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

Virtual C Machine and Integrated Development Environment for ATMS Controllers.

DOT National Transportation Integrated Search

2000-04-01

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

Terminal Area ATM Research at NASA Ames

NASA Technical Reports Server (NTRS)

Tobias, Leonard

1997-01-01

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

NPP After Launch: Characterizing ATMS Performance

NASA Technical Reports Server (NTRS)

Lambrigtsen, Bjorn

2011-01-01

The NPOESS Preparatory Project (NPP) mission is scheduled to launch in the fall of 2011. Although several teams from the government and the instrument contractor will be assessing and characterizing the performance of the Advanced Technology Microwave Sounder (ATMS) and the Cross-track Infrared Sounder (CrIS) sounding suite, the NASA NPP Science Team will be paying particular attention to the aspects of these sensors that affect their utility for atmospheric and climate research. In this talk we discuss relevant aspects of ATMS and our post launch analysis approach.

IN31A-1734 Development and Evaluation of a Gridded CrIS/ATMS Visualization for Operational Forecasting

NASA Technical Reports Server (NTRS)

Zavodsky, Bradley; Smith, Nadia; Dostalek, Jack; Stevens, Eric; Nelson, Kristine; Weisz, Elisabeth; Berndt, Emily; Line, Bill; Barnet, Chris; Gambacorta, Antonia;

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…

Health ATMs in Saudi Arabia: A Perspective.

PubMed

Aldosari, Bakheet

2017-06-01

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

Health ATMs in Saudi Arabia: A Perspective

PubMed Central

Aldosari, Bakheet

2017-01-01

Background: Health ATMs are terminals which are connected to a centrally located database storing patients’ electronic healthcare records (EHR). These machines are capable of collecting information in a far superior fashion than humans and are also able to rectify obsolete data in a manner that humans are generally not inclined to. Objectives: The main goal of this study is to assess the importance of adopting health ATMs in the Kingdom of Saudi Arabia (KSA), which can improve the confidence of patients, reward health self-management, and achieve positive health outcomes through their easy-to-use applications that are secure and accessible through various devices. Methods: Strength, Weakness, Opportunity, and Threat (SWOT) analysis was used to assess the efficiency of adopting health ATMs in KSA and reveal the said characteristics. Three focus groups assembled in the cities of Riyadh, Jeddah and Dammam during the period 2013-2014. The groups consisted of individuals experienced in the function of health ATMs. Results: It was found that the sector possessed a number of strengths that would help it in reaching the goals outlined therein, thereby achieving successful outcomes. Conclusions: Health ATMs could be a promising new advancement in the field of health if the project were to be planned and implemented correctly. Their benefits would consequently reach organizational and national levels. It is, therefore, crucial to educate the project managers about the benefits of learning from others as well as educating them about the needs and the requirements of the concerned organization. PMID:28883680

Sample Handling in Extreme Environments

NASA Technical Reports Server (NTRS)

Avellar, Louisa; Badescu, Mircea; Sherrit, Stewart; Bar-Cohen, Yoseph

2013-01-01

Harsh environments, such as that on Venus, preclude the use of existing equipment for functions that involve interaction with the environment. The operating limitations of current high temperature electronics are well below the actual temperature and pressure found on Venus (460 deg C and 92 atm), so proposed lander configurations typically include a pressure vessel where the science instruments are kept at Earth-like temperature and pressure (25 deg C and 1 atm). The purpose of this project was to develop and demonstrate a method for sample transfer from an external drill to internal science instruments for a lander on Venus. The initial concepts were string and pneumatically driven systems; and the latter system was selected for its ability to deliver samples at very high speed. The pneumatic system was conceived to be driven by the pressure difference between the Venusian atmosphere and the inside of the lander. The pneumatic transfer of a small capsule was demonstrated, and velocity data was collected from the lab experiment. The sample transfer system was modeled using CAD software and prototyped using 3D printing. General structural and thermal analyses were performed to approximate the proposed system's mass and effects on the temperature and pressure inside of the lander. Additionally, a sampler breadboard for use on Titan was tested and functionality problems were resolved.

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.

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.

A novel pathogenic variant in an Iranian Ataxia telangiectasia family revealed by next-generation sequencing followed by in silico analysis.

PubMed

Tabatabaiefar, Mohammad Amin; Alipour, Paria; Pourahmadiyan, Azam; Fattahi, Najmeh; Shariati, Laleh; Golchin, Neda; Mohammadi-Asl, Javad

2017-08-15

Ataxia telangiectasia (A-T) is a neurodegenerative autosomal recessive disorder with the main characteristics of progressive cerebellar degeneration, sensitivity to ionizing radiation, immunodeficiency, telangiectasia, premature aging, recurrent sinopulmonary infections, and increased risk of malignancy, especially of lymphoid origin. Ataxia Telangiectasia Mutated gene, ATM, as a causative gene for the A-T disorder, encodes the ATM protein, which plays an important role in the activation of cell-cycle checkpoints and initiation of DNA repair in response to DNA damage. Targeted next-generation sequencing (NGS) was performed on an Iranian 5-year-old boy presented with truncal and limb ataxia, telangiectasia of the eye, Hodgkin lymphoma, hyper pigmentation, total alopecia, hepatomegaly, and dysarthria. Sanger sequencing was used to confirm the candidate pathogenic variants. Computational docking was done using the HEX software to examine how this change affects the interactions of ATM with the upstream and downstream proteins. Three different variants were identified comprising two homozygous SNPs and one novel homozygous frameshift variant (c.80468047delTA, p.Thr2682ThrfsX5), which creates a stop codon in exon 57 leaving the protein truncated at its C-terminal portion. Therefore, the activation and phosphorylation of target proteins are lost. Moreover, the HEX software confirmed that the mutated protein lost its interaction with upstream and downstream proteins. The variant was classified as pathogenic based on the American College of Medical Genetics and Genomics guideline. This study expands the spectrum of ATM pathogenic variants in Iran and demonstrates the utility of targeted NGS in genetic diagnostics. Copyright © 2017. Published by Elsevier B.V.

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…

Industry Support

NASA Technical Reports Server (NTRS)

2003-01-01

NASA Glenn Research Center (GRC) is responsible for the Advanced Communications for Air Traffic Management (AC/ATM) Project, a sub-element task of the Advanced Air Transportation Technologies (AATT) Project of the NASA Aviation System Capacity Program (ASC). The AC/ATM Project is developing new communications technologies and tools that will improve throughput in the U.S. Air Traffic Control System. The goal of the AC/ATM Project is to enable a communications infrastructure providing the capacity, efficiency, and flexibility necessary to realize benefits of the future mature Free-Flight environment. The capabilities and scope of communications technologies needed to accomplish this goal depend on characteristics of the future Free-Flight environment. There are many operational concepts being proposed for a future ATM system to enable user flexibility and efficiency. GRC s focus is on developing new technologies and techniques to support the digital communication of information involving airborne and ground-based users. However, the technologies and techniques must be integrated with the systems and services that industry and the Federal Aviation Administration (FAA) are developing. Thus, GRC needs to monitor and provide input to the various industry and FAA organizations and committees that are specifying new systems and services. Adoption of technologies by the FAA is partially dependent on acceptance of the technology by the aviation community. The commercial aviation community in particular would like to adopt technologies that can be used throughout the world. As a result, the adoption of common or at least compatible technologies by European countries is a key factor in getting commitments to those technologies by the US aviation community. GRC desires to keep informed of European activities that relate to aviation communication technologies, particularly those that are being supported by Eurocontrol.

The Utility of Handheld Programmable Calculators in Aircraft Life Cycle Cost Estimation.

DTIC Science & Technology

1982-09-01

are available for extended mem - ory, hardcopy printout, video interface, and special application software. Any calculator of comparable memory could...condi- tioning system. OG Total number of engine, air turbine motor (ATM) and auxiliary power unit (APU) driven generator/alternators. OHP Total number

Modeling support for Alabama MPOs

DOT National Transportation Integrated Search

2010-07-29

The Fort Collins Advance Traffic Management System (ATMS) was a FY01 earmarked project. The objective of the overall project was to rebuild the City's entire traffic management system to utilize and provide Intelligent Transportation System (ITS) cap...

ATM Technology Demonstration 1 (ATD-1) Project: Terminal Airspace Technologies for NextGen (Public)

NASA Technical Reports Server (NTRS)

Robinson, John E.; Wang, Easter

2015-01-01

This video highlights the human-in-the-loop (HITL) simulations conducted by the ATD-1 project and features visual elements developed for Traffic Management Advisor - Terminal Metering, Controller Managed Spacing, and Flight Deck Interval Management. The video content is fairly technical and intended for audiences that have some knowledge of air traffic management issues. This includes researchers and management from NASA, FAA, industry partners, and others interested in terminal metering, controller managed spacing, and interval management technologies. Please note that the media release only clears the video for peer audiences such as ATM conferences or as part of presentations to researchers.

AES Cardless Automatic Teller Machine (ATM) Biometric Security System Design Using FPGA Implementation

NASA Astrophysics Data System (ADS)

Ahmad, Nabihah; Rifen, A. Aminurdin M.; Helmy Abd Wahab, Mohd

2016-11-01

Automated Teller Machine (ATM) is an electronic banking outlet that allows bank customers to complete a banking transactions without the aid of any bank official or teller. Several problems are associated with the use of ATM card such card cloning, card damaging, card expiring, cast skimming, cost of issuance and maintenance and accessing customer account by third parties. The aim of this project is to give a freedom to the user by changing the card to biometric security system to access the bank account using Advanced Encryption Standard (AES) algorithm. The project is implemented using Field Programmable Gate Array (FPGA) DE2-115 board with Cyclone IV device, fingerprint scanner, and Multi-Touch Liquid Crystal Display (LCD) Second Edition (MTL2) using Very High Speed Integrated Circuit Hardware (VHSIC) Description Language (VHDL). This project used 128-bits AES for recommend the device with the throughput around 19.016Gbps and utilized around 520 slices. This design offers a secure banking transaction with a low rea and high performance and very suited for restricted space environments for small amounts of RAM or ROM where either encryption or decryption is performed.

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.

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.

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.

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;

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.

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.

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.

Simulation Tool for Dielectric Barrier Discharge Plasma Actuators at Atmospheric and Sub-Atmospheric Pressures: SBIR Phase I Final Report

NASA Technical Reports Server (NTRS)

Likhanskii, Alexandre

2012-01-01

This report is the final report of a SBIR Phase I project. It is identical to the final report submitted, after some proprietary information of administrative nature has been removed. The development of a numerical simulation tool for dielectric barrier discharge (DBD) plasma actuator is reported. The objectives of the project were to analyze and predict DBD operation at wide range of ambient gas pressures. It overcomes the limitations of traditional DBD codes which are limited to low-speed applications and have weak prediction capabilities. The software tool allows DBD actuator analysis and prediction for subsonic to hypersonic flow regime. The simulation tool is based on the VORPAL code developed by Tech-X Corporation. VORPAL's capability of modeling DBD plasma actuator at low pressures (0.1 to 10 torr) using kinetic plasma modeling approach, and at moderate to atmospheric pressures (1 to 10 atm) using hydrodynamic plasma modeling approach, were demonstrated. In addition, results of experiments with pulsed+bias DBD configuration that were performed for validation purposes are reported.

Computer Simulations of Epoxy Adhesive Monomer Interactions with Alumina Surfaces

DTIC Science & Technology

1992-08-01

using Sybyl"’ molecular modeling software 9 on a Digital Equipment Corporation microVAXw cluster. The Tripos force field was employed in the...Ave, N, Ft Leonard Wood, MO 65473-5000 1 ATM- Libary Commander, US. Army Enginer Waterways Expenment Station, P.O. Box 631, Vicksburg, MS 39180 1 ATTN

A Richer Understanding of Algebra

ERIC Educational Resources Information Center

Foy, Michelle

2008-01-01

Algebra is one of those hard-to-teach topics where pupils seem to struggle to see it as more than a set of rules to learn, but this author recently used the software "Grid Algebra" from ATM, which engaged her Year 7 pupils in exploring algebraic concepts for themselves. "Grid Algebra" allows pupils to experience number,…

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

DTIC Science & Technology

2006-07-01

patients who are carriers of an alteration in this gene . This project is innovative as it represents the first study to use the powerful DHPLC mutation ...development of adverse responses to radiotherapy (5-6). The first gene to have received significant attention was the mutated in ataxia telangiectasia (AT...Group and Concannon PJ. 2003. Designing and implementing quality control for multi-center screening of mutations in the ATM gene among women with

City of Fort Collins advanced traffic management system : final report

DOT National Transportation Integrated Search

2009-01-01

The Fort Collins Advance Traffic Management System (ATMS) was a FY01 earmarked project. The objective of the overall project was to rebuild the Citys entire traffic management system to utilize and provide Intelligent Transportation System (ITS) c...

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

PubMed

DeClaris, John-William

2009-01-01

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

Low-cost Tools for Aerial Video Geolocation and Air Traffic Analysis for Delay Reduction Using Google Earth

NASA Astrophysics Data System (ADS)

Zetterlind, V.; Pledgie, S.

2009-12-01

Low-cost, low-latency, robust geolocation and display of aerial video is a common need for a wide range of earth observing as well as emergency response and security applications. While hardware costs for aerial video collection systems, GPS, and inertial sensors have been decreasing, software costs for geolocation algorithms and reference imagery/DTED remain expensive and highly proprietary. As part of a Federal Small Business Innovative Research project, MosaicATM and EarthNC, Inc have developed a simple geolocation system based on the Google Earth API and Google's 'built-in' DTED and reference imagery libraries. This system geolocates aerial video based on platform and camera position, attitude, and field-of-view metadata using geometric photogrammetric principles of ray-intersection with DTED. Geolocated video can be directly rectified and viewed in the Google Earth API during processing. Work is underway to extend our geolocation code to NASA World Wind for additional flexibility and a fully open-source platform. In addition to our airborne remote sensing work, MosaicATM has developed the Surface Operations Data Analysis and Adaptation (SODAA) tool, funded by NASA Ames, which supports analysis of airport surface operations to optimize aircraft movements and reduce fuel burn and delays. As part of SODAA, MosaicATM and EarthNC, Inc have developed powerful tools to display national airspace data and time-animated 3D flight tracks in Google Earth for 4D analysis. The SODAA tool can convert raw format flight track data, FAA National Flight Data (NFD), and FAA 'Adaptation' airport surface data to a spatial database representation and then to Google Earth KML. The SODAA client provides users with a simple graphical interface through which to generate queries with a wide range of predefined and custom filters, plot results, and export for playback in Google Earth in conjunction with NFD and Adaptation overlays.

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.

NPOESS Preparatory Project Validation Program for the Cross-track Infrared Sounder

NASA Astrophysics Data System (ADS)

Barnet, C.; Gu, D.; Nalli, N. R.

2009-12-01

The National Polar-orbiting Operational Environmental Satellite System (NPOESS) Program, in partnership with National Aeronautical Space Administration (NASA), will launch the NPOESS Preparatory Project (NPP), a risk reduction and data continuity mission, prior to the first operational NPOESS launch. The NPOESS Program, in partnership with Northrop Grumman Aerospace Systems, will execute the NPP Calibration and Validation (Cal/Val) program to ensure the data products comply with the requirements of the sponsoring agencies. The Cross-track Infrared Sounder (CrIS) and the Advanced Technology Microwave Sounder (ATMS) are two of the instruments that make up the suite of sensors on NPP. Together, CrIS and ATMS will produce three Environmental Data Records (EDRs) including the Atmospheric Vertical Temperature Profile (AVTP), Atmospheric Vertical Moisture Profile (AVMP), and the Atmospheric Vertical Pressure Profile (AVPP). The AVTP and the AVMP are both NPOESS Key Performance Parameters (KPPs). The validation plans establish science and user community leadership and participation, and demonstrated, cost-effective Cal/Val approaches. This presentation will provide an overview of the collaborative data, techniques, and schedule for the validation of the NPP CrIS and ATMS environmental data products.

The development of a Flight Test Engineer's Workstation for the Automated Flight Test Management System

NASA Technical Reports Server (NTRS)

Tartt, David M.; Hewett, Marle D.; Duke, Eugene L.; Cooper, James A.; Brumbaugh, Randal W.

