A hybrid lightwave transmission system based on light injection/optoelectronic feedback techniques and fiber-VLLC integration

International Nuclear Information System (INIS)

Tsai, Wen-Shing; Lu, Hai-Han; Li, Chung-Yi; Chen, Bo-Rui; Lin, Hung-Hsien; Lin, Dai-Hua

2016-01-01

A hybrid lightwave transmission system based on light injection/optoelectronic feedback techniques and fiber-visible laser light communication (VLLC) integration is proposed and experimentally demonstrated. To be the first one of its kind in employing light injection and optoelectronic feedback techniques in a fiber-VLLC integration lightwave transmission system, the light is successfully directly modulated with Community Access Television (CATV), 16-QAM, and 16-QAM-OFDM signals. Over a 40 km SMF and a 10 m free-space VLLC transport, good performances of carrier-to-noise ratio (CNR)/composite second-order (CSO)/composite triple-beat (CTB)/bit error rate (BER) are achieved for CATV/16-QAM/16-QAM-OFDM signals transmission. Such a hybrid lightwave transmission system would be very useful since it can provide broadband integrated services including CATV, Internet, and telecommunication services over both distribute fiber and in-building networks. (letter)

Interconnection of Broadband Islands via Satellite-Experiments on the Race II Catalyst Project

National Research Council Canada - National Science Library

Sun, Z

1996-01-01

.... The purpose of the project was to develop an ATM satellite link for the future B-ISDN services, particularly for the interconnections of the ATM testbeds which are in the form of broadband islands...

Telemedicina: a multimedia broadband teleradiology and radiosurgery project

Science.gov (United States)

de Blas-Garcia, Pedro; Lopez-Viver, Rodolfo; Martinez, Demetrio; Ruiz, Ignacio; Barriuso, Daniel; Janez-Escalada, Luis; Gomez, Jose L.; Luyando, Luis

1996-05-01

Telemedicina is a Spanish project that covers teleradiology and radiosurgery areas. This project is under the frame of the Spanish Broadband National Plan (PLANBA). The final technical tests are being ended over Ethernet and ATM and it is planned to get their first clinical results on February-96. Two pilots will be installed: one in Madrid linking two sites through a ATM network (provided by Telefonica, Spanish PTT) and a second one in Asturias (north of Spain) using ISDN primary access (2 Mbps). The system handles still images, voice and video records, scanned documents, text and slides allowing doctors to interchange this data using cooperative tools. The system is based on a multimedia Unix platform with voice, video and videoconference devices and boards. The platform will be used in several ways: as desktop videoconferencing, primary diagnosis and review. Communications are based on ATM (over AAL5) at 155 Mbps and ISDN (primary access). The protocol used in both networks is TCP/IP. The application is written in C++ (object oriented design and programming) and C. GUI is built under X-Windows and Motif. The codification of video is MJPEG done through dedicated hardware. The system is integrated in a small PACS (previously installed); the images are captured from the modalities such as CT using the DICOM standard and it is connected with the Radiological Information System. The application allows collaborative work: telepointer, shared windows, editors and actions. Main news of the Telemedicina project will be the incorporation of broadband networks (ATM at 155 Mbps) and the integration of collaborative work. This two aspects allow the doctors to improve their work speeding up the transmission and retrieval of medical records. Also this platform can be used to achieve several goals: such as primary diagnosis, videoconference, review.

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.

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

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

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, ...

Bidirectional fiber-wireless and fiber-IVLLC integrated system based on polarization-orthogonal modulation scheme.

Science.gov (United States)

Lu, Hai-Han; Li, Chung-Yi; Chen, Hwan-Wei; Ho, Chun-Ming; Cheng, Ming-Te; Huang, Sheng-Jhe; Yang, Zih-Yi; Lin, Xin-Yao

2016-07-25

A bidirectional fiber-wireless and fiber-invisible laser light communication (IVLLC) integrated system that employs polarization-orthogonal modulation scheme for hybrid cable television (CATV)/microwave (MW)/millimeter-wave (MMW)/baseband (BB) signal transmission is proposed and demonstrated. To our knowledge, it is the first one that adopts a polarization-orthogonal modulation scheme in a bidirectional fiber-wireless and fiber-IVLLC integrated system with hybrid CATV/MW/MMW/BB signal. For downlink transmission, carrier-to-noise ratio (CNR), composite second-order (CSO), composite triple-beat (CTB), and bit error rate (BER) perform well over 40-km single-mode fiber (SMF) and 10-m RF/50-m optical wireless transport scenarios. For uplink transmission, good BER performance is obtained over 40-km SMF and 50-m optical wireless transport scenario. Such a bidirectional fiber-wireless and fiber-IVLLC integrated system for hybrid CATV/MW/MMW/BB signal transmission will be an attractive alternative for providing broadband integrated services, including CATV, Internet, and telecommunication services. It is shown to be a prominent one to present the advancements for the convergence of fiber backbone and RF/optical wireless feeder.

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.

Hybrid wireless-over-fiber transmission system based on multiple injection-locked FP LDs.

Science.gov (United States)

Li, Chung-Yi; Lu, Hai-Han; Chu, Chien-An; Ying, Cheng-Ling; Lu, Ting-Chien; Peng, Peng-Chun

2015-07-27

A hybrid wireless-over-fiber (WoF) transmission system based on multiple injection-locked Fabry-Perot laser diodes (FP LDs) is proposed and experimentally demonstrated. Unlike the traditional hybrid WoF transmission systems that require multiple distributed feedback (DFB) LDs to support different kinds of services, the proposed system employs multiple injection-locked FP LDs to provide different kinds of applications. Such a hybrid WoF transmission system delivers downstream intensity-modulated 20-GHz microwave (MW)/60-GHz millimeter-wave (MMW)/550-MHz cable television (CATV) signals and upstream phase-remodulated 20-GHz MW signal. Excellent bit error rate (BER), carrier-to-noise ratio (CNR), composite second-order (CSO), and composite triple-beat (CTB) are observed over a 40-km single-mode fiber (SMF) and a 4-m radio frequency (RF) wireless transport. Such a hybrid WoF transmission system has practical applications for fiber-wireless convergence to provide broadband integrated services, including telecommunication, data communication, and CATV services.

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.

Application of SNMP on CATV

Science.gov (United States)

Huang, Hong-bin; Liu, Wei-ping; Chen, Shun-er; Zheng, Liming

2005-02-01

A new type of CATV network management system developed by universal MCU, which supports SNMP, is proposed in this paper. From the point of view in both hardware and software, the function and method of every modules inside the system, which include communications in the physical layer, protocol process, data process, and etc, are analyzed. In our design, the management system takes IP MAN as data transmission channel and every controlled object in the management structure has a SNMP agent. In the SNMP agent developed, there are four function modules, including physical layer communication module, protocol process module, internal data process module and MIB management module. In the paper, the structure and function of every module are designed and demonstrated while the related hardware circuit, software flow as well as the experimental results are tested. Furthermore, by introducing RTOS into the software programming, the universal MCU procedure can conducts such multi-thread management as fast Ethernet controller driving, TCP/IP process, serial port signal monitoring and so on, which greatly improves efficiency of CPU.

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.

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.

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...

Fiber to the serving area: telephone-like star architecture for CATV

Science.gov (United States)

Fellows, David M.

1992-02-01

CATV systems traditionally use a tree and branch architecture to bring up to 550 MHz of analog bandwidth to every home in a franchise area. This changed slightly with the advent of AM fiber optic equipment, as fiber optics were used in an overlay fashion to reduce coaxial amplifier cascades and improve subscriber quality and reliability. Within the last year, fiber has economically replaced coaxial trunking. The resulting fiber to the serving area architecture combines fiber and coaxial stars for a network that looks much like the carrier serving area architectures used by telephone companies.

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)

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

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.

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.

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.

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.

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.

Communication system for the Tristan accelerators

International Nuclear Information System (INIS)

Katoh, T.; Takeda, S.; Kudo, K.; Akiyama, A.

1987-01-01

Communication system used for operation of the TRISTAN accelerators consists of a ring network for control computer system, a video information network, and a broadband video/digital data network. In this paper the video information network using optical fiber cables and the broadband CATV and Local Area network are described

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

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...

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

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.

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.

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...

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.

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 ...

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.

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...

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

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.

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....

Broadband unidirectional cloaks based on flat metasurface focusing lenses

International Nuclear Information System (INIS)

Li, Yongfeng; Zhang, Jieqiu; Qu, Shaobo; Wang, Jiafu; Pang, Yongqiang; Xu, Zhuo; Zhang, Anxue

2015-01-01

Bandwidth extension and thickness reduction are now the two key issues of cloaks. In this paper, we propose to achieve broadband, thin uni-directional electromagnetic (EM) cloaks using metasurfaces. To this end, a wideband flat focusing lens is firstly devised based on high-efficiency transmissive metasurfaces. Due to the nearly dispersionless parabolic phase profile along the metasurface in the operating band, incident plane waves can be focused efficiently after passing through the metasurface. Broadband unidirectional EM cloaks were then designed by combining two identical flat lenses. Upon illumination, the incident plane waves are firstly focused by one lens and then are restored by the other lens, avoiding the cloaked region. Both simulation and experiment results verify the broadband unidirectional cloak. The broad bandwidth and small thickness of such cloaks have potential applications in achieving invisibility for electrically large objects. (paper)

Broadband unidirectional cloaks based on flat metasurface focusing lenses

Science.gov (United States)

Li, Yongfeng; Zhang, Jieqiu; Qu, Shaobo; Wang, Jiafu; Pang, Yongqiang; Xu, Zhuo; Zhang, Anxue

2015-08-01

Bandwidth extension and thickness reduction are now the two key issues of cloaks. In this paper, we propose to achieve broadband, thin uni-directional electromagnetic (EM) cloaks using metasurfaces. To this end, a wideband flat focusing lens is firstly devised based on high-efficiency transmissive metasurfaces. Due to the nearly dispersionless parabolic phase profile along the metasurface in the operating band, incident plane waves can be focused efficiently after passing through the metasurface. Broadband unidirectional EM cloaks were then designed by combining two identical flat lenses. Upon illumination, the incident plane waves are firstly focused by one lens and then are restored by the other lens, avoiding the cloaked region. Both simulation and experiment results verify the broadband unidirectional cloak. The broad bandwidth and small thickness of such cloaks have potential applications in achieving invisibility for electrically large objects.

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.

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.

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)

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

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

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.

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

Broadband illusion optical devices based on conformal mappings

Science.gov (United States)

Xiong, Zhan; Xu, Lin; Xu, Ya-Dong; Chen, Huan-Yang

2017-10-01

In this paper, we propose a simple method of illusion optics based on conformal mappings. By carefully developing designs with specific conformal mappings, one can make an object look like another with a significantly different shape. In addition, the illusion optical devices can work in a broadband of frequencies.

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…

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.)

Water-based metamaterial absorbers for optical transparency and broadband microwave absorption

Science.gov (United States)

Pang, Yongqiang; Shen, Yang; Li, Yongfeng; Wang, Jiafu; Xu, Zhuo; Qu, Shaobo

2018-04-01

Naturally occurring water is a promising candidate for achieving broadband absorption. In this work, by virtue of the optically transparent character of the water, the water-based metamaterial absorbers (MAs) are proposed to achieve the broadband absorption at microwave frequencies and optical transparence simultaneously. For this purpose, the transparent indium tin oxide (ITO) and polymethyl methacrylate (PMMA) are chosen as the constitutive materials. The water is encapsulated between the ITO backed plate and PMMA, serving as the microwave loss as well as optically transparent material. Numerical simulations show that the broadband absorption with the efficiency over 90% in the frequency band of 6.4-30 GHz and highly optical transparency of about 85% in the visible region can be achieved and have been well demonstrated experimentally. Additionally, the proposed water-based MA displays a wide-angle absorption performance for both TE and TM waves and is also robust to the variations of the structure parameters, which is much desired in a practical application.

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.

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.

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.

Fiber-based broadband black-light source

OpenAIRE

Sylvestre , Thibaut; Lee , Min Won; Ragueh , A. R.; Stiller , Birgit; Fanjoux , Gil; Barviau , B.; Mussot , A.; Kudlinski , A.

2012-01-01

International audience; Black-Light or Wood's lamp refers to sources that emit long-wavelength ultraviolet radiation (UV-A) from 315 nm and little visible light till 410 nm (blue). In this paper, we present a new fibre-based source of "black light", a source that emits broadband ultraviolet radiation but only small amounts of visible light and no infrared light. We made this source by pumping a specially designed silica photonic crystal fibre (PCF) with 355 nm light pulses from a Q-switched f...

Mirror-based broadband scanner with minimized aberration

Science.gov (United States)

Yu, Jiun-Yann; Tzeng, Yu-Yi; Huang, Chen-Han; Chui, Hsiang-Chen; Chu, Shi-Wei

2009-02-01

To obtain specific biochemical information in optical scanning microscopy, labeling technique is routinely required. Instead of the complex and invasive sample preparation procedures, incorporating spectral acquisition, which commonly requires a broadband light source, provides another mechanism to enhance molecular contrast. But most current optical scanning system is lens-based and thus the spectral bandwidth is limited to several hundred nanometers due to anti-reflection coating and chromatic aberration. The spectral range of interest in biological research covers ultraviolet to infrared. For example, the absorption peak of water falls around 3 μm, while most proteins exhibit absorption in the UV-visible regime. For imaging purpose, the transmission window of skin and cerebral tissues fall around 1300 and 1800 nm, respectively. Therefore, to extend the spectral bandwidth of an optical scanning system from visible to mid-infrared, we propose a system composed of metallic coated mirrors. A common issue in such a mirror-based system is aberrations induced by oblique incidence. We propose to compensate astigmatism by exchanging the sagittal and tangential planes of the converging spherical mirrors in the scanning system. With the aid of an optical design software, we build a diffraction-limited broadband scanning system with wavefront flatness better than λ/4 at focal plane. Combined with a mirror-based objective this microscopic system will exhibit full spectral capability and will be useful in microscopic imaging and therapeutic applications.

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

A Broadband Metasurface-Based Terahertz Flat-Lens Array

KAUST Repository

Wang, Qiu; Zhang, Xueqian; Xu, Yuehong; Tian, Zhen; Gu, Jianqiang; Yue, Weisheng; Zhang, Shuang; Han, Jiaguang; Zhang, Weili; Zhang, Weili

2015-01-01

A metasurface-based terahertz flat-lens array is proposed, comprising C-shaped split-ring resonators exhibiting locally engineerable phase discontinuities. Possessing a high numerical aperture, the planar lens array is flexible, robust, and shows excellent focusing characteristics in a broadband terahertz frequency. It could be an important step towards the development of planar terahertz focusing devices for practical applications.

A Broadband Metasurface-Based Terahertz Flat-Lens Array

KAUST Repository

Wang, Qiu

2015-02-12

A metasurface-based terahertz flat-lens array is proposed, comprising C-shaped split-ring resonators exhibiting locally engineerable phase discontinuities. Possessing a high numerical aperture, the planar lens array is flexible, robust, and shows excellent focusing characteristics in a broadband terahertz frequency. It could be an important step towards the development of planar terahertz focusing devices for practical applications.

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

Pyrolysis of Helical Coordination Polymers for Metal-Sulfide-Based Helices with Broadband Chiroptical Activity.

Science.gov (United States)

Hirai, Kenji; Yeom, Bongjun; Sada, Kazuki

2017-06-27

Fabrication of chiroptical materials with broadband response in the visible light region is vital to fully realize their potential applications. One way to achieve broadband chiroptical activity is to fabricate chiral nanostructures from materials that exhibit broadband absorption in the visible light region. However, the compounds used for chiroptical materials have predominantly been limited to materials with narrowband spectral response. Here, we synthesize Ag 2 S-based nanohelices derived from helical coordination polymers. The right- and left-handed coordination helices used as precursors are prepared from l- and d-glutathione with Ag + and a small amount of Cu 2+ . The pyrolysis of the coordination helices yields right- and left-handed helices of Cu 0.12 Ag 1.94 S/C, which exhibit chiroptical activity spanning the entire visible light region. Finite element method simulations substantiate that the broadband chiroptical activity is attributed to synergistic broadband light absorption and light scattering. Furthermore, another series of Cu 0.10 Ag 1.90 S/C nanohelices are synthesized by choosing the l- or d-Glu-Cys as starting materials. The pitch length of nanohelicies is controlled by changing the peptides, which alters their chiroptical properties. The pyrolysis of coordination helices enables one to fabricate helical Ag 2 S-based materials that enable broadband chiroptical activity but have not been explored owing to the lack of synthetic routes.

Volterra series based predistortion for broadband RF power amplifiers with memory effects

Institute of Scientific and Technical Information of China (English)

Jin Zhe; Song Zhihuan; He Jiaming

2008-01-01

RF power amplifiers(PAs)are usually considered as memoryless devices in most existing predistortion techniques.However,in broadband communication systems,such as WCDMA,the PA memory effects are significant,and memoryless predistortion cannot linearize the PAs effectively.After analyzing the PA memory effects,a novel predistortion method based on the simplified Volterra series is proposed to linearize broadband RF PAs with memory effects.The indirect learning architecture is adopted to design the predistortion scheme and the recursive least squares algorithm with forgetting factor is applied to identify the parameters of the predistorter.Simulation results show that the proposed predistortion method can compensate the nonlinear distortion and memory effects of broadband RF PAs effectively.

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.

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

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...

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.

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

Broadband Radiometric LED Measurements

OpenAIRE

Eppeldauer, G. P.; Cooksey, C. C.; Yoon, H. W.; Hanssen, L. M.; Podobedov, V. B.; Vest, R. E.; Arp, U.; Miller, C. C.

2016-01-01

At present, broadband radiometric measurements of LEDs with uniform and low-uncertainty results are not available. Currently, either complicated and expensive spectral radiometric measurements or broadband photometric LED measurements are used. The broadband photometric measurements are based on the CIE standardized V(��) function, which cannot be used in the UV range and leads to large errors when blue or red LEDs are measured in its wings, where the realization is always poor. Reference irr...

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

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

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.

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.

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....

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.

Broadband Access

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. Broadband Access. Worldwide market for broadband access $30 Billion! Over 200 million broadband subscribers worldwide! Various Competing Broadband access. Digital Subscriber line; Wireless; Optical Fiber.

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.

