INIS)

    Bernstein, Jonine L; Seminara, Daniela; Børresen-Dale, Anne-Lise

    2002-01-01

    The role of ataxia-telangiectasia mutated (ATM) heterozygosity in cancer is uncertain. In vitro studies of cells from ATM heterozygotes provide strong evidence of radiation sensitivity. Some, but not all, clinical studies suggest an increased risk of breast cancer among ATM gene carriers, and this risk may be greater among those exposed to radiation. This possible excess risk of breast cancer associated with ATM heterozygosity constitutes the basis for several genetic epidemiological studies designed to clarify the role that the ATM gene plays in the etiology of breast and other cancers. The primary focus of this international, multidisciplinary, National Cancer Institute-sponsored workshop was to discuss ongoing and planned epidemiologic studies aimed at understanding the complexities of the ATM gene and its role in carcinogenesis. The invited participants were from diverse disciplines including molecular and clinical genetics, radiation biology and physics, epidemiology, biostatistics, pathology, and medicine. In the present meeting report, the aims of each project are described

  11. 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.

  12. KOMUNIKASI TRANS BUDAYA DALAM BIDANG KESEHATAN ANALISIS KASUS: IKLAN KONDOM DAN ATM KONDOM MASUK KAMPUS

    Directory of Open Access Journals (Sweden)

    Bani Eka Dartiningsih

    2017-01-01

    Full Text Available ABSTRACTCommunication and culture reciprocally influence each other mutually. A culture where individuals are socialized, will affect the way they communicate. And how individuals that communicate, can change the culture that they have from time to time. Culture declined to patterns of behavior associated with certain groups of people, namely to “custom” or to “life principle” someone. Culture as a development towardsbalance. Condoms ATM case is a form of trans cultural communication where meaning contained inthese products is that students are expected to behave safe (secure way to have sex. Safe refers to healthybehaviors. The tool is not just a place to put a condom, but more contain message of healthy behaviors insex. Despite the healthy word is reserved for people who are still categorized as deviant.ABSTRAKKomunikasi dan budaya secara timbal balik saling berpengaruh satu sama lain. Budaya dimana secara individu-individu disosialisasikan, akan berpengaruh terhadap cara mereka dalam berkomunikasi. Dancara bagaimana individu-individu itu berkomunikasi, dapat mengubah budaya yang mereka miliki dariwaktu ke waktu. Budaya menurun kepada pola perilaku yang diasosiasikan dengan kelompok orangtertentu, yaitu untuk “kebiasaan” atau untuk “prinsip hidup” seseorang. Budaya sebagai perkembanganmenuju keseimbangan. Kasus ATM Kondom merupakan bentuk komunikasi trans budaya dimanamakna yang terkandung dalam produk tersebut adalah bahwa mahasiswa diharapkan berperilaku safe(aman dalam melakukan hubungan seks. Aman (safe merujuk pada perilaku sehat. Alat tersebut bukansekedar tempat menaruh kondom, tetapi lebih mengandung pesan perilaku sehat dalam berhubunganseks. Meskipun kata sehat tersebut dikhususkan bagi orang yang masih dikategorikan menyimpang.Keywords: Komunikasi trans budaya, ATM kondom

  13. ATM suppresses SATB1-induced malignant progression in breast epithelial cells.

    Directory of Open Access Journals (Sweden)

    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.

  14. Fabrication and characterization of MCC approved testing material: ATM-9 glass

    International Nuclear Information System (INIS)

    Wald, J.W.