1989-01-01

The Automated Flight Test Management System (ATMS) is being developed as part of the NASA Aircraft Automation Program. This program focuses on the application of interdisciplinary state-of-the-art technology in artificial intelligence, control theory, and systems methodology to problems of operating and flight testing high-performance aircraft. The development of a Flight Test Engineer's Workstation (FTEWS) is presented, with a detailed description of the system, technical details, and future planned developments. The goal of the FTEWS is to provide flight test engineers and project officers with an automated computer environment for planning, scheduling, and performing flight test programs. The FTEWS system is an outgrowth of the development of ATMS and is an implementation of a component of ATMS on SUN workstations.

Airspace Technology Demonstration 3 (ATD-3): Applied Traffic Flow Management Project Overview

NASA Technical Reports Server (NTRS)

Gong, Chester

2016-01-01

ATD-3 Project Overview for 3rd Joint Workshop for KAIA-KARI - NASA ATM Research Collaboration. This presentation gives a high level description of the ATD-3 project and related technologies. These technologies include Multi-Flight Common Routes (MFCR), Traffic Aware Strategic Aircrew Requests (TASAR) and Dynamic Routes for Arrivals in Weather (DRAW).

Attitudes Toward Medications and the Relationship to Outcomes in Patients with Schizophrenia.

PubMed

Campbell, Angela H; Scalo, Julieta F; Crismon, M Lynn; Barner, Jamie C; Argo, Tami R; Lawson, Kenneth A; Miller, Alexander

The determinants of attitudes toward medication (ATM) are not well elucidated. In particular, literature remains equivocal regarding the influence of cognition, adverse events, and psychiatric symptomatology. This study evaluated relationships between those outcomes in schizophrenia and ATM. This is a retrospective analysis of data collected during the Texas Medication Algorithm Project (TMAP, n=307 with schizophrenia-related diagnoses), in outpatient clinics at baseline and every 3 months for ≥1 year (for cognition: 3rd and 9th month only). The Drug Attitude Inventory (DAI-30) measured ATM, and independent variables were: cognition (Trail Making Test [TMT], Verbal Fluency Test, Hopkins Verbal Learning Test), adverse events (Systematic Assessment for Treatment-Emergent Adverse Events, Barnes Akathisia Rating Scale), psychiatric symptomatology (Brief Psychiatric Rating Scale, Scale for Assessment of Negative Symptoms [SANS]), and medication adherence (Medication Compliance Scale). Analyses included binary logistic regression (cognition, psychiatric symptoms) and chi-square (adverse events, adherence) for baseline comparisons, and linear regression (cognition) or ANOVA (adverse events, adherence) for changes over time. Mean DAI-30 scores did not change over 12 months. Odds of positive ATM increased with higher TMT Part B scores (p=0.03) and lower SANS scores (p=0.02). Worsening of general psychopathology (p<0.001), positive symptoms (p<0.001), and negative symptoms (p=0.007) correlated with negative changes in DAI-30 scores. Relationships between cognition, negative symptoms, and ATM warrant further investigation. Studies evaluating therapies for cognitive deficits and negative symptoms should consider including ATM measures as endpoints. Patterns and inconsistencies in findings across studies raise questions about whether some factors thought to influence ATM have nonlinear relationships.

ATM Technology Demonstration-1 Phase II Boeing Configurable Graphical Display (CGD) Software Design Description

NASA Technical Reports Server (NTRS)

Wilber, George F.

2017-01-01

This Software Description Document (SDD) captures the design for developing the Flight Interval Management (FIM) system Configurable Graphics Display (CGD) software. Specifically this SDD describes aspects of the Boeing CGD software and the surrounding context and interfaces. It does not describe the Honeywell components of the CGD system. The SDD provides the system overview, architectural design, and detailed design with all the necessary information to implement the Boeing components of the CGD software and integrate them into the CGD subsystem within the larger FIM system. Overall system and CGD system-level requirements are derived from the CGD SRS (in turn derived from the Boeing System Requirements Design Document (SRDD)). Display and look-and-feel requirements are derived from Human Machine Interface (HMI) design documents and working group recommendations. This Boeing CGD SDD is required to support the upcoming Critical Design Review (CDR).

RAD-ADAPT: Software for modelling clonogenic assay data in radiation biology.

PubMed

Zhang, Yaping; Hu, Kaiqiang; Beumer, Jan H; Bakkenist, Christopher J; D'Argenio, David Z

2017-04-01

We present a comprehensive software program, RAD-ADAPT, for the quantitative analysis of clonogenic assays in radiation biology. Two commonly used models for clonogenic assay analysis, the linear-quadratic model and single-hit multi-target model, are included in the software. RAD-ADAPT uses maximum likelihood estimation method to obtain parameter estimates with the assumption that cell colony count data follow a Poisson distribution. The program has an intuitive interface, generates model prediction plots, tabulates model parameter estimates, and allows automatic statistical comparison of parameters between different groups. The RAD-ADAPT interface is written using the statistical software R and the underlying computations are accomplished by the ADAPT software system for pharmacokinetic/pharmacodynamic systems analysis. The use of RAD-ADAPT is demonstrated using an example that examines the impact of pharmacologic ATM and ATR kinase inhibition on human lung cancer cell line A549 after ionizing radiation. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of the impact of the I-66 active traffic management system : final report.

DOT National Transportation Integrated Search

2016-09-01

Construction of a Virginia Department of Transportation project to install an Active Traffic Management (ATM) system on Interstate-66 (I-66) from U.S. 29 in Centreville to the Capital Beltway (I-495) was completed in September 2015. The project was c...

Our turbulent Sun

NASA Astrophysics Data System (ADS)

Smith, K.

2003-12-01

Sunspots in H-alpha. Image taken at the Equinox Star Camp at Thetford on 2002 September 12 by Kevin Smith. Equipment used was a Daystar 0.7ATM H-alpha filter on a Takahashi FS128, and a Televue x4 Powermate. The image was made using a Basler digital camera with Aquinto A4I Docu software. Slight adjustments to highlight surface detail were made with Adobe Photoshop.

National Air Space (NAS) Data Exchange Environment Through 2060

NASA Technical Reports Server (NTRS)

Roy, Aloke

2015-01-01

NASA's NextGen Concepts and Technology Development (CTD) Project focuses on capabilities to improve safety, capacity and efficiency of the National Air Space (NAS). In order to achieve those objectives, NASA sought industry-Government partnerships to research and identify solutions for traffic flow management, dynamic airspace configuration, separation assurance, super density operations, airport surface operations and similar forward-looking air-traffic modernization (ATM) concepts. Data exchanges over NAS being the key enabler for most of these ATM concepts, the Sub-Topic area 3 of the CTD project sought to identify technology candidates that can satisfy air-to-air and air/ground communications needs of the NAS in the year 2060 timeframe. Honeywell, under a two-year contract with NASA, is working on this communications technology research initiative. This report summarizes Honeywell's research conducted during the second year of the study task.

Odor tracking in sharks is reduced under future ocean acidification conditions.

PubMed

Dixson, Danielle L; Jennings, Ashley R; Atema, Jelle; Munday, Philip L

2015-04-01

Recent studies show that ocean acidification impairs sensory functions and alters the behavior of teleost fishes. If sharks and other elasmobranchs are similarly affected, this could have significant consequences for marine ecosystems globally. Here, we show that projected future CO2 levels impair odor tracking behavior of the smooth dogfish (Mustelus canis). Adult M. canis were held for 5 days in a current-day control (405 ± 26 μatm) and mid (741 ± 22 μatm) or high CO2 (1064 ± 17 μatm) treatments consistent with the projections for the year 2100 on a 'business as usual' scenario. Both control and mid CO2 -treated individuals maintained normal odor tracking behavior, whereas high CO2 -treated sharks significantly avoided the odor cues indicative of food. Control sharks spent >60% of their time in the water stream containing the food stimulus, but this value fell below 15% in high CO2 -treated sharks. In addition, sharks treated under mid and high CO2 conditions reduced attack behavior compared to the control individuals. Our findings show that shark feeding could be affected by changes in seawater chemistry projected for the end of this century. Understanding the effects of ocean acidification on critical behaviors, such as prey tracking in large predators, can help determine the potential impacts of future ocean acidification on ecosystem function. © 2014 John Wiley & Sons Ltd.

Surface protection overview

NASA Technical Reports Server (NTRS)

Levine, S. R.

1982-01-01

A first-cut integrated environmental attack life prediction methodology for hot section components is addressed. The HOST program is concerned with oxidation and hot corrosion attack of metallic coatings as well as their degradation by interdiffusion with the substrate. The effects of the environment and coatings on creep/fatigue behavior are being addressed through a joint effort with the Fatigue sub-project. An initial effort will attempt to scope the problem of thermal barrier coating life prediction. Verification of models will be carried out through benchmark rig tests including a 4 atm. replaceable blade turbine and a 50 atm. pressurized burner rig.

Simultaneous ATM/BRCA1/RAD51 expression variations associated with prognostic factors in Iranian sporadic breast cancer patients.

PubMed

Hallajian, Zeinab; Mahjoubi, Frouzandeh; Nafissi, Nahid

2017-07-01

DNA double-strand breaks (DSBs) as a serious lesion are repaired by non-homologous end-joining and homologous recombination pathways. ATM, BRCA1, RAD51 genes are involved in HR pathways. While some studies have revealed individual expression changes of these genes in different types of cancer, there are limited studies attempting to evaluate correlation of expression variations of these genes in breast cancer pathogenesis. This study aimed to determine RAD51, ATM and BRCA1 gene expression level and its association with clinicopathological factors in fresh breast cancer tissues. Moreover, this study evaluates potential correlations among expression levels of these genes. 50 breast cancer tissues were collected and examined for BRCA1, RAD51 and ATM gene expression by Real Time PCR. Expression changes were analyzed with REST software version 2009. mRNA expression was reduced in all these three genes when compared with β-Actin as a control gene (P value  < 0.001). Spearman's test demonstrated a significant positive correlation among ATM, BRCA1 and RAD51 gene down expression (P value  < 0.0001). There was a significant association between down expression of ATM with stage (P value  < 0.05), necrosis (P value  < 0.05), perineural invasion (P value  < 0.05), vascular invasion (P value  < 0.01), malignancy (P value  ≤ 0.001), PR (P value  < 0.05) and ER status (P value  < 0.01). In addition, there was a significant association between down expression of BRCA1 with Ki67 (P value  ≤ 0.001). Moreover, there was a significant association between down expression of RAD51 with lymph node involvement (P value  < 0.01), auxiliary lymph node metastasis (P value  = 0.01), age (P = 0.001), grade (P value  < 0.05) and PR status (P value  < 0.05). This study suggests association between expression changes in several DSB repair genes in a common functional pathway in breast cancer and the significant association between abnormal expression of these genes and important clinical prognostic factors.

The NPOESS Crosstrack Infrared Sounder (CrIS) and Advanced Technology Microwave Sounder (ATMS) as a Companion to the New Generation AIRS/AMSU and IASI/AMSU Sounder Suites

NASA Astrophysics Data System (ADS)

Bingham, G. E.; Pougatchev, N. S.; Zavyalov, V.; Esplin, M.; Blackwell, W. J.; Barnet, C.

2009-12-01

The NPOESS Preparatory Project is serving the operations and research community as the bridge mission between the Earth Observing System and the National Polar-orbiting Operational Environmental Satellite System. The Cross-track Infrared Sounder (CrIS), combined with the Advanced Technology Microwave Sounder (ATMS) are the core instruments to provide the key performance temperature and humidity profiles (along with some other atmospheric constituent information). Both the high spectral resolution CrIS and the upgraded microwave sounder (ATMS) will be working in parallel with already orbiting Advanced Atmospheric Infrared Sounder (AIRS/AMSU) on EOS AQUA platform and Infrared Atmospheric Sounding Interferometer (IASI/AMSU) on METOP-A satellite. This presentation will review the CrIS/ATMS capabilities in the context of continuity with the excellent performance records established by AIRS and IASI. The CrIS sensor is in the process of its final calibration and characterization testing and the results and Sensor Data Record process are being validated against this excellent dataset. The comparison between CrIS, AIRS, and IASI will include spectral, spatial, radiometric performance and sounding capability comparisons.

Effects of elevated CO2 on fish behaviour undiminished by transgenerational acclimation

NASA Astrophysics Data System (ADS)

Welch, Megan J.; Watson, Sue-Ann; Welsh, Justin Q.; McCormick, Mark I.; Munday, Philip L.

2014-12-01

Behaviour and sensory performance of marine fishes are impaired at CO2 levels projected to occur in the ocean in the next 50-100 years, and there is limited potential for within-generation acclimation to elevated CO2 (refs , ). However, whether fish behaviour can acclimate or adapt to elevated CO2 over multiple generations remains unanswered. We tested for transgenerational acclimation of reef fish olfactory preferences and behavioural lateralization at moderate (656 μatm) and high (912 μatm) end-of-century CO2 projections. Juvenile spiny damselfish, Acanthochromis polyacanthus, from control parents (446 μatm) exhibited an innate avoidance to chemical alarm cue (CAC) when reared in control conditions. In contrast, juveniles lost their innate avoidance of CAC and even became strongly attracted to CAC when reared at elevated CO2 levels. Juveniles from parents maintained at mid-CO2 and high-CO2 levels also lost their innate avoidance of CAC when reared in elevated CO2, demonstrating no capacity for transgenerational acclimation of olfactory responses. Behavioural lateralization was also disrupted for juveniles reared under elevated CO2, regardless of parental conditioning. Our results show minimal potential for transgenerational acclimation in this fish, suggesting that genetic adaptation will be necessary to overcome the effects of ocean acidification on behaviour.

Ocean acidification reduces the crystallographic control in juvenile mussel shells.

PubMed

Fitzer, Susan C; Cusack, Maggie; Phoenix, Vernon R; Kamenos, Nicholas A

2014-10-01

Global climate change threatens the oceans as anthropogenic carbon dioxide causes ocean acidification and reduced carbonate saturation. Future projections indicate under saturation of aragonite, and potentially calcite, in the oceans by 2100. Calcifying organisms are those most at risk from such ocean acidification, as carbonate is vital in the biomineralisation of their calcium carbonate protective shells. This study highlights the importance of multi-generational studies to investigate how marine organisms can potentially adapt to future projected global climate change. Mytilus edulis is an economically important marine calcifier vulnerable to decreasing carbonate saturation as their shells comprise two calcium carbonate polymorphs: aragonite and calcite. M. edulis specimens were cultured under current and projected pCO2 (380, 550, 750 and 1000μatm), following 6months of experimental culture, adults produced second generation juvenile mussels. Juvenile mussel shells were examined for structural and crystallographic orientation of aragonite and calcite. At 1000μatm pCO2, juvenile mussels spawned and grown under this high pCO2 do not produce aragonite which is more vulnerable to carbonate under-saturation than calcite. Calcite and aragonite were produced at 380, 550 and 750μatm pCO2. Electron back scatter diffraction analyses reveal less constraint in crystallographic orientation with increased pCO2. Shell formation is maintained, although the nacre crystals appear corroded and crystals are not so closely layered together. The differences in ultrastructure and crystallography in shells formed by juveniles spawned from adults in high pCO2 conditions may prove instrumental in their ability to survive ocean acidification. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Lessons Learned from the Deployment and Integration of a Microwave Sounder Based Tropical Cyclone Intensity and Surface Wind Estimation Algorithm into NOAA/NESDIS Satellite Product Operations

NASA Astrophysics Data System (ADS)

Longmore, S. P.; Knaff, J. A.; Schumacher, A.; Dostalek, J.; DeMaria, R.; Chirokova, G.; Demaria, M.; Powell, D. C.; Sigmund, A.; Yu, W.

