Neural-tree call admission controller for ATM networks

NASA Astrophysics Data System (ADS)

Rughooputh, Harry C. S.

1999-03-01

Asynchronous Transfer Mode (ATM) has been recommended by ITU-T as the transport method for broadband integrated services digital networks. In high-speed ATM networks different types of multimedia traffic streams with widely varying traffic characteristics and Quality of Service (QoS) are asynchronously multiplexed on transmission links and switched without window flow control as found in X.25. In such an environment, a traffic control scheme is required to manage the required QoS of each class individually. To meet the QoS requirements, Bandwidth Allocation and Call Admission Control (CAC) in ATM networks must be able to adapt gracefully to the dynamic behavior of traffic and the time-varying nature of the network condition. In this paper, a Neural Network approach for CAC is proposed. The call admission problem is addressed by designing controllers based on Neural Tree Networks. Simulations reveal that the proposed scheme is not only simple but it also offers faster response than conventional neural/neuro-fuzzy controllers.

Multimedia information processing in the SWAN mobile networked computing system

NASA Astrophysics Data System (ADS)

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

1996-03-01

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

Versatile RED-based buffer management mechanism for the efficient support of internet traffic

NASA Astrophysics Data System (ADS)

Nelissen, Jordi; De Cnodder, Stefaan

1999-11-01

This paper presents an evaluation of various GFR (Guaranteed Frame Rate) implementation proposals. By means of extensive simulations performed in different network environments we compare two ATM Forum example implementations, namely the `simple FIFO-based GFR.2 implementation' and the `per-VC threshold and scheduling implementation'. The lessons learned from this study are as well applicable to non-ATM network technologies.

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

NASA Astrophysics Data System (ADS)

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.

Toward multidomain integrated network management for ATM and SDH networks

NASA Astrophysics Data System (ADS)

Galis, Alex; Gantenbein, Dieter; Covaci, Stefan; Bianza, Carlo; Karayannis, Fotis; Mykoniatis, George

1996-12-01

ACTS Project AC080 MISA has embarked upon the task of realizing and validating via European field trials integrated end-to-end management of hybrid SDH and ATM networks in the framework of open network provision. This paper reflects the initial work of the project and gives an overview of the proposed MISA system architecture and initial design. We describe our understanding of the underlying enterprise model in the network management context, including the concept of the MISA Global Broadband Connectivity Management service. It supports Integrated Broadband Communication by defining an end-to-end broadband connection service in a multi-domain business environment. Its implementation by the MISA consortium within trials across Europe aims for an efficient management of network resources of the SDH and ATM infrastructure, considering optimum end-to-end quality of service and the needs of a number of telecommunication actors: customers, value-added service providers, and network providers.

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

NASA Astrophysics Data System (ADS)

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

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

Satellite ATM Networks: Architectures and Guidelines Developed

NASA Technical Reports Server (NTRS)

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 opposed to implementing those functions at the Earth station components.

Functional and nonfunctional testing of ATM networks

NASA Astrophysics Data System (ADS)

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.

Perceptually tuned low-bit-rate video codec for ATM networks

NASA Astrophysics Data System (ADS)

Chou, Chun-Hsien

1996-02-01

In order to maintain high visual quality in transmitting low bit-rate video signals over asynchronous transfer mode (ATM) networks, a layered coding scheme that incorporates the human visual system (HVS), motion compensation (MC), and conditional replenishment (CR) is presented in this paper. An empirical perceptual model is proposed to estimate the spatio- temporal just-noticeable distortion (STJND) profile for each frame, by which perceptually important (PI) prediction-error signals can be located. Because of the limited channel capacity of the base layer, only coded data of motion vectors, the PI signals within a small strip of the prediction-error image and, if there are remaining bits, the PI signals outside the strip are transmitted by the cells of the base-layer channel. The rest of the coded data are transmitted by the second-layer cells which may be lost due to channel error or network congestion. Simulation results show that visual quality of the reconstructed CIF sequence is acceptable when the capacity of the base-layer channel is allocated with 2 multiplied by 64 kbps and the cells of the second layer are all lost.

Latency of TCP applications over the ATM-WAN using the GFR service category

NASA Astrophysics Data System (ADS)

Chen, Kuo-Hsien; Siliquini, John F.; Budrikis, Zigmantas

1998-10-01

The GFR service category has been proposed for data services in ATM networks. Since users are ultimately interested in data service that provide high efficiency and low latency, it is important to study the latency performance for data traffic of the GFR service category in an ATM network. Today much of the data traffic utilizes the TCP/IP protocol suite and in this paper we study through simulation the latency of TCP applications running over a wide-area ATM network utilizing the GFR service category using a realistic TCP traffic model. From this study, we find that during congestion periods the reserved bandwidth in GFR can improve the latency performance for TCP applications. However, due to TCP 'Slow Start' data segment generation dynamics, we show that a large proportion of TCP segments are discarded under network congestion even when the reserved bandwidth is equal to the average generated rate of user data. Therefore, a user experiences worse than expected latency performance when the network is congested. In this study we also examine the effects of segment size on the latency performance of TCP applications using the GFR service category.

Video transmission on ATM networks. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

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.

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

PubMed

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.

MSFC institutional area network and ATM technology

NASA Technical Reports Server (NTRS)

Amin, Ashok T.

1994-01-01

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

A Managerial Analysis of ATM in Facilitating Distance Education.

ERIC Educational Resources Information Center

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: The Key To Harnessing the Power of Networked Multimedia.

ERIC Educational Resources Information Center

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…

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

PubMed Central

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

2015-01-01

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. DOI: http://dx.doi.org/10.7554/eLife.07270.001 PMID:26030852

Integrated Service Provisioning in an Ipv6 over ATM Research Network

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

Eli Dart; Helen Chen; Jerry Friesen

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 ismore » 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.« less

IMS radionuclide monitoring after the announced nuclear test of the DPRK on 3 September 2017

NASA Astrophysics Data System (ADS)

Kusmierczyk-Michulec, J.; Kalinowski, M.; Bourgouin, P.; Boxue, L.; Gheddou, A.; Klingberg, F.; Leppaenen, A. P.; Schoeppner, M.; Werzi, R.; Wang, J.

2017-12-01

The International Monitoring System (IMS) developed by the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) is a global system of monitoring stations, using four complementary technologies: seismic, hydroacoustic, infrasound and radionuclide. The radionuclide network comprises 80 stations, out of which 40 are to be equipped with noble gas systems. The aim of radionuclide stations is a global monitoring of radioactive aerosols, radioactive noble gases and atmospheric transport modelling (ATM). To investigate the transport of radionuclide emissions, the Provisional Technical Secretariat (PTS) operates an Atmospheric Transport Modelling (ATM) system based on the Lagrangian Particle Dispersion Model FLEXPART. The air mass trajectory provides a "link" between a radionuclide release and a detection confirmed by radionuclide measurements. The aim of this study is to demonstrate the RN analysis and the application of ATM to investigate the episodes of elevated levels of radioxenon observed by IMS stations after the sixth nuclear test, announced by the Democratic People's Republic of Korea (DPRK) at the Punggye-ri Nuclear Test Site on 3 September 2017. A comparison to the previous tests will be presented.

Buffer Management Simulation in ATM Networks

NASA Technical Reports Server (NTRS)

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

1998-01-01

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

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

ERIC Educational Resources Information Center

Yao, Engui

1998-01-01

Determines the relationships between ATM (Asynchronous Transfer Mode) adoption and four organizational variables: university size, type, finances, and information-processing maturity. Identifies the current status of ATM adoption in campus networking in the United States. Contains 33 references. (DDR)

The Path to NGATS

NASA Technical Reports Server (NTRS)

Scardina, John

2006-01-01

NGATS operational Improvements and benefits include: 1) Broad area and precision navigation to access and capacity; 2) Airspace access and management to capacity; 3) 4D trajectory based ATM to capacity and efficiency; 4) Reduced separation between aircraft to capacity; 5) Flight deck situational awareness and delegation to capacity and safety; 6) ATM decision support to capacity; 7) Improved weather data and dissemination to capacity and safety; 8) Reduced cost to deliver ATM services to cost; 9) Greatly expanded airport network and improved terminals to capacity.

ATM Technology Adoption in U.S. Campus Networking.

ERIC Educational Resources Information Center

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…

Performance Evaluation in Network-Based Parallel Computing

NASA Technical Reports Server (NTRS)

Dezhgosha, Kamyar

1996-01-01

Network-based parallel computing is emerging as a cost-effective alternative for solving many problems which require use of supercomputers or massively parallel computers. The primary objective of this project has been to conduct experimental research on performance evaluation for clustered parallel computing. First, a testbed was established by augmenting our existing SUNSPARCs' network with PVM (Parallel Virtual Machine) which is a software system for linking clusters of machines. Second, a set of three basic applications were selected. The applications consist of a parallel search, a parallel sort, a parallel matrix multiplication. These application programs were implemented in C programming language under PVM. Third, we conducted performance evaluation under various configurations and problem sizes. Alternative parallel computing models and workload allocations for application programs were explored. The performance metric was limited to elapsed time or response time which in the context of parallel computing can be expressed in terms of speedup. The results reveal that the overhead of communication latency between processes in many cases is the restricting factor to performance. That is, coarse-grain parallelism which requires less frequent communication between processes will result in higher performance in network-based computing. Finally, we are in the final stages of installing an Asynchronous Transfer Mode (ATM) switch and four ATM interfaces (each 155 Mbps) which will allow us to extend our study to newer applications, performance metrics, and configurations.

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

PubMed

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.

Modelling of nanoscale quantum tunnelling structures using algebraic topology method

NASA Astrophysics Data System (ADS)

Sankaran, Krishnaswamy; Sairam, B.

2018-05-01

We have modelled nanoscale quantum tunnelling structures using Algebraic Topology Method (ATM). The accuracy of ATM is compared to the analytical solution derived based on the wave nature of tunnelling electrons. ATM provides a versatile, fast, and simple model to simulate complex structures. We are currently expanding the method for modelling electrodynamic systems.

The Passive Microwave Neural Network Precipitation Retrieval (PNPR) for AMSU/MHS and ATMS cross-track scanning radiometers

NASA Astrophysics Data System (ADS)

Sano', Paolo; Casella, Daniele; Panegrossi, Giulia; Cinzia Marra, Anna; Dietrich, Stefano

2016-04-01

Spaceborne microwave cross-track scanning radiometers, originally developed for temperature and humidity sounding, have shown great capabilities to provide a significant contribution in precipitation monitoring both in terms of measurement quality and spatial/temporal coverage. The Passive microwave Neural network Precipitation Retrieval (PNPR) algorithm for cross-track scanning radiometers, originally developed for the Advanced Microwave Sounding Unit/Microwave Humidity Sounder (AMSU-A/MHS) radiometers (on board the European MetOp and U.S. NOAA satellites), was recently newly designed to exploit the Advanced Technology Microwave Sounder (ATMS) on board the Suomi-NPP satellite and the future JPSS satellites. The PNPR algorithm is based on the Artificial Neural Network (ANN) approach. The main PNPR-ATMS algorithm changes with respect to PNPR-AMSU/MHS are the design and implementation of a new ANN able to manage the information derived from the additional ATMS channels (respect to the AMSU-A/MHS radiometer) and a new screening procedure for not-precipitating pixels. In order to achieve maximum consistency of the retrieved surface precipitation, both PNPR algorithms are based on the same physical foundation. The PNPR is optimized for the European and the African area. The neural network was trained using a cloud-radiation database built upon 94 cloud-resolving simulations over Europe and the Mediterranean and over the African area and radiative transfer model simulations of TB vectors consistent with the AMSU-A/MHS and ATMS channel frequencies, viewing angles, and view-angle dependent IFOV sizes along the scan projections. As opposed to other ANN precipitation retrieval algorithms, PNPR uses a unique ANN that retrieves the surface precipitation rate for all types of surface backgrounds represented in the training database, i.e., land (vegetated or arid), ocean, snow/ice or coast. This approach prevents different precipitation estimates from being inconsistent with one another when an observed precipitation system extends over two or more types of surfaces. As input data, the PNPR algorithm incorporates the TBs from selected channels, and various additional TBs-derived variables. Ancillary geographical/geophysical inputs (i.e., latitude, terrain height, surface type, season) are also considered during the training phase. The PNPR algorithm outputs consist of both the surface precipitation rate (along with the information on precipitation phase: liquid, mixed, solid) and a pixel-based quality index. We will illustrate the main features of the PNPR algorithm and will show results of a verification study over Europe and Africa. The study is based on the available ground-based radar and/or rain gauge network observations over the European area. In addition, results of the comparison with rainfall products available from the NASA/JAXA Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) (over the African area) and Global Precipitation Measurement (GPM) Dual frequency Precipitation Radar (DPR) will be shown. The analysis is built upon a two-years coincidence dataset of AMSU/MHS and ATMS observations with PR (2013-2014) and DPR (2014-2015). The PNPR is developed within the EUMETSAT H/SAF program (Satellite Application Facility for Operational Hydrology and Water Management), where it is used operationally towards the full exploitation of all microwave radiometers available in the GPM era. The algorithm will be tailored to the future European Microwave Sounder (MWS) onboard the MetOp-Second Generation (MetOp-SG) satellites.

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

PubMed Central

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

2016-01-01

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 (AtmKD/-) 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 AtmKD/-, 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. DOI: http://dx.doi.org/10.7554/eLife.14709.001 PMID:27304073

Mixture block coding with progressive transmission in packet video. Appendix 1: Item 2. M.S. Thesis

NASA Technical Reports Server (NTRS)

Chen, Yun-Chung

1989-01-01

Video transmission will become an important part of future multimedia communication because of dramatically increasing user demand for video, and rapid evolution of coding algorithm and VLSI technology. Video transmission will be part of the broadband-integrated services digital network (B-ISDN). Asynchronous transfer mode (ATM) is a viable candidate for implementation of B-ISDN due to its inherent flexibility, service independency, and high performance. According to the characteristics of ATM, the information has to be coded into discrete cells which travel independently in the packet switching network. A practical realization of an ATM video codec called Mixture Block Coding with Progressive Transmission (MBCPT) is presented. This variable bit rate coding algorithm shows how a constant quality performance can be obtained according to user demand. Interactions between codec and network are emphasized including packetization, service synchronization, flow control, and error recovery. Finally, some simulation results based on MBCPT coding with error recovery are presented.

FPGA Based Reconfigurable ATM Switch Test Bed

NASA Technical Reports Server (NTRS)

Chu, Pong P.; Jones, Robert E.

1998-01-01

Various issues associated with "FPGA Based Reconfigurable ATM Switch Test Bed" are presented in viewgraph form. Specific topics include: 1) Network performance evaluation; 2) traditional approaches; 3) software simulation; 4) hardware emulation; 5) test bed highlights; 6) design environment; 7) test bed architecture; 8) abstract sheared-memory switch; 9) detailed switch diagram; 10) traffic generator; 11) data collection circuit and user interface; 12) initial results; and 13) the following conclusions: Advances in FPGA make hardware emulation feasible for performance evaluation, hardware emulation can provide several orders of magnitude speed-up over software simulation; due to the complexity of hardware synthesis process, development in emulation is much more difficult than simulation and requires knowledge in both networks and digital design.

Performance of a Regional Aeronautical Telecommunications Network

NASA Technical Reports Server (NTRS)

Bretmersky, Steven C.; Ripamonti, Claudio; Konangi, Vijay K.; Kerczewski, Robert J.

2001-01-01

This paper reports the findings of the simulation of the ATN (Aeronautical Telecommunications Network) for three typical average-sized U.S. airports and their associated air traffic patterns. The models of the protocols were designed to achieve the same functionality and meet the ATN specifications. The focus of this project is on the subnetwork and routing aspects of the simulation. To maintain continuous communication between the aircrafts and the ground facilities, a model based on mobile IP is used. The results indicate that continuous communication is indeed possible. The network can support two applications of significance in the immediate future FTP and HTTP traffic. Results from this simulation prove the feasibility of development of the ATN concept for AC/ATM (Advanced Communications for Air Traffic Management).

A CDMA Spotbeam Architecture for the Next Generation Satellite System (NGSS) for the Aeronautical Telecommunications Network (ATN)

NASA Technical Reports Server (NTRS)

Raghavan, Rajesh S.; Shamma, Mohammed A.

2003-01-01

This paper will present work being done to model and simulate a CDMA based Mobile Satellite System architecture for providing all or part of the future Air Traffic Management (ATM) services. Such a system, will help in relieving the dependence on ground based networks, if not eliminate it. Additionally such an architecture can be used in parallel or as a supplementary service along with ground based links to help alleviate any capacity bottlenecks, or in areas where such services are difficult to make available such as in oceanic, remote areas outside the jet highways, or in developing countries where ground services are less available.

Campus Nets for the Nineties.

ERIC Educational Resources Information Center

Neff, Raymond K.

1994-01-01

Describes present and future plans for the campuswide communications network at Case Western Reserve University (Ohio). Highlights include upgrading from baseband to broadband technologies; ATM (Asynchronous Transfer Mode)-based networks that allow simultaneous voice, video, and data transmission; strategic planning goals; implications for…

Fast packet switching algorithms for dynamic resource control over ATM networks

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

Tsang, R.P.; Keattihananant, P.; Chang, T.

1996-12-01

Real-time continuous media traffic, such as digital video and audio, is expected to comprise a large percentage of the network load on future high speed packet switch networks such as ATM. A major feature which distinguishes high speed networks from traditional slower speed networks is the large amount of data the network must process very quickly. For efficient network usage, traffic control mechanisms are essential. Currently, most mechanisms for traffic control (such as flow control) have centered on the support of Available Bit Rate (ABR), i.e., non real-time, traffic. With regard to ATM, for ABR traffic, two major types ofmore » schemes which have been proposed are rate- control and credit-control schemes. Neither of these schemes are directly applicable to Real-time Variable Bit Rate (VBR) traffic such as continuous media traffic. Traffic control for continuous media traffic is an inherently difficult problem due to the time- sensitive nature of the traffic and its unpredictable burstiness. In this study, we present a scheme which controls traffic by dynamically allocating/de- allocating resources among competing VCs based upon their real-time requirements. This scheme incorporates a form of rate- control, real-time burst-level scheduling and link-link flow control. We show analytically potential performance improvements of our rate- control scheme and present a scheme for buffer dimensioning. We also present simulation results of our schemes and discuss the tradeoffs inherent in maintaining high network utilization and statistically guaranteeing many users` Quality of Service.« less

Planning and cost analysis of digital radiography services for a network of hospitals (the Veterans Integrated Service Network).

PubMed

Duerinckx, A J; Kenagy, J J; Grant, E G

1998-01-01

This study analysed the design and cost of a picture archiving and communications system (PACS), computerized radiography (CR) and a wide-area network for teleradiology. The Desert Pacific Healthcare Network comprises 10 facilities, including four tertiary medical centres and one small hospital. Data were collected on radiologists' workloads, and patient and image flow within and between these medical centres. These were used to estimate the size and cash flows associated with a system-wide implementation of PACS, CR and teleradiology services. A cost analysis model was used to estimate the potential cost savings in a filmless radiology environment. ATM technology was selected as the communications medium between the medical centres. A strategic plan and business plan were successfully developed. The cost model predicted the cost-effectiveness of the proposed PACS/CR configuration within four to six years, if the base costs were kept low. The experience gained in design and cost analysis of a PACS/teleradiology network will serve as a model for similar projects.

ATM LAN Emulation: Getting from Here to There.

ERIC Educational Resources Information Center

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)

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

NASA Astrophysics Data System (ADS)

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.

Parallel ALLSPD-3D: Speeding Up Combustor Analysis Via Parallel Processing

NASA Technical Reports Server (NTRS)

Fricker, David M.

1997-01-01

The ALLSPD-3D Computational Fluid Dynamics code for reacting flow simulation was run on a set of benchmark test cases to determine its parallel efficiency. These test cases included non-reacting and reacting flow simulations with varying numbers of processors. Also, the tests explored the effects of scaling the simulation with the number of processors in addition to distributing a constant size problem over an increasing number of processors. The test cases were run on a cluster of IBM RS/6000 Model 590 workstations with ethernet and ATM networking plus a shared memory SGI Power Challenge L workstation. The results indicate that the network capabilities significantly influence the parallel efficiency, i.e., a shared memory machine is fastest and ATM networking provides acceptable performance. The limitations of ethernet greatly hamper the rapid calculation of flows using ALLSPD-3D.

GLOBECOM '92 - IEEE Global Telecommunications Conference, Orlando, FL, Dec. 6-9, 1992, Conference Record. Vols. 1-3

NASA Astrophysics Data System (ADS)

Papers are presented on such topics as the wireless data network in PCS, advances in digital mobile networks, ATM switching experiments, broadband applications, network planning, and advances in SONET/SDH implementations. Consideration is also given to gigabit computer networks, techniques for modeling large high-speed networks, coding and modulation, the next-generation lightwave system, signaling systems for broadband ISDN, satellite technologies, and advances in standardization of low-rate signal processing.

Use of FEC coding to improve statistical multiplexing performance for video transport over ATM networks

NASA Astrophysics Data System (ADS)

Kurceren, Ragip; Modestino, James W.

1998-12-01

The use of forward error-control (FEC) coding, possibly in conjunction with ARQ techniques, has emerged as a promising approach for video transport over ATM networks for cell-loss recovery and/or bit error correction, such as might be required for wireless links. Although FEC provides cell-loss recovery capabilities it also introduces transmission overhead which can possibly cause additional cell losses. A methodology is described to maximize the number of video sources multiplexed at a given quality of service (QoS), measured in terms of decoded cell loss probability, using interlaced FEC codes. The transport channel is modelled as a block interference channel (BIC) and the multiplexer as single server, deterministic service, finite buffer supporting N users. Based upon an information-theoretic characterization of the BIC and large deviation bounds on the buffer overflow probability, the described methodology provides theoretically achievable upper limits on the number of sources multiplexed. Performance of specific coding techniques using interlaced nonbinary Reed-Solomon (RS) codes and binary rate-compatible punctured convolutional (RCPC) codes is illustrated.

Neural network model for automatic traffic incident detection : executive summary.

DOT National Transportation Integrated Search

2001-04-01

Automatic freeway incident detection is an important component of advanced transportation management systems (ATMS) that provides information for emergency relief and traffic control and management purposes. In this research, a multi-paradigm intelli...

Impact of ultrasound video transfer on the practice of ultrasound

NASA Astrophysics Data System (ADS)

Duerinckx, Andre J.; Hayrapetian, Alek S.; Grant, Edward G.; Valentino, Daniel J.; Rahbar, Darius; Kiszonas, Mike; Franco, Ricky; Melany, Michelle; Narin, Sherelle L.; Ragavendra, Nagesh

1996-05-01

Sonography can be highly dependent on real-time imaging and as such is highly physician intensive. Such situations arise mostly during complicated ultrasound radiology studies or echocardiology examinations. Under those circumstances it would be of benefit to transmit real-time images beyond the immediate area of the ultrasound laboratory when a physician is not on location. We undertook this study to determine if both static and dynamic image transfer to remote locations might be accomplished using an ultrafast ATM network and PACS. Image management of the local image files was performed by a commercial PACS from AGFA corporation. The local network was Ethernet based, and the global network was based on Asynchronous Transfer Mode (ATM, rates up to 100 Mbits/sec). Real-time image transfer involved two teaching hospitals, one of which had 2 separate ultrasound facilities. Radiologists consulted with technologists via telephone while the examinations were being performed. The applications of ATM network providing real time video for ultrasound imaging in a clinical environment and its potential impact on health delivery and clinical teaching. This technology increased technologist and physician productivity due to the elimination of commute time for physicians and waiting time for technologists and patients. Physician confidence in diagnosis increased compared to reviewing static images alone. This system provided instant access for radiologists to real-time scans from remote sites. Image quality and frame rate were equivalent to the original. The system increased productivity by allowing physicians to monitor studies at multiple sites simultaneously.

Recent Greenland Thinning from Operation IceBridge ATM and LVIS Data

NASA Astrophysics Data System (ADS)

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.

Neural network model for automatic traffic incident detection : final report, August 2001.

DOT National Transportation Integrated Search

2001-08-01

Automatic freeway incident detection is an important component of advanced transportation management systems (ATMS) that provides information for emergency relief and traffic control and management purposes. In this research, a multi-paradigm intelli...

Privacy-preserving self-helped medical diagnosis scheme based on secure two-party computation in wireless sensor networks.

PubMed

Sun, Yi; Wen, Qiaoyan; Zhang, Yudong; Li, Wenmin

2014-01-01

With the continuing growth of wireless sensor networks in pervasive medical care, people pay more and more attention to privacy in medical monitoring, diagnosis, treatment, and patient care. On one hand, we expect the public health institutions to provide us with better service. On the other hand, we would not like to leak our personal health information to them. In order to balance this contradiction, in this paper we design a privacy-preserving self-helped medical diagnosis scheme based on secure two-party computation in wireless sensor networks so that patients can privately diagnose themselves by inputting a health card into a self-helped medical diagnosis ATM to obtain a diagnostic report just like drawing money from a bank ATM without revealing patients' health information and doctors' diagnostic skill. It makes secure self-helped disease diagnosis feasible and greatly benefits patients as well as relieving the heavy pressure of public health institutions.

Privacy-Preserving Self-Helped Medical Diagnosis Scheme Based on Secure Two-Party Computation in Wireless Sensor Networks

PubMed Central

Wen, Qiaoyan; Zhang, Yudong; Li, Wenmin

2014-01-01

With the continuing growth of wireless sensor networks in pervasive medical care, people pay more and more attention to privacy in medical monitoring, diagnosis, treatment, and patient care. On one hand, we expect the public health institutions to provide us with better service. On the other hand, we would not like to leak our personal health information to them. In order to balance this contradiction, in this paper we design a privacy-preserving self-helped medical diagnosis scheme based on secure two-party computation in wireless sensor networks so that patients can privately diagnose themselves by inputting a health card into a self-helped medical diagnosis ATM to obtain a diagnostic report just like drawing money from a bank ATM without revealing patients' health information and doctors' diagnostic skill. It makes secure self-helped disease diagnosis feasible and greatly benefits patients as well as relieving the heavy pressure of public health institutions. PMID:25126107

Enhancing End-to-End Performance of Information Services Over Ka-Band Global Satellite Networks

NASA Technical Reports Server (NTRS)

Bhasin, Kul B.; Glover, Daniel R.; Ivancic, William D.; vonDeak, Thomas C.

1997-01-01

The Internet has been growing at a rapid rate as the key medium to provide information services such as e-mail, WWW and multimedia etc., however its global reach is limited. Ka-band communication satellite networks are being developed to increase the accessibility of information services via the Internet at global scale. There is need to assess satellite networks in their ability to provide these services and interconnect seamlessly with existing and proposed terrestrial telecommunication networks. In this paper the significant issues and requirements in providing end-to-end high performance for the delivery of information services over satellite networks based on various layers in the OSI reference model are identified. Key experiments have been performed to evaluate the performance of digital video and Internet over satellite-like testbeds. The results of the early developments in ATM and TCP protocols over satellite networks are summarized.

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

NASA Astrophysics Data System (ADS)

Kusmierczyk-Michulec, Jolanta

2017-04-01

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

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

DOT National Transportation Integrated Search

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...

XUNET experimental high-speed network testbed CRADA 1136, DOE TTI No. 92-MULT-020-B2

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

Palmer, R.E.

1996-04-01

XUNET is a research program with AT&T and other partners to study high-speed wide area communication between local area networks over a backbone using Asynchronous Transfer Mode (ATM) switches. Important goals of the project are to develop software techniques for network control and management, and applications for high-speed networks. The project entails building a testbed between member sites to explore performance issues for mixed network traffic such as congestion control, multimedia communications protocols, segmentation and reassembly of ATM cells, and overall data throughput rates.

Snowfall Rate Retrieval using NPP ATMS Passive Microwave Measurements

NASA Technical Reports Server (NTRS)

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

2014-01-01

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., 2014). 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. The ATMS SFR product is validated against radar and gauge snowfall data and shows that the ATMS algorithm outperforms the AMSU/MHS SFR.

ATM: Restructing Learning for Deaf Students.

ERIC Educational Resources Information Center

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…

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

NASA Technical Reports Server (NTRS)

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

1996-01-01

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

Performance of Duplex Communication Between a LEO Satellite and Terrestrial Location Using a GEO Constellation

NASA Technical Reports Server (NTRS)

Robinson, Daryl C.; Konangi, Vijay K.; Wallett, Thomas M.

1998-01-01

A network comprised of a terrestrial site, a constellation of three GEO satellites and a LEO satellite is modeled and simulated. Continuous communication between the terrestrial site and the LEO satellite is facilitated by the GEO satellites. The LEO satellite has the orbital characteristics of the International Space Station. Communication in the network is based on TCP/IP over ATM, with the ABR service category providing the QoS, at OC-3 data rate. The OSPF protocol is used for routing. We simulate FTP file transfers, with the terrestrial site serving as the client and the LEO satellite being the server. The performance characteristics are presented.

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

DTIC Science & Technology

1994-06-01

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

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

NASA Technical Reports Server (NTRS)

Ivancic, William D.

1998-01-01

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

NPP ATMS Snowfall Rate Product

NASA Technical Reports Server (NTRS)

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.

Testbed for Satellite and Terrestrial Interoperability (TSTI)

NASA Technical Reports Server (NTRS)

Gary, J. Patrick

1998-01-01

Various issues associated with the "Testbed for Satellite and Terrestrial Interoperability (TSTI)" are presented in viewgraph form. Specific topics include: 1) General and specific scientific technical objectives; 2) ACTS experiment No. 118: 622 Mbps network tests between ATDNet and MAGIC via ACTS; 3) ATDNet SONET/ATM gigabit network; 4) Testbed infrastructure, collaborations and end sites in TSTI based evaluations; 5) the Trans-Pacific digital library experiment; and 6) ESDCD on-going network projects.

Technology Directions for the 21st Century. Volume 3

NASA Technical Reports Server (NTRS)

Crimi, Giles F.; Botta, Robert; Ditanna, Thomas; Verheggen, Henry; Stancati, Michael; Feingold, Harvey; Jacobs, Mark

1996-01-01

New technologies will unleash the huge capacity of fiber-optic cable to meet growing demands for bandwidth. Companies will continue to replace private networks with public network bandwidth-on-demand. Although asynchronous transfer mode (ATM) is the transmission technology favored by many, its penetration will be slower than anticipated. Hybrid networks - e.g., a mix of ATM, frame relay, and fast Ethernet - may predominate, both as interim and long-term solutions, based on factors such as availability, interoperability, and cost. Telecommunications equipment and services prices will decrease further due to increased supply and more competition. Explosive Internet growth will continue, requiring additional backbone transmission capacity and enhanced protocols, but it is not clear who will fund the upgrade. Within ten years, space-based constellations of satellites in Low Earth orbit (LEO) will serve mobile users employing small, low-power terminals. 'Little LEO's' will provide packet transmission services and geo-position determination. 'Big LEO's' will function as global cellular telephone networks, with some planning to offer video and interactive multimedia services. Geosynchronous satellites also are proposed for mobile voice grade links and high-bandwidth services. NASA may benefit from resulting cost reductions in components, space hardware, launch services, and telecommunications services.

Achieving High Throughput for Data Transfer over ATM Networks

NASA Technical Reports Server (NTRS)

Johnson, Marjory J.; Townsend, Jeffrey N.

1996-01-01

File-transfer rates for ftp are often reported to be relatively slow, compared to the raw bandwidth available in emerging gigabit networks. While a major bottleneck is disk I/O, protocol issues impact performance as well. Ftp was developed and optimized for use over the TCP/IP protocol stack of the Internet. However, TCP has been shown to run inefficiently over ATM. In an effort to maximize network throughput, data-transfer protocols can be developed to run over UDP or directly over IP, rather than over TCP. If error-free transmission is required, techniques for achieving reliable transmission can be included as part of the transfer protocol. However, selected image-processing applications can tolerate a low level of errors in images that are transmitted over a network. In this paper we report on experimental work to develop a high-throughput protocol for unreliable data transfer over ATM networks. We attempt to maximize throughput by keeping the communications pipe full, but still keep packet loss under five percent. We use the Bay Area Gigabit Network Testbed as our experimental platform.

Application of AirCell Cellular AMPS Network and Iridium Satellite System Dual Mode Service to Air Traffic Management

NASA Technical Reports Server (NTRS)

Shamma, Mohammed A.

2004-01-01

The AirCell/Iridium dual mode service is evaluated for potential applications to Air Traffic Management (ATM) communication needs. The AirCell system which is largely based on the Advanced Mobile Phone System (AMPS) technology, and the Iridium FDMA/TDMA system largely based on the Global System for Mobile Communications(GSM) technology, can both provide communication relief for existing or future aeronautical communication links. Both have a potential to serve as experimental platforms for future technologies via a cost effective approach. The two systems are well established in the entire CONUS and globally hence making it feasible to utilize in all regions, for all altitudes, and all classes of aircraft. Both systems have been certified for air usage. The paper summarizes the specifications of the AirCell/Iridium system, as well as the ATM current and future links, and application specifications. the paper highlights the scenarios, applications, and conditions under which the AirCell/Iridium technology can be suited for ATM Communication.

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

PubMed Central

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

Optical implementation of a parallel out-of-band controller for large broadband ATM switch applications

NASA Astrophysics Data System (ADS)

Cloonan, Thomas J.; Richards, Gaylord W.; Lentine, Anthony L.

1996-03-01

Asynchronous transfer mode (ATM) is rapidly becoming the transport mechanism of choice for the information superhighway, because it promises the bandwidth and flexibility needed for many voice, video and data service offerings. Some industry experts project that the required sizes for ATM switching equipment in the public-switched environment will reach the Tbps range by the beginning of the next decade. This paper analyzes the problems associated with controlling the flow of packets within a broadband ATM switch of this size. The analysis is based on the requirements of the growable packet switch architecture. The paper proposes a novel solution to the problem of hunting paths within an ATM packet switch network. The resulting control scheme is unconventional in two ways. First, it uses an out-of-band control algorithm instead of the more common self-routing approach. In particular, we explore the benefits of using a parallel processor as an out-of-band controller for a growable packet switch distribution network. The processor permits additional levels of parallelism to be added to the out-of-band control function so that path hunts can be performed for all N of the input ports within a single cell interval. The proposed approach is also unconventional because it uses free-space digital optics to guide signals between successive stages of the controller. The paper describes the underlying motivations for implementing an optical out-of-band controller for an ATM switch, and it also describes the logic within a controller node that has been fabricated using a hybrid Si CMOS/GaAs SEED technology. The node uses optical detectors (in GaAs), amplifiers and digital control logic (in Si), and optical modulators (in GaAs). Free-space optical connections between successive device arrays can be provided using either bulk optical elements or micro-optics, but the optical interconnects must provide massive fanout capability. An architectural analysis studying the feasibility of applying free-space optics in this proposed ATM switch controller also is presented.

Performance Evaluation of the NASA/KSC Transmission System

NASA Technical Reports Server (NTRS)

Christensen, Kenneth J.

2000-01-01

NASA-KSC currently uses three bridged 100-Mbps FDDI segments as its backbone for data traffic. The FDDI Transmission System (FTXS) connects the KSC industrial area, KSC launch complex 39 area, and the Cape Canaveral Air Force Station. The report presents a performance modeling study of the FTXS and the proposed ATM Transmission System (ATXS). The focus of the study is on performance of MPEG video transmission on these networks. Commercial modeling tools - the CACI Predictor and Comnet tools - were used. In addition, custom software tools were developed to characterize conversation pairs in Sniffer trace (capture) files to use as input to these tools. A baseline study of both non-launch and launch day data traffic on the FTXS is presented. MPEG-1 and MPEG-2 video traffic was characterized and the shaping of it evaluated. It is shown that the characteristics of a video stream has a direct effect on its performance in a network. It is also shown that shaping of video streams is necessary to prevent overflow losses and resulting poor video quality. The developed models can be used to predict when the existing FTXS will 'run out of room' and for optimizing the parameters of ATM links used for transmission of MPEG video. Future work with these models can provide useful input and validation to set-top box projects within the Advanced Networks Development group in NASA-KSC Development Engineering.

Retrieval of atmospheric elemental carbon records using lake sediments: Implications in radiative forcing

NASA Astrophysics Data System (ADS)

Ahmed, Tanveer

Elemental or black carbon (EC or BC) aerosols produced during incomplete combustion strongly absorb solar radiation and contribute to global warming, and cause cardiopulmonary disease. Long-term atmospheric EC measurements, [EC]atm, are needed to validate global climate models to estimate the impact of EC on earth's temperature. Such data is sparse. In this work, a new technique was developed to retrieve the historical record of [EC]atm in the Northeastern US for the past two centuries. Measurements of [EC]atm were made in the monthly composites of daily filters collected over ˜30 yr at Whiteface Mountain (WFM), NY using the thermal optical method. Bottom sediment cores were collected from four lakes near WFM. They were sliced in horizontal sections, freeze dried, and their ages determined 210Pb dating technique. EC in sediments was chemically separated and its concentration determined using the same thermal-optical method. It was shown that [EC]sed = K [EC]atm where K is constant (m3/g). Measurements of [EC]atm and [EC]sed for the ˜1978 to 2005 period was used to determine the value for K. The value of K and [EC]sed for periods before 1978 were used to determine [EC]atm for the past ˜100 yrs. [EC]atm in the preindustrial period in US, ˜1850, varied between 38 and 73 ng/m3, with a mean value of 56 +/- 14 ng/m3. [EC]atm was found to increase sharply with rapid industrialization and reached its maximum value of 751 +/- 265 ng/m3 during 1920s, which was a factor of ˜12 higher compared to the mean preindustrial level. The [EC]atm declined gradually until ˜1980 and then decreased sharply. Directly measured values of [EC]atm are only ˜25% higher compared to the mean preindustrial level. Model US EC emissions estimates of Novakov et al. (2003), based on energy consumptions, reproduce our [EC]sed trends quite well for the ˜1900 to 1930 period. Subsequently, the model EC values drop-off more rapidly than our [EC]atm. To extend the technique where long tern [EC]atm are not available, a new generalized mathematical model expression to determine K was developed. The value of K calculated using the model agreed within +/-30% with the measurements.

Network Solutions.

ERIC Educational Resources Information Center

Vietzke, Robert; And Others

1996-01-01

This special section explains the latest developments in networking technologies, profiles school districts benefiting from successful implementations, and reviews new products for building networks. Highlights include ATM (asynchronous transfer mode), cable modems, networking switches, Internet screening software, file servers, network management…

MoNET: media over net gateway processor for next-generation network

NASA Astrophysics Data System (ADS)

Elabd, Hammam; Sundar, Rangarajan; Dedes, John

2001-12-01

MoNETTM (Media over Net) SX000 product family is designed using a scalable voice, video and packet-processing platform to address applications with channel densities from few voice channels to four OC3 per card. This platform is developed for bridging public circuit-switched network to the next generation packet telephony and data network. The platform consists of a DSP farm, RISC processors and interface modules. DSP farm is required to execute voice compression, image compression and line echo cancellation algorithms for large number of voice, video, fax, and modem or data channels. RISC CPUs are used for performing various packetizations based on RTP, UDP/IP and ATM encapsulations. In addition, RISC CPUs also participate in the DSP farm load management and communication with the host and other MoP devices. The MoNETTM S1000 communications device is designed for voice processing and for bridging TDM to ATM and IP packet networks. The S1000 consists of the DSP farm based on Carmel DSP core and 32-bit RISC CPU, along with Ethernet, Utopia, PCI, and TDM interfaces. In this paper, we will describe the VoIP infrastructure, building blocks of the S500, S1000 and S3000 devices, algorithms executed on these device and associated channel densities, detailed DSP architecture, memory architecture, data flow and scheduling.

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

ERIC Educational Resources Information Center

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…

12 CFR 235.5 - Exemptions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED... rely on lists published by the Board to determine whether an issuer, together with its affiliates, has... calendar month from an ATM that is part of the issuer's designated ATM network. ...

12 CFR 235.5 - Exemptions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED... rely on lists published by the Board to determine whether an issuer, together with its affiliates, has... calendar month from an ATM that is part of the issuer's designated ATM network. ...

12 CFR 235.5 - Exemptions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED... rely on lists published by the Board to determine whether an issuer, together with its affiliates, has... calendar month from an ATM that is part of the issuer's designated ATM network. ...

Genetic ataxia telangiectasia porcine model phenocopies the multisystemic features of the human disease.

PubMed

Beraldi, Rosanna; Meyerholz, David K; Savinov, Alexei; Kovács, Attila D; Weimer, Jill M; Dykstra, Jordan A; Geraets, Ryan D; Pearce, David A

2017-11-01

Ataxia telangiectasia (AT) is a progressive multisystem autosomal recessive disorder caused by mutations in the AT-mutated (ATM) gene. Early onset AT in children is characterized by cerebellar degeneration, leading to motor impairment. Lung disease and cancer are the two most common causes of death in AT patients. Accelerated thymic involution may contribute to the cancer, and recurrent and/or chronic respiratory infections may be a contributing factor to lung disease in AT. AT patients have fertility issues, are highly sensitive to ionizing radiation and they present oculocutaneous telangiectasia. Current treatments only slightly ameliorate disease symptoms; therapy that alters or reverses the course of the disease has not yet been discovered. Previously, we have shown that ATM -/- pigs, a novel model of AT, present with a loss of Purkinje cells, altered cerebellar cytoarchitecture and motor coordination deficits. ATM -/- porcine model not only recapitulates the neurological phenotype, but also other multifaceted clinical features of the human disease. Our current study shows that ATM -/- female pigs are infertile, with anatomical and functional signs of an immature reproductive system. Both male and female ATM -/- pigs show abnormal thymus structure with decreased cell cycle and apoptosis markers in the gland. Moreover, ATM -/- pigs have an altered immune system with decreased CD8 + and increased natural killer and CD4 + CD8 + double-positive cells. Nevertheless, ATM -/- pigs manifest a deficient IgG response after a viral infection. Based on the neurological and peripheral phenotypes, the ATM -/- pig is a novel genetic model that may be used for therapeutic assessments and to identify pathomechanisms of this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical experience with a high-performance ATM-connected DICOM archive for cardiology

NASA Astrophysics Data System (ADS)

Solomon, Harry P.

1997-05-01

A system to archive large image sets, such as cardiac cine runs, with near realtime response must address several functional and performance issues, including efficient use of a high performance network connection with standard protocols, an architecture which effectively integrates both short- and long-term mass storage devices, and a flexible data management policy which allows optimization of image distribution and retrieval strategies based on modality and site-specific operational use. Clinical experience with such as archive has allowed evaluation of these systems issues and refinement of a traffic model for cardiac angiography.

Join Us in a Participatory Approach to Training, Learning & Production. A Practical Guide to the Action Training Model.

ERIC Educational Resources Information Center

Frings, A.; And Others

This handbook is intended to help trainers and development workers plan and conduct training programs based on the Action Training Model (ATM). The ATM combines training with action and learning with production by building upon participants' knowledge and learning needs and involving participants in a process of active learning and cooperative…

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

NASA Astrophysics Data System (ADS)

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.

Reduced Synchronization Persistence in Neural Networks Derived from Atm-Deficient Mice

PubMed Central

Levine-Small, Noah; Yekutieli, Ziv; Aljadeff, Jonathan; Boccaletti, Stefano; Ben-Jacob, Eshel; Barzilai, Ari

2011-01-01

Many neurodegenerative diseases are characterized by malfunction of the DNA damage response. Therefore, it is important to understand the connection between system level neural network behavior and DNA. Neural networks drawn from genetically engineered animals, interfaced with micro-electrode arrays allowed us to unveil connections between networks’ system level activity properties and such genome instability. We discovered that Atm protein deficiency, which in humans leads to progressive motor impairment, leads to a reduced synchronization persistence compared to wild type synchronization, after chemically imposed DNA damage. Not only do these results suggest a role for DNA stability in neural network activity, they also establish an experimental paradigm for empirically determining the role a gene plays on the behavior of a neural network. PMID:21519382

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

PubMed

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.

ATM protein is deficient in over 40% of lung adenocarcinomas

PubMed Central

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.

2016-01-01

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. PMID:27259260

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

PubMed

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).

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

PubMed

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

1997-01-01

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

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

NASA Technical Reports Server (NTRS)

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.

Existing and Required Modeling Capabilities for Evaluating ATM Systems and Concepts

NASA Technical Reports Server (NTRS)

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

1997-01-01

ATM systems throughout the world are entering a period of major transition and change. The combination of important technological developments and of the globalization of the air transportation industry has necessitated a reexamination of some of the fundamental premises of existing Air Traffic Management (ATM) concepts. New ATM concepts have to be examined, concepts that may place more emphasis on: strategic traffic management; planning and control; partial decentralization of decision-making; and added reliance on the aircraft to carry out strategic ATM plans, with ground controllers confined primarily to a monitoring and supervisory role. 'Free Flight' is a case in point. In order to study, evaluate and validate such new concepts, the ATM community will have to rely heavily on models and computer-based tools/utilities, covering a wide range of issues and metrics related to safety, capacity and efficiency. The state of the art in such modeling support is adequate in some respects, but clearly deficient in others. It is the objective of this study to assist in: (1) assessing the strengths and weaknesses of existing fast-time models and tools for the study of ATM systems and concepts and (2) identifying and prioritizing the requirements for the development of additional modeling capabilities in the near future. A three-stage process has been followed to this purpose: 1. Through the analysis of two case studies involving future ATM system scenarios, as well as through expert assessment, modeling capabilities and supporting tools needed for testing and validating future ATM systems and concepts were identified and described. 2. Existing fast-time ATM models and support tools were reviewed and assessed with regard to the degree to which they offer the capabilities identified under Step 1. 3 . The findings of 1 and 2 were combined to draw conclusions about (1) the best capabilities currently existing, (2) the types of concept testing and validation that can be carried out reliably with such existing capabilities and (3) the currently unavailable modeling capabilities that should receive high priority for near-term research and development. It should be emphasized that the study is concerned only with the class of 'fast time' analytical and simulation models. 'Real time' models, that typically involve humans-in-the-loop, comprise another extensive class which is not addressed in this report. However, the relationship between some of the fast-time models reviewed and a few well-known real-time models is identified in several parts of this report and the potential benefits from the combined use of these two classes of models-a very important subject-are discussed in chapters 4 and 7.

Scalable and reusable emulator for evaluating the performance of SS7 networks

NASA Astrophysics Data System (ADS)

Lazar, Aurel A.; Tseng, Kent H.; Lim, Koon Seng; Choe, Winston

1994-04-01

A scalable and reusable emulator was designed and implemented for studying the behavior of SS7 networks. The emulator design was largely based on public domain software. It was developed on top of an environment supported by PVM, the Parallel Virtual Machine, and managed by OSIMIS-the OSI Management Information Service platform. The emulator runs on top of a commercially available ATM LAN interconnecting engineering workstations. As a case study for evaluating the emulator, the behavior of the Singapore National SS7 Network under fault and unbalanced loading conditions was investigated.

Asynchronous transfer mode link performance over ground networks

NASA Technical Reports Server (NTRS)

Chow, E. T.; Markley, R. W.

1993-01-01

The results of an experiment to determine the feasibility of using asynchronous transfer mode (ATM) technology to support advanced spacecraft missions that require high-rate ground communications and, in particular, full-motion video are reported. Potential nodes in such a ground network include Deep Space Network (DSN) antenna stations, the Jet Propulsion Laboratory, and a set of national and international end users. The experiment simulated a lunar microrover, lunar lander, the DSN ground communications system, and distributed science users. The users were equipped with video-capable workstations. A key feature was an optical fiber link between two high-performance workstations equipped with ATM interfaces. Video was also transmitted through JPL's institutional network to a user 8 km from the experiment. Variations in video depending on the networks and computers were observed, the results are reported.

Disease severity in a mouse model of ataxia telangiectasia is modulated by the DNA damage checkpoint gene Hus1

PubMed Central

Balmus, Gabriel; Zhu, Min; Mukherjee, Sucheta; Lyndaker, Amy M.; Hume, Kelly R.; Lee, Jaesung; Riccio, Mark L.; Reeves, Anthony P.; Sutter, Nathan B.; Noden, Drew M.; Peters, Rachel M.; Weiss, Robert S.

2012-01-01

The human genomic instability syndrome ataxia telangiectasia (A-T), caused by mutations in the gene encoding the DNA damage checkpoint kinase ATM, is characterized by multisystem defects including neurodegeneration, immunodeficiency and increased cancer predisposition. ATM is central to a pathway that responds to double-strand DNA breaks, whereas the related kinase ATR leads a parallel signaling cascade that is activated by replication stress. To dissect the physiological relationship between the ATM and ATR pathways, we generated mice defective for both. Because complete ATR pathway inactivation causes embryonic lethality, we weakened the ATR mechanism to different degrees by impairing HUS1, a member of the 911 complex that is required for efficient ATR signaling. Notably, simultaneous ATM and HUS1 defects caused synthetic lethality. Atm/Hus1 double-mutant embryos showed widespread apoptosis and died mid-gestationally. Despite the underlying DNA damage checkpoint defects, increased DNA damage signaling was observed, as evidenced by H2AX phosphorylation and p53 accumulation. A less severe Hus1 defect together with Atm loss resulted in partial embryonic lethality, with the surviving double-mutant mice showing synergistic increases in genomic instability and specific developmental defects, including dwarfism, craniofacial abnormalities and brachymesophalangy, phenotypes that are observed in several human genomic instability disorders. In addition to identifying tissue-specific consequences of checkpoint dysfunction, these data highlight a robust, cooperative configuration for the mammalian DNA damage response network and further suggest HUS1 and related genes in the ATR pathway as candidate modifiers of disease severity in A-T patients. PMID:22575700

Telemedicine with integrated data security in ATM-based networks

NASA Astrophysics Data System (ADS)

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.

The Aeronautical Data Link: Taxonomy, Architectural Analysis, and Optimization

NASA Technical Reports Server (NTRS)

Morris, A. Terry; Goode, Plesent W.

2002-01-01

The future Communication, Navigation, and Surveillance/Air Traffic Management (CNS/ATM) System will rely on global satellite navigation, and ground-based and satellite based communications via Multi-Protocol Networks (e.g. combined Aeronautical Telecommunications Network (ATN)/Internet Protocol (IP)) to bring about needed improvements in efficiency and safety of operations to meet increasing levels of air traffic. This paper will discuss the development of an approach that completely describes optimal data link architecture configuration and behavior to meet the multiple conflicting objectives of concurrent and different operations functions. The practical application of the approach enables the design and assessment of configurations relative to airspace operations phases. The approach includes a formal taxonomic classification, an architectural analysis methodology, and optimization techniques. The formal taxonomic classification provides a multidimensional correlation of data link performance with data link service, information protocol, spectrum, and technology mode; and to flight operations phase and environment. The architectural analysis methodology assesses the impact of a specific architecture configuration and behavior on the local ATM system performance. Deterministic and stochastic optimization techniques maximize architectural design effectiveness while addressing operational, technology, and policy constraints.

Atm reactivation reverses ataxia telangiectasia phenotypes in vivo.

PubMed

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.

Distributed health care imaging information systems

NASA Astrophysics Data System (ADS)

Thompson, Mary R.; Johnston, William E.; Guojun, Jin; Lee, Jason; Tierney, Brian; Terdiman, Joseph F.

1997-05-01

We have developed an ATM network-based system to collect and catalogue cardio-angiogram videos from the source at a Kaiser central facility and make them available for viewing by doctors at primary care Kaiser facilities. This an example of the general problem of diagnostic data being generated at tertiary facilities, while the images, or other large data objects they produce, need to be used from a variety of other locations such as doctor's offices or local hospitals. We describe the use of a highly distributed computing and storage architecture to provide all aspects of collecting, storing, analyzing, and accessing such large data-objects in a metropolitan area ATM network. Our large data-object management system provides network interface between the object sources, the data management system and the user of the data. As the data is being stored, a cataloguing system automatically creates and stores condensed versions of the data, textural metadata and pointers to the original data. The catalogue system provides a Web-based graphical interface to the data. The user is able the view the low-resolution data with a standard Internet connection and Web browser. If high-resolution is required, a high-speed connection and special application programs can be used to view the high-resolution original data.

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

PubMed

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.

Atmospheric transport modelling in support of CTBT verification—overview and basic concepts

NASA Astrophysics Data System (ADS)

Wotawa, Gerhard; De Geer, Lars-Erik; Denier, Philippe; Kalinowski, Martin; Toivonen, Harri; D'Amours, Real; Desiato, Franco; Issartel, Jean-Pierre; Langer, Matthias; Seibert, Petra; Frank, Andreas; Sloan, Craig; Yamazawa, Hiromi

Under the provisions of the Comprehensive Nuclear-Test-Ban Treaty (CTBT), a global monitoring system comprising different verification technologies is currently being set up. The network will include 80 radionuclide (RN) stations distributed all over the globe that measure treaty-relevant radioactive species. While the seismic subsystem cannot distinguish between chemical and nuclear explosions, RN monitoring would provide the "smoking gun" of a possible treaty violation. Atmospheric transport modelling (ATM) will be an integral part of CTBT verification, since it provides a geo-temporal location capability for the RN technology. In this paper, the basic concept for the future ATM software system to be installed at the International Data Centre is laid out. The system is based on the operational computation of multi-dimensional source-receptor sensitivity fields for all RN samples by means of adjoint tracer transport modelling. While the source-receptor matrix methodology has already been applied in the past, the system that we suggest will be unique and unprecedented, since it is global, real-time and aims at uncovering source scenarios that are compatible with measurements. Furthermore, it has to deal with source dilution ratios that are by orders of magnitude larger than in typical transport model applications. This new verification software will need continuous scientific attention, and may well provide a prototype system for future applications in areas of environmental monitoring, emergency response and verification of other international agreements and treaties.