Broadband asymmetric transmission of linearly polarized electromagnetic waves based on chiral metamaterial

Science.gov (United States)

Stephen, Lincy; Yogesh, N.; Subramanian, V.

2018-01-01

The giant optical activity of chiral metamaterials (CMMs) holds great potential for tailoring the polarization state of an electromagnetic (EM) wave. In controlling the polarization state, the aspect of asymmetric transmission (AT), where a medium allows the EM radiation to pass through in one direction while restricting it in the opposite direction, adds additional degrees of freedom such as one-way channelling functionality. In this work, a CMM formed by a pair of mutually twisted slanted complementary metal strips is realized for broadband AT accompanied with cross-polarization (CP) conversion for linearly polarized EM waves. Numerically, the proposed ultra-thin (˜λ/42) CMM shows broadband AT from 8.58 GHz to 9.73 GHz (bandwidth of 1.15 GHz) accompanied with CP transmission magnitude greater than 0.9. The transmission and reflection spectra reveal the origin of the asymmetric transmission as the direction sensitive cross polarization conversion and anisotropic electric coupling occurring in the structure which is then elaborated with the surface current analysis and electric field distribution within the structure. An experiment is carried out to verify the broadband AT based CP conversion of the proposed CMM at microwave frequencies, and a reliable agreement between numerical and experimental results is obtained. Being ultra-thin, the reported broadband AT based CP conversion of the proposed CMM is useful for controlling radiation patterns in non-reciprocal EM devices and communication networks.

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...

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.

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.

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

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

Broadband terahertz wave deflection based on C-shape complex metamaterials with phase discontinuities

KAUST Repository

Zhang, Xueqian; Tian, Zhen; Yue, Weisheng; Gu, Jianqiang; Zhang, Shuang; Han, Jiaguang; Zhang, Weili

2013-01-01

A broadband terahertz wave deflector based on metasurface induced phase discontinuities is reported. Various frequency components ranging from 0.43 to 1.0 THz with polarization orthogonal to the incidence are deflected into a broad range of angles from 25° to 84°. A Fresnel zone plate consequently developed from the beam deflector is capable of focusing a broadband terahertz radiation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Broadband terahertz wave deflection based on C-shape complex metamaterials with phase discontinuities

KAUST Repository

Zhang, Xueqian

2013-06-21

A broadband terahertz wave deflector based on metasurface induced phase discontinuities is reported. Various frequency components ranging from 0.43 to 1.0 THz with polarization orthogonal to the incidence are deflected into a broad range of angles from 25° to 84°. A Fresnel zone plate consequently developed from the beam deflector is capable of focusing a broadband terahertz radiation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

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.

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.

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.

Exposure estimates based on broadband elf magnetic field measurements versus the ICNIRP multiple frequency rule

International Nuclear Information System (INIS)

Paniagua, Jesus M.; Rufo, Montana; Jimenez, Antonio; Pachon, Fernando T.; Carrero, Julian

2015-01-01

The evaluation of exposure to extremely low-frequency (ELF) magnetic fields using broadband measurement techniques gives satisfactory results when the field has essentially a single frequency. Nevertheless, magnetic fields are in most cases distorted by harmonic components. This work analyses the harmonic components of the ELF magnetic field in an outdoor urban context and compares the evaluation of the exposure based on broadband measurements with that based on spectral analysis. The multiple frequency rule of the International Commission on Non-ionizing Radiation Protection (ICNIRP) regulatory guidelines was applied. With the 1998 ICNIRP guideline, harmonics dominated the exposure with a 55 % contribution. With the 2010 ICNIRP guideline, however, the primary frequency dominated the exposure with a 78 % contribution. Values of the exposure based on spectral analysis were significantly higher than those based on broadband measurements. Hence, it is clearly necessary to determine the harmonic components of the ELF magnetic field to assess exposure in urban contexts. (authors)

A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase

International Nuclear Information System (INIS)

Stagni, Venturina; Santini, Simonetta; Barilà, Daniela

2012-01-01

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCCs are genetically and phenotypically heterogeneous tumors characterized by very poor prognosis, mainly due to the lack, at present, of effective therapeutic options, as these tumors are rarely suitable for radiotherapy and often resistant to chemotherapy protocols. In the last years, agonists targeting the Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL) death receptor, has been investigated as a valuable promise for cancer therapy, based on their selectivity for malignant cells and low toxicity for healthy cells. However, many cancer models display resistance to death receptor induced apoptosis, pointing to the requirement for the development of combined therapeutic approaches aimed to selectively sensitize cancer cells to TRAIL. Recently, we identified ATM kinase as a novel modulator of the ability of chemotherapeutic agents to enhance TRAIL sensitivity. Here, we review the biological determinants of HCC responsiveness to TRAIL and provide an exhaustive and updated analysis of the molecular mechanisms exploited for combined therapy in this context. The role of ATM kinase as potential novel predictive biomarker for combined therapeutic approaches based on TRAIL and chemotherapeutic drugs will be closely discussed

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...

Broadband radiometric LED measurements

Science.gov (United States)

Eppeldauer, G. P.; Cooksey, C. C.; Yoon, H. W.; Hanssen, L. M.; Podobedov, V. B.; Vest, R. E.; Arp, U.; Miller, C. C.

2016-09-01

At present, broadband radiometric LED measurements with uniform and low-uncertainty results are not available. Currently, either complicated and expensive spectral radiometric measurements or broadband photometric LED measurements are used. The broadband photometric measurements are based on the CIE standardized V(λ) function, which cannot be used in the UV range and leads to large errors when blue or red LEDs are measured in its wings, where the realization is always poor. Reference irradiance meters with spectrally constant response and high-intensity LED irradiance sources were developed here to implement the previously suggested broadband radiometric LED measurement procedure [1, 2]. Using a detector with spectrally constant response, the broadband radiometric quantities of any LEDs or LED groups can be simply measured with low uncertainty without using any source standard. The spectral flatness of filtered-Si detectors and low-noise pyroelectric radiometers are compared. Examples are given for integrated irradiance measurement of UV and blue LED sources using the here introduced reference (standard) pyroelectric irradiance meters. For validation, the broadband measured integrated irradiance of several LED-365 sources were compared with the spectrally determined integrated irradiance derived from an FEL spectral irradiance lamp-standard. Integrated responsivity transfer from the reference irradiance meter to transfer standard and field UV irradiance meters is discussed.

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.

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

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

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.

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.

Broadband Polarization-Insensitive Wavelength Conversion Based on Non-Degenerate Four-Wave Mixing in a Silicon Nanowire

DEFF Research Database (Denmark)

Pu, Minhao; Hu, Hao; Ji, Hua

2012-01-01

We experimentally demonstrate broadband polarization-insensitive one-to-two wavelength conversion of a 10-Gb/s DPSK data signal based on non-degenerate four-wave mixing in a silicon nanowire with bit-error rate measurements.......We experimentally demonstrate broadband polarization-insensitive one-to-two wavelength conversion of a 10-Gb/s DPSK data signal based on non-degenerate four-wave mixing in a silicon nanowire with bit-error rate measurements....

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.

Customer Churn Prediction for Broadband Internet Services

Science.gov (United States)

Huang, B. Q.; Kechadi, M.-T.; Buckley, B.

Although churn prediction has been an area of research in the voice branch of telecommunications services, more focused studies on the huge growth area of Broadband Internet services are limited. Therefore, this paper presents a new set of features for broadband Internet customer churn prediction, based on Henley segments, the broadband usage, dial types, the spend of dial-up, line-information, bill and payment information, account information. Then the four prediction techniques (Logistic Regressions, Decision Trees, Multilayer Perceptron Neural Networks and Support Vector Machines) are applied in customer churn, based on the new features. Finally, the evaluation of new features and a comparative analysis of the predictors are made for broadband customer churn prediction. The experimental results show that the new features with these four modelling techniques are efficient for customer churn prediction in the broadband service field.

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.

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…

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…

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

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

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

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

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.

Direct UV-written broadband directional broadband planar waveguide couplers

DEFF Research Database (Denmark)

Olivero, Massimo; Svalgaard, Mikael

2005-01-01

We report the fabrication of broadband directional couplers by direct UV-writing. The fabrication process is shown to be beneficial, robust and flexible. The components are compact and show superior performance in terms of loss and broadband operation.......We report the fabrication of broadband directional couplers by direct UV-writing. The fabrication process is shown to be beneficial, robust and flexible. The components are compact and show superior performance in terms of loss and broadband operation....

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.

Silicon-on-insulator-based polarization-independent 1×3 broadband beam splitter with adiabatic coupling

Science.gov (United States)

Gong, Yuanhao; Liu, Lei; Chang, Limin; Li, Zhiyong; Tan, Manqing; Yu, Yude

2017-10-01

We propose and numerically simulate a polarization-independent 1×3 broadband beam splitter based on silicon-on-insulator (SOI) technology with adiabatic coupling. The designed structure is simulated by beam-propagation-method (BPM) and gets simulated transmission uniformity of three outputs better than 0.3dB for TE-polarization and 0.8dB for TM-polarization in a broadband of 180nm.

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

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..

Broadband and high-efficiency vortex beam generator based on a hybrid helix array.

Science.gov (United States)

Fang, Chaoqun; Wu, Chao; Gong, Zhijie; Zhao, Song; Sun, Anqi; Wei, Zeyong; Li, Hongqiang

2018-04-01

The vortex beam which carries the orbital angular momentum has versatile applications, such as high-resolution imaging, optical communications, and particle manipulation. Generating vortex beams with the Pancharatnam-Berry (PB) phase has drawn considerable attention for its unique spin-to-orbital conversion features. Despite the PB phase being frequency independent, an optical element with broadband high-efficiency circular polarization conversion feature is still needed for the broadband high-efficiency vortex beam generation. In this work, a broadband and high-efficiency vortex beam generator based on the PB phase is built with a hybrid helix array. Such devices can generate vortex beams with arbitrary topological charge. Moreover, vortex beams with opposite topological charge can be generated with an opposite handedness incident beam that propagates backward. The measured efficiency of our device is above 65% for a wide frequency range, with the relative bandwidth of 46.5%.

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.

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.

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.

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.

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.

Wide-angle, polarization-insensitive and broadband absorber based on eight-fold symmetric SRRs metamaterial

Science.gov (United States)

Wu, Dong; Liu, Yumin; Yu, Zhongyuan; Chen, Lei; Ma, Rui; Li, Yutong; Li, Ruifang; Ye, Han

2016-12-01

In this paper, we propose a novel three dimensional metamaterial design with eight-fold rotational symmetry that shows a polarization-insensitive, wide-angle and broadband perfect absorption in the microwave band. By simulation, the polarization-insensitive absorption is over 90% between 26.9 GHz to 32.9 GHz, and the broadband absorption remains a good absorption performance to a wide incident angles for both TE and TM polarizations. The magnetic field distribution are investigated to interpret the physical mechanism of broadband absorption. The broadband absorption is based on overlapping the multiple magnetic resonances at the neighboring frequencies by coupling effects of multiple metallic split-ring resonators (SRRs). Moreover, it is demonstrate that the designed structure can be extended to other frequencies by scale down the size of the unit cell, such as the visible frequencies. The simulated results show that the absorption of the smaller absorber is above 90% in the frequency range from 467 THz to 765 THz(392-642 nm), which include orange to purple light in visible region(400-760nm). The wide-angle and polarization-insensitive stabilities of the smaller absorber is also demonstrated at visible region. The proposed work provides a new design of realization of a polarization-insensitive, wide-angle and broadband absorber ranging different frequency bands, and such a structure has potential application in the fields of solar cell, imaging and detection.

Techno-economic evaluation of broadband access technologies

DEFF Research Database (Denmark)

Sigurdsson, Halldór Matthias; Skouby, Knud Erik

2005-01-01

Broadband for all is an essential element in the EU policy concerning the future of ICT-based society. The overall purpose of this paper is to present a model for evaluation of different broadband access technologies and to present some preliminary results based on the model that has been carried...

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

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 ...

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...

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.

Design of a broadband ultra-large area acoustic cloak based on a fluid medium

Science.gov (United States)

Zhu, Jian; Chen, Tianning; Liang, Qingxuan; Wang, Xiaopeng; Jiang, Ping

2014-10-01

A broadband ultra-large area acoustic cloak based on fluid medium was designed and numerically implemented with homogeneous metamaterials according to the transformation acoustics. In the present work, fluid medium as the body of the inclusion could be tuned by changing the fluid to satisfy the variant acoustic parameters instead of redesign the whole cloak. The effective density and bulk modulus of the composite materials were designed to agree with the parameters calculated from the coordinate transformation methodology by using the effective medium theory. Numerical simulation results showed that the sound propagation and scattering signature could be controlled in the broadband ultra-large area acoustic invisibility cloak, and good cloaking performance has been achieved and physically realized with homogeneous materials. The broadband ultra-large area acoustic cloaking properties have demonstrated great potentials in the promotion of the practical applications of acoustic cloak.

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.

Terahertz broadband polarization converter based on metamaterials

Science.gov (United States)

Li, Yonghua; Zhao, Guozhong

2018-01-01

Based on the metamaterial composed of symmetrical split resonant ring, a broadband reflective terahertz polarization converter is proposed. The numerical simulation shows that it can rotate the polarization direction of linear polarized wave 90° in the range of 0.7-1.8THz and the polarization conversion ratio is over 90%. The reflection coefficient of the two electric field components in the diagonal direction is the same and the phase difference is 180° ,which leads to the cross-polarization rotation.In order to further study the physical mechanism of high polarization conversion, we analyze the surface current distribution of the resonant ring. The polarization converter has potential applications in terahertz wave plate and metamaterial antenna design.

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.

Adoption of Broadband Services

DEFF Research Database (Denmark)

Falch, Morten

2008-01-01

Broadband is seen as a key infrastructure for developing the information society. For this reason many Governments are actively engaged in stimulating investments in broadband infrastructures and use of broadband services. This chapter compares a wide range of broadband strategies in the most suc....... Many countries have provided active support for stimulating diffusion of broadband and national variants of this type of policies in different countries are important for an explanation of national differences in adoption of broadband....

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)

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

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.

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.

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.

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.

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 ...

Service Differentiation in Residential Broadband Networks

DEFF Research Database (Denmark)

Sigurdsson, Halldór Matthias

2004-01-01

As broadband gains widespread adoption with residential users, revenue generating voice- and video-services have not yet taken off. This slow uptake is often attributed to lack of Quality of Service management in residential broadband networks. To resolve this and induce service variety, network...... access providers are implementing service differentiation in their networks where voice and video gets prioritised before data. This paper discusses the role of network access providers in multipurpose packet based networks and the available migration strategies for supporting multimedia services...... in digital subscriber line (DSL) based residential broadband networks. Four possible implementation scenarios and their technical characteristics and effects are described. To conclude, the paper discusses how network access providers can be induced to open their networks for third party service providers....

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)

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.

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.

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.

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.

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.

Scattering Fields Control by Metamaterial Device Based on Ultra-Broadband Polarization Converters

Directory of Open Access Journals (Sweden)

Si-Jia Li

2016-12-01

Full Text Available We proposed a novel ultra-broadband meta¬material screen with controlling the electromagnetic scat¬tering fields based on the three layers wideband polariza¬tion converter (TLW-PC. The unit cell of TLW-PC was composed of a three layers substrate loaded with double metallic split-rings structure and a metal ground plane. We observed that the polarization converter primarily per¬formed ultra-broadband cross polarization conversion from 5.71 GHz to 14.91 GHz. Furthermore, a metamaterial screen, which contributed to the low scattering charac¬teristics, had been exploited with the orthogonal array based on TLW-PC. The near scattering electronic fields are controlled due to the change of phase and amplitude for incident wave. The metamaterial screen significantly exhibited low scattering characteristics from 5.81 GHz to 15.06 GHz. To demonstrate design, a metamaterial device easily implemented by the common printed circuit board method has been fabricated and measured. Experimental results agreed well with the simulated results.

Local government broadband policies for areas with limited Internet access

Directory of Open Access Journals (Sweden)

Yoshio Arai

2014-03-01

Full Text Available Despite their wide diffusion in developed countries, broadband services are still limited in areas where providing them is not profitable for private telecom carriers. To address this, many local governments in Japan have implemented broadband deployment projects subsidized by the national government. In this paper, we discuss local government broadband policies based on survey data collected from municipalities throughout the country. With the support of national promotion policies, broadband services were rapidly introduced to most local municipalities in Japan during the 2000s. Local government deployment policies helped to reduce the number of areas with no broadband access. A business model based on the Indefeasible Right of Use (IRU contract between a private telecom carrier and a local government has been developed in recent years. Even local governments without the technical capacity to operate a broadband business can introduce broadband services into their territory using the IRU business model.

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.

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.

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…

Novel ring resonator-based integrated photonic beamformer for broadband phased array receive antennas - part 1: design and performance analysis

NARCIS (Netherlands)

Meijerink, Arjan; Roeloffzen, C.G.H.; Meijerink, Roland; Zhuang, L.; Marpaung, D.A.I.; Bentum, Marinus Jan; Burla, M.; Verpoorte, Jaco; Jorna, Pieter; Huizinga, Adriaan; van Etten, Wim

2010-01-01

A novel optical beamformer concept is introduced that can be used for seamless control of the reception angle in broadband wireless receivers employing a large phased array antenna (PAA). The core of this beamformer is an optical beamforming network (OBFN), using ring resonator-based broadband

Rail-based Broadband Synthetic Aperture Ocean Measurement System

Data.gov (United States)

Federal Laboratory Consortium — FUNCTION: Enables collection of broadband acoustic scattering databases where acoustic sources and receivers can be translated on a precise linear path under program...

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

Broadband tunable electromagnetically induced transparency analogue metamaterials based on graphene in terahertz band

Science.gov (United States)

Wang, Yue; Leng, Yanbing; Wang, Li; Dong, Lianhe; Liu, Shunrui; Wang, Jun; Sun, Yanjun

2018-06-01

Most of the actively controlled electromagnetically induced transparency analogue (EIT-like) metamaterials were implemented with narrowband modulations. In this paper, a broadband tunable EIT-like metamaterial based on graphene in the terahertz band is presented. It consists of a cut wire as the bright resonator and two couples of H-shaped resonators in mirror symmetry as the dark resonators. A broadband tunable property of transmission amplitude is realized by changing the Fermi level of graphene. Furthermore, the geometries of the metamaterial structure are optimized to achieve the ideal curve through the simulation. Such EIT-like metamaterials proposed here are promising candidates for designing active wide-band slow-light devices, wide-band terahertz active filters, and wide-band terahertz modulators.