2014-12-01

The Colorado State University (CSU) Cooperative Institute for Research in the Atmosphere (CIRA) has recently deployed a tropical cyclone (TC) intensity and surface wind radii estimation algorithm that utilizes Suomi National Polar-orbiting Partnership (S-NPP) satellite Advanced Technology Microwave Sounder (ATMS) and Advanced Microwave Sounding Unit (AMSU) from the NOAA18, NOAA19 and METOPA polar orbiting satellites for testing, integration and operations for the Product System Development and Implementation (PSDI) projects at NOAA's National Environmental Satellite, Data, and Information Service (NESDIS). This presentation discusses the evolution of the CIRA NPP/AMSU TC algorithms internally at CIRA and its migration and integration into the NOAA Data Exploitation (NDE) development and testing frameworks. The discussion will focus on 1) the development cycle of internal NPP/AMSU TC algorithms components by scientists and software engineers, 2) the exchange of these components into the NPP/AMSU TC software systems using the subversion version control system and other exchange methods, 3) testing, debugging and integration of the NPP/AMSU TC systems both at CIRA/NESDIS and 4) the update cycle of new releases through continuous integration. Lastly, a discussion of the methods that were effective and those that need revision will be detailed for the next iteration of the NPP/AMSU TC system.

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.

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.

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

Evaluation of the effectiveness of ATM messages used during incidents : final report.

DOT National Transportation Integrated Search

2016-01-01

This project investigated the use of Intelligent Lane Control Signs based Active Traffic Management for : Incident Management on a heavily traveled urban freeway. The subject of the research was the ILCS : system on I-94 westbound in downtown Minneap...

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.

Additional Cultural Resources Investigations at Selected Portions of the State-Road Coulee - Pammel Creek Flood Control Project at La Crosse, Wisconsin

DTIC Science & Technology

1986-05-01

Mammals: Ten mammal taxa are represented in the Lc176 assemblage. Two of these, the short-tailed shrew (Blarina brevivicauda) and a vole (Microtus sp...ADDITIONAL CULTURAL RESOURCES INVESTIGATIONS AT SELECTED PORTIONS OF THE STATE-ROAD COULEE - PAMMEL CREEK FLOOD CONTROL PROJECT ATm LA CROSSE...INVESTIGATIONS AT SELECTED PORTIONS OF THE STATE-ROAD COULEE- PAMMEL CREEK FLOOD CONTROL PROJECT AT LA CROSSE. WISCONSIN 12. PERSONAL AUTHOR(S

PACS in Töölö hospital.

PubMed

Kinnunen, J; Pohjonen, H

2001-07-01

A 3-year PACS project was started in 1997 and completed in 1999 with filmless radiology and surgery. An efficient network for transferring images provides the infrastructure for integration of different distributed imaging systems and enables efficient handling of all patient-related information on one display station. Because of the need for high-speed communications and the massive amount of image data transferred in radiology, ATM (25, 155 Mbit/s) was chosen to be the main technology used. Both hardware and software redundancy of the system have been carefully planned. The size of the Dicom image library utilizing MO discs is currently 1.2 TB with 300 GB RAID capacity. For the increasing amount of teleradiologic consultations, a special Dicom gateway is planned. It allows a centralized and resilient handling and routing of received images around the hospital. Hospital-wide PACS has already improved the speed and quality of patient care by providing instant access to diagnostic information at multiple locations simultaneously. The benefits of PACS are considered from the viewpoint of the entire hospital: PACS offers a method for efficiently transporting patient-related images and reports to the referring physicians.

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.

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.

ATM Coastal Topography-Alabama 2001

USGS Publications Warehouse

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

2009-01-01

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

ATM Coastal Topography-Florida 2001: Eastern Panhandle

USGS Publications Warehouse

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

2009-01-01

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

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.

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.

ATM supports gammaherpesvirus replication by attenuating type I interferon pathway.

PubMed

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

2017-10-01

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

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.

Requirements: Towards an understanding on why software projects fail

NASA Astrophysics Data System (ADS)

Hussain, Azham; Mkpojiogu, Emmanuel O. C.

2016-08-01

Requirement engineering is at the foundation of every successful software project. There are many reasons for software project failures; however, poorly engineered requirements process contributes immensely to the reason why software projects fail. Software project failure is usually costly and risky and could also be life threatening. Projects that undermine requirements engineering suffer or are likely to suffer from failures, challenges and other attending risks. The cost of project failures and overruns when estimated is very huge. Furthermore, software project failures or overruns pose a challenge in today's competitive market environment. It affects the company's image, goodwill, and revenue drive and decreases the perceived satisfaction of customers and clients. In this paper, requirements engineering was discussed. Its role in software projects success was elaborated. The place of software requirements process in relation to software project failure was explored and examined. Also, project success and failure factors were also discussed with emphasis placed on requirements factors as they play a major role in software projects' challenges, successes and failures. The paper relied on secondary data and empirical statistics to explore and examine factors responsible for the successes, challenges and failures of software projects in large, medium and small scaled software companies.

EPA AND ERDA HIGH-TEMPERATURE/HIGH-PRESSURE PARTICULATE CONTROL PROGRAMS

EPA Science Inventory

The report describes and compares current projects sponsored by EPA and the U.S. Energy Research and Development Administration (ERDA), relating to the control of particulate matter in fuel gas streams at high temperatures (1000 to 2000F) and high pressures (5 atm and greater). T...

Guidance and Control Software Project Data - Volume 4: Configuration Management and Quality Assurance Documents

NASA Technical Reports Server (NTRS)

Hayhurst, Kelly J. (Editor)

2008-01-01

The Guidance and Control Software (GCS) project was the last in a series of software reliability studies conducted at Langley Research Center between 1977 and 1994. The technical results of the GCS project were recorded after the experiment was completed. Some of the support documentation produced as part of the experiment, however, is serving an unexpected role far beyond its original project context. Some of the software used as part of the GCS project was developed to conform to the RTCA/DO-178B software standard, "Software Considerations in Airborne Systems and Equipment Certification," used in the civil aviation industry. That standard requires extensive documentation throughout the software development life cycle, including plans, software requirements, design and source code, verification cases and results, and configuration management and quality control data. The project documentation that includes this information is open for public scrutiny without the legal or safety implications associated with comparable data from an avionics manufacturer. This public availability has afforded an opportunity to use the GCS project documents for DO-178B training. This report provides a brief overview of the GCS project, describes the 4-volume set of documents and the role they are playing in training, and includes configuration management and quality assurance documents from the GCS project. Volume 4 contains six appendices: A. Software Accomplishment Summary for the Guidance and Control Software Project; B. Software Configuration Index for the Guidance and Control Software Project; C. Configuration Management Records for the Guidance and Control Software Project; D. Software Quality Assurance Records for the Guidance and Control Software Project; E. Problem Report for the Pluto Implementation of the Guidance and Control Software Project; and F. Support Documentation Change Reports for the Guidance and Control Software Project.

Guidance and Control Software Project Data - Volume 1: Planning Documents

NASA Technical Reports Server (NTRS)

Hayhurst, Kelly J. (Editor)

2008-01-01

The Guidance and Control Software (GCS) project was the last in a series of software reliability studies conducted at Langley Research Center between 1977 and 1994. The technical results of the GCS project were recorded after the experiment was completed. Some of the support documentation produced as part of the experiment, however, is serving an unexpected role far beyond its original project context. Some of the software used as part of the GCS project was developed to conform to the RTCA/DO-178B software standard, "Software Considerations in Airborne Systems and Equipment Certification," used in the civil aviation industry. That standard requires extensive documentation throughout the software development life cycle, including plans, software requirements, design and source code, verification cases and results, and configuration management and quality control data. The project documentation that includes this information is open for public scrutiny without the legal or safety implications associated with comparable data from an avionics manufacturer. This public availability has afforded an opportunity to use the GCS project documents for DO-178B training. This report provides a brief overview of the GCS project, describes the 4-volume set of documents and the role they are playing in training, and includes the planning documents from the GCS project. Volume 1 contains five appendices: A. Plan for Software Aspects of Certification for the Guidance and Control Software Project; B. Software Development Standards for the Guidance and Control Software Project; C. Software Verification Plan for the Guidance and Control Software Project; D. Software Configuration Management Plan for the Guidance and Control Software Project; and E. Software Quality Assurance Activities.

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

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.

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.

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

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.

ATM encryption testing

NASA Astrophysics Data System (ADS)

Capell, Joyce; Deeth, David

1996-01-01

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

Traffic Management for Satellite-ATM Networks

NASA Technical Reports Server (NTRS)

Goyal, Rohit; Jain, Raj; Fahmy, Sonia; Vandalore, Bobby; Goyal, Mukul

1998-01-01

Various issues associated with "Traffic Management for Satellite-ATM Networks" are presented in viewgraph form. Specific topics include: 1) Traffic management issues for TCP/IP based data services over satellite-ATM networks; 2) Design issues for TCP/IP over ATM; 3) Optimization of the performance of TCP/IP over ATM for long delay networks; and 4) Evaluation of ATM service categories for TCP/IP traffic.

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.

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.

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.

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.

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

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

Gangwal, S.K.; Gupta, R.P.; Khare, G.P.

The objectives of this project are to determine the long-term chemical reactivity and mechanical durability of a fluidized version of Phillips Petroleum Company`s proprietary Z-SORB sorbent for the desulfurization of coal-derived gases in a high-pressure (20 atm) fluidized-bed reactor under simulated U-Gas conditions and at a moderate operating temperature of 538 degrees C.

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.

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.

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.

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.

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

Air To Air Helicopter Fire Control Equations and Software Generation.

DTIC Science & Technology

1979-11-01

A A A A v D1. Bin), velocity (VTs, VTI. VTm). and acceleration (ATs, ATI. ATm) using the measured values of range. Rm. angular rate of the LOS W s...10 second time constant. Note that the input to each integrator also has cross channel coupling terms which are cross products of the LOS angular rate...ownship’s velocity (Vs. V1. Vm). This is subtracted from the estimated target velocity ( VsT . 01T. VmT) before the inal integration so that the

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.

Develop advanced nonlinear signal analysis topographical mapping system

NASA Technical Reports Server (NTRS)

Jong, Jen-Yi

1993-01-01

This study will provide timely assessment of SSME component operational status, identify probable causes of malfunction, and indicate feasible engineering solutions. The final result of this program will yield an advanced nonlinear signal analysis topographical mapping system (ATMS) of nonlinear and nonstationary spectral analysis software package integrated with the Compressed SSME TOPO Data Base (CSTDB) on the same platform. This system will allow NASA engineers to retrieve any unique defect signatures and trends associated with different failure modes and anomalous phenomena over the entire SSME test history across turbopump families.

Software Program: Software Management Guidebook

NASA Technical Reports Server (NTRS)

1996-01-01

The purpose of this NASA Software Management Guidebook is twofold. First, this document defines the core products and activities required of NASA software projects. It defines life-cycle models and activity-related methods but acknowledges that no single life-cycle model is appropriate for all NASA software projects. It also acknowledges that the appropriate method for accomplishing a required activity depends on characteristics of the software project. Second, this guidebook provides specific guidance to software project managers and team leaders in selecting appropriate life cycles and methods to develop a tailored plan for a software engineering project.

Lessons from two high CO2 worlds - future oceans and intensive aquaculture.

PubMed

Ellis, Robert P; Urbina, Mauricio A; Wilson, Rod W

2017-06-01

Exponentially rising CO 2 (currently ~400 μatm) is driving climate change and causing acidification of both marine and freshwater environments. Physiologists have long known that CO 2 directly affects acid-base and ion regulation, respiratory function and aerobic performance in aquatic animals. More recently, many studies have demonstrated that elevated CO 2 projected for end of this century (e.g. 800-1000 μatm) can also impact physiology, and have substantial effects on behaviours linked to sensory stimuli (smell, hearing and vision) both having negative implications for fitness and survival. In contrast, the aquaculture industry was farming aquatic animals at CO 2 levels that far exceed end-of-century climate change projections (sometimes >10 000 μatm) long before the term 'ocean acidification' was coined, with limited detrimental effects reported. It is therefore vital to understand the reasons behind this apparent discrepancy. Potential explanations include 1) the use of 'control' CO 2 levels in aquaculture studies that go beyond 2100 projections in an ocean acidification context; 2) the relatively benign environment in aquaculture (abundant food, disease protection, absence of predators) compared to the wild; 3) aquaculture species having been chosen due to their natural tolerance to the intensive conditions, including CO 2 levels; or 4) the breeding of species within intensive aquaculture having further selected traits that confer tolerance to elevated CO 2 . We highlight this issue and outline the insights that climate change and aquaculture science can offer for both marine and freshwater settings. Integrating these two fields will stimulate discussion on the direction of future cross-disciplinary research. In doing so, this article aimed to optimize future research efforts and elucidate effective mitigation strategies for managing the negative impacts of elevated CO 2 on future aquatic ecosystems and the sustainability of fish and shellfish aquaculture. © 2016 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

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.

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

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

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

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.

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.

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.

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.

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.

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 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.

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

Measuring $$\

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

Mitchell, Jessica Sarah

2011-01-01

The MINOS Experiment consists of two steel-scintillator calorimeters, sampling the long baseline NuMI muon neutrino beam. It was designed to make a precise measurement of the ‘atmospheric’ neutrino mixing parameters, Δm 2 atm. and sin 2 (2 atm.). The Near Detector measures the initial spectrum of the neutrino beam 1km from the production target, and the Far Detector, at a distance of 735 km, measures the impact of oscillations in the neutrino energy spectrum. Work performed to validate the quality of the data collected by the Near Detector is presented as part of this thesis. This thesis primarily details themore » results of a v μ disappearance analysis, and presents a new sophisticated fitting software framework, which employs a maximum likelihood method to extract the best fit oscillation parameters. The software is entirely decoupled from the extrapolation procedure between the detectors, and is capable of fitting multiple event samples (defined by the selections applied) in parallel, and any combination of energy dependent and independent sources of systematic error. Two techniques to improve the sensitivity of the oscillation measurement were also developed. The inclusion of information on the energy resolution of the neutrino events results in a significant improvement in the allowed region for the oscillation parameters. The degree to which sin 2 (2θ )= 1.0 could be disfavoured with the exposure of the current dataset if the true mixing angle was non-maximal, was also investigated, with an improved neutrino energy reconstruction for very low energy events. The best fit oscillation parameters, obtained by the fitting software and incorporating resolution information were: | Δm 2| = 2.32 +0.12 -0.08×10 -3 eV 2 and sin 2 (2θ ) > 0.90(90% C.L.). The analysis provides the current world best measurement of the atmospheric neutrino mass splitting Δm 2. The alternative models of neutrino decay and decoherence are disfavoured by 7.8σ and 9.7σ respectively.« less

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

USGS Publications Warehouse

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

2009-01-01

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

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

USGS Publications Warehouse

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

2010-01-01

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

ATM Coastal Topography-Texas, 2001: UTM Zone 14

USGS Publications Warehouse

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

2009-01-01

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

ATM Coastal Topography-Texas, 2001: UTM Zone 15

USGS Publications Warehouse

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

2009-01-01

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

ATM Coastal Topography-Florida 2001: Western Panhandle

USGS Publications Warehouse

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

2009-01-01

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

ATM Coastal Topography-Mississippi, 2001

USGS Publications Warehouse

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

2009-01-01

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

Better quality of mother-child interaction at 4 years of age decreases emotional overeating in IUGR girls.

PubMed

Escobar, R S; O'Donnell, K A; Colalillo, S; Pawlby, S; Steiner, M; Meaney, M J; Levitan, R D; Silveira, P P

2014-10-01

While most "fetal programming" area focused on metabolic disease, intrauterine growth restriction (IUGR) is also associated with a preference for less healthy food. Post-natal factors such as strained maternal-child interactions are equally related to obesogenic eating behaviors. We investigated if IUGR and the quality of the mother/child relationship affect emotional overeating in children. Participants were 196 children from a prospective birth cohort (the MAVAN project). As part of the protocol at 4 years of age, mothers completed the Children Eating Behavior Questionnaire (CEBQ) and mother-child interactions were scored during a structured task. A GLM adjusted for BMI examined the interaction between the "Atmosphere" score (ATM) task, sex and IUGR on the emotional over-eating domain of the CEBQ. There was a significant interaction of BWR vs. sex vs. ATM (P = .02), with no effects of IUGR, sex or ATM. The model was significant for girls with low ATM scores (B = -2.035, P = .014), but not for girls with high (P = 0.94) or boys with high (P = .27) or low (P = .19) ATM scores. Only in IUGR girls, 48 months emotional over-eating correlated with BMI at that age (r = 0.560, P = 0.013) and predicted BMI in the subsequent years (r = 0.654, P = 0.006 at 60 months and r = 0.750, P = 0.005 at 72 months). IUGR and exposure to a negative emotional atmosphere during maternal-child interactions predicted emotional overeating in girls but not in boys. The quality of mother-infant interaction may be an important target for interventions to prevent emotional overeating and overweight in early development, particularly in girls with a history of IUGR. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impacts of food availability and pCO2 on planulation, juvenile survival, and calcification of the azooxanthellate scleractinian coral Balanophyllia elegans

NASA Astrophysics Data System (ADS)

Crook, E. D.; Cooper, H.; Potts, D. C.; Lambert, T.; Paytan, A.