MFehi adipose tissue macrophages compensate for tissue iron pertubations in mice.

PubMed

Hubler, Merla J; Erikson, Keith M; Kennedy, Arion J; Hasty, Alyssa H

2018-05-16

Resident adipose tissue macrophages (ATMs) play multiple roles to maintain tissue homeostasis, such as removing excess FFAs and regulation of extracellular matrix. The phagocytic nature and oxidative resiliency of macrophages not only allows them to function as innate immune cells but also to respond to specific tissue needs, such as iron homeostasis. MFe hi ATMs are a subtype of resident ATMs that we recently identified to have twice the intracellular iron content as other ATMs and elevated expression of iron handling genes. While studies have demonstrated iron homeostasis is important for adipocyte health, little is known about how MFe hi ATMs may respond to and influence AT iron availability. Two methodologies were used to address this question - dietary iron supplementation and intraperitoneal iron injection. Upon exposure to high dietary iron, MFe hi ATMs accumulated excess iron, while the iron content of MFe lo ATMs and adipocytes remained unchanged. In this model of chronic iron excess, MFe hi ATMs exhibited increased expression of genes involved in iron storage. In the injection model, MFe hi ATMs incorporated high levels of iron and adipocytes were spared iron overload. This acute model of iron overload was associated with increased numbers of MFe hi ATMs; 17% could be attributed to monocyte recruitment and 83% to MFe lo ATM incorporation into the MFe hi pool. The MFe hi ATM population maintained its low inflammatory profile and iron cycling expression profile. These studies expand the field's understanding of ATMs and confirm that they can respond as a tissue iron sink in models of iron overload.

A broadband multimedia TeleLearning system

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

Wang, Ruiping; Karmouch, A.

1996-12-31

In this paper we discuss a broadband multimedia TeleLearning system under development in the Multimedia Information Research Laboratory at the University of Ottawa. The system aims at providing a seamless environment for TeleLearning using the latest telecommunication and multimedia information processing technology. It basically consists of a media production center, a courseware author site, a courseware database, a courseware user site, and an on-line facilitator site. All these components are distributed over an ATM network and work together to offer a multimedia interactive courseware service. An MHEG-based model is exploited in designing the system architecture to achieve the real-time, interactive,more » and reusable information interchange through heterogeneous platforms. The system architecture, courseware processing strategies, courseware document models are presented.« less

Telomerase reverse transcriptase (TERT) - enhancer of zeste homolog 2 (EZH2) network regulates lipid metabolism and DNA damage responses in glioblastoma.

PubMed

Ahmad, Fahim; Patrick, Shruti; Sheikh, Touseef; Sharma, Vikas; Pathak, Pankaj; Malgulwar, Prit Benny; Kumar, Anupam; Joshi, Shanker Datt; Sarkar, Chitra; Sen, Ellora

2017-12-01

Elevated expression of enhancer of zeste homolog 2 (EZH2), a histone H3K27 methyltransferase, was observed in gliomas harboring telomerase reverse transcriptase (TERT) promoter mutations. Given the known involvement of TERT and EZH2 in glioma progression, the correlation between the two and subsequently its involvement in metabolic programming was investigated. Inhibition of human telomerase reverse transcriptase either pharmacologically or through genetic manipulation not only decreased EZH2 expression, but also (i) abrogated FASN levels, (ii) decreased de novo fatty acid accumulation, and (iii) increased ataxia-telangiectasia-mutated (ATM) phosphorylation levels. Conversely, diminished TERT and FASN levels upon siRNA-mediated EZH2 knockdown indicated a positive correlation between TERT and EZH2. Interestingly, ATM kinase inhibitor rescued TERT inhibition-mediated decrease in FASN and EZH2 levels. Importantly, TERT promoter mutant tumors exhibited greater microsatellite instability, heightened FASN levels and lipid accumulation. Coherent with in vitro findings, pharmacological inhibition of TERT by costunolide decreased lipid accumulation and elevated ATM expression in heterotypic xenograft glioma mouse model. By bringing TERT-EZH2 network at the forefront as driver of dysregulated metabolism, our findings highlight the non-canonical but distinct role of TERT in metabolic reprogramming and DNA damage responses in glioblastoma. © 2017 International Society for Neurochemistry.

A Physical Mechanism and Global Quantification of Breast Cancer

PubMed Central

Yu, Chong; Wang, Jin

2016-01-01

Initiation and progression of cancer depend on many factors. Those on the genetic level are often considered crucial. To gain insight into the physical mechanisms of breast cancer, we construct a gene regulatory network (GRN) which reflects both genetic and environmental aspects of breast cancer. The construction of the GRN is based on available experimental data. Three basins of attraction, representing the normal, premalignant and cancer states respectively, were found on the phenotypic landscape. The progression of breast cancer can be seen as switching transitions between different state basins. We quantified the stabilities and kinetic paths of the three state basins to uncover the biological process of breast cancer formation. The gene expression levels at each state were obtained, which can be tested directly in experiments. Furthermore, by performing global sensitivity analysis on the landscape topography, six key genes (HER2, MDM2, TP53, BRCA1, ATM, CDK2) and four regulations (HER2⊣TP53, CDK2⊣BRCA1, ATM→MDM2, TP53→ATM) were identified as being critical for breast cancer. Interestingly, HER2 and MDM2 are the most popular targets for treating breast cancer. BRCA1 and TP53 are the most important oncogene of breast cancer and tumor suppressor gene, respectively. This further validates the feasibility of our model and the reliability of our prediction results. The regulation ATM→MDM2 has been extensive studied on DNA damage but not on breast cancer. We notice the importance of ATM→MDM2 on breast cancer. Previous studies of breast cancer have often focused on individual genes and the anti-cancer drugs are mainly used to target the individual genes. Our results show that the network-based strategy is more effective on treating breast cancer. The landscape approach serves as a new strategy for analyzing breast cancer on both the genetic and epigenetic levels and can help on designing network based medicine for breast cancer. PMID:27410227

The SMART-NAS Testbed

NASA Technical Reports Server (NTRS)

Aquilina, Rudolph A.

2015-01-01

The SMART-NAS Testbed for Safe Trajectory Based Operations Project will deliver an evaluation capability, critical to the ATM community, allowing full NextGen and beyond-NextGen concepts to be assessed and developed. To meet this objective a strong focus will be placed on concept integration and validation to enable a gate-to-gate trajectory-based system capability that satisfies a full vision for NextGen. The SMART-NAS for Safe TBO Project consists of six sub-projects. Three of the sub-projects are focused on exploring and developing technologies, concepts and models for evolving and transforming air traffic management operations in the ATM+2 time horizon, while the remaining three sub-projects are focused on developing the tools and capabilities needed for testing these advanced concepts. Function Allocation, Networked Air Traffic Management and Trajectory Based Operations are developing concepts and models. SMART-NAS Test-bed, System Assurance Technologies and Real-time Safety Modeling are developing the tools and capabilities to test these concepts. Simulation and modeling capabilities will include the ability to assess multiple operational scenarios of the national airspace system, accept data feeds, allowing shadowing of actual operations in either real-time, fast-time and/or hybrid modes of operations in distributed environments, and enable integrated examinations of concepts, algorithms, technologies, and NAS architectures. An important focus within this project is to enable the development of a real-time, system-wide safety assurance system. The basis of such a system is a continuum of information acquisition, analysis, and assessment that enables awareness and corrective action to detect and mitigate potential threats to continuous system-wide safety at all levels. This process, which currently can only be done post operations, will be driven towards "real-time" assessments in the 2035 time frame.

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

PubMed

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.

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

NASA Technical Reports Server (NTRS)

Matolak, David W.

2017-01-01

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

Strategy for Developing Expert-System-Based Internet Protocols (TCP/IP)

NASA Technical Reports Server (NTRS)

Ivancic, William D.

1997-01-01

The Satellite Networks and Architectures Branch of NASA's Lewis Research is addressing the issue of seamless interoperability of satellite networks with terrestrial networks. One of the major issues is improving reliable transmission protocols such as TCP over long latency and error-prone links. Many tuning parameters are available to enhance the performance of TCP including segment size, timers and window sizes. There are also numerous congestion avoidance algorithms such as slow start, selective retransmission and selective acknowledgment that are utilized to improve performance. This paper provides a strategy to characterize the performance of TCP relative to various parameter settings in a variety of network environments (i.e. LAN, WAN, wireless, satellite, and IP over ATM). This information can then be utilized to develop expert-system-based Internet protocols.

Network planning study of the metro-optical-network-oriented 3G application

NASA Astrophysics Data System (ADS)

Gong, Qian; Xu, Rong; Lin, Jin Tong

2005-02-01

To compare with the 2G mobile communication, 3G technologies can supply the perfect service scope and performance. 3G is the trend of the mobile communication. So now to build the transmission network, it is needed to consider how the transmission network to support the 3G applications. For the 3G network architecture, it include the 2 part: Utran access network and core network. So the metro optical network should consider how to build the network to adapt the 3G applications. Include the metro core and access layer. In the metro core, we should consider the network should evolved towards the Mesh architecture with ASON function to realize the fast protection and restoration, quick end-to-end service provision, and high capacity cross-connect matrix etc. In the access layer, the network should have the ability to access the 3G services such as ATM interface with IMA function. In addition, the traffic grooming should be provided to improve the bandwidth utility. In this paper, first we present the MCC network situation, the network planning model will be introduced. Then we present the topology architecture, node capacity and traffic forecast. At last, based on our analysis, we will give a total solution to MCC to build their metro optical network toward to the mesh network with the consideration of 3G services.

Multimedia Networks: Mission Impossible?

ERIC Educational Resources Information Center

Weiss, Andrew M.

1996-01-01

Running multimedia on a network, often difficult because of the memory and processing power required, is becoming easier thanks to new protocols and products. Those developing network design criteria may wish to consider making use of Fast Ethernet, Asynchronous Transfer Method (ATM), switches, "fat pipes", additional network…

A constrained joint source/channel coder design and vector quantization of nonstationary sources

NASA Technical Reports Server (NTRS)

Sayood, Khalid; Chen, Y. C.; Nori, S.; Araj, A.

1993-01-01

The emergence of broadband ISDN as the network for the future brings with it the promise of integration of all proposed services in a flexible environment. In order to achieve this flexibility, asynchronous transfer mode (ATM) has been proposed as the transfer technique. During this period a study was conducted on the bridging of network transmission performance and video coding. The successful transmission of variable bit rate video over ATM networks relies on the interaction between the video coding algorithm and the ATM networks. Two aspects of networks that determine the efficiency of video transmission are the resource allocation algorithm and the congestion control algorithm. These are explained in this report. Vector quantization (VQ) is one of the more popular compression techniques to appear in the last twenty years. Numerous compression techniques, which incorporate VQ, have been proposed. While the LBG VQ provides excellent compression, there are also several drawbacks to the use of the LBG quantizers including search complexity and memory requirements, and a mismatch between the codebook and the inputs. The latter mainly stems from the fact that the VQ is generally designed for a specific rate and a specific class of inputs. In this work, an adaptive technique is proposed for vector quantization of images and video sequences. This technique is an extension of the recursively indexed scalar quantization (RISQ) algorithm.

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

Kim, Young June; Ahn, Kwang Sung; Kim, Minjeong

Highlights: • ATM gene-targeted pigs were produced by somatic cell nuclear transfer. • A novel large animal model for ataxia telangiectasia was developed. • The new model may provide an alternative to the mouse model. - Abstract: Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None ofmore » the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A-T, we produced gene-targeted pigs with mutations in the ATM gene by somatic cell nuclear transfer. The disrupted allele in the ATM gene of cloned piglets was confirmed via PCR and Southern blot analysis. The ATM gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies.« less

Rock Hill Business, Education, and Community Online Network.

ERIC Educational Resources Information Center

Broyles, Alan

The Business, Education & Community On-line Network (BEACON) is designed to support development and implementation of demonstration applications operating in an asynchronous transfer mode (ATM) fiber optic network environment. Initial origination and destination sites include high schools and universities around Rock Hill (South Carolina). The…

Multimedia on the Network: Has Its Time Come?

ERIC Educational Resources Information Center

Galbreath, Jeremy

1995-01-01

Examines the match between multimedia data and local area network (LAN) infrastructures. Highlights include applications for networked multimedia, i.e., asymmetric and symmetric; alternate LAN technology, including stream management software, Ethernet, FDDI (Fiber Distributed Data Interface), and ATM (Asynchronous Transfer Mode); WAN (Wide Area…

Can Ceftazidime-Avibactam and Aztreonam Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae?

PubMed

Marshall, Steven; Hujer, Andrea M; Rojas, Laura J; Papp-Wallace, Krisztina M; Humphries, Romney M; Spellberg, Brad; Hujer, Kristine M; Marshall, Emma K; Rudin, Susan D; Perez, Federico; Wilson, Brigid M; Wasserman, Ronald B; Chikowski, Linda; Paterson, David L; Vila, Alejandro J; van Duin, David; Kreiswirth, Barry N; Chambers, Henry F; Fowler, Vance G; Jacobs, Michael R; Pulse, Mark E; Weiss, William J; Bonomo, Robert A

2017-04-01

Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram-negative bacteria, we tested the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ-AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included bla IMP , bla NDM , bla OXA-48 , bla CTX-M , bla AmpC , and combinations thereof. Time-kill assays were conducted, and the in vivo efficacy of this combination was assessed in a murine neutropenic thigh infection model. By disk diffusion assay, all 21 isolates were resistant to CAZ-AVI alone, and 19/21 were resistant to ATM. The in vitro activity of CAZ-AVI in combination with ATM against diverse Enterobacteriaceae possessing MBLs was demonstrated in 17/21 isolates, where the zone of inhibition was ≥21 mm. All isolates demonstrated a reduction in CAZ-AVI agar dilution MICs with the addition of ATM. At 2 h, time-kill assays demonstrated a ≥4-log 10 -CFU decrease for all groups that had CAZ-AVI with ATM (8 μg/ml) added, compared to the group treated with CAZ-AVI alone. In the murine neutropenic thigh infection model, an almost 4-log 10 -CFU reduction was noted at 24 h for CAZ-AVI (32 mg/kg every 8 h [q8h]) plus ATM (32 mg/kg q8h) versus CAZ-AVI (32 mg/kg q8h) alone. The data presented herein require us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing Enterobacteriaceae . Copyright © 2017 American Society for Microbiology.

Alterations of ATM and CADM1 in chromosomal 11q22.3-23.2 region are associated with the development of invasive cervical carcinoma.

PubMed

Mazumder Indra, Dipanjana; Mitra, Sraboni; Roy, Anup; Mondal, Ranajit Kumar; Basu, Partha Sarathi; Roychoudhury, Susanta; Chakravarty, Runu; Panda, Chinmay Kumar

2011-12-01

To understand the importance of chr11q22.3-23.2 region in the development of cervical cancer, we have studied the genetic and epigenetic alterations of the candidate genes ATM, PPP2R1B, SDHD and CADM1 in cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CACX) samples. Our study revealed low expression and high alterations (methylation/deletion) (55-59%) of ATM and CADM1 genes along with poor patient outcome. The alterations of ATM and CADM1 are associated with the progression of tumor from CIN to Stage I/II, thus implying their role in early invasiveness. The two genes, PPP2R1B and SDHD, lying in between ATM and CADM1, have low frequency of alterations, and majority of the alterations are in CACX samples, indicating that their alterations might be associated with disease progression. Expressions (mRNA/protein) of the genes showed concordance with their molecular alterations. Significant co-alteration of ATM and CADM1 points to their synergic action for the development of CACX. Mutation is, however, a rare phenomenon for inactivation of ATM. Association between the alteration of ATM and CHEK1 and poor survival of the patients having co-alterations of ATM and CHEK1 points to the DNA damage response pathway disruption in development of CACX. Thus, our data suggest that inactivation of ATM-CHEK1-associated DNA damage response pathway and CADM1-associated signaling network might have an important role in the development of CACX.

Modeling Air Traffic Management Technologies with a Queuing Network Model of the National Airspace System

NASA Technical Reports Server (NTRS)

Long, Dou; Lee, David; Johnson, Jesse; Gaier, Eric; Kostiuk, Peter

1999-01-01

This report describes an integrated model of air traffic management (ATM) tools under development in two National Aeronautics and Space Administration (NASA) programs -Terminal Area Productivity (TAP) and Advanced Air Transport Technologies (AATT). The model is made by adjusting parameters of LMINET, a queuing network model of the National Airspace System (NAS), which the Logistics Management Institute (LMI) developed for NASA. Operating LMINET with models of various combinations of TAP and AATT will give quantitative information about the effects of the tools on operations of the NAS. The costs of delays under different scenarios are calculated. An extension of Air Carrier Investment Model (ACIM) under ASAC developed by the Institute for NASA maps the technologies' impacts on NASA operations into cross-comparable benefits estimates for technologies and sets of technologies.

Direct Radiative Effects of Aerosols Over South Asia From Observations and Modeling

NASA Technical Reports Server (NTRS)

Nair, Vijayakumar S.; Babu, S. Suresh; Manoj, M. R.; Moorthy, Krishna K.; Chin, Mian

2016-01-01

Quantitative assessment of the seasonal variations in the direct radiative effect (DRE) of composite aerosols as well as the constituent species over the Indian sub continent has been carried out using a synergy of observations from a dense network of ground based aerosol observatories and modeling based on chemical transport model simulations. Seasonal variation of aerosol constituents depict significant influence of anthropogenic aerosol sources in winter and the dominance of natural sources in spring, even though the aerosol optical depth doesn't change significantly between these two seasons. A significant increase in the surface cooling and atmospheric warming has been observed as season changes from winter DRE(sub SUR) = -28 +/- 12 W m(exp -2) and DRE(sub ATM) = +19.6 +/- 9 W m(exp -2) to spring DRE(sub SUR) = -33.7 +/- 12 W m(exp -2) and DRE(sub ATM) = +27 +/- 9 W m(exp-2). Interestingly, springtime aerosols are more absorptive in nature compared to winter and consequently the aerosol induced diabatic heating of the atmosphere goes as high as approximately 1 K day(exp -1) during spring, especially over eastern India. The atmospheric DRE due to dust aerosols (+14 +/- 7 W m(exp 2) during spring overwhelms that of black carbon DRE (+11.8 +/- 6 W m(exp -2) during winter. The DRE at the top of the atmosphere is mostly governed by the anthropogenic aerosols during all the seasons. The columnar aerosol loading, its anthropogenic fraction and radiative effects shows a steady increase with latitude across Indian mainland leading to a larger aerosol-induced atmospheric warming during spring than in winter.

Radar tracking with an interacting multiple model and probabilistic data association filter for civil aviation applications.

PubMed

Jan, Shau-Shiun; Kao, Yu-Chun

2013-05-17

The current trend of the civil aviation technology is to modernize the legacy air traffic control (ATC) system that is mainly supported by many ground based navigation aids to be the new air traffic management (ATM) system that is enabled by global positioning system (GPS) technology. Due to the low receiving power of GPS signal, it is a major concern to aviation authorities that the operation of the ATM system might experience service interruption when the GPS signal is jammed by either intentional or unintentional radio-frequency interference. To maintain the normal operation of the ATM system during the period of GPS outage, the use of the current radar system is proposed in this paper. However, the tracking performance of the current radar system could not meet the required performance of the ATM system, and an enhanced tracking algorithm, the interacting multiple model and probabilistic data association filter (IMMPDAF), is therefore developed to support the navigation and surveillance services of the ATM system. The conventional radar tracking algorithm, the nearest neighbor Kalman filter (NNKF), is used as the baseline to evaluate the proposed radar tracking algorithm, and the real flight data is used to validate the IMMPDAF algorithm. As shown in the results, the proposed IMMPDAF algorithm could enhance the tracking performance of the current aviation radar system and meets the required performance of the new ATM system. Thus, the current radar system with the IMMPDAF algorithm could be used as an alternative system to continue aviation navigation and surveillance services of the ATM system during GPS outage periods.

Radar Tracking with an Interacting Multiple Model and Probabilistic Data Association Filter for Civil Aviation Applications

PubMed Central

Jan, Shau-Shiun; Kao, Yu-Chun

2013-01-01

The current trend of the civil aviation technology is to modernize the legacy air traffic control (ATC) system that is mainly supported by many ground based navigation aids to be the new air traffic management (ATM) system that is enabled by global positioning system (GPS) technology. Due to the low receiving power of GPS signal, it is a major concern to aviation authorities that the operation of the ATM system might experience service interruption when the GPS signal is jammed by either intentional or unintentional radio-frequency interference. To maintain the normal operation of the ATM system during the period of GPS outage, the use of the current radar system is proposed in this paper. However, the tracking performance of the current radar system could not meet the required performance of the ATM system, and an enhanced tracking algorithm, the interacting multiple model and probabilistic data association filter (IMMPDAF), is therefore developed to support the navigation and surveillance services of the ATM system. The conventional radar tracking algorithm, the nearest neighbor Kalman filter (NNKF), is used as the baseline to evaluate the proposed radar tracking algorithm, and the real flight data is used to validate the IMMPDAF algorithm. As shown in the results, the proposed IMMPDAF algorithm could enhance the tracking performance of the current aviation radar system and meets the required performance of the new ATM system. Thus, the current radar system with the IMMPDAF algorithm could be used as an alternative system to continue aviation navigation and surveillance services of the ATM system during GPS outage periods. PMID:23686142

Volatile Reaction Products From Silicon-Based Ceramics in Combustion Environments Identified

NASA Technical Reports Server (NTRS)

Opila, Elizabeth J.

1997-01-01

Silicon-based ceramics and composites are prime candidates for use as components in the hot sections of advanced aircraft engines. These materials must have long-term durability in the combustion environment. Because water vapor is always present as a major product of combustion in the engine environment, its effect on the durability of silicon-based ceramics must be understood. In combustion environments, silicon-based ceramics react with water vapor to form a surface silica (SiO2) scale. This SiO2 scale, in turn, has been found to react with water vapor to form volatile hydroxides. Studies to date have focused on how water vapor reacts with high-purity silicon carbide (SiC) and SiO2 in model combustion environments. Because the combustion environment in advanced aircraft engines is expected to contain about 10-percent water vapor at 10-atm total pressure, the durability of SiC and SiO2 in gas mixtures containing 0.1- to 1-atm water vapor is of interest. The reactions of SiC and SiO2 with water vapor were monitored by measuring weight changes of sample coupons in a 0.5-atm water vapor/0.5-atm oxygen gas mixture with thermogravimetric analysis.

Development of a model and test equipment for cold flow tests at 500 atm of small nuclear light bulb configurations

NASA Technical Reports Server (NTRS)

Jaminet, J. F.

1972-01-01

A model and test equipment were developed and cold-flow-tested at greater than 500 atm in preparation for future high-pressure rf plasma experiments and in-reactor tests with small nuclear light bulb configurations. With minor exceptions, the model chamber is similar in design and dimensions to a proposed in-reactor geometry for tests with fissioning uranium plasmas in the nuclear furnace. The model and the equipment were designed for use with the UARL 1.2-MW rf induction heater in tests with rf plasmas at pressures up to 500 atm. A series of cold-flow tests of the model was then conducted at pressures up to about 510 atm. At 504 atm, the flow rates of argon and cooling water were 3.35 liter/sec (STP) and 26 gal/min, respectively. It was demonstrated that the model is capable of being operated for extended periods at the 500-atm pressure level and is, therefore, ready for use in initial high-pressure rf plasma experiments.

Adaptation technology between IP layer and optical layer in optical Internet

NASA Astrophysics Data System (ADS)

Ji, Yuefeng; Li, Hua; Sun, Yongmei

2001-10-01

Wavelength division multiplexing (WDM) optical network provides a platform with high bandwidth capacity and is supposed to be the backbone infrastructure supporting the next-generation high-speed multi-service networks (ATM, IP, etc.). In the foreseeable future, IP will be the predominant data traffic, to make fully use of the bandwidth of the WDM optical network, many attentions have been focused on IP over WDM, which has been proposed as the most promising technology for new kind of network, so-called Optical Internet. According to OSI model, IP is in the 3rd layer (network layer) and optical network is in the 1st layer (physical layer), so the key issue is what adaptation technology should be used in the 2nd layer (data link layer). In this paper, firstly, we analyze and compare the current adaptation technologies used in backbone network nowadays. Secondly, aiming at the drawbacks of above technologies, we present a novel adaptation protocol (DONA) between IP layer and optical layer in Optical Internet and describe it in details. Thirdly, the gigabit transmission adapter (GTA) we accomplished based on the novel protocol is described. Finally, we set up an experiment platform to apply and verify the DONA and GTA, the results and conclusions of the experiment are given.

Current status of the UCSF second-generation PACS

NASA Astrophysics Data System (ADS)

Huang, H. K.; Arenson, Ronald L.; Wong, Albert W. K.; Bazzill, Todd M.; Lou, Shyhliang A.; Andriole, Katherine P.; Wang, Jun; Zhang, Jianguo; Wong, Stephen T. C.

1996-05-01

This paper describes the current status of the second generation PACS at UCSF commenced in October 1992. The UCSF PACS is designed in-house as a hospital-integrated PACS based on an open architecture concept using industrial standards including UNIX operating system, C programming language, X-Window user interface, TCP/IP communication protocol, DICOM 3.0 image standard and HL7 health data format. Other manufacturer's PACS components which conform with these standards can be easily integrated into the system. Relevant data from HIS and RIS is automatically incorporated into the PACS using HL7 data format and TCP/IP communication protocol. The UCSF system also takes advantage of state-of-the-art communication, storage, and software technologies in ATM, multiple storage media, automatic programming, multilevel processes for a better cost-performance system. The primary PACS network is the 155 Mbits/sec OC3 ATM with the Ethernet as the back-up. The UCSF PACS also connects Mt. Zion Hospital and San Francisco VA Medical Center in the San Francisco Bay area via an ATM wide area network with a T1 line as the back-up. Currently, five MR and five CT scanners from multiple sites, two computed radiography systems, two film digitizers, one US PACS module, the hospital HIS and the department RIS have been connected to the PACS network. The image data is managed by a mirrored database (Sybase). The PACS controller, with its 1.3 terabyte optical disk library, acquires 2.5 gigabytes digital data daily. Four 2K, five, 1,600-line multiple monitor display workstations are on line in neuroradiology, pediatric radiology and intensive care units for clinical use. In addition, the PACS supports over 100 Macintosh users in the department and selected hospital sites for both images and textual retrieval through a client/server mechanism. We are also developing a computation and visualization node in the PACS network for advancing radiology research.

Real-time transmission of full-motion echocardiography over a high-speed data network: impact of data rate and network quality of service.

PubMed

Main, M L; Foltz, D; Firstenberg, M S; Bobinsky, E; Bailey, D; Frantz, B; Pleva, D; Baldizzi, M; Meyers, D P; Jones, K; Spence, M C; Freeman, K; Morehead, A; Thomas, J D

2000-08-01

With high-resolution network transmission required for telemedicine, education, and guided-image acquisition, the impact of errors and transmission rates on image quality needs evaluation. We transmitted clinical echocardiograms from 2 National Aeronautics and Space Administration (NASA) research centers with the use of Motion Picture Expert Group-2 (MPEG-2) encoding and asynchronous transmission mode (ATM) network protocol over the NASA Research and Education Network. Data rates and network quality (cell losses [CLR], errors [CER], and delay variability [CVD]) were altered and image quality was judged. At speeds of 3 to 5 megabits per second (Mbps), digital images were superior to those on videotape; at 2 Mbps, images were equivalent. Increasing CLR caused occasional, brief pauses. Extreme CER and CDV increases still yielded high-quality images. Real-time echocardiographic acquisition, guidance, and transmission is feasible with the use of MPEG-2 and ATM with broadcast quality seen above 3 Mbps, even with severe network quality degradation. These techniques can be applied to telemedicine and used for planned echocardiography aboard the International Space Station.

Real-time transmission of full-motion echocardiography over a high-speed data network: impact of data rate and network quality of service

NASA Technical Reports Server (NTRS)

Main, M. L.; Foltz, D.; Firstenberg, M. S.; Bobinsky, E.; Bailey, D.; Frantz, B.; Pleva, D.; Baldizzi, M.; Meyers, D. P.; Jones, K.;

Simulation of Ames Backbone Network

NASA Technical Reports Server (NTRS)

Shahnasser, Hamid

1998-01-01

The networking demands of Ames Research Center are dramatically increasing. More and more workstations are requested to run video and audio applications on the network. These applications require a much greater bandwidth than data applications. The existing ARCLAN 2000 network bandwidth is insufficient, due to the use of FDDI as its backbone, for accommodating video applications. Operating at a maximum of 100 Mbps, FDDI can handle only a few workstations running multimedia applications. The ideal solution is to replace the current ARCLAN 2000 FDDI backbone with an ATM backbone. ATM has the capability to handle the increasing traffic loads on the ARCLAN 2000 that results from these new applications. As it can be seen from Figure 1, ARCLAN 2000 have a total of 32 routers (5 being core routers) each connected to the FDDI backbone via a 100 Mbps link. This network serves 34 different locations by using 34 hubs that are connected to secondary routers. End users are connected to the secondary routers with 10 Mbps links.

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.

PubMed

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.

Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice.

PubMed

Yamamoto, Kenta; Wang, Yunyue; Jiang, Wenxia; Liu, Xiangyu; Dubois, Richard L; Lin, Chyuan-Sheng; Ludwig, Thomas; Bakkenist, Christopher J; Zha, Shan

2012-08-06

Ataxia telangiectasia (A-T) mutated (ATM) kinase orchestrates deoxyribonucleic acid (DNA) damage responses by phosphorylating numerous substrates implicated in DNA repair and cell cycle checkpoint activation. A-T patients and mouse models that express no ATM protein undergo normal embryonic development but exhibit pleiotropic DNA repair defects. In this paper, we report that mice carrying homozygous kinase-dead mutations in Atm (Atm(KD/KD)) died during early embryonic development. Atm(KD/-) cells exhibited proliferation defects and genomic instability, especially chromatid breaks, at levels higher than Atm(-/-) cells. Despite this increased genomic instability, Atm(KD/-) lymphocytes progressed through variable, diversity, and joining recombination and immunoglobulin class switch recombination, two events requiring nonhomologous end joining, at levels comparable to Atm(-/-) lymphocytes. Together, these results reveal an essential function of ATM during embryogenesis and an important function of catalytically inactive ATM protein in DNA repair.

Atm knock-in mice harboring an in-frame deletion corresponding to the human ATM 7636del9 common mutation exhibit a variant phenotype.

PubMed

Spring, K; Cross, S; Li, C; Watters, D; Ben-Senior, L; Waring, P; Ahangari, F; Lu, S L; Chen, P; Misko, I; Paterson, C; Kay, G; Smorodinsky, N I; Shiloh, Y; Lavin, M F

2001-06-01

ATM, the gene mutated in the human immunodeficiency disorder ataxia-telangiectasia (A-T), plays a central role in recognizing ionizing radiation damage in DNA and in controlling several cell cycle checkpoints. We describe here a murine model in which a nine-nucleotide in-frame deletion has been introduced into the Atm gene by homologous recombination followed by removal of the selectable marker cassette by Cre-loxP site-specific, recombination-mediated excision. This mouse, Atm-DeltaSRI, was designed as a model of one of the most common deletion mutations (7636del9) found in A-T patients. The murine Atm deletion results in the loss of three amino acid residues (SRI; 2556-2558) but produces near full-length detectable Atm protein that lacks protein kinase activity. Radiosensitivity was observed in Atm-DeltaSRI mice, whereas the immunological profile of these mice showed greater heterogeneity of T-cell subsets than observed in Atm(-/-) mice. The life span of Atm-DeltaSRI mice was significantly longer than that of Atm(-/-) mice when maintained under nonspecific pathogen-free conditions. This can be accounted for by a lower incidence of thymic lymphomas in Atm-DeltaSRI mice up to 40 weeks, after which time the animals died of other causes. The thymic lymphomas in Atm-DeltaSRI mice were characterized by extensive apoptosis, which appears to be attributable to an increased number of cells expressing Fas ligand. A variety of other tumors including B-cell lymphomas, sarcomas, and carcinomas not seen in Atm(-/-) mice were observed in older Atm-DeltaSRI animals. Thus, expression of mutant protein in Atm-DeltaSRI knock-in mice gives rise to a discernibly different phenotype to Atm(-/-) mice, which may account for the heterogeneity seen in A-T patients with different mutations.

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

PubMed

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.

75 FR 65511 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-Network Centric...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

... Production Act of 1993--Network Centric Operations Industry Consortium, Inc. Notice is hereby given that, on..., 15 U.S.C. 4301 et seq. (``the Act''), Network Centric Operations Industry Consortium, Inc. (``NCOIC... circumstances. Specifically, Mosaic ATM, Leesburg, VA; NorthStar Group, LLC, Washington, DC; Luciad, Leuven...

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

PubMed Central

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-dependence for translocation from the cytoplasm to the nucleus. These data provide new insights into the activation of ATM by oxidative stress through identification of novel substrates for ATM in the cytoplasm. PMID:26699800

Cardiology-oriented PACS

NASA Astrophysics Data System (ADS)

Silva, Augusto F. d.; Costa, Carlos; Abrantes, Pedro; Gama, Vasco; Den Boer, Ad

1998-07-01

This paper describes an integrated system designed to provide efficient means for DICOM compliant cardiac imaging archival, transmission and visualization based on a communications backbone matching recent enabling telematic technologies like Asynchronous Transfer Mode (ATM) and switched Local Area Networks (LANs). Within a distributed client-server framework, the system was conceived on a modality based bottom-up approach, aiming ultrafast access to short term archives and seamless retrieval of cardiac video sequences throughout review stations located at the outpatient referral rooms, intensive and intermediate care units and operating theaters.

Nonaminoglycoside compounds induce readthrough of nonsense mutations

PubMed Central

Damoiseaux, Robert; Nahas, Shareef; Gao, Kun; Hu, Hailiang; Pollard, Julianne M.; Goldstine, Jimena; Jung, Michael E.; Henning, Susanne M.; Bertoni, Carmen

2009-01-01

Large numbers of genetic disorders are caused by nonsense mutations for which compound-induced readthrough of premature termination codons (PTCs) might be exploited as a potential treatment strategy. We have successfully developed a sensitive and quantitative high-throughput screening (HTS) assay, protein transcription/translation (PTT)–enzyme-linked immunosorbent assay (ELISA), for identifying novel PTC-readthrough compounds using ataxia-telangiectasia (A-T) as a genetic disease model. This HTS PTT-ELISA assay is based on a coupled PTT that uses plasmid templates containing prototypic A-T mutated (ATM) mutations for HTS. The assay is luciferase independent. We screened ∼34,000 compounds and identified 12 low-molecular-mass nonaminoglycosides with potential PTC-readthrough activity. From these, two leading compounds consistently induced functional ATM protein in ATM-deficient cells containing disease-causing nonsense mutations, as demonstrated by direct measurement of ATM protein, restored ATM kinase activity, and colony survival assays for cellular radiosensitivity. The two compounds also demonstrated readthrough activity in mdx mouse myotube cells carrying a nonsense mutation and induced significant amounts of dystrophin protein. PMID:19770270

Trans-Pacific HDR Satellite Communications Experiment Phase-2 Project Plan and Experimental Network

NASA Technical Reports Server (NTRS)

Hsu, Eddie; Kadowaki, Naoto; Yoshimura, Naoko; Takahashi, Takashi; Yoshikawa, Makoto; Bergman, Larry; Bhasin, Kul

2000-01-01

The trans-Pacific high data rate (TP-HDR) satellite communications experiment was proposed at the Japan-U.S. Cooperation in Space (JUCS) Program Workshop held in Hawaii in 1993 and remote high definition video post-production was demonstrated as the first phase trial. ATM-based 45 Mbps trans-Pacific link was established in the first phase, and the following experiments with 155 Mbps was planned as the phase 2. This paper describes the experimental network configuration and project plan of TP-HDR experiment phase 2. Additional information is provided in the original.

The ATM signaling network in development and disease.

PubMed

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.

The ATM signaling network in development and disease

PubMed Central

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

Asynchronous transfer mode distribution network by use of an optoelectronic VLSI switching chip.

PubMed

Lentine, A L; Reiley, D J; Novotny, R A; Morrison, R L; Sasian, J M; Beckman, M G; Buchholz, D B; Hinterlong, S J; Cloonan, T J; Richards, G W; McCormick, F B

1997-03-10

We describe a new optoelectronic switching system demonstration that implements part of the distribution fabric for a large asynchronous transfer mode (ATM) switch. The system uses a single optoelectronic VLSI modulator-based switching chip with more than 4000 optical input-outputs. The optical system images the input fibers from a two-dimensional fiber bundle onto this chip. A new optomechanical design allows the system to be mounted in a standard electronic equipment frame. A large section of the switch was operated as a 208-Mbits/s time-multiplexed space switch, which can serve as part of an ATM switch by use of an appropriate out-of-band controller. A larger section with 896 input light beams and 256 output beams was operated at 160 Mbits/s as a slowly reconfigurable space switch.

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

PubMed

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.

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

NASA Technical Reports Server (NTRS)

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 <1.0K for channels 1, 2, and 16-22 and <0.75 K for channels 3-15). A thorough evaluation of the performance of 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.

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

PubMed Central

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

2018-01-01

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. PMID:29717979

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

PubMed

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.

Navigating the Functional Landscape of Transcription Factors via Non-Negative Tensor Factorization Analysis of MEDLINE Abstracts

PubMed Central

Roy, Sujoy; Yun, Daqing; Madahian, Behrouz; Berry, Michael W.; Deng, Lih-Yuan; Goldowitz, Daniel; Homayouni, Ramin

2017-01-01

In this study, we developed and evaluated a novel text-mining approach, using non-negative tensor factorization (NTF), to simultaneously extract and functionally annotate transcriptional modules consisting of sets of genes, transcription factors (TFs), and terms from MEDLINE abstracts. A sparse 3-mode term × gene × TF tensor was constructed that contained weighted frequencies of 106,895 terms in 26,781 abstracts shared among 7,695 genes and 994 TFs. The tensor was decomposed into sub-tensors using non-negative tensor factorization (NTF) across 16 different approximation ranks. Dominant entries of each of 2,861 sub-tensors were extracted to form term–gene–TF annotated transcriptional modules (ATMs). More than 94% of the ATMs were found to be enriched in at least one KEGG pathway or GO category, suggesting that the ATMs are functionally relevant. One advantage of this method is that it can discover potentially new gene–TF associations from the literature. Using a set of microarray and ChIP-Seq datasets as gold standard, we show that the precision of our method for predicting gene–TF associations is significantly higher than chance. In addition, we demonstrate that the terms in each ATM can be used to suggest new GO classifications to genes and TFs. Taken together, our results indicate that NTF is useful for simultaneous extraction and functional annotation of transcriptional regulatory networks from unstructured text, as well as for literature based discovery. A web tool called Transcriptional Regulatory Modules Extracted from Literature (TREMEL), available at http://binf1.memphis.edu/tremel, was built to enable browsing and searching of ATMs. PMID:28894735

Trial Watch: Targeting ATM–CHK2 and ATR–CHK1 pathways for anticancer therapy

PubMed Central

Manic, Gwenola; Obrist, Florine; Sistigu, Antonella; Vitale, Ilio

2015-01-01

The ataxia telangiectasia mutated serine/threonine kinase (ATM)/checkpoint kinase 2 (CHEK2, best known as CHK2) and the ATM and Rad3-related serine/threonine kinase (ATR)/CHEK1 (best known as CHK1) cascades are the 2 major signaling pathways driving the DNA damage response (DDR), a network of processes crucial for the preservation of genomic stability that act as a barrier against tumorigenesis and tumor progression. Mutations and/or deletions of ATM and/or CHK2 are frequently found in tumors and predispose to cancer development. In contrast, the ATR–CHK1 pathway is often upregulated in neoplasms and is believed to promote tumor growth, although some evidence indicates that ATR and CHK1 may also behave as haploinsufficient oncosuppressors, at least in a specific genetic background. Inactivation of the ATM–CHK2 and ATR–CHK1 pathways efficiently sensitizes malignant cells to radiotherapy and chemotherapy. Moreover, ATR and CHK1 inhibitors selectively kill tumor cells that present high levels of replication stress, have a deficiency in p53 (or other DDR players), or upregulate the ATR–CHK1 module. Despite promising preclinical results, the clinical activity of ATM, ATR, CHK1, and CHK2 inhibitors, alone or in combination with other therapeutics, has not yet been fully demonstrated. In this Trial Watch, we give an overview of the roles of the ATM-CHK2 and ATR-CHK1 pathways in cancer initiation and progression, and summarize the results of clinical studies aimed at assessing the safety and therapeutic profile of regimens based on inhibitors of ATR and CHK1, the only 2 classes of compounds that have so far entered clinics. PMID:27308506

Introduction to multiprotocol over ATM (MPOA)

NASA Astrophysics Data System (ADS)

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.

TME10/380: Remote Transmission of Radiological Images by means of Intranet/Internet Technology

PubMed Central

Sicurello, F; Pizzi, R

1999-01-01

At the Istituto Nazionale Neurologico C. Besta in Milano a network architecture has been developed to connect computers and diagnostic modalities, based on Intranet technology in order to allow the hospital to have an external access through the Internet. The Internet technology has become the "glue" that allows to link different computers and to develop applications able to work independently from the hardware/software platform. Using a PACS (Picture Archiving and Communication System) system integrated to the diagnostic modalities by means of the standardized DICOM image format, the digital radiological images can be transferred, displayed and processed on special visualization workstations all around the hospital. From the workstations the same images can be transferred in DICOM format to a teleconsulting workstation. In fact the hospital is involved in a national project for the remote connection between many Italian hospitals. This national network is linked to already developed regional networks like the Toscana MAN and the ATM Sirius Network. Some links are performed directly in ATM (155 Mbps), others are based on CDN (Direct Numerical Connection, 2Mbps), others are simply based on ISDN connections. The system allows to make it simpler and faster the already established daily exchange of radiological reports between the involved hospitals, especially from Istituto Nazionale Neurologico and Istituto Nazionale deiTumori. All the actions performed by the radiologist are translated by the software into "events" and replied to the remote workstation and vice-versa. In this way the radiologists can see each others, speak together and act in real time on a common "board" of diagnostic images, each one with his own pointer. The adopted technology is evolving on a system based on a web architecture and Java applications, useful for small clinical centers not endowed with expensive information systems. These centers will be able to get consulting performances by the excellence centers, making available accurate diagnoses and therapy protocols.

Semantic Service Matchmaking in the ATM Domain Considering Infrastructure Capability Constraints

NASA Astrophysics Data System (ADS)

Moser, Thomas; Mordinyi, Richard; Sunindyo, Wikan Danar; Biffl, Stefan

In a service-oriented environment business processes flexibly build on software services provided by systems in a network. A key design challenge is the semantic matchmaking of business processes and software services in two steps: 1. Find for one business process the software services that meet or exceed the BP requirements; 2. Find for all business processes the software services that can be implemented within the capability constraints of the underlying network, which poses a major problem since even for small scenarios the solution space is typically very large. In this chapter we analyze requirements from mission-critical business processes in the Air Traffic Management (ATM) domain and introduce an approach for semi-automatic semantic matchmaking for software services, the “System-Wide Information Sharing” (SWIS) business process integration framework. A tool-supported semantic matchmaking process like SWIS can provide system designers and integrators with a set of promising software service candidates and therefore strongly reduces the human matching effort by focusing on a much smaller space of matchmaking candidates. We evaluate the feasibility of the SWIS approach in an industry use case from the ATM domain.

ATM facilitates mouse gammaherpesvirus reactivation from myeloid cells during chronic infection

PubMed Central

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.

2015-01-01

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. PMID:26001649

Influence of atmospheric convection on the long and short-range transport of Xe133 emissions.

NASA Astrophysics Data System (ADS)

Kusmierczyk-Michulec, Jolanta; Krysta, Monika; Gheddou, Abdelhakim; Nikkinen, Mika

2014-05-01

The International Monitoring System (IMS) developed by the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) is a global system of monitoring stations, using four complementary technologies: seismic, hydroacoustic, infrasound and radionuclide. Data from all stations, belonging to IMS, are collected and transmitted to the International Data Centre (IDC) in Vienna, Austria. The radionuclide network comprises 79 stations, of which more than 60 are certified. The aim of radionuclide stations is a global monitoring of radioactive aerosols and radioactive noble gases supported by the atmospheric transport modelling (ATM). The ATM system is based on the Lagrangian Particle Dispersion Model, FLEXPART, designed for calculating the long-range and mesoscale dispersion of air pollution from point sources. In the operational configuration only the transport of the passive tracer is simulated. The question arises whether including other atmospheric processes, like convection, will improve results. To answer this question a series of forward simulations was conducted, assuming the maximum transport of 14 days. Each time 2 runs were performed: one with convection and one without convection. The release point was at the ANSTO facility in Australia. Due to the fact that CTBTO has recently received a noble gas emission inventory from the ANSTO facility we had a chance to do more accurate simulations. Studies have been performed to link Xe133 emissions with detections at the IMS stations supported by the ATM. The geographical localization to some extend justifies the assumption that the only source of Xe133 observed at the neighbouring stations, e.g. AUX04, AUX09 and NZX46, comes from the ANSTO facility. In simulations the analysed wind data provided by the European Centre for Medium-Range Weather Forecasts (ECMWF) were used with the spatial resolution of 0.5 degree. The results of quantitative and qualitative comparison will be presented.

Initial Conceptualization and Application of the Alaska Thermokarst Model

NASA Astrophysics Data System (ADS)

Bolton, W. R.; Lara, M. J.; Genet, H.; Romanovsky, V. E.; McGuire, A. D.

2015-12-01

Thermokarst topography forms whenever ice-rich permafrost thaws and the ground subsides due to the volume loss when ground ice transitions to water. The Alaska Thermokarst Model (ATM) is a large-scale, state-and-transition model designed to simulate transitions between landscape units affected by thermokarst disturbance. The ATM uses a frame-based methodology to track transitions and proportion of cohorts within a 1-km2 grid cell. In the arctic tundra environment, the ATM tracks thermokarst-related transitions among wetland tundra, graminoid tundra, shrub tundra, and thermokarst lakes. In the boreal forest environment, the ATM tracks transitions among forested permafrost plateau, thermokarst lakes, collapse scar fens and bogs. The transition from one cohort to another due to thermokarst processes can take place if thaw reaches ice-rich ground layers either due to pulse disturbance (i.e. large precipitation event or fires), or due to gradual active layer deepening that eventually results in penetration of the protective layer. The protective layer buffers the ice-rich soils from the land surface and is critical to determine how susceptible an area is to thermokarst degradation. The rate of terrain transition in our model is determined by a set of rules that are based upon the ice-content of the soil, the drainage efficiency (or the ability of the landscape to store or transport water), the cumulative probability of thermokarst initiation, distance from rivers, lake dynamics (increasing, decreasing, or stable), and other factors. Tundra types are allowed to transition from one type to another (for example, wetland tundra to graminoid tundra) under favorable climatic conditions. In this study, we present our conceptualization and initial simulation results from in the arctic (the Barrow Peninsula) and boreal (the Tanana Flats) regions of Alaska.

Pathway Model of the Kinetics of the TGFbeta Antagonist Smad7 and Cross-Talk with the ATM and WNT Pathways

NASA Technical Reports Server (NTRS)

Carra, Claudio; Wang, Minli; Huff, Janice L.; Hada, Megumi; ONeill, Peter; Cucinotta, Francis A.

2010-01-01

Signal transduction controls cellular and tissue responses to radiation. Transforming growth factor beta (TGFbeta) is an important regulator of cell growth and differentiation and tissue homeostasis, and is often dis-regulated in tumor formation. Mathematical models of signal transduction pathways can be used to elucidate how signal transduction varies with radiation quality, and dose and dose-rate. Furthermore, modeling of tissue specific responses can be considered through mechanistic based modeling. We developed a mathematical model of the negative feedback regulation by Smad7 in TGFbeta-Smad signaling and are exploring possible connections to the WNT/beta -catenin, and ATM/ATF2 signaling pathways. A pathway model of TGFbeta-Smad signaling that includes Smad7 kinetics based on data in the scientific literature is described. Kinetic terms included are TGFbeta/Smad transcriptional regulation of Smad7 through the Smad3-Smad4 complex, Smad7-Smurf1 translocation from nucleus to cytoplasm, and Smad7 negative feedback regulation of the TGFO receptor through direct binding to the TGFO receptor complex. The negative feedback controls operating in this pathway suggests non-linear responses in signal transduction, which are described mathematically. We then explored possibilities for cross-talk mediated by Smad7 between DNA damage responses mediated by ATM, and with the WNT pathway and consider the design of experiments to test model driven hypothesis. Numerical comparisons of the mathematical model to experiments and representative predictions are described.

Fuel consumption modeling in support of ATM environmental decision-making

DOT National Transportation Integrated Search

2009-07-01

The FAA has recently updated the airport terminal : area fuel consumption methods used in its environmental models. : These methods are based on fitting manufacturers fuel : consumption data to empirical equations. The new fuel : consumption metho...

An Assessment of Gigabit Ethernet Technology and Its Applications at the NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Bakes, Catherine Murphy; Kim, Chan M.; Ramos, Calvin T.

2000-01-01

This paper describes Gigabit Ethernet and its role in supporting R&D programs at NASA Glenn. These programs require an advanced high-speed network capable of transporting multimedia traffic, including real-time visualization, high- resolution graphics, and scientific data. GigE is a 1 Gbps extension to 10 and 100 Mbps Ethernet. The IEEE 802.3z and 802.3ab standards define the MAC layer and 1000BASE-X and 1000BASE-T physical layer specifications for GigE. GigE switches and buffered distributors support IEEE 802.3x flow control. The paper also compares GigE with ATM in terms of quality of service, data rate, throughput, scalability, interoperability, network management, and cost of ownership.

76 FR 31252 - Fixed and Mobile Services in the Mobile Satellite Service Bands at 1525-1559 MHz and 1626.5-1660...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-31

... also claims that MSS networks provide the only means to create a next generation air traffic management..., articulated their plans to offer high-speed data services, especially in connection with terrestrial networks... claimed that MSS networks provide the only means to create a next generation air traffic management (ATM...

Stability and sensitivity of ABR flow control protocols

NASA Astrophysics Data System (ADS)

Tsai, Wie K.; Kim, Yuseok; Chiussi, Fabio; Toh, Chai-Keong

1998-10-01

This tutorial paper surveys the important issues in stability and sensitivity analysis of ABR flow control of ATM networks. THe stability and sensitivity issues are formulated in a systematic framework. Four main cause of instability in ABR flow control are identified: unstable control laws, temporal variations of available bandwidth with delayed feedback control, misbehaving components, and interactions between higher layer protocols and ABR flow control. Popular rate-based ABR flow control protocols are evaluated. Stability and sensitivity is shown to be the fundamental issues when the network has dynamically-varying bandwidth. Simulation result confirming the theoretical studies are provided. Open research problems are discussed.

Controller–Pilot Data Link Communication Security

PubMed Central

Polishchuk, Tatiana; Wernberg, Max

2018-01-01

The increased utilization of the new types of cockpit communications, including controller–pilot data link communications (CPDLC), puts the airplane at higher risk of hacking or interference than ever before. We review the technological characteristics and properties of the CPDLC and construct the corresponding threat model. Based on the limitations imposed by the system parameters, we propose several solutions for the improved security of the data messaging communication used in air traffic management (ATM). We discuss the applicability of elliptical curve cryptography (ECC), protected aircraft communications addressing and reporting systems (PACARs) and the Host Identity Protocol (HIP) as possible countermeasures to the identified security threats. In addition, we consider identity-defined networking (IDN) as an example of a genuine security solution which implies global changes in the whole air traffic communication system. PMID:29783791

Controller⁻Pilot Data Link Communication Security.

PubMed

Gurtov, Andrei; Polishchuk, Tatiana; Wernberg, Max

2018-05-20

The increased utilization of the new types of cockpit communications, including controller⁻pilot data link communications (CPDLC), puts the airplane at higher risk of hacking or interference than ever before. We review the technological characteristics and properties of the CPDLC and construct the corresponding threat model. Based on the limitations imposed by the system parameters, we propose several solutions for the improved security of the data messaging communication used in air traffic management (ATM). We discuss the applicability of elliptical curve cryptography (ECC), protected aircraft communications addressing and reporting systems (PACARs) and the Host Identity Protocol (HIP) as possible countermeasures to the identified security threats. In addition, we consider identity-defined networking (IDN) as an example of a genuine security solution which implies global changes in the whole air traffic communication system.

Systems Biology Model of Interactions between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFβ and ATM Signaling

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

Cucinotta, Francis A

The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently, the transforming growth factor β (TGFβ)more » pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses, and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low-dose responses and cross-talk between the ATM and TGFβ pathways initiated by low- and high-LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to crosstalk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental approaches to apply to these problems using confocal microscopy and flow cytometry to detail changes at low dose/dose-rate in order to understand individual cell responses, and will establish our mathematical models based on the experimental findings resulting from changes in DNA repair, apoptosis and proliferation.« less

Systems Biology Model of Interactions Between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFbeta and ATM Signaling

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

O'Neill, Peter; Anderson, Jennifer

The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently the transforming growth factor β (TGFβ)more » pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low dose responses and cross-talk between the ATM and TGFβ pathways initiated by low and high LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to cross- talk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental approaches to apply to these problems using confocal microscopy and flow cytometry to detail changes at low dose/dose-rate in order to understand individual cell responses, and will establish our mathematical models based on the experimental findings resulting from changes in DNA repair, apoptosis and proliferation.« less

Molecular Regulation of DNA Damage-Induced Apoptosis in Neurons of Cerebral Cortex

PubMed Central

Liu, Zhiping; Pipino, Jacqueline; Chestnut, Barry; Landek, Melissa A.