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.

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.

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.

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

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.

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.

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

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

Epoxy-based broadband anti-reflection coating for millimeter-wave optics

OpenAIRE

Rosen, Darin; Suzuki, Aritoki; Keating, Brian; Krantz, William; Lee, Adrian T.; Quealy, Erin; Richards, Paul L.; Siritanasak, Praween; Walker, William

2013-01-01

We have developed epoxy-based, broadband anti-reflection coatings for millimeter-wave astrophysics experiments with cryogenic optics. By using multiple-layer coatings where each layer steps in dielectric constant, we achieved low reflection over a wide bandwidth. We suppressed the reflection from an alumina disk to 10% over fractional bandwidths of 92% and 104% using two-layer and three-layer coatings, respectively. The dielectric constants of epoxies were tuned between 2.06 and 7.44 by mixin...

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.

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

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.

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

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

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)

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.

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

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.

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...

Record power, ultra-broadband supercontinuum source based on highly GeO2 doped silica fiber

DEFF Research Database (Denmark)

Jain, Deepak; Sidharthan, R.; Moselund, Peter M.

2016-01-01

the potential of germania based photonic crystal fiber or a step-index fiber supercontinuum source for high power ultra-broad band emission being by pumped a 1060 nm or a 1550 nm laser source. To the best of our knowledge, this is the record power, ultra-broadband, and all-fiberized supercontinuum light source...... based on silica and germania fiber ever demonstrated to the date. (C) 2016 Optical Society of America......We demonstrate highly germania doped fibers for mid-infrared supercontinuum generation. Experiments ensure a highest output power of 1.44 W for a broadest spectrum from 700 nm to 3200 nm and 6.4 W for 800 nm to 2700 nm from these fibers, while being pumped by a broadband Erbium-Ytterbium doped...

Community Broadband Networks and the Opportunity for E-Government Services

DEFF Research Database (Denmark)

Williams, Idongesit

2017-01-01

Community Broadband Networks (CBN) facilitate Broadband connectivity in underserved areas in many countries. The lack of Broadband connectivity is one of the reasons for the slow diffusion of e-government services in many countries.This article explains how CBNs can be enabled by governments...... to facilitate the delivery of e–government services in underserved areas in the developed and developing countries.The Community Based Broadband Mobilization (CBNM) models are used as explanatory tools....

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...

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.

Fiber To The Subscriber: Look At Narrowband Services First

Science.gov (United States)

Mangum, Karen L.

1990-01-01

Today, it's not easy to find a telecommunications publication that doesn't have a feature article on fiber to the home. Not only do these articles appear in telecommunications publications but in newspapers like in the Wall Street Journal and USA Today. What concerns me about these articles is the immediate emphasis on CATV and video on demand services. Fiber is indeed a broadband transmission medium. However, from BellSouths point of view, the video services are not necessary to the economic equation for placing fiber to the subscriber. Our objective is to place fiber in the network for POTS like services first and upgrade the electronics based on customer demand.

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

Broadband set-top box using MAP-CA processor

Science.gov (United States)

Bush, John E.; Lee, Woobin; Basoglu, Chris

2001-12-01

Advances in broadband access are expected to exert a profound impact in our everyday life. It will be the key to the digital convergence of communication, computer and consumer equipment. A common thread that facilitates this convergence comprises digital media and Internet. To address this market, Equator Technologies, Inc., is developing the Dolphin broadband set-top box reference platform using its MAP-CA Broadband Signal ProcessorT chip. The Dolphin reference platform is a universal media platform for display and presentation of digital contents on end-user entertainment systems. The objective of the Dolphin reference platform is to provide a complete set-top box system based on the MAP-CA processor. It includes all the necessary hardware and software components for the emerging broadcast and the broadband digital media market based on IP protocols. Such reference design requires a broadband Internet access and high-performance digital signal processing. By using the MAP-CA processor, the Dolphin reference platform is completely programmable, allowing various codecs to be implemented in software, such as MPEG-2, MPEG-4, H.263 and proprietary codecs. The software implementation also enables field upgrades to keep pace with evolving technology and industry demands.

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.

An in-building network based on community access television integration with quadrature phase-shift keying orthogonal frequency-division multiplexing

International Nuclear Information System (INIS)

Chen, Chia-Yi; Lin, Ying-Pyng; Lu, Hai-Han; Wu, Po-Yi; Lin, Huang-Chang; Wu, Hsiao-Wen

2012-01-01

An in-building network based on cable television (CATV) integration with quadrature phase-shift keying (QPSK) orthogonal frequency-division multiplexing (OFDM) transport over a combination of single-mode fibers (SMF) and perfluorinated graded-index plastic optical fibers (GI-POF) is proposed and experimentally demonstrated. In this system, a 1558.5 nm optical signal is directly transmitted along two fiber spans (20 km SMF + 25 m GI-POF). An optimum guard band is carefully established to ensure that no very substantial signal interference is induced between the CATV and QPSK OFDM bands. Error free transmission with sufficiently low bit error rate values was achieved for 1.25 Gbps/771.5 MHz QPSK OFDM signals; also, acceptable carrier-to-noise ratio, composite second-order, and composite triple-beat performances were obtained for CATV signals. This proposed network is significant because it is economical and convenient to install. (paper)

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.

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.

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

Multistep Cylindrical Structure Analysis at Normal Incidence Based on Water-Substrate Broadband Metamaterial Absorbers

Science.gov (United States)

Fang, Chonghua

2018-01-01

A new multistep cylindrical structure based on water-substrate broadband metamaterial absorbers is designed to reduce the traditional radar cross-section (RCS) of a rod-shaped object. The proposed configuration consists of two distinct parts. One of these components is formed by a four-step cylindrical metal structure, whereas the other one is formed by a new water-substrate broadband metamaterial absorber. The designed structure can significantly reduce the radar cross section more than 10 dB from 4.58 to 18.42 GHz which is the 86.5 % bandwidth of from C-band to 20 GHz. The results of measurement show reasonably good accordance with the simulated ones, which verifies the ability and effect of the proposed design.

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.

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

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

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.

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.

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).

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

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.

Broadband Optical Access Technologies to Converge towards a Broadband Society in Europe

Science.gov (United States)

Coudreuse, Jean-Pierre; Pautonnier, Sophie; Lavillonnière, Eric; Didierjean, Sylvain; Hilt, Benoît; Kida, Toshimichi; Oshima, Kazuyoshi

This paper provides insights on the status of broadband optical access market and technologies in Europe and on the expected trends for the next generation optical access networks. The final target for most operators, cities or any other player is of course FTTH (Fibre To The Home) deployment although we can expect intermediate steps with copper or wireless technologies. Among the two candidate architectures for FTTH, PON (Passive Optical Network) is by far the most attractive and cost effective solution. We also demonstrate that Ethernet based optical access network is very adequate to all-IP networks without any incidence on the level of quality of service. Finally, we provide feedback from a FTTH pilot network in Colmar (France) based on Gigabit Ethernet PON technology. The interest of this pilot lies on the level of functionality required for broadband optical access networks but also on the development of new home network configurations.

Ultra-small and broadband polarization splitters based on double-slit interference

Energy Technology Data Exchange (ETDEWEB)

Sun, Chengwei; Li, Hongyun [State Key Laboratory for Mesoscopic Physics, Collaborative Innovation Center of Quantum Matter, Department of Physics, Peking University, Beijing 100871 (China); Gong, Qihuang; Chen, Jianjun, E-mail: jjchern@pku.edu.cn [State Key Laboratory for Mesoscopic Physics, Collaborative Innovation Center of Quantum Matter, Department of Physics, Peking University, Beijing 100871 (China); Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan, Shanxi 030006 (China)

2016-03-07

An ultra-small and broadband polarization splitter is numerically and experimentally demonstrated based on the double-slit interference in a polymer-film-coated double-slit structure. The hybrid slab waveguide (air-polymer-Au) supports both the transverse-magnetic and transverse-electric modes. The incident beam from the back side can excite these two guided modes of orthogonally polarized states in the hybrid structure. By exploiting the difference slit widths and the large mode birefringence, these two guided modes propagate to the opposite directions along the front metal surface. Moreover, the short interference length broadens the operation bandwidth. Experimentally, a polarization splitter with a lateral dimension of only about 1.6 μm and an operation bandwidth of 50 nm is realized. By designing the double-slit structure in a hybrid strip waveguide, the device dimension can be significant downscaled to about 0.3 × 1.3 μm{sup 2}. Such an ultra-small and broadband polarization splitter may find important applications in the integrated photonic circuits.

NEBULAS A High Performance Data-Driven Event-Building Architecture based on an Asynchronous Self-Routing Packet-Switching Network

CERN Multimedia

Costa, M; Letheren, M; Djidi, K; Gustafsson, L; Lazraq, T; Minerskjold, M; Tenhunen, H; Manabe, A; Nomachi, M; Watase, Y

2002-01-01

RD31 : The project is evaluating a new approach to event building for level-two and level-three processor farms at high rate experiments. It is based on the use of commercial switching fabrics to replace the traditional bus-based architectures used in most previous data acquisition sytems. Switching fabrics permit the construction of parallel, expandable, hardware-driven event builders that can deliver higher aggregate throughput than the bus-based architectures. A standard industrial switching fabric technology is being evaluated. It is based on Asynchronous Transfer Mode (ATM) packet-switching network technology. Commercial, expandable ATM switching fabrics and processor interfaces, now being developed for the future Broadband ISDN infrastructure, could form the basis of an implementation. The goals of the project are to demonstrate the viability of this approach, to evaluate the trade-offs involved in make versus buy options, to study the interfacing of the physics frontend data buffers to such a fabric, a...

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.

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.

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

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

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....

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.

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.

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

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.

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.

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.

The promise of downlink MU-MIMO for high-capacity next generation mobile broadband networks based on IEEE 802.16 m

Directory of Open Access Journals (Sweden)

Papathanassiou Apostolos

2011-01-01

Full Text Available Abstract The dramatic increase of the demand for mobile broadband services poses stringent requirements on the performance evolution of currently deployed mobile broadband networks, such as Mobile WiMAX Release 1 and 3GPP LTE Release 8. Although the combination of single-user multiple-input multiple-output (SU-MIMO and orthogonal frequency division multiple access (OFDMA provide the appropriate technologies for improving the downlink performance of third generation (3G code division multiple access (CDMA-based mobile radio systems and, thus, address the current mobile internet requirements, a fundamental paradigm shift is required to cope with the constantly increasing mobile broadband data rate and spectral efficiency requirements. Among the different technologies available for making the paradigm shift from current to next-generation mobile broadband networks, multiuser MIMO (MU-MIMO constitutes the most promising technology because of its significant performance improvement advantages. In this article, we analyze the performance of MU-MIMO under a multitude of deployment scenarios and system parameters through extensive system-level simulations which are based on widely used system-level evaluation methodologies. The target mobile broadband system used in the simulations is IEEE 802.16 m which was recently adopted by ITU-R as an IMT-Advanced technology along with 3GPP LTE-Advanced. The results provide insights into different aspects of MU-MIMO with respect to system-level performance, parameter sensitivity, and deployment scenarios, and they can be used by the mobile broadband network designer for maximizing the benefits of MU-MIMO in a scenario with specific deployment requirements and goals.

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.

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. .

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…

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.

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.

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

Highly Efficient Broadband Yellow Phosphor Based on Zero-Dimensional Tin Mixed-Halide Perovskite.

Science.gov (United States)

Zhou, Chenkun; Tian, Yu; Yuan, Zhao; Lin, Haoran; Chen, Banghao; Clark, Ronald; Dilbeck, Tristan; Zhou, Yan; Hurley, Joseph; Neu, Jennifer; Besara, Tiglet; Siegrist, Theo; Djurovich, Peter; Ma, Biwu

2017-12-27

Organic-inorganic hybrid metal halide perovskites have emerged as a highly promising class of light emitters, which can be used as phosphors for optically pumped white light-emitting diodes (WLEDs). By controlling the structural dimensionality, metal halide perovskites can exhibit tunable narrow and broadband emissions from the free-exciton and self-trapped excited states, respectively. Here, we report a highly efficient broadband yellow light emitter based on zero-dimensional tin mixed-halide perovskite (C 4 N 2 H 14 Br) 4 SnBr x I 6-x (x = 3). This rare-earth-free ionically bonded crystalline material possesses a perfect host-dopant structure, in which the light-emitting metal halide species (SnBr x I 6-x 4- , x = 3) are completely isolated from each other and embedded in the wide band gap organic matrix composed of C 4 N 2 H 14 Br - . The strongly Stokes-shifted broadband yellow emission that peaked at 582 nm from this phosphor, which is a result of excited state structural reorganization, has an extremely large full width at half-maximum of 126 nm and a high photoluminescence quantum efficiency of ∼85% at room temperature. UV-pumped WLEDs fabricated using this yellow emitter together with a commercial europium-doped barium magnesium aluminate blue phosphor (BaMgAl 10 O 17 :Eu 2+ ) can exhibit high color rendering indexes of up to 85.

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...

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

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.

Broadband working-waveband-tunable polarization converter based on anisotropic metasurface

Science.gov (United States)

Lin, Yu; Wang, Lei; Gao, Jun; Lu, Yichao; Jiang, Suhua; Zeng, Wei

2017-03-01

We experimentally and theoretically demonstrate an ultrathin, broadband, and highly efficient metamaterial-based polarization converter with a metasurface/insulator/metal (MIM) configuration. In such a system, the resonance undergoes a transition from a vertical Fabry-Pérot type to a transverse type as the spacer thickness decreases. By changing the spacer thickness from 1 to 15 mm, the working waveband of this device could be tuned from 10.9-12.9 to 6-8 GHz without compromising the polarization conversion efficiency. Equivalent circuit theory and the transfer matrix method are used for demonstrating the physical mechanism of our device.

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)

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

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)

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

Broadband Faraday isolator.

Science.gov (United States)

Berent, Michał; Rangelov, Andon A; Vitanov, Nikolay V

2013-01-01

Driving on an analogy with the technique of composite pulses in quantum physics, we theoretically propose a broadband Faraday rotator and thus a broadband optical isolator, which is composed of sequences of ordinary Faraday rotators and achromatic quarter-wave plates rotated at the predetermined angles.

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)

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.

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

which significantly improved results of AIRS Version-6. Version-5.70 CrIS/ATMS temperature profile and surface skin temperature retrievals are of very good quality, and are better than AIRS Version-5 retrievals, but are still significantly poorer than those of AIRS Version-6. CrIS/ATMS retrievals should improve when a Neural-Net start-up system is ready for use. We also examined CrIS/ATMS retrievals generated by NOAA using their NUCAPS retrieval algorithm, which is based on earlier versions of the AIRS Science Team retrieval algorithms. We show that the NUCAPS algorithm as currently configured is not well suited for climate monitoring purposes.

Silicon graphene waveguide tunable broadband microwave photonics phase shifter.

Science.gov (United States)

Capmany, José; Domenech, David; Muñoz, Pascual

2014-04-07

We propose the use of silicon graphene waveguides to implement a tunable broadband microwave photonics phase shifter based on integrated ring cavities. Numerical computation results show the feasibility for broadband operation over 40 GHz bandwidth and full 360° radiofrequency phase-shift with a modest voltage excursion of 0.12 volt.

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.

Spatial-temporal dynamics of broadband terahertz Bessel beam propagation

International Nuclear Information System (INIS)

Semenova, V A; Kulya, M S; Bespalov, V G

2016-01-01

The unique properties of narrowband and broadband terahertz Bessel beams have led to a number of their applications in different fields, for example, for the depth of focusing and resolution enhancement in terahertz imaging. However, broadband terahertz Bessel beams can probably be also used for the diffraction minimization in the short-range broadband terahertz communications. For this purpose, the study of spatial-temporal dynamics of the broadband terahertz Bessel beams is needed. Here we present a simulation-based study of the propagating in non-dispersive medium broadband Bessel beams generated by a conical axicon lens. The algorithm based on scalar diffraction theory was used to obtain the spatial amplitude and phase distributions of the Bessel beam in the frequency range from 0.1 to 3 THz at the distances 10-200 mm from the axicon. Bessel beam field is studied for the different spectral components of the initial pulse. The simulation results show that for the given parameters of the axicon lens one can obtain the Gauss-Bessel beam generation in the spectral range from 0.1 to 3 THz. The length of non-diffraction propagation for a different spectral components was measured, and it was shown that for all spectral components of the initial pulse this length is about 130 mm. (paper)

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

Broadband Internet and Income Inequality

OpenAIRE

HOUNGBONON , Georges Vivien; Liang , Julienne

2017-01-01

Policy makers are aiming for a large coverage of high-speed broadband Internet. However , there is still a lack of evidence about its effects on income distribution. In this paper, we investigate the effects of fixed broadband Internet on mean income and income inequality using a unique town-level data on broadband adoption and quality in France. We find that broadband adoption and quality raise mean income and lower income inequality. These results are robust to initial conditions, and yield...

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.

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.

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...

Epoxy-based broadband antireflection coating for millimeter-wave optics.

Science.gov (United States)

Rosen, Darin; Suzuki, Aritoki; Keating, Brian; Krantz, William; Lee, Adrian T; Quealy, Erin; Richards, Paul L; Siritanasak, Praween; Walker, William

2013-11-20

We have developed epoxy-based, broadband antireflection coatings for millimeter-wave astrophysics experiments with cryogenic optics. By using multiple-layer coatings where each layer steps in dielectric constant, we achieved low reflection over a wide bandwidth. We suppressed the reflection from an alumina disk to 10% over fractional bandwidths of 92% and 104% using two-layer and three-layer coatings, respectively. The dielectric constants of epoxies were tuned between 2.06 and 7.44 by mixing three types of epoxy and doping with strontium titanate powder required for the high dielectric mixtures. At 140 K, the band-integrated absorption loss in the coatings was suppressed to less than 1% for the two-layer coating, and below 10% for the three-layer coating.

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.

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.