    1986-06-01

    The Materials Characterization Center ATM-9 glass is designed to be representative of glass to be produced by the Defense Waste Processing Facility at the Savannah River Plant, Aiken, South Carolina. ATM-9 glass contains all of the major components of the DWPF glass and corresponds to a waste loading of 29 wt %. The feedstock material for this glass was supplied by Savannah River Laboratory, Aiken, SC, as SRL-165 Black Frit to which was added Ba, Cs, Md, Nd, Zr, as well as 99 Tc, depleted U, 237 Np, 239+240 Pu, and 243 Am. The glass was produced under reducing conditions by the addition of 0.7 wt % graphite during the final melting process. Three kilograms of the glass were produced from April to May of 1984. On final melting, the glass was formed into stress-annealed rectangular bars of two sizes: 1.9 x 1.9 x 10 cm and 1.3 x 1.3 x 10 cm. Seventeen bars of each size were made. The analyzed composition of ATM-9 glass is listed. Examination by optical microscopy of a single transverse section from one bar showed random porosity estimated at 0.36 vol % with nominal pore diameters ranging from approx. 5 μm to 200 μm. Only one distinct second phase was observed and it was at a low concentraction level in the glass matrix. The phase appeared as spherical metallic particles. X-ray diffraction analysis of this same sample did not show any diffraction peaks from crystalline components, indicating that the glass contained less than 5 wt % of crystalline devitrification products. The even shading on the radiograph exposure indicated a generally uniform distribution of radioactivity throughout the glass matrix, with no distinct high-concentration regions

  15. 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

  16. ATM Technology Demonstration 1 (ATD-1) Project: Terminal Airspace Technologies for NextGen (Public)

    Science.gov (United States)

    Robinson, John E.; Wang, Easter

    2015-01-01

    This video highlights the human-in-the-loop (HITL) simulations conducted by the ATD-1 project and features visual elements developed for Traffic Management Advisor - Terminal Metering, Controller Managed Spacing, and Flight Deck Interval Management. The video content is fairly technical and intended for audiences that have some knowledge of air traffic management issues. This includes researchers and management from NASA, FAA, industry partners, and others interested in terminal metering, controller managed spacing, and interval management technologies. Please note that the media release only clears the video for peer audiences such as ATM conferences or as part of presentations to researchers.

  17. 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.

  18. Almacenamiento refrigerado de cerezas : efecto de madurez y atmósfera modificada

    OpenAIRE

    Yommi, Alejandra; Godoy, Carlos; Horvitz, Sandra; López Camelo, Andrés

    2002-01-01

    Se estudió el efecto de cosechar cerezas en dos estados de madurez: rojo pálido y rojo maduro y la utilización de atmósferas modificadas, empleando PBD de 11 y 40 m, sobre la calidad de fruta almacenada a 0 °C y después de 3 días a temperatura ambiente. La calidad fue evaluada en términos de pérdida de peso (%), color (ángulo hue), firmeza, contenido de sólidos solubles, aspecto de los pedicelos y presen...

  19. Application of PC-SAFT to glycol containing systems - PC-SAFT towards a predictive approach

    DEFF Research Database (Denmark)

    Grenner, Andreas; Kontogeorgis, Georgios; von Solms, Nicolas

    2007-01-01

    for estimating pure compound parameters from low molecular weight data and extrapolate to complex compounds. For associating compounds this is not trivial since the two parameters for association (association energy and association volume) need to be fixed for a group. In this work, which focuses on glycols, new...... general pure compound parameters were obtained for PC-SAFT which are able to perform well for both vapor-liquid equilibria (VLE) and liquid-liquid equilibria (LLE). Linear trends of non-association parameters were obtained with respect to the molar mass. However, identical values for the association...

  20. Economic impact of off-line PC viewer for private folder management

    Science.gov (United States)

    Song, Koun-Sik; Shin, Myung J.; Lee, Joo Hee; Auh, Yong H.

    1999-07-01

    We developed a PC-based clinical workstation and implemented at Asan Medical Center in Seoul, Korea, Hardwares used were Pentium-II, 8M video memory, 64-128 MB RAM, 19 inch color monitor, and 10/100Mbps network adaptor. One of the unique features of this workstation is management tool for folders reside both in PACS short-term storage unit and local hard disk. Users can copy the entire study or part of the study to local hard disk, removable storages, or CD recorder. Even the images in private folders in PACS short-term storage can be copied to local storage devices. All images are saved as DICOM 3.0 file format with 2:1 lossless compression. We compared the prices of copy films and storage medias considering the possible savings of expensive PACS short- term storage and network traffic. Price savings of copy film is most remarkable in MR exam. Price savings arising from minimal use of short-term unit was 50,000 dollars. It as hard to calculate the price savings arising from the network usage. Off-line PC viewer is a cost-effective way of handling private folder management under the PACS environment.