2013-11-01

Ocean acidification, the assimilation of atmospheric CO2 by the oceans that decreases the pH and CaCO3 saturation state (Ω) of seawater, is projected to have severe adverse consequences for calcifying organisms. While strong evidence suggests calcification by tropical reef-building corals containing algal symbionts (zooxanthellae) will decline over the next century, likely responses of azooxanthellate corals to ocean acidification are less well understood. Because azooxanthellate corals do not obtain photosynthetic energy from symbionts, they provide a system for studying the direct effects of acidification on energy available for calcification. The solitary azooxanthellate orange cup coral Balanophyllia elegans often lives in low-pH, upwelled waters along the California coast. In an 8-month factorial experiment, we measured the effects of three pCO2 treatments (410, 770, and 1220 μatm) and two feeding frequencies (3-day and 21-day intervals) on "planulation" (larval release) by adult B. elegans, and on the survival, skeletal growth, and calcification of newly settled juveniles. Planulation rates were affected by food level but not pCO2. Juvenile mortality was highest under high pCO2 (1220 μatm) and low food (21-day intervals). Feeding rate had a greater impact on calcification of B. elegans than pCO2. While net calcification was positive even at 1220 μatm (~3 times current atmospheric pCO2), overall calcification declined by ~25-45%, and skeletal density declined by ~35-45% as pCO2 increased from 410 to 1220 μatm. Aragonite crystal morphology changed at high pCO2, becoming significantly shorter but not wider at 1220 μatm. We conclude that food abundance is critical for azooxanthellate coral calcification, and that B. elegans may be partially protected from adverse consequences of ocean acidification in habitats with abundant heterotrophic food.

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.

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.

Management of ATM-based networks supporting multimedia medical information systems

NASA Astrophysics Data System (ADS)

Whitman, Robert A.; Blaine, G. James; Fritz, Kevin; Goodgold, Ken; Heisinger, Patrick

1997-05-01

Medical information systems are acquiring the ability to collect and deliver many different types of medical information. In support of the increased network demands necessitated by these expanded capabilities, asynchronous transfer mode (ATM) based networks are being deployed in medical care systems. While ATM supplies a much greater line rate than currently deployed networks, the management and standards surrounding ATM are yet to mature. This paper explores the management and control issues surrounding an ATM network supporting medical information systems, and examines how management impacts network performance and robustness. A multivendor ATM network at the BJC Health System/Washington University and the applications using the network are discussed. Performance information for specific applications is presented and analyzed. Network management's influence on application reliability is outlined. The information collected is used to show how ATM network standards and management tools influence network reliability and performance. Performance of current applications using the ATM network is discussed. Special attention is given to issues encountered in implementation of hypertext transfer protocol over ATM internet protocol (IP) communications. A classical IP ATM implementation yields greater than twenty percent higher network performance over LANE. Maximum performance for a host's suite of applications can be obtained by establishing multiple individually engineered IP links through its ATM network connection.

Four applications of a software data collection and analysis methodology

NASA Technical Reports Server (NTRS)

Basili, Victor R.; Selby, Richard W., Jr.

1985-01-01

The evaluation of software technologies suffers because of the lack of quantitative assessment of their effect on software development and modification. A seven-step data collection and analysis methodology couples software technology evaluation with software measurement. Four in-depth applications of the methodology are presented. The four studies represent each of the general categories of analyses on the software product and development process: blocked subject-project studies, replicated project studies, multi-project variation studies, and single project strategies. The four applications are in the areas of, respectively, software testing, cleanroom software development, characteristic software metric sets, and software error analysis.

Hard-to-Teach Topics: Using ICT Part 1

ERIC Educational Resources Information Center

Tanner, Ruth

2009-01-01

In November 2007 a joint ATM/MA team began working together to consider how ICT can be used to support the teaching and learning of topics that are considered to be "hard to teach" in secondary mathematics, within a project that complements that of the Secondary National Strategy. In the best subject association spirit, it was decided to…

Security Services Discovery by ATM Endsystems

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

Sholander, Peter; Tarman, Thomas

This contribution proposes strawman techniques for Security Service Discovery by ATM endsystems in ATM networks. Candidate techniques include ILMI extensions, ANS extensions and new ATM anycast addresses. Another option is a new protocol based on an IETF service discovery protocol, such as Service Location Protocol (SLP). Finally, this contribution provides strawman requirements for Security-Based Routing in ATM networks.

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.

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.

Guidance and Control Software Project Data - Volume 3: Verification Documents

NASA Technical Reports Server (NTRS)

Hayhurst, Kelly J. (Editor)

2008-01-01

The Guidance and Control Software (GCS) project was the last in a series of software reliability studies conducted at Langley Research Center between 1977 and 1994. The technical results of the GCS project were recorded after the experiment was completed. Some of the support documentation produced as part of the experiment, however, is serving an unexpected role far beyond its original project context. Some of the software used as part of the GCS project was developed to conform to the RTCA/DO-178B software standard, "Software Considerations in Airborne Systems and Equipment Certification," used in the civil aviation industry. That standard requires extensive documentation throughout the software development life cycle, including plans, software requirements, design and source code, verification cases and results, and configuration management and quality control data. The project documentation that includes this information is open for public scrutiny without the legal or safety implications associated with comparable data from an avionics manufacturer. This public availability has afforded an opportunity to use the GCS project documents for DO-178B training. This report provides a brief overview of the GCS project, describes the 4-volume set of documents and the role they are playing in training, and includes the verification documents from the GCS project. Volume 3 contains four appendices: A. Software Verification Cases and Procedures for the Guidance and Control Software Project; B. Software Verification Results for the Pluto Implementation of the Guidance and Control Software; C. Review Records for the Pluto Implementation of the Guidance and Control Software; and D. Test Results Logs for the Pluto Implementation of the Guidance and Control Software.

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.

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.

Automated support for experience-based software management

NASA Technical Reports Server (NTRS)

Valett, Jon D.

1992-01-01

To effectively manage a software development project, the software manager must have access to key information concerning a project's status. This information includes not only data relating to the project of interest, but also, the experience of past development efforts within the environment. This paper describes the concepts and functionality of a software management tool designed to provide this information. This tool, called the Software Management Environment (SME), enables the software manager to compare an ongoing development effort with previous efforts and with models of the 'typical' project within the environment, to predict future project status, to analyze a project's strengths and weaknesses, and to assess the project's quality. In order to provide these functions the tool utilizes a vast corporate memory that includes a data base of software metrics, a set of models and relationships that describe the software development environment, and a set of rules that capture other knowledge and experience of software managers within the environment. Integrating these major concepts into one software management tool, the SME is a model of the type of management tool needed for all software development organizations.

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.

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.

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.

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.

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

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

Experiences with the AEROnet/PSCN ATM Prototype

NASA Technical Reports Server (NTRS)

Kurak, Richard S.; Lisotta, Anthony J.; McCabe, James D.; Nothaft, Alfred E.; Russell, Kelly R.; Lasinski, T. A. (Technical Monitor)

1995-01-01

This paper discusses the experience gained by the AEROnet/PSCN networking team in deploying a prototype Asynchronous Transfer Mode (ATM) based network as part of the wide-area network for the Numerical Aerodynamic Simulation (NAS) Program at NASA Ames Research Center. The objectives of this prototype were to test concepts in using ATM over wide-area Internet Protocol (IP) networks and measure end-to-end system performance. This testbed showed that end-to-end ATM over a DS3 reaches approximately 80% of the throughput achieved from a FDDI to DS3 network. The 20% reduction in through-put can be attributed to the overhead associated with running ATM. As a result, we conclude that if the loss in capacity due to ATM overhead is balanced by the reduction in cost of ATM services, as compared to dedicated circuits, then ATM can be a viable alternative.

Tolerance to Elevated Temperature and Ocean Acidification of the Larvae of the Solitary Corals Fungia fungites (Linnaues, 1758) and Lithophyllon repanda (Dana, 1846).

PubMed

Baria, Maria Vanessa B; Kurihara, Haruko; Harii, Saki

2015-10-01

Increase in atmospheric CO₂is the main driver of global climate change and is projected to elevate sea surface temperature by at least 2°C and to decrease oceanic pH by 0.3 to 0.4 units by the end of the century. These factors seriously threaten coral reef ecosystems worldwide. In Okinawa, solitary corals are an important feature of the coral community structure. While previous studies on the effects of ocean warming (OW), ocean acidification (OA) and its combination on larval survival focused on colonial coral species, the present study assessed the effect of high temperature on larvae from solitary corals. In this study, we examined the influence of OW (control = 28°C; control +3 = 31°C; control + 6 = 34°C) and OA (control, pCO₂= 400 to 500 μatm; medium, pCO₂= 1000 to 1300 μatm; high, pCO₂= 1700 to 2200 μatm) on the larval survival of two solitary corals, Fungia fungites and Lithophyllon repanda for eight days. Results showed that F. fungites was neither affected by OW, OA, nor its combination. Similarly, survival of L. repanda was not affected by OA however it was significantly affected by temperature. Temperature tolerance varies between species; L. repanda (+3°C above ambient) has lower tolerance than F. fungites (+6°C above ambient). This observation suggests that fungiid larvae had higher tolerance to elevated temperature stress relative to other scleractinian corals. With the projected increase in OW and OA in the future, fungiidsmay retain good potential to widely disperse and successfully recruit to natal and other neighbouring reefs.

Contrasting effects of ocean acidification on reproduction in reef fishes

NASA Astrophysics Data System (ADS)

Welch, Megan J.; Munday, Philip L.

2016-06-01

Differences in the sensitivity of marine species to ocean acidification will influence the structure of marine communities in the future. Reproduction is critical for individual and population success, yet is energetically expensive and could be adversely affected by rising CO2 levels in the ocean. We investigated the effects of projected future CO2 levels on reproductive output of two species of coral reef damselfish, Amphiprion percula and Acanthochromis polyacanthus. Adult breeding pairs were maintained at current-day control (446 μatm), moderate (652 μatm) or high CO2 (912 μatm) for a 9-month period that included the summer breeding season. The elevated CO2 treatments were consistent with CO2 levels projected by 2100 under moderate (RCP6) and high (RCP8) emission scenarios. Reproductive output increased in A. percula, with 45-75 % more egg clutches produced and a 47-56 % increase in the number of eggs per clutch in the two elevated CO2 treatments. In contrast, reproductive output decreased at high CO2 in Ac. polyacanthus, with approximately one-third as many clutches produced compared with controls. Egg survival was not affected by CO2 for A. percula, but was greater in elevated CO2 for Ac. polyacanthus. Hatching success was also greater for Ac. polyacanthus at elevated CO2, but there was no effect of CO2 treatments on offspring size. Despite the variation in reproductive output, body condition of adults did not differ between control and CO2 treatments in either species. Our results demonstrate different effects of high CO2 on fish reproduction, even among species within the same family. A greater understanding of the variation in effects of ocean acidification on reproductive performance is required to predict the consequences for future populations of marine organisms.

Certification of Safety-Critical Software Under DO-178C and DO-278A

NASA Technical Reports Server (NTRS)

Jacklin, Stephen A.

2012-01-01

The RTCA has recently released DO-178C and DO-278A as new certification guidance for the production of airborne and ground-based air traffic management software, respectively. Additionally, RTCA special committee SC-205 has also produced, at the same time, five other companion documents. These documents are RTCA DO-248C, DO-330, DO-331, DO- 332, and DO-333. These supplements address frequently asked questions about software certification, provide guidance on tool qualification requirements, and illustrate the modifications recommended to DO-178C when using model-based software design, object oriented programming, and formal methods. The objective of this paper is to first explain the relationship of DO-178C to the former DO-178B in order to give those familiar with DO- 178B an indication of what has been changed and what has not been changed. With this background, the relationship of DO-178C and DO-278 to the new DO-278A document for ground-based software development is shown. Last, an overview of the new guidance contained in the tool qualification document and the three new supplements to DO-178C and DO-278A is presented. For those unfamiliar with DO-178B, this paper serves to provide an entry point to this new certification guidance for airborne and ground-based CNS/ATM software certification.

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…

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

ATM technology and beyond

NASA Technical Reports Server (NTRS)

Cheung, Nim K.

1993-01-01

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

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.

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.

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.

MSFC Skylab Kohoutek project report

NASA Technical Reports Server (NTRS)

1974-01-01

Skylab 4 experiment's selection for observing of the Comet Kohoutek, 1973f is documented. The report also reflects premission planning versus the actual experiment performance based upon the changing cometary parameters. The experiment concepts, hardware, operational performance and anaomalies are discussed. Experiments which viewed the comet were mainly through the SAL and ATM, but some were handheld and EVA. A complete astronaut commentary appears as appendixes.

Implementing Large Projects in Software Engineering Courses

ERIC Educational Resources Information Center

Coppit, David

2006-01-01

In software engineering education, large projects are widely recognized as a useful way of exposing students to the real-world difficulties of team software development. But large projects are difficult to put into practice. First, educators rarely have additional time to manage software projects. Second, classrooms have inherent limitations that…

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.

Surface Operations Systems Improve Airport Efficiency

NASA Technical Reports Server (NTRS)

2009-01-01

With Small Business Innovation Research (SBIR) contracts from Ames Research Center, Mosaic ATM of Leesburg, Virginia created software to analyze surface operations at airports. Surface surveillance systems, which report locations every second for thousands of air and ground vehicles, generate massive amounts of data, making gathering and analyzing this information difficult. Mosaic?s Surface Operations Data Analysis and Adaptation (SODAA) tool is an off-line support tool that can analyze how well the airport surface operation is working and can help redesign procedures to improve operations. SODAA helps researchers pinpoint trends and correlations in vast amounts of recorded airport operations data.

Implementing large projects in software engineering courses

NASA Astrophysics Data System (ADS)

Coppit, David

2006-03-01

In software engineering education, large projects are widely recognized as a useful way of exposing students to the real-world difficulties of team software development. But large projects are difficult to put into practice. First, educators rarely have additional time to manage software projects. Second, classrooms have inherent limitations that threaten the realism of large projects. Third, quantitative evaluation of individuals who work in groups is notoriously difficult. As a result, many software engineering courses compromise the project experience by reducing the team sizes, project scope, and risk. In this paper, we present an approach to teaching a one-semester software engineering course in which 20 to 30 students work together to construct a moderately sized (15KLOC) software system. The approach combines carefully coordinated lectures and homeworks, a hierarchical project management structure, modern communication technologies, and a web-based project tracking and individual assessment system. Our approach provides a more realistic project experience for the students, without incurring significant additional overhead for the instructor. We present our experiences using the approach the last 2 years for the software engineering course at The College of William and Mary. Although the approach has some weaknesses, we believe that they are strongly outweighed by the pedagogical benefits.

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.

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

NASA Technical Reports Server (NTRS)

Zakrajsek, Robert J.