2009-01-01

Cerebral cortical neuron degeneration occurs in brain disorders manifesting throughout life, but the mechanisms are understood poorly. We used cultured embryonic mouse cortical neurons and an in vivo mouse model to study mechanisms of DNA damaged-induced apoptosis in immature and differentiated neurons. p53 drives apoptosis of immature and differentiated cortical neurons through its rapid and prominent activation stimulated by DNA strand breaks induced by topoisomerase-I and -II inhibition. Blocking p53-DNA transactivation with α-pifithrin protects immature neurons; blocking p53-mitochondrial functions with μ-pifithrin protects differentiated neurons. Mitochondrial death proteins are upregulated in apoptotic immature and differentiated neurons and have nonredundant proapoptotic functions; Bak is more dominant than Bax in differentiated neurons. p53 phosphorylation is mediated by ataxia telangiectasia mutated (ATM) kinase. ATM inactivation is antiapoptotic, particularly in differentiated neurons, whereas inhibition of c-Abl protects immature neurons but not differentiated neurons. Cell death protein expression patterns in mouse forebrain are mostly similar to cultured neurons. DNA damage induces prominent p53 activation and apoptosis in cerebral cortex in vivo. Thus, DNA strand breaks in cortical neurons induce rapid p53-mediated apoptosis through actions of upstream ATM and c-Abl kinases and downstream mitochondrial death proteins. This molecular network operates through variations depending on neuron maturity. PMID:18820287

Carbon dioxide induced plasticity of branchial acid-base pathways in an estuarine teleost

PubMed Central

Allmon, Elizabeth B.; Esbaugh, Andrew J.

2017-01-01

Anthropogenic CO2 is expected to drive ocean pCO2 above 1,000 μatm by 2100 – inducing respiratory acidosis in fish that must be corrected through branchial ion transport. This study examined the time course and plasticity of branchial metabolic compensation in response to varying levels of CO2 in an estuarine fish, the red drum, which regularly encounters elevated CO2 and may therefore have intrinsic resilience. Under control conditions fish exhibited net base excretion; however, CO2 exposure resulted in a dose dependent increase in acid excretion during the initial 2 h. This returned to baseline levels during the second 2 h interval for exposures up to 5,000 μatm, but remained elevated for exposures above 15,000 μatm. Plasticity was assessed via gene expression in three CO2 treatments: environmentally realistic 1,000 and 6,000 μatm exposures, and a proof-of-principle 30,000 μatm exposure. Few differences were observed at 1,000 or 6,000 μatm; however, 30,000 μatm stimulated widespread up-regulation. Translocation of V-type ATPase after 1 h of exposure to 30,000 μatm was also assessed; however, no evidence of translocation was found. These results indicate that red drum can quickly compensate to environmentally relevant acid-base disturbances using baseline cellular machinery, yet are capable of plasticity in response to extreme acid-base challenges. PMID:28378831

Carbon dioxide induced plasticity of branchial acid-base pathways in an estuarine teleost

NASA Astrophysics Data System (ADS)

Allmon, Elizabeth B.; Esbaugh, Andrew J.

2017-04-01

Anthropogenic CO2 is expected to drive ocean pCO2 above 1,000 μatm by 2100 - inducing respiratory acidosis in fish that must be corrected through branchial ion transport. This study examined the time course and plasticity of branchial metabolic compensation in response to varying levels of CO2 in an estuarine fish, the red drum, which regularly encounters elevated CO2 and may therefore have intrinsic resilience. Under control conditions fish exhibited net base excretion; however, CO2 exposure resulted in a dose dependent increase in acid excretion during the initial 2 h. This returned to baseline levels during the second 2 h interval for exposures up to 5,000 μatm, but remained elevated for exposures above 15,000 μatm. Plasticity was assessed via gene expression in three CO2 treatments: environmentally realistic 1,000 and 6,000 μatm exposures, and a proof-of-principle 30,000 μatm exposure. Few differences were observed at 1,000 or 6,000 μatm however, 30,000 μatm stimulated widespread up-regulation. Translocation of V-type ATPase after 1 h of exposure to 30,000 μatm was also assessed; however, no evidence of translocation was found. These results indicate that red drum can quickly compensate to environmentally relevant acid-base disturbances using baseline cellular machinery, yet are capable of plasticity in response to extreme acid-base challenges.

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

PubMed

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.

Application of Computer Simulation to Teach ATM Access to Individuals with Intellectual Disabilities

ERIC Educational Resources Information Center

Davies, Daniel K.; Stock, Steven E.; Wehmeyer, Michael L.

2003-01-01

This study investigates use of computer simulation for teaching ATM use to adults with intellectual disabilities. ATM-SIM is a computer-based trainer used for teaching individuals with intellectual disabilities how to use an automated teller machine (ATM) to access their personal bank accounts. In the pilot evaluation, a prototype system was…

Revealing determinants of two-phase dynamics of P53 network under gamma irradiation based on a reduced 2D relaxation oscillator model.

PubMed

Demirkıran, Gökhan; Kalaycı Demir, Güleser; Güzeliş, Cüneyt

2018-02-01

This study proposes a two-dimensional (2D) oscillator model of p53 network, which is derived via reducing the multidimensional two-phase dynamics model into a model of ataxia telangiectasia mutated (ATM) and Wip1 variables, and studies the impact of p53-regulators on cell fate decision. First, the authors identify a 6D core oscillator module, then reduce this module into a 2D oscillator model while preserving the qualitative behaviours. The introduced 2D model is shown to be an excitable relaxation oscillator. This oscillator provides a mechanism that leads diverse modes underpinning cell fate, each corresponding to a cell state. To investigate the effects of p53 inhibitors and the intrinsic time delay of Wip1 on the characteristics of oscillations, they introduce also a delay differential equation version of the 2D oscillator. They observe that the suppression of p53 inhibitors decreases the amplitudes of p53 oscillation, though the suppression increases the sustained level of p53. They identify Wip1 and P53DINP1 as possible targets for cancer therapies considering their impact on the oscillator, supported by biological findings. They model some mutations as critical changes of the phase space characteristics. Possible cancer therapeutic strategies are then proposed for preventing these mutations' effects using the phase space approach.

Impact of advanced technology microwave sounder data in the NCMRWF 4D-VAR data assimilation system

NASA Astrophysics Data System (ADS)

Rani, S. Indira; Srinivas, D.; Mallick, Swapan; George, John P.

2016-05-01

This study demonstrates the added benefits of assimilating the Advanced Technology Microwave Sounder (ATMS) radiances from the Suomi-NPP satellite in the NCMRWF Unified Model (NCUM). ATMS is a cross-track scanning microwave radiometer inherited the legacy of two very successful instrument namely, Advanced Microwave Sounding Unit-A (AMSU-A) and Microwave Humidity Sounder (MHS). ATMS has 22 channels: 11 temperature sounding channels around 50-60 GHz oxygen band and 6 moisture sounding channels around the 183GHz water vapour band in addition to 5 channels sensitive to the surface in clear conditions, or to water vapour, rain, and cloud when conditions are not clear (at 23, 31, 50, 51 and 89 GHz). Before operational assimilation of any new observation by NWP centres it is standard practice to assess data quality with respect to NWP model background (short-forecast) fields. Quality of all channels is estimated against the model background and the biases are computed and compared against that from the similar observations. The impact of the ATMS data on global analyses and forecasts is tested by adding the ATMS data in the NCUM Observation Processing system (OPS) and 4D-Var variational assimilation (VAR) system. This paper also discusses the pre-operational numerical experiments conducted to assess the impact of ATMS radiances in the NCUM assimilation system. It is noted that the performance of ATMS is stable and it contributes to the performance of the model, complimenting observations from other instruments.

Hyper-Spectral Networking Concept of Operations and Future Air Traffic Management Simulations

NASA Technical Reports Server (NTRS)

Davis, Paul; Boisvert, Benjamin

2017-01-01

The NASA sponsored Hyper-Spectral Communications and Networking for Air Traffic Management (ATM) (HSCNA) project is conducting research to improve the operational efficiency of the future National Airspace System (NAS) through diverse and secure multi-band, multi-mode, and millimeter-wave (mmWave) wireless links. Worldwide growth of air transportation and the coming of unmanned aircraft systems (UAS) will increase air traffic density and complexity. Safe coordination of aircraft will require more capable technologies for communications, navigation, and surveillance (CNS). The HSCNA project will provide a foundation for technology and operational concepts to accommodate a significantly greater number of networked aircraft. This paper describes two of the HSCNA projects technical challenges. The first technical challenge is to develop a multi-band networking concept of operations (ConOps) for use in multiple phases of flight and all communication link types. This ConOps will integrate the advanced technologies explored by the HSCNA project and future operational concepts into a harmonized vision of future NAS communications and networking. The second technical challenge discussed is to conduct simulations of future ATM operations using multi-bandmulti-mode networking and technologies. Large-scale simulations will assess the impact, compared to todays system, of the new and integrated networks and technologies under future air traffic demand.

Multimedia Applications in Heterogeneous Internet/ATM Environments.

ERIC Educational Resources Information Center

Wolf, Lars C.

1999-01-01

Discussion of multimedia systems focuses on interaction approaches for the quality of service (QoS) architectures developed for the Internet and for asynchronous transfer mode (ATM). Highlights include interactions, videoconferencing, video on demand, a comparison of the ATM and IntServ QoS architectures, interaction models, and subordination…

Low threshold all-optical crossbar switch on GaAs-GaAlAs channel waveguide arrays

NASA Astrophysics Data System (ADS)

Jannson, Tomasz; Kostrzewski, Andrew

1994-09-01

During the Phase 2 project entitled 'Low Threshold All-Optical Crossbar Switch on GaAs - GaAlAs Channel Waveguide Array,' Physical Optics Corporation (POC) developed the basic principles for the fabrication of all-optical crossbar switches. Based on this development. POC fabricated a 2 x 2 GaAs/GaAlAs switch that changes the direction of incident light with minimum insertion loss and nonlinear distortion. This unique technology can be used in both analog and digital networks. The applications of this technology are widespread. Because the all-optical network does not have any speed limitations (RC time constant), POC's approach will be beneficial to SONET networks, phased array radar networks, very high speed oscilloscopes, all-optical networks, IR countermeasure systems, BER equipment, and the fast growing video conferencing network market. The novel all-optical crossbar switch developed in this program will solve interconnect problems. and will be a key component in the widely proposed all-optical 200 Gb/s SONET/ATM networks.

Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice

NASA Technical Reports Server (NTRS)

Weil, M. M.; Kittrell, F. S.; Yu, Y.; McCarthy, M.; Zabriskie, R. C.; Ullrich, R. L.

2001-01-01

Ataxia-telangiectasia (AT) is a genetic syndrome resulting from the inheritance of two defective copies of the ATM gene that includes among its stigmata radiosensitivity and cancer susceptibility. Epidemiological studies have demonstrated that although women with a single defective copy of ATM (AT heterozygotes) appear clinically normal, they may never the less have an increased relative risk of developing breast cancer. Whether they are at increased risk for radiation-induced breast cancer from medical exposures to ionizing radiation is unknown. We have used a murine model of AT to investigate the effect of a single defective Atm allele, the murine homologue of ATM, on the susceptibility of mammary epithelial cells to radiation-induced transformation. Here we report that mammary epithelial cells from irradiated mice with one copy of Atm truncated in the PI-3 kinase domain were susceptible to radiation-induced genomic instability and generated a 10% incidence of dysplastic mammary ducts when transplanted into syngenic recipients, whereas cells from Atm(+/+) mice were stable and formed only normal ducts. Since radiation-induced ductal dysplasia is a precursor to mammary cancer, the results indicate that AT heterozygosity increases susceptibility to radiogenic breast cancer in this murine model system.

End-to-end QoS bounds for RTP-based service subnetworks

NASA Astrophysics Data System (ADS)

Pitts, Jonathan M.; Schormans, John A.

1999-11-01

With the increasing focus on traffic prioritization to support voice-data integration in corporate intranets, practical methods are needed to dimension and manage cost efficient service partitions. This is particularly important for the provisioning of real time, delay sensitive services such as telephony and voice/video conferencing applications. Typically these can be provided over RTP/UDP/IP or ATM DBR/SBR bearers but, irrespective of the specific networking technology, the switches or routers need to implement some form of virtual buffer management with queue scheduling mechanisms to provide partitioning. The key requirement is for operators of such networks to be able to dimension the partitions and virtual buffer sizes for efficient resource utilization, instead of simply over-dimensioning. This paper draws on recent work at Queen Mary, University of London, supported by the UK Engineering and Physical Sciences Research Council, to investigate approximate analytical methods for assessing end to end delay variation bounds in cell based and packet based networks.

Measurement of Atmospheric Black Carbon Concentrations, [BC]atm, in the Arctic Region from ~1700 to 2013

NASA Astrophysics Data System (ADS)

Husain, L.; Sarkar, S.; Jyethi, D. S.; Ruppel, M.; Dutkiewicz, V. A.

2015-12-01

Atmospheric black carbon (BC) aerosols play a key role in Earth's climate through direct and indirect effects. Due to a lack of long-term BC data, climate models are used to estimate BC based on fuel inventories, which have large uncertainties. Hence, long term BC data is needed to verify global models. We report here the first measurements of atmospheric BC concentrations, [BC]atm, from ~1700 to 2013 using sediments from Finnish lakes, Saanajarvi (SJ)(690 44' N, 200 52' E), and Vuoskojarvi (VJ)(69044'N, 26057'E). The cores were collected from the deepest parts of the lakes using a HTH gravity corer, sliced in 0.25 cm sections; freeze dried, and ages determined using 210Pb dating method. The BC was chemically separated, and [BC] determined by the thermal optical method. The [BC] varied from 50 to 1140µg/gdry weight in SJ; and 20 to 130µg/gdry weight in VJ. Husain et al.,(JGR, vol 113, D13102,doi:10.1029/2007JD009398, 2008) showed that the atmospheric deposition of BC into lake sediments depends on the characteristic of individual lakes, BC washout ratios, precipitation intensity, and sedimentation rates. The deposition rate, K, for a lake is defined by, [BC]sed = K[BC]atm where [BC]sed, is the concentration of BC in the sediment. We have measured [BC]atm from 1970 to 2010 in Kevo, Finland, where VJ and SJ are located. The [BC]atm from Kevo, and [BC]sed from VJ, and SJ were used to determine K for each of the lake. Owing to the availability of the long term atmospheric BC data from 1970 to 2010 multiple measurements of K were made, and provided a high measure of precision. The mean values of K for VJ, and SJ were 226 ± 60, and 830 ± 290 (m3air/ gdry weight). The K values were used to determine [BC]atm for the years before 1970. The [BC]atm from 2013 to 2006 was 82ng/m3. It increased slowly reaching a peak value of about 947 ± 322 ng/m3.The concentrations decreased subsequently to 244 ± 83ng/m3 in 1920, and changed little ~ 1774.The lowest concentration, 77 ± 26 ng/m3, was observed ~ 1700. The high atmospheric concentrations beyond 1850, perhaps, suggest a proportionally larger component from wood burning for heating. We plan to estimate [BC]atm using OsloCTM3 model, and inventory of fossil fuel, and biomass burning, and compare it with our measurements.

Gigabit ATM: another technical mistake?

NASA Astrophysics Data System (ADS)

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, many of the elements mentioned above are now being presented by standard 'Gigabit Ethernet and Gigabit ATM -- friends or foes' conferences. In- depth analyses are given concerning the canonical elements of such a setting: legacy, new use requirements, manageability, security LAN-WAN, architectures, standards, technologies and products, complexity, evolution-transition strategies, manufacturers, player organizations etc. Often in such conferences, Fiber Channel, being one of Gigabit Ethernet's physical media, is presented as the only other Gigabit LAN technology. In an attempt to sum up: Given the present state of ATM deployment measured in terms of functionalities and sophistication, after ten years of CCCITT/ITU and almost as many years of ATM Forum effort, does the question still being asked now represent the answer -- ATM is or was a mistake there some elements still missing? Here's a technical and a political example:

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

PubMed Central

Yang, Di; Fletcher, Sally C.; Vendrell, Iolanda; Fischer, Roman; Legrand, Arnaud J.

2017-01-01

Abstract 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. PMID:28973444

Snowfall Rate Retrieval Using Passive Microwave Measurements and Its Applications in Weather Forecast and Hydrology

NASA Technical Reports Server (NTRS)

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

2015-01-01

(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 also been developed. 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. It employs a combination of temperature and water vapor sounding channels to detect the scattering signal from falling snow and derives the probability of snowfall. Cloud properties are retrieved using an inversion method with an iteration algorithm and a two-stream radiative transfer model. A method adopted to calculate snow particle terminal velocity. Finally, snowfall rate is computed by numerically solving a complex integral. The SFR products are being used mainly in two communities: hydrology and weather forecast. Global blended precipitation products traditionally do not include snowfall derived from satellites because such products were not available operationally in the past. The ATMS and AMSU/MHS SFR now provide the winter precipitation information for these blended precipitation products. Weather forecasters mainly rely on radar and station observations for snowfall forecast. The SFR products can fill in gaps where no conventional snowfall data are available to forecasters. The products can also be used to confirm radar and gauge snowfall data and increase forecasters' confidence in their prediction.

Evaluation of Pharmacodynamic Interactions Between Telavancin and Aztreonam or Piperacillin/Tazobactam Against Pseudomonas aeruginosa, Escherichia coli and Methicillin-Resistant Staphylococcus aureus.

PubMed

Yim, Juwon; Smith, Jordan R; Barber, Katie E; Hallesy, Jessica A; Rybak, Michael J

2016-09-01

In clinical trials comparing telavancin (TLV) with vancomycin for treatment of hospital-acquired pneumonia, TLV demonstrated lower clinical cure rates than vancomycin in patients who had mixed gram-positive and -negative infections and were concomitantly treated with either aztreonam (ATM) or piperacillin/tazobactam (PTZ). Here, we investigated therapeutic interactions between TLV and ATM or PTZ in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model under simulated reduced renal function conditions. In vitro one-compartment PK/PD models were run over 96 h simulating TLV 10 mg/kg every 48 h, ATM 500 mg every 8 h and PTZ continuous infusion 13.5 g over 24 h alone and in combination against P. aeruginosa, E. coli and methicillin-resistant S. aureus (MRSA). The efficacy of antimicrobials was evaluated by plotting time-kill curves and calculating the reduction in log10 cfu/ml over 96 h. Against both MRSA strains, TLV was rapidly bactericidal at 4 h and maintained its activity over 96 h with no observed antagonism by either ATM or PTZ. PTZ maintained bacteriostatic and bactericidal activities against E. coli ATCC 25922 and clinical strain R1022 at 96 h, whereas both strains regrew as soon as 24 h in ATM models. Against P. aeruginosa ATCC 27853, regrowth was noted at 24 h in models simulating ATM and PTZ. The addition of TLV to ATM or PTZ had no appreciable impact on activity against the two E. coli strains and P. aeruginosa strain. The combinations of TLV and either ATM or PTZ did not demonstrate any antagonistic activity. Clinical variables and patient characteristics should be further explored to determine possible reasons for discrepancies in outcomes. Theravance Biopharma Antibiotics, Inc.

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

PubMed

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

2017-07-15

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

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

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

Morita, Akinori, E-mail: morita@tokushima-u.ac.jp; Department of Radiological Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509; Tanimoto, Keiji

2014-01-24

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

ATM activation in normal human tissues and testicular cancer.

PubMed

Bartkova, Jirina; Bakkenist, Christopher J; Rajpert-De Meyts, Ewa; Skakkebaek, Niels E; Sehested, Maxwell; Lukas, Jiri; Kastan, Michael B; Bartek, Jiri

2005-06-01

The ATM kinase is a tumor suppressor and key regulator of biological responses to DNA damage. Cultured cells respond to genotoxic insults that induce DNA double-strand breaks by prompt activation of ATM through its autophosphorylation on serine 1981. However, whether ATM-S1981 becomes phosphorylated in vivo, for example during physiological processes that generate DSBs, is unknown. Here we produced phospho-specific monoclonal antibodies against S1981-phosphorylated ATM (pS-ATM), and applied them to immunohistochemical analyses of a wide range of normal human tissues and testicular tumors. Our data show that regardless of proliferation and differentiation, most human tissues contain only the S1981-nonphosphorylated, inactive form of ATM. In contrast, nuclear staining for pS-ATM was detected in subsets of bone-marrow lymphocytes and primary spermatocytes in the adult testes, cell types in which DSBs are generated during physiological V(D)J recombination and meiotic recombination, respectively. Among testicular germ-cell tumors, an aberrant constitutive pS-ATM was observed especially in embryonal carcinomas, less in seminomas, and only modestly in teratomas and the pre-invasive carcinoma-in-situ stage. Compared with pS-ATM, phosphorylated histone H2AX (gammaH2AX), another DNA damage marker and ATM substrate, was detected in a higher proportion of cancer cells, and also in normal fetal gonocytes, and a wider range of adult spermatocyte differentiation stages. Collectively, our results strongly support the physiological relevance of the recently proposed model of ATM autoactivation, and provide further evidence for constitutive activation of the DNA damage machinery during cancer development. The new tools characterized here should facilitate monitoring of ATM activation in clinical specimens, and help develop future treatment strategies.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

Satellite Communications for ATM

NASA Technical Reports Server (NTRS)

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 applications that generally will enhance the standard services provided. All of those possibilities were investigated and comments, as well as descriptions of those analyses are put forward, as well as suggestions for future areas of study.

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

PubMed

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.

Comparing IceBridge and CryoSat-2 sea ice observations over the Arctic and the Southern Ocean

NASA Astrophysics Data System (ADS)

Yi, D.; Kurtz, N. T.; Harbeck, J.; Hofton, M. A.; Manizade, S.; Cornejo, H.

2016-12-01

From 2009 to 2015, CryoSat-2 and IceBridge had 34 coincident lines over sea ice, 23 over the Arctic (20 with ATM, 2 with LVIS, and 1 with both ATM and LVIS) and 11 over the Southern Ocean (9 with ATM and 2 with both ATM and LVIS). In this study, we will compare both surface elevation and sea ice freeboard from CryoSat-2, ATM, and LVIS. We will apply identical ellipsoid, geoid, tide models, and atmospheric corrections to CryoSat-2, ATM, and LVIS data. For CryoSat-2, we will use surface elevation and sea ice freeboard both in the standard CryoSat-2 data product and calculated through a waveform fitting method. For ATM and LVIS, we will use surface elevation and sea ice freeboard in the OIB data product and the elevation and sea ice freeboard calculated through Gaussian waveform fitting method. The results of this study are important for using ATM and LVIS to calibrate/validate CryoSat-2 results and bridging the data gap between ICESat and ICESat-2.

Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage.

PubMed

Quek, Hazel; Luff, John; Cheung, KaGeen; Kozlov, Sergei; Gatei, Magtouf; Lee, C Soon; Bellingham, Mark C; Noakes, Peter G; Lim, Yi Chieh; Barnett, Nigel L; Dingwall, Steven; Wolvetang, Ernst; Mashimo, Tomoji; Roberts, Tara L; Lavin, Martin F

2017-04-01

Mutations in the ataxia-telangiectasia (A-T)-mutated ( ATM ) gene give rise to the human genetic disorder A-T, characterized by immunodeficiency, cancer predisposition, and neurodegeneration. Whereas a series of animal models recapitulate much of the A-T phenotype, they fail to present with ataxia or neurodegeneration. We describe here the generation of an Atm missense mutant [amino acid change of leucine (L) to proline (P) at position 2262 (L2262P)] rat by intracytoplasmic injection (ICSI) of mutant sperm into oocytes. Atm -mutant rats ( Atm L2262P/L2262P ) expressed low levels of ATM protein, suggesting a destabilizing effect of the mutation, and had a significantly reduced lifespan compared with Atm +/+ Whereas these rats did not show cerebellar atrophy, they succumbed to hind-limb paralysis (45%), and the remainder developed tumors. Closer examination revealed the presence of both dsDNA and ssDNA in the cytoplasm of cells in the hippocampus, cerebellum, and spinal cord of Atm L2262P/L2262P rats. Significantly increased levels of IFN-β and IL-1β in all 3 tissues were indicative of DNA damage induction of the type 1 IFN response. This was further supported by NF-κB activation, as evidenced by p65 phosphorylation (P65) and translocation to the nucleus in the spinal cord and parahippocampus. Other evidence of neuroinflammation in the brain and spinal cord was the loss of motor neurons and the presence of increased activation of microglia. These data provide support for a proinflammatory phenotype that is manifested in the Atm mutant rat as hind-limb paralysis. This mutant represents a useful model to investigate the importance of neuroinflammation in A-T. © Society for Leukocyte Biology.

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

PubMed

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.

The effect of char structure on burnout during pulverized coal combustion at pressure

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

Liu, G.; Wu, H.; Benfell, K.E.

An Australian bituminous coal sample was burnt in a drop tube furnace (DTF) at 1 atm and a pressurized drop tube furnace (PDTF) at 15 atm. The char samples were collected at different burnout levels, and a scanning electron microscope was used to examine the structures of chars. A model was developed to predict the burnout of char particles with different structures. The model accounts for combustion of the thin-walled structure of cenospheric char and its fragmentation during burnout. The effect of pressure on reaction rate was also considered in the model. As a result, approximately 40% and 70% cenosphericmore » char particles were observed in the char samples collected after coal pyrolysis in the DTF and PDTF respectively. A large number of fine particles (< 30 mm) were observed in the 1 atm char samples at burnout levels between 30% and 50%, which suggests that significant fragmentation occurred during early combustion. Ash particle size distributions show that a large number of small ash particles formed during burnout at high pressure. The time needed for 70% char burnout at 15 atm is approximately 1.6 times that at 1 atm under the same temperature and gas environment conditions, which is attributed to the different pressures as well as char structures. The overall reaction rate for cenospheric char was predicted to be approximately 2 times that of the dense chars, which is consistent with previous experimental results. The predicted char burnout including char structures agrees reasonably well with the experimental measurements that were obtained at 1 atm and 15 atm pressures.« less

A high-speed network for cardiac image review.

PubMed

Elion, J L; Petrocelli, R R

1994-01-01

A high-speed fiber-based network for the transmission and display of digitized full-motion cardiac images has been developed. Based on Asynchronous Transfer Mode (ATM), the network is scaleable, meaning that the same software and hardware is used for a small local area network or for a large multi-institutional network. The system can handle uncompressed digital angiographic images, considered to be at the "high-end" of the bandwidth requirements. Along with the networking, a general-purpose multi-modality review station has been implemented without specialized hardware. This station can store a full injection sequence in "loop RAM" in a 512 x 512 format, then interpolate to 1024 x 1024 while displaying at 30 frames per second. The network and review stations connect to a central file server that uses a virtual file system to make a large high-speed RAID storage disk and associated off-line storage tapes and cartridges all appear as a single large file system to the software. In addition to supporting archival storage and review, the system can also digitize live video using high-speed Direct Memory Access (DMA) from the frame grabber to present uncompressed data to the network. Fully functional prototypes have provided the proof of concept, with full deployment in the institution planned as the next stage.

A high-speed network for cardiac image review.

PubMed Central

Elion, J. L.; Petrocelli, R. R.

1994-01-01

A high-speed fiber-based network for the transmission and display of digitized full-motion cardiac images has been developed. Based on Asynchronous Transfer Mode (ATM), the network is scaleable, meaning that the same software and hardware is used for a small local area network or for a large multi-institutional network. The system can handle uncompressed digital angiographic images, considered to be at the "high-end" of the bandwidth requirements. Along with the networking, a general-purpose multi-modality review station has been implemented without specialized hardware. This station can store a full injection sequence in "loop RAM" in a 512 x 512 format, then interpolate to 1024 x 1024 while displaying at 30 frames per second. The network and review stations connect to a central file server that uses a virtual file system to make a large high-speed RAID storage disk and associated off-line storage tapes and cartridges all appear as a single large file system to the software. In addition to supporting archival storage and review, the system can also digitize live video using high-speed Direct Memory Access (DMA) from the frame grabber to present uncompressed data to the network. Fully functional prototypes have provided the proof of concept, with full deployment in the institution planned as the next stage. PMID:7949964

Multi-National Banknote Classification Based on Visible-light Line Sensor and Convolutional Neural Network.

PubMed

Pham, Tuyen Danh; Lee, Dong Eun; Park, Kang Ryoung

2017-07-08

Automatic recognition of banknotes is applied in payment facilities, such as automated teller machines (ATMs) and banknote counters. Besides the popular approaches that focus on studying the methods applied to various individual types of currencies, there have been studies conducted on simultaneous classification of banknotes from multiple countries. However, their methods were conducted with limited numbers of banknote images, national currencies, and denominations. To address this issue, we propose a multi-national banknote classification method based on visible-light banknote images captured by a one-dimensional line sensor and classified by a convolutional neural network (CNN) considering the size information of each denomination. Experiments conducted on the combined banknote image database of six countries with 62 denominations gave a classification accuracy of 100%, and results show that our proposed algorithm outperforms previous methods.

Multi-National Banknote Classification Based on Visible-light Line Sensor and Convolutional Neural Network

PubMed Central

Pham, Tuyen Danh; Lee, Dong Eun; Park, Kang Ryoung

2017-01-01

Automatic recognition of banknotes is applied in payment facilities, such as automated teller machines (ATMs) and banknote counters. Besides the popular approaches that focus on studying the methods applied to various individual types of currencies, there have been studies conducted on simultaneous classification of banknotes from multiple countries. However, their methods were conducted with limited numbers of banknote images, national currencies, and denominations. To address this issue, we propose a multi-national banknote classification method based on visible-light banknote images captured by a one-dimensional line sensor and classified by a convolutional neural network (CNN) considering the size information of each denomination. Experiments conducted on the combined banknote image database of six countries with 62 denominations gave a classification accuracy of 100%, and results show that our proposed algorithm outperforms previous methods. PMID:28698466

A bibliometric analysis on tobacco regulation investigators.

PubMed

Li, Dingcheng; Okamoto, Janet; Liu, Hongfang; Leischow, Scott

2015-01-01

To facilitate the implementation of the Family Smoking Prevention and Tobacco Control Act of 2009, the Federal Drug Agency (FDA) Center for Tobacco Products (CTP) has identified research priorities under the umbrella of tobacco regulatory science (TRS). As a newly integrated field, the current boundaries and landscape of TRS research are in need of definition. In this work, we conducted a bibliometric study of TRS research by applying author topic modeling (ATM) on MEDLINE citations published by currently-funded TRS principle investigators (PIs). We compared topics generated with ATM on dataset collected with TRS PIs and topics generated with ATM on dataset collected with a TRS keyword list. It is found that all those topics show a good alignment with FDA's funding protocols. More interestingly, we can see clear interactive relationships among PIs and between PIs and topics. Based on those interactions, we can discover how diverse each PI is, how productive they are, which topics are more popular and what main components each topic involves. Temporal trend analysis of key words shows the significant evaluation in four prime TRS areas. The results show that ATM can efficiently group articles into discriminative categories without any supervision. This indicates that we may incorporate ATM into author identification systems to infer the identity of an author of articles using topics generated by the model. It can also be useful to grantees and funding administrators in suggesting potential collaborators or identifying those that share common research interests for data harmonization or other purposes. The incorporation of temporal analysis can be employed to assess the change over time in TRS as new projects are funded and the extent to which new research reflects the funding priorities of the FDA.

Small-Maturity Asymptotics for the At-The-Money Implied Volatility Slope in Lévy Models

PubMed Central

Gerhold, Stefan; Gülüm, I. Cetin; Pinter, Arpad

2016-01-01

ABSTRACT We consider the at-the-money (ATM) strike derivative of implied volatility as the maturity tends to zero. Our main results quantify the behaviour of the slope for infinite activity exponential Lévy models including a Brownian component. As auxiliary results, we obtain asymptotic expansions of short maturity ATM digital call options, using Mellin transform asymptotics. Finally, we discuss when the ATM slope is consistent with the steepness of the smile wings, as given by Lee’s moment formula. PMID:27660537

Evaluation of the impacts of ITS technologies on the Borman Expressway Network

DOT National Transportation Integrated Search

1998-10-01

The Indiana Department of Transportation (INDOT) is currently implementing (or has implemented) several components of Intelligent Transportation Systems (ITS). This includes a mini Advanced Traffic Management Systems (ATMS) implemented on a three-mil...

EU-US standards harmonization task group report : on GeoNetworking.

DOT National Transportation Integrated Search

1996-03-01

TRAVTEK WAS AN OPERATIONAL FIELD TEST OF AN ADVANCED TRAVELER INFORMATION SYSTEMS (ATIS) AND ADVANCED TRAFFIC MANAGEMENT SYSTEMS (ATMS) TECHNOLOGIES. THIS PAPER SUMMARIZESS THE FINDINGS FROM THE SERIES OF STUDIES THAT CONSTITUTED THE TRAVTEK EVALUATI...

Cellphone probes as an ATMS tool

DOT National Transportation Integrated Search

2003-06-01

The foundation of traffic operations and management is the ability to monitor traffic conditions. One approach to traffic monitoring is to sample conditions by tracking a limited number of probe vehicles as they traverse a network. An emerging techno...

The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo.

PubMed

Vendetti, Frank P; Lau, Alan; Schamus, Sandra; Conrads, Thomas P; O'Connor, Mark J; Bakkenist, Christopher J

2015-12-29

ATR and ATM are DNA damage signaling kinases that phosphorylate several thousand substrates. ATR kinase activity is increased at damaged replication forks and resected DNA double-strand breaks (DSBs). ATM kinase activity is increased at DSBs. ATM has been widely studied since ataxia telangiectasia individuals who express no ATM protein are the most radiosensitive patients identified. Since ATM is not an essential protein, it is widely believed that ATM kinase inhibitors will be well-tolerated in the clinic. ATR has been widely studied, but advances have been complicated by the finding that ATR is an essential protein and it is widely believed that ATR kinase inhibitors will be toxic in the clinic. We describe AZD6738, an orally active and bioavailable ATR kinase inhibitor. AZD6738 induces cell death and senescence in non-small cell lung cancer (NSCLC) cell lines. AZD6738 potentiates the cytotoxicity of cisplatin and gemcitabine in NSCLC cell lines with intact ATM kinase signaling, and potently synergizes with cisplatin in ATM-deficient NSCLC cells. In contrast to expectations, daily administration of AZD6738 and ATR kinase inhibition for 14 consecutive days is tolerated in mice and enhances the therapeutic efficacy of cisplatin in xenograft models. Remarkably, the combination of cisplatin and AZD6738 resolves ATM-deficient lung cancer xenografts.

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

PubMed Central

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

2017-01-01

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 Brca1S1598F 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 Brca1S1598F cells. Consistent with a critical role for ATM in HDR in this background, loss of ATM leads to synthetic lethality of Brca1S1598F 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. PMID:28659469

Advisor-Teller Money Manager (ATM) therapy for substance use disorders.

PubMed

Rosen, Marc I; Rounsaville, Bruce J; Ablondi, Karen; Black, Anne C; Rosenheck, Robert A

2010-07-01

Patients with concomitant psychiatric and substance use disorders are commonly assigned representative payees or case managers to help manage their funds, but money management has not been conceptualized as a theory-based treatment. This randomized clinical trial was conducted to determine the effect of a money management-based therapy, advisor-teller money manager (ATM), on substance abuse or dependence. Ninety patients at a community mental health center who had a history of cocaine or alcohol abuse or dependence were assessed after random assignment to 36 weeks of ATM (N=47) or a control condition in which use of a financial workbook was reviewed (N=43). Patients assigned to ATM were encouraged to deposit their funds into a third-party account, plan weekly expenditures, and negotiate monthly budgets. Substance use calendars and urine toxicology tests were collected every other week for 36 weeks and again 52 weeks after randomization. Patients assigned to ATM had significantly more negative toxicologies for cocaine metabolite over time than patients in the control group, and treating clinicians rated ATM patients as significantly more likely to be abstinent from illicit drugs. Self-reported abstinence from alcohol did not significantly differ between groups. Unexpectedly, patients assigned to ATM were more likely to be assigned a representative payee or a conservator than control participants during the follow-up period (ten of 47 versus two of 43). One patient in ATM assaulted the therapist when his check had not arrived. ATM is an efficacious therapy for the treatment of cocaine abuse or dependence among people with concomitant psychiatric illness but requires protection of patient autonomy and staff safety.

Incorporating Truncating Variants in PALB2, CHEK2 and ATM into the BOADICEA Breast Cancer Risk Model

PubMed Central

Lee, Andrew J.; Cunningham, Alex P.; Tischkowitz, Marc; Simard, Jacques; Pharoah, Paul D.; Easton, Douglas F.; Antoniou, Antonis C.

2016-01-01

Purpose The proliferation of gene-panel testing precipitates the need for a breast cancer (BC) risk model that incorporates the effects of mutations in several genes and family history (FH). We extended the BOADICEA model to incorporate the effects of truncating variants in PALB2, CHEK2 and ATM. Methods The BC incidence was modelled via the explicit effects of truncating variants in BRCA1/2, PALB2, CHEK2 and ATM and other unobserved genetic effects using segregation analysis methods. Results The predicted average BC risk by age 80 for an ATM mutation carrier is 28%, 30% for CHEK2, 50% for PALB2, 74% for BRCA1 and BRCA2. However, the BC risks are predicted to increase with FH-burden. In families with mutations, predicted risks for mutation-negative members depend on both FH and the specific mutation. The reduction in BC risk after negative predictive-testing is greatest when a BRCA1 mutation is identified in the family, but for women whose relatives carry a CHEK2 or ATM mutation, the risks decrease slightly. Conclusions The model may be a valuable tool for counselling women who have undergone gene-panel testing for providing consistent risks and harmonizing their clinical management. A web-application can be used to obtain BC- risks in clinical practice (http://ccge.medschl.cam.ac.uk/boadicea/). PMID:27464310

Incorporating truncating variants in PALB2, CHEK2, and ATM into the BOADICEA breast cancer risk model.

PubMed

Lee, Andrew J; Cunningham, Alex P; Tischkowitz, Marc; Simard, Jacques; Pharoah, Paul D; Easton, Douglas F; Antoniou, Antonis C

2016-12-01

The proliferation of gene panel testing precipitates the need for a breast cancer (BC) risk model that incorporates the effects of mutations in several genes and family history (FH). We extended the BOADICEA model to incorporate the effects of truncating variants in PALB2, CHEK2, and ATM. The BC incidence was modeled via the explicit effects of truncating variants in BRCA1/2, PALB2, CHEK2, and ATM and other unobserved genetic effects using segregation analysis methods. The predicted average BC risk by age 80 for an ATM mutation carrier is 28%, 30% for CHEK2, 50% for PALB2, and 74% for BRCA1 and BRCA2. However, the BC risks are predicted to increase with FH burden. In families with mutations, predicted risks for mutation-negative members depend on both FH and the specific mutation. The reduction in BC risk after negative predictive testing is greatest when a BRCA1 mutation is identified in the family, but for women whose relatives carry a CHEK2 or ATM mutation, the risks decrease slightly. The model may be a valuable tool for counseling women who have undergone gene panel testing for providing consistent risks and harmonizing their clinical management. A Web application can be used to obtain BC risks in clinical practice (http://ccge.medschl.cam.ac.uk/boadicea/).Genet Med 18 12, 1190-1198.

The ATM protein kinase and cellular redox signaling: beyond the DNA damage response

PubMed Central

Ditch, Scott; Paull, Tanya T.

2011-01-01

The ataxia-telangiectasia mutated (ATM) protein kinase is best known for its role in the DNA damage response, but recent findings suggest that it also functions as a redox sensor that controls the levels of reactive oxygen species in human cells. Here, we review the evidence supporting the conclusion that ATM can be directly activated by oxidation, as well as various observations from ATM-deficient patients and mouse models that point toward the importance of ATM in oxidative stress responses. We also discuss the roles of this kinase in regulating mitochondrial function and metabolic control through its action on tumor suppressor p53, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and hypoxia-inducible factor-1 (HIF-1), and how the regulation of these enzymes may be affected in ATM-deficient patients and in cancer cells. PMID:22079189

The ATM protein kinase and cellular redox signaling: beyond the DNA damage response.

PubMed

Ditch, Scott; Paull, Tanya T

2012-01-01

The ataxia-telangiectasia mutated (ATM) protein kinase is best known for its role in the DNA damage response, but recent findings suggest that it also functions as a redox sensor that controls the levels of reactive oxygen species in human cells. Here, we review evidence supporting the conclusion that ATM can be directly activated by oxidation, as well as various observations from ATM-deficient patients and mouse models that point to the importance of ATM in oxidative stress responses. We also discuss the roles of this kinase in regulating mitochondrial function and metabolic control through its action on tumor suppressor p53, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and hypoxia-inducible factor 1 (HIF1), and how the regulation of these enzymes may be affected in ATM-deficient patients and in cancer cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

Providing QoS guarantee in 3G wireless networks

NASA Astrophysics Data System (ADS)

Chuah, MooiChoo; Huang, Min; Kumar, Suresh

2001-07-01

The third generation networks and services present opportunities to offer multimedia applications and services that meet end-to-end quality of service requirements. In this article, we present UMTS QoS architecture and its requirements. This includes the definition of QoS parameters, traffic classes, the end-to-end data delivery model, and the mapping of end-to-end services to the services provided by the network elements of the UMTS. End-to-end QoS of a user flow is achieved by the combination of the QoS control over UMTS Domain and the IP core Network. In the Third Generation Wireless network, UMTS bearer service manager is responsible to manage radio and transport resources to QoS-enabled applications. The UMTS bearer service consists of the Radio Access Bearer Service between Mobile Terminal and SGSN and Core Network bearer service between SGSN and GGSN. The Radio Access Bearer Service is further realized by the Radio Bearer Service (mostly air interface) and Iu bearer service. For the 3G air interface, one can provide differentiated QoS via intelligent burst allocation scheme, adaptive spreading factor control and weighted fair queueing scheduling algorithms. Next, we discuss the requirements for the transport technologies in the radio access network to provide differentiated QoS to multiple classes of traffic. We discuss both ATM based and IP based transport solutions. Last but not least, we discuss how QoS mechanism is provided in the core network to ensure e2e quality of service requirements. We discuss how mobile terminals that use RSVP as QoS signaling mechanisms can be are supported in the 3G network which may implement only IETF diffserv mechanism. . We discuss how one can map UMTS QoS classes with IETF diffserv code points. We also discuss 2G/3G handover scenarios and how the 2G/3G QoS parameters can be mapped.

Impacts of ocean acidification on respiratory gas exchange and acid-base balance in a marine teleost, Opsanus beta.

PubMed

Esbaugh, Andrew J; Heuer, Rachael; Grosell, Martin

2012-10-01

The oceanic carbonate system is changing rapidly due to rising atmospheric CO(2), with current levels expected to rise to between 750 and 1,000 μatm by 2100, and over 1,900 μatm by year 2300. The effects of elevated CO(2) on marine calcifying organisms have been extensively studied; however, effects of imminent CO(2) levels on teleost acid-base and respiratory physiology have yet to be examined. Examination of these physiological processes, using a paired experimental design, showed that 24 h exposure to 1,000 and 1,900 μatm CO(2) resulted in a characteristic compensated respiratory acidosis response in the gulf toadfish (Opsanus beta). Time course experiments showed the onset of acidosis occurred after 15 min of exposure to 1,900 and 1,000 μatm CO(2), with full compensation by 2 and 4 h, respectively. 1,900-μatm exposure also resulted in significantly increased intracellular white muscle pH after 24 h. No effect of 1,900 μatm was observed on branchial acid flux; however, exposure to hypercapnia and HCO(3)(-) free seawater compromised compensation. This suggests branchial HCO(3)(-) uptake rather than acid extrusion is part of the compensatory response to low-level hypercapnia. Exposure to 1,900 μatm resulted in downregulation in branchial carbonic anhydrase and slc4a2 expression, as well as decreased Na(+)/K(+) ATPase activity after 24 h of exposure. Infusion of bovine carbonic anhydrase had no effect on blood acid-base status during 1,900 μatm exposures, but eliminated the respiratory impacts of 1,000 μatm CO(2). The results of the current study clearly show that predicted near-future CO(2) levels impact respiratory gas transport and acid-base balance. While the full physiological impacts of increased blood HCO(3)(-) are not known, it seems likely that chronically elevated blood HCO(3)(-) levels could compromise several physiological systems and furthermore may explain recent reports of increased otolith growth during exposure to elevated CO(2).

FACET: Future ATM Concepts Evaluation Tool

NASA Technical Reports Server (NTRS)

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

2000-01-01

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

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

PubMed

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 treated with and without pharmacological kinase inhibitors revealed ATM-dependent chromatin remodeling at the MLL break site giving access to DNA repair proteins but also nucleases triggering MLL rearrangements. This chapter summarizes these methods for functional characterization of ATM in patient LCLs and human cell lines.

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

PubMed

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 cisplatin-resistance of lung cancer.

Laboratory Evaluation of Dynamic Traffic Assignment Systems: Requirements, Framework, and System Design

DOT National Transportation Integrated Search

1997-01-01

The success of Advanced Traveler Information Systems (ATIS) and Advanced Traffic Management Systems (ATMS) depends on the availability and dissemination of timely and accurate estimates of current and emerging traffic network conditions. Real-time Dy...

Gigabit Ethernet: A Technical Assessment.

ERIC Educational Resources Information Center

Axner, David

1997-01-01

Describes gigabit ethernet for LAN (local area network) technology that will expand ethernet bandwidth. Technical details are discussed, including protocol stacks, optical fiber, deployment strategy for performance improvement, ATM (Asynchronous Transfer Mode), real-time protocol, reserve reservation protocol, and standards. (LRW)

Videoconferencing Comes of Age.

ERIC Educational Resources Information Center

Bosak, Steve

2000-01-01

Hundreds of districts are using high-speed videoconferencing for distance learning and resource sharing, inservice training, and districtwide meetings. Speed matters. Districts will need either Ethernet or ATM (asynchronous transfer mode) forms of wide-area networks to connect schools and offices. (MLH)

QoS for Real Time Applications over Next Generation Data Networks

NASA Technical Reports Server (NTRS)

Ivancic, William; Atiquzzaman, Mohammed; Bai, Haowei; Su, Hongjun; Chitri, Jyotsna; Ahamed, Faruque

2001-01-01

Viewgraphs on Qualtity of Service (QOS) for real time applications over next generation data networks are presented. The progress to date include: Task 1: QoS in Integrated Services over DiffServ networks (UD); Task 2: Interconnecting ATN with the next generation Internet (UD); Task 3: QoS in DiffServ over ATM (UD); Task 4: Improving Explicit Congestion Notification with the Mark-Front Strategy (OSU); Task 5: Multiplexing VBR over VBR (OSU); and Task 6: Achieving QoS for TCP traffic in Satellite Networks with Differentiated Services (OSU).

Decompression tables for inside chamber attendants working at altitude.

PubMed

Bell, James; Thombs, Paul A; Davison, William J; Weaver, Lindell K

2014-01-01

Hyperbaric oxygen (HBO2) multiplace chamber inside attendants (IAs) are at risk for decompression sickness (DCS). Standard decompression tables are formulated for sea-level use, not for use at altitude. At Presbyterian/St. Luke's Medical Center (Denver, Colorado, 5,924 feet above sea level) and Intermountain Medical Center (Murray, Utah, 4,500 feet), the decompression obligation for IAs is managed with U.S. Navy Standard Air Tables corrected for altitude, Bühlmann Tables, and the Nobendem© calculator. IAs also breathe supplemental oxygen while compressed. Presbyterian/St. Luke's (0.83 atmospheres absolute/atm abs) uses gauge pressure, uncorrected for altitude, at 45 feet of sea water (fsw) (2.2 atm abs) for routine wound care HBO2 and 66 fsw (2.8 atm abs) for carbon monoxide/cyanide poisoning. Presbyterian/St. Luke's provides oxygen breathing for the IAs at 2.2 atm abs. At Intermountain (0.86 atm abs), HBO2 is provided at 2.0 atm abs for routine treatments and 3.0 atm abs for carbon monoxide poisoning. Intermountain IAs breathe intermittent 50% nitrogen/50% oxygen at 3.0 atm abs and 100% oxygen at 2.0 atm abs. The chamber profiles include a safety stop. From 1990-2013, Presbyterian/St. Luke's had 26,900 total IA exposures: 25,991 at 45 fsw (2.2 atm abs) and 646 at 66 fsw (2.8 atm abs); there have been four cases of IA DCS. From 2008-2013, Intermountain had 1,847 IA exposures: 1,832 at 2 atm abs and 15 at 3 atm abs, with one case of IA DCS. At both facilities, DCS incidents occurred soon after the chambers were placed into service. Based on these results, chamber inside attendant risk for DCS at increased altitude is low when the inside attendants breathe supplemental oxygen.

An HTRF® Assay for the Protein Kinase ATM.

PubMed

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.

Detection of ATM germline variants by the p53 mitotic centrosomal localization test in BRCA1/2-negative patients with early-onset breast cancer.

PubMed

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.

Advisor-Teller Money Manager (ATM) Therapy for Substance Use Disorders

PubMed Central

Rosen, Marc I.; Rounsaville, Bruce J.; Ablondi, Karen; Black, Anne C.; Rosenheck, Robert A.

2011-01-01

Objective Patients with concomitant psychiatric and substance use disorders are commonly assigned representative payees or case managers to help manage their funds, but money management has not been conceptualized as a theory-based treatment. This randomized clinical trial was conducted to determine the effect of a money management–based therapy, advisor-teller money manager (ATM), on substance abuse or dependence. Methods Ninety patients at a community mental health center who had a history of cocaine or alcohol abuse or dependence were assessed after random assignment to 36 weeks of ATM (N=47) or a control condition in which use of a financial workbook was reviewed (N=43). Patients assigned to ATM were encouraged to deposit their funds into a third-party account, plan weekly expenditures, and negotiate monthly budgets. Substance use calendars and urine toxicology tests were collected every other week for 36 weeks and again 52 weeks after randomization. Results Patients assigned to ATM had significantly more negative toxicologies for cocaine metabolite over time than patients in the control group, and treating clinicians rated ATM patients as significantly more likely to be abstinent from illicit drugs. Self-reported abstinence from alcohol did not significantly differ between groups. Unexpectedly, patients assigned to ATM were more likely to be assigned a representative payee or a conservator than control participants during the follow-up period (ten of 47 versus two of 43). One patient in ATM assaulted the therapist when his check had not arrived. Conclusions ATM is an efficacious therapy for the treatment of cocaine abuse or dependence among people with concomitant psychiatric illness but requires protection of patient autonomy and staff safety. PMID:20592006

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

PubMed

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.

Ames Research Center Mars/Pathfinder Heat Shield Design Verification ARC-JET Test

NASA Technical Reports Server (NTRS)

Tran, Huy K.; Hui, Frank; Wercinski, Paul; Cartledge, Alan; Tauber, Mike; Tran, Duoc T.; Chen, Y. K.; Arnold, James O. (Technical Monitor)

1995-01-01

Design verification tests were performed on samples representing the aerobrake of the Mars/Pathfinder vehicle. The test specimens consisted of the SLA-561V ablator bonded to the honeycomb structure. The primary objective was to evaluate the ablation materials performance and to measure temperatures within the ablator, at the structural bondline and at the back sheet of the honeycomb structure. Other objectives were to evaluate the effect of ablative repair plug material treatment and voids in the heat shield. A total of 29 models were provided for testing in the Ames 60MW arc-jet facility. Of these, 23 models were flat-faced and six remaining models were curved edge ones, intended to simulate the conditions on the curved rim of the forebody where the maximum shear occurred. Eight sets of test conditions were used. The stagnation point heating rates varied from 47 to 240 W/cm2 and the stagnation pressures from 0.15 to 0.27 atm. (The maximum flight values are 132 W/cm2 and 0.25 atm) The majority of these runs were made at a nominal stagnation pressure of 0.25 atm. Two higher pressure runs were made to check the current (denser) ablation material for spallation, or other forms of thermal stress failure. Over 60% of the flatfaced models yielded good thermocouple data and all produced useful surface recession information. Of the five curved-edge models that were tested, only one gave good data; the remaining ones experienced model-holder failure. The test results can be summarized by noting that no failure of the ablative material was observed on any model. Also, the bondline temperature design limit of 250 C was never reached within an equivalent flight time despite a stagnation point heat load that exceeded the maximum flight value by up to 130%. At heating rates of over 200W/cm2 and stagnation pressures of 0.25 atm, or greater, the average surface recessions exceeded 0.5 cm on some models. The surface roughness increased dramatically at pressures above 0.25 atm and was four times greater at 0.27 atm than at 0.25 atm. Procured repair plug material performed much better than room-temperature cured plugs, as observed in the previous tests. Voids in the ablator did not increase local temperatures and gaps did not grow during testing.

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

PubMed

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, <.001 and .001, respectively). Two variants, rs1042059 and rs201024480, in BMI-1 gene were low penetrant, with no detectable significance. After adjustment, rs189037 and rs1801516 were significantly associated with breast cancer under the additive model (OR: 1.37 and 1.52, 95% CI: 1.10-1.71 and 1.14-2.04, P: .005 and .005, respectively). In haplotype analysis, haplotypes A-C-G-G (in order of rs189037, rs3092856, rs1801516 and rs373759) and A-C-A-A in 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.

The Advanced Technology Microwave Sounder (ATMS): A New Operational Sensor Series

NASA Technical Reports Server (NTRS)

Kim, Edward; Lyu, Cheng-H Joseph; Leslie, R. Vince; Baker, Neal; Mo, Tsan; Sun, Ninghai; Bi, Li; Anderson, Mike; Landrum, Mike; DeAmici, Giovanni;

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

PubMed

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.

Usability of a virtual reality environment simulating an automated teller machine for assessing and training persons with acquired brain injury.