Analisis Perkembangan Internet Broadband di Daerah Perbatasan Sulawesi Utara

Directory of Open Access Journals (Sweden)

Riva'atul Adaniah Wahab

2016-12-01

Full Text Available Adopsi teknologi internet broadband dapat memberikan dampak ekonomi bagi masyarakat perbatasan. Karenanya pemerataan pembangunan internet broadband di wilayah  ini harus segera diwujudkan. Penelitian deskriptif kuantitatif ini dilaksanakan di wilayah perbatasan Provinsi Sulawesi Utara untuk mengetahui kondisi aspek supply dan demand perkembangan internet broadband di wilayah tersebut. Berdasarkan hasil penelitian, dapat disimpulkan bahwa dari aspek supply, kondisi infrastruktur masih sangat kurang, ketersediaan layanan internet broadband berkualitas tinggi dengan tarif rendah juga masih sulit diwujudkan. Dari aspek demand, stigma atau persepsi masyarakat bahwa internet tidak penting menjadi salah satu faktor penyebab tidak memiliki akses internet. Adapun hambatan yang paling dominan adalah ketidakpahaman dalam penggunaan internet. Faktor ini juga menjadi mendasari literasi internet broadband masyarakat pada level 0 yaitu  tidak peduli akan pentinya internet. Menanggapai kondisi ini, penyusunan dan penetapan kebijakan serta regulasi seperti QoS layanan, tarif interkoneksi, infrastructure sharing dibuat untuk menyediakan internet broadband berkualitas tinggi dengan harga murah. Selain itu distribusi perangkat mobile berharga murah (smartphone juga perlu didorong dengan penerapan TKDN untuk produksi perangkat. Tidak kalah pentingnya adalah peningkatan literasi internet broadband masyarakat melalui sosialisasi atau pelatihan baik formal maupun nonformal. Abstract   Adoption of internet broadband internet can provide the economic impact for border communities. Hence equitable development of internet broadband in the region should be immediately implemented. This quantitative descriptive study was conducted in the border region of North Sulawesi to determine the condition of supply and demand aspects of the development of internet broadband. Based on the results, it can be concluded that from the aspect of supply, the condition of the

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.

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

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

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

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

Broadband polymer microstructured THz fiber coupler with downdoped cores

DEFF Research Database (Denmark)

Nielsen, Kristian; Rasmussen, Henrik K.; Bang, Ole

2010-01-01

We demonstrate a broadband THz directional coupler based on a dual core photonic crystal fiber (PCF) design with mechanically down-doped core regions. For a center frequency of 1.3 THz we demonstrate a bandwidth of 0.65 THz.......We demonstrate a broadband THz directional coupler based on a dual core photonic crystal fiber (PCF) design with mechanically down-doped core regions. For a center frequency of 1.3 THz we demonstrate a bandwidth of 0.65 THz....

Visible light broadband perfect absorbers

Energy Technology Data Exchange (ETDEWEB)

Jia, X. L.; Meng, Q. X.; Yuan, C. X.; Zhou, Z. X.; Wang, X. O., E-mail: wxo@hit.edu.cn [School of Science, Harbin Institute of Technology, Harbin 150001 (China)

2016-03-15

The visible light broadband perfect absorbers based on the silver (Ag) nano elliptical disks and holes array are studied using finite difference time domain simulations. The semiconducting indium silicon dioxide thin film is introduced as the space layer in this sandwiched structure. Utilizing the asymmetrical geometry of the structures, polarization sensitivity for transverse electric wave (TE)/transverse magnetic wave (TM) and left circular polarization wave (LCP)/right circular polarization wave (RCP) of the broadband absorption are gained. The absorbers with Ag nano disks and holes array show several peaks absorbance of 100% by numerical simulation. These simple and flexible perfect absorbers are particularly desirable for various potential applications including the solar energy absorber.

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.

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

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

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.

Metamaterial-based half Maxwell fish-eye lens for broadband directive emissions

Science.gov (United States)

Dhouibi, Abdallah; Nawaz Burokur, Shah; de Lustrac, André; Priou, Alain

2013-01-01

The broadband directive emission from a metamaterial surface is numerically and experimentally reported. The metasurface, composed of non-resonant complementary closed ring structures, is designed to obey the refractive index of a half Maxwell fish-eye lens. A planar microstrip Vivaldi antenna is used as transverse magnetic polarized wave launcher for the lens. A prototype of the lens associated with its feed structure has been fabricated using standard lithography techniques. To experimentally demonstrate the broadband focusing properties and directive emissions, both the far-field radiation patterns and the near-field distributions have been measured. Measurements agree quantitatively and qualitatively with theoretical simulations.

Broadband Liner Optimization for the Source Diagnostic Test Fan

Science.gov (United States)

Nark, Douglas M.; Jones, Michael G.

2012-01-01

The broadband component of fan noise has grown in relevance with the utilization of increased bypass ratio and advanced fan designs. Thus, while the attenuation of fan tones remains paramount, the ability to simultaneously reduce broadband fan noise levels has become more appealing. This paper describes a broadband acoustic liner optimization study for the scale model Source Diagnostic Test fan. Specifically, in-duct attenuation predictions with a statistical fan source model are used to obtain optimum impedance spectra over a number of flow conditions for three liner locations in the bypass duct. The predicted optimum impedance information is then used with acoustic liner modeling tools to design liners aimed at producing impedance spectra that most closely match the predicted optimum values. Design selection is based on an acceptance criterion that provides the ability to apply increased weighting to specific frequencies and/or operating conditions. Typical tonal liner designs targeting single frequencies at one operating condition are first produced to provide baseline performance information. These are followed by multiple broadband design approaches culminating in a broadband liner targeting the full range of frequencies and operating conditions. The broadband liner is found to satisfy the optimum impedance objectives much better than the tonal liner designs. In addition, the broadband liner is found to provide better attenuation than the tonal designs over the full range of frequencies and operating conditions considered. Thus, the current study successfully establishes a process for the initial design and evaluation of novel broadband liner concepts for complex engine configurations.

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.

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.

A Design of 45-Degree Dual-Polarization Broadband Plane Station Antenna

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Jianming Zhou

2015-01-01

Full Text Available A new broadband planar dual-polarization base station antenna is proposed, the antenna consists of two broadband plane coplanar base station antenna units, and so it has features of plane antenna. Two broadband plane station antenna units can, respectively, form double polarization in the direction. We analyzed the relative positions between the two antenna units and their effects on the performances of the antenna, especially for the influence of isolation. Broadband antenna has the characteristics of the broadband station antenna, and bandwidth is also guaranteed. The measured results show that the antenna can obtain 45% relative bandwidth, and 30 dB isolation degree also can be got, and the radiation performance is also good. Measurement results confirmed that the antenna gain can be guaranteed among 48% relative bandwidth, 15 dB of gain is got among bandwidth of 1.69–2.78 GHz, the isolation degree of different polarization method can reach 30 dB, and the measurement gain of two polarization methods of antenna both can reach 8.5 dBi.

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

Driving demand for broadband networks and services

CERN Document Server

Katz, Raul L

2014-01-01

This book examines the reasons why various groups around the world choose not to adopt broadband services and evaluates strategies to stimulate the demand that will lead to increased broadband use. It introduces readers to the benefits of higher adoption rates while examining the progress that developed and emerging countries have made in stimulating broadband demand. By relying on concepts such as a supply and demand gap, broadband price elasticity, and demand promotion, this book explains differences between the fixed and mobile broadband demand gap, introducing the notions of substitution and complementarity between both platforms. Building on these concepts, ‘Driving Demand for Broadband Networks and Services’ offers a set of best practices and recommendations aimed at promoting broadband demand.  The broadband demand gap is defined as individuals and households that could buy a broadband subscription because they live in areas served by telecommunications carriers but do not do so because of either ...

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...

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

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.

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.

High power, ultra-broadband supercontinuum source based on highly GeO2 doped silica fiber

DEFF Research Database (Denmark)

Jain, Deepak; Sidharthan, Raghuraman; Moselund, Peter M.

2017-01-01

We demonstrate a 74 mol % GeO2 doped fiber for mid-infrared supercontinuum generation. Experiments ensure a highest output power for a broadest spectrum from 700nm to 3200nm from this fiber, while being pumped by a broadband 4 stage Erbium fiber based MOPA. The effect of repetition rate of pump...

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

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

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...

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…

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

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

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.

Chaotic Dynamics-Based Analysis of Broadband Piezoelectric Vibration Energy Harvesting Enhanced by Using Nonlinearity

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Zhongsheng Chen

2016-01-01

Full Text Available Nonlinear magnetic forces are always used to enlarge resonant bandwidth of vibration energy harvesting systems with piezoelectric cantilever beams. However, how to determine properly the distance between two magnets is one of the key engineering problems. In this paper, the Melnikov theory is introduced to overcome it. Firstly, the Melnikov state-space model of the nonlinear piezoelectric vibration energy harvesting (PVEH system is built. Based on it, chaotic dynamics mechanisms of achieving broadband PVEH by nonlinearity are exposed by potential function of the unperturbed nonlinear PVEH system. Then the corresponding Melnikov function of the nonlinear PVEH system is defined, based on which two Melnikov necessary conditions of determining the distance are obtained. Finally, numerical simulations are done to testify the theoretic results. The results demonstrate that the distance is closely related to the excitation amplitude and frequency once geometric and material parameters are fixed. Under a single-frequency excitation, the nonlinear PVEH system can generate a periodic vibration around a stable point, a large-amplitude vibration around two stable points, or a chaotic vibration. The proposed method is very valuable for optimally designing and utilizing nonlinear broadband PVEH devices in engineering applications.

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

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.

A broadband metamaterial absorber based on multi-layer graphene in the terahertz region

Science.gov (United States)

Fu, Pan; Liu, Fei; Ren, Guang Jun; Su, Fei; Li, Dong; Yao, Jian Quan

2018-06-01

A broadband metamaterial absorber, composed of the periodic graphene pattern on SiO2 dielectric with the double layer graphene films inserted in it and all of them backed by metal plan, is proposed and investigated. The simulation results reveal that the wide absorption band can be flexibly tuned between the low-frequency band and the high-frequency band by adjusting graphene's Fermi level. The absorption can achieve 90% in 5.50-7.10 THz, with Fermi level of graphene is 0.3 eV, while in 6.98-9.10 THz with Fermi level 0.6 eV. Furthermore, the proposed structure can be switched from reflection (>81%) to absorption (>90%) over the whole operation band, when the Fermi level of graphene varies from 0 to 0.6 eV. Besides, the proposed absorber is insensitive to the polarization and can work over a wide range of incident angle. Compared with the previous broadband absorber, our graphene based wideband terahertz absorber can enable a wide application of high performance terahertz devices, including sensors, imaging devices and electro-optic switches.

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

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

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.

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...

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...

Reconstrucción de Atmósferas Sonoras Tridimensionales

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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.

Microfluidic-based Broadband Measurements of Fluid Permittivity and Permeability to 100 GHz

Science.gov (United States)

Little, Charles A. E.

This dissertation concerns the development of unique microfluidic microwave devices and associated microwave calibrations to quantitatively extract the broadband permittivity and permeability of fluids between 100 kHz and 110 GHz. The devices presented here consist of SU-8- and PDMS-based microfluidic channels integrated lithographically with coplanar waveguides (CPWs), measured via an external vector network analyzer (VNA). By applying our hybrid set of microwave calibrations to the raw data we extract distributed circuit parameters, representative of the electromagnetic response of the microfluidic channel. We then correlate these parameters to the permittivity and permeability of the fluid within the channels. We are primarily focused on developing devices, calibrations, and analyses to characterize various chemical and biological systems. The small fluid volumes and overall scale of our devices lends the technique to point-of-care blood and cell analysis, as well as to the analysis of high-value chemicals. Broadband microwave microfluidics is sensitive to three primary categories of phenomena: Ionic, dipolar, and magnetic resonances. All three can occur in complex fluids such as blood, proteins and particle suspensions. In order to make quantitative measurements, we need to be able to model and separate all three types of responses. Here we first measure saline solutions (NaCl and water) as an ideal system to better understanding both the ionic and dipolar response. Specifically, we are targeting the electrical double-layer (EDL) response, an ionic effect, which dominates over the intrinsic fluid response at lower frequencies. We have found that the EDL response for saline obeys a strict Debye-type relaxation model, the frequency response of which is dependent solely on the conductivity of the solution. To develop a better understanding of the magnetic response, we first measure magnetic nanoparticles; showing it is possible to detect the magnetic resonances of

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

Broadband Impedance Transformer Based on Asymmetric Coupled Transmission Lines in Nonhomogeneous Medium

DEFF Research Database (Denmark)

Zhurbenko, Vitaliy; Krozer, Viktor; Meincke, Peter

2007-01-01

A new broadband quarter-wavelength impedance transformer based on an asymmetric coupled line section is presented. The bandwidth of the coupled line transformer is extended with the help of an interconnecting transmission line. An analytical model for the transformer is developed. The analysis...... of the structure reveals that a fractional bandwidth of more than 100% at –20 dB reflection level can be achieved with such a structure. An experimental transformer circuit has been designed, fabricated and tested. Theoretical and experimental results are fair agreement and confirm the established theory...

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

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

Broadband sub-THz spectroscopy modules integrated in 65-nm CMOS technology

NARCIS (Netherlands)

Matters-Kammerer, M.K.; van Goor, D.; Tripodi, L.

2017-01-01

The design and characterization of a broadband 20-480 GHz continuously tuneable on-chip spectrometer based on non-linear transmission lines in 65-nm CMOS technology is presented. The design procedure of the sampler that detects the ultra-broadband signal from the transmitter in time and frequency

Broadband image sensor array based on graphene-CMOS integration

Science.gov (United States)

Goossens, Stijn; Navickaite, Gabriele; Monasterio, Carles; Gupta, Shuchi; Piqueras, Juan José; Pérez, Raúl; Burwell, Gregory; Nikitskiy, Ivan; Lasanta, Tania; Galán, Teresa; Puma, Eric; Centeno, Alba; Pesquera, Amaia; Zurutuza, Amaia; Konstantatos, Gerasimos; Koppens, Frank

2017-06-01

Integrated circuits based on complementary metal-oxide-semiconductors (CMOS) are at the heart of the technological revolution of the past 40 years, enabling compact and low-cost microelectronic circuits and imaging systems. However, the diversification of this platform into applications other than microcircuits and visible-light cameras has been impeded by the difficulty to combine semiconductors other than silicon with CMOS. Here, we report the monolithic integration of a CMOS integrated circuit with graphene, operating as a high-mobility phototransistor. We demonstrate a high-resolution, broadband image sensor and operate it as a digital camera that is sensitive to ultraviolet, visible and infrared light (300-2,000 nm). The demonstrated graphene-CMOS integration is pivotal for incorporating 2D materials into the next-generation microelectronics, sensor arrays, low-power integrated photonics and CMOS imaging systems covering visible, infrared and terahertz frequencies.

Governing Practices of Cable Television and Its Relationship to the Telephone Common Carriers.

Science.gov (United States)

Miller, David Martin

This dissertation examines the legislative, economic, political, and technological influences that have governed cable television (CATV) during the years of its existence. Separate chapters deal with the beginnings of CATV, the economics of CATV, the problems incurred in CATV franchising, and the relationship of CATV to the telephone common…

Temperature and Pressure Sensors Based on Spin-Allowed Broadband Luminescence of Doped Orthorhombic Perovskite Structures

Science.gov (United States)

Eldridge, Jeffrey I. (Inventor); Chambers, Matthew D. (Inventor)

2014-01-01

Systems and methods that are capable of measuring pressure or temperature based on luminescence are discussed herein. These systems and methods are based on spin-allowed broadband luminescence of sensors with orthorhombic perovskite structures of rare earth aluminates doped with chromium or similar transition metals, such as chromium-doped gadolinium aluminate. Luminescence from these sensors can be measured to determine at least one of temperature or pressure, based on either the intense luminescence of these sensors, even at high temperatures, or low temperature techniques discussed herein.

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

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.

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.

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)

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

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

Gain-assisted broadband ring cavity enhanced spectroscopy

Science.gov (United States)

Selim, Mahmoud A.; Adib, George A.; Sabry, Yasser M.; Khalil, Diaa

2017-02-01

Incoherent broadband cavity enhanced spectroscopy can significantly increase the effective path length of light-matter interaction to detect weak absorption lines over broad spectral range, for instance to detect gases in confined environments. Broadband cavity enhancement can be based on the decay time or the intensity drop technique. Decay time measurement is based on using tunable laser source that is expensive and suffers from long scan time. Intensity dependent measurement is usually reported based on broadband source using Fabry-Perot cavity, enabling short measurement time but suffers from the alignment tolerance of the cavity and the cavity insertion loss. In this work we overcome these challenges by using an alignment-free ring cavity made of an optical fiber loop and a directional coupler, while having a gain medium pumped below the lasing threshold to improve the finesse and reduce the insertion loss. Acetylene (C2H2) gas absorption is measured around 1535 nm wavelength using a semiconductor optical amplifier (SOA) gain medium. The system is analyzed for different ring resonator forward coupling coefficient and loses, including the 3-cm long gas cell insertion loss and fiber connector losses used in the experimental verification. The experimental results are obtained for a coupler ratio of 90/10 and a fiber length of 4 m. The broadband source is the amplified spontaneous emission of another SOA and the output is measured using a 70pm-resolution optical spectrum analyzer. The absorption depth and the effective interaction length are improved about an order of magnitude compared to the direct absorption of the gas cell. The presented technique provides an engineering method to improve the finesse and, consequently the effective length, while relaxing the technological constraints on the high reflectivity mirrors and free-space cavity alignment.