2000-01-01

The goal of the Advanced Communications for Air Traffic Management (AC/ATM) Project at the NASA Glenn Research Center at Lewis Field is to enable a communications infrastructure that provides the capacity, efficiency, and flexibility necessary to realize a mature free-flight environment. The technical thrust of the AC/ATM Project is targeted at the design, development, integration, test, and demonstration of enabling technologies for global broadband aeronautical communications. Since Ku-band facilities and equipment are readily available, one of the near-term demonstrations involves a link through a Kuband communications satellite. Two conformally mounted antennas will support the initial AC/ATM communications links. Both of these are steered electronically through monolithic microwave integrated circuit (MMIC) amplifiers and phase shifters. This link will be asymmetrical with the downlink to the aircraft (mobile vehicle) at a throughput rate of greater than 1.5 megabits per second (Mbps), whereas the throughput rate of the uplink from the aircraft will be greater than 100 kilobits per second (kbps). The data on the downlink can be narrow-band, wide-band, or a combination of both, depending on the requirements of the experiment. The AC/ATM project is purchasing a phased-array Ku-band transmitting antenna for the uplink from the test vehicle. Many Ku-band receiving antennas have been built, and one will be borrowed for a short time to perform the initial experiments at the NASA Glenn Research Center at Lewis Field. The Ku-band transmitting antenna is a 254-element MMIC phased-array antenna being built by Boeing Phantom Works. Each element can radiate 100 mW. The antenna is approximately 43-cm high by 24-cm wide by 3.3-cm thick. It can be steered beyond 60 from broadside. The beamwidth varies from 6 at broadside to 12 degrees at 60 degrees, which is typical of phased-array antennas. When the antenna is steered to 60 degrees, the beamwidth will illuminate approximately five satellites on the orbital arc. Spread spectrum techniques will be employed to keep the power impinging on the adjacent satellites below their noise floor so that no interference results. This antenna is power limited. If the antenna elements (currently 254) are increased by a factor of 4 (1024) or 16 (4096), the gain will increase and the beamwidth will decrease in proportion. For the latter two antenna sizes, the power must be "backed off" to prevent interference with the neighboring satellites. The receiving antenna, which is approximately 90-cm high, 60-cm wide, and 3.5-cm thick, is composed of 1500 phased-array elements. The system phased-array controller can control both a 1500-element receiving antenna and a 500-element transmitting antenna. For ground testing, this controller will allow manual beam pointing and polarization alignment. For normal operation, the system can be connected to the receiving antenna and the navigation system for real-time autonomous track operation. This will be accomplished by first pointing both antennas at the satellite using information from the aircraft data bus. Then, the system phased-array controller will electronically adjust the antenna pointing of the receiving antenna to find the peak signal. After the peak signal has been found, the beam of the transmitting antenna will be pointed to the same steering angles as the receiving antenna. For initial ground testing without an aircraft, the ARINC 429 data bus (ARINC Inc., Annapolis, Maryland) will be simulated by a gyro system purchased for the follow-on to the Monolithic Microwave Integrated Circuit (MMIC) Arrays for Satellite Communication on the Move (MASCOM) Project. MASCOM utilized the Advanced Communications Technology Satellite (ACTS) with a pair of Ka-band experimental phased-array antennas.

Managing the Software Development Process

NASA Technical Reports Server (NTRS)

Lubelczky, Jeffrey T.; Parra, Amy

1999-01-01

The goal of any software development project is to produce a product that is delivered on time, within the allocated budget, and with the capabilities expected by the customer and unfortunately, this goal is rarely achieved. However, a properly managed project in a mature software engineering environment can consistently achieve this goal. In this paper we provide an introduction to three project success factors, a properly managed project, a competent project manager, and a mature software engineering environment. We will also present an overview of the benefits of a mature software engineering environment based on 24 years of data from the Software Engineering Lab, and suggest some first steps that an organization can take to begin benefiting from this environment. The depth and breadth of software engineering exceeds this paper, various references are cited with a goal of raising awareness and encouraging further investigation into software engineering and project management practices.

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.

Running TCP/IP over ATM Networks.

ERIC Educational Resources Information Center

Witt, Michael

1995-01-01

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

Guidance and Control Software Project Data - Volume 2: Development Documents

NASA Technical Reports Server (NTRS)

Hayhurst, Kelly J. (Editor)

2008-01-01

The Guidance and Control Software (GCS) project was the last in a series of software reliability studies conducted at Langley Research Center between 1977 and 1994. The technical results of the GCS project were recorded after the experiment was completed. Some of the support documentation produced as part of the experiment, however, is serving an unexpected role far beyond its original project context. Some of the software used as part of the GCS project was developed to conform to the RTCA/DO-178B software standard, "Software Considerations in Airborne Systems and Equipment Certification," used in the civil aviation industry. That standard requires extensive documentation throughout the software development life cycle, including plans, software requirements, design and source code, verification cases and results, and configuration management and quality control data. The project documentation that includes this information is open for public scrutiny without the legal or safety implications associated with comparable data from an avionics manufacturer. This public availability has afforded an opportunity to use the GCS project documents for DO-178B training. This report provides a brief overview of the GCS project, describes the 4-volume set of documents and the role they are playing in training, and includes the development documents from the GCS project. Volume 2 contains three appendices: A. Guidance and Control Software Development Specification; B. Design Description for the Pluto Implementation of the Guidance and Control Software; and C. Source Code for the Pluto Implementation of the Guidance and Control Software

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.

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

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

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.

Airborne Laser/GPS Mapping of Assateague National Seashore Beach

NASA Technical Reports Server (NTRS)

Kradill, W. B.; Wright, C. W.; Brock, John C.; Swift, R. N.; Frederick, E. B.; Manizade, S. S.; Yungel, J. K.; Martin, C. F.; Sonntag, J. G.; Duffy, Mark;

Food availability and pCO2 impacts on planulation, juvenile survival, and calcification of the azooxanthellate scleractinian coral, Balanophyllia elegans

NASA Astrophysics Data System (ADS)

Crook, E. D.; Cooper, H.; Potts, D. C.; Lambert, T.; Paytan, A.

2013-05-01

Ocean acidification, the assimilation of atmospheric CO2 by the oceans that decreases the pH and CaCO3 saturation state (Ω) of seawater, is projected to have severe consequences for calcifying organisms. Strong evidence suggests that tropical reef-building corals containing algal symbionts (zooxanthellae) will experience dramatic declines in calcification over the next century. The responses of azooxanthellate corals to ocean acidification are less well understood, and because they cannot obtain extra photosynthetic energy from symbionts, they provide a system for studying the direct effects of acidification on the energy available for calcification. The orange cup coral Balanophyllia elegans is a solitary, azooxanthellate scleractinian species common on the California coast where it thrives in the low pH waters of an upwelling regime. During an 8 month study, we addressed the effects of three pCO2 treatments (410, 770, and 1230 μatm) and two feeding frequencies (High Food and Low Food) on adult Balanophyllia elegans planulation (larval release) rates, and on the survival, growth, and calcification of their juvenile offspring. Planulation rates were affected by food level but not pCO2, while juvenile survival was highest under 410 μatm and High Food conditions. Our results suggest that feeding rate has a greater impact on calcification of B. elegans than pCO2. Net calcification was positive even at 1230 μatm (~ 3 times current atmospheric pCO2), although the increase from 410 to 1230 μatm reduced overall calcification by ~ 25-45%, and reduced skeletal density by ~ 35-45%. Higher pCO2 also altered aragonite crystal morphology significantly. We discuss how feeding frequency affects azooxanthellate coral calcification, and how B. elegans may respond to ocean acidification in coastal upwelling waters.

User systems guidelines for software projects

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

Abrahamson, L.

1986-04-01

This manual presents guidelines for software standards which were developed so that software project-development teams and management involved in approving the software could have a generalized view of all phases in the software production procedure and the steps involved in completing each phase. Guidelines are presented for six phases of software development: project definition, building a user interface, designing software, writing code, testing code, and preparing software documentation. The discussions for each phase include examples illustrating the recommended guidelines. 45 refs. (DWL)

Implementation of virtual LANs over ATM WANs

NASA Astrophysics Data System (ADS)

Braun, Torsten; Maehler, Martin

1998-09-01

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

Large-scale visualization projects for teaching software engineering.

PubMed

Müller, Christoph; Reina, Guido; Burch, Michael; Weiskopf, Daniel

2012-01-01

The University of Stuttgart's software engineering major complements the traditional computer science major with more practice-oriented education. Two-semester software projects in various application areas offered by the university's different computer science institutes are a successful building block in the curriculum. With this realistic, complex project setting, students experience the practice of software engineering, including software development processes, technologies, and soft skills. In particular, visualization-based projects are popular with students. Such projects offer them the opportunity to gain profound knowledge that would hardly be possible with only regular lectures and homework assignments.

Develop advanced nonlinear signal analysis topographical mapping system

NASA Technical Reports Server (NTRS)

1994-01-01

The Space Shuttle Main Engine (SSME) has been undergoing extensive flight certification and developmental testing, which involves some 250 health monitoring measurements. Under the severe temperature, pressure, and dynamic environments sustained during operation, numerous major component failures have occurred, resulting in extensive engine hardware damage and scheduling losses. To enhance SSME safety and reliability, detailed analysis and evaluation of the measurements signal are mandatory to assess its dynamic characteristics and operational condition. Efficient and reliable signal detection techniques will reduce catastrophic system failure risks and expedite the evaluation of both flight and ground test data, and thereby reduce launch turn-around time. The basic objective of this contract are threefold: (1) develop and validate a hierarchy of innovative signal analysis techniques for nonlinear and nonstationary time-frequency analysis. Performance evaluation will be carried out through detailed analysis of extensive SSME static firing and flight data. These techniques will be incorporated into a fully automated system; (2) develop an advanced nonlinear signal analysis topographical mapping system (ATMS) to generate a Compressed SSME TOPO Data Base (CSTDB). This ATMS system will convert tremendous amount of complex vibration signals from the entire SSME test history into a bank of succinct image-like patterns while retaining all respective phase information. High compression ratio can be achieved to allow minimal storage requirement, while providing fast signature retrieval, pattern comparison, and identification capabilities; and (3) integrate the nonlinear correlation techniques into the CSTDB data base with compatible TOPO input data format. Such integrated ATMS system will provide the large test archives necessary for quick signature comparison. This study will provide timely assessment of SSME component operational status, identify probable causes of malfunction, and indicate feasible engineering solutions. The final result of this program will yield an ATMS system of nonlinear and nonstationary spectral analysis software package integrated with the Compressed SSME TOPO Data Base (CSTDB) on the same platform. This system will allow NASA engineers to retrieve any unique defect signatures and trends associated with different failure modes and anomalous phenomena over the entire SSME test history across turbo pump families.

Develop advanced nonlinear signal analysis topographical mapping system

NASA Technical Reports Server (NTRS)

Jong, Jen-Yi

1993-01-01

The SSME has been undergoing extensive flight certification and developmental testing, which involves some 250 health monitoring measurements. Under the severe temperature pressure, and dynamic environments sustained during operation, numerous major component failures have occurred, resulting in extensive engine hardware damage and scheduling losses. To enhance SSME safety and reliability, detailed analysis and evaluation of the measurements signal are mandatory to assess its dynamic characteristics and operational condition. Efficient and reliable signal detection techniques will reduce catastrophic system failure risks and expedite the evaluation of both flight and ground test data, and thereby reduce launch turn-around time. The basic objective of this contract are threefold: (1) Develop and validate a hierarchy of innovative signal analysis techniques for nonlinear and nonstationary time-frequency analysis. Performance evaluation will be carried out through detailed analysis of extensive SSME static firing and flight data. These techniques will be incorporated into a fully automated system. (2) Develop an advanced nonlinear signal analysis topographical mapping system (ATMS) to generate a Compressed SSME TOPO Data Base (CSTDB). This ATMS system will convert tremendous amounts of complex vibration signals from the entire SSME test history into a bank of succinct image-like patterns while retaining all respective phase information. A high compression ratio can be achieved to allow the minimal storage requirement, while providing fast signature retrieval, pattern comparison, and identification capabilities. (3) Integrate the nonlinear correlation techniques into the CSTDB data base with compatible TOPO input data format. Such integrated ATMS system will provide the large test archives necessary for a quick signature comparison. This study will provide timely assessment of SSME component operational status, identify probable causes of malfunction, and indicate feasible engineering solutions. The final result of this program will yield an ATMS system of nonlinear and nonstationary spectral analysis software package integrated with the Compressed SSME TOPO Data Base (CSTDB) on the same platform. This system will allow NASA engineers to retrieve any unique defect signatures and trends associated with different failure modes and anomalous phenomena over the entire SSME test history across turbo pump families.

NASA PC software evaluation project

NASA Technical Reports Server (NTRS)

Dominick, Wayne D. (Editor); Kuan, Julie C.

1986-01-01

The USL NASA PC software evaluation project is intended to provide a structured framework for facilitating the development of quality NASA PC software products. The project will assist NASA PC development staff to understand the characteristics and functions of NASA PC software products. Based on the results of the project teams' evaluations and recommendations, users can judge the reliability, usability, acceptability, maintainability and customizability of all the PC software products. The objective here is to provide initial, high-level specifications and guidelines for NASA PC software evaluation. The primary tasks to be addressed in this project are as follows: to gain a strong understanding of what software evaluation entails and how to organize a structured software evaluation process; to define a structured methodology for conducting the software evaluation process; to develop a set of PC software evaluation criteria and evaluation rating scales; and to conduct PC software evaluations in accordance with the identified methodology. Communication Packages, Network System Software, Graphics Support Software, Environment Management Software, General Utilities. This report represents one of the 72 attachment reports to the University of Southwestern Louisiana's Final Report on NASA Grant NGT-19-010-900. Accordingly, appropriate care should be taken in using this report out of context of the full Final Report.

Traffic Management in ATM Networks Over Satellite Links

NASA Technical Reports Server (NTRS)

Goyal, Rohit; Jain, Raj; Goyal, Mukul; Fahmy, Sonia; Vandalore, Bobby; vonDeak, Thomas

1999-01-01

This report presents a survey of the traffic management Issues in the design and implementation of satellite Asynchronous Transfer Mode (ATM) networks. The report focuses on the efficient transport of Transmission Control Protocol (TCP) traffic over satellite ATM. First, a reference satellite ATM network architecture is presented along with an overview of the service categories available in ATM networks. A delay model for satellite networks and the major components of delay and delay variation are described. A survey of design options for TCP over Unspecified Bit Rate (UBR), Guaranteed Frame Rate (GFR) and Available Bit Rate (ABR) services in ATM is presented. The main focus is on traffic management issues. Several recommendations on the design options for efficiently carrying data services over satellite ATM networks are presented. Most of the results are based on experiments performed on Geosynchronous (GEO) latencies. Some results for Low Earth Orbits (LEO) and Medium Earth Orbit (MEO) latencies are also provided.

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

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.

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.

ATM over hybrid fiber-coaxial cable networks: practical issues in deploying residential ATM services

NASA Astrophysics Data System (ADS)

Laubach, Mark

1996-11-01

Residential broadband access network technology based on asynchronous transfer modem (ATM) will soon reach commercial availability. The capabilities provided by ATM access network promise integrated services bandwidth available in excess of those provided by traditional twisted pair copper wire public telephone networks. ATM to the side of the home placed need quality of service capability closest to the subscriber allowing immediate support for Internet services and traditional voice telephony. Other services such as desktop video teleconferencing and enhanced server-based application support can be added as part of future evolution of the network. Additionally, advanced subscriber home networks can be supported easily. This paper presents an updated summary of the standardization efforts for the ATM over HFC definition work currently taking place in the ATM forum's residential broadband working group and the standards progress in the IEEE 802.14 cable TV media access control and physical protocol working group. This update is fundamental for establishing the foundation for delivering ATM-based integrated services via a cable TV network. An economic model for deploying multi-tiered services is presenting showing that a single-tier service is insufficient for a viable cable operator business. Finally, the use of an ATM based system lends itself well to various deployment scenarios of synchronous optical networks (SONET).

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

Novel Image Processing Interface to Relate DSB Spatial Distribution from Immunofluorescence Foci Experiments to the State-of-the-Art Models of DNA Breakage

NASA Technical Reports Server (NTRS)

Ponomarev, A. L.; Cucinotta, F. A.

2004-01-01

A recently developed software (NASARadiationTrackImage) allows a quick and automatic segmentation of foci that indicate spatial localization of specific proteins that are visualized by immunofluorescence. Of interest are the spatial and temporal distribution of foci such as gammaH2AX, a signal of the phosphorylation of a variant of the histone H2A that has been shown to correspond to DSBs, or proteins involved in DSB processing, such as ATM, Rad51, and p53, following exposures of human cells to high charge and energy (HZE) ion irradiation. Experimental data are recorded as sets of two-dimensional images in color with cells and foci of gammaH2AX, ATM, Rad51 or others shown. Different cells, levels of radiation and timing after radiation were recorded. The software allows us to calculate the number of foci per cell, overall intensity of light in foci and their spatial organization. A simple statistical model allows for testing of foci overlap (eclipse). A more complex statistical model previously known as DNAbreak simulates track structure and random chromosome geometry. It has one adjustable parameter corresponding to an average intensity of DSB creation in cubic micrometers of DNA volume per particle track or unit dose. Its limitation is the low-resolution limit both in physical space and DSB's along DNA. It works adequately on the scale of a cell and provides further insights on how the geometry of tracks and DNA affects genomic damage of the cell and subsequent repair. Future developments of the model for the description of the time evolution of DNA damage response proteins, and more robust track structure models will be discussed.