PubMed

Fong, Kenneth N K; Chow, Kathy Y Y; Chan, Bianca C H; Lam, Kino C K; Lee, Jeff C K; Li, Teresa H Y; Yan, Elaine W H; Wong, Asta T Y

2010-04-30

This study aimed to examine the usability of a newly designed virtual reality (VR) environment simulating the operation of an automated teller machine (ATM) for assessment and training. Part I involved evaluation of the sensitivity and specificity of a non-immersive VR program simulating an ATM (VR-ATM). Part II consisted of a clinical trial providing baseline and post-intervention outcome assessments. A rehabilitation hospital and university-based teaching facilities were used as the setting. A total of 24 persons in the community with acquired brain injury (ABI)--14 in Part I and 10 in Part II--made up the participants in the study. In Part I, participants were randomized to receive instruction in either an "early" or a "late" VR-ATM program and were assessed using both the VR program and a real ATM. In Part II, participants were assigned in matched pairs to either VR training or computer-assisted instruction (CAI) teaching programs for six 1-hour sessions over a three-week period. Two behavioral checklists based on activity analysis of cash withdrawals and money transfers using a real ATM were used to measure average reaction time, percentage of incorrect responses, level of cues required, and time spent as generated by the VR system; also used was the Neurobehavioral Cognitive Status Examination. The sensitivity of the VR-ATM was 100% for cash withdrawals and 83.3% for money transfers, and the specificity was 83% and 75%, respectively. For cash withdrawals, the average reaction time of the VR group was significantly shorter than that of the CAI group (p = 0.021). We found no significant differences in average reaction time or accuracy between groups for money transfers, although we did note positive improvement for the VR-ATM group. We found the VR-ATM to be usable as a valid assessment and training tool for relearning the use of ATMs prior to real-life practice in persons with ABI.

Roadway usage patterns : urban case studies - final report

DOT National Transportation Integrated Search

1996-01-01

The Orlando Test Network Study was one of a series of investigations conducted as part of the TravTek operational test of an advanced traveler information and traffic management system (ATIS/ATMS). The TravTek system consisted of the Orlando Traffic ...

Arterial link travel time estimation using loop detector data : phase 1

DOT National Transportation Integrated Search

1997-11-01

The envisioned operational tests of Advanced Traveler Information Systems (ATIS) and Advanced Traffic Management Systems (ATMS) in the Minneapolis/St. Paul area call for the provision of timely and reliable travel times over an entire rod network. Un...

JPRS Report Science & Technology, Europe

DTIC Science & Technology

1991-08-22

MHS has already been manu- facturing two other components developed by CNET which have proved to be indispensable companions of the CTA4 for...SSGRR Alcatel-Face Standard, Sistema , Telettra Network-related problem areas Feasibility study of an ATM system via satellite Participants

Exploring Factors that Affect Purchase Intention of Athletic Team Merchandise

ERIC Educational Resources Information Center

Lee, Donghun; Trail, Galen T.; Lee, Cindy; Schoenstedt, Linda J.

2013-01-01

The purpose of this study was to test a structural model to determine which psychosocial constructs affected the purchase intention of athletic team merchandise (ATM). Results from the analyses indicated that the twelve-factor ATM model fit the data from collegiate athletic events well, explaining the various impact factors that lead to purchase…

The potential impact of ocean acidification upon eggs and larvae of yellowfin tuna (Thunnus albacares)

NASA Astrophysics Data System (ADS)

Bromhead, Don; Scholey, Vernon; Nicol, Simon; Margulies, Daniel; Wexler, Jeanne; Stein, Maria; Hoyle, Simon; Lennert-Cody, Cleridy; Williamson, Jane; Havenhand, Jonathan; Ilyina, Tatiana; Lehodey, Patrick

2015-03-01

Anthropogenic carbon dioxide (CO2) emissions are resulting in increasing absorption of CO2 by the earth's oceans, which has led to a decline in ocean pH, a process known as ocean acidification (OA). Evidence suggests that OA may have the potential to affect the distribution and population dynamics of many marine organisms. Early life history processes (e.g. fertilization) and stages (eggs, larvae, juveniles) may be relatively more vulnerable to potential OA impacts, with implications for recruitment in marine populations. The potential impact of OA upon tuna populations has not been investigated, although tuna are key components of pelagic ecosystems and, in the Pacific Ocean, form the basis of one of the largest and most valuable fisheries in the world. This paper reviews current knowledge of potential OA impacts on fish and presents results from a pilot study investigating how OA may affect eggs and larvae of yellowfin tuna, Thunnus albacares. Two separate trials were conducted to test the impact of pCO2 on yellowfin egg stage duration, larval growth and survival. The pCO2 levels tested ranged from present day ( 400 μatm) to levels predicted to occur in some areas of the spawning habitat within the next 100 years (<2500 μatm) to 300 years ( <5000 μatm) to much more extreme levels ( 10,000 μatm). In trial 1, there was evidence for significantly reduced larval survival (at mean pCO2 levels≥4730 μatm) and growth (at mean pCO2 levels≥2108 μatm), while egg hatch time was increased at extreme pCO2 levels≥10,000 μatm (*intermediate levels were not tested). In trial 2, egg hatch times were increased at mean pCO2 levels≥1573 μatm, but growth was only impacted at higher pCO2 (≥8800 μatm) and there was no relationship with survival. Unstable ambient conditions during trial 2 are likely to have contributed to the difference in results between trials. Despite the technical challenges with these experiments, there is a need for future empirical work which can in turn support modeling-based approaches to assess how OA will affect the ecologically and economically important tropical tuna resources.

Skylab

NASA Image and Video Library

1971-12-01

The Apollo Telescope Mount (ATM) was designed and constructed at the Marshall Space Flight Center and served as the primary scientific instrument unit aboard Skylab. The ATM consisted of eight scientific instruments as well as a number of smaller experiments. This photograph shows the flight unit solar shield for the ATM that formed the base for the rack, a complex frame, and the canister that contained the instruments.

Quantitative and Dynamic Imaging of ATM Kinase Activity by Bioluminescence Imaging.

PubMed

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.

Quantitative and Dynamic Imaging of ATM Kinase Activity.

PubMed

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.

Integration of Weather Data into Airspace and Traffic Operations Simulation (ATOS) for Trajectory- Based Operations Research

NASA Technical Reports Server (NTRS)

Peters, Mark; Boisvert, Ben; Escala, Diego

2009-01-01

Explicit integration of aviation weather forecasts with the National Airspace System (NAS) structure is needed to improve the development and execution of operationally effective weather impact mitigation plans and has become increasingly important due to NAS congestion and associated increases in delay. This article considers several contemporary weather-air traffic management (ATM) integration applications: the use of probabilistic forecasts of visibility at San Francisco, the Route Availability Planning Tool to facilitate departures from the New York airports during thunderstorms, the estimation of en route capacity in convective weather, and the application of mixed-integer optimization techniques to air traffic management when the en route and terminal capacities are varying with time because of convective weather impacts. Our operational experience at San Francisco and New York coupled with very promising initial results of traffic flow optimizations suggests that weather-ATM integrated systems warrant significant research and development investment. However, they will need to be refined through rapid prototyping at facilities with supportive operational users We have discussed key elements of an emerging aviation weather research area: the explicit integration of aviation weather forecasts with NAS structure to improve the effectiveness and timeliness of weather impact mitigation plans. Our insights are based on operational experiences with Lincoln Laboratory-developed integrated weather sensing and processing systems, and derivative early prototypes of explicit ATM decision support tools such as the RAPT in New York City. The technical components of this effort involve improving meteorological forecast skill, tailoring the forecast outputs to the problem of estimating airspace impacts, developing models to quantify airspace impacts, and prototyping automated tools that assist in the development of objective broad-area ATM strategies, given probabilistic weather forecasts. Lincoln Laboratory studies and prototype demonstrations in this area are helping to define the weather-assimilated decision-making system that is envisioned as a key capability for the multi-agency Next Generation Air Transportation System [1]. The Laboratory's work in this area has involved continuing, operations-based evolution of both weather forecasts and models for weather impacts on the NAS. Our experience has been that the development of usable ATM technologies that address weather impacts must proceed via rapid prototyping at facilities whose users are highly motivated to participate in system evolution.

Traffic handling capability of a broadband indoor wireless network using CDMA multiple access

NASA Astrophysics Data System (ADS)

Zhang, Chang G.; Hafez, H. M.; Falconer, David D.

1994-05-01

CDMA (code division multiple access) may be an attractive technique for wireless access to broadband services because of its multiple access simplicity and other appealing features. In order to investigate traffic handling capabilities of a future network providing a variety of integrated services, this paper presents a study of a broadband indoor wireless network supporting high-speed traffic using CDMA multiple access. The results are obtained through the simulation of an indoor environment and the traffic capabilities of the wireless access to broadband 155.5 MHz ATM-SONET networks using the mm-wave band. A distributed system architecture is employed and the system performance is measured in terms of call blocking probability and dropping probability. The impacts of the base station density, traffic load, average holding time, and variable traffic sources on the system performance are examined. The improvement of system performance by implementing various techniques such as handoff, admission control, power control and sectorization are also investigated.

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

PubMed

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.

GMPLS-based control plane for optical networks: early implementation experience

NASA Astrophysics Data System (ADS)

Liu, Hang; Pendarakis, Dimitrios; Komaee, Nooshin; Saha, Debanjan

2002-07-01

Generalized Multi-Protocol Label Switching (GMPLS) extends MPLS signaling and Internet routing protocols to provide a scalable, interoperable, distributed control plane, which is applicable to multiple network technologies such as optical cross connects (OXCs), photonic switches, IP routers, ATM switches, SONET and DWDM systems. It is intended to facilitate automatic service provisioning and dynamic neighbor and topology discovery across multi-vendor intelligent transport networks, as well as their clients. Efforts to standardize such a distributed common control plane have reached various stages in several bodies such as the IETF, ITU and OIF. This paper describes the design considerations and architecture of a GMPLS-based control plane that we have prototyped for core optical networks. Functional components of GMPLS signaling and routing are integrated in this architecture with an application layer controller module. Various requirements including bandwidth, network protection and survivability, traffic engineering, optimal utilization of network resources, and etc. are taken into consideration during path computation and provisioning. Initial experiments with our prototype demonstrate the feasibility and main benefits of GMPLS as a distributed control plane for core optical networks. In addition to such feasibility results, actual adoption and deployment of GMPLS as a common control plane for intelligent transport networks will depend on the successful completion of relevant standardization activities, extensive interoperability testing as well as the strengthening of appropriate business drivers.

Advanced Traffic Management Systems (ATMS) research analysis database system

DOT National Transportation Integrated Search

2001-06-01

The ATMS Research Analysis Database Systems (ARADS) consists of a Traffic Software Data Dictionary (TSDD) and a Traffic Software Object Model (TSOM) for application to microscopic traffic simulation and signal optimization domains. The purpose of thi...

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

Lovill, J.E.; Sullivan, T.J.; Weichel, R.L.

A total ozone retrieval model has been developed to process radiance data gathered by a satellite-mounted multichannel filter radiometer (MFR). Extensive effort went into theoretical radiative transfer modeling, a retrieval scheme was developed, and the technique was applied to the MFR radiance measurements. The high quality of the total ozone retrieval results was determined through comparisons with Dobson measurements. Included in the report are global total ozone maps for 20 days between May 12 and July 5, 1977. A comparison of MFR results for 13 days in June 1977 with Dobson spectrophotometer measurements of ozone for the same period showedmore » good agreement: there was a root-mean-square difference of 6.2% (equivalent to 20.2 m.atm.cm). The estimated global total ozone value for June 1977 (296 m.atm.cm) was in good agreement with satellite backscatter ultraviolet data for June 1970 (304 m.atm.cm) and June 1971 (preliminary data--299 m.atm.cm).« less

Policing the Information Highway.

ERIC Educational Resources Information Center

McClure, Ben

1996-01-01

Although broadband Asynchronous Transfer Mode (ATM) can deliver much greater amounts of information than narrow-band Integrated Services Digital Networks (ISDN), in reality bottlenecks place severe constraints on its performance. This article discusses shortfalls in Internet services, technology and user behavior, and describes efforts in the…

An assessment of the impact of ATMS and CrIS data assimilation on precipitation prediction over the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Xue, Tong; Xu, Jianjun; Guan, Zhaoyong; Chen, Han-Ching; Chiu, Long S.; Shao, Min

2017-07-01

Using the National Oceanic and Atmospheric Administration's Gridpoint Statistical Interpolation data assimilation system and the National Center for Atmospheric Research's Advanced Research Weather Research and Forecasting (WRF-ARW) regional model, the impact of assimilating Advanced Technology Microwave Sounder (ATMS) and Cross-track Infrared Sounder (CrIS) satellite data on precipitation prediction over the Tibetan Plateau in July 2015 was evaluated. Four experiments were designed: a control experiment and three data assimilation experiments with different data sets injected: conventional data only, a combination of conventional and ATMS satellite data, and a combination of conventional and CrIS satellite data. The results showed that the monthly mean of precipitation is shifted northward in the simulations and showed an orographic bias described as an overestimation upwind of the mountains and an underestimation in the south of the rain belt. The rain shadow mainly influenced prediction of the quantity of precipitation, although the main rainfall pattern was well simulated. For the first 24 h and last 24 h of accumulated daily precipitation, the model generally overestimated the amount of precipitation, but it was underestimated in the heavy-rainfall periods of 3-5, 13-16, and 22-25 July. The observed water vapor conveyance from the southeastern Tibetan Plateau was larger than in the model simulations, which induced inaccuracies in the forecast of heavy rain on 3-5 July. The data assimilation experiments, particularly the ATMS assimilation, were closer to the observations for the heavy-rainfall process than the control. Overall, based on the experiments in July 2015, the satellite data assimilation improved to some extent the prediction of the precipitation pattern over the Tibetan Plateau, although the simulation of the rain belt without data assimilation shows the regional shifting.

South American foF2 database using genetic algorithms

NASA Astrophysics Data System (ADS)

Gularte, Erika; Bilitza, Dieter; Carpintero, Daniel; Jaen, Juliana

2016-07-01

We present the first step towards a new database of the ionospheric parameter foF2 for the South American region. The foF2 parameter, being the maximum of the ionospheric electronic density profile and its main sculptor, is of great interest not only in atmospheric studies but also in the realm of radio propagation. Due to its importance, its large variability and the difficulty to model it in time and space, it was the subject of an intense study since decades ago. The current databases, used by the IRI (International Reference Ionosphere) model, and based on Fourier expansions, has been built in the 60s from the available ionosondes at that time; therefore, it is still short of South American data. The main goal of this work is to upgrade the database, incorporating the now available data compiled by the RAPEAS (Red Argentina para el Estudio de la Atmósfera Superior, Argentine Network for the Study of the Upper Atmosphere) network. Also, we developed an algorithm to study the foF2 variability, based on the modern technique of genetic algorithms, which has been successfully applied on other disciplines. One of the main advantages of this technique is its ability in working with many variables and with unfavorable samples. The results are compared with the IRI databases, and improvements to the latter are suggested. Finally, it is important to notice that the new database is designed so that new available data can be easily incorporated.

AZD6738, A Novel Oral Inhibitor of ATR, Induces Synthetic Lethality with ATM Deficiency in Gastric Cancer Cells.

PubMed

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

2017-04-01

Ataxia telangiectasia and Rad3-related (ATR) can be considered an attractive target for cancer treatment due to its deleterious effect on cancer cells harboring a homologous recombination defect. The aim of this study was to investigate the potential use of the ATR inhibitor, AZD6738, to treat gastric cancer.In SNU-601 cells with dysfunctional ATM, AZD6738 treatment led to an accumulation of DNA damage due to dysfunctional RAD51 foci formation, S phase arrest, and caspase 3-dependent apoptosis. In contrast, SNU-484 cells with functional ATM were not sensitive to AZD6738. Inhibition of ATM in SNU-484 cells enhanced AZD6738 sensitivity to a level comparable with that observed in SNU-601 cells, showing that activation of the ATM-Chk2 signaling pathway attenuates AZD6738 sensitivity. In addition, decreased HDAC1 expression was found to be associated with ATM inactivation in SNU-601 cells, demonstrating the interaction between HDAC1 and ATM can affect sensitivity to AZD6738. Furthermore, in an in vivo tumor xenograft mouse model, AZD6738 significantly suppressed tumor growth and increased apoptosis.These findings suggest synthetic lethality between ATR inhibition and ATM deficiency in gastric cancer cells. Further clinical studies on the interaction between AZD 6738 and ATM deficiency are warranted to develop novel treatment strategies for gastric cancer. Mol Cancer Ther; 16(4); 566-77. ©2017 AACR . ©2017 American Association for Cancer Research.

Multicast routing for wavelength-routed WDM networks with dynamic membership

NASA Astrophysics Data System (ADS)

Huang, Nen-Fu; Liu, Te-Lung; Wang, Yao-Tzung; Li, Bo

2000-09-01

Future broadband networks must support integrated services and offer flexible bandwidth usage. In our previous work, we explore the optical link control layer on the top of optical layer that enables the possibility of bandwidth on-demand service directly over wavelength division multiplexed (WDM) networks. Today, more and more applications and services such as video-conferencing software and Virtual LAN service require multicast support over the underlying networks. Currently, it is difficult to provide wavelength multicast over the optical switches without optical/electronic conversions although the conversion takes extra cost. In this paper, based on the proposed wavelength router architecture (equipped with ATM switches to offer O/E and E/O conversions when necessary), a dynamic multicast routing algorithm is proposed to furnish multicast services over WDM networks. The goal is to joint a new group member into the multicast tree so that the cost, including the link cost and the optical/electronic conversion cost, is kept as less as possible. The effectiveness of the proposed wavelength router architecture as well as the dynamic multicast algorithm is evaluated by simulation.

TCP performance in ATM networks: ABR parameter tuning and ABR/UBR comparisons

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

Chien Fang; Lin, A.

1996-02-27

This paper explores two issues on TOP performance over ATM networks: ABR parameter tuning and performance comparison of binary mode ABR with enhanced UBR services. Of the fifteen parameters defined for ABR, two parameters dominate binary mode ABR performance: Rate Increase Factor (RIF) and Rate Decrease Factor (RDF). Using simulations, we study the effects of these two parameters on TOP over ABR performance. We compare TOP performance with different ABR parameter settings in terms of through-puts and fairness. The effects of different buffer sizes and LAN/WAN distances are also examined. We then compare TOP performance with the best ABR parametermore » setting with corresponding UBR service enhanced with Early Packet Discard and also with a fair buffer allocation scheme. The results show that TOP performance over binary mode ABR is very sensitive to parameter value settings, and that a poor choice of parameters can result in ABR performance worse than that of the much less expensive UBR-EPD scheme.« less

Reduced cost alternatives to premise wiring using ATM and microcellular technologies

NASA Technical Reports Server (NTRS)

Gejji, Raghvendra R.

1993-01-01

The cost of premises wiring keeps increasing due to personnel moves, new equipment, capacity upgrades etc. It would be desirable to have a wireless interface from the workstations to the fixed network, so as to minimize the wiring changes needed. New technologies such as microcellular personal communication systems are promising to bring down the cost of wireless communication. Another promising technology is Code Division Multiple Access (CDMA), which could dramatically increase the bandwidth available for wireless connections. In addition, Asynchronous Transfer Mode (ATM) technology is emerging as a technique for integrated management of voice, data, and video traffic on a single network. The focus of this investigation will be to assess the future utility of these new technologies for reducing the premise wiring cost at KSC. One of the issues to be studied is the cost comparison of 'old' versus 'new,' especially as time and technology progress. An additional issue for closer study is a feasible time-line for progress in technological capability.

Experimental and Numerical Analysis of Narrowband Coherent Rayleigh-Brillouin Scattering in Atomic and Molecular Species (Pre Print)

DTIC Science & Technology

2012-02-01

use of polar gas species. While current simplified models have adequately predicted CRS and CRBS line shapes for a wide variety of cases, multiple ...published simplified models are presented for argon, molecular nitrogen, and methane at 300 & 500 K and 1 atm. The simplified models require uncertain gas... models are presented for argon, molecular nitrogen, and methane at 300 & 500 K and 1 atm. The simplified models require uncertain gas properties

Digital Coin Business Model Using the Coin ATM

NASA Astrophysics Data System (ADS)

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.

Reliable prediction of three-body intermolecular interactions using dispersion-corrected second-order Møller-Plesset perturbation theory

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

Huang, Yuanhang; Beran, Gregory J. O., E-mail: gregory.beran@ucr.edu

2015-07-28

Three-body and higher intermolecular interactions can play an important role in molecular condensed phases. Recent benchmark calculations found problematic behavior for many widely used density functional approximations in treating 3-body intermolecular interactions. Here, we demonstrate that the combination of second-order Møller-Plesset (MP2) perturbation theory plus short-range damped Axilrod-Teller-Muto (ATM) dispersion accurately describes 3-body interactions with reasonable computational cost. The empirical damping function used in the ATM dispersion term compensates both for the absence of higher-order dispersion contributions beyond the triple-dipole ATM term and non-additive short-range exchange terms which arise in third-order perturbation theory and beyond. Empirical damping enables this simplemore » model to out-perform a non-expanded coupled Kohn-Sham dispersion correction for 3-body intermolecular dispersion. The MP2 plus ATM dispersion model approaches the accuracy of O(N{sup 6}) methods like MP2.5 or even spin-component-scaled coupled cluster models for 3-body intermolecular interactions with only O(N{sup 5}) computational cost.« less

Training of Evaluators in the Third World: Implementation of the Action Training Model (ATM) in Kenya and Botswana.

ERIC Educational Resources Information Center

Bhola, H. S.

The Action Training Model (ATM) was developed for the delivery of evaluation training to development workers in Kenya and Botswana and implemented under the aegis of the German Foundation for International Development. Training of evaluators is a challenge in any context, but in the Third World environment, evaluation training offers special…

MSFC Skylab ground-based astronomy program

NASA Technical Reports Server (NTRS)

Duncan, B. J.

1974-01-01

The Skylab Ground-Based Astronomy Program (SGAP) was conducted to enhance the data base of solar physics obtained during the Apollo Telescope Mount (ATM) mission flown in conjunction with the Skylab orbital station. Leading solar physicists from various observatories obtained data from the ground at the same time that orbital data were being acquired by ATM. The acquisition of corollary solar data from the ground simultaneously with the ATM orbital observations helped to provide a broader basis for understanding solar physics by increasing spectral coverage and by the use of additional sophisticated instruments of various types. This report briefly describes the individual tasks and the associated instrumentation selected for this ground-based program and contains as appendices, the final reports from the Principal Investigators.

Automated flight test management system

NASA Technical Reports Server (NTRS)

Hewett, M. D.; Tartt, D. M.; Agarwal, A.

1991-01-01

The Phase 1 development of an automated flight test management system (ATMS) as a component of a rapid prototyping flight research facility for artificial intelligence (AI) based flight concepts is discussed. The ATMS provides a flight engineer with a set of tools that assist in flight test planning, monitoring, and simulation. The system is also capable of controlling an aircraft during flight test by performing closed loop guidance functions, range management, and maneuver-quality monitoring. The ATMS is being used as a prototypical system to develop a flight research facility for AI based flight systems concepts at NASA Ames Dryden.

Usability of a virtual reality environment simulating an automated teller machine for assessing and training persons with acquired brain injury

PubMed Central

2010-01-01

Objective This study aimed to examine the usability of a newly designed virtual reality (VR) environment simulating the operation of an automated teller machine (ATM) for assessment and training. Design Part I involved evaluation of the sensitivity and specificity of a non-immersive VR program simulating an ATM (VR-ATM). Part II consisted of a clinical trial providing baseline and post-intervention outcome assessments. Setting A rehabilitation hospital and university-based teaching facilities were used as the setting. Participants A total of 24 persons in the community with acquired brain injury (ABI) - 14 in Part I and 10 in Part II - made up the participants in the study. Interventions In Part I, participants were randomized to receive instruction in either an "early" or a "late" VR-ATM program and were assessed using both the VR program and a real ATM. In Part II, participants were assigned in matched pairs to either VR training or computer-assisted instruction (CAI) teaching programs for six 1-hour sessions over a three-week period. Outcome Measures Two behavioral checklists based on activity analysis of cash withdrawals and money transfers using a real ATM were used to measure average reaction time, percentage of incorrect responses, level of cues required, and time spent as generated by the VR system; also used was the Neurobehavioral Cognitive Status Examination. Results The sensitivity of the VR-ATM was 100% for cash withdrawals and 83.3% for money transfers, and the specificity was 83% and 75%, respectively. For cash withdrawals, the average reaction time of the VR group was significantly shorter than that of the CAI group (p = 0.021). We found no significant differences in average reaction time or accuracy between groups for money transfers, although we did note positive improvement for the VR-ATM group. Conclusion We found the VR-ATM to be usable as a valid assessment and training tool for relearning the use of ATMs prior to real-life practice in persons with ABI. PMID:20429955

ATM regulates 3-Methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents

PubMed Central

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

2014-01-01

Alkylating agents are a frontline 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 a 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. PMID:25100205

Research in Satellite-Fiber Network Interoperability

NASA Technical Reports Server (NTRS)

Edelson, Burt

1997-01-01

This four part report evaluated the performance of high data rate transmission links using the ACTS satellite, and to provide a preparatory test framework for two of the space science applications that have been approved for tests and demonstrations as part of the overall ACTS program. The test plan will provide guidance and information necessary to find the optimal values of the transmission parameters and then apply these parameters to specific applications. The first part will focus on the satellite-to-earth link. The second part is a set of tests to study the performance of ATM on the ACTS channel. The third and fourth parts of the test plan will cover the space science applications, Global Climate Modeling and Keck Telescope Acquisition Modeling and Control.

A novel tele-medical environment appropriate for use in tele-advisory and tele-surgery cases.

PubMed

Chatzipapadopoulos, F; Georgantas, N; Kotaras, A; Mamais, G; Tombros, S; Tselikis, G

1996-08-01

Tele-medical systems have been recently introduced in the field of networking as promising applications that can significantly improve the offering of medical treatment by providing services such as tele-advising, tele-surgery and remote monitoring in places where the presence of doctors or any medical specialists is difficult or time consuming. Some already existent networking models can be used for the establishment of a connection between the communicating sides. The offered network's security is also a significant factor. The present paper describes a software environment implementing a particular aspect of a tele-medical system. The developed system includes features such as direct communication between doctors and medical assistants, medical information acquisition and storing and high band information transfer in real-time. TCP/IP point-to-point protocol has been used for the implementation of the non bandwidth-critical connections. The application introduces novel features with the use of ATM connection for supporting the time-critical service of video transfer to and from the medical database.

Final report for the Multiprotocol Label Switching (MPLS) control plane security LDRD project.

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

Torgerson, Mark Dolan; Michalski, John T.; Tarman, Thomas David

2003-09-01

As rapid Internet growth continues, global communications becomes more dependent on Internet availability for information transfer. Recently, the Internet Engineering Task Force (IETF) introduced a new protocol, Multiple Protocol Label Switching (MPLS), to provide high-performance data flows within the Internet. MPLS emulates two major aspects of the Asynchronous Transfer Mode (ATM) technology. First, each initial IP packet is 'routed' to its destination based on previously known delay and congestion avoidance mechanisms. This allows for effective distribution of network resources and reduces the probability of congestion. Second, after route selection each subsequent packet is assigned a label at each hop, whichmore » determines the output port for the packet to reach its final destination. These labels guide the forwarding of each packet at routing nodes more efficiently and with more control than traditional IP forwarding (based on complete address information in each packet) for high-performance data flows. Label assignment is critical in the prompt and accurate delivery of user data. However, the protocols for label distribution were not adequately secured. Thus, if an adversary compromises a node by intercepting and modifying, or more simply injecting false labels into the packet-forwarding engine, the propagation of improperly labeled data flows could create instability in the entire network. In addition, some Virtual Private Network (VPN) solutions take advantage of this 'virtual channel' configuration to eliminate the need for user data encryption to provide privacy. VPN's relying on MPLS require accurate label assignment to maintain user data protection. This research developed a working distributive trust model that demonstrated how to deploy confidentiality, authentication, and non-repudiation in the global network label switching control plane. Simulation models and laboratory testbed implementations that demonstrated this concept were developed, and results from this research were transferred to industry via standards in the Optical Internetworking Forum (OIF).« less

An Evaluation of the Hazard Prediction and Assessment Capability (HPAC) Software’s Ability to Model the Chornobyl Accident

DTIC Science & Technology

2002-03-01

source term. Several publications provided a thorough accounting of the accident, including “ Chernobyl Record” [Mould], and the NRC technical report...Report on the Accident at the Chernobyl Nuclear Power Station” [NUREG-1250]. The most comprehensive study of transport models to predict the...from the Chernobyl Accident: The ATMES Report” [Klug, et al.]. The Atmospheric Transport 5 Model Evaluation Study (ATMES) report used data

African concepts of health, disease, and treatment: an ethical inquiry.

PubMed

Omonzejele, Peter F

2008-01-01

This paper is based on the author's fieldwork experience in Edo State, Nigeria. The purpose of the article is to present and discuss African concepts of health, disease, and treatment within the framework of African Traditional Medicine (ATM). The two-fold notion of disease and treatment within the African context is also addressed. The significance of rituals and sacrifices in ATM are explained, and the interactions between ATM, African metaphysics, and cosmology are highlighted. The rules and moral precepts tenable in the practice of ATM are analyzed and discussed. The methodology employed in this study was the interviewing of African traditional healers.

Inactivation of the ATMIN/ATM pathway protects against glioblastoma formation

PubMed Central

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

2016-01-01

Glioblastoma multiforme (GBM) is the most aggressive human primary brain cancer. Using a Trp53-deficient mouse model of GBM, we show that genetic inactivation of the Atm cofactor Atmin, which is dispensable for embryonic and adult neural development, strongly suppresses GBM formation. Mechanistically, expression of several GBM-associated genes, including Pdgfra, was normalized by Atmin deletion in the Trp53-null background. Pharmacological ATM inhibition also reduced Pdgfra expression, and reduced the proliferation of Trp53-deficient primary glioma cells from murine and human tumors, while normal neural stem cells were unaffected. Analysis of GBM datasets showed that PDGFRA expression is also significantly increased in human TP53-mutant compared with TP53-wild-type tumors. Moreover, combined treatment with ATM and PDGFRA inhibitors efficiently killed TP53-mutant primary human GBM cells, but not untransformed neural stem cells. These results reveal a new requirement for ATMIN-dependent ATM signaling in TP53-deficient GBM, indicating a pro-tumorigenic role for ATM in the context of these tumors. DOI: http://dx.doi.org/10.7554/eLife.08711.001 PMID:26984279

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

NASA Astrophysics Data System (ADS)

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 heuristic strategy that leads to 'socially optimal' solutions, yielding a maximum number of contention-free cells being scheduled. A novel mixed digital-analog circuit has been designed to implement the MUCS core functionality. The MUCS circuit maps the cell scheduling computation to the capacitor charging and discharging procedures that are conducted fully in parallel. The design has a uniform circuit structure, low interconnect counts, and low chip I/O counts. Using 2 μm CMOS technology, the design operates on a 100 MHz clock and finds a near-optimal solution within a linear processing time. The circuit has been verified at the transistor level by HSPICE simulation. During this research, a five-port IQ-based optoelectronic iPOINT ATM switch has been developed and demonstrated. It has been fully functional with an aggregate throughput of 800 Mb/s. The second-generation IQ-based switch is currently under development. Equipped with iiQueue modules and MUCS module, the new switch system will deliver a multi-gigabit aggregate throughput, eliminate HOL blocking, provide per-VC QoS, and achieve near-100% link bandwidth utilization. Complete documentation of input modules and trunk module for the existing testbed, and complete documentation of 3DQ, iiQueue, and MUCS for the second-generation testbed are given in this dissertation.

Apigenin induces DNA damage through the PKCδ-dependent activation of ATM and H2AX causing down-regulation of genes involved in cell cycle control and DNA repair

PubMed Central

Arango, Daniel; Parihar, Arti; Villamena, Frederick A.; Wang, Liwen; Freitas, Michael A.; Grotewold, Erich; Doseff, Andrea I.

2014-01-01

Apigenin, an abundant plant flavonoid, exhibits anti-proliferative and anti-carcinogenic activities through mechanisms yet not fully defined. In the present study, we show that the treatment of leukemia cells with apigenin resulted in the induction of DNA damage preceding the activation of the apoptotic program. Apigenin-induced DNA damage was mediated by p38 and protein kinase C-delta (PKCδ), yet was independent of reactive oxygen species or caspase activity. Treatment of monocytic leukemia cells with apigenin induced the phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and histone H2AX, two key regulators of the DNA damage response, without affecting the ataxia-telangiectasia mutated and Rad-3-related (ATR) kinase. Silencing and pharmacological inhibition of PKCδ abrogated ATM and H2AX phosphorylation, whereas inhibition of p38 reduced H2AX phosphorylation independently of ATM. We established that apigenin delayed cell cycle progression at G1/S and increased the number of apoptotic cells. In addition, genome-wide mRNA analyses showed that apigenin-induced DNA damage led to down-regulation of genes involved in cell-cycle control and DNA repair. Taken together, the present results show that the PKCδ-dependent activation of ATM and H2AX define the signaling networks responsible for the regulation of DNA damage promoting genome-wide mRNA alterations that result in cell cycle arrest, hence contributing to the anti-carcinogenic activities of this flavonoid. PMID:22985621

Nedd4 Family Interacting Protein 1 (Ndfip1) Is Required for Ubiquitination and Nuclear Trafficking of BRCA1-associated ATM Activator 1 (BRAT1) during the DNA Damage Response*

PubMed Central

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

2015-01-01

During injury, cells are vulnerable to apoptosis from a variety of stress conditions including DNA damage causing double-stranded breaks. Without repair, these breaks lead to aberrations in DNA replication and transcription, leading to apoptosis. A major response to DNA damage is provided by the protein kinase ATM (ataxia telangiectasia mutated) that is capable of commanding a plethora of signaling networks for DNA repair, cell cycle arrest, and even apoptosis. A key element in the DNA damage response is the mobilization of activating proteins into the cell nucleus to repair damaged DNA. BRAT1 is one of these proteins, and it functions as an activator of ATM by maintaining its phosphorylated status while also keeping other phosphatases at bay. However, it is unknown how BRAT1 is trafficked into the cell nucleus to maintain ATM phosphorylation. Here we demonstrate that Ndfip1-mediated ubiquitination of BRAT1 leads to BRAT1 trafficking into the cell nucleus. Without Ndfip1, BRAT1 failed to translocate to the nucleus. Under genotoxic stress, cells showed increased expression of both Ndfip1 and phosphorylated ATM. Following brain injury, neurons show increased expression of Ndfip1 and nuclear translocation of BRAT1. These results point to Ndfip1 as a sensor protein during cell injury and Ndfip1 up-regulation as a cue for BRAT1 ubiquitination by Nedd4 E3 ligases, followed by nuclear translocation of BRAT1. PMID:25631046

Refining our estimate of atmospheric CO2 across the Eocene-Oligocene climatic transition

NASA Astrophysics Data System (ADS)

Heureux, Ana M. C.; Rickaby, Rosalind E. M.

2015-01-01

The Eocene-Oligocene transition (EOT) followed by Oligocene isotope event 1 (Oi-1) is a dramatic global switch in climate characterized by deep-sea cooling and the first formation of permanent Antarctic ice. Models and proxy evidence suggest that declining partial pressure of atmospheric carbon dioxide (CO2atm) below a threshold may explain the onset of global cooling and associated ice formation at Oi-1. However, significant uncertainty remains in the estimated values and salient features of reconstructed CO2atm across this interval. In this study, we present novel carbon isotope records from size separated diatom associated organic matter (δ13Cdiatom) preserved in silica frustules. Physical preservation of this material allows concurrent investigation of isotopic and cell size information, providing two input parameters for biogeochemical models and the reconstruction of CO2atm. We estimate CO2atm in two ways; first we use size and reaction-diffusion kinetics of a cell to calculate a CO2atm threshold. Second we use the calibrated relationship between ɛp(diatom) and carbon dioxide from culture and field studies to create a record of CO2atm prior to and across the transition. Our study, from site 1090 in the Atlantic sector of the Southern Ocean, shows CO2atm values fluctuating between 900 and 1700 ± 100 p.p.m.v. across the EOT followed by a drop to values in the order of 700 to 800 ± 100 p.p.m.v. just prior to the onset of Oi-1. Our values and magnitude of CO2atm change differ from previous estimates, but confirm the overall trends inferred from boron isotopes and alkenones, including a marked rebound following Oi-1. Due to the intricate nature of the climate system and complexities in constraining paleo-proxies, this work emphasizes the importance of a multi-proxy approach to estimating of CO2atm in order to elucidate its role in the emplacement of Antarctic ice-sheets at the EOT.

Skylab

NASA Image and Video Library

1971-08-01

The Apollo Telescope Mount (ATM) was designed and developed by the Marshall Space Flight Center and served as the primary scientific instrument unit aboard Skylab (1973-1979). The ATM consisted of eight scientific instruments as well as a number of smaller experiments. One scientific instrument was the ATM solar shield that formed the base for the rack/frame instrument and the instrument canister. The solar shield contained aperture doors for each instrument to protect against solar radiation and space contamination.

Research and emulation of ranging in BPON system

NASA Astrophysics Data System (ADS)

Yang, Guangxiang; Tao, Dexin; He, Yan

2005-12-01

Ranging is one of the key technologies in Broadband Passive Optical Network based on the ATM (BPON) system. It is complex for software designers and difficult to test. In order to simplify the ranging procedure, enhance its efficiency, and find an appropriate method to verify it, a new ranging procedure that completely satisfies the requirements specified in ITU-T G.983.1 and one verifying method is proposed in this paper. A kind of ranging procedure without serial number (SN) searching function, called one-by-one ranging are developed under the condition of cold PON, cold Optical Network Termination (ONU). The ranging procedure includes the use of OLT and ONU flow charts respectively. By using the network emulation software OPNET, the BPON system is modeled and the ranging procedure is simulated. The emulation experimental results show that the presented ranging procedure can effectively eliminate the collision of burst mode signals between ONUs, which can be ranged one-by-one under the controlling of OLT, while also enhancing the ranging efficiency. As all of the message formats used in this research conform with the ITU-T G.983.1, the ranging procedure can meet the protocol specifications with good interoperability, and is very compatible with products of other manufacturer. According to the present study of ranging procedures, guidelines and principles are provided, Also some design difficulties are eliminated in the software design.

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

PubMed

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.

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

PubMed

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 vitro cellular studies, here we demonstrate independent biological roles for the DDR kinases DNA-PKcs, ATM, and ATR during neurogenesis. We show that DNA-PKcs is central to DNA repair in nonproliferating cells, and restricts DNA damage accumulation, whereas ATR controls damage-induced G 2 checkpoint control and apoptosis in proliferating cells. Conversely, ATM is critical for controlling apoptosis in immature noncycling neural cells after DNA damage. These data demonstrate functionally distinct, but cooperative, roles for each kinase in preserving genome stability in the nervous system. Copyright © 2017 the authors 0270-6474/17/370893-13$15.00/0.

Computational Analyses of Complex Flows with Chemical Reactions

NASA Astrophysics Data System (ADS)

Bae, Kang-Sik

The heat and mass transfer phenomena in micro-scale for the mass transfer phenomena on drug in cylindrical matrix system, the simulation of oxygen/drug diffusion in a three dimensional capillary network, and a reduced chemical kinetic modeling of gas turbine combustion for Jet propellant-10 have been studied numerically. For the numerical analysis of the mass transfer phenomena on drug in cylindrical matrix system, the governing equations are derived from the cylindrical matrix systems, Krogh cylinder model, which modeling system is comprised of a capillary to a surrounding cylinder tissue along with the arterial distance to veins. ADI (Alternative Direction Implicit) scheme and Thomas algorithm are applied to solve the nonlinear partial differential equations (PDEs). This study shows that the important factors which have an effect on the drug penetration depth to the tissue are the mass diffusivity and the consumption of relevant species during the time allowed for diffusion to the brain tissue. Also, a computational fluid dynamics (CFD) model has been developed to simulate the blood flow and oxygen/drug diffusion in a three dimensional capillary network, which are satisfied in the physiological range of a typical capillary. A three dimensional geometry has been constructed to replicate the one studied by Secomb et al. (2000), and the computational framework features a non-Newtonian viscosity model for blood, the oxygen transport model including in oxygen-hemoglobin dissociation and wall flux due to tissue absorption, as well as an ability to study the diffusion of drugs and other materials in the capillary streams. Finally, a chemical kinetic mechanism of JP-10 has been compiled and validated for a wide range of combustion regimes, covering pressures of 1atm to 40atm with temperature ranges of 1,200 K--1,700 K, which is being studied as a possible Jet propellant for the Pulse Detonation Engine (PDE) and other high-speed flight applications such as hypersonic missiles. The comprehensive skeletal mechanism consists of 58 species and 315 reactions including in CPD, Benzene formation process by the theory for polycyclic aromatic hydrocarbons (PAH) and soot formation process on the constant volume combustor, premixed flame characteristics.

Army Communicator. Volume 31, Number 1, Winter 2006

DTIC Science & Technology

2006-01-01

material does not represent official policy, thinking, or endorsement by an agency of the U.S. Army. This publication contains no advertising . U.S...exercise, to simu- late the bandwidth capacity of a Joint Node Network command post node or an ATM Moblie Subscriber Equipment node. These links were

PPAR γ is highly expressed in F4/80hi adipose tissue macrophages and dampens adipose-tissue inflammation

PubMed Central

Bassaganya-Riera, Josep; Misyak, Sarah; Guri, Amir J.; Hontecillas, Raquel

2009-01-01

Macrophage infiltration into adipose tissue is a hallmark of obesity. We recently reported two phenotypically distinct subsets of adipose tissue macrophages (ATM) based on the surface expression of the glycoprotein F4/80 and responsiveness to treatment with a peroxisome proliferator-activated receptor (PPAR) γ agonist. Hence, we hypothesized that F4/80hi and F4/80lo ATM differentially express PPAR γ. This study phenotypically and functionally characterizes F4/80hi and F4/80lo ATM subsets during obesity. Changes in gene expression were also examined on sorted F4/80lo and F4/80hi ATM by quantitative real-time RT-PCR. We show that while F4/80lo macrophages predominate in adipose tissue of lean mice, obesity causes accumulation of both F4/80lo and F4/80hi ATM. Moreover, accumulation of F4/80hi ATM in adipose tissue is associated with impaired glucose tolerance. Phenotypically, F4/80hi ATM express greater amounts of CD11c, MHC II, CD49b, and CX3CR1 and produce more TNF-α, MCP-1, and IL-10 than F4/80lo ATM. Gene expression analyses of the sorted populations revealed that only the F4/80lo population produced IL-4, whereas the F4/80hi ATM expressed greater amounts of PPAR γ, δ, CD36 and toll-like receptor-4. In addition, the deficiency of PPAR γ in immune cells favors expression of M1 and impairs M2 macrophage marker expression in adipose tissue. Thus, PPAR γ is differentially expressed in F4/80hi versus F4/80low ATM subsets and its deficiency favors a predominance of M1 markers in WAT. PMID:19423085

Simultaneous depletion of Atm and Mdl rebalances cytosolic Fe-S cluster assembly but not heme import into the mitochondrion of Trypanosoma brucei.

PubMed

Horáková, Eva; Changmai, Piya; Paris, Zdeněk; Salmon, Didier; Lukeš, Julius

2015-11-01

ABC transporter mitochondrial 1 (Atm1) and multidrug resistance-like 1 (Mdl) are mitochondrial ABC transporters. Although Atm1 was recently suggested to transport different forms of glutathione from the mitochondrion, which are used for iron-sulfur (Fe-S) cluster maturation in the cytosol, the function of Mdl remains elusive. In Trypanosoma brucei, we identified one homolog of each of these genes, TbAtm and TbMdl, which were downregulated either separately or simultaneously using RNA interference. Individual depletion of TbAtm and TbMdl led to limited growth defects. In cells downregulated for TbAtm, the enzymatic activities of the Fe-S cluster proteins aconitase and fumarase significantly decreased in the cytosol but not in the mitochondrion. Downregulation of TbMdl did not cause any change in activities of the Fe-S proteins. Unexpectedly, the simultaneous downregulation of TbAtm and TbMdl did not result in any growth defect, nor were the Fe-S cluster protein activities altered in either the cytosolic or mitochondrial compartments. Additionally, TbAtm and TbMdl were able to partially restore the growth of the Saccharomyces cerevisiae Δatm1 and Δmdl2 null mutants, respectively. Because T. brucei completely lost the heme b biosynthesis pathway, this cofactor has to be obtained from the host. Based on our results, TbMdl is a candidate for mitochondrial import of heme b, which was markedly decreased in both TbMdl and TbAtm + TbMdl knockdowns. Moreover, the levels of heme a were strongly decreased in the same knockdowns, suggesting that TbMdl plays a key role in heme a biosynthesis, thus affecting the overall heme homeostasis in T. brucei. © 2015 FEBS.

PPAR gamma is highly expressed in F4/80(hi) adipose tissue macrophages and dampens adipose-tissue inflammation.

PubMed

Bassaganya-Riera, Josep; Misyak, Sarah; Guri, Amir J; Hontecillas, Raquel

2009-01-01

Macrophage infiltration into adipose tissue is a hallmark of obesity. We recently reported two phenotypically distinct subsets of adipose tissue macrophages (ATM) based on the surface expression of the glycoprotein F4/80 and responsiveness to treatment with a peroxisome proliferator-activated receptor (PPAR) gamma agonist. Hence, we hypothesized that F4/80(hi) and F4/80(lo) ATM differentially express PPAR gamma. This study phenotypically and functionally characterizes F4/80(hi) and F4/80(lo) ATM subsets during obesity. Changes in gene expression were also examined on sorted F4/80(lo) and F4/80(hi) ATM by quantitative real-time RT-PCR. We show that while F4/80(lo) macrophages predominate in adipose tissue of lean mice, obesity causes accumulation of both F4/80(lo) and F4/80(hi) ATM. Moreover, accumulation of F4/80(hi) ATM in adipose tissue is associated with impaired glucose tolerance. Phenotypically, F4/80(hi) ATM express greater amounts of CD11c, MHC II, CD49b, and CX3CR1 and produce more TNF-alpha, MCP-1, and IL-10 than F4/80(lo) ATM. Gene expression analyses of the sorted populations revealed that only the F4/80(lo) population produced IL-4, whereas the F4/80(hi) ATM expressed greater amounts of PPAR gamma, delta, CD36 and toll-like receptor-4. In addition, the deficiency of PPAR gamma in immune cells favors expression of M1 and impairs M2 macrophage marker expression in adipose tissue. Thus, PPAR gamma is differentially expressed in F4/80(hi) versus F4/80(low) ATM subsets and its deficiency favors a predominance of M1 markers in WAT.

Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation.

PubMed

Reddy, Jay P; Peddibhotla, Sirisha; Bu, Wen; Zhao, Jing; Haricharan, Svasti; Du, Yi-Chieh Nancy; Podsypanina, Katrina; Rosen, Jeffrey M; Donehower, Larry A; Li, Yi

2010-02-23

p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention.

Modified automatic teller machine prototype for older adults: a case study of participative approach to inclusive design.

PubMed

Chan, Chetwyn C H; Wong, Alex W K; Lee, Tatia M C; Chi, Iris

2009-03-01

The goal of this study was to enhance an existing automated teller machine (ATM) human-machine interface in order to accommodate the needs of older adults. Older adults were involved in the design and field test of the modified ATM prototype. The design of the user interface and functionality took the cognitive and physical abilities of older adults into account. The modified ATM system included only "cash withdrawal" and "transfer" functions based on the task demands and needs for services of older adults. One hundred and forty-one older adults (aged 60 or above) participated in the field test by operating modified or existing ATM systems. Those who operated the modified system were found to have significantly higher success rates than those who operated the existing system. The enhancement was most significant among older adults who had lower ATM-related abilities, a lower level of education, and no prior experience of using ATMs. This study demonstrates the usefulness of using a universal design and participatory approach to modify the existing ATM system for use by older adults. However, it also leads to a reduction in functionality of the enhanced system. Future studies should explore ways to develop a universal design ATM system which can satisfy the abilities and needs of all users in the entire population.

Eicosapentaenoic acid improves endothelial function and nitric oxide bioavailability in a manner that is enhanced in combination with a statin.

PubMed

Mason, R Preston; Dawoud, Hazem; Jacob, Robert F; Sherratt, Samuel C R; Malinski, Tadeusz

2018-07-01

The endothelium exerts many vasoprotective effects that are largely mediated by release of nitric oxide (NO). Endothelial dysfunction represents an early but reversible step in atherosclerosis and is characterized by a reduction in the bioavailability of NO. Previous studies have shown that eicosapentaenoic acid (EPA), an omega-3 fatty acid (O3FA), and statins individually improve endothelial cell function, but their effects in combination have not been tested. Through a series of in vitro experiments, this study evaluated the effects of a combined treatment of EPA and the active metabolite of atorvastatin (ATM) on endothelial cell function under conditions of oxidative stress. Specifically, the comparative and time-dependent effects of these agents on endothelial dysfunction were examined by measuring the levels of NO and peroxynitrite (ONOO - ) released from human umbilical vein endothelial cells (HUVECs). The data suggest that combined treatment with EPA and ATM is beneficial to endothelial function and was unique to EPA and ATM since similar improvements could not be recapitulated by substituting another O3FA docosahexaenoic acid (DHA) or other TG-lowering agents such as fenofibrate, niacin, or gemfibrozil. Comparable beneficial effects were observed when HUVECs were pretreated with EPA and ATM before exposure to oxidative stress. Interestingly, the kinetics of EPA-based protection of endothelial function in response to oxidation were found to be significantly different than those of DHA. Lastly, the beneficial effects on endothelial function generated by combined treatment of EPA and ATM were reproduced when this study was expanded to an ex vivo model utilizing rat glomerular endothelial cells. Taken together, these findings suggest that a combined treatment of EPA and ATM can inhibit endothelial dysfunction that occurs in response to conditions such as hyperglycemia, oxidative stress, and dyslipidemia. Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Fbis report. Science and technology: China, October 18, 1995

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

NONE

1995-10-18

;Partial Contents: Nanomaterials Fabrication, Applications Research Advances Noted; CAST Announces World`s First Space-Grown Large-Diameter GaAs Monocrystal; Assay of Antiviral Activity of Antisense Phosphorothioate Oligodeoxynucleotide Against Dengue Virus; Expression and Antigenicity of Chimeric Proteins of Cholera Toxin B Subunit With Hepatitis C Virus; CNCOFIEC Signs Agreement With IBM for New Intelligent Building; Latest Reports on Optical Computing, Memory; BIDC To Introduce S3 Company`s Multimedia Accelerator Chipset; Virtual Private PCN Ring Network Based on ATM VP Cross-Connection; Beijing Gets Nation`s First Frame Relay Network; Situation of Power Industry Development and International Cooperation; Diagrams of China`s Nuclear Waste Containment Vessels; Chinese-Developed Containment Vesselmore » Material Reaches World Standards; Second Fuel Elements for Qinshan Plant Passes Inspection; and Geothermal Deep-Well Electric Pump Technology Developed.« less

Multi-Sensor Fusion with Interacting Multiple Model Filter for Improved Aircraft Position Accuracy

PubMed Central

Cho, Taehwan; Lee, Changho; Choi, Sangbang

2013-01-01

The International Civil Aviation Organization (ICAO) has decided to adopt Communications, Navigation, and Surveillance/Air Traffic Management (CNS/ATM) as the 21st century standard for navigation. Accordingly, ICAO members have provided an impetus to develop related technology and build sufficient infrastructure. For aviation surveillance with CNS/ATM, Ground-Based Augmentation System (GBAS), Automatic Dependent Surveillance-Broadcast (ADS-B), multilateration (MLAT) and wide-area multilateration (WAM) systems are being established. These sensors can track aircraft positions more accurately than existing radar and can compensate for the blind spots in aircraft surveillance. In this paper, we applied a novel sensor fusion method with Interacting Multiple Model (IMM) filter to GBAS, ADS-B, MLAT, and WAM data in order to improve the reliability of the aircraft position. Results of performance analysis show that the position accuracy is improved by the proposed sensor fusion method with the IMM filter. PMID:23535715

Multi-sensor fusion with interacting multiple model filter for improved aircraft position accuracy.

PubMed

Cho, Taehwan; Lee, Changho; Choi, Sangbang

2013-03-27

The International Civil Aviation Organization (ICAO) has decided to adopt Communications, Navigation, and Surveillance/Air Traffic Management (CNS/ATM) as the 21st century standard for navigation. Accordingly, ICAO members have provided an impetus to develop related technology and build sufficient infrastructure. For aviation surveillance with CNS/ATM, Ground-Based Augmentation System (GBAS), Automatic Dependent Surveillance-Broadcast (ADS-B), multilateration (MLAT) and wide-area multilateration (WAM) systems are being established. These sensors can track aircraft positions more accurately than existing radar and can compensate for the blind spots in aircraft surveillance. In this paper, we applied a novel sensor fusion method with Interacting Multiple Model (IMM) filter to GBAS, ADS-B, MLAT, and WAM data in order to improve the reliability of the aircraft position. Results of performance analysis show that the position accuracy is improved by the proposed sensor fusion method with the IMM filter.

Enabling User Preferences Through Data Exchange

DOT National Transportation Integrated Search

1997-08-01

This paper describes a process, via user- air traffic management (ATM) data : exchange, for enabling user preferences in an ATM-based system. User : preferences may be defined in terms of a four-dimensional (4D) user-preferred : trajectory, or a seri...