Semiconductor Quantum Dash Broadband Emitters: Modeling and Experiments

KAUST Repository

Khan, Mohammed Zahed Mustafa

2013-10-01

Broadband light emitters operation, which covers multiple wavelengths of the electromagnetic spectrum, has been established as an indispensable element to the human kind, continuously advancing the living standard by serving as sources in important multi-disciplinary field applications such as biomedical imaging and sensing, general lighting and internet and mobile phone connectivity. In general, most commercial broadband light sources relies on complex systems for broadband light generation which are bulky, and energy hungry. \\tRecent demonstration of ultra-broadband emission from semiconductor light sources in the form of superluminescent light emitting diodes (SLDs) has paved way in realization of broadband emitters on a completely novel platform, which offered compactness, cost effectiveness, and comparatively energy efficient, and are already serving as a key component in medical imaging systems. The low power-bandwidth product is inherent in SLDs operating in the amplified spontaneous emission regime. A quantum leap in the advancement of broadband emitters, in which high power and large bandwidth (in tens of nm) are in demand. Recently, the birth of a new class of broadband semiconductor laser diode (LDs) producing multiple wavelength light in stimulated emission regime was demonstrated. This very recent manifestation of a high power-bandwidth-product semiconductor broadband LDs relies on interband optical transitions via quantum confined dot/dash nanostructures and exploiting the natural inhomogeneity of the self-assembled growth technology. This concept is highly interesting and extending the broad spectrum of stimulated emission by novel device design forms the central focus of this dissertation. \\tIn this work, a simple rate equation numerical technique for modeling InAs/InP quantum dash laser incorporating the properties of inhomogeneous broadening effect on lasing spectra was developed and discussed, followed by a comprehensive experimental analysis

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

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

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

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.

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.

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.

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.

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

Service Class Resource Management For Green Wireless-Optical Broadband Access NetworksWOBAN

Directory of Open Access Journals (Sweden)

SRUTHY.S

2015-08-01

Full Text Available Abstract-Broadband access networks have become an essential part of worldwide communication systems because of the exponential growth of broadband services such as video on demand high definition TV internet protocol TV and video conferencing. Exponential growth in the volume of wireless data boosted by the growing popularity of mobile devices such as smartphone and tablets has forced the telecommunication industries to rethink the way networks are currently designed and to focus on the development of high-capacity mobile broadband networks. In response to this challenge researchers have been working toward the development of an integrated wireless optical broadband access network. Two major candidate technologies which are currently known for their high capacity as well as quality of service QoS for multimedia traffic are passive optical networks PON and fourth generation 4G wireless networks. PON is a wired access technology well known for its cost efficiency and high capacity whereas 4G is a wireless broadband access technology which has achieved broad market acceptance because of its ease of deployment ability to offer mobility and its cost efficiency. Integration of PON and 4G technologies in the form of wireless-optical broadband access networks offers advantages such as extension of networks in rural areas support for mobile broadband services and quick deployment of broadband networks. These two technologies however have different design architectures for handling broadband services that require quality of service. For example 4G networks use traffic classification for supporting different QoS demands whereas the PON architecture has no such mechanism to differentiate between types of traffic. These two technologies also differ in their power saving mechanisms. Propose a service class mapping for the integrated PON-4G network which is based on the MG1 queuing model and class-based power saving mechanism which significantly improves the

Broadband in schools: towards a definition and model of broadband for South African schools

CSIR Research Space (South Africa)

Ford, Merryl

2017-05-01

Full Text Available South Africa is about to provide broadband internet connectivity to all schools in the country via the implementation of the national broadband policy. The challenge is to ensure a balance between the schools’ demand-side usage and supply...

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.

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

Measurement uncertainty in broadband radiofrequency radiation level measurements

Directory of Open Access Journals (Sweden)

Vulević Branislav D.

2014-01-01

Full Text Available For the evaluation of measurement uncertainty in the measurement of broadband radio frequency radiation, in this paper we propose a new approach based on the experience of the authors of the paper with measurements of radiofrequency electric field levels conducted in residential areas of Belgrade and over 35 municipalities in Serbia. The main objective of the paper is to present practical solutions in the evaluation of broadband measurement uncertainty for the in-situ RF radiation levels. [Projekat Ministarstva nauke Republike Srbije, br. III43009

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

Broadband giant-refractive-index material based on mesoscopic space-filling curves

Science.gov (United States)

Chang, Taeyong; Kim, Jong Uk; Kang, Seung Kyu; Kim, Hyowook; Kim, Do Kyung; Lee, Yong-Hee; Shin, Jonghwa

2016-08-01

The refractive index is the fundamental property of all optical materials and dictates Snell's law, propagation speed, wavelength, diffraction, energy density, absorption and emission of light in materials. Experimentally realized broadband refractive indices remain 1,800 resulting from a mesoscopic crystal with a dielectric constant greater than three million. This gigantic enhancement effect originates from the space-filling curve concept from mathematics. The principle is inherently very broad band, the enhancement being nearly constant from zero up to the frequency of interest. This broadband giant-refractive-index medium promises not only enhanced resolution in imaging and raised fundamental absorption limits in solar energy devices, but also compact, power-efficient components for optical communication and increased performance in many other applications.

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.

Exhaled breath profiling using broadband quantum cascade laser-based spectroscopy in healthy children and children with asthma and cystic fibrosis.

Science.gov (United States)

van Mastrigt, E; Reyes-Reyes, A; Brand, K; Bhattacharya, N; Urbach, H P; Stubbs, A P; de Jongste, J C; Pijnenburg, M W

2016-04-08

Exhaled breath analysis is a potential non-invasive tool for diagnosing and monitoring airway diseases. Gas chromatography-mass spectrometry and electrochemical sensor arrays are the main techniques to detect volatile organic compounds (VOC) in exhaled breath. We developed a broadband quantum cascade laser spectroscopy technique for VOC detection and identification. The objective of this study was to assess the repeatability of exhaled breath profiling with broadband quantum cascade laser-based spectroscopy and to explore the clinical applicability by comparing exhaled breath samples from healthy children with those from children with asthma or cystic fibrosis (CF). Healthy children and children with stable asthma or stable CF, aged 6-18 years, were included. Two to four exhaled breath samples were collected in Tedlar bags and analyzed by quantum cascade laser spectroscopy to detect VOCs with an absorption profile in the wavenumber region between 832 and 1262.55 cm(-1). We included 35 healthy children, 39 children with asthma and 15 with CF. Exhaled breath VOC profiles showed poor repeatability (Spearman's rho  =  0.36 to 0.46) and agreement of the complete profiles. However, we were able to discriminate healthy children from children with stable asthma or stable CF and identified VOCs that were responsible for this discrimination. Broadband quantum cascade laser-based spectroscopy detected differences in VOC profiles in exhaled breath samples between healthy children and children with asthma or CF. The combination of a relatively easy and fast method and the possibility of molecule identification makes broadband quantum cascade laser-based spectroscopy attractive to investigate the diagnostic and prognostic potential of volatiles in exhaled breath.

Analysis of the Proposed Ghana Broadband Strategy

DEFF Research Database (Denmark)

Williams, Idongesit; Botwe, Yvonne

This project studied the Ghana Broadband Strategy with the aim of evaluating the recommendations in the strategy side by side the broadband development in Ghana. The researchers conducted interviews both officially and unofficially with ICT stakeholders, made observations, studied Government...... intervention policies recommended in the Ghana broadband policy is used to evaluate the broadband market to find out whether the strategy consolidates with the Strengths and opportunities of the market and whether it corrects the anomalies that necessitate the weaknesses and threats to the market....... The strategy did address some threats and weaknesses of the broadband market. It also consolidated on some strengths and opportunities of the broadband market. The researchers also discovered that a market can actually grow without a policy. But a market will grow faster if a well implemented policy is guiding...

SCRLH-TL Based Sequential Rotation Feed Network for Broadband Circularly Polarized Antenna Array

Directory of Open Access Journals (Sweden)

B. F. Zong

2016-04-01

Full Text Available In this paper, a broadband circularly polarized (CP microstrip antenna array using composite right/left-handed transmission line (SCRLH-TL based sequential rotation (SR feed network is presented. The characteristics of a SCRLH-TL are initially investigated. Then, a broadband and low insertion loss 45º phase shifter is designed using the SCRLH-TL and the phase shifter is employed in constructing a SR feed network for CP antenna array. To validate the design method of the SR feed network, a 2×2 antenna array comprising sequentially rotated coupled stacked CP antenna elements is designed, fabricated and measured. Both the simulated and measured results indicate that the performances of the antenna element are further enhanced when the SR network is used. The antenna array exhibits the VSWR less than 1.8 dB from 4 GHz to 7 GHz and the 3 dB axial ratio (AR from 4.4 GHz to 6.8 GHz. Also, high peak gain of 13.7 dBic is obtained. Besides, the normalized radiation patterns at the operating frequencies are symmetrical and the side lobe levels are low at φ=0º and φ=90º.

Peramalan Pengguna Broadband di Indonesia [Forecasting of Broadband Users in Indonesia

Directory of Open Access Journals (Sweden)

Azwar Aziz

2016-07-01

Full Text Available Negara Indonesia memiliki peluang yang sangat besar untuk merealisasikan potensi pitalebar, mengingat Indonesia memiliki jumlah penduduk 253 juta orang dan pengguna internet 88,1 juta orang pada tahun 2014. Di sisi lain sektor komunikasi (salah satunya termasuk telekomunikasi merupakan satu-satunya sektor yang secara konsisten memberikan kontribusi pertumbuhan terhadap Pendapatan Domestik Bruto (PDB sebesar dua angka (double digit. Kemudian peran penting pemerintah adalah selalu mengantisipasi dalam membuat regulasi telekomunikasi, salah satu nya untuk mempercepat penggelaran prasarana pitalebar, seperti menerbitkan Peraturan Presiden RI. Nomor 96 Tahun 2014 tentang Rencana Pitalebar Indonesia 2014 – 2019.  Secara riil pembangunan jaringan pitalebar di Indonesia masih dilakukan di kota-kota besar, mengingat pengguna telekomunikasi sebagian besar berada di kota-kota besar. Selain itu perangkat hanset atau handphone, ketersediaan di pasaran masih terbatas dan harganya masih mahal. Kajian ini menggunakan metodologi penelitian kuantitatif dengan menghitung peramalan dan kualitatif, dengan melakukan observasi atau pengamatan langsung ke lapangan kepada perusahaan Telkom, Telkomsel, XL Axiata dan Indosat. Selanjutnya hasil penelitian ini diperoleh lima faktor yang mempengaruhi penggunaan pitalebar yaitu jumlah penduduk, produk domestik bruto, pendapatan per kapita, laju pertumbuhan ekonomi dan inflasi, dan laju penetrasi. Selain itu, hasil pitalebar menunjukkan pengguna pitalebar lima tahun kedepan selalu meningkat.*****Indonesia has a tremendous opportunity to implement the potential of broadband, as Indonesia has a population of 253 million people and 88.1 million Internet users in 2014. On the other hand, the communication sector (one of them including telecommunications is the only sector that is consistently contributed to the growth of Gross Domestic Product (GDP as many as two numbers (double-digit. Then the important role of government is

Broadband-Emitting 2 D Hybrid Organic-Inorganic Perovskite Based on Cyclohexane-bis(methylamonium) Cation.

Science.gov (United States)

Neogi, Ishita; Bruno, Annalisa; Bahulayan, Damodaran; Goh, Teck Wee; Ghosh, Biplab; Ganguly, Rakesh; Cortecchia, Daniele; Sum, Tze Chien; Soci, Cesare; Mathews, Nripan; Mhaisalkar, Subodh Gautam

2017-10-09

A new broadband-emitting 2 D hybrid organic-inorganic perovskite (CyBMA)PbBr 4 based on highly flexible cis-1,3-bis(methylaminohydrobromide)cyclohexane (CyBMABr) core has been designed, synthesized, and investigated, highlighting the effects of stereoisomerism of the templating cation on the formation and properties of the resulting perovskite. The new 2 D material has high exciton binding energy of 340 meV and a broad emission spanning from 380 to 750 nm, incorporating a prominent excitonic band and a less intense broad peak at room temperature. Significant changes in the photoluminescence (PL) spectrum were observed at lower temperatures, showing remarkable enhancement in the intensity of the broadband at the cost of excitonic emission. Temperature-dependent PL mapping indicates the effective role of only a narrow band of excitonic absorption in the generation of the active channel for emission. Based on the evidences obtained from the photophysical investigations, we attributed the evolution of the broad B-band of (CyBMA)PbBr 4 to excitonic self-trapped states. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

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

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.

Compact solar autoclave based on steam generation using broadband light-harvesting nanoparticles.

Science.gov (United States)

Neumann, Oara; Feronti, Curtis; Neumann, Albert D; Dong, Anjie; Schell, Kevin; Lu, Benjamin; Kim, Eric; Quinn, Mary; Thompson, Shea; Grady, Nathaniel; Nordlander, Peter; Oden, Maria; Halas, Naomi J

2013-07-16

The lack of readily available sterilization processes for medicine and dentistry practices in the developing world is a major risk factor for the propagation of disease. Modern medical facilities in the developed world often use autoclave systems to sterilize medical instruments and equipment and process waste that could contain harmful contagions. Here, we show the use of broadband light-absorbing nanoparticles as solar photothermal heaters, which generate high-temperature steam for a standalone, efficient solar autoclave useful for sanitation of instruments or materials in resource-limited, remote locations. Sterilization was verified using a standard Geobacillus stearothermophilus-based biological indicator.

Compact solar autoclave based on steam generation using broadband light-harvesting nanoparticles

Science.gov (United States)

Neumann, Oara; Feronti, Curtis; Neumann, Albert D.; Dong, Anjie; Schell, Kevin; Lu, Benjamin; Kim, Eric; Quinn, Mary; Thompson, Shea; Grady, Nathaniel; Nordlander, Peter; Oden, Maria; Halas, Naomi J.

2013-01-01

The lack of readily available sterilization processes for medicine and dentistry practices in the developing world is a major risk factor for the propagation of disease. Modern medical facilities in the developed world often use autoclave systems to sterilize medical instruments and equipment and process waste that could contain harmful contagions. Here, we show the use of broadband light-absorbing nanoparticles as solar photothermal heaters, which generate high-temperature steam for a standalone, efficient solar autoclave useful for sanitation of instruments or materials in resource-limited, remote locations. Sterilization was verified using a standard Geobacillus stearothermophilus-based biological indicator. PMID:23836642

Broadband nanophotonic waveguides and resonators based on epitaxial GaN thin films

Energy Technology Data Exchange (ETDEWEB)

Bruch, Alexander W.; Xiong, Chi; Leung, Benjamin; Poot, Menno; Han, Jung; Tang, Hong X., E-mail: hong.tang@yale.edu [Department of Electrical Engineering, Yale University, New Haven, Connecticut 06511 (United States)

2015-10-05

We demonstrate broadband, low loss optical waveguiding in single crystalline GaN grown epitaxially on c-plane sapphire wafers through a buffered metal-organic chemical vapor phase deposition process. High Q optical microring resonators are realized in near infrared, infrared, and near visible regimes with intrinsic quality factors exceeding 50 000 at all the wavelengths we studied. TEM analysis of etched waveguide reveals growth and etch-induced defects. Reduction of these defects through improved material and device processing could lead to even lower optical losses and enable a wideband photonic platform based on GaN-on-sapphire material system.

Energy savings in mobile broadband network based on load predictions

DEFF Research Database (Denmark)

Samulevicius, Saulius; Pedersen, Torben Bach; Sørensen, Troels Bundgaard

2012-01-01

Abstract—The deployment of new network equipment is resulting in increasing energy consumption in mobile broadband networks (MBNs). This contributes to higher CO2 emissions. Over the last 10 years MBNs have grown considerably, and are still growing to meet the evolution in traffic volume carried...

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.

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...

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.

47 CFR 27.1305 - Shared wireless broadband network.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Shared wireless broadband network. 27.1305... broadband network. The Shared Wireless Broadband Network developed by the 700 MHz Public/Private Partnership must be designed to meet requirements associated with a nationwide, public safety broadband network. At...

47 CFR 90.1405 - Shared wireless broadband network.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Shared wireless broadband network. 90.1405... broadband network. The Shared Wireless Broadband Network developed by the 700 MHz Public/Private Partnership must be designed to meet requirements associated with a nationwide, public safety broadband network. At...

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.

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...

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.

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...

Switched Broadband Services For The Home

Science.gov (United States)

Sawyer, Don M.

1990-01-01

In considering the deployment of fiber optics to the residence, two critical questions arise: what are the leading services that could be offered to justify the required investment; and what is the nature of the business that would offer these services to the consumer ? This talk will address these two questions together with the related issue of how the "financial engine" of today's television distribution infrastructure - TV advertising - would be affected by an open access system based on fiber optics coupled with broadband switching. On the business side, the talk concludes that the potential for open ended capacity expansion, fair competition between service providers, and new interactive services inherent in an open access, switched broadband system are the critical items in differentiating it from existing video and TV distribution systems. On the question of broadband services, the talk will highlight several new opportunities together with some findings from recent market research conducted by BNR. The talk will show that there are variations on existing services plus many new services that could be offered and which have real consumer appeal. The postulated open access system discussed here is visualized as having ultimately 1,000 to 2,000 video channels available to the consumer. Although this may appear to hopelessly fragment the TV audience and destroy the current TV advertising infrastructure, the technology of open access, switched broadband will present many new advertising techniques, which have the potential to be far more effective than those available today. Some of these techniques will be described in this talk.

Compact, low-loss and broadband photonic crystal circulator based on a star-type ferrite rod

Directory of Open Access Journals (Sweden)

Xiang Xi

Full Text Available We propose and investigate a compact, low-loss and broadband circulator based on a star-type ferrite rod in two-dimensional square-lattice photonic crystals. Only one ferrite rod is required to be inserted in our structure. Firstly, the performances of circulator based on the star-type, circle, and square ferrite rod are compared, showing that the circulator with the star-type ferrite rod performs better than the other two ones. And then, based on the star-type ferrite rod circulator, four cases of improvement, in which the background rods around the center ferrite rod are replaced respectively by the backward-triangle, forward-triangle, backward-semicircle, and forward-semicircle rods, are investigated to modulate the coupling between the center magneto-optical micro-cavity and the corresponding waveguides. The results show that, with proper parameters, all the four cases can greatly improve the output properties of the circulator, and different cases have its own advantages. The mechanism behind these improvements is also discussed. Finite-element method is used to calculate the characteristics of the circulator and Nelder-Mead optimization method is employed to obtain the optimized parameters. The ideas presented here are useful for designing broadband, low insertion loss, and high-isolation circulators which have potential application in integrated photonic crystal devices. Keywords: Photonic crystals, Circulator, Magneto-optical material, Photonic crystal waveguides

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.

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.

A broadband electromagnetic UT system

International Nuclear Information System (INIS)

Repplinger, W.; Salzburger, H.J.