Advancing Aeronautics: A Decision Framework for Selecting Research Agendas

DTIC Science & Technology

2011-01-01

Engineering Board ASME American Society of Mechanical Engineers ATA Air Transport Association ATM air traffic management ATP Aeronautics Test Program...not provide a competitive advantage for a sufficient period to justify the R&D outlay. Such projects can include technolo- gies that address...fuel efficiency improvements multiplied by the cost of fuel would provide an estimate of their value to society. Likewise, technolo- gies for

NextGen-Airportal Project Technologies: Systems Analysis, Integration, and Evaluation (SAIE)

NASA Technical Reports Server (NTRS)

Huang, Alex; Trapani, Andrew; Poage, Jim; Howell, Daniel; Slocum, Douglas

2012-01-01

NASA has been conducting Concept & Technology (C&T) research to enable capacity, efficiency, and safety improvements under the Airspace Systems Program, Aeronautics Research Mission Directorate (ARMD). These C&Ts provide various benefits (e.g., improved airport departure/arrival throughputs, fuel saving, and taxi efficiency) with costs and benefits apportioned among various Air Traffic Management (ATM) system stakeholders (e.g., FAA, aircraft operators, or public).

A Project Management Approach to Using Simulation for Cost Estimation on Large, Complex Software Development Projects

NASA Technical Reports Server (NTRS)

Mizell, Carolyn; Malone, Linda

2007-01-01

It is very difficult for project managers to develop accurate cost and schedule estimates for large, complex software development projects. None of the approaches or tools available today can estimate the true cost of software with any high degree of accuracy early in a project. This paper provides an approach that utilizes a software development process simulation model that considers and conveys the level of uncertainty that exists when developing an initial estimate. A NASA project will be analyzed using simulation and data from the Software Engineering Laboratory to show the benefits of such an approach.

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 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.

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

Software engineering project management - A state-of-the-art report

NASA Technical Reports Server (NTRS)

Thayer, R. H.; Lehman, J. H.

1977-01-01

The management of software engineering projects in the aerospace industry was investigated. The survey assessed such features as contract type, specification preparation techniques, software documentation required by customers, planning and cost-estimating, quality control, the use of advanced program practices, software tools and test procedures, the education levels of project managers, programmers and analysts, work assignment, automatic software monitoring capabilities, design and coding reviews, production times, success rates, and organizational structure of the projects.

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.

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

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

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.

Software design studies emphasizing Project LOGOS

NASA Technical Reports Server (NTRS)

1972-01-01

The results of a research project on the development of computer software are presented. Research funds of $200,000 were expended over a three year period for software design and projects in connection with Project LOGOS (computer-aided design and certification of computing systems). Abstracts of theses prepared during the project are provided.

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.

Software Effort Estimation Accuracy: A Comparative Study of Estimations Based on Software Sizing and Development Methods

ERIC Educational Resources Information Center

Lafferty, Mark T.

2010-01-01

The number of project failures and those projects completed over cost and over schedule has been a significant issue for software project managers. Among the many reasons for failure, inaccuracy in software estimation--the basis for project bidding, budgeting, planning, and probability estimates--has been identified as a root cause of a high…

GCS plan for software aspects of certification

NASA Technical Reports Server (NTRS)

Shagnea, Anita M.; Lowman, Douglas S.; Withers, B. Edward

1990-01-01

As part of the Guidance and Control Software (GCS) research project being sponsored by NASA to evaluate the failure processes of software, standard industry software development procedures are being employed. To ensure that these procedures are authentic, the guidelines outlined in the Radio Technical Commission for Aeronautics (RTCA/DO-178A document entitled, software considerations in airborne systems and equipment certification, were adopted. A major aspect of these guidelines is proper documentation. As such, this report, the plan for software aspects of certification, was produced in accordance with DO-178A. An overview is given of the GCS research project, including the goals of the project, project organization, and project schedules. It also specifies the plans for all aspects of the project which relate to the certification of the GCS implementations developed under a NASA contract. These plans include decisions made regarding the software specification, accuracy requirements, configuration management, implementation development and verification, and the development of the GCS simulator.

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…

ESO Demonstration Project with the NRAO 12-m Antenna

NASA Astrophysics Data System (ADS)

Heald, R.; Karban, R.

2000-03-01

During the months of September through November 1999, an ALMA joint demonstration project between the European Southern Observatory (ESO) and the National Radio Astronomy Observatory (NRAO) was carried out in Socorro/New Mexico. During this period, Robert Karban (ESO) and Ron Heald (NRAO) worked together on the ESO Demonstration Project. The project integrated ESO software and existing NRAO software (a prototype for the future ALMA control software) to control the motion of the Kitt Peak 12-m antenna. ESO software from the VLT provided the operator interface and coordinate transformation software, while Pat Wallace's TPOINT provided the pointing- model software.

Quantitative CMMI Assessment for Offshoring through the Analysis of Project Management Repositories

NASA Astrophysics Data System (ADS)

Sunetnanta, Thanwadee; Nobprapai, Ni-On; Gotel, Olly

The nature of distributed teams and the existence of multiple sites in offshore software development projects pose a challenging setting for software process improvement. Often, the improvement and appraisal of software processes is achieved through a turnkey solution where best practices are imposed or transferred from a company’s headquarters to its offshore units. In so doing, successful project health checks and monitoring for quality on software processes requires strong project management skills, well-built onshore-offshore coordination, and often needs regular onsite visits by software process improvement consultants from the headquarters’ team. This paper focuses on software process improvement as guided by the Capability Maturity Model Integration (CMMI) and proposes a model to evaluate the status of such improvement efforts in the context of distributed multi-site projects without some of this overhead. The paper discusses the application of quantitative CMMI assessment through the collection and analysis of project data gathered directly from project repositories to facilitate CMMI implementation and reduce the cost of such implementation for offshore-outsourced software development projects. We exemplify this approach to quantitative CMMI assessment through the analysis of project management data and discuss the future directions of this work in progress.

Monitoring software development through dynamic variables

NASA Technical Reports Server (NTRS)

Doerflinger, Carl W.; Basili, Victor R.

1983-01-01

Research conducted by the Software Engineering Laboratory (SEL) on the use of dynamic variables as a tool to monitor software development is described. Project independent measures which may be used in a management tool for monitoring software development are identified. Several FORTRAN projects with similar profiles are examined. The staff was experienced in developing these types of projects. The projects developed serve similar functions. Because these projects are similar some underlying relationships exist that are invariant between projects. These relationships, once well defined, may be used to compare the development of different projects to determine whether they are evolving the same way previous projects in this environment evolved.

Implementing Extreme Programming in Distributed Software Project Teams: Strategies and Challenges

NASA Astrophysics Data System (ADS)

Maruping, Likoebe M.

Agile software development methods and distributed forms of organizing teamwork are two team process innovations that are gaining prominence in today's demanding software development environment. Individually, each of these innovations has yielded gains in the practice of software development. Agile methods have enabled software project teams to meet the challenges of an ever turbulent business environment through enhanced flexibility and responsiveness to emergent customer needs. Distributed software project teams have enabled organizations to access highly specialized expertise across geographic locations. Although much progress has been made in understanding how to more effectively manage agile development teams and how to manage distributed software development teams, managers have little guidance on how to leverage these two potent innovations in combination. In this chapter, I outline some of the strategies and challenges associated with implementing agile methods in distributed software project teams. These are discussed in the context of a study of a large-scale software project in the United States that lasted four months.

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.

Workflow-Based Software Development Environment

NASA Technical Reports Server (NTRS)

Izygon, Michel E.

2013-01-01

The Software Developer's Assistant (SDA) helps software teams more efficiently and accurately conduct or execute software processes associated with NASA mission-critical software. SDA is a process enactment platform that guides software teams through project-specific standards, processes, and procedures. Software projects are decomposed into all of their required process steps or tasks, and each task is assigned to project personnel. SDA orchestrates the performance of work required to complete all process tasks in the correct sequence. The software then notifies team members when they may begin work on their assigned tasks and provides the tools, instructions, reference materials, and supportive artifacts that allow users to compliantly perform the work. A combination of technology components captures and enacts any software process use to support the software lifecycle. It creates an adaptive workflow environment that can be modified as needed. SDA achieves software process automation through a Business Process Management (BPM) approach to managing the software lifecycle for mission-critical projects. It contains five main parts: TieFlow (workflow engine), Business Rules (rules to alter process flow), Common Repository (storage for project artifacts, versions, history, schedules, etc.), SOA (interface to allow internal, GFE, or COTS tools integration), and the Web Portal Interface (collaborative web environment

The development and technology transfer of software engineering technology at NASA. Johnson Space Center

NASA Technical Reports Server (NTRS)

Pitman, C. L.; Erb, D. M.; Izygon, M. E.; Fridge, E. M., III; Roush, G. B.; Braley, D. M.; Savely, R. T.

1992-01-01

The United State's big space projects of the next decades, such as Space Station and the Human Exploration Initiative, will need the development of many millions of lines of mission critical software. NASA-Johnson (JSC) is identifying and developing some of the Computer Aided Software Engineering (CASE) technology that NASA will need to build these future software systems. The goal is to improve the quality and the productivity of large software development projects. New trends are outlined in CASE technology and how the Software Technology Branch (STB) at JSC is endeavoring to provide some of these CASE solutions for NASA is described. Key software technology components include knowledge-based systems, software reusability, user interface technology, reengineering environments, management systems for the software development process, software cost models, repository technology, and open, integrated CASE environment frameworks. The paper presents the status and long-term expectations for CASE products. The STB's Reengineering Application Project (REAP), Advanced Software Development Workstation (ASDW) project, and software development cost model (COSTMODL) project are then discussed. Some of the general difficulties of technology transfer are introduced, and a process developed by STB for CASE technology insertion is described.

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.

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.

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.

Improving Software Engineering on NASA Projects

NASA Technical Reports Server (NTRS)

Crumbley, Tim; Kelly, John C.

2010-01-01

Software Engineering Initiative: Reduces risk of software failure -Increases mission safety. More predictable software cost estimates and delivery schedules. Smarter buyer of contracted out software. More defects found and removed earlier. Reduces duplication of efforts between projects. Increases ability to meet the challenges of evolving software technology.

A Quantitative Study of Global Software Development Teams, Requirements, and Software Projects

ERIC Educational Resources Information Center

Parker, Linda L.

2016-01-01

The study explored the relationship between global software development teams, effective software requirements, and stakeholders' perception of successful software development projects within the field of information technology management. It examined the critical relationship between Global Software Development (GSD) teams creating effective…

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.

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.

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

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

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.

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

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.

The Effectiveness of Software Project Management Practices: A Quantitative Measurement

DTIC Science & Technology

2011-03-01

Assessment (SPMMA) model ( Ramli , 2007). The purpose of the SPMMA was to help a company measure the strength and weaknesses of its software project...Practices,” Fuazi and Ramli presented a model to assess software project management practices using their Software Project Management Maturity...Analysis The SPMMA was carried out on one mid-size Information Technology (IT) Company . Based on the questionnaire responses, interviews and discussions

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.

Software Engineering Research/Developer Collaborations in 2005

NASA Technical Reports Server (NTRS)

Pressburger, Tom

2006-01-01

In CY 2005, three collaborations between software engineering technology providers and NASA software development personnel deployed three software engineering technologies on NASA development projects (a different technology on each project). The main purposes were to benefit the projects, infuse the technologies if beneficial into NASA, and give feedback to the technology providers to improve the technologies. Each collaboration project produced a final report. Section 2 of this report summarizes each project, drawing from the final reports and communications with the software developers and technology providers. Section 3 indicates paths to further infusion of the technologies into NASA practice. Section 4 summarizes some technology transfer lessons learned. Also included is an acronym list.

GSC configuration management plan

NASA Technical Reports Server (NTRS)

Withers, B. Edward

1990-01-01

The tools and methods used for the configuration management of the artifacts (including software and documentation) associated with the Guidance and Control Software (GCS) project are described. The GCS project is part of a software error studies research program. Three implementations of GCS are being produced in order to study the fundamental characteristics of the software failure process. The Code Management System (CMS) is used to track and retrieve versions of the documentation and software. Application of the CMS for this project is described and the numbering scheme is delineated for the versions of the project artifacts.

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...

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.

CrossTalk: The Journal of Defense Software Engineering. Volume 21, Number 1

DTIC Science & Technology

2008-01-01

project manage- ment and the individual components of the software life-cycle model ; it will be awarded for...software professionals that had been formally educated in software project manage- ment. The study indicated that our industry is lacking in program managers...soft- ware developments get bigger, more complicated, and more dependent on senior software pro- fessionals to get the project on the right path

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

Diagnosing CO2 fluxes and seasonality in the Arabian Sea as an Ocean-Dominated Margin

NASA Astrophysics Data System (ADS)

Yang, W.; Dai, M.

2017-12-01

The Arabian Sea is a large marginal sea of the Indian Ocean characterized by highly predictable annual circulation cycle driven by Asian monsoon. The Arabian Sea is generally sources to atmospheric CO2. In this study, we applied the physical-biogeochemical coupled approach previously adopted for diagnosis of CO2 fluxes in Ocean-dominated margin (OceMar) to assesses the CO2 fluxes and their seasonality in Arabian Sea using data collected during five US JGOFS Arabian Sea Process Study cruises (ttn-043, ttn-045, ttn-049, ttn-053, ttn-054) conducted from September 1994 to December 1995. The pCO2 estimated during the 5 cruises was 396±5μatm, 359±7 μatm, 373±7 μatm, 379±9 μatm and 387±12 μatm, respectively, which agreed well with the pCO2 observed during the cruises of 389±8 μatm, 361±6 μatm, 366±6 μatm, 371±8 μatm and 367±11 μatm from underway measurements. This strongly suggests that our semi-analytical diagnostic approach in the OceMar framework can evaluate the pCO2 in Arabian Sea. Our coupled diagnostic approach assumes that water mass mixing, biological response and air-sea exchange under steady state over a similar time scale. This assumption should be justified at the region with intensified upwelling where decoupling between upwelling and biological response may occur, where only water mass mixing and air-sea CO2 exchange should be accounted for. This presentation will also examine the seasonality of the CO2 dynamics and its controls.

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.

ATM Expression Predicts Veliparib and Irinotecan Sensitivity in Gastric Cancer by Mediating P53-Independent Regulation of Cell Cycle and Apoptosis.

PubMed

Subhash, Vinod Vijay; Tan, Shi Hui; Yeo, Mei Shi; Yan, Fui Leng; Peethala, Praveen C; Liem, Natalia; Krishnan, Vaidehi; Yong, Wei Peng

2016-12-01

Identification of synthetically lethal cellular targets and synergistic drug combinations is important in cancer chemotherapy as they help to overcome treatment resistance and increase efficacy. The Ataxia Telangiectasia Mutated (ATM) kinase is a nuclear protein that plays a major role in the initiation of DNA repair signaling and cell-cycle check points during DNA damage. Although ATM was shown to be associated with poor prognosis in gastric cancer, its implications as a predictive biomarker for cancer chemotherapy remain unexplored. The present study evaluated ATM-induced synthetic lethality and its role in sensitization of gastric cancer cells to PARP and TOP1 inhibitors, veliparib (ABT-888) and irinotecan (CPT-11), respectively. ATM expression was detected in a panel of gastric cell lines, and the IC 50 against each inhibitors was determined. The combinatorial effect of ABT-888 and CPT-11 in gastric cancer cells was also determined both in vitro and in vivo ATM deficiency was found to be associated with enhanced sensitivity to ABT-888 and CPT-11 monotherapy, hence suggesting a mechanism of synthetic lethality. Cells with high ATM expression showed reduced sensitivity to monotherapy; however, they showed a higher therapeutic effect with ABT-888 and CPT-11 combinatorial therapy. Furthermore, ATM expression was shown to play a major role in cellular homeostasis by regulating cell-cycle progression and apoptosis in a P53-independent manner. The present study highlights the clinical utility of ATM expression as a predictive marker for sensitivity of gastric cancer cells to PARP and TOP1 inhibition and provides a deeper mechanistic insight into ATM-dependent regulation of cellular processes. Mol Cancer Ther; 15(12); 3087-96. ©2016 AACR. ©2016 American Association for Cancer Research.

Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer.

PubMed

Feng, Xiaolan; Li, Haocheng; Kornaga, Elizabeth N; Dean, Michelle; Lees-Miller, Susan P; Riabowol, Karl; Magliocco, Anthony M; Morris, Don; Watson, Peter H; Enwere, Emeka K; Bebb, Gwyn; Paterson, Alexander

2016-12-27

This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (< 4 cm) and fewer than four positive lymph nodes. 532 formalin-fixed paraffin-embedded specimens of resected primary breast tumors were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis. We detected ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC.

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

PubMed

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

2017-11-26

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

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

PubMed

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

2018-06-01

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

Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer

PubMed Central

Feng, Xiaolan; Li, Haocheng; Kornaga, Elizabeth N.; Dean, Michelle; Lees-Miller, Susan P.; Riabowol, Karl; Magliocco, Anthony M.; Morris, Don; Watson, Peter H.; Enwere, Emeka K.; Bebb, Gwyn; Paterson, Alexander

2016-01-01

Introduction This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (< 4 cm) and fewer than four positive lymph nodes. Methods 532 formalin-fixed paraffin-embedded specimens of resected primary breast tumors were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis. We detected ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Results Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). Conclusions These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC. PMID:27741524

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

PubMed

Xiong, Hui; Zhang, Jiangnan

2017-12-01

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

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.

Effect of antibrowning dips and controlled atmosphere storage on the physico-chemical, visual and nutritional quality of minimally processed "Rojo Brillante" persimmons.

PubMed

Sanchís, Elena; Mateos, Milagros; Pérez-Gago, María B

2017-01-01

The combined effect of antibrowning dips and controlled atmosphere storage on fresh-cut "Rojo Brillante" persimmon quality was investigated. Persimmon slices were dipped in 10 g L -1 ascorbic acid, 10 g L -1 citric acid or water and were stored in different controlled atmospheres at 5 ℃. Controlled atmosphere conditions were 21 kPa O 2  + 10 kPa CO 2 (Atm-B), 21 kPa O 2  + 20 kPa CO 2 (Atm-C), 5 kPa O 2  + 10 kPa CO 2 (Atm-D) and 5 kPa O 2 in the absence of CO 2 (Atm-E). Air (Atm-A) was used as a control. Atmospheres with high CO 2 concentrations induced darkening, associated with a flesh disorder known as "internal flesh browning". Only the samples placed in Atm-E, and treated with 10 g L -1 ascorbic acid or 10 g L -1 citric acid, controlled enzymatic browning, reduced firmness loss and prevented the "internal flesh browning" disorder. The maximum limit of marketability was achieved in the samples treated with 10 g L -1 citric acid and stored in Atm-E for nine storage days at 5 ℃. The total vitamin C, free radical scavenging activity, total phenolic content and total carotenoids of the fresh-cut "Rojo Brillante" persimmons were affected by maturity stage at harvest, whereas antibrowning dips and controlled atmosphere storage had no clear effect. © The Author(s) 2016.

The software product assurance metrics study: JPL's software systems quality and productivity

NASA Technical Reports Server (NTRS)

Bush, Marilyn W.

1989-01-01

The findings are reported of the Jet Propulsion Laboratory (JPL)/Software Product Assurance (SPA) Metrics Study, conducted as part of a larger JPL effort to improve software quality and productivity. Until recently, no comprehensive data had been assembled on how JPL manages and develops software-intensive systems. The first objective was to collect data on software development from as many projects and for as many years as possible. Results from five projects are discussed. These results reflect 15 years of JPL software development, representing over 100 data points (systems and subsystems), over a third of a billion dollars, over four million lines of code and 28,000 person months. Analysis of this data provides a benchmark for gauging the effectiveness of past, present and future software development work. In addition, the study is meant to encourage projects to record existing metrics data and to gather future data. The SPA long term goal is to integrate the collection of historical data and ongoing project data with future project estimations.

ATM CMG bearing failure analysis

NASA Technical Reports Server (NTRS)

1975-01-01

The cause or causes for the failure of ATM CMG S/N 5 (Skylab 1) and the anomalies associated with ATM CMG S/N 6 (Skylab 2) were investigated. Skylab telemetry data were reviewed and presented in the form of parameter distributions. The theory that the problems were caused by marginal bearing lubrication was studied along with the effects of orbital conditions on lubricants. Bearing tests were performed to investigate the effect of lubricant or lack of lubricant in the ATM CMG bearings and the dispersion and migration of the lubricant. The vacuum and weightless conditions of space were simulated in the bearing tests. Analysis of the results of the tests conducted points to inadequate lubrication as the predominant factor causing the failure of ATM CMG S/N 5 (Skylab 1) and the anomalies associated with ATM CMG S/N 6 (Skylab 2).

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.

53BP1 depletion causes PARP inhibitor resistance in ATM-deficient breast cancer cells.

PubMed

Hong, Ruoxi; Ma, Fei; Zhang, Weimin; Yu, Xiying; Li, Qing; Luo, Yang; Zhu, Changjun; Jiang, Wei; Xu, Binghe

2016-09-09

Mutations in DNA damage response factors BRCA1 and BRCA2 confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors in breast and ovarian cancers. BRCA1/BRCA2-defective tumors can exhibit resistance to PARP inhibitors via multiple mechanisms, one of which involves loss of 53BP1. Deficiency in the DNA damage response factor ataxia-telangiectasia mutated (ATM) can also sensitize tumors to PARP inhibitors, raising the question of whether the presence or absence of 53BP1 can predict sensitivity of ATM-deficient breast cancer to these inhibitors. Cytotoxicity of PARP inhibitor and ATM inhibitor in breast cancer cell lines was assessed by MTS, colony formation and apoptosis assays. ShRNA lentiviral vectors were used to knockdown 53BP1 expression in breast cancer cell lines. Phospho-ATM and 53BP1 protein expressions were determined in human breast cancer tissues by immunohistochemistry (IHC). We show that inhibiting ATM increased cytotoxicity of PARP inhibitor in triple-negative and non-triple-negative breast cancer cell lines, and depleting the cells of 53BP1 reduced this cytotoxicity. Inhibiting ATM abrogated homologous recombination induced by PARP inhibitor, and down-regulating 53BP1 partially reversed this effect. Further, overall survival was significantly better in triple-negative breast cancer patients with lower levels of phospho-ATM and tended to be better in patients with negative 53BP1. These results suggest that 53BP1 may be a predictor of PARP inhibitor resistance in patients with ATM-deficient tumors.

Using UML Modeling to Facilitate Three-Tier Architecture Projects in Software Engineering Courses

ERIC Educational Resources Information Center

Mitra, Sandeep

2014-01-01

This article presents the use of a model-centric approach to facilitate software development projects conforming to the three-tier architecture in undergraduate software engineering courses. Many instructors intend that such projects create software applications for use by real-world customers. While it is important that the first version of these…

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.

Enhanced way of securing automated teller machine to track the misusers using secure monitor tracking analysis

NASA Astrophysics Data System (ADS)

Sadhasivam, Jayakumar; Alamelu, M.; Radhika, R.; Ramya, S.; Dharani, K.; Jayavel, Senthil

2017-11-01

Now a days the people's attraction towards Automated Teller Machine(ATM) has been increasing even in rural areas. As of now the security provided by all the bank is ATM pin number. Hackers know the way to easily identify the pin number and withdraw money if they haven stolen the ATM card. Also, the Automated Teller Machine is broken and the money is stolen. To overcome these disadvantages, we propose an approach “Automated Secure Tracking System” to secure and tracking the changes in ATM. In this approach, while creating the bank account, the bank should scan the iris known (a part or movement of our eye) and fingerprint of the customer. The scanning can be done with the position of the eye movements and fingerprints identified with the shortest measurements. When the card is swiped then ATM should request the pin, scan the iris and recognize the fingerprint and then allow the customer to withdraw money. If somebody tries to break the ATM an alert message is given to the nearby police station and the ATM shutter is automatically closed. This helps in avoiding the hackers who withdraw money by stealing the ATM card and also helps the government in identifying the criminals easily.

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

PubMed

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

2018-07-01

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

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

PubMed

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

2016-01-01

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

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

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

PubMed

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

2016-05-01

Melanomas have high levels of genomic instability that can contribute to poor disease prognosis. Here, we report a novel defect of the ATM-dependent cell cycle checkpoint in melanoma cell lines that promotes genomic instability. In defective cells, ATM signalling to CHK2 is intact, but the cells are unable to maintain the cell cycle arrest due to elevated PLK1 driving recovery from the arrest. Reducing PLK1 activity recovered the ATM-dependent checkpoint arrest, and over-expressing PLK1 was sufficient to overcome the checkpoint arrest and increase genomic instability. Loss of the ATM-dependent checkpoint did not affect sensitivity to ionizing radiation demonstrating that this defect is distinct from ATM loss of function mutations. The checkpoint defective melanoma cell lines over-express PLK1, and a significant proportion of melanomas have high levels of PLK1 over-expression suggesting this defect is a common feature of melanomas. The inability of ATM to impose a cell cycle arrest in response to DNA damage increases genomic instability. This work also suggests that the ATM-dependent checkpoint arrest is likely to be defective in a higher proportion of cancers than previously expected. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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

2017-02-01

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

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.

Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue1

PubMed Central

Lumeng, Carey N.; Liu, Jianhua; Geletka, Lynn; Delaney, Colin; DelProposto, Jennifer; Desai, Anjali; Oatmen, Kelsie; Martinez-Santibanez, Gabriel; Julius, Annabelle; Garg, Sanjay; Yung, Raymond L.

2011-01-01

Age-related adiposity has been linked to chronic inflammatory diseases in late-life. To date, the studies on adipose tissue leukocytes and aging have not taken into account the heterogeneity of adipose tissue macrophages (ATMs), nor have they examined how age impacts other leukocytes such as T cell in fat. Therefore, we have performed a detailed examination of ATM subtypes in young and old mice using state of the art techniques. Our results demonstrate qualitative changes in ATMs with aging that generate a decrease in resident Type 2 (M2) ATMs. The profile of ATMs in old fat shifts towards a pro-inflammatory environment with increased numbers of CD206-CD11c- (double negative) ATMs. The mechanism of this aging-induced shift in the phenotypic profile of ATMs was found to be related to a decrease in PPARγ expression in ATMs and alterations in chemokine/chemokine receptor expression profiles. Furthermore, we have revealed a profound and unexpected expansion of adipose tissue T (ATT) cells in visceral fat with aging that includes a significant induction of regulatory T cells (Tregs) in fat. Our findings demonstrate a unique inflammatory cell signature in the physiologic context of aging adipose tissue that differs from those induced in setting of diet-induced obesity. PMID:22075699

Is talking to an automated teller machine natural and fun?

PubMed

Chan, F Y; Khalid, H M

Usability and affective issues of using automatic speech recognition technology to interact with an automated teller machine (ATM) are investigated in two experiments. The first uncovered dialogue patterns of ATM users for the purpose of designing the user interface for a simulated speech ATM system. Applying the Wizard-of-Oz methodology, multiple mapping and word spotting techniques, the speech driven ATM accommodates bilingual users of Bahasa Melayu and English. The second experiment evaluates the usability of a hybrid speech ATM, comparing it with a simulated manual ATM. The aim is to investigate how natural and fun can talking to a speech ATM be for these first-time users. Subjects performed the withdrawal and balance enquiry tasks. The ANOVA was performed on the usability and affective data. The results showed significant differences between systems in the ability to complete the tasks as well as in transaction errors. Performance was measured on the time taken by subjects to complete the task and the number of speech recognition errors that occurred. On the basis of user emotions, it can be said that the hybrid speech system enabled pleasurable interaction. Despite the limitations of speech recognition technology, users are set to talk to the ATM when it becomes available for public use.

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

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Bobinsky, Eric A.

1997-01-01

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

Regulation of oxidative stress responses by ataxia-telangiectasia mutated is required for T cell proliferation.

PubMed

Bagley, Jessamyn; Singh, Gyanesh; Iacomini, John

2007-04-15

Mutations in the gene encoding ataxia-telangiectasia (A-T) mutated (Atm) cause the disease A-T, characterized by immunodeficiency, the molecular basis of which is not known. Following stimulation through the TCR, Atm-deficient T cells and normal T cells in which Atm is inhibited undergo apoptosis rather than proliferation. Apoptosis is prevented by scavenging reactive oxygen species (ROS) during activation. Atm therefore plays a critical role in T cell proliferation by regulating responses to ROS generated following T cell activation. The inability of Atm-deficient T cells to control responses to ROS is therefore the molecular basis of immunodeficiency associated with A-T.

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

NASA Technical Reports Server (NTRS)

Susskind, Joel; Kouvaris, Louis; Iredell, Lena

2015-01-01

A main objective of AIRS/AMSU on EOS is to provide accurate sounding products that are used to generate climate data sets. Suomi NPP carries CrIS/ATMS that were designed as follow-ons to AIRS/AMSU. Our objective is to generate a long term climate data set of products derived from CrIS/ATMS to serve as a continuation of the AIRS/AMSU products. We have modified an improved version of the operational AIRS Version-6 retrieval algorithm for use with CrIS/ATMS. CrIS/ATMS products are of very good quality, and are comparable to, and consistent with, those of AIRS.

Early deployment of ATMS/ATIS for metropolitan Detroit

DOT National Transportation Integrated Search

1994-09-26

The Michigan Department of Transportation (MDOT) is currently planning for the expansion of their current Advanced Traffic Management and Advanced Traveler Information Systems (ATMS and ATIS, respectively). Current ATMS and ATIS coverage include 3...

Ocean acidification and warming scenarios increase microbioerosion of coral skeletons.

PubMed

Reyes-Nivia, Catalina; Diaz-Pulido, Guillermo; Kline, David; Guldberg, Ove-Hoegh; Dove, Sophie

2013-06-01

Biological mediation of carbonate dissolution represents a fundamental component of the destructive forces acting on coral reef ecosystems. Whereas ocean acidification can increase dissolution of carbonate substrates, the combined impact of ocean acidification and warming on the microbioerosion of coral skeletons remains unknown. Here, we exposed skeletons of the reef-building corals, Porites cylindrica and Isopora cuneata, to present-day (Control: 400 μatm - 24 °C) and future pCO2 -temperature scenarios projected for the end of the century (Medium: +230 μatm - +2 °C; High: +610 μatm - +4 °C). Skeletons were also subjected to permanent darkness with initial sodium hypochlorite incubation, and natural light without sodium hypochlorite incubation to isolate the environmental effect of acidic seawater (i.e., Ωaragonite <1) from the biological effect of photosynthetic microborers. Our results indicated that skeletal dissolution is predominantly driven by photosynthetic microborers, as samples held in the dark did not decalcify. In contrast, dissolution of skeletons exposed to light increased under elevated pCO2 -temperature scenarios, with P. cylindrica experiencing higher dissolution rates per month (89%) than I. cuneata (46%) in the high treatment relative to control. The effects of future pCO2 -temperature scenarios on the structure of endolithic communities were only identified in P. cylindrica and were mostly associated with a higher abundance of the green algae Ostreobium spp. Enhanced skeletal dissolution was also associated with increased endolithic biomass and respiration under elevated pCO2 -temperature scenarios. Our results suggest that future projections of ocean acidification and warming will lead to increased rates of microbioerosion. However, the magnitude of bioerosion responses may depend on the structural properties of coral skeletons, with a range of implications for reef carbonate losses under warmer and more acidic oceans. © 2013 Blackwell Publishing Ltd.

SAGA: A project to automate the management of software production systems

NASA Technical Reports Server (NTRS)

Campbell, Roy H.; Laliberte, D.; Render, H.; Sum, R.; Smith, W.; Terwilliger, R.

1987-01-01

The Software Automation, Generation and Administration (SAGA) project is investigating the design and construction of practical software engineering environments for developing and maintaining aerospace systems and applications software. The research includes the practical organization of the software lifecycle, configuration management, software requirements specifications, executable specifications, design methodologies, programming, verification, validation and testing, version control, maintenance, the reuse of software, software libraries, documentation, and automated management.