Immersed boundary method for Boltzmann model kinetic equations

NASA Astrophysics Data System (ADS)

Pekardan, Cem; Chigullapalli, Sruti; Sun, Lin; Alexeenko, Alina

2012-11-01

Three different immersed boundary method formulations are presented for Boltzmann model kinetic equations such as Bhatnagar-Gross-Krook (BGK) and Ellipsoidal statistical Bhatnagar-Gross-Krook (ESBGK) model equations. 1D unsteady IBM solution for a moving piston is compared with the DSMC results and 2D quasi-steady microscale gas damping solutions are verified by a conformal finite volume method solver. Transient analysis for a sinusoidally moving beam is also carried out for the different pressure conditions (1 atm, 0.1 atm and 0.01 atm) corresponding to Kn=0.05,0.5 and 5. Interrelaxation method (Method 2) is shown to provide a faster convergence as compared to the traditional interpolation scheme used in continuum IBM formulations. Unsteady damping in rarefied regime is characterized by a significant phase-lag which is not captured by quasi-steady approximations.

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

PubMed

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 characteristics and genomic alterations, and they are also distinguishable from sporadic breast tumours, thus opening up the possibility to identify ATM variant carriers outside the ataxia-telangiectasia disorder and direct them towards effective cancer risk management and therapeutic strategies.

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

NASA Technical Reports Server (NTRS)

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

The atmosphere- and hydrosphere-correlated signals in GPS observations

NASA Astrophysics Data System (ADS)

Bogusz, Janusz; Boy, Jean-Paul; Klos, Anna; Figurski, Mariusz

2015-04-01

The circulation of surface geophysical fluids (e.g. atmosphere, ocean, continental hydrology, etc.) induces global mass redistribution at the Earth's surface, and then surface deformations and gravity variations. The deformations can be reliably recorded by permanent GPS observations nowadays. The loading effects can be precisely modelled by convolving outputs from global general circulation models and Green's functions describing the Earth's response. Previously published papers showed that either surface gravity records or space-based observations can be efficiently corrected for atmospheric loading effects using surface pressure fields from atmospheric models. In a similar way, loading effects due to continental hydrology can be corrected from precise positioning observations. We evaluated 3-D displacement at the selected ITRF2008 core sites that belong to IGS (International GNSS Service) network due to atmospheric, oceanic and hydrological circulation using different models. Atmospheric and induced oceanic loading estimates were computed using the ECMWF (European Centre for Medium Range Weather Forecasts) operational and reanalysis (ERA interim) surface pressure fields, assuming an inverted barometer ocean response or a barotropic ocean model forced by air pressure and winds (MOG2D). The IB (Inverted Barometer) hypothesis was classically chosen, in which atmospheric pressure variations are fully compensated by static sea height variations. This approximation is valid for periods exceeding typically 5 to 20 days. At higher frequencies, dynamic effects cannot be neglected. Hydrological loading were provided using MERRA land (Modern-Era Retrospective Analysis for Research and Applications - NASA reanalysis for the satellite era using a major new version of the Goddard Earth Observing System Data Assimilation System Version 5 (GEOS-5)) for the different stations. After that we compared the results to the GPS-derived time series of North, East and Up components. The analysis of satellite data was performed twofold: firstly, the time series from network solution (NS) processed in Bernese 5.0 software by the Military University of Technology EPN Local Analysis Centre, secondly, the ones from PPP (Precise Point Positioning) from JPL (Jet Propulsion Laboratory) processing in Gipsy-Oasis were analyzed. Both were modelled with wavelet decomposition with Meyer orthogonal mother wavelet. Here, nine levels of decomposition were applied and eighth detail of it was interpreted as changes close to one year. In this way, both NS and PPP time series where presented as curves with annual period with amplitudes and phases changeable in time. The same analysis was performed for atmospheric (ATM) and hydrospheric (HYDR) models. All annual curves (modelled from NS, PPP, ATM and HYDR) were then compared to each other to investigate whether GPS observations contain the atmosphere and hydrosphere correlated signals and in what way the amplitudes of them may disrupt the GPS time series.

Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response.

PubMed

Ciccia, Alberto; Huang, Jen-Wei; Izhar, Lior; Sowa, Mathew E; Harper, J Wade; Elledge, Stephen J

2014-12-30

The signal transduction pathway of the DNA damage response (DDR) is activated to maintain genomic integrity following DNA damage. The DDR promotes genomic integrity by regulating a large network of cellular activities that range from DNA replication and repair to transcription, RNA splicing, and metabolism. In this study we define an interaction between the DDR factor NBS1 and TCOF1, a nucleolar protein that regulates ribosomal DNA (rDNA) transcription and is mutated in Treacher Collins syndrome. We show that NBS1 relocalizes to nucleoli after DNA damage in a manner dependent on TCOF1 and on casein kinase II and ATM, which are known to modify TCOF1 by phosphorylation. Moreover, we identify a putative ATM phosphorylation site that is required for NBS1 relocalization to nucleoli in response to DNA damage. Last, we report that TCOF1 promotes cellular resistance to DNA damaging agents. Collectively, our findings identify TCOF1 as a DDR factor that could cooperate with ATM and NBS1 to suppress inappropriate rDNA transcription and maintain genomic integrity after DNA damage.

Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response

PubMed Central

Ciccia, Alberto; Huang, Jen-Wei; Izhar, Lior; Sowa, Mathew E.; Harper, J. Wade; Elledge, Stephen J.

2014-01-01

The signal transduction pathway of the DNA damage response (DDR) is activated to maintain genomic integrity following DNA damage. The DDR promotes genomic integrity by regulating a large network of cellular activities that range from DNA replication and repair to transcription, RNA splicing, and metabolism. In this study we define an interaction between the DDR factor NBS1 and TCOF1, a nucleolar protein that regulates ribosomal DNA (rDNA) transcription and is mutated in Treacher Collins syndrome. We show that NBS1 relocalizes to nucleoli after DNA damage in a manner dependent on TCOF1 and on casein kinase II and ATM, which are known to modify TCOF1 by phosphorylation. Moreover, we identify a putative ATM phosphorylation site that is required for NBS1 relocalization to nucleoli in response to DNA damage. Last, we report that TCOF1 promotes cellular resistance to DNA damaging agents. Collectively, our findings identify TCOF1 as a DDR factor that could cooperate with ATM and NBS1 to suppress inappropriate rDNA transcription and maintain genomic integrity after DNA damage. PMID:25512513

Confirmatory Analysis of the Athletic Team Merchandise Model

ERIC Educational Resources Information Center

Lee, Donghun; Trail, Galen T.

2012-01-01

Although sales of athletic team merchandise (ATM) contribute to the overall consumption of sport, a research effort that comprehensively measures aspects that trigger the consumption of ATM is lacking. In light of the gap, utilizing multiple theories and other concepts that describe product consumption, the authors of this article empirically…

Tree versus Geometric Representation of Tests and Items.

ERIC Educational Resources Information Center

Beller, Michael

1990-01-01

Geometric approaches to representing interrelations among tests and items are compared with an additive tree model (ATM), using 2,644 examinees and 2 other data sets. The ATM's close fit to the data and its coherence of presentation indicate that it is the best means of representing tests and items. (TJH)

ATM traffic experiments: A laboratory study of service interaction, loss fairness and loss characteristics

NASA Astrophysics Data System (ADS)

Helvik, B. E.; Stol, N.

1995-04-01

A reference measurement scenario is defined, where an ATM switch (OCTOPUS) is offered traffic from three source types representing the traffic resulting from typical services to be carried by an ATM network. These are high quality video (HQTV), high speed data (HSD) and constant bitrate transfer (CBR). In addition to be typical, these have widely different characteristics. Detailed definitions for these, and other actual source types, are made and entered into the Synthetic Traffic Generator (STG) database. Recommended traffic mixes of these sources are also made. Based on the above, laboratory measurements are carried out to study how the various kinds of traffic influence each other, how fairly the loss is distributed over services and connections, and what are the loss characteristics experienced. (Due to a software error detected in the measurement equipment after the work was concluded, the measurements are carried out with a HSD source with a load less 'aggressive' than intended.) The main findings are: Cell loss is very unfairly distributed among the various connections. During a loss burst, which occurs less frequently than the duration of a typical connection, affects mainly one or a few connections; Cell loss is unfairly distributed among the services. The ratios in the range from HSD: HQTV: CBR = 5 : 1 : 0.85 are observed, and unfairness increases with decreasing load burstiness; The loss characteristics vary during a loss burst, from one burst to the next and between services. Hence, it does not seem feasible to use 'typical-loss-statistics' to study the impairments on various services. In addition some supplementing work is reported.

Orphan Nuclear Receptor Small Heterodimer Partner Negatively Regulates Growth Hormone-mediated Induction of Hepatic Gluconeogenesis through Inhibition of Signal Transducer and Activator of Transcription 5 (STAT5) Transactivation*

PubMed Central

Kim, Yong Deuk; Li, Tiangang; Ahn, Seung-Won; Kim, Don-Kyu; Lee, Ji-Min; Hwang, Seung-Lark; Kim, Yong-Hoon; Lee, Chul-Ho; Lee, In-Kyu; Chiang, John Y. L.; Choi, Hueng-Sik

2012-01-01

Growth hormone (GH) is a key metabolic regulator mediating glucose and lipid metabolism. Ataxia telangiectasia mutated (ATM) is a member of the phosphatidylinositol 3-kinase superfamily and regulates cell cycle progression. The orphan nuclear receptor small heterodimer partner (SHP: NR0B2) plays a pivotal role in regulating metabolic processes. Here, we studied the role of ATM on GH-dependent regulation of hepatic gluconeogenesis in the liver. GH induced phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase gene expression in primary hepatocytes. GH treatment and adenovirus-mediated STAT5 overexpression in hepatocytes increased glucose production, which was blocked by a JAK2 inhibitor, AG490, dominant negative STAT5, and STAT5 knockdown. We identified a STAT5 binding site on the PEPCK gene promoter using reporter assays and point mutation analysis. Up-regulation of SHP by metformin-mediated activation of the ATM-AMP-activated protein kinase pathway led to inhibition of GH-mediated induction of hepatic gluconeogenesis, which was abolished by an ATM inhibitor, KU-55933. Immunoprecipitation studies showed that SHP physically interacted with STAT5 and inhibited STAT5 recruitment on the PEPCK gene promoter. GH-induced hepatic gluconeogenesis was decreased by either metformin or Ad-SHP, whereas the inhibition by metformin was abolished by SHP knockdown. Finally, the increase of hepatic gluconeogenesis following GH treatment was significantly higher in the liver of SHP null mice compared with that of wild-type mice. Overall, our results suggest that the ATM-AMP-activated protein kinase-SHP network, as a novel mechanism for regulating hepatic glucose homeostasis via a GH-dependent pathway, may be a potential therapeutic target for insulin resistance. PMID:22977252

Environmental considerations of the NGATS ATM-airportal concept

DOT National Transportation Integrated Search

2008-01-31

This report discusses some of the environmental considerations of the Airportal Concept. This information in this report is based on the NGATS ATM-Airportal Concept by J. Lee, et al., version 1.0 dated September 28, 2007. This report is intended to p...

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

PubMed

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.

ACTS 118x: High Speed TCP Interoperability Testing

NASA Technical Reports Server (NTRS)

Brooks, David E.; Buffinton, Craig; Beering, Dave R.; Welch, Arun; Ivancic, William D.; Zernic, Mike; Hoder, Douglas J.

1999-01-01

With the recent explosion of the Internet and the enormous business opportunities available to communication system providers, great interest has developed in improving the efficiency of data transfer over satellite links using the Transmission Control Protocol (TCP) of the Internet Protocol (IP) suite. The NASA's ACTS experiments program initiated a series of TCP experiments to demonstrate scalability of TCP/IP and determine to what extent the protocol can be optimized over a 622 Mbps satellite link. Through partnerships with the government technology oriented labs, computer, telecommunication, and satellite industries NASA Glenn was able to: (1) promote the development of interoperable, high-performance TCP/IP implementations across multiple computing / operating platforms; (2) work with the satellite industry to answer outstanding questions regarding the use of standard protocols (TCP/IP and ATM) for the delivery of advanced data services, and for use in spacecraft architectures; and (3) conduct a series of TCP/IP interoperability tests over OC12 ATM over a satellite network in a multi-vendor environment using ACTS. The experiments' various network configurations and the results are presented.

[Audiovisual telecommunication by multimedia technology in HNO medicine. ISDN--internet--ATM].

PubMed

Plinkert, P K; Plinkert, B; Kurek, R; Zenner, H P

2000-11-01

Telemedicine includes all medical activities in diagnosis, therapeutics, or social medicine undertaken by means of an electronic transfer medium, enabling the transmission of visual and acoustic information over long distances to doctors not personally present at the place of the requested consultation. Most experience with telemedicine applications has been gained in the field of diagnosis (teleconsultation, teleradiology, telepathology) and is expanding to quality control and quality assurance. Decisive for each form of application is its availability, practicability, cost, safety, and especially quality of audiovisual transmission. For telesurgical applications, particularly the use of minimally invasive techniques in otorhinolaryngology, head, and neck surgery, the high quality transmission of audiovisual data in real time is necessary. Rapid expansion and further developments in transmission technologies and networks in the last decade have created several technologies with increased quality and costs. In this paper, we tested different transmission media for audiovisual telecommunication--integrated services digital network (ISDN), Internet, and asynchronous transfer mode (ATM)--using real time video transmission of typical operations in otorhinolaryngology. Their applications, costs, and future perspectives are discussed.

Chip-set for quality of service support in passive optical networks

NASA Astrophysics Data System (ADS)

Ringoot, Edwin; Hoebeke, Rudy; Slabbinck, B. Hans; Verhaert, Michel

1998-10-01

In this paper the design of a chip-set for QoS provisioning in ATM-based Passive Optical Networks is discussed. The implementation of a general-purpose switch chip on the Optical Network Unit is presented, with focus on the design of the cell scheduling and buffer management logic. The cell scheduling logic supports `colored' grants, priority jumping and weighted round-robin scheduling. The switch chip offers powerful buffer management capabilities enabling the efficient support of GFR and UBR services. Multicast forwarding is also supported. In addition, the architecture of a MAC controller chip developed for a SuperPON access network is introduced. In particular, the permit scheduling logic and its implementation on the Optical Line Termination will be discussed. The chip-set enables the efficient support of services with different service requirements on the SuperPON. The permit scheduling logic built into the MAC controller chip in combination with the cell scheduling and buffer management capabilities of the switch chip can be used by network operators to offer guaranteed service performance to delay sensitive services, and to efficiently and fairly distribute any spare capacity to delay insensitive services.

Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation

PubMed Central

Reddy, Jay P.; Peddibhotla, Sirisha; Bu, Wen; Zhao, Jing; Haricharan, Svasti; Du, Yi-Chieh Nancy; Podsypanina, Katrina; Rosen, Jeffrey M.; Donehower, Larry A.; Li, Yi

2010-01-01

p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention. PMID:20133707

A Network of Direct Broadcast Antenna Systems to Provide Real-Time Infrared and Microwave Sounder Data for Numerical Weather Prediction

NASA Astrophysics Data System (ADS)

Gumley, L.

2013-12-01

The Space Science and Engineering Center at the University of Wisconsin-Madison is creating a network of direct broadcast satellite data reception stations to acquire and process infrared and microwave sounder data in real-time from polar orbiting meteorological satellites and deliver the resulting products to NOAA with low latency for assimilation in NCEP numerical weather prediction models. The network will include 4 antenna sites that will be operated directly by SSEC, including Madison WI, Honolulu HI, Miami FL, and Mayaguez PR. The network will also include partner antenna sites not directly controlled by SSEC, including Corvallis OR, Monterey CA, Suitland MD, Fairbanks AK, and Guam. All of the antenna sites will have a combined X/L-band reception system capable of receiving data via direct broadcast from polar orbiting satellites including Suomi NPP and JPSS-1, Metop-A/B, POES,Terra, and Aqua. Each site will collect raw data from these satellites locally, process it to Level 1 (SDR) and Level 2 (EDR) products, and transmit the products back to SSEC for delivery to NOAA/NCEP. The primary purpose of the antenna systems is to provide real-time infrared and microwave sounder data from Metop and Suomi-NPP to NOAA to support data assimilation for NOAA/NCEP operational numerical weather prediction models. At present, NOAA/NCEP use of advanced infrared (CrIS, IASI, AIRS) and microwave (ATMS, AMSU) sounder data over North America in NWP data assimilation is limited because of the latency of the products in relation to the cutoff times for assimilation runs. This network will deliver infrared and microwave sounder data to NCEP with the lowest latency possible, via the reception and processing of data received via direct broadcast. CIMSS/SSEC is managing the procurement and installation of the antenna systems at the two new sites, and will operate the stations remotely. NOAA will establish the reception priorities (Metop and SNPP will be at the highest priority) and SSEC will set the reception schedule to acquire data from these satellites, and any other satellites at lower priority as determined jointly by NOAA, CIMSS/SSEC, and the antenna site hosts. SSEC is providing a product generation server at each site (where applicable) as part of the installed hardware to create satellite products in real-time. The host locations will provide the necessary network resources to enable infrared sounder (CrIS, IASI, and AIRS) and microwave sounder (ATMS and AMSU) data to be sent back to SSEC (and hence to NOAA/NCEP) with low latency (< 15 minutes). This presentation will described how the network realizes the goal of providing data to end users within 15 minutes of observation, and will give examples of the positive impact already observed on NCEP forecast model skill from assimilating real-time infrared and microwave sounder data in the NAM regional domain.

The profiles of gamma-H2AX along with ATM/DNA-PKcs activation in the lymphocytes and granulocytes of rat and human blood exposed to gamma rays.

PubMed

Wang, Jing; Yin, Lina; Zhang, Junxiang; Zhang, Yaping; Zhang, Xuxia; Ding, Defang; Gao, Yun; Li, Qiang; Chen, Honghong

2016-08-01

Establishing a rat model suitable for γ-H2AX biodosimeter studies has important implications for dose assessment of internal radionuclide contamination in humans. In this study, γ-H2AX, p-ATM and p-DNA-PKcs foci were enumerated using immunocytofluorescence method, and their protein levels were measured by Western blot in rat blood lymphocytes and granulocytes exposed to γ-rays compared with human blood lymphocytes and granulocytes. It was found that DNA double-strand break repair kinetics and linear dose responses in rat lymphocytes were similar to those observed in the human counterparts. Moreover, radiation induced clear p-ATM and p-DNA-PKcs foci formation and an increase in ratio of co-localization of p-ATM or p-DNA-PKcs with γ-H2AX foci in rat lymphocytes similar to those of human lymphocytes. The level of γ-H2AX protein in irradiated rat and human lymphocytes was significantly reduced by inhibitors of ATM and DNA-PKcs. Surprisingly, unlike human granulocytes, rat granulocytes with DNA-PKcs deficiency displayed a rapid accumulation, but delayed disappearance of γ-H2AX foci with essentially no change from 10 h to 48 h post-irradiation. Furthermore, inhibition of ATM activity in rat granulocytes also decreased radiation-induced γ-H2AX foci formation. In comparison, human granulocytes showed no response to irradiation regarding γ-H2AX, p-ATM or p-DNA-PKcs foci. Importantly, incidence of γ-H2AX foci in lymphocytes after total-body radiation of rats was consistent with that of in vitro irradiation of rat lymphocytes. These findings show that rats are a useful in vivo model for validation of γ-H2AX biodosimetry for dose assessment in humans. ATM and DNA-PKcs participate together in DSB repair in rat lymphocytes similar to that of human lymphocytes. Further, rat granulocytes, which have the characteristic of delayed disappearance of γ-H2AX foci in response to radiation, may be a useful experimental system for biodosimetry studies.

A robust low-rate coding scheme for packet video

NASA Technical Reports Server (NTRS)

Chen, Y. C.; Sayood, Khalid; Nelson, D. J.; Arikan, E. (Editor)

1991-01-01

Due to the rapidly evolving field of image processing and networking, video information promises to be an important part of telecommunication systems. Although up to now video transmission has been transported mainly over circuit-switched networks, it is likely that packet-switched networks will dominate the communication world in the near future. Asynchronous transfer mode (ATM) techniques in broadband-ISDN can provide a flexible, independent and high performance environment for video communication. For this paper, the network simulator was used only as a channel in this simulation. Mixture blocking coding with progressive transmission (MBCPT) has been investigated for use over packet networks and has been found to provide high compression rate with good visual performance, robustness to packet loss, tractable integration with network mechanics and simplicity in parallel implementation.

Marine phytoplankton stoichiometry mediates nonlinear interactions between nutrient supply, temperature, and atmospheric CO2

NASA Astrophysics Data System (ADS)

Moreno, Allison R.; Hagstrom, George I.; Primeau, Francois W.; Levin, Simon A.; Martiny, Adam C.

2018-05-01

Marine phytoplankton stoichiometry links nutrient supply to marine carbon export. Deviations of phytoplankton stoichiometry from Redfield proportions (106C : 1P) could therefore have a significant impact on carbon cycling, and understanding which environmental factors drive these deviations may reveal new mechanisms regulating the carbon cycle. To explore the links between environmental conditions, stoichiometry, and carbon cycling, we compared four different models of phytoplankton C : P: a fixed Redfield model, a model with C : P given as a function of surface phosphorus concentration (P), a model with C P given as a function of temperature, and a new multi-environmental model that predicts C : P as a function of light, temperature, and P. These stoichiometric models were embedded into a five-box ocean circulation model, which resolves the three major ocean biomes (high-latitude, subtropical gyres, and tropical upwelling regions). Contrary to the expectation of a monotonic relationship between surface nutrient drawdown and carbon export, we found that lateral nutrient transport from lower C : P tropical waters to high C : P subtropical waters could cause carbon export to decrease with increased tropical nutrient utilization. It has been hypothesized that a positive feedback between temperature and pCO2, atm will play an important role in anthropogenic climate change, with changes in the biological pump playing at most a secondary role. Here we show that environmentally driven shifts in stoichiometry make the biological pump more influential, and may reverse the expected positive relationship between temperature and pCO2, atm. In the temperature-only model, changes in tropical temperature have more impact on the Δ pCO2, atm (˜ 41 ppm) compared to subtropical temperature changes (˜ 4.5 ppm). Our multi-environmental model predicted a decline in pCO2, atm of ˜ 46 ppm when temperature spanned a change of 10 °C. Thus, we find that variation in marine phytoplankton stoichiometry and its environmental controlling factors can lead to nonlinear controls on pCO2, atm, suggesting the need for further studies of ocean C : P and the impact on ocean carbon cycling.

Ataxia-telangiectasia: founder effect among north African Jews.

PubMed

Gilad, S; Bar-Shira, A; Harnik, R; Shkedy, D; Ziv, Y; Khosravi, R; Brown, K; Vanagaite, L; Xu, G; Frydman, M; Lavin, M F; Hill, D; Tagle, D A; Shiloh, Y

1996-12-01

The ATM gene is responsible for the autosomal recessive disorder ataxia-telangiectasia (A-T), characterized by cerebellar degeneration, immunodeficiency and cancer predisposition. A-T carriers were reported to be moderately cancer-prone. A wide variety of A-T mutations, most of which are unique to single families, were identified in various ethnic groups, precluding carrier screening with mutation-specific assays. However, a single mutation was observed in 32/33 defective ATM alleles in Jewish A-T families of North African origin, coming from various regions of Morocco and Tunisia. This mutation, 103C-->T, results in a stop codon at position 35 of the ATM protein. In keeping with the nature of this mutation, various antibodies directed against the ATM protein failed to defect this protein in patient cells. A rapid carrier detection assay detected this mutation in three out of 488 ATM alleles of Jewish Moroccan or Tunisian origin. This founder effect provides a unique opportunity for population-based screening for A-T carriers in a large Jewish community.

High-speed network for delivery of education-on-demand

NASA Astrophysics Data System (ADS)

Cordero, Carlos; Harris, Dale; Hsieh, Jeff

1996-03-01

A project to investigate the feasibility of delivering on-demand distance education to the desktop, known as the Asynchronous Distance Education ProjecT (ADEPT), is presently being carried out. A set of Stanford engineering classes is digitized on PC, Macintosh, and UNIX platforms, and is made available on servers. Students on campus and in industry may then access class material on these servers via local and metropolitan area networks. Students can download class video and audio, encoded in QuickTimeTM and Show-Me TVTM formats, via file-transfer protocol or the World Wide Web. Alternatively, they may stream a vector-quantized version of the class directly from a server for real-time playback. Students may also download PostscriptTM and Adobe AcrobatTM versions of class notes. Off-campus students may connect to ADEPT servers via the internet, the Silicon Valley Test Track (SVTT), or the Bay-Area Gigabit Network (BAGNet). The SVTT and BAGNet are high-speed metropolitan-area networks, spanning the Bay Area, which provide IP access over asynchronous transfer mode (ATM). Student interaction is encouraged through news groups, electronic mailing lists, and an ADEPT home page. Issues related to having multiple platforms and interoperability are examined in this paper. The ramifications of providing a reliable service are discussed. System performance and the parameters that affect it are then described. Finally, future work on expanding ATM access, real-time delivery of classes, and enhanced student interaction is described.

Curcumin combined with turmerones, essential oil components of turmeric, abolishes inflammation-associated mouse colon carcinogenesis.

PubMed

Murakami, Akira; Furukawa, Ikuyo; Miyamoto, Shingo; Tanaka, Takuji; Ohigashi, Hajime

2013-01-01

Curcumin (CUR), a yellow pigment in turmeric, has marked potential for preventing colon cancer. We recently reported that ar-turmerone (ATM) suppressed nitric oxide (NO) generation in macrophages. In the present study, we explored the molecular mechanisms by which ATM attenuates NO generation and examined the anti-carcinogenesis activity of turmerones (TUR, a mixture of 5 sesquiterpenes including ATM). Both CUR and ATM inhibited lipopolysaccharide (LPS)-induced expression of inducible forms of both nitric oxide synthase and cyclooxygenase (iNOS and COX-2, respectively). A chase experiment using actinomycin D revealed that ATM accelerated the decay of iNOS and COX-2 mRNA, suggesting a post-transcriptional mechanism. ATM prevented LPS-induced translocation of HuR, an AU-rich element-binding protein that determines mRNA stability of certain inflammatory genes. In a colitis model, oral administration of TUR significantly suppressed 2% dextran sulfate sodium (DSS)-induced shortening of the large bowel by 52-58%. We also evaluated the chemopreventive effects of oral feeding of TUR, CUR, and their combinations using a model of dimethylhydradine-initiated and DSS-promoted mouse colon carcinogenesis. At the low dose, TUR markedly suppressed adenoma multiplicity by 73%, while CUR at both doses suppressed adenocarcinoma multiplicity by 63-69%. Interestingly, the combination of CUR and TUR at both low and high doses abolished tumor formation. Collectively, our results led to our hypothesis that TUR is a novel candidate for colon cancer prevention. Furthermore, we consider that its use in combination with CUR may become a powerful method for prevention of inflammation-associated colon carcinogenesis. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models.

PubMed

Durant, Stephen T; Zheng, Li; Wang, Yingchun; Chen, Kan; Zhang, Lingli; Zhang, Tianwei; Yang, Zhenfan; Riches, Lucy; Trinidad, Antonio G; Fok, Jacqueline H L; Hunt, Tom; Pike, Kurt G; Wilson, Joanne; Smith, Aaron; Colclough, Nicola; Reddy, Venkatesh Pilla; Sykes, Andrew; Janefeldt, Annika; Johnström, Peter; Varnäs, Katarina; Takano, Akihiro; Ling, Stephanie; Orme, Jonathan; Stott, Jonathan; Roberts, Caroline; Barrett, Ian; Jones, Gemma; Roudier, Martine; Pierce, Andrew; Allen, Jasmine; Kahn, Jenna; Sule, Amrita; Karlin, Jeremy; Cronin, Anna; Chapman, Melissa; Valerie, Kristoffer; Illingworth, Ruth; Pass, Martin

2018-06-01

Poor survival rates of patients with tumors arising from or disseminating into the brain are attributed to an inability to excise all tumor tissue (if operable), a lack of blood-brain barrier (BBB) penetration of chemotherapies/targeted agents, and an intrinsic tumor radio-/chemo-resistance. Ataxia-telangiectasia mutated (ATM) protein orchestrates the cellular DNA damage response (DDR) to cytotoxic DNA double-strand breaks induced by ionizing radiation (IR). ATM genetic ablation or pharmacological inhibition results in tumor cell hypersensitivity to IR. We report the primary pharmacology of the clinical-grade, exquisitely potent (cell IC 50 , 0.78 nM), highly selective [>10,000-fold over kinases within the same phosphatidylinositol 3-kinase-related kinase (PIKK) family], orally bioavailable ATM inhibitor AZD1390 specifically optimized for BBB penetration confirmed in cynomolgus monkey brain positron emission tomography (PET) imaging of microdosed 11 C-labeled AZD1390 ( K p,uu , 0.33). AZD1390 blocks ATM-dependent DDR pathway activity and combines with radiation to induce G 2 cell cycle phase accumulation, micronuclei, and apoptosis. AZD1390 radiosensitizes glioma and lung cancer cell lines, with p53 mutant glioma cells generally being more radiosensitized than wild type. In in vivo syngeneic and patient-derived glioma as well as orthotopic lung-brain metastatic models, AZD1390 dosed in combination with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induced tumor regressions and increased animal survival compared to IR treatment alone. We established a pharmacokinetic-pharmacodynamic-efficacy relationship by correlating free brain concentrations, tumor phospho-ATM/phospho-Rad50 inhibition, apoptotic biomarker (cleaved caspase-3) induction, tumor regression, and survival. On the basis of the data presented here, AZD1390 is now in early clinical development for use as a radiosensitizer in central nervous system malignancies.

The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models

PubMed Central

Wang, Yingchun; Chen, Kan; Zhang, Lingli; Zhang, Tianwei; Yang, Zhenfan; Riches, Lucy; Trinidad, Antonio G.; Pike, Kurt G.; Wilson, Joanne; Smith, Aaron; Colclough, Nicola; Johnström, Peter; Varnäs, Katarina; Takano, Akihiro; Ling, Stephanie; Orme, Jonathan; Stott, Jonathan; Barrett, Ian; Jones, Gemma; Allen, Jasmine; Kahn, Jenna; Sule, Amrita; Cronin, Anna; Chapman, Melissa; Illingworth, Ruth; Pass, Martin

2018-01-01

Poor survival rates of patients with tumors arising from or disseminating into the brain are attributed to an inability to excise all tumor tissue (if operable), a lack of blood-brain barrier (BBB) penetration of chemotherapies/targeted agents, and an intrinsic tumor radio-/chemo-resistance. Ataxia-telangiectasia mutated (ATM) protein orchestrates the cellular DNA damage response (DDR) to cytotoxic DNA double-strand breaks induced by ionizing radiation (IR). ATM genetic ablation or pharmacological inhibition results in tumor cell hypersensitivity to IR. We report the primary pharmacology of the clinical-grade, exquisitely potent (cell IC50, 0.78 nM), highly selective [>10,000-fold over kinases within the same phosphatidylinositol 3-kinase–related kinase (PIKK) family], orally bioavailable ATM inhibitor AZD1390 specifically optimized for BBB penetration confirmed in cynomolgus monkey brain positron emission tomography (PET) imaging of microdosed 11C-labeled AZD1390 (Kp,uu, 0.33). AZD1390 blocks ATM-dependent DDR pathway activity and combines with radiation to induce G2 cell cycle phase accumulation, micronuclei, and apoptosis. AZD1390 radiosensitizes glioma and lung cancer cell lines, with p53 mutant glioma cells generally being more radiosensitized than wild type. In in vivo syngeneic and patient-derived glioma as well as orthotopic lung-brain metastatic models, AZD1390 dosed in combination with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induced tumor regressions and increased animal survival compared to IR treatment alone. We established a pharmacokinetic-pharmacodynamic-efficacy relationship by correlating free brain concentrations, tumor phospho-ATM/phospho-Rad50 inhibition, apoptotic biomarker (cleaved caspase-3) induction, tumor regression, and survival. On the basis of the data presented here, AZD1390 is now in early clinical development for use as a radiosensitizer in central nervous system malignancies. PMID:29938225

The Advanced Technology Microwave Sounder (ATMS): The First 10 Months On-Orbit

NASA Technical Reports Server (NTRS)

Kim, Edward; Lyu, C-H Joseph; Blackwell, Willaim; Leslie, R. Vince; Baker, Neal; Mo, Tsan; Sun, Ninghai; Bi, Li; Anderson, Kent; Landrum, Mike;

WSB1 overcomes oncogene-induced senescence by targeting ATM for degradation

PubMed Central

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

[Progress of the ATM Crew

NASA Technical Reports Server (NTRS)

2003-01-01

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

Effects of prenatal low protein and postnatal high fat diets on visceral adipose tissue macrophage phenotypes and IL-6 expression in Sprague Dawley rat offspring

USDA-ARS?s Scientific Manuscript database

Adipose tissue macrophages (ATM) are implicated in adipose tissue inflammation and obesity-related insulin resistance. Maternal low protein models result in fetal programming of obesity. However, it is not known whether maternal undernutrition increases ATM phenotypic expression in F1 offspring. Us...

How long would SDH/SONET be prolonged?

NASA Astrophysics Data System (ADS)

Tao, Zhiyong; Mao, Qian

2004-04-01

As we all know, the increasing speed of data traffic is exceeding gradually from voice in today"s communication network. The main reason is the explosive of Internet. The controversy with IP over ATM/SDH/Optical becomes hotter and hotter, Many people in the telecommunication field are doubt: HOW LONG WOULD SDH/SONET BE PROLONGED? WHAT KIND OF SDH EQUIPMENTS COULD BE USED IN THE NETWORK? With the analysis from several aspects: services in the network, new development with SDH technology, market in transport equipment, This paper is considered that the SDH with some new features would be predominant transport technology in the recent years.

Client/Server data serving for high performance computing

NASA Technical Reports Server (NTRS)

Wood, Chris

1994-01-01

This paper will attempt to examine the industry requirements for shared network data storage and sustained high speed (10's to 100's to thousands of megabytes per second) network data serving via the NFS and FTP protocol suite. It will discuss the current structural and architectural impediments to achieving these sorts of data rates cost effectively today on many general purpose servers and will describe and architecture and resulting product family that addresses these problems. The sustained performance levels that were achieved in the lab will be shown as well as a discussion of early customer experiences utilizing both the HIPPI-IP and ATM OC3-IP network interfaces.

Functional Characterization of ATM Kinase Using Acetylation-Specific Antibodies.

PubMed

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.

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

NASA Astrophysics Data System (ADS)

Ferrandiz, Ana; Scallan, Gavin

1995-10-01

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

Verifying Secrets and Relative Secrecy

DTIC Science & Technology

2000-01-01

Systems that authenticate a user based on a shared secret (such as a password or PIN) normally allow anyone to query whether the secret is a given...value. For example, an ATM machine allows one to ask whether a string is the secret PIN of a (lost or stolen) ATM card. Yet such queries are prohibited

ATMS Step By Step.

ERIC Educational Resources Information Center

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…

Comparison of HIPWAC and Mars Express SPICAM Observations of Ozone on Mars 2006-2008 and Variation from 1993 IRHS Observations

NASA Technical Reports Server (NTRS)

Fast, Kelly E.; Kostiuk, Theodor; Lefevre, Frank; Hewagama, Tilak; Livengood, Timothy A.; Delgado, Juan D.; Annen, John; Sonnabend, Guido

2009-01-01

Ozone is a tracer of photochemistry in the atmosphere of Mars and an observable used to test predictions of photochemical models. We present a comparison of retrieved ozone abundances on Mars using ground-based infrared heterodyne measurements by NASA Goddard Space Flight Center's Heterodyne Instrument for Planetary Wind And Composition (HIPWAC) and space-based Mars Express Spectroscopy for the Investigation of the Characteristics of the Atmosphere of Mars (SPICAM) ultraviolet measurements. Ozone retrievals from simultaneous measurements in February 2008 were very consistent (0.8 microns-atm), as were measurements made close in time (ranging from less than 1 to greater than 8 microns-atm) during this period and during opportunities in October 2006 and February 2007. The consistency of retrievals from the two different observational techniques supports combining the measurements for testing photochemistry-coupled general circulation models and for investigating variability over the long-term between spacecraft missions. Quantitative comparison with ground-based measurements by NASA'GSFC's Infrared Heterodyne Spectrometer (IRHS) in 1993 reveals 2-4 times more ozone at low latitudes than in 2008 at the same season, and such variability was not evident over the shorter period of the Mars Express mission. This variability may be due to cloud activity.

Ablation of silicate particles in high-speed continuum and transition flow with application to the collection of interplanetary dust particles

NASA Technical Reports Server (NTRS)

Rulison, Aaron J.; Flagan, Richard C.; Ahrens, Thomas J.; Miller, Wayne F.

1991-01-01

The ablative deceleration of spheres in the continuum and slip regimes is studied using spherical 7.1-micron-diam soda-lime glass particles launched from vacuum at about 4500 m/sec speed through a 13-micron-thick plastic film into a capture chamber containing Xe at 0.1 or 0.2 atm pressure and 295 K temperature. The results of SEM examinations of the collected ablated particles showed that the ratio of the ablated-particle radius (Rf) to the initial radius (R0) increased with gas pressure (from Rf/R0 about 0.67 at 0.1 atm, to about 0.88 at 0.2 atm). A model was developed to describe the ablation and deceleration of spheres in high-speed continuum and slip flow. The pressure dependence predicted by the model agreed with experimental results.

The Passive microwave Neural network Precipitation Retrieval (PNPR) algorithm for AMSU/MHS observations: description and application to European case studies

NASA Astrophysics Data System (ADS)

Sanò, P.; Panegrossi, G.; Casella, D.; Di Paola, F.; Milani, L.; Mugnai, A.; Petracca, M.; Dietrich, S.

2015-02-01

The purpose of this study is to describe a new algorithm based on a neural network approach (Passive microwave Neural network Precipitation Retrieval - PNPR) for precipitation rate estimation from AMSU/MHS observations, and to provide examples of its performance for specific case studies over the European/Mediterranean area. The algorithm optimally exploits the different characteristics of Advanced Microwave Sounding Unit-A (AMSU-A) and the Microwave Humidity Sounder (MHS) channels, and their combinations, including the brightness temperature (TB) differences of the 183.31 channels, with the goal of having a single neural network for different types of background surfaces (vegetated land, snow-covered surface, coast and ocean). The training of the neural network is based on the use of a cloud-radiation database, built from cloud-resolving model simulations coupled to a radiative transfer model, representative of the European and Mediterranean Basin precipitation climatology. The algorithm provides also the phase of the precipitation and a pixel-based confidence index for the evaluation of the reliability of the retrieval. Applied to different weather conditions in Europe, the algorithm shows good performance both in the identification of precipitation areas and in the retrieval of precipitation, which is particularly valuable over the extremely variable environmental and meteorological conditions of the region. The PNPR is particularly efficient in (1) screening and retrieval of precipitation over different background surfaces; (2) identification and retrieval of heavy rain for convective events; and (3) identification of precipitation over a cold/iced background, with increased uncertainties affecting light precipitation. In this paper, examples of good agreement of precipitation pattern and intensity with ground-based data (radar and rain gauges) are provided for four different case studies. The algorithm has been developed in order to be easily tailored to new radiometers as they become available (such as the cross-track scanning Suomi National Polar-orbiting Partnership (NPP) Advanced Technology Microwave Sounder (ATMS)), and it is suitable for operational use as it is computationally very efficient. PNPR has been recently extended for applications to the regions of Africa and the South Atlantic, and an extended validation over these regions (using 2 yr of data acquired by the Tropical Rainfall Measuring Mission precipitation radar for comparison) is the subject of a paper in preparation. The PNPR is currently used operationally within the EUMETSAT Hydrology Satellite Application Facility (H-SAF) to provide instantaneous precipitation from passive microwave cross-track scanning radiometers. It undergoes routinely thorough extensive validation over Europe carried out by the H-SAF Precipitation Products Validation Team.

[The enigma of the biological interpretation of the linear-quadratic model finally resolved? A summary for non-mathematicians].

PubMed

Bodgi, L; Canet, A; Granzotto, A; Britel, M; Puisieux, A; Bourguignon, M; Foray, N

2016-06-01

The linear-quadratic (LQ) model is the only mathematical formula linking cellular survival and radiation dose that is sufficiently consensual to help radiation oncologists and radiobiologists in describing the radiation-induced events. However, this formula proposed in the 1970s and α and β parameters on which it is based remained without relevant biological meaning. From a collection of cutaneous fibroblasts with different radiosensitivity, built over 12 years by more than 50 French radiation oncologists, we recently pointed out that the ATM protein, major actor of the radiation response, diffuses from the cytoplasm to the nucleus after irradiation. The evidence of this nuclear shuttling of ATM allowed us to provide a biological interpretation of the LQ model in its mathematical features, validated by a hundred of radiosensitive cases. A mechanistic explanation of the radiosensitivity of syndromes caused by the mutation of cytoplasmic proteins and of the hypersensitivity to low-dose phenomenon has been proposed, as well. In this review, we present our resolution of the LQ model in the most didactic way. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons

PubMed Central

Dobbin, Matthew M; Madabhushi, Ram; Pan, Ling; Chen, Yue; Kim, Dohoon; Gao, Jun; Ahononu, Biafra; Pao, Ping-Chieh; Qiu, Yi; Zhao, Yingming; Tsai, Li-Huei

2016-01-01

Summary Defects in DNA repair have been linked to cognitive decline with age and neurodegenerative disease. Yet the mechanisms that protect neurons from genotoxic stress remain largely obscure. In this report, we characterize the roles of the NAD+-dependent deacetylase, SIRT1, in the neuronal response to DNA double-strand breaks (DSBs). We show that SIRT1 is rapidly recruited to DSBs in postmitotic neurons, where it exhibits a synergistic relationship with ATM. SIRT1 recruitment to breaks is ATM-dependent; however, SIRT1 also stimulates ATM auto-phosphorylation and activity and stabilizes ATM at DSB sites. Upon DSB induction, SIRT1 also binds the neuroprotective class I histone deacetylase, HDAC1. We show that SIRT1 deacetylates HDAC1 and stimulates its enzymatic activity, which is necessary for DSB repair through the nonhomologous end-joining (NHEJ) pathway. HDAC1 mutants that mimic a constitutively acetylated state render neurons more susceptible to DNA damage, whereas pharmacological SIRT1 activators that promote HDAC1 deacetylation also reduce DNA damage in two mouse models of neurodegeneration. We propose that SIRT1 is an apical transducer of the DSB response and that SIRT1 activation offers an important therapeutic avenue in neurodegeneration. PMID:23852118

Compressed sensing of ECG signal for wireless system with new fast iterative method.

PubMed

Tawfic, Israa; Kayhan, Sema

2015-12-01

Recent experiments in wireless body area network (WBAN) show that compressive sensing (CS) is a promising tool to compress the Electrocardiogram signal ECG signal. The performance of CS is based on algorithms use to reconstruct exactly or approximately the original signal. In this paper, we present two methods work with absence and presence of noise, these methods are Least Support Orthogonal Matching Pursuit (LS-OMP) and Least Support Denoising-Orthogonal Matching Pursuit (LSD-OMP). The algorithms achieve correct support recovery without requiring sparsity knowledge. We derive an improved restricted isometry property (RIP) based conditions over the best known results. The basic procedures are done by observational and analytical of a different Electrocardiogram signal downloaded them from PhysioBankATM. Experimental results show that significant performance in term of reconstruction quality and compression rate can be obtained by these two new proposed algorithms, and help the specialist gathering the necessary information from the patient in less time if we use Magnetic Resonance Imaging (MRI) application, or reconstructed the patient data after sending it through the network. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cycle Checkpoint Abnormalities during Dementia: A Plausible Association with the Loss of Protection against Oxidative Stress in Alzheimer’s Disease

PubMed Central

Katsel, Pavel; Tan, Weilun; Fam, Peter; Purohit, Dushyant P.; Haroutunian, Vahram

2013-01-01

Background Increasing evidence suggests an association between neuronal cell cycle (CCL) events and the processes that underlie neurodegeneration in Alzheimer’s disease (AD). Elevated levels of oxidative stress markers and mitochondrial dysfunction are also among early events in AD. Recent studies have reported the role of CCL checkpoint proteins and tumor suppressors, such as ATM and p53 in the control of glycolysis and oxidative metabolism in cancer, but their involvement in AD remains uncertain. Methods and Findings In this postmortem study, we measured gene expression levels of eight CCL checkpoint proteins in the superior temporal cortex (STC) of persons with varying severities of AD dementia and compare them to those of cognitively normal controls. To assess whether the CCL changes associated with cognitive impairment in AD are specific to dementia, gene expression of the same proteins was also measured in STC of persons with schizophrenia (SZ), which is also characterized by mitochondrial dysfunction. The expression of CCL-checkpoint and DNA damage response genes: MDM4, ATM and ATR was strongly upregulated and associated with progression of dementia (cognitive dementia rating, CDR), appearing as early as questionable or mild dementia (CDRs 0.5–1). In addition to gene expression changes, the downstream target of ATM-p53 signaling - TIGAR, a p53-inducible protein, the activation of which can regulate energy metabolism and protect against oxidative stress was progressively decreased as severity of dementia evolved, but it was unaffected in subjects with SZ. In contrast to AD, different CCL checkpoint proteins, which include p53, CHEK1 and BRCA1 were significantly downregulated in SZ. Conclusions These results support the activation of an ATM signaling and DNA damage response network during the progression of AD dementia, while the progressive decrease in the levels of TIGAR suggests loss of protection initiated by ATM-p53 signaling against intensifying oxidative stress in AD. PMID:23861893

Effect of water vapor on sound absorption in nitrogen at low frequency/pressure ratios

NASA Technical Reports Server (NTRS)

Zuckerwar, A. J.; Griffin, W. A.

1981-01-01

Sound absorption measurements were made in N2-H2O binary mixtures at 297 K over the frequency/pressure range f/P of 0.1-2500 Hz/atm to investigate the vibrational relaxation peak of N2 and its location on f/P axis as a function of humidity. At low humidities the best fit to a linear relationship between the f/P(max) and humidity yields an intercept of 0.013 Hz/atm and a slope of 20,000 Hz/atm-mole fraction. The reaction rate constants derived from this model are lower than those obtained from the extrapolation of previous high-temperature data.

The NASA Air Traffic Management Ontology: Technical Documentation

NASA Technical Reports Server (NTRS)

Keller, Richard M.

2017-01-01

This document is intended to serve as comprehensive documentation for the NASA Air Traffic Management (ATM) Ontology. The ATM Ontology is a conceptual model that defines key classes of entities and relationships pertaining to the US National Airspace System (NAS) and the management of air traffic through that system. A wide variety of classes are represented in the ATM Ontology, including classes corresponding to flights, aircraft, manufacturers, airports, airlines, air routes, NAS facilities, air traffic control advisories, weather phenomena, and many others. The Ontology can be useful in the context of a variety of information management tasks relevant to NAS, including information exchange, data query and search, information organization, information integration, and terminology standardization.

Degradation forecast for PEMFC cathode-catalysts under cyclic loads

NASA Astrophysics Data System (ADS)

Moein-Jahromi, M.; Kermani, M. J.; Movahed, S.

2017-08-01

Degradation of Fuel Cell (FC) components under cyclic loads is one of the biggest bottlenecks in FC commercialization. In this paper, a novel experimental based algorithm is presented to predict the Catalyst Layer (CL) performance loss during cyclic load. The algorithm consists of two models namely Models 1 and 2. The Model 1 calculates the Electro-Chemical Surface Area (ECSA) and agglomerate size (e.g. agglomerate radius, rt,agg) for the catalyst layer under cyclic load. The Model 2 is the already-existing model from our earlier studies that computes catalyst performance with fixed structural parameters. Combinations of these two Models predict the CL performance under an arbitrary cyclic load. A set of parametric/sensitivity studies is performed to investigate the effects of operating parameters on the percentage of Voltage Degradation Rate (VDR%) with rank 1 for the most influential one. Amongst the considered parameters (such as: temperature, relative humidity, pressure, minimum and maximum voltage of the cyclic load), the results show that temperature and pressure have the most and the least influences on the VDR%, respectively. So that, increase of temperature from 60 °C to 80 °C leads to over 20% VDR intensification, the VDR will also reduce 1.41% by increasing pressure from 2 atm to 4 atm.

Development of Geospatial Map Based Portal for New Delhi Municipal Council

NASA Astrophysics Data System (ADS)

Gupta, A. Kumar Chandra; Kumar, P.; Sharma, P. Kumar

2017-09-01

The Geospatial Delhi Limited (GSDL), a Govt. of NCT of Delhi Company formed in order to provide the geospatial information of National Capital Territory of Delhi (NCTD) to the Government of National Capital Territory of Delhi (GNCTD) and its organs such as DDA, MCD, DJB, State Election Department, DMRC etc., for the benefit of all citizens of Government of National Capital Territory of Delhi (GNCTD). This paper describes the development of Geospatial Map based Portal (GMP) for New Delhi Municipal Council (NDMC) of NCT of Delhi. The GMP has been developed as a map based spatial decision support system (SDSS) for planning and development of NDMC area to the NDMC department and It's heaving the inbuilt information searching tools (identifying of location, nearest utilities locations, distance measurement etc.) for the citizens of NCTD. The GMP is based on Client-Server architecture model. It has been developed using Arc GIS Server 10.0 with .NET (pronounced dot net) technology. The GMP is scalable to enterprise SDSS with enterprise Geo Database & Virtual Private Network (VPN) connectivity. Spatial data to GMP includes Circle, Division, Sub-division boundaries of department pertaining to New Delhi Municipal Council, Parcels of residential, commercial, and government buildings, basic amenities (Police Stations, Hospitals, Schools, Banks, ATMs and Fire Stations etc.), Over-ground and Underground utility network lines, Roads, Railway features. GMP could help achieve not only the desired transparency and easiness in planning process but also facilitates through efficient & effective tools for development and management of MCD area. It enables a faster response to the changing ground realities in the development planning, owing to its in-built scientific approach and open-ended design.

In Vivo and In Vitro Effects of ATM/ATR Signaling Pathway on Proliferation, Apoptosis, and Radiosensitivity of Nasopharyngeal Carcinoma Cells.

PubMed

Wang, Ming; Liu, Gang; Shan, Guo-Ping; Wang, Bing-Bing

2017-08-01

The study investigated the ability of ataxia-telangiectasia mutated (ATM)/Rad3-related (ATR) signaling pathway to influence the proliferation, apoptosis, and radiosensitivity of nasopharyngeal carcinoma (NPC) cells. NPC tissues and corresponding adjacent normal tissues were collected from 143 NPC patients. The NPC CNE2 cells were assigned into a control group, X-ray group, CGK-733 group, and X-ray+CGK-733 group. The mRNA levels of ATM and ATR were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) and the protein levels of ATM and ATR using western blotting. The positive expression of ATM and ATR in tissues and nude mouse tumor tissues was determined by immunohistochemistry. Cell proliferation, migration, invasion, and apoptosis rates were analyzed by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, scratch test, transwell assay, and flow cytometry, respectively. A nude mouse model of NPC was established to observe tumor volume and growth. The mRNA levels of ATR and ATM and the expression of ATR and ATM protein in NPC tissues were significantly higher than those in adjacent normal tissues. The colony formation assay showed that the colony-forming rate decreased, showing radiation dose-dependent and CGK-733 concentration-dependent manners. Expression of ATM, ATR, Chk1, and Chk2 was evidently increased in the X-ray, CGK-733, and X-ray+CGK-733groups compared with the control group, and the aforementioned expression was highest in the X-ray+CGK-733 group among the four groups. The cell proliferation, invasion, and migration were decreased, tumor volume decreased and cell apoptosis increased in the X-ray, CGK-733, and X-ray+CGK-733 groups compared with the control group; the X-ray+CGK-733 group exhibited lowest cell proliferation, invasion and migration, smallest tumor volume, and highest cell apoptosis among the four groups. Inhibition of ATM/ATR signaling pathway reduces proliferation and enhances apoptosis and radiosensitivity of NPC cells.

Genetic programming-based mathematical modeling of influence of weather parameters in BOD5 removal by Lemna minor.

PubMed

Chandrasekaran, Sivapragasam; Sankararajan, Vanitha; Neelakandhan, Nampoothiri; Ram Kumar, Mahalakshmi

2017-11-04

This study, through extensive experiments and mathematical modeling, reveals that other than retention time and wastewater temperature (T w ), atmospheric parameters also play important role in the effective functioning of aquatic macrophyte-based treatment system. Duckweed species Lemna minor is considered in this study. It is observed that the combined effect of atmospheric temperature (T atm ), wind speed (U w ), and relative humidity (RH) can be reflected through one parameter, namely the "apparent temperature" (T a ). A total of eight different models are considered based on the combination of input parameters and the best mathematical model is arrived at which is validated through a new experimental set-up outside the modeling period. The validation results are highly encouraging. Genetic programming (GP)-based models are found to reveal deeper understandings of the wetland process.

Regulation of the DNA damage response by DNA-PKcs inhibitory phosphorylation of ATM

PubMed Central

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

2017-01-01

SUMMARY 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. PMID:27939942

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

PubMed

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.

Gadd45a deletion aggravates hematopoietic stem cell dysfunction in ATM-deficient mice.