1985-01-01

An ultrasonic testing system based on contactless electromagnetic acoustic (E.M.A.) transduction has been developed by which broadband ultrasonic pulses are excited. This system overcomes disadvantages of usual E.M.A. transducers with meanderlike coil configuration, namely the excitation of narrowband pulses and the symmetrical radiation pattern. By dividing up a meanderlike coil into single elements and a time-delayed firing of the elements, whereby the time delay is given by the distance of the elements and the phase velocity of the wave propagating along the surface, the ultrasonic pulse radiated in one preferred direction becomes broadband by constructive interference. The signals radiated in the opposite direction do no more interfere. Its amplitude is smaller than that of the other direction, so that the transducer becomes uni-directional. This technique can be applied for the excitation of all dispersionless waves (bulk waves and guided waves)

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.

Design and fabrication of broadband rugate filter

International Nuclear Information System (INIS)

Zhang Jun-Chao; Fang Ming; Shao Yu-Chuan; Jin Yun-Xia; He Hong-Bo

2012-01-01

The design and the deposition of a rugate filter for broadband applications are discussed. The bandwidth is extended by increasing the rugate period continuously with depth. The width and the smoothness of the reflection band with the distribution of the periods are investigated. The improvement of the steepness of the stopband edges and the suppression of the side lobes in the transmission zone are realized by adding two apodized rugate structures with fixed periods at the external broadband rugate filter interfaces. The rapidly alternating deposition technology is used to fabricate a rugate filter sample. The measured transmission spectrum with a reflection bandwidth of approximately 505 nm is close to that of the designed broadband rugate filter except a transmittance peak in the stopband. Based on the analysis of the cross-sectional scanning electron microscopic image of the sample, it is found that the transmission peak is most likely to be caused by the instability of the deposition rate. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

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.

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. 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(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. 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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

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

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

Principles of broadband switching and networking

CERN Document Server

Liew, Soung C

2010-01-01

An authoritative introduction to the roles of switching and transmission in broadband integrated services networks Principles of Broadband Switching and Networking explains the design and analysis of switch architectures suitable for broadband integrated services networks, emphasizing packet-switched interconnection networks with distributed routing algorithms. The text examines the mathematical properties of these networks, rather than specific implementation technologies. Although the pedagogical explanations in this book are in the context of switches, many of the fundamenta

Technologies for developing an advanced intelligent ATM with self-defence capabilities

Science.gov (United States)

Sako, Hiroshi

2010-01-01

We have developed several technologies for protecting automated teller machines. These technologies are based mainly on pattern recognition and are used to implement various self-defence functions. They include (i) banknote recognition and information retrieval for preventing machines from accepting counterfeit and damaged banknotes and for retrieving information about detected counterfeits from a relational database, (ii) form processing and character recognition for preventing machines from accepting remittance forms without due dates and/or insufficient payment, (iii) person identification to prevent machines from transacting with non-customers, and (iv) object recognition to guard machines against foreign objects such as spy cams that might be surreptitiously attached to them and to protect users against someone attempting to peek at their user information such as their personal identification number. The person identification technology has been implemented in most ATMs in Japan, and field tests have demonstrated that the banknote recognition technology can recognise more then 200 types of banknote from 30 different countries. We are developing an "advanced intelligent ATM" that incorporates all of these technologies.

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.

Broadband infrared metamaterial absorber based on anodic aluminum oxide template

Science.gov (United States)

Yang, Jingfan; Qu, Shaobo; Ma, Hua; Wang, Jiafu; Yang, Shen; Pang, Yongqiang

2018-05-01

In this work, a broadband infrared metamaterial absorber is proposed based on trapezoid-shaped anodic aluminum oxide (AAO) template. Unlike traditional metamaterial absorber constructed from metal-dielectric-metal sandwich structure, our proposed absorber is composed of trapezoid-shaped AAO template with metallic nanowires inside. The infrared absorption efficiency is numerically calculated and the mechanism analysis is given in the paper. Owing to the superposition of multiple resonances produced by the nanowires with different heights, the infrared metamatrial absorber can keep high absorption efficiency during broad working wavelength band from 3.4 μm to 6.1 μm. In addition, the resonance wavelength is associated with the height of nanowires, which indicates that the resonance wavelength can be modulated flexibly through changing the heights of nanowires. This kind of design can also be adapted to other wavelength regions.

Multilayer tungsten-alumina-based broadband light absorbers for high-temperature applications

DEFF Research Database (Denmark)

Chirumamilla, Manohar; Roberts, Alexander Sylvester; Ding, Fei

2016-01-01

Efficient broadband absorption of visible and near-infrared light by low quality-factor metal-insulator-metal (MIM) resonators using refractory materials is reported. Omnidirectional absorption of incident light for broad angles of incidence and polarization insensitivity are observed for the fab...

Estimating carbon dioxide fluxes from temperate mountain grasslands using broad-band vegetation indices

Directory of Open Access Journals (Sweden)

G. Wohlfahrt

2010-02-01

Full Text Available The broad-band normalised difference vegetation index (NDVI and the simple ratio (SR were calculated from measurements of reflectance of photosynthetically active and short-wave radiation at two temperate mountain grasslands in Austria and related to the net ecosystem CO₂ exchange (NEE measured concurrently by means of the eddy covariance method. There was no significant statistical difference between the relationships of midday mean NEE with narrow- and broad-band NDVI and SR, measured during and calculated for that same time window, respectively. The skill of broad-band NDVI and SR in predicting CO₂ fluxes was higher for metrics dominated by gross photosynthesis and lowest for ecosystem respiration, with NEE in between. A method based on a simple light response model whose parameters were parameterised based on broad-band NDVI allowed to improve predictions of daily NEE and is suggested to hold promise for filling gaps in the NEE time series. Relationships of CO₂ flux metrics with broad-band NDVI and SR however generally differed between the two studied grassland sites indicting an influence of additional factors not yet accounted for.

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

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

Broadband terahertz generation using the semiconductor-metal transition in VO2

Directory of Open Access Journals (Sweden)

Nicholas A. Charipar

2016-01-01

Full Text Available We report the design, fabrication, and characterization of broadband terahertz emitters based on the semiconductor-metal transition in thin film VO2 (vanadium dioxide. With the appropriate geometry, picosecond electrical pulses are generated by illuminating 120 nm thick VO2 with 280 fs pulses from a femtosecond laser. These ultrafast electrical pulses are used to drive a simple dipole antenna, generating broadband terahertz radiation.

Dual electrically and thermally responsive broadband reflectors based on polymer network stabilized chiral nematic liquid crystals: the role of crosslink density

NARCIS (Netherlands)

Khandelwal, H.; Timmermans, G.H.; Debije, M.G.; Schenning, A.P.H.J.

2016-01-01

A broadband reflector based on a polymer stabilized chiral nematic liquid crystal has been fabricated. The reflection bandwidth can be manually controlled by an electric field and autonomously by temperature.

The social surplus of broadband initiatives in compulsory education

Directory of Open Access Journals (Sweden)

David Peter Parsons

2016-10-01

Full Text Available In 2010, the New Zealand government embarked upon an ambitious programme of broadband infrastructure investment, a process that will continue until at least 2019. Part of this investment is specifically targeted at compulsory education, with initiatives that include bringing fibre connections to the school gate, supporting on-site network upgrades (including wireless and providing teaching, learning and support services delivered through these networks. Such investments are not made without some projections of the likely rate of return, but calculating return on investment (ROI in educational broadband is complex, as it encompasses a range of factors. This article reports on an interview-based study engaging a range of stakeholders in educational broadband provision. The study utilises a research model that considers the various elements of social surplus, namely; producer surplus (savings, producer surplus (profit and consumer surplus (perceived value over and above cost, to explore the elements of social surplus that have been used to define educational broadband ROI calculations and justify the scale of investment. The results indicate that all three components of social surplus are relevant, though the concept of profit can only be seen in the broader context of long term contributions to the economy. A note of caution is that projections of ROI based only on positive returns fail to acknowledge the potential for some innovations to actually increase costs. Further, purely quantitative models do not properly take into account qualitative components of consumer surplus.

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.

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.

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.

Advent of broadband public-switched communications

Science.gov (United States)

Casey, John J.

1992-02-01

Advances in data communications infrastructure, display technology, and man-machine interfaces have changed business applications and the requirements of public network data transport. These changes have created opportunities for a new generation of public broadband services to more efficiently extend high speed communications capabilities beyond the customer premises. This paper provides a view of the technology and market evolution of these public broadband data communications services, and suggests early customer networked applications that justify the deployment of a public switched broadband network infrastructure.

Si Substrate-Based Meta materials for Ultra broadband Perfect Absorption in Visible Regime

International Nuclear Information System (INIS)

Han, Q.; Jin, L.; Fu, Y.; Yu, W.; Yu, W.

2014-01-01

We report the broadband efficient light absorbing property of a structure of quadrangular frustum pyramid array in visible regime. The structure can absorb light efficiently with an average absorptivity of 0.98 over the whole visible waveband. In addition, it is found that this kind of super light absorbing can maintain an average of 0.9 for a wide incident angle range. The perfect absorbing property of the meta material-based nano ring array is attributed to the effect of the Fabry-Perot resonance. The structure is possible to be used as a type of Si photonics devices in future photonic circuits

Near-perfect broadband absorption from hyperbolic metamaterial nanoparticles

Science.gov (United States)

Riley, Conor T.; Smalley, Joseph S. T.; Brodie, Jeffrey R. J.; Fainman, Yeshaiahu; Sirbuly, Donald J.; Liu, Zhaowei

2017-02-01

Broadband absorbers are essential components of many light detection, energy harvesting, and camouflage schemes. Current designs are either bulky or use planar films that cause problems in cracking and delamination during flexing or heating. In addition, transferring planar materials to flexible, thin, or low-cost substrates poses a significant challenge. On the other hand, particle-based materials are highly flexible and can be transferred and assembled onto a more desirable substrate but have not shown high performance as an absorber in a standalone system. Here, we introduce a class of particle absorbers called transferable hyperbolic metamaterial particles (THMMP) that display selective, omnidirectional, tunable, broadband absorption when closely packed. This is demonstrated with vertically aligned hyperbolic nanotube (HNT) arrays composed of alternating layers of aluminum-doped zinc oxide and zinc oxide. The broadband absorption measures >87% from 1,200 nm to over 2,200 nm with a maximum absorption of 98.1% at 1,550 nm and remains large for high angles. Furthermore, we show the advantages of particle-based absorbers by transferring the HNTs to a polymer substrate that shows excellent mechanical flexibility and visible transparency while maintaining near-perfect absorption in the telecommunications region. In addition, other material systems and geometries are proposed for a wider range of applications.

Low doses of X-rays induce prolonged and ATM-independent persistence of γH2AX foci in human gingival mesenchymal stem cells.

Science.gov (United States)

Osipov, Andreyan N; Pustovalova, Margarita; Grekhova, Anna; Eremin, Petr; Vorobyova, Natalia; Pulin, Andrey; Zhavoronkov, Alex; Roumiantsev, Sergey; Klokov, Dmitry Y; Eremin, Ilya

2015-09-29

Diagnostic imaging delivering low doses of radiation often accompany human mesenchymal stem cells (MSCs)-based therapies. However, effects of low dose radiation on MSCs are poorly characterized. Here we examine patterns of phosphorylated histone H2AX (γH2AX) and phospho-S1981 ATM (pATM) foci formation in human gingiva-derived MSCs exposed to X-rays in time-course and dose-response experiments. Both γH2AX and pATM foci accumulated linearly with dose early after irradiation (5-60 min), with a maximum induction observed at 30-60 min (37 ± 3 and 32 ± 3 foci/cell/Gy for γH2AX and pATM, respectively). The number of γH2AX foci produced by intermediate doses (160 and 250 mGy) significantly decreased (40-60%) between 60 and 240 min post-irradiation, indicating rejoining of DNA double-strand breaks. In contrast, γH2AX foci produced by low doses (20-80 mGy) did not change after 60 min. The number of pATM foci between 60 and 240 min decreased down to control values in a dose-independent manner. Similar kinetics was observed for pATM foci co-localized with γH2AX foci. Collectively, our results suggest differential DNA double-strand break signaling and processing in response to low vs. intermediate doses of X-rays in human MSCs. Furthermore, mechanisms governing the prolonged persistence of γH2AX foci in these cells appear to be ATM-independent.

Broadband Radio Service (BRS) and Educational Broadband Service (EBS) Transmitters

Data.gov (United States)

Department of Homeland Security — The Broadband Radio Service (BRS), formerly known as the Multipoint Distribution Service (MDS)/Multichannel Multipoint Distribution Service (MMDS), is a commercial...

Broadband Internet Based Service to Passengers and Crew On-board Aircraft

Science.gov (United States)

Azzarelli, Tony

2003-07-01

The Connexion by BoeingSM (CbB) global network will provide broadband information services to aircraft passengers and crews. Through this Ku-band (14 GHz (uplink) and 11/12 GHz (downlink)) satellite-based system, aircraft passengers and crew will no longer be limited to pre-packaged services, but instead will be able to access the full range of broadband services from their seats using their laptop, PDA or the on-board IFE console.The kind of services offered to passengers are based on the internet/intranet access via their own laptops and PDA (using Ethernet wired cable, or wireless 802.11b access), while those offered to the crew can range between various crew application (such as weather updates and travel information) and aircraft health monitoring.The CbB system is divided into four basic layers of infrastructure:(1) an airborne segment, i.e. the Aircraft Earth Station (AES) consisting of proprietary high gain antenna, transceivers and other on-board subsystems providing a nominal return link data rate of 1 Mbps and a forward link data rates up to 20 Mbps;(2) a space segment consisting of leased satellite transponders on existing in-orbit Geostationary satellites;(3) a ground segment consisting of one or more leased satellite land earth stations (LESs) and redundant interconnection facilities; and;(4) a network operations centre (NOC) segment.During 2003, trials with Lufthansa (DLH) and British Airways (BA) have proved very successful. This has resulted in the recent signing of an agreement with Lufthansa which calls for the Connexion by BoeingSM service to be installed on Lufthansa's fleet of approximately 80 long-haul aircraft, including Boeing 747-400 and Airbus A330 and A340 aircraft, beginning in early 2004. BA is expected to follow soon. In addition to the successful recent service demonstrations, both Japan Airlines (JAL) and Scandinavian Airlines System (SAS) have announced their intent to install the revolutionary service on their long-range aircraft.

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

Broadband electrical impedance matching for piezoelectric ultrasound transducers.

Science.gov (United States)

Huang, Haiying; Paramo, Daniel

2011-12-01

This paper presents a systematic method for designing broadband electrical impedance matching networks for piezoelectric ultrasound transducers. The design process involves three steps: 1) determine the equivalent circuit of the unmatched piezoelectric transducer based on its measured admittance; 2) design a set of impedance matching networks using a computerized Smith chart; and 3) establish the simulation model of the matched transducer to evaluate the gain and bandwidth of the impedance matching networks. The effectiveness of the presented approach is demonstrated through the design, implementation, and characterization of impedance matching networks for a broadband acoustic emission sensor. The impedance matching network improved the power of the acquired signal by 9 times.

Fixed Broadband Deployment Data: June, 2016 Status V2

Data.gov (United States)

Federal Communications Commission — This data contains status reports for June 2016, with revisions accepted through May 2017. All facilities-based broadband providers are required to file data with...

Phosphorene/ZnO Nano-Heterojunctions for Broadband Photonic Nonvolatile Memory Applications.

Science.gov (United States)

Hu, Liang; Yuan, Jun; Ren, Yi; Wang, Yan; Yang, Jia-Qin; Zhou, Ye; Zeng, Yu-Jia; Han, Su-Ting; Ruan, Shuangchen

2018-06-10

High-performance photonic nonvolatile memory combining photosensing and data storage with low power consumption ensures the energy efficiency of computer systems. This study first reports in situ derived phosphorene/ZnO hybrid heterojunction nanoparticles and their application in broadband-response photonic nonvolatile memory. The photonic nonvolatile memory consistently exhibits broadband response from ultraviolet (380 nm) to near infrared (785 nm), with controllable shifts of the SET voltage. The broadband resistive switching is attributed to the enhanced photon harvesting, a fast exciton separation, as well as the formation of an oxygen vacancy filament in the nano-heterojunction. In addition, the device exhibits an excellent stability under air exposure compared with reported pristine phosphorene-based nonvolatile memory. The superior antioxidation capacity is believed to originate from the fast transfer of lone-pair electrons of phosphorene. The unique assembly of phosphorene/ZnO nano-heterojunctions paves the way toward multifunctional broadband-response data-storage techniques. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Broadband standard dipole antenna for antenna calibration

Science.gov (United States)

Koike, Kunimasa; Sugiura, Akira; Morikawa, Takao

1995-06-01

Antenna calibration of EMI antennas is mostly performed by the standard antenna method at an open-field test site using a specially designed dipole antenna as a reference. In order to develop broadband standard antennas, the antenna factors of shortened dipples are theoretically investigated. First, the effects of the dipole length are analyzed using the induced emf method. Then, baluns and loads are examined to determine their influence on the antenna factors. It is found that transformer-type baluns are very effective for improving the height dependence of the antenna factors. Resistive loads are also useful for flattening the frequency dependence. Based on these studies, a specification is developed for a broadband standard antenna operating in the 30 to 150 MHz frequency range.

Broadband non-polarizing beam splitter based on guided mode resonance effect

Science.gov (United States)

Ma, Jian-Yong; Xu, Cheng; Qiang, Ying-Huai; Zhu, Ya-Bo

2011-10-01

A broadband non-polarizing beam splitter (NPBS) operating in the telecommunication C+L band is designed by using the guided mode resonance effect of periodic silicon-on-insulator (SOI) elements. It is shown that this double layer SOI structure can provide ~50/50 beam ratio with the maximum divergences between reflection and transmission being less than 8% over the spectrum of 1.4 μm~1.7 μm and 1% in the telecommunication band for both TE and TM polarizations. The physical basis of this broadband non-polarizing property is on the simultaneous excitation of the TE and TM strong modulation waveguide modes near the designed spectrum band. Meanwhile, the electric field distributions for both TE and TM polarizations verify the resonant origin of spectrum in the periodic SOI structure. Furthermore, it is demonstrated with our calculations that the beam splitter proposed here is tolerant to the deviations of incident angle and structure parameters, which make it very easy to be fabricated with current IC technology.