PubMed

Chen, Yulin; Yang, Runan; Guo, Peng; Ju, Zhenyu

2014-01-01

Ataxia telangiectasia mutated (ATM) kinase plays an essential role in the maintenance of genomic stability. ATM-deficient (ATM(-/-)) mice exhibit hematopoietic stem cell (HSC) dysfunction and a high incidence of lymphoma. Gadd45a controls cell cycle arrest, apoptosis and DNA repair, and is involved in the ATM-p53 mediated DNA damage response. However, the role of Gadd45a in regulating the functionality of ATM(-/-) HSCs is unknown. Here we report that Gadd45a deletion did not rescue the defects of T-cells and B-cells development in ATM(-/-) mice. Instead, ATM and Gadd45a double knockout (ATM(-/-) Gadd45a(-/-)) HSCs exhibited an aggravated defect in long-term self-renewal capacity compared to ATM(-/-) HSCs in HSC transplantation experiments. Further experiments revealed that the aggravated defect of ATM(-/-) Gadd45a(-/-) HSCs was due to a reduction of cell proliferation, associated with an accumulation of DNA damage and subsequent activation of DNA damage response including an up-regulation of p53-p21 signaling pathway. Additionally, ATM(-/-) Gadd45a(-/-) mice showed an increased incidence of hematopoietic malignancies, as well as an increased rate of metastasis than ATM(-/-) mice. In conclusion, Gadd45a deletion aggravated the DNA damage accumulation, which subsequently resulted in a further impaired self-renewal capacity and an increased malignant transformation in ATM(-/-) HSCs.

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

PubMed Central

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

A pair of polymorphous metal-organic frameworks based on an angular diisophthalate linker: synthesis, characterization and gas adsorption properties.

PubMed

Chen, Fengli; Bai, Dongjie; Wang, Yao; He, Minghui; Gao, Xiaoxia; He, Yabing

2018-01-15

The combination of an angular diisophthalate ligand, 5,5'-(naphthyl-2,7-yl)diisophthalate (H 4 L), and copper ions under different solvothermal conditions afforded two polymorphous metal-organic frameworks (ZJNU-77 and ZJNU-78) with the same framework composition of [Cu 2 (L)(H 2 O) 2 ], providing a platform to investigate the relationship between MOF polymorphism and gas adsorption properties. As determined by single-crystal X-ray diffraction, ZJNU-77 and ZJNU-78 exhibited three-dimensional networks crystallizing in different space groups. Their structural differences were mainly manifested by the ligand's conformation, the level of framework interpenetration and the network's topology. Interestingly, gas adsorption studies showed that the two compounds after desolvation displayed comparable gas adsorption properties with respect to C 2 H 2 , CO 2 and CH 4 , despite their different surface areas and pore volumes. The C 2 H 2 , CO 2 , and CH 4 uptake capacities at 298 K and 1 atm are 120.2, 78.1, and 18.4 cm 3 (STP) g -1 for ZJNU-77, and 122.0, 82.0, and 18.9 cm 3 (STP) g -1 for ZJNU-78, respectively. The IAST adsorption selectivities for the equimolar C 2 H 2 /CH 4 and CO 2 /CH 4 mixtures are 28.6 and 5.7 for ZJNU-77, and 28.4 and 5.9 for ZJNU-78 at 298 K and 1 atm. These results indicate that besides the surface area, the pore size also plays a crucial role in gas adsorption. This work not only represents an intriguing example of MOF polymorphism achieved by controlling solvothermal conditions, but also provides an insight into the correlation between MOF polymorphism and gas adsorption properties.

Greenland GPS network: Measurements and Models of 3D Elastic deformation

NASA Astrophysics Data System (ADS)

Khan, S. A.; van Dam, T. M.; Bevis, M. G.; Sasgen, I.; Bamber, J. L.; Helm, V.; Bjork, A. A.; Liu, L.; Kjaer, K. H.; Knudsen, P.; Kjeldsen, K. K.

2017-12-01

The Greenland GPS Network (GNET) uses the Global Positioning System (GPS) to measure the displacement of bedrock exposed near the margins of the Greenland ice sheet. The entire network is uplifting in response to past and present-day changes in ice mass. Here, we focus on present-day changes and compare measurements with models. To retrieve 3D elastic displacements from GPS time series, we correct our observations for glacial-isostatic adjustment and tectonic plate motion, and study the effect of the underlying mantle viscosity, ice load history and Euler parameters. To model 3D elastic displacements, we first estimate mass loss using 1995-2014 NASA's Airborne Topographic Mapper (ATM) flights derived altimetry, supplemented with laser altimetry observations from the Ice, Cloud, and Land Elevation Satellite (ICESat) during 2003-2009; the airborne Land, Vegetation, and Ice Sensor (LVIS) instrument during 2007-2013; radar altimetry from the CryoSat-2 satellite during 2010-2017; and European Remote-Sensing Satellite-1 (ERS-1) and ERS-2 data during 1995-2003. We converted the volume loss rate into a mass loss rate accounting for firn compaction as described by Kuipers Munneke et al. (2015). We predict the elastic displacements by convolving mass loss estimates with Green's functions for vertical and horizontal displacements. We use a variety of elastic Green's functions and mass change grid resolutions, respectively, to study the sensitivity of 3D elastic deformation on Earth model parameters different from the Preliminary Reference Earth Reference Model (PREM; Dziewonski & Anderson 1981) and the forcing ice load.

Sea Ice Freeboard and Thickness from the 2013 IceBridge ATM and DMS Data in Ross Sea, Antarctica

NASA Astrophysics Data System (ADS)

Xie, H.; Tian, L.; Tang, J.; Ackley, S. F.

2016-12-01

In November (20, 21, 27, and 28) 2013, NASA's IceBridge mission flew over the Ross Sea, Antarctica and collected important sea ice data with the ATM and DMS for the first time. We will present our methods to derive the local sea level and total freeboard for ice thickness retrieval from these two datasets. The methods include (1) leads classification from DMS data using an automated lead detection method, (2) potential leads from the reflectance of less than 0.25 from the ATM laser shots of L1B data, (3) local sea level retrieval based on these qualified ATM laser shots (L1B) within the DMS-derived leads (after outliers removal from the mean ± 2 standard deviation of these ATM elevations), (4) establishment of an empirical equation of local sea level as a function of distance from the starting point of each IceBridge flight, (5) total freeboard retrieval from the ATM L2 elevations by subtracting the local sea level derived from the empirical equation, and (6) ice thickness retrieval. The ice thickness derived from this method will be analyzed and compared with ICESat data (2003-2009) and other available data for the same region at the similar time period. Possible change and potential reasons will be identified and discussed.

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

PubMed

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

1999-01-01

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

Relationship between Weather, Traffic and Delay Based on Empirical Methods

NASA Technical Reports Server (NTRS)

Sridhar, Banavar; Swei, Sean S. M.

2006-01-01

The steady rise in demand for air transportation over the years has put much emphasis on the need for sophisticated air traffic flow management (TFM) within the National Airspace System (NAS). The NAS refers to hardware, software and people, including runways, radars, networks, FAA, airlines, etc., involved in air traffic management (ATM) in the US. One of the metrics that has been used to assess the performance of NAS is the actual delays provided through FAA's Air Traffic Operations Network (OPSNET). The OPSNET delay data includes those reportable delays, i.e. delays of 15 minutes or more experienced by Instrument Flight Rule (IFR) flights, submitted by the FAA facilities. These OPSNET delays are caused by the application of TFM initiatives in response to, for instance, weather conditions, increased traffic volume, equipment outages, airline operations, and runway conditions. TFM initiatives such as, ground stops, ground delay programs, rerouting, airborne holding, and miles-in-trail restrictions, are actions which are needed to control the air traffic demand to mitigate the demand-capacity imbalance due to the reduction in capacity. Consequently, TFM initiatives result in NAS delays. Of all the causes, weather has been identified as the most important causal factor for NAS delays. Therefore, in order to accurately assess the NAS performance, it has become necessary to create a baseline for NAS performance and establish a model which characterizes the relation between weather and NAS delays.

The development of an automated flight test management system for flight test planning and monitoring

NASA Technical Reports Server (NTRS)

Hewett, Marle D.; Tartt, David M.; Duke, Eugene L.; Antoniewicz, Robert F.; Brumbaugh, Randal W.

1988-01-01

The development of an automated flight test management system (ATMS) as a component of a rapid-prototyping flight research facility for AI-based flight systems concepts is described. The rapid-prototyping facility includes real-time high-fidelity simulators, numeric and symbolic processors, and high-performance research aircraft modified to accept commands for a ground-based remotely augmented vehicle facility. The flight system configuration of the ATMS includes three computers: the TI explorer LX and two GOULD SEL 32/27s.

Measurements of near-IR water vapor absorption at high pressure and temperature

NASA Astrophysics Data System (ADS)

Rieker, G. B.; Liu, X.; Li, H.; Jeffries, J. B.; Hanson, R. K.

2007-03-01

Tunable diode lasers (TDLs) are used to measure high resolution (0.1 cm-1), near-infrared (NIR) water vapor absorption spectra at 700 K and pressures up to 30 atm within a high-pressure and -temperature optical cell in a high-uniformity tube furnace. Both direct absorption and wavelength modulation with second harmonic detection (WMS-2f) spectra are obtained for 6 cm-1 regions near 7204 cm-1 and 7435 cm-1. Direct absorption measurements at 700 K and 10 atm are compared with simulations using spectral parameters from HITRAN and a hybrid database combining HITRAN with measured spectral constants for transitions in the two target spectral regions. The hybrid database reduces RMS error between the simulation and the measurements by 45% for the 7204 cm-1 region and 28% for the 7435 cm-1 region. At pressures above 10 atm, the breakdown of the impact approximation inherent to the Lorentzian line shape model becomes apparent in the direct absorption spectra, and measured results are in agreement with model results and trends at elevated temperatures reported in the literature. The wavelength-modulation spectra are shown to be less affected by the breakdown of the impact approximation and measurements agree well with the hybrid database predictions to higher pressures (30 atm).

Identification and chromosomal localization of Atm, the mouse homolog of the ataxia-telangiectasia gene.

PubMed

Pecker, I; Avraham, K B; Gilbert, D J; Savitsky, K; Rotman, G; Harnik, R; Fukao, T; Schröck, E; Hirotsune, S; Tagle, D A; Collins, F S; Wynshaw-Boris, A; Ried, T; Copeland, N G; Jenkins, N A; Shiloh, Y; Ziv, Y

1996-07-01

Atm, the mouse homolog of the human ATM gene defective in ataxia-telangiectasia (A-T), has been identified. The entire coding sequence of the Atm transcript was cloned and found to contain an open reading frame encoding a protein of 3066 amino acids with 84% overall identity and 91% similarity to the human ATM protein. Variable levels of expression of Atm were observed in different tissues. Fluorescence in situ hybridization and linkage analysis located the Atm gene on mouse chromosome 9, band 9C, in a region homologous to the ATM region on human chromosome 11q22-q23.

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

PubMed

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 new leads for understanding the biological and molecular roles of ATM and for the treatment of A-T.

Estimating surface pCO2 in the northern Gulf of Mexico: Which remote sensing model to use?

NASA Astrophysics Data System (ADS)

Chen, Shuangling; Hu, Chuanmin; Cai, Wei-Jun; Yang, Bo

2017-12-01

Various approaches and models have been proposed to remotely estimate surface pCO2 in the ocean, with variable performance as they were designed for different environments. Among these, a recently developed mechanistic semi-analytical approach (MeSAA) has shown its advantage for its explicit inclusion of physical and biological forcing in the model, yet its general applicability is unknown. Here, with extensive in situ measurements of surface pCO2, the MeSAA, originally developed for the summertime East China Sea, was tested in the northern Gulf of Mexico (GOM) where river plumes dominate water's biogeochemical properties during summer. Specifically, the MeSAA-predicted surface pCO2 was estimated by combining the dominating effects of thermodynamics, river-ocean mixing and biological activities on surface pCO2. Firstly, effects of thermodynamics and river-ocean mixing (pCO2@Hmixing) were estimated with a two-endmember mixing model, assuming conservative mixing. Secondly, pCO2 variations caused by biological activities (ΔpCO2@bio) was determined through an empirical relationship between sea surface temperature (SST)-normalized pCO2 and MODIS (Moderate Resolution Imaging Spectroradiometer) 8-day composite chlorophyll concentration (CHL). The MeSAA-modeled pCO2 (sum of pCO2@Hmixing and ΔpCO2@bio) was compared with the field-measured pCO2. The Root Mean Square Error (RMSE) was 22.94 μatm (5.91%), with coefficient of determination (R2) of 0.25, mean bias (MB) of - 0.23 μatm and mean ratio (MR) of 1.001, for pCO2 ranging between 316 and 452 μatm. To improve the model performance, a locally tuned MeSAA was developed through the use of a locally tuned ΔpCO2@bio term. A multi-variate empirical regression model was also developed using the same dataset. Both the locally tuned MeSAA and the regression models showed improved performance comparing to the original MeSAA, with R2 of 0.78 and 0.84, RMSE of 12.36 μatm (3.14%) and 10.66 μatm (2.68%), MB of 0.00 μatm and - 0.10 μatm, MR of 1.001 and 1.000, respectively. A sensitivity analysis was conducted to study the uncertainties in the predicted pCO2 as a result of the uncertainties in the input variables of each model. Although the MeSAA was more sensitive to variations in SST and CHL than in sea surface salinity (SSS), and the locally tuned MeSAA and the empirical regression models were more sensitive to changes in SST and SSS than in CHL, generally for these three models the bias induced by the uncertainties in the empirically derived parameters (river endmember total alkalinity (TA) and dissolved inorganic carbon (DIC), biological coefficient of the MeSAA and locally tuned MeSAA models) and environmental variables (SST, SSS, CHL) was within or close to the uncertainty of each model. While all these three models showed that surface pCO2 was positively correlated to SST, the MeSAA showed negative correlation between surface pCO2 and SSS and CHL but the locally tuned MeSAA and the empirical regression showed the opposite. These results suggest that the locally tuned MeSAA worked better in the river-dominated northern GOM than the original MeSAA, with slightly worse statistics but more meaningful physical and biogeochemical interpretations than the empirical regression model. Because data from abnormal upwelling were not used to train the models, they are not applicable for waters with strong upwelling, yet the empirical regression approach showed ability to be further tuned to adapt to such cases.

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

PubMed Central

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

2017-01-01

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 < 0.01). This effect was pronounced in stage II/III patients, even after adjusting for other clinical co-variates (p < 0.001). Additionally, we provide evidence that 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. PMID:28418844

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

PubMed

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 < 0.01). This effect was pronounced in stage II/III patients, even after adjusting for other clinical co-variates (p < 0.001). Additionally, we provide evidence that 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.

Effects of total pressure on non-grey gas radiation transfer in oxy-fuel combustion using the LBL, SNB, SNBCK, WSGG, and FSCK methods

NASA Astrophysics Data System (ADS)

Chu, Huaqiang; Gu, Mingyan; Consalvi, Jean-Louis; Liu, Fengshan; Zhou, Huaichun

2016-03-01

The effects of total pressure on gas radiation heat transfer are investigated in 1D parallel plate geometry containing isothermal and homogeneous media and an inhomogeneous and non-isothermal CO2-H2O mixture under conditions relevant to oxy-fuel combustion using the line-by-line (LBL), statistical narrow-band (SNB), statistical narrow-band correlated-k (SNBCK), weighted-sum-of-grey-gases (WSGG), and full-spectrum correlated-k (FSCK) models. The LBL calculations were conducted using the HITEMP2010 and CDSD-1000 databases and the LBL results serve as the benchmark solution to evaluate the accuracy of the other models. Calculations of the SNB, SNBCK, and FSCK were conducted using both the 1997 EM2C SNB parameters and their recently updated 2012 parameters to investigate how the SNB model parameters affect the results under oxy-fuel combustion conditions at high pressures. The WSGG model considered is the recently developed one by Bordbar et al. [19] for oxy-fuel combustion based on LBL calculations using HITEMP2010. The total pressure considered ranges from 1 up to 30 atm. The total pressure significantly affects gas radiation transfer primarily through the increase in molecule number density and only slightly through spectral line broadening. Using the 1997 EM2C SNB model parameters the accuracy of SNB and SNBCK is very good and remains essentially independent of the total pressure. When using the 2012 EM2C SNB model parameters the SNB and SNBCK results are less accurate and their error increases with increasing the total pressure. The WSGG model has the lowest accuracy and the best computational efficiency among the models investigated. The errors of both WSGG and FSCK using the 2012 EM2C SNB model parameters increase when the total pressure is increased from 1 to 10 atm, but remain nearly independent of the total pressure beyond 10 atm. When using the 1997 EM2C SNB model parameters the accuracy of FSCK only slightly decreases with increasing the total pressure.

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

PubMed

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.

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

PubMed Central

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

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

PubMed

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.

Estimates of atmospheric O2 in the Paleoproterozoic from paleosols

NASA Astrophysics Data System (ADS)

Kanzaki, Yoshiki; Murakami, Takashi

2016-02-01

A weathering model was developed to constrain the partial pressure of atmospheric O2 (PO2) in the Paleoproterozoic from the Fe records in paleosols. The model describes the Fe behavior in a weathering profile by dissolution/precipitation of Fe-bearing minerals, oxidation of dissolved Fe(II) to Fe(III) by oxygen and transport of dissolved Fe by water flow, in steady state. The model calculates the ratio of the precipitated Fe(III)-(oxyhydr)oxides from the dissolved Fe(II) to the dissolved Fe(II) during weathering (ϕ), as a function of PO2 . An advanced kinetic expression for Fe(II) oxidation by O2 was introduced into the model from the literature to calculate accurate ϕ-PO2 relationships. The model's validity is supported by the consistency of the calculated ϕ-PO2 relationships with those in the literature. The model can calculate PO2 for a given paleosol, once a ϕ value and values of the other parameters relevant to weathering, namely, pH of porewater, partial pressure of carbon dioxide (PCO2), water flow, temperature and O2 diffusion into soil, are obtained for the paleosol. The above weathering-relevant parameters were scrutinized for individual Paleoproterozoic paleosols. The values of ϕ, temperature, pH and PCO2 were obtained from the literature on the Paleoproterozoic paleosols. The parameter value of water flow was constrained for each paleosol from the mass balance of Si between water and rock phases and the relationships between water saturation ratio and hydraulic conductivity. The parameter value of O2 diffusion into soil was calculated for each paleosol based on the equation for soil O2 concentration with the O2 transport parameters in the literature. Then, we conducted comprehensive PO2 calculations for individual Paleoproterozoic paleosols which reflect all uncertainties in the weathering-relevant parameters. Consequently, robust estimates of PO2 in the Paleoproterozoic were obtained: 10-7.1-10-5.4 atm at ∼2.46 Ga, 10-5.0-10-2.5 atm at ∼2.15 Ga, 10-5.2-10-1.7 atm at ∼2.08 Ga and more than 10-4.6-10-2.0 atm at ∼1.85 Ga. Comparison of the present PO2 estimates to those in the literature suggests that a drastic rise of oxygen would not have occurred at ∼2.4 Ga, supporting a slightly rapid rise of oxygen at ∼2.4 Ga and a gradual rise of oxygen in the Paleoproterozoic in long term.

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

PubMed

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.

Conceptualization and Simulation of the Alaskan Arctic Tundra Landscape Evolution Using the Alaska Thermokarst Model

NASA Astrophysics Data System (ADS)

Bolton, W. R.; Lara, M. J.; Genet, H.; Romanovsky, V. E.; McGuire, A. D.

2016-12-01

The Arctic, including Alaska, is currently undergoing a change in climate, with observed increases in both mean surface temperature and precipitation. The combination of these increases in precipitation and temperature has resulted in a permafrost condition that is susceptible to thermokarst. Changes in the landscape due to thermokarst takes place whenever ice-rich permafrost thaws and the land surface subsides due to the volume loss when ground-ice transitions to water. The important processes associated with thermokarst include surface ponding, changes in topography, vegetation distribution, soil moisture conditions, drainage patterns, and related erosion. The Alaska Thermokarst Model (ATM) is a large-scale, state-and-transition model designed to simulate transitions between landscape units affected by thermokarst disturbance. The ATM using a frame-based methodology to track cohorts transitions and their respective proportions within each model grid cell. In the arctic tundra environment, the ATM tracks thermokarst related transitions among wetland tundra, graminoid tundra,shrub tundra and lakes. The transition from one cohort to another due to thermokarst processes can take place if thaw reaches ice-rich ground layers either due to pulse disturbance or due to gradual active layer deepening that eventually results in penetration of the protective layer. The protective layer buffers the ice-rich soils from the land surface and is critical to determine how susceptible an area is to thermokarst degradation. The initial landcover distribution is based upon analysis of compiled remote sensing data sets at 30-m resolution. Remote sensing analysis and field measurements from previous and ongoing studies are used to determine the ice-content of the soil, the drainage efficiency (or the ability of the landscape to store or transport water), the cumulative probability of thermokarst initiation, distance from rivers, lake dynamics (increasing, decreasing, or stable), and other factors which help determine landscape transition rates. Tundra types are allowed to transition from one type to another (for example, wetland tundra to graminoid tundra) under favorable climatic conditions. In this study, we present our conceptualization and initial simulation results from in the arctic regions of Alaska.

Development of UV Optical Measurements of Nitric Oxide and Hydroxyl Radical at the Exit of High Pressure Gas Turbine Combustors

NASA Technical Reports Server (NTRS)

Liscinsky, D. S.; Knight, B. A.; Shirley, J. A.

1998-01-01

Measurements of nitric oxide (NO) and hydroxyl radical (OR) have been made in a laboratory flat flame at pressures up to 30 atm using line-of-sight resonant absorption. Data are reported at equivalence ratios of 0.98 and 1.3 and pressures of 1, 5, 10, 20 and 30 atm. The performance of the in-situ LTV absorption technique with assessed at these elevated pressures by comparing the measured absorption with those predicted by detailed theoretical spectroscopic models for NO and OH. Previous to this experiment the resonant models had not been verified at pressures greater than two atmospheres. Agreement within 25% was found between the measurements and predictions with only slight modification of the existing models for both NO and OH to account for line center shifting and pressure broadening. Continuum interference of hot oxygen (O2) on the NO absorption spectra was not significant in the interpretation of the data. The optical methods used in this study are distinct from laser-based diagnostics such as laser induced fluorescence and, hence, have the potential to provide independent verification of the laser-based measurements. The methodology is also of sufficient simplicity to be hardened into a portable optical measurement system that can be deployed in gas turbine engine test cells. A miniature fiber optic couple portable instrument is described.

Single Nucleotide Polymorphism in ATM Gene, Cooking Oil Fumes and Lung Adenocarcinoma Susceptibility in Chinese Female Non-Smokers: A Case-Control Study

PubMed Central

Shen, Li; Yin, Zhihua; Wu, Wei; Ren, Yangwu; Li, Xuelian; Zhou, Baosen

2014-01-01

Background The ataxia-telangiectasia mutated (ATM) gene plays an important role in the DNA double-strand breaks repair pathway. Single nucleotide polymorphisms (SNPs) of DNA repair genes are suspected to influence the risk of lung cancer. This study aimed to investigate the association between the ATM -111G>A (rs189037) polymorphism, environmental risk factors and the risk of lung adenocarcinoma in Chinese female non-smokers. Methods A hospital-based case-control study of 487 lung cancer patients and 516 matched cancer-free controls was conducted. Information concerning demographic and environmental risk factors was obtained for each case and control by a trained interviewer. After informed consent was obtained, 10 ml venous blood was collected from each subject for biomarker testing. Single nucleotide polymorphism was determined by using TaqMan method. Results This study showed that the individuals with ATM rs189037 AA genotype were at an increased risk for lung adenocarcinoma compared with those carrying the GA or GG genotype (adjusted odds ratios (OR) 1.44, 95% confidence interval (CI) 1.02–2.02, P = 0.039). The stratified analysis suggested that increased risk associated with ATM rs189037 AA genotype in individuals who never or seldom were exposed to cooking oil fumes (adjusted OR 1.89, 95%CI 1.03–3.49, P = 0.040). Conclusions ATM rs189037 might be associated with the risk of lung adenocarcinoma in Chinese non-smoking females. Furthermore, ATM rs189037 AA genotype might be a risk factor of lung adenocarcinoma among female non-smokers without cooking oil fume exposure. PMID:24819391

ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1.

PubMed

You, Zhongsheng; Chahwan, Charly; Bailis, Julie; Hunter, Tony; Russell, Paul

2005-07-01

ATM has a central role in controlling the cellular responses to DNA damage. It and other phosphoinositide 3-kinase-related kinases (PIKKs) have giant helical HEAT repeat domains in their amino-terminal regions. The functions of these domains in PIKKs are not well understood. ATM activation in response to DNA damage appears to be regulated by the Mre11-Rad50-Nbs1 (MRN) complex, although the exact functional relationship between the MRN complex and ATM is uncertain. Here we show that two pairs of HEAT repeats in fission yeast ATM (Tel1) interact with an FXF/Y motif at the C terminus of Nbs1. This interaction resembles nucleoporin FXFG motif binding to HEAT repeats in importin-beta. Budding yeast Nbs1 (Xrs2) appears to have two FXF/Y motifs that interact with Tel1 (ATM). In Xenopus egg extracts, the C terminus of Nbs1 recruits ATM to damaged DNA, where it is subsequently autophosphorylated. This interaction is essential for ATM activation. A C-terminal 147-amino-acid fragment of Nbs1 that has the Mre11- and ATM-binding domains can restore ATM activation in an Nbs1-depleted extract. We conclude that an interaction between specific HEAT repeats in ATM and the C-terminal FXF/Y domain of Nbs1 is essential for ATM activation. We propose that conformational changes in the MRN complex that occur upon binding to damaged DNA are transmitted through the FXF/Y-HEAT interface to activate ATM. This interaction also retains active ATM at sites of DNA damage.

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

PubMed

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.

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

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

Kinoshita, Taisuke; Nagamatsu, Go, E-mail: gonag@sc.itc.keio.ac.jp; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012

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 cellularmore » 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.« less

High Reynolds number tests of a Douglas DLBA 032 airfoil in the Langley 0.3-meter transonic cryogenic tunnel

NASA Technical Reports Server (NTRS)

Johnson, Charles B.; Dress, David A.; Hill, Acquilla S.; Wilcox, Peter A.; Bui, Minh H.

1986-01-01

A wind-tunnel investigation of a Douglas advanced-technology airfoil was conducted in the Langley 0.3-Meter Transonic Cryogenic Tunnel (0.3-m TCT). The temperature was varied from 227 K (409 R) to 100 K (180 R) at pressures ranging from about 159 kPa (1.57 atm) to about 514 kPa (5.07 atm). Mach number was varied from 0.50 to 0.78. These variables provided a Reynolds number range (based on airfoil chord) from 6.0 to 30.0 x 10 to the 6th power. This investigation was specifically designed to: (1) test a Douglas airfoil from moderately low to flight-equivalent Reynolds numbers, and (2) evaluate sidewall-boundary-layer effects on transonic airfoil performance characteristics by a systematic variation of Mach number, Reynolds number, and sidewall-boundary-layer removal. Data are included which demonstrate the effects of fixing transition, Mach number, Reynolds number, and sidewall-boundary-layer removal on the aerodynamic characteristics of the airfoil. Also included are remarks on model design and model structural integrity.

Crystal growth of calcite from calcium bicarbonate solutions at constant PCO2 and 25°C: a test of a calcite dissolution model

USGS Publications Warehouse

Reddy, Michael M.; Plummer, Niel; Busenberg, E.

1981-01-01

A highly reproducible seeded growth technique was used to study calcite crystallization from calcium bicarbonate solutions at 25°C and fixed carbon dioxide partial pressures between 0.03 and 0.3 atm. The results are not consistent with empirical crystallization models that have successfully described calcite growth at low PCO2 (< 10−3 atm). Good agreement was found between observed crystallization rates and those calculated from the calcite dissolution rate law and mechanism proposed by Plummer et al. (1978).

Long- range transport of Xe-133 emissions under convective and non-convective conditions.

NASA Astrophysics Data System (ADS)

Kusmierczyk-Michulec, Jolanta; Gheddou, Abdelhakim

2015-04-01

The International Monitoring System (IMS) developed by the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) is a global system of monitoring stations, using four complementary technologies: seismic, hydroacoustic, infrasound and radionuclide. Data from all stations, belonging to IMS, are collected and transmitted to the International Data Centre (IDC) in Vienna, Austria. The radionuclide network comprises 80 stations, of which more than 60 are certified. The aim of radionuclide stations is a global monitoring of radioactive aerosols and radioactive noble gases, in particular xenon isotopes, supported by the atmospheric transport modeling (ATM). The aim of this study is to investigate the long-range transport of Xe-133 emissions under convective and non-convective conditions. For that purpose a series of 14 days forward simulations was conducted using the Lagrangian Particle Diffusion Model FLEXPART, designed for calculating the long-range and mesoscale dispersion of air pollution from point sources. The release point was at the ANSTO facility in Australia. The geographical localization to some extent justifies the assumption that the only source of Xe-133 observed at the neighbouring stations, comes from the ANSTO facility. In the simulations the analysed wind data provided by the European Centre for Medium-Range Weather Forecasts (ECMWF) were used with the spatial resolution of 0.5 degree. Studies have been performed to link Xe-133 emissions with detections at the IMS stations supported by the ATM, and to assess the impact of atmospheric convection on non-detections at the IMS stations. The results of quantitative and qualitative comparison will be presented.

Metropolitian area network services comprised of virtual local area networks running over hybrid fiber-coax and asynchronous transfer mode technologies

NASA Astrophysics Data System (ADS)

Biedron, William S.

1995-11-01

Since 1990 there has been a rapid increase in the demand for communication services, especially local and wide area network (LAN/WAN) oriented services. With the introduction of the DFB laser transmitter, hybrid-fiber-coax (HFC) cable plant designs, ATM transport technologies and rf modems, new LAN/WAN services can now be defined and marketed to residential and business customers over existing cable TV systems. The term metropolitan area network (MAN) can be used to describe this overall network. This paper discusses the technical components needed to provision these services as well as provides some perspectives on integration issues. Architecture at the headend and in the backbone is discussed, as well as specific service definitions and the technology issues associated with each. The TCP/IP protocol is suggested as a primary protocol to be used throughout the MAN.

Proceedings of the Air Transportation Management Workshop

NASA Technical Reports Server (NTRS)

Tobias, Leonard (Editor); Tashker, Michael G. (Editor); Boyle, Angela M. (Editor)

1995-01-01

The Air Transportation Management (ATM) Workshop was held 31 Jan. - 1 Feb. 1995 at NASA Ames Research Center. The purpose of the workshop was to develop an initial understanding of user concerns and requirements for future ATM capabilities and to initiate discussions of alternative means and technologies for achieving more effective ATM capabilities. The topics for the sessions were as follows: viewpoints of future ATM capabilities, user requirements, lessons learned, and technologies for ATM. In addition, two panel sessions discussed priorities for ATM, and potential contributions of NASA to ATM. The proceedings contain transcriptions of all sessions.

Study of ATM Phosphorylation by Cdk5 in Neuronal Cells.

PubMed

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.

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

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

Du, Fengxia; Zhang, Minjie; University of Chinese Academy of Sciences, Beijing 100049

2014-10-03

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.more » 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.« less

NASA/DARPA advanced communications technology satellite project for evaluation of telemedicine outreach using next-generation communications satellite technology: Mayo Foundation participation.

PubMed

Gilbert, B K; Mitchell, M P; Bengali, A R; Khandheria, B K

1999-08-01

To describe the development of telemedicine capabilities-application of remote consultation and diagnostic techniques-and to evaluate the feasibility and practicality of such clinical outreach to rural and underserved communities with limited telecommunications infrastructures. In 1992, Mayo Foundation (Rochester, Minn, Jacksonville, Fla, and Scottsdale, Ariz), the National Aeronautics and Space Administration, and the Defense Advanced Research Projects Agency collaborated to create a complex network of fiberoptic landlines, video recording systems, satellite terminals, and specially developed data translators linking Mayo sites with other locations in the continental United States on an on-demand basis. The purpose was to transmit data via the asynchronous transfer mode (ATM) digital communications protocol over the Advanced Communications Technology Satellite. The links were intended to provide a conduit for transmission of data for patient-specific consultations between physicians, evaluation of medical imagery, and medical education for clinical staffs at remote sites. Low-data-rate (LDR) experiments went live late in 1993. Mayo Clinic Rochester successfully provided medical consultation and services to 2 small regional medical facilities. High-data-rate (HDR) experiments included studies of remote digital echocardiography, store-and-forward telemedicine, cardiac catheterization, and teleconsultation for congenital heart disease. These studies combined landline data transmission with use of the satellite. The complexity of the routing paths and network components, immaturity of available software, and inexperience with existing telecommunications caused significant study delays. These experiments demonstrated that next-generation satellite technology can provide batch and real-time imagery for telemedicine. The first-generation of the ATM and satellite network technology used in these experiments created several technical problems and inconveniences that should be overcome as the network infrastructure matures.

Loss of PPAR gamma in immune cells impairs the ability of abscisic acid to improve insulin sensitivity by suppressing monocyte chemoattractant protein-1 expression and macrophage infiltration into white adipose tissue.

PubMed

Guri, Amir J; Hontecillas, Raquel; Ferrer, Gerardo; Casagran, Oriol; Wankhade, Umesh; Noble, Alexis M; Eizirik, Decio L; Ortis, Fernanda; Cnop, Miriam; Liu, Dongmin; Si, Hongwei; Bassaganya-Riera, Josep

2008-04-01

Abscisic acid (ABA) is a natural phytohormone and peroxisome proliferator-activated receptor gamma (PPARgamma) agonist that significantly improves insulin sensitivity in db/db mice. Although it has become clear that obesity is associated with macrophage infiltration into white adipose tissue (WAT), the phenotype of adipose tissue macrophages (ATMs) and the mechanisms by which insulin-sensitizing compounds modulate their infiltration remain unknown. We used a loss-of-function approach to investigate whether ABA ameliorates insulin resistance through a mechanism dependent on immune cell PPARgamma. We characterized two phenotypically distinct ATM subsets in db/db mice based on their surface expression of F4/80. F4/80(hi) ATMs were more abundant and expressed greater concentrations of chemokine receptor (CCR) 2 and CCR5 when compared to F4/80(lo) ATMs. ABA significantly decreased CCR2(+) F4/80(hi) infiltration into WAT and suppressed monocyte chemoattractant protein-1 (MCP-1) expression in WAT and plasma. Furthermore, the deficiency of PPARgamma in immune cells, including macrophages, impaired the ability of ABA to suppress the infiltration of F4/80(hi) ATMs into WAT, to repress WAT MCP-1 expression and to improve glucose tolerance. We provide molecular evidence in vivo demonstrating that ABA improves insulin sensitivity and obesity-related inflammation by inhibiting MCP-1 expression and F4/80(hi) ATM infiltration through a PPARgamma-dependent mechanism.

Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors.

PubMed

Landais, Igor; Hiddingh, Sanne; McCarroll, Matthew; Yang, Chao; Sun, Aiming; Turker, Mitchell S; Snyder, James P; Hoatlin, Maureen E

2009-12-31

The Fanconi anemia (FA) pathway is a multigene DNA damage response network implicated in the repair of DNA lesions that arise during replication or after exogenous DNA damage. The FA pathway displays synthetic lethal relationship with certain DNA repair genes such as ATM (Ataxia Telangectasia Mutated) that are frequently mutated in tumors. Thus, inhibition of FANCD2 monoubiquitylation (FANCD2-Ub), a key step in the FA pathway, might target tumor cells defective in ATM through synthetic lethal interaction. Curcumin was previously identified as a weak inhibitor of FANCD2-Ub. The aim of this study is to identify derivatives of curcumin with better activity and specificity. Using a replication-free assay in Xenopus extracts, we screened monoketone analogs of curcumin for inhibition of FANCD2-Ub and identified analog EF24 as a strong inhibitor. Mechanistic studies suggest that EF24 targets the FA pathway through inhibition of the NF-kB pathway kinase IKK. In HeLa cells, nanomolar concentrations of EF24 inhibited hydroxyurea (HU)-induced FANCD2-Ub and foci in a cell-cycle independent manner. Survival assays revealed that EF24 specifically sensitizes FA-competent cells to the DNA crosslinking agent mitomycin C (MMC). In addition, in contrast with curcumin, ATM-deficient cells are twofold more sensitive to EF24 than matched wild-type cells, consistent with a synthetic lethal effect between FA pathway inhibition and ATM deficiency. An independent screen identified 4H-TTD, a compound structurally related to EF24 that displays similar activity in egg extracts and in cells. These results suggest that monoketone analogs of curcumin are potent inhibitors of the FA pathway and constitute a promising new class of targeted anticancer compounds.

Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors

PubMed Central

2009-01-01

Background The Fanconi anemia (FA) pathway is a multigene DNA damage response network implicated in the repair of DNA lesions that arise during replication or after exogenous DNA damage. The FA pathway displays synthetic lethal relationship with certain DNA repair genes such as ATM (Ataxia Telangectasia Mutated) that are frequently mutated in tumors. Thus, inhibition of FANCD2 monoubiquitylation (FANCD2-Ub), a key step in the FA pathway, might target tumor cells defective in ATM through synthetic lethal interaction. Curcumin was previously identified as a weak inhibitor of FANCD2-Ub. The aim of this study is to identify derivatives of curcumin with better activity and specificity. Results Using a replication-free assay in Xenopus extracts, we screened monoketone analogs of curcumin for inhibition of FANCD2-Ub and identified analog EF24 as a strong inhibitor. Mechanistic studies suggest that EF24 targets the FA pathway through inhibition of the NF-kB pathway kinase IKK. In HeLa cells, nanomolar concentrations of EF24 inhibited hydroxyurea (HU)-induced FANCD2-Ub and foci in a cell-cycle independent manner. Survival assays revealed that EF24 specifically sensitizes FA-competent cells to the DNA crosslinking agent mitomycin C (MMC). In addition, in contrast with curcumin, ATM-deficient cells are twofold more sensitive to EF24 than matched wild-type cells, consistent with a synthetic lethal effect between FA pathway inhibition and ATM deficiency. An independent screen identified 4H-TTD, a compound structurally related to EF24 that displays similar activity in egg extracts and in cells. Conclusions These results suggest that monoketone analogs of curcumin are potent inhibitors of the FA pathway and constitute a promising new class of targeted anticancer compounds. PMID:20043851

Comparing the 12-month patency of low- versus high-pressure dilation in failing arteriovenous fistulae: A prospective multicenter trial (YOROI study).

PubMed

Wakamoto, Koki; Doi, Shigehiro; Nakashima, Ayumu; Kawai, Toru; Kyuden, Yasufumi; Naito, Takayuki; Asai, Mariko; Takahashi, Shunsuke; Murakami, Masaaki; Masaki, Takao

2018-03-01

This study was performed to investigate the effect of the balloon dilation pressure on the 12-month patency rate in patients with failed arteriovenous fistulas undergoing hemodialysis. In this multicenter, prospective, randomized trial, the 4-mm-diameter YOROI balloon was used for dilation of stenotic lesions. The balloons were inflated to a pressure of 8 atm (low-pressure group) or 30 atm to achieve complete expansion (high-pressure group). The 12-month patency rate after balloon angioplasty was analyzed by the Kaplan-Meier method and log-rank test and/or a Cox proportional hazard model. We also investigated the dilation pressure required to achieve complete expansion in the high-pressure group. In total, 71 patients were enrolled and allocated to either the low-pressure group (n = 34) or the high-pressure group (n = 37). The 12-month patency rates showed no significant difference between the low- and high-pressure groups (47% and 49%, respectively; p = 0.87). In the low-pressure group, the patency rate was not different between patients with complete dilation and residual stenosis (44% and 50%, respectively; p = 0.87). The Cox proportional hazard model revealed that the 12-month patency rate was associated with the stenosis diameter (hazard ratio 0.36; p = 0.001) and the presence of diabetes (hazard ratio 0.33; p = 0.018). Finally, the pressure required to achieve complete dilation was ≤20 atm in 76% of patients and ≤30 atm in 97% of patients. One patient required a dilation pressure of >30 atm. The patency rate does not differ between low-pressure dilation and high-pressure dilation.

ATM and MET kinases are synthetic lethal with non-genotoxic activation of p53

PubMed Central

Sullivan, Kelly D.; Padilla-Just, Nuria; Henry, Ryan E.; Porter, Christopher C.; Kim, Jihye; Tentler, John J.; Eckhardt, S. Gail; Tan, Aik Choon; DeGregori, James; Espinosa, Joaquín M.

2012-01-01

The p53 tumor suppressor orchestrates alternative stress responses including cell cycle arrest and apoptosis, but the mechanisms defining cell fate upon p53 activation are poorly understood. Several small molecule activators of p53 have been developed, including Nutlin-3, but their therapeutic potential is limited by the fact that they induce reversible cell cycle arrest in most cancer cell types. We report here the results of a ‘Synthetic Lethal with Nutlin-3’ genome-wide shRNA screen, which revealed that the ATM and MET kinases govern cell fate choice upon p53 activation. Genetic or pharmacological interference with ATM or MET activity converts the cellular response from cell cycle arrest into apoptosis in diverse cancer cell types without affecting expression of key p53 target genes. ATM and MET inhibitors enable Nutlin-3 to kill tumor spheroids. These results identify novel pathways controlling the cellular response to p53 activation and aid in the design of p53-based therapies. PMID:22660439

Activation of the kinase activity of ATM by retinoic acid is required for CREB-dependent differentiation of neuroblastoma cells.

PubMed

Fernandes, Norvin D; Sun, Yingli; Price, Brendan D

2007-06-01

The ATM protein kinase is mutated in ataxia telangiectasia, a genetic disease characterized by defective DNA repair, neurodegeneration, and growth factor signaling defects. The activity of ATM kinase is activated by DNA damage, and this activation is required for cells to survive genotoxic events. In addition to this well characterized role in DNA repair, we now demonstrate a novel role for ATM in the retinoic acid (RA)-induced differentiation of SH-SY5Y neuroblastoma cells into post-mitotic, neuronal-like cells. RA rapidly activates the activity of ATM kinase, leading to the ATM-dependent phosphorylation of the CREB protein, extrusion of neuritic processes, and differentiation of SH-SY5Y cells into neuronal-like cells. When ATM protein expression was suppressed by short hairpin RNA, the ATM-dependent phosphorylation of CREB was blocked. Furthermore, ATM-negative cells failed to differentiate into neuronal-like cells when exposed to retinoic acid; instead, they underwent cell death. Expression of a constitutively active CREBVP16 construct, or exposure to forskolin to induce CREB phosphorylation, rescued ATM negative cells and restored differentiation. Furthermore, when dominant negative CREB proteins with mutations in either the CREB phosphorylation site (CREBS133A) or the DNA binding domain (KCREB) were introduced into SH-SY5Y cells, retinoic acid-induced differentiation was blocked and the cells underwent cell death. The results demonstrate that ATM is required for the retinoic acid-induced differentiation of SH-SY5Y cells through the ATM dependent-phosphorylation of serine 133 of CREB. These results therefore define a novel mechanism for activation of the activity of ATM kinase by RA, and implicate ATM in the regulation of CREB function during RA-induced differentiation.

Immunoglobulin class switch recombination is impaired in Atm-deficient mice.

PubMed

Lumsden, Joanne M; McCarty, Thomas; Petiniot, Lisa K; Shen, Rhuna; Barlow, Carrolee; Wynn, Thomas A; Morse, Herbert C; Gearhart, Patricia J; Wynshaw-Boris, Anthony; Max, Edward E; Hodes, Richard J

2004-11-01

Immunoglobulin class switch recombination (Ig CSR) involves DNA double strand breaks (DSBs) at recombining switch regions and repair of these breaks by nonhomologous end-joining. Because the protein kinase ataxia telengiectasia (AT) mutated (ATM) plays a critical role in DSB repair and AT patients show abnormalities of Ig isotype expression, we assessed the role of ATM in CSR by examining ATM-deficient mice. In response to T cell-dependent antigen (Ag), Atm-/- mice secreted substantially less Ag-specific IgA, IgG1, IgG2b, and IgG3, and less total IgE than Atm+/+ controls. To determine whether Atm-/- B cells have an intrinsic defect in their ability to undergo CSR, we analyzed in vitro responses of purified B cells. Atm-/- cells secreted substantially less IgA, IgG1, IgG2a, IgG3, and IgE than wild-type (WT) controls in response to stimulation with lipopolysaccharide, CD40 ligand, or anti-IgD plus appropriate cytokines. Molecular analysis of in vitro responses indicated that WT and Atm-/- B cells produced equivalent amounts of germline IgG1 and IgE transcripts, whereas Atm-/- B cells produced markedly reduced productive IgG1 and IgE transcripts. The reduction in isotype switching by Atm-/- B cells occurs at the level of genomic DNA recombination as measured by digestion-circularization PCR. Analysis of sequences at CSR sites indicated that there is greater microhomology at the mu-gamma1 switch junctions in ATM B cells than in wild-type B cells, suggesting that ATM function affects the need or preference for sequence homology in the CSR process. These findings suggest a role of ATM in DNA DSB recognition and/or repair during CSR.

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

PubMed

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.

ATM Polymorphisms Predict Severe Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

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

Xiong, Huihua; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Liao, Zhongxing, E-mail: zliao@mdanderson.org

2013-03-15

Purpose: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP). Methods and Materials: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered. Results: Of 362more » patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites. Conclusions: ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.« less

Pre-Launch Characterization of the Advanced Technology Microwave Sounder (ATMS) on the Joint Polar Satellite System-1 Satellite (JPSS-1)

NASA Astrophysics Data System (ADS)

Kim, Edward; Leslie, Vince; Lyu, Joseph; Smith, Craig; McCormick, Lisa; Anderson, Kent

2016-04-01

The Advanced Technology Microwave Sounder (ATMS) is the newest generation of microwave sounder in the international fleet of polar-orbiting weather satellites, replacing the Advanced Microwave Sounding Unit (AMSU) which first entered service in 1998. The first ATMS was launched aboard the Suomi NPP (S-NPP) satellite in late 2011. The second ATMS is manifested on the Joint Polar Satellite System-1 Satellite (JPSS-1). ATMS provides 22 channels of temperature and humidity sounding observations over a frequency range from 23 to 183 GHz. These microwave soundings provide the highest impact data ingested by operational Numerical Weather Prediction (NWP) models, and are the most critical of the polar-orbiting satellite observations, particularly because microwave sensing can penetrate clouds. This paper will present performance characterizations from pre-launch calibration measurements of the JPSS-1 ATMS just completed in December, 2015. The measurements were conducted in a thermal vacuum chamber with blackbody targets simulating cold space, ambient, and a variable Earth scene. They represent the best opportunity for calibration characterization of the instrument since the environment can be carefully controlled. We will present characterizations of the sensitivity (NEDT), accuracy, nonlinearity, noise spectral characteristics, gain stability, repeatability, and inter-channel correlation. An estimate of expected "striping" will be presented, and a discussion of reflector emissivity effects will also be provided. Comparisons will be made with the S-NPP flight unit. Finally, we will describe planned on-orbit characterizations - such as pitch and roll maneuvers - that will further improve both the measurement quality and the understanding of various error contributions.

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

DTIC Science & Technology

2006-07-01

ATM genetic variant identified affects radiosensitivity and levels of the protein encoded by the ATM gene for each mutation examined. 15. SUBJECT...women without breast cancer. An additional objective is to determine the functional impact upon the protein encoded by the ATM gene for each mutation ...each ATM variant identified affects radiosensitivity and levels of the protein encoded by the ATM gene for mutations identified. Body STATEMENT

Absence of Wip1 partially rescues Atm deficiency phenotypes in mice

PubMed Central

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

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

PubMed

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 directs DNA damage responses and proteostasis via genetically separable pathways

PubMed Central

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

2018-01-01

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. Here, we genetically separated DNA damage activation of ATM from oxidative activation using separation-of-function mutations. We found that deficiency in ATM activation by Mre11-Rad50-Nbs1 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 ATM lacking oxidative activation generates 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 implicates ATM in the control of protein homeostasis. PMID:29317520

Complexity analysis of the Next Gen Air Traffic Management System: trajectory based operations.

PubMed

Lyons, Rhonda

2012-01-01

According to Federal Aviation Administration traffic predictions currently our Air Traffic Management (ATM) system is operating at 150 percent capacity; forecasting that within the next two decades, the traffic with increase to a staggering 250 percent [17]. This will require a major redesign of our system. Today's ATM system is complex. It is designed to safely, economically, and efficiently provide air traffic services through the cost-effective provision of facilities and seamless services in collaboration with multiple agents however, contrary the vision, the system is loosely integrated and is suffering tremendously from antiquated equipment and saturated airways. The new Next Generation (Next Gen) ATM system is designed to transform the current system into an agile, robust and responsive set of operations that are designed to safely manage the growing needs of the projected increasingly complex, diverse set of air transportation system users and massive projected worldwide traffic rates. This new revolutionary technology-centric system is dynamically complex and is much more sophisticated than it's soon to be predecessor. ATM system failures could yield large scale catastrophic consequences as it is a safety critical system. This work will attempt to describe complexity and the complex nature of the NextGen ATM system and Trajectory Based Operational. Complex human factors interactions within Next Gen will be analyzed using a proposed dual experimental approach designed to identify hazards, gaps and elicit emergent hazards that would not be visible if conducted in isolation. Suggestions will be made along with a proposal for future human factors research in the TBO safety critical Next Gen environment.

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

PubMed

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.

MOF phosphorylation by ATM regulates 53BP1-mediated DSB repair pathway choice

PubMed Central

Gupta, Arun; Hunt, Clayton R.; Hegdec, Muralidhar L.; Chakraborty, Sharmistha; Udayakumar, Durga; Horikoshi, Nobuo; Singh1, Mayank; Ramnarain, Deepti B.; Hittelman, Walter N.; Namjoshi, Sarita; Asaithamby, Aroumougame; Hazra, Tapas K.; Ludwig, Thomas; Pandita, Raj K.; Tyler, Jessica K.; Pandita, Tej K.

2014-01-01

Cell cycle phase is a critical determinant of the choice between DNA damage repair by non-homologous end joining (NHEJ) or homologous recombination (HR). Here we report that DSBs induce ATM-dependent MOF (a histone H4 acetyl-transferase) phosphorylation (p-T392-MOF) and that phosphorylated MOF co-localizes with γ-H2AX, ATM, and 53BP1 foci. Mutation of the phosphorylation site (MOF-T392A) impedes DNA repair in S- and G2-phase but not G1-phase cells. Expression of MOF-T392A also reverses the reduction in DSB associated 53BP1 seen in wild type S/G2-phase cells, resulting in enhanced 53BP1 and reduced BRCA1 association. Decreased BRCA1 levels at DSB sites correlates with defective repairosome formation, reduced HR repair and decreased cell survival following irradiation. These data support a model whereby ATM mediated MOF-T392 phosphorylation modulates 53BP1 function to facilitate the subsequent recruitment of HR repair proteins, uncovering a regulatory role for MOF in DSB repair pathway choice during S/G2-phase. PMID:24953651

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

PubMed Central

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

2013-01-01

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

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

PubMed

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.

Improving information retrieval using Medical Subject Headings Concepts: a test case on rare and chronic diseases.

PubMed

Darmoni, Stéfan J; Soualmia, Lina F; Letord, Catherine; Jaulent, Marie-Christine; Griffon, Nicolas; Thirion, Benoît; Névéol, Aurélie

2012-07-01

As more scientific work is published, it is important to improve access to the biomedical literature. Since 2000, when Medical Subject Headings (MeSH) Concepts were introduced, the MeSH Thesaurus has been concept based. Nevertheless, information retrieval is still performed at the MeSH Descriptor or Supplementary Concept level. The study assesses the benefit of using MeSH Concepts for indexing and information retrieval. Three sets of queries were built for thirty-two rare diseases and twenty-two chronic diseases: (1) using PubMed Automatic Term Mapping (ATM), (2) using Catalog and Index of French-language Health Internet (CISMeF) ATM, and (3) extrapolating the MEDLINE citations that should be indexed with a MeSH Concept. Type 3 queries retrieve significantly fewer results than type 1 or type 2 queries (about 18,000 citations versus 200,000 for rare diseases; about 300,000 citations versus 2,000,000 for chronic diseases). CISMeF ATM also provides better precision than PubMed ATM for both disease categories. Using MeSH Concept indexing instead of ATM is theoretically possible to improve retrieval performance with the current indexing policy. However, using MeSH Concept information retrieval and indexing rules would be a fundamentally better approach. These modifications have already been implemented in the CISMeF search engine.

ATM inhibitor KU-55933 increases the TMZ responsiveness of only inherently TMZ sensitive GBM cells.

PubMed

Nadkarni, Aditi; Shrivastav, Meena; Mladek, Ann C; Schwingler, Paul M; Grogan, Patrick T; Chen, Junjie; Sarkaria, Jann N

2012-12-01

Ataxia telangiectasia mutated (ATM) kinase is critical in sensing and repairing DNA double-stranded breaks (DSBs) such as those induced by temozolomide (TMZ). ATM deficiency increases TMZ sensitivity, which suggests that ATM inhibitors may be effective TMZ sensitizing agents. In this study, the TMZ sensitizing effects of 2 ATM specific inhibitors were studied in established and xenograft-derived glioblastoma (GBM) lines that are inherently sensitive to TMZ and derivative TMZ-resistant lines. In parental U251 and U87 glioma lines, the addition of KU-55933 to TMZ significantly increased cell killing compared to TMZ alone [U251 survival: 0.004 ± 0.0015 vs. 0.08 ± 0.01 (p < 0.001), respectively, and U87 survival: 0.02 ± 0.005 vs. 0.04 ± 0.002 (p < 0.001), respectively] and also elevated the fraction of cells arrested in G2/M [U251 G2/M fraction: 61.8 ± 1.1 % vs. 35 ± 0.8 % (p < 0.001), respectively, and U87 G2/M fraction 25 ± 0.2 % vs.18.6 ± 0.4 % (p < 0.001), respectively]. In contrast, KU-55933 did not sensitize the resistant lines to TMZ, and neither TMZ alone or combined with KU-55933 induced a G2/M arrest. While KU-55933 did not enhance TMZ induced Chk1/Chk2 activation, it increased TMZ-induced residual γ-H2AX foci in the parental cells but not in the TMZ resistant cells. Similar sensitization was observed with either KU-55933 or CP-466722 combined with TMZ in GBM12 xenograft line but not in GBM12TMZ, which is resistant to TMZ due to MGMT overexpression. These findings are consistent with a model where ATM inhibition suppresses the repair of TMZ-induced DSBs in inherently TMZ-sensitive tumor lines, which suggests an ATM inhibitor potentially could be deployed with an improvement in the therapeutic window when combined with TMZ.

Characterization, adaptive traffic shaping, and multiplexing of real-time MPEG II video

NASA Astrophysics Data System (ADS)

Agrawal, Sanjay; Barry, Charles F.; Binnai, Vinay; Kazovsky, Leonid G.

1997-01-01

We obtain network traffic model for real-time MPEG-II encoded digital video by analyzing video stream samples from real-time encoders from NUKO Information Systems. MPEG-II sample streams include a resolution intensive movie, City of Joy, an action intensive movie, Aliens, a luminance intensive (black and white) movie, Road To Utopia, and a chrominance intensive (color) movie, Dick Tracy. From our analysis we obtain a heuristic model for the encoded video traffic which uses a 15-stage Markov process to model the I,B,P frame sequences within a group of pictures (GOP). A jointly-correlated Gaussian process is used to model the individual frame sizes. Scene change arrivals are modeled according to a gamma process. Simulations show that our MPEG-II traffic model generates, I,B,P frame sequences and frame sizes that closely match the sample MPEG-II stream traffic characteristics as they relate to latency and buffer occupancy in network queues. To achieve high multiplexing efficiency we propose a traffic shaping scheme which sets preferred 1-frame generation times among a group of encoders so as to minimize the overall variation in total offered traffic while still allowing the individual encoders to react to scene changes. Simulations show that our scheme results in multiplexing gains of up to 10% enabling us to multiplex twenty 6 Mbps MPEG-II video streams instead of 18 streams over an ATM/SONET OC3 link without latency or cell loss penalty. This scheme is due for a patent.

Susceptibility of ATM-deficient pancreatic cancer cells to radiation.

PubMed

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.

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

PubMed

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.

Quality of Service for Real-Time Applications Over Next Generation Data Networks

NASA Technical Reports Server (NTRS)

Ivancic, William; Atiquzzaman, Mohammed; Bai, Haowei; Su, Hongjun; Jain, Raj; Duresi, Arjan; Goyal, Mukyl; Bharani, Venkata; Liu, Chunlei; Kota, Sastri

2001-01-01

This project, which started on January 1, 2000, was funded by NASA Glenn Research Center for duration of one year. The deliverables of the project included the following tasks: Study of QoS mapping between the edge and core networks envisioned in the Next Generation networks will provide us with the QoS guarantees that can be obtained from next generation networks. Buffer management techniques to provide strict guarantees to real-time end-to-end applications through preferential treatment to packets belonging to real-time applications. In particular, use of ECN to help reduce the loss on high bandwidth-delay product satellite networks needs to be studied. Effect of Prioritized Packet Discard to increase goodput of the network and reduce the buffering requirements in the ATM switches. Provision of new IP circuit emulation services over Satellite IP backbones using MPLS will be studied. Determine the architecture and requirements for internetworking ATN and the Next Generation Internet for real-time applications.

A native IP satellite communications system

NASA Astrophysics Data System (ADS)

Koudelka, O.; Schmidt, M.; Ebert, J.; Schlemmer, H.; Kastner-Puschl, S.; Riedler, W.

2004-08-01

≪ In the framework of ESA's ARTES-5 program the Institute of Applied Systems Technology (Joanneum Research) in cooperation with the Department of Communications and Wave Propagation has developed a novel meshed satellite communications system which is optimised for Internet traffic and applications (L*IP—Local Network Interconnection via Satellite Systems Using the IP Protocol Suite). Both symmetrical and asymmetrical connections are supported. Bandwidth on demand and guaranteed quality of service are key features of the system. A novel multi-frequency TDMA access scheme utilises efficient methods of IP encapsulation. In contrast to other solutions it avoids legacy transport network techniques. While the DVB-RCS standard is based on ATM or MPEG transport cells, the solution of the L*IP system uses variable-length cells which reduces the overhead significantly. A flexible and programmable platform based on Linux machines was chosen to allow the easy implementation and adaptation to different standards. This offers the possibility to apply the system not only to satellite communications, but provides seamless integration with terrestrial fixed broadcast wireless access systems. The platform is also an ideal test-bed for a variety of interactive broadband communications systems. The paper describes the system architecture and the key features of the system.

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

PubMed

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 < .0001), and the primary sites of metastatic carcinomas (P < .0001) compared with normal mammary glands. No significant differences in 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.

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

PubMed

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.

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

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

Fukumoto, Yasunori, E-mail: fukumoto@faculty.chiba-u.jp; Kuki, Kazumasa; Morii, Mariko

2014-09-26

Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the processmore » 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.« less

Does temperature nudging overwhelm aerosol radiative effects in regional integrated climate models?

NASA Astrophysics Data System (ADS)

He, Jian; Glotfelty, Timothy; Yahya, Khairunnisa; Alapaty, Kiran; Yu, Shaocai

2017-04-01

Nudging (data assimilation) is used in many regional integrated meteorology-air quality models to reduce biases in simulated climatology. However, in such modeling systems, temperature changes due to nudging could compete with temperature changes induced by radiatively active and hygroscopic short-lived tracers leading to two interesting dilemmas: when nudging is continuously applied, what are the relative sizes of these two radiative forces at regional and local scales? How do these two forces present in the free atmosphere differ from those present at the surface? This work studies these two issues by converting temperature changes due to nudging into pseudo radiative effects (PRE) at the surface (PRE_sfc), in troposphere (PRE_atm), and at the top of atmosphere (PRE_toa), and comparing PRE with the reported aerosol radiative effects (ARE). Results show that the domain-averaged PRE_sfc is smaller than ARE_sfc estimated in previous studies and this work, but could be significantly larger than ARE_sfc at local scales. PRE_atm is also much smaller than ARE_atm. These results indicate that appropriate nudging methodology could be applied to the integrated models to study aerosol radiative effects at continental/regional scales, but it should be treated with caution for local scale applications.

Changes in Intestinal Microbiota Affect Metabolism of Ginsenoside Re.

PubMed

Zhang, Lei; Li, Fei; Qin, Wang-Jun; Fu, Chao; Zhang, Xiang-Lin

2018-05-10

Ginsenoside Re, an active ingredient in Panax ginseng, is widely used as a therapeutic and nutriment. Intestinal microbiota plays crucial roles in modulating the pharmacokinetics and pharmacological actions of ginsenoside Re. The aim of this study was to explore the relationship between bacterial community variety and the metabolic profiles of ginsenoside Re. We developed two models with intestinal dysbacteriosis: a pseudo-germ-free model induced by a non-absorbable antimicrobial mixture (ATM), and Qi-deficiency model established via over-fatigue and acute cold stress (OACS). First, the bacterial community structures in control, ATM, and OACS rats were compared via 16S rRNA amplicon sequencing. Then, gut microbial metabolism of ginsenoside Re was assessed qualitatively and quantitatively in the three groups by UPLC-Q-TOF/MS and HPLC-TQ-MS, respectively. Ten metabolites of ginsenoside Re were detected and tentatively identified, three of which were novel. Moreover, due to significant differences in bacterial communities, deglycosylated products, as the main metabolites of ginsenoside Re, were produced at lower levels in ATM and OACS models. Importantly, the levels of these deglycosylated metabolites correlated with alterations in Prevotella, Lactobacillus, and Bacteroides populations, as well as glycosidase activities. Collectively, biotransformation of ginsenoside Re is potentially influenced by regulating the composition of intestinal microbiota and glycosidase activities. This article is protected by copyright. All rights reserved.

Structure of the intact ATM/Tel1 kinase

NASA Astrophysics Data System (ADS)

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.

Tyrosine 370 phosphorylation of ATM positively regulates DNA damage response

PubMed Central

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

Poor adherence to P2Y12 antagonists increased cardiovascular risks in Chinese PCI-treated patients.

PubMed

Sun, Yang; Li, Chenze; Zhang, Lina; Hu, Dong; Zhang, Xudong; Yu, Ting; Tao, Min; Wang, Dao Wen; Shen, Xiaoqing

2017-03-01

Low adherence to secondary prevention medications (ATM) of patients after acute coronary syndrome (ACS) is associated with poor clinical outcomes. However, literature provides limited data on assessment of ATM and risks associated with poor in Chinese patients with ACS. In the current work, ATM was assessed in consecutively recruited patients with ACS in Tongji Hospital from November 5, 2013 to December 31, 2014. A total of 2126 patients were classified under low adherence (proportion of days covered (PDC) C< 50%) and high adherence (PDC>50%) groups based on their performance after discharge. All patients were followed up at the 1st, 6th, and 12th month of discharge while recording ATM and major adverse cardiac events (MACE). Bivariate logistic regression was used to identify the factors associated with ATM. Cox regression was used to analyze the association between ATM and MACE within one year after discharge. Results showed that coronary artery bypass grafting (CABG) alone had significantly lower proportion of high adherence to P2Y12 antagonists (83.0% vs. 90.7%, P < 0.01) than patients treated with percutaneous coronary intervention (PCI) only. Moreover, in patients undergoing PCI, high adherence to P2Y12 antagonists decreased the risk of MACE (hazard ratio = 0.172, 95% confidence interval: 0.039-0.763; P = 0.021). In conclusion, PCI-treated patients are more prone to remaining adherent to medications than CABG-treated patients. High adherence to P2Y12 antagonists was associated with lower risk of MACE.

A minimally invasive assay for individual assessment of the ATM/CHEK2/p53 pathway activity.

PubMed

Kabacik, Sylwia; Ortega-Molina, Ana; Efeyan, Alejo; Finnon, Paul; Bouffler, Simon; Serrano, Manuel; Badie, Christophe

2011-04-01

Ionizing radiation induces DNA Double-Strand Breaks (DSBs) which activate the ATM/CHEK2/p53 pathway leading to cell cycle arrest and apoptosis through transcription of genes including CDKN1A (p21) and BBC3 (PUMA). This pathway prevents genomic instability and tumorigenesis as demonstrated in heritable syndromes [e.g. Ataxia Telangiectasia (AT); Li-Fraumeni syndrome (LFS)]. Here, a simple assay based on gene expression in peripheral blood to measure accurately ATM/CHEK2/p53 pathway activity is described. The expression of p21, Puma and Sesn2 was determined in blood from mice with different gene copy numbers of Atm, Trp53 (p53), Chek2 or Arf and in human blood and mitogen stimulated T-lymphocyte (MSTL) cultures from AT, AT carriers, LFS patients, and controls, both before and after ex vivo ionizing irradiation. Mouse Atm/Chek2/p53 activity was highly dependent on the copy number of each gene except Arf. In human MSTL, an AT case, AT carriers and LFS patients showed responses distinct from healthy donors. The relationship between gene copy number and transcriptional induction upon radiation was linear for p21 and Puma and correlated well with cancer incidence in p53 variant mice. This reliable blood test provides an assay to determine ATM/CHEK2/p53 pathway activity and demonstrates the feasibility of assessing the activity of this essential cancer protection pathway in simple assays. These findings may have implications for the individualized prediction of cancer susceptibility.

Variability in Anxiety for Teaching Mathematics among Pre-service Elementary School Teachers Enrolled in a Mathematics Course.

ERIC Educational Resources Information Center

Levine, Gavrielle

This investigation traced changes in anxiety for teaching mathematics (ATM) among pre-service elementary school teachers (n=36) enrolled in a mathematics methods course by analyzing their weekly journal entries. Journal entries were coded for high level of ATM (ATM-high) or absence of ATM (ATM-absent) during the first class session, as well as…

A Model Action Pla to Reduce the Use and Release of CFCs in Air- Conditioning and Refrigeration Systems

DTIC Science & Technology

1992-09-01

ccmpounds discussed in the research. Chiorofluorocarbon nolecules consist entirely of chlorine, fluorine, and carbon atoms. When a hydrogen atm is bonded...of carbon, hydrogen, and fluorine atoms contained in the compound. Chlorine atms miake up the remaining available bond sites. For exanple, CFC-l1...HCFC-22 has been successfully tested as a substitute for CFC-12 and CFC-502 in retrofitted supermarket refrigeration systems. There is same loss of

The Role of the DNA Damage Response in Breast Cancer

DTIC Science & Technology

2010-02-01

p53, ATM, Chk2, BRCA1, 53BP1, and MDC1 are mutated or inactivated in many human malignancies including breast cancer [6, 9-15]. ATM nullizygosity...receptor family of receptor tyrosine kinases, is amplified in 20-30% of human breast cancers [32, 33]. The genes encoding ErbB1, ErbB3, and insulin-like...engender a robust DDR that has been previously observed in human breast clinical samples but not in established mouse models of mammary cancer

NPP ATMS Prelaunch Performance Assessment and Sensor Data Record Validation

DTIC Science & Technology

2011-04-29

TMS to sense scattering of cold cosmic background radiance from the tops of preci pitating clouds allows the retrieval of preCipitation intensities...operational and research missions over the last 40 years. The Cross-track Infrared and Microwave Sounding Suite (CrIMSS), consisting of the Cross-track...Infrared Sounder (CrrS) and the flIst space-based, Nyquist-sampled cross-track microwave sounder, the Advanced Technology Microwave Sounder (ATMS), will

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

Kim, Byung Hak; Lee, Jun-Young; Seo, Jee Hee

Nuclear factor (NF)-{kappa}B regulates a central common signaling for immunity and cell survival. Artemisolide (ATM) was previously isolated as a NF-{kappa}B inhibitor from a plant of Artemisia asiatica. However, molecular basis of ATM on NF-{kappa}B activation remains to be defined. Here, we demonstrate that ATM is a typical inhibitor of I{kappa}B kinase {beta} (IKK{beta}), resulting in inhibition of lipopolysaccharide (LPS)-induced NF-{kappa}B activation in RAW 264.7 macrophages. ATM inhibited the kinase activity of highly purified IKK{beta} and also LPS-induced IKK activity in the cells. Moreover, the effect of ATM on IKK{beta} activity was completely abolished by substitution of Cys-179 residue ofmore » IKK{beta} to Ala residue, indicating direct targeting site of ATM. ATM could inhibit I{kappa}B{alpha} phosphorylation in LPS-activated RAW 264.7 cells and subsequently prevent NF-{kappa}B activation. Further, we demonstrate that ATM down-regulates NF-{kappa}B-dependent TNF-{alpha} expression. Taken together, this study provides a pharmacological potential of ATM in NF-{kappa}B-dependent inflammatory disorders.« less

CDRD and PNPR passive microwave precipitation retrieval algorithms: verification study over Africa and Southern Atlantic

NASA Astrophysics Data System (ADS)

Panegrossi, Giulia; Casella, Daniele; Cinzia Marra, Anna; Petracca, Marco; Sanò, Paolo; Dietrich, Stefano

2015-04-01

The ongoing NASA/JAXA Global Precipitation Measurement mission (GPM) requires the full exploitation of the complete constellation of passive microwave (PMW) radiometers orbiting around the globe for global precipitation monitoring. In this context the coherence of the estimates of precipitation using different passive microwave radiometers is a crucial need. We have developed two different passive microwave precipitation retrieval algorithms: one is the Cloud Dynamics Radiation Database algorithm (CDRD), a physically ¬based Bayesian algorithm for conically scanning radiometers (i.e., DMSP SSMIS); the other one is the Passive microwave Neural network Precipitation Retrieval (PNPR) algorithm for cross¬-track scanning radiometers (i.e., NOAA and MetOp¬A/B AMSU-¬A/MHS, and NPP Suomi ATMS). The algorithms, originally created for application over Europe and the Mediterranean basin, and used operationally within the EUMETSAT Satellite Application Facility on Support to Operational Hydrology and Water Management (H-SAF, http://hsaf.meteoam.it), have been recently modified and extended to Africa and Southern Atlantic for application to the MSG full disk area. The two algorithms are based on the same physical foundation, i.e., the same cloud-radiation model simulations as a priori information in the Bayesian solver and as training dataset in the neural network approach, and they also use similar procedures for identification of frozen background surface, detection of snowfall, and determination of a pixel based quality index of the surface precipitation retrievals. In addition, similar procedures for the screening of not ¬precipitating pixels are used. A novel algorithm for the detection of precipitation in tropical/sub-tropical areas has been developed. The precipitation detection algorithm shows a small rate of false alarms (also over arid/desert regions), a superior detection capability in comparison with other widely used screening algorithms, and it is applicable to all available PMW radiometers in the GPM constellation of satellites (including NPP Suomi ATMS, and GMI). Three years of SSMIS and AMSU/MHS data have been considered to carry out a verification study over Africa of the retrievals from the CDRD and PNPR algorithms. The precipitation products from the TRMM ¬Precipitation radar (PR) (TRMM product 2A25 and 2A23) have been used as ground truth. The results of this study aimed at assessing the accuracy of the precipitation retrievals in different climatic regions and precipitation regimes will be presented. Particular emphasis will be given to the analysis of the level of coherence of the precipitation estimates and patterns between the two algorithms exploiting different radiometers. Recent developments aimed at the full exploitation of the GPM constellation of satellites for optimal precipitation/drought monitoring will be also presented.

Progress Toward Standards for the Seamless Interoperability of Broadband Satellite Communication Networks

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Glover, Daniel R.; vonDeak, Thomas C.; Bhasin, Kul B.

1998-01-01

The realization of the full potential of the National Information Infrastructure (NH) and Global Information Infrastructure (GII) requires seamless interoperability of emerging satellite networks with terrestrial networks. This requires a cooperative effort between industry, academia and government agencies to develop and advocate new, satellite-friendly communication protocols and modifications to existing communication protocol standards. These groups have recently come together to actively participating in a number of standards making bodies including: the Internet Engineering Task Force (IETF), the Asynchronous Transfer Mode (ATM) Forum, the International Telecommunication Union (ITU) and the Telecommunication Industry Association MA) to ensure that issues regarding efficient use of these protocols over satellite links are not overlooked. This paper will summarize the progress made toward standards development to achieve seamless integration and accelerate the deployment of multimedia applications.

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

PubMed

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

2016-01-01

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

ATM and KAT5 safeguard replicating chromatin against formaldehyde damage

PubMed Central

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

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

PubMed

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.

Status of the Suomi-NPP VIIRS Moisture Products

NASA Astrophysics Data System (ADS)

Borbas, E. E.; Li, Z.; Menzel, W. P.; Rada, M.

2017-12-01

The goal of the Soumi NPP VIIRS Moisture Project is to provide total column water vapor (TPW) properties from merged VIIRS infrared measurements and CrIS plus ATMS water vapor soundings to continue the depiction of global moisture at high spatial resolution started with MODIS. While MODIS has two water vapor channels within the 6.5 μm H2O absorption band and four channels within the 15 μm CO2 absorption band, VIIRS has no channels in either IR absorption band. The VIIRS/CrIS+ATMS TPW algorithm being developed at CIMSS is similar to the MOD07 synthetic regression algorithm. It uses the three VIIRS longwave IR window bands in a regression relation and adds the NUCAPS (CrIS+ATMS) water vapor product to compensate for the absence of VIIRS water vapor channels. This poster presents the methodology and evaluation of the S-NPP TPW Level 2 and 3 products with TPW data from ground-based and satellite-based measurements.

Reactive system verification case study: Fault-tolerant transputer communication

NASA Technical Reports Server (NTRS)

Crane, D. Francis; Hamory, Philip J.

1993-01-01

A reactive program is one which engages in an ongoing interaction with its environment. A system which is controlled by an embedded reactive program is called a reactive system. Examples of reactive systems are aircraft flight management systems, bank automatic teller machine (ATM) networks, airline reservation systems, and computer operating systems. Reactive systems are often naturally modeled (for logical design purposes) as a composition of autonomous processes which progress concurrently and which communicate to share information and/or to coordinate activities. Formal (i.e., mathematical) frameworks for system verification are tools used to increase the users' confidence that a system design satisfies its specification. A framework for reactive system verification includes formal languages for system modeling and for behavior specification and decision procedures and/or proof-systems for verifying that the system model satisfies the system specifications. Using the Ostroff framework for reactive system verification, an approach to achieving fault-tolerant communication between transputers was shown to be effective. The key components of the design, the decoupler processes, may be viewed as discrete-event-controllers introduced to constrain system behavior such that system specifications are satisfied. The Ostroff framework was also effective. The expressiveness of the modeling language permitted construction of a faithful model of the transputer network. The relevant specifications were readily expressed in the specification language. The set of decision procedures provided was adequate to verify the specifications of interest. The need for improved support for system behavior visualization is emphasized.

Evaluation of airborne topographic lidar for quantifying beach changes

USGS Publications Warehouse

2003-01-01

A scanning airborne topographic lidar was evaluated for its ability to quantify beach topography and changes during the Sandy Duck experiment in 1997 along the North Carolina coast. Elevation estimates, acquired with NASA's Airborne Topographic Mapper (ATM), were compared to elevations measured with three types of ground-based mea- surements-1) differential GPS equipped all-terrain vehicle (ATV) that surveyed a 3-km reach of beach from the shoreline to the dune, 2) GPS antenna mounted on a stadia rod used to intensely survey a different 100 m reach of beach, and 3) a second GPS-equipped ATV that surveyed a 70-km-long transect along the coast. Over 40,000 individual intercomparisons between ATM and ground surveys were calculated. RMS vertical differences associated with the ATM when compared to ground measurements ranged from 13 to 19 cm. Considering all of the intercomparisons together, RMS ≃15 cm. This RMS error represents a total error for individual elevation estimates including uncertainties associated with random and mean errors. The latter was the largest source of error and was attributed to drift in differential GPS. The ≃15cm vertical accuracy of the ATM is adequate to resolve beach-change signals typical of the impact of storms. For example, ATM surveys of Assateague Island (spanning the border of MD and VA) prior to and immediately following a severe northeaster showed vertical beach changes in places greater than 2 m, much greater than expected errors associated with the ATM. A major asset of airborne lidar is the high spatial data density. Measurements of elevation are acquired every few m2 over regional scales of hundreds of kilometers. Hence, many scales of beach morphology and change can be resolved, from beach cusps tens of meters in wavelength to entire coastal cells com- prising tens to hundreds of kilometers of coast. Topographic lidars similar to the ATM are becoming increasingly available from commercial vendors and should, in the future, be widely used in beach su

Evaluation of airborne topographic lidar for quantifying beach changes

USGS Publications Warehouse

Sallenger, A.H.; Krabill, W.B.; Swift, R.N.; Brock, J.; List, J.; Hansen, M.; Holman, R.A.; Manizade, S.; Sontag, J.; Meredith, A.; Morgan, K.; Yunkel, J.K.; Frederick, E.B.; Stockdon, H.

2003-01-01

A scanning airborne topographic lidar was evaluated for its ability to quantify beach topography and changes during the Sandy Duck experiment in 1997 along the North Carolina coast. Elevation estimates, acquired with NASA's Airborne Topographic Mapper (ATM), were compared to elevations measured with three types of ground-based measurements - 1) differential GPS equipped all-terrain vehicle (ATV) that surveyed a 3-km reach of beach from the shoreline to the dune, 2) GPS antenna mounted on a stadia rod used to intensely survey a different 100 m reach of beach, and 3) a second GPS-equipped ATV that surveyed a 70-km-long transect along the coast. Over 40,000 individual intercomparisons between ATM and ground surveys were calculated. RMS vertical differences associated with the ATM when compared to ground measurements ranged from 13 to 19 cm. Considering all of the intercomparisons together, RMS ??? 15 cm. This RMS error represents a total error for individual elevation estimates including uncertainties associated with random and mean errors. The latter was the largest source of error and was attributed to drift in differential GPS. The ??? 15 cm vertical accuracy of the ATM is adequate to resolve beach-change signals typical of the impact of storms. For example, ATM surveys of Assateague Island (spanning the border of MD and VA) prior to and immediately following a severe northeaster showed vertical beach changes in places greater than 2 m, much greater than expected errors associated with the ATM. A major asset of airborne lidar is the high spatial data density. Measurements of elevation are acquired every few m2 over regional scales of hundreds of kilometers. Hence, many scales of beach morphology and change can be resolved, from beach cusps tens of meters in wavelength to entire coastal cells comprising tens to hundreds of kilometers of coast. Topographic lidars similar to the ATM are becoming increasingly available from commercial vendors and should, in the future, be widely used in beach surveying.

DNA Repair Defects and Chromosomal Aberrations

NASA Technical Reports Server (NTRS)

Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

2009-01-01

Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of the DNA repair-defective cell lines were smaller than those of normal cells, with the DNA-PK-deficient cells having RBEs near unity. To further investigate the sensitivity differences that were observed in ATM and NBS deficient cells, chromosomal aberrations were analyzed in normal lung fibroblast cells treated with KU-55933 (a specific ATM kinase inhibitor) or Mirin (an Mre11- Rad50-Nbs1 complex inhibitor involved in activation of ATM). We also performed siRNA knockdown of these proteins. Preliminary data indicate that chromosome exchanges increase in cells treated with the specific ATM inhibitor. Possible cytogenetic signatures of acute and low dose-rate gamma irradiation in ATM or nibrin deficient and suppressed cells will be discussed.

Identification of ATM Protein Kinase Phosphorylation Sites by Mass Spectrometry.

PubMed

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.

PubMed

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.

Ocean acidification narrows the acute thermal and salinity tolerance of the Sydney rock oyster Saccostrea glomerata.

PubMed

Parker, Laura M; Scanes, Elliot; O'Connor, Wayne A; Coleman, Ross A; Byrne, Maria; Pörtner, Hans-O; Ross, Pauline M

2017-09-15

Coastal and estuarine environments are characterised by acute changes in temperature and salinity. Organisms living within these environments are adapted to withstand such changes, yet near-future ocean acidification (OA) may challenge their physiological capacity to respond. We tested the impact of CO 2 -induced OA on the acute thermal and salinity tolerance, energy metabolism and acid-base regulation capacity of the oyster Saccostrea glomerata. Adult S. glomerata were acclimated to three CO 2 levels (ambient 380μatm, moderate 856μatm, high 1500μatm) for 5weeks (24°C, salinity 34.6) before being exposed to a series of acute temperature (15-33°C) and salinity (34.2-20) treatments. Oysters acclimated to elevated CO 2 showed a significant metabolic depression and extracellular acidosis with acute exposure to elevated temperature and reduced salinity, especially at the highest CO 2 of 1500μatm. Our results suggest that the acute thermal and salinity tolerance of S. glomerata and thus its distribution will reduce as OA continues to worsen. Copyright © 2017 Elsevier Ltd. All rights reserved.

ATR- and ATM-Mediated DNA Damage Response Is Dependent on Excision Repair Assembly during G1 but Not in S Phase of Cell Cycle.

PubMed

Ray, Alo; Blevins, Chessica; Wani, Gulzar; Wani, Altaf A

2016-01-01

Cell cycle checkpoint is mediated by ATR and ATM kinases, as a prompt early response to a variety of DNA insults, and culminates in a highly orchestrated signal transduction cascade. Previously, we defined the regulatory role of nucleotide excision repair (NER) factors, DDB2 and XPC, in checkpoint and ATR/ATM-dependent repair pathway via ATR and ATM phosphorylation and recruitment to ultraviolet radiation (UVR)-induced damage sites. Here, we have dissected the molecular mechanisms of DDB2- and XPC- mediated regulation of ATR and ATM recruitment and activation upon UVR exposures. We show that the ATR and ATM activation and accumulation to UVR-induced damage not only depends on DDB2 and XPC, but also on the NER protein XPA, suggesting that the assembly of an active NER complex is essential for ATR and ATM recruitment. ATR and ATM localization and H2AX phosphorylation at the lesion sites occur as early as ten minutes in asynchronous as well as G1 arrested cells, showing that repair and checkpoint-mediated by ATR and ATM starts early upon UV irradiation. Moreover, our results demonstrated that ATR and ATM recruitment and H2AX phosphorylation are dependent on NER proteins in G1 phase, but not in S phase. We reasoned that in G1 the UVR-induced ssDNA gaps or processed ssDNA, and the bound NER complex promote ATR and ATM recruitment. In S phase, when the UV lesions result in stalled replication forks with long single-stranded DNA, ATR and ATM recruitment to these sites is regulated by different sets of proteins. Taken together, these results provide evidence that UVR-induced ATR and ATM recruitment and activation differ in G1 and S phases due to the existence of distinct types of DNA lesions, which promote assembly of different proteins involved in the process of DNA repair and checkpoint activation.

ATM CMG/EPEA

NASA Technical Reports Server (NTRS)

Abramowitz, R.; Kovek, J.; Teimer, W.; Haddad, S. P.

1975-01-01

The Apollo Telescope mount double gimballed control moment gyro ATM CMG is described. Photographs of the CMG and its subassemblies are presented along with a functional block diagram of the CMG subsystem. Analog processing electronics for ATM vehicle pointing control and ATM experiment package pointing control are also described.

ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis.

PubMed

Takagi, Masatoshi; Uno, Hatsume; Nishi, Rina; Sugimoto, Masataka; Hasegawa, Setsuko; Piao, Jinhua; Ihara, Norimasa; Kanai, Sayaka; Kakei, Saori; Tamura, Yoshifumi; Suganami, Takayoshi; Kamei, Yasutomi; Shimizu, Toshiaki; Yasuda, Akio; Ogawa, Yoshihiro; Mizutani, Shuki

2015-02-11

Ataxia-telangiectasia (A-T) patients occasionally develop diabetes mellitus. However, only limited attempts have been made to gain insight into the molecular mechanism of diabetes mellitus development in A-T patients. We found that Atm -/- mice were insulin resistant and possessed less subcutaneous adipose tissue as well as a lower level of serum adiponectin than Atm +/+ mice. Furthermore, in vitro studies revealed impaired adipocyte differentiation in Atm -/- cells caused by the lack of induction of C/EBPα and PPARγ, crucial transcription factors involved in adipocyte differentiation. Interestingly, ATM was activated by stimuli that induced differentiation, and the binding of ATM to C/EBPβ and p300 was involved in the transcriptional regulation of C/EBPα and adipocyte differentiation. Thus, our study sheds light on the poorly understood role of ATM in the pathogenesis of glucose intolerance in A-T patients and provides insight into the role of ATM in glucose metabolism. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Reinvestigation of the Henry's law constant for hydrogen peroxide with temperature and acidity variation.

PubMed

Huang, Daoming; Chen, Zhongming

2010-01-01

Hydrogen peroxide is not only an important oxidant in itself; it also serves as both sink and temporary reservoir for other important oxidants including HOx (OH and HO2) radicals and O3 in the atmosphere. Its partitioning between gas and aqueous phases in the atmosphere, usually described by its Henry's law constant (K(H)), significantly influences its role in atmospheric processes. Large discrepancies between the K(H) values reported in previous work, however, have created uncertainty for atmospheric modelers. Based on our newly developed online instrumentation, we have re-determined the temperature and acidity dependence of K(H) for hydrogen peroxide at an air pressure of (0.960 +/- 0.013) atm (1 atm = 1.01325 x 10(5) Pa). The results indicated that the temperature dependence of K(H) for hydrogen peroxide fits to the Van't Hoff equation form, expressed as lnK(H) = a/T - b, and a = -deltaH/R, where K(H) is in M/atm (M is mol/L), T is in degrees Kelvin, R is the ideal gas constant, and deltaH is the standard heat of solution. For acidity dependence, results demonstrated that the K(H) value of hydrogen peroxide appeared to have no obvious dependence on decreasing pH level (from pH 7 to pH 1). Combining the dependence of both temperature and acidity, the obtained a and b were 7024 +/- 138 and 11.97 +/- 0.48, respectively, deltaH was (58.40 +/- 1.15) kJ/(K x mol), and the uncertainties represent sigma. Our determined K(H) values for hydrogen peroxide will therefore be of great use in atmospheric models.

Radiative absorption enhancement of dust mixed with anthropogenic pollution over East Asia

NASA Astrophysics Data System (ADS)

Tian, Pengfei; Zhang, Lei; Ma, Jianmin; Tang, Kai; Xu, Lili; Wang, Yuan; Cao, Xianjie; Liang, Jiening; Ji, Yuemeng; Jiang, Jonathan H.; Yung, Yuk L.; Zhang, Renyi

2018-06-01

The particle mixing state plays a significant yet poorly quantified role in aerosol radiative forcing, especially for the mixing of dust (mineral absorbing) and anthropogenic pollution (black carbon absorbing) over East Asia. We have investigated the absorption enhancement of mixed-type aerosols over East Asia by using the Aerosol Robotic Network observations and radiative transfer model calculations. The mixed-type aerosols exhibit significantly enhanced absorbing ability than the corresponding unmixed dust and anthropogenic aerosols, as revealed in the spectral behavior of absorbing aerosol optical depth, single scattering albedo, and imaginary refractive index. The aerosol radiative efficiencies for the dust, mixed-type, and anthropogenic aerosols are -101.0, -112.9, and -98.3 Wm-2 τ-1 at the bottom of the atmosphere (BOA); -42.3, -22.5, and -39.8 Wm-2 τ-1 at the top of the atmosphere (TOA); and 58.7, 90.3, and 58.5 Wm-2 τ-1 in the atmosphere (ATM), respectively. The BOA cooling and ATM heating efficiencies of the mixed-type aerosols are significantly higher than those of the unmixed aerosol types over the East Asia region, resulting in atmospheric stabilization. In addition, the mixed-type aerosols correspond to a lower TOA cooling efficiency, indicating that the cooling effect by the corresponding individual aerosol components is partially counteracted. We conclude that the interaction between dust and anthropogenic pollution not only represents a viable aerosol formation pathway but also results in unfavorable dispersion conditions, both exacerbating the regional air pollution in East Asia. Our results highlight the necessity to accurately account for the mixing state of aerosols in atmospheric models over East Asia in order to better understand the formation mechanism for regional air pollution and to assess its impacts on human health, weather, and climate.

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

PubMed

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.

Global Interoperability of High Definition Video Streams Via ACTS and Intelsat

NASA Technical Reports Server (NTRS)

Hsu, Eddie; Wang, Charles; Bergman, Larry; Pearman, James; Bhasin, Kul; Clark, Gilbert; Shopbell, Patrick; Gill, Mike; Tatsumi, Haruyuki; Kadowaki, Naoto

2000-01-01

In 1993, a proposal at the Japan.-U.S. Cooperation in Space Program Workshop lead to a subsequent series of satellite communications experiments and demonstrations, under the title of Trans-Pacific High Data Rate Satellite Communications Experiments. The first of which is a joint collaboration between government and industry teams in the United States and Japan that successfully demonstrated distributed high definition video (HDV) post-production on a global scale using a combination of high data rate satellites and terrestrial fiber optic asynchronous transfer mode (ATM) networks. The HDV experiment is the first GIBN experiment to establish a dual-hop broadband satellite link for the transmission of digital HDV over ATM. This paper describes the team's effort in using the NASA Advanced Communications Technology Satellite (ACTS) at rates up to OC-3 (155 Mbps) between Los Angeles and Honolulu, and using Intelsat at rates up to DS-3 (45 Mbps) between Kapolei and Tokyo, with which HDV source material was transmitted between Sony Pictures High Definition Center (SPHDC) in Los Angeles and Sony Visual Communication Center (VCC) in Shinagawa, Tokyo. The global-scale connection also used terrestrial networks in Japan, the States of Hawaii and California. The 1.2 Gbps digital HDV stream was compressed down to 22.5 Mbps using a proprietary Mitsubishi MPEG-2 codec that was ATM AAL-5 compatible. The codec: employed four-way parallel processing. Improved versions of the codec are now commercially available. The successful post-production activity performed in Tokyo with a HDV clip transmitted from Los Angeles was predicated on the seamless interoperation of all the equipment between the sites, and was an exciting example in deploying a global-scale information infrastructure involving a combination of broadband satellites and terrestrial fiber optic networks. Correlation of atmospheric effects with cell loss, codec drop-out, and picture quality were made. Current efforts in the Trans-Pacific series plan to examine the use of Internet Protocol (IP)-related technologies over such an infrastructure. The use of IP allows the general public to be an integral part of the exciting activities, helps to examine issues in constructing the solar-system internet, and affords an opportunity to tap the research results from the (reliable) multicast and distributed systems communities. The current Trans- Pacific projects, including remote astronomy and digital library (visible human) are briefly described.

Using ATM laser altimetry to constrain surface mass balance estimates and supraglacial hydrology of the Greenland Ice Sheet

NASA Astrophysics Data System (ADS)

Studinger, M.; Medley, B.; Manizade, S.; Linkswiler, M. A.

2016-12-01

Repeat airborne laser altimetry measurements can provide large-scale field observations to better quantify spatial and temporal variability of surface processes contributing to seasonal elevation change and therefore surface mass balance. As part of NASA's Operation IceBridge the Airborne Topographic Mapper (ATM) laser altimeter measured the surface elevation of the Greenland Ice Sheet during spring (March - May) and fall (September - October) of 2015. Comparison of the two surveys reveals a general trend of thinning for outlet glaciers and for the ice sheet in a manner related to elevation and latitude. In contrast, some thickening is observed on the west (but not on the east) side of the ice divide above 2200 m elevation in the southern half, below latitude 69°N.The observed magnitude and spatial patterns of the summer melt signal can be utilized as input into ice sheet models and for validating reanalysis of regional climate models such as RACMO and MAR. We use seasonal anomalies in MERRA-2 climate fields (temperature, precipitation) to understand the observed spatial signal in seasonal change. Aside from surface elevation change, runoff from meltwater pooling in supraglacial lakes and meltwater channels accounts for at least half of the total mass loss. The ability of the ATM laser altimeters to image glacial hydrological features in 3-D and determine the depth of supraglacial lakes could be used for process studies and for quantifying melt processes over large scales. The 1-meter footprint diameter of ATM laser on the surface, together with a high shot density, allows for the production of large-scale, high-resolution, geodetic quality DEMs (50 x 50 cm) suitable for fine-scale glacial hydrology research and as input to hydrological models quantifying runoff.

Requirement of ATR for maintenance of intestinal stem cells in aging Drosophila.

PubMed

Park, Joung-Sun; Na, Hyun-Jin; Pyo, Jung-Hoon; Jeon, Ho-Jun; Kim, Young-Shin; Yoo, Mi-Ae

2015-05-01

The stem cell genomic stability forms the basis for robust tissue homeostasis, particularly in high-turnover tissues. For the genomic stability, DNA damage response (DDR) is essential. This study was focused on the role of two major DDR-related factors, ataxia telangiectasia-mutated (ATM) and ATM- and RAD3-related (ATR) kinases, in the maintenance of intestinal stem cells (ISCs) in the adultDrosophila midgut. We explored the role of ATM and ATR, utilizing immunostaining with an anti-pS/TQ antibody as an indicator of ATM/ATR activation, γ-irradiation as a DNA damage inducer, and the UAS/GAL4 system for cell type-specific knockdown of ATM, ATR, or both during adulthood. The results showed that the pS/TQ signals got stronger with age and after oxidative stress. The pS/TQ signals were found to be more dependent on ATR rather than on ATM in ISCs/enteroblasts (EBs). Furthermore, an ISC/EB-specific knockdown of ATR, ATM, or both decreased the number of ISCs and oxidative stress-induced ISC proliferation. The phenotypic changes that were caused by the ATR knockdown were more pronounced than those caused by the ATM knockdown; however, our data indicate that ATR and ATM are both needed for ISC maintenance and proliferation; ATR seems to play a bigger role than does ATM.

Novel targets for ATM-deficient malignancies

PubMed Central

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

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

NASA Astrophysics Data System (ADS)

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.

MOF phosphorylation by ATM regulates 53BP1-mediated double-strand break repair pathway choice.

PubMed

Gupta, Arun; Hunt, Clayton R; Hegde, Muralidhar L; Chakraborty, Sharmistha; Chakraborty, Sharmistha; Udayakumar, Durga; Horikoshi, Nobuo; Singh, Mayank; Ramnarain, Deepti B; Hittelman, Walter N; Namjoshi, Sarita; Asaithamby, Aroumougame; Hazra, Tapas K; Ludwig, Thomas; Pandita, Raj K; Tyler, Jessica K; Pandita, Tej K

2014-07-10

Cell-cycle phase is a critical determinant of the choice between DNA damage repair by nonhomologous end-joining (NHEJ) or homologous recombination (HR). Here, we report that double-strand breaks (DSBs) induce ATM-dependent MOF (a histone H4 acetyl-transferase) phosphorylation (p-T392-MOF) and that phosphorylated MOF colocalizes with γ-H2AX, ATM, and 53BP1 foci. Mutation of the phosphorylation site (MOF-T392A) impedes DNA repair in S and G2 phase but not G1 phase cells. Expression of MOF-T392A also blocks the reduction in DSB-associated 53BP1 seen in wild-type S/G2 phase cells, resulting in enhanced 53BP1 and reduced BRCA1 association. Decreased BRCA1 levels at DSB sites correlates with defective repairosome formation, reduced HR repair, and decreased cell survival following irradiation. These data support a model whereby ATM-mediated MOF-T392 phosphorylation modulates 53BP1 function to facilitate the subsequent recruitment of HR repair proteins, uncovering a regulatory role for MOF in DSB repair pathway choice during S/G2 phase. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2016-01-01

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. PMID:27503884

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

PubMed

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.

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

PubMed

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.

Obesity alters adipose tissue macrophage iron content and tissue iron distribution.

PubMed

Orr, Jeb S; Kennedy, Arion; Anderson-Baucum, Emily K; Webb, Corey D; Fordahl, Steve C; Erikson, Keith M; Zhang, Yaofang; Etzerodt, Anders; Moestrup, Søren K; Hasty, Alyssa H

2014-02-01

Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFe(hi), and the remaining ATMs are referred to as MFe(lo). In lean mice, ~25% of the ATMs are MFe(hi); this percentage decreases in obesity owing to the recruitment of MFe(lo) macrophages. Similar to MFe(lo) cells, MFe(hi) ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFe(hi) ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFe(hi) iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFe(hi) ATM phenotype and their reduced capacity to handle iron.

Low expression levels of ATM may substitute for CHEK2 /TP53 mutations predicting resistance towards anthracycline and mitomycin chemotherapy in breast cancer.

PubMed

Knappskog, Stian; Chrisanthar, Ranjan; Løkkevik, Erik; Anker, Gun; Østenstad, Bjørn; Lundgren, Steinar; Risberg, Terje; Mjaaland, Ingvil; Leirvaag, Beryl; Miletic, Hrvoje; Lønning, Per E

2012-03-15

Mutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in response to genotoxic stress. Here, we sought to evaluate ATM's potential role in resistance to chemotherapy. We sequenced ATM and assessed gene expression levels in pre-treatment biopsies from 71 locally advanced breast cancers treated in the neoadjuvant setting with doxorubicin monotherapy or mitomycin combined with 5-fluorouracil. Findings were confirmed in a separate patient cohort treated with epirubicin monotherapy. Each tumor was previously analyzed for CHEK2 and TP53 mutation status. While ATM mutations were not associated with chemo-resistance, low ATM expression levels predicted chemo-resistance among patients with tumors wild-type for TP53 and CHEK2 (P = 0.028). Analyzing the ATM-chk2-p53 cascade, low ATM levels (defined as the lower 5 to 50% percentiles) or mutations inactivating TP53 or CHEK2 robustly predicted anthracycline resistance (P-values varying between 0.001 and 0.027 depending on the percentile used to define "low" ATM levels). These results were confirmed in an independent cohort of 109 patients treated with epirubicin monotherapy. In contrast, ATM-levels were not suppressed in resistant tumors harboring TP53 or CHEK2 mutations (P > 0.5). Our data indicate loss of function of the ATM-Chk2-p53 cascade to be strongly associated with resistance to anthracycline/mitomycin-containing chemotherapy in breast cancer.

Antibiogram of bacteria isolated from automated teller machines in Hamadan, West Iran

PubMed Central

Mahmoudi, Hassan; Arabestani, Mohammad Reza; Alikhani, Mohammad Yousef; Sedighi, Iraj; Kohan, Hamed Farhadi; Molavi, Mohammad

2017-01-01

Aim: Bacteria are ubiquitous in the environment. In keeping with the continued expansion of urbanization and the growing population, an increasing number of people use automated banking, i.e. automated teller machines (ATMs). The aim of this study was to investigate the bacterial contamination and its antibiotic sensitivity on computer keyboards located at ATMs in Hamadan province, Iran. Method: Out of 360 ATMs at four locations in Hamadan, 96 were randomly selected for this study. The antibiotic susceptibility pattern of all isolates was determined by the agar disk diffusion method using gentamicin (10 µg), vancomycin (30 µg), trimethoprim/sulfamethoxazole (25 µg), amikacin (30 µg), tobramycin (10 µg), cephalotin (30 µg), norfloxacin (5 µg), and ceftizoxim (30 µg) disks. Results: Melli and Saderat Banks had the most frequently contaminated ATMS, with 18 (27.7%) and 12 (18.5%), respectively. The most frequently isolated bacteria were Staphylococcus epidermidis in 12 (18.5%) ATMs, Pseudomonas aeruginosa in 12 (18.5%), Bacillus subtilis in 11 (16.9%), Escherichia coli in 6 (9.2%), Klebsiella spp. in 8 (12.3%), Enterobacter spp. in 2 (3.1%), Bacillus cereus in 6 (9.2%), Staphylococcus aureus in 3 (4.6%), and Micrococcaceae spp. in 5 (7.69%) cases. All isolated bacteria were susceptible to gentamicin, cephalotin, tobramycin, amikacin, norfloxacin, and vancomycin. The S. aureus resistance rate to trimethoprim/sulfamethoxazole was 50%. Conclusion: All tested ATM keyboards were contaminated with at least one species of bacteria. Based on these findings, it is recommendable to disinfect the hands after entering one’s own apartment, work area or a hospital, in order to hinder the spread of critical pathogens in the personal environment or in the hospital. PMID:28197394

Develop Advanced Nonlinear Signal Analysis Topographical Mapping System

NASA Technical Reports Server (NTRS)

Jong, Jen-Yi

1997-01-01

During the development of the SSME, a hierarchy of advanced signal analysis techniques for mechanical signature analysis has been developed by NASA and AI Signal Research Inc. (ASRI) to improve the safety and reliability for Space Shuttle operations. These techniques can process and identify intelligent information hidden in a measured signal which is often unidentifiable using conventional signal analysis methods. Currently, due to the highly interactive processing requirements and the volume of dynamic data involved, detailed diagnostic analysis is being performed manually which requires immense man-hours with extensive human interface. To overcome this manual process, NASA implemented this program to develop an Advanced nonlinear signal Analysis Topographical Mapping System (ATMS) to provide automatic/unsupervised engine diagnostic capabilities. The ATMS will utilize a rule-based Clips expert system to supervise a hierarchy of diagnostic signature analysis techniques in the Advanced Signal Analysis Library (ASAL). ASAL will perform automatic signal processing, archiving, and anomaly detection/identification tasks in order to provide an intelligent and fully automated engine diagnostic capability. The ATMS has been successfully developed under this contract. In summary, the program objectives to design, develop, test and conduct performance evaluation for an automated engine diagnostic system have been successfully achieved. Software implementation of the entire ATMS system on MSFC's OISPS computer has been completed. The significance of the ATMS developed under this program is attributed to the fully automated coherence analysis capability for anomaly detection and identification which can greatly enhance the power and reliability of engine diagnostic evaluation. The results have demonstrated that ATMS can significantly save time and man-hours in performing engine test/flight data analysis and performance evaluation of large volumes of dynamic test data.

Performance Evaluation of Communication Software Systems for Distributed Computing

NASA Technical Reports Server (NTRS)

Fatoohi, Rod

1996-01-01

In recent years there has been an increasing interest in object-oriented distributed computing since it is better quipped to deal with complex systems while providing extensibility, maintainability, and reusability. At the same time, several new high-speed network technologies have emerged for local and wide area networks. However, the performance of networking software is not improving as fast as the networking hardware and the workstation microprocessors. This paper gives an overview and evaluates the performance of the Common Object Request Broker Architecture (CORBA) standard in a distributed computing environment at NASA Ames Research Center. The environment consists of two testbeds of SGI workstations connected by four networks: Ethernet, FDDI, HiPPI, and ATM. The performance results for three communication software systems are presented, analyzed and compared. These systems are: BSD socket programming interface, IONA's Orbix, an implementation of the CORBA specification, and the PVM message passing library. The results show that high-level communication interfaces, such as CORBA and PVM, can achieve reasonable performance under certain conditions.

Assessment of Glacial Isostatic Adjustment in Greenland using GPS

NASA Astrophysics Data System (ADS)

Khan, S. A.; Bevis, M. G.; Sasgen, I.; van Dam, T. M.; Wahr, J. M.; Wouters, B.; Bamber, J. L.; Willis, M. J.; Knudsen, P.; Helm, V.; Kuipers Munneke, P.; Muresan, I. S.

2015-12-01

The Greenland GPS network (GNET) was constructed to provide a new means to assess viscoelastic and elastic adjustments driven by past and present-day changes in ice mass. Here we assess existing glacial isostatic adjustments (GIA) predictions by analysing 1995-2015 data from 61 continuous GPS receivers located along the margin of the Greenland ice sheet. Since GPS receivers measure both the GIA and elastic signals, we isolate GIA, by removing the elastic adjustments of the lithosphere due to present-day mass changes using high-resolution fields of ice surface elevation change derived from satellite and airborne altimetry measurements (ERS1/2, ICESat, ATM, ENVISAT, and CryoSat-2). For most GPS stations, our observed GIA rates contradict GIA predictions; particularly, we find huge uplift rates in southeast Greenland of up to 14 mm/yr while models predict rates of 0-2 mm/yr. Our results suggest possible improvements of GIA predictions, and hence of the poorly constrained ice load history and Earth structure models for Greenland.

Future ATM Concepts Evaluation Tool (FACET) Interface Control Document

NASA Technical Reports Server (NTRS)

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 from the National Weather Service to summarize NAS performance. This information allows system operators to reroute flights around congested airspace and severe weather to maintain safety and minimize delay. FACET also supports the planning and post-operational evaluation of reroute strategies at the national level to maximize system efficiency. For the commercial airline passenger, strategic planning with FACET can result in fewer flight delays and cancellations. The performance capabilities of FACET are largely due to its architecture, which strikes a balance between flexibility and fidelity. FACET is capable of modeling the airspace operations for the continental United States, processing thousands of aircraft on a single computer. FACET was written in Java and C, enabling the portability of its software to a variety of operating systems. In addition, FACET was designed with a modular software architecture to facilitate rapid prototyping of diverse ATM concepts. Several advanced ATM concepts have already been implemented in FACET, including aircraft self-separation, prediction of aircraft demand and sector congestion, system-wide impact assessment of traffic flow management constraints, and wind-optimal routing.

ATM/cable arch and beam structural test program

NASA Technical Reports Server (NTRS)

Housley, J. A.

1972-01-01

The structural testing is described of an Apollo Telescope Mount (ATM) cable arch and beam assembly, using static loads to simulate the critical conditions expected during transportation and launch of the ATM. All test objectives were met. Stress and deflection data show that the assembly is structurally adequate for use in the ATM.

Scenarios for control and data flows in multiprotocol over ATM

NASA Astrophysics Data System (ADS)

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.

Assimilation of all-weather GMI and ATMS observations into HWRF

NASA Astrophysics Data System (ADS)

Moradi, I.; Evans, F.; McCarty, W.; Marks, F.; Eriksson, P.

2017-12-01

We propose a novel Bayesian Monte Carlo Integration (BMCI) technique to retrieve the profiles of temperature, water vapor, and cloud liquid/ice water content from microwave cloudy measurements in the presence of TCs. These retrievals then can either be directly used by meteorologists to analyze the structure of TCs or be assimilated to provide accurate initial conditions for the NWP models. The technique is applied to the data from the Advanced Technology Microwave Sounder (ATMS) onboard Suomi National Polar-orbiting Partnership (NPP) and Global Precipitation Measurement (GPM) Microwave Imager (GMI).

Protocol and Topology Issues for Wide-Area Satellite Interconnection of Terrestrial Optical LANs

NASA Astrophysics Data System (ADS)

Parraga, N.

2002-01-01

Apart from broadcasting, the satellite business is targeting niche markets. Wide area interconnection is considered as one of these niche markets, since it addresses operators and business LANs (B2B, business to business) in remote areas where terrestrial infrastructure is not available. These LANs - if high-speed - are typically based on optical networks such as SONET. One of the advantages of SONET is its architecture flexibility and capacity to transport all kind of applications including multimedia with a range of different transmission rates. The applications can be carried by different protocols among which the Internet Protocol (IP) or the Asynchronous Transfer Mode (ATM) are the most prominent ones. Thus, the question arises how these protocols can be interconnected via the satellite segment. The paper addresses several solutions for interworking with different protocols. For this investigation we distinguish first of all between the topology and the switching technology of the satellites. In case of a star network with transparent satellite, the satellite protocol consists of physical layer and data layer which can be directly interconnected with layer 2 interworking function to their terrestrial counterparts in the SONET backbone. For regenerative satellites the situation is more complex: here we need to distinguish the types of transport protocols being used in the terrestrial and satellite segment. Whereas IP, ATM, MPEG dominate in the terrestrial networks, satellite systems usually do not follow these standards. Some might employ minor additions (for instance, satellite specific packet headers), some might be completely proprietary. In general, interworking must be done for the data plane on top of layer 2 (data link layer), whereas for the signaling plane the interworking is on top of layer 3. In the paper we will discuss the protocol stacks for ATM, IP, and MPEG with a regenerative satellite system. As an example we will use the EuroSkyWay satellite system for multimedia services. EuroSkyWay uses a GEO satellite with onboard switching. It has its own proprietary protocol stack for data link control (DLC), logical link control (LLC) and layer 3 functions such as resource management, call admission control and authentication. Special attention is paid to the IP interworking with Layer 3 function since IP does not support connection set-up and session protocols, thus proper interworking functions with IP signaling protocols for resource reservation routing such as RSVP, BGP, and ICMP need to be developed. Whereas the EuroSkyWay system is an representative for a meshed topology, DVB-RCS systems have usually star configuration with a central hub station. Different data streams are distinguished by program identifiers (PIDs). Recent proposals aim at the evolution of DVB-RCS towards a fully meshed structure. The paper will also discuss the protocol architecture for interconnect SONET LANs over these systems. Finally, a performance comparison of the different solutions will be given in terms of cell overhead rate and signalling effort for selected scenarios.