Atmospheric effect on the ground-based measurements of broadband surface albedo

Directory of Open Access Journals (Sweden)

T. Manninen

2012-11-01

Full Text Available Ground-based pyranometer measurements of the (clear-sky broadband surface albedo are affected by the atmospheric conditions (mainly by aerosol particles, water vapour and ozone. A new semi-empirical method for estimating the magnitude of the effect of atmospheric conditions on surface albedo measurements in clear-sky conditions is presented. Global and reflected radiation and/or aerosol optical depth (AOD at two wavelengths are needed to apply the method. Depending on the aerosol optical depth and the solar zenith angle values, the effect can be as large as 20%. For the cases we tested using data from the Cabauw atmospheric test site in the Netherlands, the atmosphere caused typically up to 5% overestimation of surface albedo with respect to corresponding black-sky surface albedo values.

Note: A flexible light emitting diode-based broadband transient-absorption spectrometer

Science.gov (United States)

Gottlieb, Sean M.; Corley, Scott C.; Madsen, Dorte; Larsen, Delmar S.

2012-05-01

This Note presents a simple and flexible ns-to-ms transient absorption spectrometer based on pulsed light emitting diode (LED) technology that can be incorporated into existing ultrafast transient absorption spectrometers or operate as a stand-alone instrument with fixed-wavelength laser sources. The LED probe pulses from this instrument exhibit excellent stability (˜0.5%) and are capable of producing high signal-to-noise long-time (>100 ns) transient absorption signals either in a broadband multiplexed (spanning 250 nm) or in tunable narrowband (20 ns) operation. The utility of the instrument is demonstrated by measuring the photoinduced ns-to-ms photodynamics of the red/green absorbing fourth GMP phosphodiesterase/adenylyl cyclase/FhlA domain of the NpR6012 locus of the nitrogen-fixing cyanobacterium Nostoc punctiforme.

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

Chaos-assisted broadband momentum transformation in optical microresonators

Science.gov (United States)

Jiang, Xuefeng; Shao, Linbo; Zhang, Shu-Xin; Yi, Xu; Wiersig, Jan; Wang, Li; Gong, Qihuang; Lončar, Marko; Yang, Lan; Xiao, Yun-Feng

2017-10-01

The law of momentum conservation rules out many desired processes in optical microresonators. We report broadband momentum transformations of light in asymmetric whispering gallery microresonators. Assisted by chaotic motions, broadband light can travel between optical modes with different angular momenta within a few picoseconds. Efficient coupling from visible to near-infrared bands is demonstrated between a nanowaveguide and whispering gallery modes with quality factors exceeding 10 million. The broadband momentum transformation enhances the device conversion efficiency of the third-harmonic generation by greater than three orders of magnitude over the conventional evanescent-wave coupling. The observed broadband and fast momentum transformation could promote applications such as multicolor lasers, broadband memories, and multiwavelength optical networks.

Antennas Designed for Advanced Communications for Air Traffic Management (AC/ATM) Project

Science.gov (United States)

Zakrajsek, Robert J.

2000-01-01

The goal of the Advanced Communications for Air Traffic Management (AC/ATM) Project at the NASA Glenn Research Center at Lewis Field is to enable a communications infrastructure that provides the capacity, efficiency, and flexibility necessary to realize a mature free-flight environment. The technical thrust of the AC/ATM Project is targeted at the design, development, integration, test, and demonstration of enabling technologies for global broadband aeronautical communications. Since Ku-band facilities and equipment are readily available, one of the near-term demonstrations involves a link through a Kuband communications satellite. Two conformally mounted antennas will support the initial AC/ATM communications links. Both of these are steered electronically through monolithic microwave integrated circuit (MMIC) amplifiers and phase shifters. This link will be asymmetrical with the downlink to the aircraft (mobile vehicle) at a throughput rate of greater than 1.5 megabits per second (Mbps), whereas the throughput rate of the uplink from the aircraft will be greater than 100 kilobits per second (kbps). The data on the downlink can be narrow-band, wide-band, or a combination of both, depending on the requirements of the experiment. The AC/ATM project is purchasing a phased-array Ku-band transmitting antenna for the uplink from the test vehicle. Many Ku-band receiving antennas have been built, and one will be borrowed for a short time to perform the initial experiments at the NASA Glenn Research Center at Lewis Field. The Ku-band transmitting antenna is a 254-element MMIC phased-array antenna being built by Boeing Phantom Works. Each element can radiate 100 mW. The antenna is approximately 43-cm high by 24-cm wide by 3.3-cm thick. It can be steered beyond 60 from broadside. The beamwidth varies from 6 at broadside to 12 degrees at 60 degrees, which is typical of phased-array antennas. When the antenna is steered to 60 degrees, the beamwidth will illuminate

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

ATM loss leads to synthetic lethality in BRCA1 BRCT mutant mice associated with exacerbated defects in homology-directed repair.

Science.gov (United States)

Chen, Chun-Chin; Kass, Elizabeth M; Yen, Wei-Feng; Ludwig, Thomas; Moynahan, Mary Ellen; Chaudhuri, Jayanta; Jasin, Maria

2017-07-18

BRCA1 is essential for homology-directed repair (HDR) of DNA double-strand breaks in part through antagonism of the nonhomologous end-joining factor 53BP1. The ATM kinase is involved in various aspects of DNA damage signaling and repair, but how ATM participates in HDR and genetically interacts with BRCA1 in this process is unclear. To investigate this question, we used the Brca1 S1598F mouse model carrying a mutation in the BRCA1 C-terminal domain of BRCA1. Whereas ATM loss leads to a mild HDR defect in adult somatic cells, we find that ATM inhibition leads to severely reduced HDR in Brca1 S1598F cells. Consistent with a critical role for ATM in HDR in this background, loss of ATM leads to synthetic lethality of Brca1 S1598F mice. Whereas both ATM and BRCA1 promote end resection, which can be regulated by 53BP1, 53bp1 deletion does not rescue the HDR defects of Atm mutant cells, in contrast to Brca1 mutant cells. These results demonstrate that ATM has a role in HDR independent of the BRCA1-53BP1 antagonism and that its HDR function can become critical in certain contexts.

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

Fixed Broadband Deployment Data: June, 2016 Status V1

Data.gov (United States)

Federal Communications Commission — Version 1 reflects data filed by the March 1, 2016 filing deadline and any revisions made before February 10, 2017. All facilities-based broadband providers are...

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

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....

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...

Broad-Band Visually Evoked Potentials: Re(convolution in Brain-Computer Interfacing.

Directory of Open Access Journals (Sweden)

Jordy Thielen

Full Text Available Brain-Computer Interfaces (BCIs allow users to control devices and communicate by using brain activity only. BCIs based on broad-band visual stimulation can outperform BCIs using other stimulation paradigms. Visual stimulation with pseudo-random bit-sequences evokes specific Broad-Band Visually Evoked Potentials (BBVEPs that can be reliably used in BCI for high-speed communication in speller applications. In this study, we report a novel paradigm for a BBVEP-based BCI that utilizes a generative framework to predict responses to broad-band stimulation sequences. In this study we designed a BBVEP-based BCI using modulated Gold codes to mark cells in a visual speller BCI. We defined a linear generative model that decomposes full responses into overlapping single-flash responses. These single-flash responses are used to predict responses to novel stimulation sequences, which in turn serve as templates for classification. The linear generative model explains on average 50% and up to 66% of the variance of responses to both seen and unseen sequences. In an online experiment, 12 participants tested a 6 × 6 matrix speller BCI. On average, an online accuracy of 86% was reached with trial lengths of 3.21 seconds. This corresponds to an Information Transfer Rate of 48 bits per minute (approximately 9 symbols per minute. This study indicates the potential to model and predict responses to broad-band stimulation. These predicted responses are proven to be well-suited as templates for a BBVEP-based BCI, thereby enabling communication and control by brain activity only.

An Assessment of Emerging Wireless Broadband Technologies

National Research Council Canada - National Science Library

Fountanas, Leonidas

2001-01-01

... technologies in providing broadband services today, emerging wireless broadband technologies are expected to significantly increase their market share over the next years, Deploying a wireless network...

Broadband wavelength conversion in hydrogenated amorphous silicon waveguide with silicon nitride layer

Science.gov (United States)

Wang, Jiang; Li, Yongfang; Wang, Zhaolu; Han, Jing; Huang, Nan; Liu, Hongjun

2018-01-01

Broadband wavelength conversion based on degenerate four-wave mixing is theoretically investigated in a hydrogenated amorphous silicon (a-Si:H) waveguide with silicon nitride inter-cladding layer (a-Si:HN). We have found that enhancement of the non-linear effect of a-Si:H waveguide nitride intermediate layer facilitates broadband wavelength conversion. Conversion bandwidth of 490 nm and conversion efficiency of 11.4 dB were achieved in a numerical simulation of a 4 mm-long a-Si:HN waveguide under 1.55 μm continuous wave pumping. This broadband continuous-wave wavelength converter has potential applications in photonic networks, a type of readily manufactured low-cost highly integrated optical circuits.

Fabrication and characterization of MCC approved testing material - ATM-8 glass

International Nuclear Information System (INIS)

Wald, J.W.

1985-10-01

The Materials Characterization Center (MCC) Approved Testing Material ATM-8 is a borosilicate glass that incorporates elements typical of 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 (Mendel, J.E. et al., 1977, Annual Report of the Characteristics of High-Level Waste Glasses, BNWL-2252, Pacific Northwest Laboratory, Richland, Washington), to which depleted uranium, technetium-99, neptunium-237 and plutonium-239 have been added at moderate to low levels. The glass was requested by the Nevada Nuclear Waste Storage Investigations (NNWSI) Project. It was produced by the MCC at the Pacific Northwest Laboratory (PNL) operated for the Department of Energy (DOE) by Battelle Memorial Institute. ATM-8 glass was produced in April of 1984, and is the second in a series of testing materials for NNWSI. This report discusses its fabrication (starting materials, batch and glass preparation, measurement and testing equipment, other equipment, procedures, identification system and materials availability and storage, and characterization (bulk density) measurements, chemical analysis, microscopic examination, and x-ray diffraction analysis. 4 refs., 2 figs., 10 tabs

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.

Broadband Wireline Provider Service Summary; BBRI_wirelineSum12

Data.gov (United States)

University of Rhode Island Geospatial Extension Program — This dataset represents the availability of broadband Internet access in Rhode Island via all wireline technologies assessed by Broadband Rhode Island. Broadband...

Self-biased broadband magnet-free linear isolator based on one-way space-time coherency

Science.gov (United States)

Taravati, Sajjad

2017-12-01

This paper introduces a self-biased broadband magnet-free and linear isolator based on one-way space-time coherency. The incident wave and the space-time-modulated medium share the same temporal frequency and are hence temporally coherent. However, thanks to the unidirectionally of the space-time modulation, the space-time-modulated medium and the incident wave are spatially coherent only in the forward direction and not in the opposite direction. As a consequence, the energy of the medium strongly couples to the propagating wave in the forward direction, while it conflicts with the propagating wave in the opposite direction, yielding strong isolation. We first derive a closed-form solution for the wave scattering from a spatiotemporally coherent medium and then show that a perfectly coherent space-time-modulated medium provides a moderate isolation level which is also subject to one-way transmission gain. To overcome this issue, we next investigate the effect of space-coherency imperfection between the medium and the wave, while they are still perfectly temporally coherent. Leveraging the spatial-coherency imperfection, the medium exhibits a quasiarbitrary and strong nonreciprocal transmission. Finally, we present the experimental demonstration of the self-biased version of the proposed broadband isolator, exhibiting more than 122 % fractional operation bandwidth.

Functional intersection of ATM and DNA-dependent protein kinase catalytic subunit in coding end joining during V(D)J recombination

DEFF Research Database (Denmark)

Lee, Baeck-Seung; Gapud, Eric J; Zhang, Shichuan

2013-01-01

V(D)J recombination is initiated by the RAG endonuclease, which introduces DNA double-strand breaks (DSBs) at the border between two recombining gene segments, generating two hairpin-sealed coding ends and two blunt signal ends. ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) ar......V(D)J recombination is initiated by the RAG endonuclease, which introduces DNA double-strand breaks (DSBs) at the border between two recombining gene segments, generating two hairpin-sealed coding ends and two blunt signal ends. ATM and DNA-dependent protein kinase catalytic subunit (DNA......-PKcs) are serine-threonine kinases that orchestrate the cellular responses to DNA DSBs. During V(D)J recombination, ATM and DNA-PKcs have unique functions in the repair of coding DNA ends. ATM deficiency leads to instability of postcleavage complexes and the loss of coding ends from these complexes. DNA...... when ATM is present and its kinase activity is intact. The ability of ATM to compensate for DNA-PKcs kinase activity depends on the integrity of three threonines in DNA-PKcs that are phosphorylation targets of ATM, suggesting that ATM can modulate DNA-PKcs activity through direct phosphorylation of DNA...

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.

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...

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.

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.

Broadband spectral shaping in regenerative amplifier based on modified polarization-encoded chirped pulse amplification

Science.gov (United States)

Wang, Xinliang; Lu, Xiaoming; Liu, Yanqi; Xu, Yi; Wang, Cheng; Li, Shuai; Yu, Linpeng; Liu, Xingyan; Liu, Keyang; Xu, Rongjie; Leng, Yuxin

2018-06-01

We present an intra-cavity spectral shaping method to suppress the spectral narrowing in a Ti:sapphire (Ti:Sa) regenerative amplifier. The spectral shaping is realized by manipulating the stored energies of two Ti:Sa crystals with orthogonal c-axes, changing the length of a quartz plate, and rotating a broadband achromatic half-wave plate. Using this method, in our proof-of-concept experiment, an 84-nm-(FWHM)-broadband amplified pulse with an energy gain larger than 106 is obtained, which supports a 17.8 fs Fourier-transform-limited pulse duration. The pulse is compressed to 18.9 fs.

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)

Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations.

Science.gov (United States)

Sun, Jiying; Shi, Lin; Kinomura, Aiko; Fukuto, Atsuhiko; Horikoshi, Yasunori; Oma, Yukako; Harata, Masahiko; Ikura, Masae; Ikura, Tsuyoshi; Kanaar, Roland; Tashiro, Satoshi

2018-05-08

Chromosomal translocations are hallmarks of various types of cancers and leukemias. However, the molecular mechanisms of chromosome translocations remain largely unknown. The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. Previously, we showed that ATM deficiency led to the 11q23 chromosome translocation, the most frequent chromosome abnormalities in secondary leukemia. Here, we show that ARP8, a subunit of the INO80 chromatin remodeling complex, is phosphorylated after etoposide treatment. The etoposide-induced phosphorylation of ARP8 is regulated by ATM and ATR, and attenuates its interaction with INO80. The ATM-regulated phosphorylation of ARP8 reduces the excessive loading of INO80 and RAD51 onto the breakpoint cluster region. These findings suggest that the phosphorylation of ARP8, regulated by ATM, plays an important role in maintaining the fidelity of DNA repair to prevent the etoposide-induced 11q23 abnormalities. © 2018, Sun et al.

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

Ultraflat and broadband optical frequency comb generator based on cascaded two dual-electrode Mach-Zehnder modulators

Science.gov (United States)

Qu, Kun; Zhao, Shanghong; Li, Xuan; Tan, Qinggui; Zhu, Zihang

2018-04-01

A novel scheme for the generation of ultraflat and broadband optical frequency comb (OFC) is proposed based on cascaded two dual-electrode Mach-Zehnder modulators (DE-MZM). The first DE-MZM can generate a four-comb-line OFC, then the OFC is injected into the second DE-MZM as a carrier, which can increase the number of comb lines. Our modified scheme finally can generate a broadband OFC with high flatness by simply modifying the electrical power and the bias voltage of the DE-MZM. Theoretical analysis and simulation results reveal that a 16-comb-line OFC with a frequency spacing that two times the frequency of the RF signal can be obtained. The power fluctuation of the OFC lines is 0.48 dB and the unwanted-mode suppression ratio (UMSR) can reach 16.5 dB. Additionally, whether the bias drift of the DE-MZMs has little influence on the power fluctuation is also analyzed. These results demonstrate the robustness of our scheme and verify its good accuracy and high stability with perfect flatness.

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.

Comparison of VP broadband tiltmeter and VS vertical pendulum tiltmeter

Directory of Open Access Journals (Sweden)

Wugang Ma

2015-05-01

Full Text Available Vertical pendulum (VP tiltmeter is a kind of earthquake precursor observation equipment, which is used to record the interaction force associated with astronomical tidal tilts caused. Currently, VP broadband tiltmeter and vertical sensor (VS vertical pendulum tiltmeter are primarily used. In this paper, we compare the two different instruments by using four aspects—mechanical structure, circuitry, zeroing, and bandwidth—based on their working principles and applications. We conclude that VP broadband tiltmeter is more superior compared with VS vertical pendulum tiltmeter because of its higher bandwidth and degree of automation.

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.

Broadband non-polarizing beam splitter based on guided mode resonance effect

International Nuclear Information System (INIS)

Ma Jian-Yong; Xu Cheng; Qiang Ying-Huai; Zhu Ya-Bo

2011-01-01

A broadband non-polarizing beam splitter (NPBS) operating in the telecommunication C+L band is designed by using the guided mode resonance effect of periodic silicon-on-insulator (SOI) elements. It is shown that this double layer SOI structure can provide ∼50/50 beam ratio with the maximum divergences between reflection and transmission being less than 8% over the spectrum of 1.4 μm∼1.7 μm and 1% in the telecommunication band for both TE and TM polarizations. The physical basis of this broadband non-polarizing property is on the simultaneous excitation of the TE and TM strong modulation waveguide modes near the designed spectrum band. Meanwhile, the electric field distributions for both TE and TM polarizations verify the resonant origin of spectrum in the periodic SOI structure. Furthermore, it is demonstrated with our calculations that the beam splitter proposed here is tolerant to the deviations of incident angle and structure parameters, which make it very easy to be fabricated with current IC technology. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

Digital Divides and the 'First Mile': Framing First Nations Broadband Development in Canada

Directory of Open Access Journals (Sweden)

Rob McMahon

2011-05-01

Full Text Available Across Canada, rural and remote First Nations face a significant 'digital divide'. As self-determining autonomous nations in Canada, these communities are building broadband systems to deliver public services to their members and residents. To address this challenge, First Nations are working towards a variety of innovative, locally driven broadband development initiatives. This paper contributes a theoretical discussion that frames our understanding of these initiatives by drawing on the paradigm of the 'First Mile' (Paisley & Richardson, 1998. We argue that broadband development policy in Canada must be re-framed to address the specific needs of First Nations. The First Mile position foregrounds community-based involvement, control, and ownership: a consideration we suggest has particular resonance for First Nations. This is because it holds potential to move beyond the historical context of paternalistic, colonial-derived development policies, in the context of broadband systems development. We argue First Nations broadband projects offer on-the-ground examples of a First Mile approach, and call for more research in this area.

Broadband back grating design for thin film solar cells

KAUST Repository

Janjua, Bilal; Jabbour, Ghassan E.

2013-01-01

In this paper, design based on tapered circular grating structure was studied, to provide broadband enhancement in thin film amorphous silicon solar cells. In comparison to planar structure an absorption enhancement of ~ 7% was realized.

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.

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

Chaos-assisted broadband momentum transformation in optical microresonators.

Science.gov (United States)

Jiang, Xuefeng; Shao, Linbo; Zhang, Shu-Xin; Yi, Xu; Wiersig, Jan; Wang, Li; Gong, Qihuang; Lončar, Marko; Yang, Lan; Xiao, Yun-Feng

2017-10-20

The law of momentum conservation rules out many desired processes in optical microresonators. We report broadband momentum transformations of light in asymmetric whispering gallery microresonators. Assisted by chaotic motions, broadband light can travel between optical modes with different angular momenta within a few picoseconds. Efficient coupling from visible to near-infrared bands is demonstrated between a nanowaveguide and whispering gallery modes with quality factors exceeding 10 million. The broadband momentum transformation enhances the device conversion efficiency of the third-harmonic generation by greater than three orders of magnitude over the conventional evanescent-wave coupling. The observed broadband and fast momentum transformation could promote applications such as multicolor lasers, broadband memories, and multiwavelength optical networks. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Broadband availability in metropolitan and non-metropolitan Pennsylvania

Directory of Open Access Journals (Sweden)

Lawrence E. Wood

2016-09-01

Full Text Available Over the past few years having a broadband connection has become essential for many Internet activities. As broadband increases in importance, it becomes imperative to assess how its use and availability may vary, especially in relation to issues such as geographic location. For rural areas in particular, the availability of broadband service is especially important. This research assesses broadband service availability in rural areas of Pennsylvania, USA. In particular, it examines the extent to which Digital Subscriber Line (DSL and broadband cable modem services are being deployed throughout rural Pennsylvania. It compares this deployment with the availability of such services in the state’s urban and metropolitan areas. The results of this research suggest that there is a “digital divide” in terms of broadband availability between rural and urban areas of Pennsylvania. However, this “divide” is perhaps not as wide as might be expected. Thus, as broadband is becoming increasingly available in rural areas of the U.S. and throughout much of the rest of the world, this research concludes that while research must remain vigilant in terms of assessing advanced telecommunications availability in rural areas, future research should also be sure to focus on how such technologies can be used to promote economic and social concerns, including in relation to building online networks and diminishing social and professional isolation in rural areas.

Radio over fiber transceiver employing phase modulation of an optical broadband source.

Science.gov (United States)

Grassi, Fulvio; Mora, José; Ortega, Beatriz; Capmany, José

2010-10-11

This paper proposes a low-cost RoF transceiver for multichannel SCM/WDM signal distribution suitable for future broadband access networks. The transceiver is based on the phase modulation of an optical broadband source centered at third transmission window. Prior to phase modulation the optical broadband source output signal is launched into a Mach-Zehnder interferometer structure, as key device enabling radio signals propagation over the optical link. Furthermore, an optical CWDM is employed to create a multichannel scenario by performing the spectral slicing of the modulated optical signal into a number of channels each one conveying the information from the central office to different base stations. The operation range is up to 20 GHz with a modulation bandwidth around of 500 MHz. Experimental results of the transmission of SCM QPSK and 64-QAM data through 20 Km of SMF exhibit good EVM results in the operative range determined by the phase-to-intensity conversion process. The proposed approach shows a great suitability for WDM networks based on RoF signal transport and also represents a cost-effective solution for passive optical networks.

Analyzing Broadband Divide in the Farming Sector

DEFF Research Database (Denmark)

Jensen, Michael; Gutierrez Lopez, Jose Manuel; Pedersen, Jens Myrup

2013-01-01

, upstream and downstream connection. The main constraint is that farms are naturally located in rural areas where the required access broadband data rates are not available. This paper studies the broadband divide in relation to the Danish agricultural sector. Results show how there is an important......Agriculture industry has been evolving for centuries. Currently, the technological development of Internet oriented farming tools allows to increase the productivity and efficiency of this sector. Many of the already available tools and applications require high bandwidth in both directions...... difference between the broadband availability for farms and the rest of the households/buildings the country. This divide may be slowing down the potential technological development of the farming industry, in order to keep their competitiveness in the market. Therefore, broadband development in rural areas...

76 FR 13769 - Rural Broadband Access Loans and Loan Guarantees

Science.gov (United States)

2011-03-14

... pharmacy work, and savings to health facilities from outsourcing specialized medical procedures. One study... international markets and enables new, small, and home-based businesses to thrive. Broadband access affords...

Femtosecond Broadband Stimulated Raman Spectroscopy

International Nuclear Information System (INIS)

Lee, Soo-Y; Yoon, Sagwoon; Mathies, Richard A

2006-01-01

Femtosecond broadband stimulated Raman spectroscopy (FSRS) is a new technique where a narrow bandwidth picosecond Raman pump pulse and a red-shifted broadband femtosecond Stokes probe pulse (with or without time delay between the pulses) act on a sample to produce a high resolution Raman gain spectrum with high efficiency and speed, free from fluorescence background interference. It can reveal vibrational structural information and dynamics of stationary or transient states. Here, the quantum picture for femtosecond broadband stimulated Raman spectroscopy (FSRS) is used to develop the semiclassical coupled wave theory of the phenomenon and to derive an expression for the measurable Raman gain in FSRS. The semiclassical theory is applied to study the dependence of lineshapes in FSRS on the pump-probe time delay and to deduce vibrational dephasing times in cyclohexane in the ground state

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

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.

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.

Tapered fluorotellurite microstructured fibers for broadband supercontinuum generation.

Science.gov (United States)

Wang, Fang; Wang, Kangkang; Yao, Chuanfei; Jia, Zhixu; Wang, Shunbin; Wu, Changfeng; Qin, Guanshi; Ohishi, Yasutake; Qin, Weiping

2016-02-01

Fluorotellurite microstructured fibers (MFs) based on TeO2-BaF2-Y2O3 glasses are fabricated by using a rod-in-tube method. Tapered fluorotellurite MFs with varied transition region lengths are prepared by employing an elongation machine. By using a tapered fluorotellurite MF with a transition region length of ∼3.3  cm as the nonlinear medium and a 1560 nm femtosecond fiber laser as the pump source, broadband supercontinuum generation covering from 470 to 2770 nm is obtained. The effects of the transition region length of the tapered fluorotellurite MF on supercontinuum generation are also investigated. Our results show that tapered fluorotellurite MFs are promising nonlinear media for generating broadband supercontinuum light expanding from visible to mid-infrared spectral region.

The SCEC Broadband Platform: A Collaborative Open-Source Software Package for Strong Ground Motion Simulation and Validation

Science.gov (United States)

Silva, F.; Maechling, P. J.; Goulet, C. A.; Somerville, P.; Jordan, T. H.

2014-12-01

The Southern California Earthquake Center (SCEC) Broadband Platform is a collaborative software development project involving geoscientists, earthquake engineers, graduate students, and the SCEC Community Modeling Environment. The SCEC Broadband Platform (BBP) is open-source scientific software that can generate broadband (0-100Hz) ground motions for earthquakes, integrating complex scientific modules that implement rupture generation, low and high-frequency seismogram synthesis, non-linear site effects calculation, and visualization into a software system that supports easy on-demand computation of seismograms. The Broadband Platform operates in two primary modes: validation simulations and scenario simulations. In validation mode, the Platform runs earthquake rupture and wave propagation modeling software to calculate seismograms for a well-observed historical earthquake. Then, the BBP calculates a number of goodness of fit measurements that quantify how well the model-based broadband seismograms match the observed seismograms for a certain event. Based on these results, the Platform can be used to tune and validate different numerical modeling techniques. In scenario mode, the Broadband Platform can run simulations for hypothetical (scenario) earthquakes. In this mode, users input an earthquake description, a list of station names and locations, and a 1D velocity model for their region of interest, and the Broadband Platform software then calculates ground motions for the specified stations. Working in close collaboration with scientists and research engineers, the SCEC software development group continues to add new capabilities to the Broadband Platform and to release new versions as open-source scientific software distributions that can be compiled and run on many Linux computer systems. Our latest release includes 5 simulation methods, 7 simulation regions covering California, Japan, and Eastern North America, the ability to compare simulation results

Dissemination of optical-comb-based ultra-broadband frequency reference through a fiber network.

Science.gov (United States)

Nagano, Shigeo; Kumagai, Motohiro; Li, Ying; Ido, Tetsuya; Ishii, Shoken; Mizutani, Kohei; Aoki, Makoto; Otsuka, Ryohei; Hanado, Yuko

2016-08-22

We disseminated an ultra-broadband optical frequency reference based on a femtosecond (fs)-laser optical comb through a kilometer-scale fiber link. Its spectrum ranged from 1160 nm to 2180 nm without additional fs-laser combs at the end of the link. By employing a fiber-induced phase noise cancellation technique, the linewidth and fractional frequency instability attained for all disseminated comb modes were of order 1 Hz and 10-18 in a 5000 s averaging time. The ultra-broad optical frequency reference, for which absolute frequency is traceable to Japan Standard Time, was applied in the frequency stabilization of an injection-seeded Q-switched 2051 nm pulse laser for a coherent light detection and ranging LIDAR system.

Graphene based tunable fractal Hilbert curve array broadband radar absorbing screen for radar cross section reduction

Energy Technology Data Exchange (ETDEWEB)

Huang, Xianjun, E-mail: xianjun.huang@manchester.ac.uk [School of Electrical and Electronic Engineering, University of Manchester, Manchester M13 9PL (United Kingdom); College of Electronic Science and Engineering, National University of Defense Technology, Changsha 410073 (China); Hu, Zhirun [School of Electrical and Electronic Engineering, University of Manchester, Manchester M13 9PL (United Kingdom); Liu, Peiguo [College of Electronic Science and Engineering, National University of Defense Technology, Changsha 410073 (China)

2014-11-15

This paper proposes a new type of graphene based tunable radar absorbing screen. The absorbing screen consists of Hilbert curve metal strip array and chemical vapour deposition (CVD) graphene sheet. The graphene based screen is not only tunable when the chemical potential of the graphene changes, but also has broadband effective absorption. The absorption bandwidth is from 8.9GHz to 18.1GHz, ie., relative bandwidth of more than 68%, at chemical potential of 0eV, which is significantly wider than that if the graphene sheet had not been employed. As the chemical potential varies from 0 to 0.4eV, the central frequency of the screen can be tuned from 13.5GHz to 19.0GHz. In the proposed structure, Hilbert curve metal strip array was designed to provide multiple narrow band resonances, whereas the graphene sheet directly underneath the metal strip array provides tunability and averagely required surface resistance so to significantly extend the screen operation bandwidth by providing broadband impedance matching and absorption. In addition, the thickness of the screen has been optimized to achieve nearly the minimum thickness limitation for a nonmagnetic absorber. The working principle of this absorbing screen is studied in details, and performance under various incident angles is presented. This work extends applications of graphene into tunable microwave radar cross section (RCS) reduction applications.

Graphene based tunable fractal Hilbert curve array broadband radar absorbing screen for radar cross section reduction

International Nuclear Information System (INIS)

Huang, Xianjun; Hu, Zhirun; Liu, Peiguo

2014-01-01

This paper proposes a new type of graphene based tunable radar absorbing screen. The absorbing screen consists of Hilbert curve metal strip array and chemical vapour deposition (CVD) graphene sheet. The graphene based screen is not only tunable when the chemical potential of the graphene changes, but also has broadband effective absorption. The absorption bandwidth is from 8.9GHz to 18.1GHz, ie., relative bandwidth of more than 68%, at chemical potential of 0eV, which is significantly wider than that if the graphene sheet had not been employed. As the chemical potential varies from 0 to 0.4eV, the central frequency of the screen can be tuned from 13.5GHz to 19.0GHz. In the proposed structure, Hilbert curve metal strip array was designed to provide multiple narrow band resonances, whereas the graphene sheet directly underneath the metal strip array provides tunability and averagely required surface resistance so to significantly extend the screen operation bandwidth by providing broadband impedance matching and absorption. In addition, the thickness of the screen has been optimized to achieve nearly the minimum thickness limitation for a nonmagnetic absorber. The working principle of this absorbing screen is studied in details, and performance under various incident angles is presented. This work extends applications of graphene into tunable microwave radar cross section (RCS) reduction applications

Photonic crystal fiber design for broadband directional coupling

DEFF Research Database (Denmark)

Lægsgaard, Jesper; Bang, Ole; Bjarklev, Anders Overgaard

2004-01-01

A novel design for a broadband directional coupler based on a photonic crystal fiber is investigated numerically. It is shown that suitable index-depressing doping of the core regions in an index-guiding twin-core photonic crystal fiber can stabilize the coupling coefficient between the cores over...

PHEMT Distributed Power Amplifier Adopting Broadband Impedance Transformer

DEFF Research Database (Denmark)

Narendra, K.; Limiti, E.; Paoloni, C.

2013-01-01

A non-uniform drain line distributed power amplifier (DPA) employing a broadband impedance transformer is presented. The DPA is based on GaAs PHEMT technology. The impedance transformer employs asymmetric coupled lines and transforms a low output impedance of the amplifier to a standard 50 Ω...

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.

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.

The effect of ATM kinase inhibition on the initial response of human dental pulp and periodontal ligament mesenchymal stem cells to ionizing radiation.

Science.gov (United States)

Cmielova, Jana; Havelek, Radim; Kohlerova, Renata; Soukup, Tomas; Bruckova, Lenka; Suchanek, Jakub; Vavrova, Jirina; Mokry, Jaroslav; Rezacova, Martina

2013-07-01

This study evaluates early changes in human mesenchymal stem cells (MSC) isolated from dental pulp and periodontal ligament after γ-irradiation and the effect of ataxia-telangiectasia mutated (ATM) inhibition. MSC were irradiated with 2 and 20 Gy by (60)Co. For ATM inhibition, specific inhibitor KU55933 was used. DNA damage was measured by Comet assay and γH2AX detection. Cell cycle distribution and proteins responding to DNA damage were analyzed 2-72 h after the irradiation. The irradiation of MSC causes an increase in γH2AX; the phosphorylation was ATM-dependent. Irradiation activates ATM kinase, and the level of p53 protein is increased due to its phosphorylation on serine15. While this phosphorylation of p53 is ATM-dependent in MSC, the increase in p53 was not prevented by ATM inhibition. A similar trend was observed for Chk1 and Chk2. The increase in p21 is greater without ATM inhibition. ATM inhibition also does not fully abrogate the accumulation of irradiated MSC in the G2-phase of the cell-cycle. In irradiated MSC, double-strand breaks are tagged quickly by γH2AX in an ATM-dependent manner. Although phosphorylations of p53(ser15), Chk1(ser345) and Chk2(thr68) are ATM-dependent, the overall amount of these proteins increases when ATM is inhibited. In both types of MSC, ATM-independent mechanisms for cell-cycle arrest in the G2-phase are triggered.

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

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.

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...

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

Hsp90α regulates ATM and NBN functions in sensing and repair of DNA double-strand breaks.

Science.gov (United States)

Pennisi, Rosa; Antoccia, Antonio; Leone, Stefano; Ascenzi, Paolo; di Masi, Alessandra

2017-08-01

The molecular chaperone heat shock protein 90 (Hsp90α) regulates cell proteostasis and mitigates the harmful effects of endogenous and exogenous stressors on the proteome. Indeed, the inhibition of Hsp90α ATPase activity affects the cellular response to ionizing radiation (IR). Although the interplay between Hsp90α and several DNA damage response (DDR) proteins has been reported, its role in the DDR is still unclear. Here, we show that ataxia-telangiectasia-mutated kinase (ATM) and nibrin (NBN), but not 53BP1, RAD50, and MRE11, are Hsp90α clients as the Hsp90α inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) induces ATM and NBN polyubiquitination and proteosomal degradation in normal fibroblasts and lymphoblastoid cell lines. Hsp90α-ATM and Hsp90α-NBN complexes are present in unstressed and irradiated cells, allowing the maintenance of ATM and NBN stability that is required for the MRE11/RAD50/NBN complex-dependent ATM activation and the ATM-dependent phosphorylation of both NBN and Hsp90α in response to IR-induced DNA double-strand breaks (DSBs). Hsp90α forms a complex also with ph-Ser1981-ATM following IR. Upon phosphorylation, NBN dissociates from Hsp90α and translocates at the DSBs, while phThr5/7-Hsp90α is not recruited at the damaged sites. The inhibition of Hsp90α affects nuclear localization of MRE11 and RAD50, impairs DDR signaling (e.g., BRCA1 and CHK2 phosphorylation), and slows down DSBs repair. Hsp90α inhibition does not affect DNA-dependent protein kinase (DNA-PK) activity, which possibly phosphorylates Hsp90α and H2AX after IR. Notably, Hsp90α inhibition causes H2AX phosphorylation in proliferating cells, this possibly indicating replication stress events. Overall, present data shed light on the regulatory role of Hsp90α on the DDR, controlling ATM and NBN stability and influencing the DSBs signaling and repair. © 2017 Federation of European Biochemical Societies.

Management of broadband technology and innovation policy, deployment, and use

CERN Document Server

Choudrie, Jyoti

2013-01-01

When one considers broadband, the Internet immediately springs to mind. However, broadband is impacting society in many ways. For instance, broadband networks can be used to deliver healthcare or community related services to individuals who don't have computers, have distance as an issue to contend with, or don't use the internet. Broadband can support better management of scarce energy resources with the advent of smart grids, enables improved teleworking capacity and opens up a world of new entertainment possibilities. Yet scholarly examinations of broadband technology have so far examin