DNA Damage Signaling Is Induced in the Absence of Epstein-Barr Virus (EBV) Lytic DNA Replication and in Response to Expression of ZEBRA.

PubMed

Wang'ondu, Ruth; Teal, Stuart; Park, Richard; Heston, Lee; Delecluse, Henri; Miller, George

2015-01-01

Epstein Barr virus (EBV), like other oncogenic viruses, modulates the activity of cellular DNA damage responses (DDR) during its life cycle. Our aim was to characterize the role of early lytic proteins and viral lytic DNA replication in activation of DNA damage signaling during the EBV lytic cycle. Our data challenge the prevalent hypothesis that activation of DDR pathways during the EBV lytic cycle occurs solely in response to large amounts of exogenous double stranded DNA products generated during lytic viral DNA replication. In immunofluorescence or immunoblot assays, DDR activation markers, specifically phosphorylated ATM (pATM), H2AX (γH2AX), or 53BP1 (p53BP1), were induced in the presence or absence of viral DNA amplification or replication compartments during the EBV lytic cycle. In assays with an ATM inhibitor and DNA damaging reagents in Burkitt lymphoma cell lines, γH2AX induction was necessary for optimal expression of early EBV genes, but not sufficient for lytic reactivation. Studies in lytically reactivated EBV-positive cells in which early EBV proteins, BGLF4, BGLF5, or BALF2, were not expressed showed that these proteins were not necessary for DDR activation during the EBV lytic cycle. Expression of ZEBRA, a viral protein that is necessary for EBV entry into the lytic phase, induced pATM foci and γH2AX independent of other EBV gene products. ZEBRA mutants deficient in DNA binding, Z(R183E) and Z(S186E), did not induce foci of pATM. ZEBRA co-localized with HP1β, a heterochromatin associated protein involved in DNA damage signaling. We propose a model of DDR activation during the EBV lytic cycle in which ZEBRA induces ATM kinase phosphorylation, in a DNA binding dependent manner, to modulate gene expression. ATM and H2AX phosphorylation induced prior to EBV replication may be critical for creating a microenvironment of viral and cellular gene expression that enables lytic cycle progression.

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

PubMed Central

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

Climatic sensitivity, water-use efficiency, and growth decline in boreal jack pine (Pinus banksiana) forests in Northern Ontario

NASA Astrophysics Data System (ADS)

Dietrich, Rachel; Bell, F. Wayne; Silva, Lucas C. R.; Cecile, Alice; Horwath, William R.; Anand, Madhur

2016-10-01

Rises in atmospheric carbon dioxide (atmCO2) levels are known to stimulate photosynthesis and increase intrinsic water-use efficiency (iWUE) in trees. Stand-level increases in iWUE depend on the physiological response of dominant species to increases in atmCO2, while tree-level response to increasing atmCO2 depends on the balance between the direct effects of atmCO2 on photosynthetic rate and the indirect effects of atmCO2 on drought conditions. The aim of this study was to characterize the response of boreal jack pine (Pinus banksiana) stands in Northern Ontario to changes in atmCO2 and associated climatic change over the past 100 years. The impact of changes in growing season length, temperature, and precipitation, as well as atmCO2 on tree growth, was determined using stable carbon isotopes and dendrochronological analysis. Jack pine stands in this study were shown to be in progressive decline. As expected, iWUE was found to increase in association with rising atmCO2. However, increases in iWUE were not directly coupled with atmCO2, suggesting that the degree of iWUE improvement is limited by alternative factors. Water-use efficiency was negatively associated with tree growth, suggesting that warming- and drought-induced stomatal closure has likely led to deviations from expected atmCO2-enhanced growth. This finding corroborates that boreal forest stands are likely to face continued stress under future climatic warming.

Access to medicines from a health system perspective

PubMed Central

Bigdeli, Maryam; Jacobs, Bart; Tomson, Goran; Laing, Richard; Ghaffar, Abdul; Dujardin, Bruno; Van Damme, Wim

2013-01-01

Most health system strengthening interventions ignore interconnections between systems components. In particular, complex relationships between medicines and health financing, human resources, health information and service delivery are not given sufficient consideration. As a consequence, populations' access to medicines (ATM) is addressed mainly through fragmented, often vertical approaches usually focusing on supply, unrelated to the wider issue of access to health services and interventions. The objective of this article is to embed ATM in a health system perspective. For this purpose, we perform a structured literature review: we examine existing ATM frameworks, review determinants of ATM and define at which level of the health system they are likely to occur; we analyse to which extent existing ATM frameworks take into account access constraints at different levels of the health system. Our findings suggest that ATM barriers are complex and interconnected as they occur at multiple levels of the health system. Existing ATM frameworks only partially address the full range of ATM barriers. We propose three essential paradigm shifts that take into account complex and dynamic relationships between medicines and other components of the health system. A holistic view of demand-side constraints in tandem with consideration of multiple and dynamic relationships between medicines and other health system resources should be applied; it should be recognized that determinants of ATM are rooted in national, regional and international contexts. These are schematized in a new framework proposing a health system perspective on ATM. PMID:23174879

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

PubMed

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.

Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction.

PubMed

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.

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

PubMed

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

2017-08-01

To explore the clinicopathological significance of ATM gene in the occurrence and prognosis of gastric cancer (GC) from different nationalities in Xinjiang. The expression of ATM in 385 patients with GC (including 98 Uygurs, 231 Hans and 56 Kazaks) and its corresponding adjacent tissues were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry assay to, analyze its correlations with clinicopathological features and prognosis of GC. The ATM expression in GC tissues was significantly decreased when compared to that in adjacent normal tissues of Uygur, Han and Kazak patients in Xinjiang, while Uygurs and Kazaks were much lower than Hans in the ATM expression of GC tissues (all P<0.05). Kaplan-Meier analysis showed that Uygur and Kazak patients with ATM-negative tumors had a markedly lower survival rate than patients in Hans (P=0.028), and GC patients with ATM negative expression presented more unfavorable overall survival rate than those with positive expression among the three different nationalities (all P<0.05). Multivariate Cox regression analysis revealed that nationality, ATM expression, TNM staging, depth of invasion, and lymph node metastasis were independent factors affecting the prognosis of GC patients in Xinjiang (all P<0.05). ATM was downregulated in GC patients in Xinjiang, especially for Uygurs and Kazaks, which suggested ATM to be an independent indicator of prognosis for GC therapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

ATM regulates NF-κB-dependent immediate-early genes via RelA Ser 276 phosphorylation coupled to CDK9 promoter recruitment

PubMed Central

Fang, Ling; Choudhary, Sanjeev; Zhao, Yingxin; Edeh, Chukwudi B; Yang, Chunying; Boldogh, Istvan; Brasier, Allan R.

2014-01-01

Ataxia-telangiectasia mutated (ATM), a member of the phosphatidylinositol 3 kinase-like kinase family, is a master regulator of the double strand DNA break-repair pathway after genotoxic stress. Here, we found ATM serves as an essential regulator of TNF-induced NF-kB pathway. We observed that TNF exposure of cells rapidly induced DNA double strand breaks and activates ATM. TNF-induced ROS promote nuclear IKKγ association with ubiquitin and its complex formation with ATM for nuclear export. Activated cytoplasmic ATM is involved in the selective recruitment of the E3-ubiquitin ligase β-TrCP to phospho-IκBα proteosomal degradation. Importantly, ATM binds and activates the catalytic subunit of protein kinase A (PKAc), ribosmal S6 kinase that controls RelA Ser 276 phosphorylation. In ATM knockdown cells, TNF-induced RelA Ser 276 phosphorylation is significantly decreased. We further observed decreased binding and recruitment of the transcriptional elongation complex containing cyclin dependent kinase-9 (CDK9; a kinase necessary for triggering transcriptional elongation) to promoters of NF-κB-dependent immediate-early cytokine genes, in ATM knockdown cells. We conclude that ATM is a nuclear damage-response signal modulator of TNF-induced NF-κB activation that plays a key scaffolding role in IκBα degradation and RelA Ser 276 phosphorylation. Our study provides a mechanistic explanation of decreased innate immune response associated with A-T mutation. PMID:24957606

Modular and Stochastic Approaches to Molecular Pathway Models of ATM, TGF beta, and WNT Signaling

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; O'Neill, Peter; Ponomarev, Artem; Carra, Claudio; Whalen, Mary; Pluth, Janice M.

2009-01-01

Deterministic pathway models that describe the biochemical interactions of a group of related proteins, their complexes, activation through kinase, etc. are often the basis for many systems biology models. Low dose radiation effects present a unique set of challenges to these models including the importance of stochastic effects due to the nature of radiation tracks and small number of molecules activated, and the search for infrequent events that contribute to cancer risks. We have been studying models of the ATM, TGF -Smad and WNT signaling pathways with the goal of applying pathway models to the investigation of low dose radiation cancer risks. Modeling challenges include introduction of stochastic models of radiation tracks, their relationships to more than one substrate species that perturb pathways, and the identification of a representative set of enzymes that act on the dominant substrates. Because several pathways are activated concurrently by radiation the development of modular pathway approach is of interest.

Low expression levels of ATM may substitute for CHEK2 /TP53 mutations predicting resistance towards anthracycline and mitomycin chemotherapy in breast cancer

PubMed Central

2012-01-01

Introduction Mutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in response to genotoxic stress. Here, we sought to evaluate ATM's potential role in resistance to chemotherapy. Methods We sequenced ATM and assessed gene expression levels in pre-treatment biopsies from 71 locally advanced breast cancers treated in the neoadjuvant setting with doxorubicin monotherapy or mitomycin combined with 5-fluorouracil. Findings were confirmed in a separate patient cohort treated with epirubicin monotherapy. Each tumor was previously analyzed for CHEK2 and TP53 mutation status. Results While ATM mutations were not associated with chemo-resistance, low ATM expression levels predicted chemo-resistance among patients with tumors wild-type for TP53 and CHEK2 (P = 0.028). Analyzing the ATM-chk2-p53 cascade, low ATM levels (defined as the lower 5 to 50% percentiles) or mutations inactivating TP53 or CHEK2 robustly predicted anthracycline resistance (P-values varying between 0.001 and 0.027 depending on the percentile used to define "low" ATM levels). These results were confirmed in an independent cohort of 109 patients treated with epirubicin monotherapy. In contrast, ATM-levels were not suppressed in resistant tumors harboring TP53 or CHEK2 mutations (P > 0.5). Conclusions Our data indicate loss of function of the ATM-Chk2-p53 cascade to be strongly associated with resistance to anthracycline/mitomycin-containing chemotherapy in breast cancer. PMID:22420423

Design and mathematical analysis of a three-mirror X-ray telescope based on ATM S-056 X-ray telescope hardware

NASA Technical Reports Server (NTRS)

Foreman, J. W., Jr.; Cardone, J. M.

1973-01-01

The mathematical design of the aspheric third mirror for the three-mirror X-ray telescope (TMXRT) is presented, along with the imaging characteristics of the telescope obtained by a ray trace analysis. The present design effort has been directed entirely toward obtaining an aspheric third mirror which will be compatible with existing S-056 paraboloidal-hyperboloidal mirrors. This compatability will facilitate the construction of a prototype model of the TMXRT, since it will only be necessary to fabricate one new mirror in order to obtain a working model.

Engineering rules for evaluating the efficiency of multiplexing traffic streams

NASA Astrophysics Data System (ADS)

Klincewicz, John G.

2004-09-01

It is common, either for a telecommunications service provider or for a corporate enterprise, to have multiple data networks. For example, both an IP network and an ATM or Frame Relay network could be in operation to serve different applications. This can result in parallel transport links between the same two locations, each carrying data traffic under a different protocol. In this paper, we consider some practical engineering rules, for particular situations, to evaluate whether or not it is advantageous to combine these parallel traffic streams onto a single transport link. Combining the streams requires additional overhead (a so-called "cell tax" ) but, in at least some situations, can result in more efficient use of modular transport capacity. Simple graphs can be used to summarize the analysis. Some interesting, and perhaps unexpected, observations can be made.

Comparison of three retrievals of COSMIC GPS radio occultation results in the tropical upper troposphere and lower stratosphere

NASA Astrophysics Data System (ADS)

Noersomadi; Tsuda, Toshitaka

2017-09-01

Combining geometrical optics (GO) and wave optics (WO), the COSMIC data analysis and archive center (CDAAC) retrieved two sets of dry atmosphere temperatures ( T) from COSMIC GPS radio occultation (GPS-RO), which are called atmPrf2010 and atmPrf2013. In atmPrf2010, the sewing height between WO and GO varies between 10 and 20 km, but is fixed at 20 km for atmPrf2013. The height resolution of the atmPrf2010 depends on the sewing height, while the T profiles by atmPrf2013 are smoothed over 500 m. We also derived T by applying WO throughout the troposphere and the stratosphere up to a 30-km altitude, which is called rishfsi2013. The three retrievals have different characteristics in the height resolution around the tropopause. Therefore, we aim to examine a possible discrepancy in the statistical results of the cold-point tropopause (CPT) and the lapse rate tropopause (LRT) among the three datasets, conducting their inter-comparisons as well as the comparison between GPS-RO and the simultaneous radiosonde dataset. We investigate the T variations in the upper troposphere and lower stratosphere (UTLS) over the tropics from October 1, 2011, to March 31, 2012, when radiosonde soundings were conducted as the CINDY-DYNAMO 2011 campaign. The mean T profiles are consistent between atmPrf2010 and atmPrf2013, but rishfsi2013 results are colder (warmer) than the CDAAC retrievals below (above) the tropopause. The mean T difference between atmPrf2013 and atmPrf2010 is 0.17 K at the cold-point tropopause (CPT) and -0.38 K at the lapse rate tropopause (LRT). On the other hand, rishfsi2013 shows a colder T at CPT by -0.77 and -0.59 K relative to atmPrf2013 and atmPrf2010, respectively, and the warmer T by 0.60 and 0.20 Kd at LRT. During CINDY-DYNAMO, we found 134 radiosonde soundings that coincide with GPS-RO within ±3 h and are collocated within 200 km from GPS-RO. The mean T difference at CPT from the radiosondes is 0.32, 0.49 and -0.24 K for atmPrf2010, atmPrf2013 and rishfsi2013, respectively. Both atmPrf2013 and atmPrf2010 have a positive bias at CPT, while rishfsi2013 has a negative one. Similar comparisons at LRT are -0.45, -0.69 and -0.41 K, respectively, showing a negative bias for all GPS-RO retrievals. The results show that rishfsi2013 is consistent with the retrievals at CDAAC and the radiosondes. Due to its good height resolution, rishfsi2013 is useful for studies on mesoscale T perturbations in the UTLS.[Figure not available: see fulltext.

Capture and playback synchronization in video conferencing

NASA Astrophysics Data System (ADS)

Shae, Zon-Yin; Chang, Pao-Chi; Chen, Mon-Song

1995-03-01

Packet-switching based video conferencing has emerged as one of the most important multimedia applications. Lip synchronization can be disrupted in the packet network as the result of the network properties: packet delay jitters at the capture end, network delay jitters, packet loss, packet arrived out of sequence, local clock mismatch, and video playback overlay with the graphic system. The synchronization problem become more demanding as the real time and multiparty requirement of the video conferencing application. Some of the above mentioned problem can be solved in the more advanced network architecture as ATM having promised. This paper will present some of the solutions to the problems that can be useful at the end station terminals in the massively deployed packet switching network today. The playback scheme in the end station will consist of two units: compression domain buffer management unit and the pixel domain buffer management unit. The pixel domain buffer management unit is responsible for removing the annoying frame shearing effect in the display. The compression domain buffer management unit is responsible for parsing the incoming packets for identifying the complete data blocks in the compressed data stream which can be decoded independently. The compression domain buffer management unit is also responsible for concealing the effects of clock mismatch, lip synchronization, and packet loss, out of sequence, and network jitters. This scheme can also be applied to the multiparty teleconferencing environment. Some of the schemes presented in this paper have been implemented in the Multiparty Multimedia Teleconferencing (MMT) system prototype at the IBM watson research center.

Photogrammetric Processing of IceBridge DMS Imagery into High-Resolution Digital Surface Models (DEM and Visible Overlay)

NASA Astrophysics Data System (ADS)

Arvesen, J. C.; Dotson, R. C.

2014-12-01

The DMS (Digital Mapping System) has been a sensor component of all DC-8 and P-3 IceBridge flights since 2009 and has acquired over 3 million JPEG images over Arctic and Antarctic land and sea ice. The DMS imagery is primarily used for identifying and locating open leads for LiDAR sea-ice freeboard measurements and documenting snow and ice surface conditions. The DMS is a COTS Canon SLR camera utilizing a 28mm focal length lens, resulting in a 10cm GSD and swath of ~400 meters from a nominal flight altitude of 500 meters. Exterior orientation is provided by an Applanix IMU/GPS which records a TTL pulse coincident with image acquisition. Notable for virtually all IceBridge flights is that parallel grids are not flown and thus there is no ability to photogrammetrically tie any imagery to adjacent flight lines. Approximately 800,000 Level-3 DMS Surface Model data products have been delivered to NSIDC, each consisting of a Digital Elevation Model (GeoTIFF DEM) and a co-registered Visible Overlay (GeoJPEG). Absolute elevation accuracy for each individual Elevation Model is adjusted to concurrent Airborne Topographic Mapper (ATM) Lidar data, resulting in higher elevation accuracy than can be achieved by photogrammetry alone. The adjustment methodology forces a zero mean difference to the corresponding ATM point cloud integrated over each DMS frame. Statistics are calculated for each DMS Elevation Model frame and show RMS differences are within +/- 10 cm with respect to the ATM point cloud. The DMS Surface Model possesses similar elevation accuracy to the ATM point cloud, but with the following advantages: · Higher and uniform spatial resolution: 40 cm GSD · 45% wider swath: 435 meters vs. 300 meters at 500 meter flight altitude · Visible RGB co-registered overlay at 10 cm GSD · Enhanced visualization through 3-dimensional virtual reality (i.e. video fly-through) Examples will be presented of the utility of these advantages and a novel use of a cell phone camera for aerial photogrammetry will also be presented.

Learning topic models by belief propagation.

PubMed

Zeng, Jia; Cheung, William K; Liu, Jiming

2013-05-01

Latent Dirichlet allocation (LDA) is an important hierarchical Bayesian model for probabilistic topic modeling, which attracts worldwide interest and touches on many important applications in text mining, computer vision and computational biology. This paper represents the collapsed LDA as a factor graph, which enables the classic loopy belief propagation (BP) algorithm for approximate inference and parameter estimation. Although two commonly used approximate inference methods, such as variational Bayes (VB) and collapsed Gibbs sampling (GS), have gained great success in learning LDA, the proposed BP is competitive in both speed and accuracy, as validated by encouraging experimental results on four large-scale document datasets. Furthermore, the BP algorithm has the potential to become a generic scheme for learning variants of LDA-based topic models in the collapsed space. To this end, we show how to learn two typical variants of LDA-based topic models, such as author-topic models (ATM) and relational topic models (RTM), using BP based on the factor graph representations.

Greenhouse gases emissions in rivers of the Tibetan Plateau.

PubMed

Qu, Bin; Aho, Kelly Sue; Li, Chaoliu; Kang, Shichang; Sillanpää, Mika; Yan, Fangping; Raymond, Peter A

2017-11-29

Greenhouse gases (GHGs) emissions from streams are important to regional biogeochemical budgets. This study is one of the first to incorporate stream GHGs (CO 2 , CH 4 and N 2 O) concentrations and emissions in rivers of the Tibetan Plateau. With one-time sampling from 32 sites in rivers of the plateau, we found that most of the rivers were supersaturated with CO 2 , CH 4 and N 2 O during the study period. Medians of partial pressures of CO 2 (pCO 2 ), pCH 4 and pN 2 O were presented 864 μatm, 6.3 μatm, and 0.25 μatm respectively. Based on a scaling model of the flux of gas, the calculated fluxes of CO 2 , CH 4 and N 2 O (3,452 mg-C m 2 d -1 , 26.7 mg-C m 2 d -1 and 0.18 mg-N m 2 d -1 , respectively) in rivers of the Tibetan Plateau were found comparable with most other rivers in the world; and it was revealed that the evasion rates of CO 2 and CH 4 in tributaries of the rivers of the plateau were higher than those in the mainstream despite its high altitude. Furthermore, concentrations of GHGs in the studied rivers were related to dissolved carbon and nitrogen, indicating that riverine dissolved components could be used to scale GHGs envision in rivers of the Tibetan Plateau.

Lithospheric radial anisotropy beneath the Gulf of Mexico

NASA Astrophysics Data System (ADS)

Chu, Risheng; Ko, Justin Yen-Ting; Wei, Shengji; Zhan, Zhongwen; Helmberger, Don

2017-05-01

The Lithosphere-Asthenosphere Boundary (LAB), where a layer of low viscosity asthenosphere decouples with the upper plate motion, plays an essential role in plate tectonics. Most dynamic modeling assumes that the shear velocity can be used as a surrogate for viscosity which provides key information about mantle flow. Here, we derive a shear velocity model for the LAB structure beneath the Gulf of Mexico allowing a detailed comparison with that beneath the Pacific (PAC) and Atlantic (ATL). Our study takes advantage of the USArray data from the March 25th, 2013 Guatemala earthquake at a depth of 200 km. Such data is unique in that we can observe a direct upward traveling lid arrival which remains the first arrival ahead of the triplications beyond 18°. This extra feature in conjunction with upper-mantle triplication sampling allows good depth control of the LAB and a new upper-mantle seismic model ATM, a modification of ATL, to be developed. ATM has a prominent low velocity zone similar to the structure beneath the western Atlantic. The model contains strong radial anisotropy in the lid where VSH is about 6% faster than VSV. This anisotropic feature ends at the bottom of the lithosphere at about the depth of 175 km in contrast to the Pacific where it extends to over 300 km. Another important feature of ATM is the weaker velocity gradient from the depth of 175 to 350 km compared to Pacific models, which may be related to differences in mantle flow.

A QoS adaptive multimedia transport system: design, implementation and experiences

NASA Astrophysics Data System (ADS)

Campbell, Andrew; Coulson, Geoff

1997-03-01

The long awaited `new environment' of high speed broadband networks and multimedia applications is fast becoming a reality. However, few systems in existence today, whether they be large scale pilots or small scale test-beds in research laboratories, offer a fully integrated and flexible environment where multimedia applications can maximally exploit the quality of service (QoS) capabilities of supporting networks and end-systems. In this paper we describe the implementation of an adaptive transport system that incorporates a QoS oriented API and a range of mechanisms to assist applications in exploiting QoS and adapting to fluctuations in QoS. The system, which is an instantiation of the Lancaster QoS Architecture, is implemented in a multi ATM switch network environment with Linux based PC end systems and continuous media file servers. A performance evaluation of the system configured to support video-on-demand application scenario is presented and discussed. Emphasis is placed on novel features of the system and on their integration into a complete prototype. The most prominent novelty of our design is a `distributed QoS adaptation' scheme which allows applications to delegate to the system responsibility for augmenting and reducing the perceptual quality of video and audio flows when resource availability increases or decreases.

Quasi-real-time telemedical checkup system for x-ray examination of UGI tract based on high-speed network

NASA Astrophysics Data System (ADS)

Sakano, Toshikazu; Yamaguchi, Takahiro; Fujii, Tatsuya; Okumura, Akira; Furukawa, Isao; Ono, Sadayasu; Suzuki, Junji; Ando, Yutaka; Kohda, Ehiichi; Sugino, Yoshinori; Okada, Yoshiyuki; Amaki, Sachi

2000-05-01

We constructed a high-speed medical information network testbed, which is one of the largest testbeds in Japan, and applied it to practical medical checkups for the first time. The constructed testbed, which we call IMPACT, consists of a Super-High Definition Imaging system, a video conferencing system, a remote database system, and a 6 - 135 Mbps ATM network. The interconnected facilities include the School of Medicine in Keio University, a company's clinic, and an NTT R&D center, all in and around Tokyo. We applied IMPACT to the mass screening of the upper gastrointestinal (UGI) tract at the clinic. All 5419 radiographic images acquired at them clinic for 523 employees were digitized (2048 X 1698 X 12 bits) and transferred to a remote database in NTT. We then picked up about 50 images from five patients and sent them to nine radiological specialists at Keio University. The processing, which includes film digitization, image data transfer, and database registration, took 574 seconds per patient in average. The average reading time at Keio Univ. was 207 seconds. The overall processing time was estimated to be 781 seconds per patient. From these experimental results, we conclude that quasi-real time tele-medical checkups are possible with our prototype system.

An Integrated Gate Turnaround Management Concept Leveraging Big Data Analytics for NAS Performance Improvements

NASA Technical Reports Server (NTRS)

Chung, William W.; Ingram, Carla D.; Ahlquist, Douglas Kurt; Chachad, Girish H.

2016-01-01

"Gate Turnaround" plays a key role in the National Air Space (NAS) gate-to-gate performance by receiving aircraft when they reach their destination airport, and delivering aircraft into the NAS upon departing from the gate and subsequent takeoff. The time spent at the gate in meeting the planned departure time is influenced by many factors and often with considerable uncertainties. Uncertainties such as weather, early or late arrivals, disembarking and boarding passengers, unloading/reloading cargo, aircraft logistics/maintenance services and ground handling, traffic in ramp and movement areas for taxi-in and taxi-out, and departure queue management for takeoff are likely encountered on the daily basis. The Integrated Gate Turnaround Management (IGTM) concept is leveraging relevant historical data to support optimization of the gate operations, which include arrival, at the gate, departure based on constraints (e.g., available gates at the arrival, ground crew and equipment for the gate turnaround, and over capacity demand upon departure), and collaborative decision-making. The IGTM concept provides effective information services and decision tools to the stakeholders, such as airline dispatchers, gate agents, airport operators, ramp controllers, and air traffic control (ATC) traffic managers and ground controllers to mitigate uncertainties arising from both nominal and off-nominal airport gate operations. IGTM will provide NAS stakeholders customized decision making tools through a User Interface (UI) by leveraging historical data (Big Data), net-enabled Air Traffic Management (ATM) live data, and analytics according to dependencies among NAS parameters for the stakeholders to manage and optimize the NAS performance in the gate turnaround domain. The application will give stakeholders predictable results based on the past and current NAS performance according to selected decision trees through the UI. The predictable results are generated based on analysis of the unique airport attributes (e.g., runway, taxiway, terminal, and gate configurations and tenants), and combined statistics from past data and live data based on a specific set of ATM concept-of-operations (ConOps) and operational parameters via systems analysis using an analytic network learning model. The IGTM tool will then bound the uncertainties that arise from nominal and off-nominal operational conditions with direct assessment of the gate turnaround status and the impact of a certain operational decision on the NAS performance, and provide a set of recommended actions to optimize the NAS performance by allowing stakeholders to take mitigation actions to reduce uncertainty and time deviation of planned operational events. An IGTM prototype was developed at NASA Ames Simulation Laboratories (SimLabs) to demonstrate the benefits and applicability of the concept. A data network, using the System Wide Information Management (SWIM)-like messaging application using the ActiveMQ message service, was connected to the simulated data warehouse, scheduled flight plans, a fast-time airport simulator, and a graphic UI. A fast-time simulation was integrated with the data warehouse or Big Data/Analytics (BAI), scheduled flight plans from Aeronautical Operational Control AOC, IGTM Controller, and a UI via a SWIM-like data messaging network using the ActiveMQ message service, illustrated in Figure 1, to demonstrate selected use-cases showing the benefits of the IGTM concept on the NAS performance.

Architectural and engineering issues for building an optical Internet

NASA Astrophysics Data System (ADS)

St. Arnaud, Bill

1998-10-01

Recent developments in high density Wave Division Multiplexing fiber systems allows for the deployment of a dedicated optical Internet network for large volume backbone pipes that does not require an underlying multi-service SONET/SDH and ATM transport protocol. Some intrinsic characteristics of Internet traffic such as its self similar nature, server bound congestion, routing and data asymmetry allow for highly optimized traffic engineered networks using individual wavelengths. By transmitting GigaBit Ethernet or SONET/SDH frames natively over WDM wavelengths that directly interconnect high performance routers the original concept of the Internet as an intrinsically survivable datagram network is possible. Traffic engineering, restoral, protection and bandwidth management of the network must now be carried out at the IP layer and so new routing or switching protocols such as MPLS that allow for uni- directional paths with fast restoral and protection at the IP layer become essential for a reliable production network. The deployment of high density WDM municipal and campus networks also gives carriers and ISPs the flexibility to offer customers as integrated and seamless set of optical Internet services.

[Phytic phosphorus and phytase activity in cereal-based infant formulas].

PubMed

Ojeda, Alvaro; Villavicencio, Iraidis; Linares, Zoraida

2012-12-01

Phytic acid is an organic acid present in cereal grains. The phosphorus inside its molecule (PPhy) is not available because of its low solubility, though the bioavailability could be increased by the activity of phytase enzymes (PhyA). With the purpose of quantifying the PPhy and PhyA in supplements manufactured from cereals and intended for lactating infants, five formulas of wide distribution in local markets were selected and identified depending on the main vegetable ingredients as A (rice), T (wheat), ATS (rice, wheat and soy isolate), ATM (rice, wheat and maize) and ATMS (rice, wheat, maize and soy isolate). Five samples were taken from each formula, each one corresponded to a commercial brand (400 to 500 g), coming from different batches and before their expiration date. The crude protein ranged from 7.2 to 16.8%, with de highest value for ATS and the lowest for T and ATM (P < 0.01). Ether extract varied from 0.31 to 0.75%, while the calcium: phosphorus ratio from 1.6 for ATM, to 1.1 for the rest. The PPhy was 61.5% of the total phosphorus in T, with differences (P < 0.01) compared to the other formulas (39.9 +/- 6.8%). PhyA was only detected in ATS, T and ATM (152, 300 and 570 U/kg, respectively). The chemical composition complied with the manufacturer report, with a high content of PPhy and PhyA associated to the wheat presence in the formula.

Calibration and Validation of Airborne LiDAR at McMurdo Station, Antarctica for Operation IceBridge

NASA Astrophysics Data System (ADS)

Sonntag, J. G.

2014-12-01

Airborne LiDAR flight operations based at McMurdo Station, Antarctica, present unusual challenges for calibrating and validating the sensor measurements at the level of a few centimeters. NASA's Airborne Topographic Mapper (ATM) team prefers to perform regular, near-daily calibrations of range and angular biases of our sensor for the lengthy field deployments typical for Operation IceBridge (OIB). For the fall 2013 OIB deployment to McMurdo, we had to adapt our usual technique of regular overflights of an independently-surveyed airport parking ramp to deal with the fact that the McMurdo airfield was located on tidally-influenced sea ice, and that very few nearby durable surfaces were free of variable-depth snow during the OIB deployment. We detail our approach for dealing with these challenges, which included multiple GPS/vehicle surveys of the sea ice runway to quantify surface changes due to grooming operations, combined with GPS tide-gauge measurements of the runway's tidal motion. We also conducted a remote GPS/vehicle survey of a mostly snow-free road on Black Island, and included both sites during near-daily overflights with the ATM. We discuss the quantitative results of these surveys and the associated ATM overflights, and present conclusions for future deployments. Finally we discuss a related validation effort in which we compare ATM results from overflights of snow-free areas in the Dry Valleys with ATM surveys of the same area from a 2001 effort there.

A randomized controlled trial of a money management-based substance use intervention.

PubMed

Rosen, Marc I; Carroll, Kathleen M; Stefanovics, Elina; Rosenheck, Robert A

2009-04-01

Money management has been implemented, often in bundled interventions, as a strategy to counteract spending of public support checks and other funds on drugs and alcohol. The authors conducted a randomized controlled trial of a voluntary money management program as an adjunctive treatment for patients in treatment for mental illness, substance use disorders, or both. In the advisor-teller money manager (ATM) intervention, a money manager stores patients' checkbooks and automated bank cards, trains patients to manage their own funds, and links spending to activities related to their treatment goals. Eighty-five veterans with recent use of alcohol or cocaine were randomly assigned to 36 weeks of the ATM intervention or a control intervention (completion of a simple financial workbook). With ATM, 75% of veterans gave their checkbook to their money manager to hold, and participants attended significantly more therapy sessions than those assigned to the control therapy (mean of 20.6 versus 8.1 sessions). Although participants assigned to ATM did not show significantly greater improvement over time on the primary outcomes (self-reported abstinence from alcohol and cocaine and negative urine tests for cocaine metabolite), they reduced their Addiction Severity Index drug and alcohol use composite scale scores more rapidly than the control group. High rates of abstinence in both groups created a ceiling effect, limiting the power to detect improved abstinence rates. In this relatively small trial, ATM, a money management intervention, showed promise in engaging patients, improving their money management, and improving some substance abuse outcomes.

A money management-based substance use treatment increases valuation of future rewards.

PubMed

Black, Anne C; Rosen, Marc I

2011-01-01

A positive association between delay discounting and substance use has been documented; substance users tend to discount future rewards more than non-users. However, studies detailing the responsiveness of delay discounting to interventions are lacking, and few have examined how any behavioral intervention affects delay discounting and whether these effects moderate changes in substance abuse. This study assesses the effectiveness of a money management intervention, Advisor-Teller Money Manager (ATM), in reducing delay discounting over time and the relationship of these effects to changes in cocaine use. Ninety psychiatric patients with histories of cocaine and/or alcohol use were randomly assigned to 36-weeks of ATM treatment or to a minimal-attention control condition. Delay discounting and cocaine use were measured throughout the intervention with a 52-week follow up measure of cocaine use. Analyses were conducted of (a) the effect of ATM on slopes of delay discounting and cocaine abstinence and (b) the relationship between change in delay discounting and change in cocaine abstinence. The ATM intervention was associated with significantly less delay discounting and less cocaine use over time relative to controls. Increases in delay discounting were associated with decreased abstinence from cocaine. ATM treatment decreased delay discounting rates and these effects extended to cocaine use. Concrete conceptualizations of future events, as occur in financial planning, with higher perceived probability may account for higher valuation of future rewards in counseled patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Carbon dioxide and methane dynamics in a human-dominated lowland coastal river network (Shanghai, China)

NASA Astrophysics Data System (ADS)

Yu, Zhongjie; Wang, Dongqi; Li, Yangjie; Deng, Huanguang; Hu, Beibei; Ye, Mingwu; Zhou, Xuhui; Da, Liangjun; Chen, Zhenlou; Xu, Shiyuan

2017-07-01

Evasion of carbon dioxide (CO2) and methane (CH4) in streams and rivers play a critical role in global carbon (C) cycle, offsetting the C uptake by terrestrial ecosystems. However, little is known about CO2 and CH4 dynamics in lowland coastal rivers profoundly modified by anthropogenic perturbations. Here we report results from a long-term, large-scale study of CO2 and CH4 partial pressures (pCO2 and pCH4) and evasion rates in the Shanghai river network. The spatiotemporal variabilities of pCO2 and pCH4 were examined along a land use gradient, and the annual CO2 and CH4 evasion were estimated to assess its role in regional C budget. During the study period (August 2009 to October 2011), the overall mean pCO2 and median pCH4 from 87 surveyed rivers were 5846 ± 2773 μatm and 241 μatm, respectively. Internal metabolic CO2 production and dissolved inorganic carbon input via upstream runoff were the major sources sustaining the widespread CO2 supersaturation, coupling pCO2 to biogeochemical and hydrological controls, respectively. While CH4 was oversaturated throughout the river network, CH4 hot spots were concentrated in the small urban rivers and highly discharge-dependent. The Shanghai river network played a disproportionately important role in regional C budget, offsetting up to 40% of the regional terrestrial net ecosystem production and 10% of net C uptake in the river-dominated East China Sea fueled by anthropogenic nutrient input. Given the rapid urbanization in global coastal areas, more research is needed to quantify the role of lowland coastal rivers as a major landscape C source in global C budget.

Antisense Oligonucleotides Modulating Activation of a Nonsense-Mediated RNA Decay Switch Exon in the ATM Gene.

PubMed

Kralovicova, Jana; Moreno, Pedro M D; Cross, Nicholas C P; Pêgo, Ana Paula; Vorechovsky, Igor

2016-12-01

ATM (ataxia-telangiectasia, mutated) is an important cancer susceptibility gene that encodes a key apical kinase in the DNA damage response pathway. ATM mutations in the germ line result in ataxia-telangiectasia (A-T), a rare genetic syndrome associated with hypersensitivity to double-strand DNA breaks and predisposition to lymphoid malignancies. ATM expression is limited by a tightly regulated nonsense-mediated RNA decay (NMD) switch exon (termed NSE) located in intron 28. In this study, we identify antisense oligonucleotides that modulate NSE inclusion in mature transcripts by systematically targeting the entire 3.1-kb-long intron. Their identification was assisted by a segmental deletion analysis of transposed elements, revealing NSE repression upon removal of a distant antisense Alu and NSE activation upon elimination of a long terminal repeat transposon MER51A. Efficient NSE repression was achieved by delivering optimized splice-switching oligonucleotides to embryonic and lymphoblastoid cells using chitosan-based nanoparticles. Together, these results provide a basis for possible sequence-specific radiosensitization of cancer cells, highlight the power of intronic antisense oligonucleotides to modify gene expression, and demonstrate transposon-mediated regulation of NSEs.

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

PubMed

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.

Systems-Level Analysis of EGFR Inhibition-DNA Damage Combination Treatment in Breast Cancer

DTIC Science & Technology

2012-09-01

treatment strategy for potentiating the effects of chemotherapy in these cells (Figure 1). The goal of this current work is to gain a molecular...2000 DEGs (Figure 2B-C). By comparison, in the HER2+ MDA-MB- 453 cells, which were desensitized to doxorubicin by erlotinib exposure, we observed only...identify which cancer genes were likely to be targeted. Using CGN analysis, we identified two networks as being of potential interest: ATM and Caspase

Blocking CXCR7-mediated adipose tissue macrophages chemotaxis attenuates insulin resistance and inflammation in obesity.

PubMed

Peng, Hongxia; Zhang, Hu; Zhu, Honglei

2016-10-28

Adipose tissue macrophages (ATMs) have been considered to have a pivotal role in the chronic inflammation development during obesity. Although chemokine-chemokine receptor interaction has been studied in ATMs infiltration, most chemokine receptors remain incompletely understood and little is known about their mechanism of actions that lead to ATMs chemotaxis and pathogenesis of insulin resistance during obesity. In this study, we reported that CXCR7 expression is upregulated in adipose tissue, and specifically in ATMs during obesity. In addition, CXCL11 or CXCL12-induced ATMs chemotaxis is mediated by CXCR7 in obesity but not leanness, whereas CXCR3 and CXCR4 are not involved. Additional mechanism study shows that NF-κB activation is essential in ATMs chemotaxis, and manipulates chemotaxis of ATMs via CXCR7 expression regulation in obesity. Most importantly, CXCR7 neutralizing therapy dose dependently leads to less infiltration of macrophages into adipose tissue and thus reduces inflammation and improves insulin sensitivity in obesity. In conclusion, these findings demonstrated that blocking CXCR7-mediated ATMs chemotaxis ameliorates insulin resistance and inflammation in obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

MPEG-2 Over Asynchronous Transfer Mode (ATM) Over Satellite Quality of Service (QoS) Experiments: Laboratory Tests

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Frantz, Brian D.; Spells, Marcus J.

1998-01-01

Asynchronous transfer mode (ATM) quality of service (QoS) experiments were performed using MPEG-2 (ATM application layer 5, AAL5) over ATM over an emulated satellite link. The purpose of these experiments was to determine the free-space link quality necessary to transmit high-quality multimedia information by using the ATM protocol. The detailed test plan and test configuration are described herein as are the test results. MPEG-2 transport streams were baselined in an errored environment, followed by a series of tests using, MPEG-2 over ATM. Errors were created both digitally as well as in an IF link by using a satellite modem and commercial gaussian noise test set for two different MPEG-2 decoder implementations. The results show that ITU-T Recommendation 1.356 Class 1, stringent ATM applications will require better link quality than currently specified; in particular, cell loss ratios of better than 1.0 x 10(exp -8) and cell error ratios of better than 1.0 x 10(exp -7) are needed. These tests were conducted at the NASA Lewis Research Center in support of satellite-ATM interoperability research.

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

PubMed Central

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

Biallelic ATM alterations detected at diagnosis identify a subset of treatment-naïve chronic lymphocytic leukemia patients with reduced overall survival similar to patients with p53 deletion.

PubMed

Lozano-Santos, Carol; García-Vela, José A; Pérez-Sanz, Nuria; Nova-Gurumeta, Sara; Fernandez-Cuevas, Belen; Gomez-Lozano, Natalia; Sánchez-Beato, Margarita; Sanchez-Godoy, Pedro; Bueno, José Luis; Garcia-Marco, José A

2017-04-01

The prognostic impact of biallelic ATM abnormalities (ATM mutation and concurrent 11q deletion) remains unknown. We studied ATM, BIRC3, SF3B1, and NOTCH1 genes in 118 treatment-naïve CLL patients at diagnosis. Patients with biallelic ATM alteration had a similar time to first treatment (TTFT) and shorter overall survival (OS) compared with patients with isolated 11q deletion and shorter TTFT and OS when compared to patients with wild-type ATM. Furthermore, biallelic ATM alteration (HR: 6.4; p ≤ 0.007) was significantly associated with an increased risk of death similar to p53 deletion (HR: 6.1; p ≤ 0.004), superior to 11q deletion alone (HR: 2.8; p ≤ 0.022) and independent of other significant parameters such as age, advanced clinical stage, and complex karyotype. Our results suggest the identification of ATM mutations in CLL patients with 11q deletion at diagnosis is clinically relevant and predicts disease progression, poor response to the treatment, and reduced OS independent of other molecular prognostic factors.

Optical storage networking

NASA Astrophysics Data System (ADS)

Mohr, Ulrich

2001-11-01

For efficient business continuance and backup of mission- critical data an inter-site storage network is required. Where traditional telecommunications costs are prohibitive for all but the largest organizations, there is an opportunity for regional carries to deliver an innovative storage service. This session reveals how a combination of optical networking and protocol-aware SAN gateways can provide an extended storage networking platform with the lowest cost of ownership and the highest possible degree of reliability, security and availability. Companies of every size, with mainframe and open-systems environments, can afford to use this integrated service. Three mayor applications are explained; channel extension, Network Attached Storage (NAS), Storage Area Networks (SAN) and how optical networks address the specific requirements. One advantage of DWDM is the ability for protocols such as ESCON, Fibre Channel, ATM and Gigabit Ethernet, to be transported natively and simultaneously across a single fiber pair, and the ability to multiplex many individual fiber pairs over a single pair, thereby reducing fiber cost and recovering fiber pairs already in use. An optical storage network enables a new class of service providers, Storage Service Providers (SSP) aiming to deliver value to the enterprise by managing storage, backup, replication and restoration as an outsourced service.

Parametric analysis of ATM solar array.

NASA Technical Reports Server (NTRS)

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

1973-01-01

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

Loss of the DNA Damage Repair Kinase ATM Impairs Inflammasome-Dependent Anti-Bacterial Innate Immunity.

PubMed

Erttmann, Saskia F; Härtlova, Anetta; Sloniecka, Marta; Raffi, Faizal A M; Hosseinzadeh, Ava; Edgren, Tomas; Rofougaran, Reza; Resch, Ulrike; Fällman, Maria; Ek, Torben; Gekara, Nelson O

2016-07-19

The ATM kinase is a central component of the DNA damage repair machinery and redox balance. ATM dysfunction results in the multisystem disease ataxia-telangiectasia (AT). A major cause of mortality in AT is respiratory bacterial infections. Whether ATM deficiency causes innate immune defects that might contribute to bacterial infections is not known. Here we have shown that loss of ATM impairs inflammasome-dependent anti-bacterial innate immunity. Cells from AT patients or Atm(-/-) mice exhibited diminished interleukin-1β (IL-1β) production in response to bacteria. In vivo, Atm(-/-) mice were more susceptible to pulmonary S. pneumoniae infection in a manner consistent with inflammasome defects. Our data indicate that such defects were due to oxidative inhibition of inflammasome complex assembly. This study reveals an unanticipated function of reactive oxygen species (ROS) in negative regulation of inflammasomes and proposes a theory for the notable susceptibility of AT patients to pulmonary bacterial infection. Copyright © 2016 Elsevier Inc. All rights reserved.

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

NASA Technical Reports Server (NTRS)

Susskind, Joel; Kouvaris, Louis C.

2013-01-01

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

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

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

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-/-more » 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.« less

The impact of glutamine supplementation on the symptoms of ataxia-telangiectasia: a preclinical assessment.

PubMed

Chen, Jianmin; Chen, Yanping; Vail, Graham; Chow, Heiman; Zhang, Yang; Louie, Lauren; Li, Jiali; Hart, Ronald P; Plummer, Mark R; Herrup, Karl

2016-08-18

Our previous studies of Alzheimer's disease (AD) suggested that glutamine broadly improves cellular readiness to respond to stress and acts as a neuroprotectant both in vitro and in AD mouse models. We now expand our studies to a second neurodegenerative disease, ataxia-telangiectasia (A-T). Unlike AD, where clinically significant cognitive decline does not typically occur before age 65, A-T symptoms appear in early childhood and are caused exclusively by mutations in the ATM (A-T mutated) gene. Genetically ATM-deficient mice and wild type littermates were maintained with or without 4 % glutamine in their drinking water for several weeks. In ATM mutants, glutamine supplementation restored serum glutamine and glucose levels and reduced body weight loss. Lost neurophysiological function assessed through the magnitude of hippocampal long term potentiation was significantly restored. Glutamine supplemented mice also showed reduced thymus pathology and, remarkably, a full one-third extension of lifespan. In vitro assays revealed that ATM-deficient cells are more sensitive to glutamine deprivation, while supra-molar glutamine (8 mM) partially rescued the reduction of BDNF expression and HDAC4 nuclear translocation of genetically mutant Atm(-/-) neurons. Analysis of microarray data suggested that glutamine metabolism is significantly altered in human A-T brains as well. Glutamine is a powerful part of an organism's internal environment. Changes in its concentrations can have a huge impact on the function of all organ systems, especially the brain. Glutamine supplementation thus bears consideration as a therapeutic strategy for the treatment of human A-T and perhaps other neurodegenerative diseases.

ATM test and integration. [Skylab Apollo Telescope Mount

NASA Technical Reports Server (NTRS)

Moore, J. W.; Mitchell, J. R.

1974-01-01

The test and checkout philosophy of the test program for the Skylab ATM module and the overall test flow including in-process, post-manufacturing, vibration, thermal vacuum, and prelaunch checkout activities are described. Capabilities and limitations of the test complex and its use of automation are discussed. Experiences with the organizational principle of using a dedicated test team for all checkout activities are reported. Material on the development of the ATM subsystems, the experimental program and the requirements of the scientific community, and the integration and verification of the complex systems/subsystems of the ATM are presented. The performance of the ATM test program in such areas as alignment, systems and subsystems, contamination control, and experiment operation is evaluated. The conclusions and recommendations resulting from the ATM test program are enumerated.

Modeling of a Reaction-Distillation-Recycle System to Produce Dimethyl Ether through Methanol Dehydration

NASA Astrophysics Data System (ADS)

Muharam, Y.; Zulkarnain, L. M.; Wirya, A. S.

2018-03-01

The increase in the dimethyl ether yield through methanol dehydration due to a recycle integration to a reaction-distillation system was studied in this research. A one-dimensional phenomenological model of a methanol dehydration reactor and a shortcut model of distillation columns were used to achieve the aim. Simulation results show that 10.7 moles/s of dimethyl ether is produced in a reaction-distillation system with the reactor length being 4 m, the reactor inlet pressure being 18 atm, the reactor inlet temperature being 533 K, the reactor inlet velocity being 0.408 m/s, and the distillation pressure being 8 atm. The methanol conversion is 90% and the dimethyl ether yield is 48%. The integration of the recycle stream to the system increases the dimethyl ether yield by 8%.

End-to-End QoS for Differentiated Services and ATM Internetworking

NASA Technical Reports Server (NTRS)

Su, Hongjun; Atiquzzaman, Mohammed

2001-01-01

The Internet was initially design for non real-time data communications and hence does not provide any Quality of Service (QoS). The next generation Internet will be characterized by high speed and QoS guarantee. The aim of this paper is to develop a prioritized early packet discard (PEPD) scheme for ATM switches to provide service differentiation and QoS guarantee to end applications running over next generation Internet. The proposed PEPD scheme differs from previous schemes by taking into account the priority of packets generated from different application. We develop a Markov chain model for the proposed scheme and verify the model with simulation. Numerical results show that the results from the model and computer simulation are in close agreement. Our PEPD scheme provides service differentiation to the end-to-end applications.

MSFC Skylab Apollo Telescope Mount summary mission report

NASA Technical Reports Server (NTRS)

Morse, A. R.

1974-01-01

A summary of the Apollo Telescope Mount (ATM) performance during the 8.5-month Skylab mission is presented. A brief description of each ATM system, system performance summaries, discussion of all significant ATM anomalies which occurred during the Skylab mission, and, in an appendix, a summary of the Skylab ATM Calibration Rocket Project (CALROC) are provided. The text is supplemented and amplified by photographs, drawings, curves, and tables. The report shows that the ATM not only met, but exceeded premission performance criteria, and that participation of man in space for this scientific investigation greatly enhanced the quality and quantity of the data attained.

Seasonal and Interannual Variations of Heat Fluxes in the Barents Sea Region

NASA Astrophysics Data System (ADS)

Bashmachnikov, I. L.; Yurova, A. Yu.; Bobylev, L. P.; Vesman, A. V.

2018-03-01

Seasonal and interannual variations in adjective heat fluxes in the ocean ( dQ oc) and the convergence of advective heat fluxes in the atmosphere ( dQ atm) in the Barents Sea region have been investigated over the period of 1993-2012 using the results of the MIT regional eddy-permitting model and ERA-Interim atmospheric reanalysis. Wavelet analysis and singular spectrum analysis are used to reveal concealed periodicities. Seasonal 2- to 4- and 5- to 8-year cycles are revealed in the dQ oc and dQ atm data. It is also found that seasonal variations in dQ oc are primarily determined by the integrated volume fluxes through the western boundary of the Barents Sea, whereas the 20-year trend is determined by the temperature variation of the transported water. A cross-wavelet analysis of dQ oc and dQ atm in the Barents Sea region shows that the seasonal variations in dQ oc and dQ atm are nearly in-phase, while their interannual variations are out-of-phase. It is concluded that the basin of the Barents Sea plays an important role in maintaining the feedback mechanism (the Bjerknes compensation) of the ocean-atmosphere system in the Arctic region.

12 CFR 229.16 - Specific availability policy disclosure.

Code of Federal Regulations, 2010 CFR

2010-01-01

... can differentiate between a proprietary and a nonproprietary ATM, if the bank makes funds from deposits at nonproprietary ATMs available for withdrawal later than funds from deposits at proprietary ATMs...

Thermodynamic analysis of low-temperature carbon dioxide and sulfur dioxide capture from coal-burning power plants.

PubMed

Swanson, Charles E; Elzey, John W; Hershberger, Robert E; Donnelly, Russell J; Pfotenhauer, John

2012-07-01

We discuss the possibility of capturing carbon dioxide from the flue gas of a coal-fired electrical power plant by cryogenically desublimating the carbon dioxide and then preparing it for transport in a pipeline to a sequestration site. Various other means have been proposed to accomplish the same goal. The problem discussed here is to estimate the "energy penalty" or "parasitic energy loss,' defined as the fraction of electrical output that will be needed to provide the refrigeration and that will then not be deliverable. We compute the energy loss (7.9-9.2% at 1 atm) based on perfect Carnot efficiency and estimate the achievable parasitic energy loss (22-26% at 1 atm) by incorporating the published coefficient of performance values for appropriately sized refrigeration or liquefaction cycles at the relevant temperatures. The analyses at 1 atm represent a starting point for future analyses using elevated pressures.

Thermodynamic analysis of low-temperature carbon dioxide and sulfur dioxide capture from coal-burning power plants

NASA Astrophysics Data System (ADS)

Swanson, Charles E.; Elzey, John W.; Hershberger, Robert E.; Donnelly, Russell J.; Pfotenhauer, John

2012-07-01

We discuss the possibility of capturing carbon dioxide from the flue gas of a coal-fired electrical power plant by cryogenically desublimating the carbon dioxide and then preparing it for transport in a pipeline to a sequestration site. Various other means have been proposed to accomplish the same goal. The problem discussed here is to estimate the “energy penalty” or “parasitic energy loss,' defined as the fraction of electrical output that will be needed to provide the refrigeration and that will then not be deliverable. We compute the energy loss (7.9-9.2% at 1 atm) based on perfect Carnot efficiency and estimate the achievable parasitic energy loss (22-26% at 1 atm) by incorporating the published coefficient of performance values for appropriately sized refrigeration or liquefaction cycles at the relevant temperatures. The analyses at 1 atm represent a starting point for future analyses using elevated pressures.