Evaluation and application of an algorithm for atmospheric profiling continuity from Aqua to Suomi-NPP

NASA Astrophysics Data System (ADS)

Lipton, A.; Moncet, J. L.; Lynch, R.; Payne, V.; Alvarado, M. J.

2016-12-01

We will present results from an algorithm that is being developed to produce climate-quality atmospheric profiling earth system data records (ESDRs) for application to data from hyperspectral sounding instruments, including the Atmospheric InfraRed Sounder (AIRS) on EOS Aqua and the Cross-track Infrared Sounder (CrIS) on Suomi-NPP, along with their companion microwave sounders, AMSU and ATMS, respectively. The ESDR algorithm uses an optimal estimation approach and the implementation has a flexible, modular software structure to support experimentation and collaboration. Data record continuity benefits from the fact that the same algorithm can be applied to different sensors, simply by providing suitable configuration and data files. For analysis of satellite profiles over multi-decade periods, a concern is that the algorithm could respond inadequately to climate change if it uses a static background as a retrieval constraint, leading to retrievals that underestimate secular changes over extended periods of time and become biased toward an outdated climatology. We assessed the ability of our algorithm to respond appropriately to changes in temperature and water vapor profiles associated with climate change and, in particular, on the impact of using a climatological background in retrievals when the climatology is not static. We simulated a scenario wherein our algorithm processes 30 years of data from CrIS and ATMS (CrIMSS) with a static background based on data from the start of the 30-year period. We performed simulations using products from Coupled Model Intercomparison Project 5 (CMIP5), and in particular the "representative concentration pathways" midrange emissions (RCP4.5) scenario from the GISS-E2-R model. We will present results indicating that regularization using empirical orthogonal functions (EOFs) from a 30-year outdated covariance had a negligible effect on results. For temperature, the secular change is represented with high fidelity with the CrIMSS retrievals. For water vapor, an outdated background adds distortion to the secular moistening trend in the troposphere only above 300 mb, where the sensor information content is less than at lower levels. We will also present results illustrating the consistency between retrievals from near-simultaneous AIRS and CrIMSS measurements.

Activation of ATM by DNA Damaging Agents

DTIC Science & Technology

2004-09-01

risk for breast cancer . Since many anti-tumor chemotherapeutics used in breast cancer treatment have the capacity to induce DNA DSBs, I have...of a subset of downstream effectors of ATM in two human breast cancer cell lines. Studies are now underway to identify proteins that interact with ATM...implications for the treatment of breast cancer patients harboring mutations in ATM. 14. SUBJECT TERMS 15. NUMBER OF PAGES signal transduction, DNA damage and

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.

Experiences with ATM in a multivendor pilot system at Forschungszentrum Julich

NASA Astrophysics Data System (ADS)

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

1998-08-01

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

ATM kinase is required for telomere elongation in mouse and human cells

PubMed Central

Lee, Stella Suyong; Bohrson, Craig; Pike, Alexandra Mims; Wheelan, Sarah Jo; Greider, Carol Widney

2015-01-01

Summary Short telomeres induce a DNA damage response, senescence and apoptosis; thus, maintaining telomere length equilibrium is essential for cell viability. Telomerase addition of telomere repeats is tightly regulated in cells. To probe pathways that regulate telomere addition, we developed the ADDIT assay to measure new telomere addition at a single telomere in vivo. Sequence analysis showed telomerase specific addition of repeats onto a new telomere occurred in just 48 hr. Using the ADDIT assay, we found that ATM is required for addition of new repeats onto telomeres in mouse cells. Evaluation of bulk telomeres, in both human and mouse cells, showed that blocking ATM inhibited telomere elongation. Finally, the activation of ATM through the inhibition of PARP1 resulted in increased telomere elongation, supporting the central role of the ATM pathway in regulating telomere addition. Understanding this role of ATM may yield new areas for possible therapeutic intervention in telomere-mediated disease. PMID:26586427

Asynchronous Transfer Mode Quality-of-Service Testing

NASA Technical Reports Server (NTRS)

Ivancic, William D.

1998-01-01

In support of satellite-ATM interoperability, researchers at the NASA Lewis Research Center performed asynchronous transfer mode (ATM) quality-of-service experiments 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 use the ATM protocol to transmit high-quality multimedia information. The experimental results have been submitted to various International Telecommunications Union (ITU) study groups in order to improve and modify current standards and recommendations for the telecommunications industry. Quality-of-service parameters for Class I, stringent class requirements for ITU-T I.356 are currently being debated. The experimental results presented will help to establish these quality-of-service thresholds. This material will also be useful in the development of the ITU-R WP-4B's Draft Preliminary New Recommendation on the Transmission of Asynchronous Transfer Mode Traffic via Satellite (Rec. S.atm).

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).

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

PubMed

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

2017-09-01

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

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:

NASA's Software Safety Standard

NASA Technical Reports Server (NTRS)

Ramsay, Christopher M.

2007-01-01

NASA relies more and more on software to control, monitor, and verify its safety critical systems, facilities and operations. Since the 1960's there has hardly been a spacecraft launched that does not have a computer on board that will provide command and control services. There have been recent incidents where software has played a role in high-profile mission failures and hazardous incidents. For example, the Mars Orbiter, Mars Polar Lander, the DART (Demonstration of Autonomous Rendezvous Technology), and MER (Mars Exploration Rover) Spirit anomalies were all caused or contributed to by software. The Mission Control Centers for the Shuttle, ISS, and unmanned programs are highly dependant on software for data displays, analysis, and mission planning. Despite this growing dependence on software control and monitoring, there has been little to no consistent application of software safety practices and methodology to NASA's projects with safety critical software. Meanwhile, academia and private industry have been stepping forward with procedures and standards for safety critical systems and software, for example Dr. Nancy Leveson's book Safeware: System Safety and Computers. The NASA Software Safety Standard, originally published in 1997, was widely ignored due to its complexity and poor organization. It also focused on concepts rather than definite procedural requirements organized around a software project lifecycle. Led by NASA Headquarters Office of Safety and Mission Assurance, the NASA Software Safety Standard has recently undergone a significant update. This new standard provides the procedures and guidelines for evaluating a project for safety criticality and then lays out the minimum project lifecycle requirements to assure the software is created, operated, and maintained in the safest possible manner. This update of the standard clearly delineates the minimum set of software safety requirements for a project without detailing the implementation for those requirements. This allows the projects leeway to meet these requirements in many forms that best suit a particular project's needs and safety risk. In other words, it tells the project what to do, not how to do it. This update also incorporated advances in the state of the practice of software safety from academia and private industry. It addresses some of the more common issues now facing software developers in the NASA environment such as the use of Commercial-Off-the-Shelf Software (COTS), Modified OTS (MOTS), Government OTS (GOTS), and reused software. A team from across NASA developed the update and it has had both NASA-wide internal reviews by software engineering, quality, safety, and project management. It has also had expert external review. This presentation and paper will discuss the new NASA Software Safety Standard, its organization, and key features. It will start with a brief discussion of some NASA mission failures and incidents that had software as one of their root causes. It will then give a brief overview of the NASA Software Safety Process. This will include an overview of the key personnel responsibilities and functions that must be performed for safety-critical software.

On-Orbit Software Analysis

NASA Technical Reports Server (NTRS)

Moran, Susanne I.

2004-01-01

The On-Orbit Software Analysis Research Infusion Project was done by Intrinsyx Technologies Corporation (Intrinsyx) at the National Aeronautics and Space Administration (NASA) Ames Research Center (ARC). The Project was a joint collaborative effort between NASA Codes IC and SL, Kestrel Technology (Kestrel), and Intrinsyx. The primary objectives of the Project were: Discovery and verification of software program properties and dependencies, Detection and isolation of software defects across different versions of software, and Compilation of historical data and technical expertise for future applications

Electronic Nose: Evaluation of Kamina Prototype Unit

NASA Technical Reports Server (NTRS)

Schattke, Nathan

2001-01-01

The Kamina, Sam and Cyranose electronic nose systems were evaluated and partially trained. Much work was performed on the Kamina as it has the ability to respond to low (less than 10 ppb) concentrations of hydrazine compounds. We were able to tell the difference between Hydrazine (Hz) and Monomethylhydrazine (MMH) in standard clean humid air. We were able to detect MMH in reduced pressure (1/3 atm) at about 250 ppb, however the training set was to far from the real situation to be useful now. Various engineering and usability aspects of both the noses was noted, especially the software. One serious physical engineering flaw was remedied in the Kamina system. A gas flow manifold was created for the Sam system. Different chips were evaluated for the Kamina system. It is still unclear if they can be exchanged without retraining the software.The Sam Detect commercial unit was evaluated for solvent detection and evaluation. It was able to successfully identify some solvents. The Cyranose, was observed and evaluated for two days. It has the ability to detect gasses in the 100 parts per million level but not the 10 parts per billion level. It is very sensitive to humidity changes; there is software to partially handle this.

Network, system, and status software enhancements for the autonomously managed electrical power system breadboard. Volume 1: Project summary

NASA Technical Reports Server (NTRS)

Mckee, James W.

1990-01-01

This volume (1 of 4) gives a summary of the original AMPS software system configuration, points out some of the problem areas in the original software design that this project is to address, and in the appendix collects all the bimonthly status reports. The purpose of AMPS is to provide a self reliant system to control the generation and distribution of power in the space station. The software in the AMPS breadboard can be divided into three levels: the operating environment software, the protocol software, and the station specific software. This project deals only with the operating environment software and the protocol software. The present station specific software will not change except as necessary to conform to new data formats.

Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts

NASA Technical Reports Server (NTRS)

Worgul, Basil V.; Smilenov, Lubomir; Brenner, David J.; Junk, Anna; Zhou, Wei; Hall, Eric J.

2002-01-01

It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM(+/-) cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.

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.

Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation.

PubMed

Vendetti, Frank P; Leibowitz, Brian J; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O'Connor, Mark J; Yu, Jian; Beumer, Jan H; Bakkenist, Christopher J

2017-02-01

We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21 CIP/WAF1 )-/- mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21 CIP/WAF1 )-/- mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21 CIP/WAF1 )-/-, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21 CIP/WAF1 )-/- mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI.

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

PubMed

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

2017-01-24

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

Adipose tissue macrophages in non-rodent mammals: a comparative study.

PubMed

Ampem, Grace; Azegrouz, Hind; Bacsadi, Árpád; Balogh, Lajos; Schmidt, Susanne; Thuróczy, Julianna; Röszer, Tamás

2016-02-01

The stromal vascular fraction (SVF) of adipose tissue in rodents and primates contains mesenchymal stem cells and immune cells. SVF cells have complex metabolic, immune and endocrine functions with biomedical impact. However, in other mammals, the amount of data on SVF stem cells is negligible and whether the SVF hosts immune cells is unknown. In this study, we show that the SVF is rich in immune cells, with a dominance of adipose tissue macrophages (ATMs) in cattle (Bos primigenius taurus), domestic goat (Capra aegagrus hircus), domestic sheep (Ovis aries), domestic cat (Felis catus) and domestic dog (Canis familiaris). ATMs of these species are granulated lysosome-rich cells with lamellipodial protrusions and express the lysosome markers acid phosphatase 5 (ACP-5) and Mac-3/Lamp-2. Using ACP-5 and Mac-3/Lamp-2 as markers, we additionally detected ATMs in other species, such as the domestic horse (Equus ferus caballus), wild boar (Sus scrofa) and red fox (Vulpes vulpes). Feline and canine ATMs also express the murine macrophage marker F4/80 antigen. In the lean condition, the alternative macrophage activation marker CD206 is expressed by feline and canine ATMs and arginase-1 by feline ATMs. Obesity is associated with interleukin-6 and interferon gamma expression and with overt tyrosine nitration in both feline and canine ATMs. This resembles the obesity-induced phenotype switch of murine and human ATMs. Thus, we show, for the first time, that the presence of ATMs is a general trait of mammals. The interaction between the adipose cells and SVF immune cells might be evolutionarily conserved among mammals.

Mobility of an elastic glove for extravehicular activity without prebreathing.

PubMed

Tanaka, Kunihiko; Ikeda, Mizuki; Mochizuki, Yosuke; Katafuchi, Tetsuro

2011-09-01

The current U.S. extravehicular activity (EVA) suit is pressurized at 0.29 atm, which is much lower than the pressures of sea level and inside a space station. Higher pressure can reduce the risk of decompression sickness (DCS), but mobility would be sacrificed. We have demonstrated that a glove and sleeve made of elastic material increased mobility when compared with those made of nonelastic material, such as that found in the current suit. We hypothesized that an elastic glove of 0.65 atm that has no risk of DCS also has greater mobility compared with a non-elastic glove of 0.29 atm. The right hands of 10 healthy volunteers were studied in a chamber with their bare hands at normal ambient pressure, after donning a non-elastic glove with a pressure differential of 0.29 atm, and after donning an elastic glove with a pressure differential of 0.29 and 0.65 atm. Range of motion (ROM) of the index finger and surface electromyography (EMG) amplitudes during finger flexion were measured. ROM with gloves was significantly smaller than that of bare hands, but was similar between conditions of gloves regardless of elasticity and pressure differentials. However, EMG amplitudes with the elastic glove of 0.29 and 0.65 atm were significantly smaller than those with the non-elastic glove of 0.29 atm. The results suggest that mobility of the elastic glove of 0.65 atm may be better than that of the non-elastic glove of 0.29 atm, similar to that used in the current EVA suit.

Software management tools: Lessons learned from use

NASA Technical Reports Server (NTRS)

Reifer, D. J.; Valett, J.; Knight, J.; Wenneson, G.

1985-01-01

Experience in inserting software project planning tools into more than 100 projects producing mission critical software are discussed. The problems the software project manager faces are listed along with methods and tools available to handle them. Experience is reported with the Project Manager's Workstation (PMW) and the SoftCost-R cost estimating package. Finally, the results of a survey, which looked at what could be done in the future to overcome the problems experienced and build a set of truly useful tools, are presented.

GNSS real time performance monitoring and CNS/ATM implementation

DOT National Transportation Integrated Search

2006-07-01

The global transition to communications, navigation, surveillance / air traffic management (CNS/ATM) technology is moving forward at an increasing pace. A critical part of the CNS/ATM concept is the ability to monitor, analyze, and distribute aeronau...

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.

Airborne laser mapping of Assateague National Seashore Beach

USGS Publications Warehouse

Krabill, W.B.; Wright, C.W.; Swift, R.N.; Frederick, E.B.; Manizade, S.S.; Yungel, J.K.; Martin, C.F.; Sonntag, J.G.; Duffy, Mark; Hulslander, William; Brock, John C.

2000-01-01

Results are presented from topographic surveys of the Assateague Island National Seashore using an airborne scanning laser altimeter and kinematic Global Positioning System (GPS) technology. The instrument used was the Airborne Topographic Mapper (ATM), developed by the NASA Arctic Ice Mapping (AIM) group from the Goddard Space Flight Center's Wallops Flight Facility. In November, 1995, and again in May, 1996, these topographic surveys were flown as a functionality check prior to conducting missions to measure the elevation of extensive sections of the Greenland Ice Sheet as part of NASA's Global Climate Change program. Differences between overlapping portions of both surveys are compared for quality control. An independent assessment of the accuracy of the ATM survey is provided by comparison to surface surveys which were conducted using standard techniques. The goal of these projects is to make these measurements to an accuracy of ± 10 cm. Differences between the fall 1995 and 1996 surveys provides an assessment of net changes in the beach morphology over an annual cycle.

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.

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.

Challenges in Achieving Trajectory-Based Operations

NASA Technical Reports Server (NTRS)

Cate, Karen Tung

2012-01-01

In the past few years much of the global ATM research community has proposed advanced systems based on Trajectory-Based Operations (TBO). The concept of TBO uses four-dimensional aircraft trajectories as the base information for managing safety and capacity. Both the US and European advanced ATM programs call for the sharing of trajectory data across different decision support tools for successful operations. However, the actual integration of TBO systems presents many challenges. Trajectory predictors are built to meet the specific needs of a particular system and are not always compatible with others. Two case studies are presented which examine the challenges of introducing a new concept into two legacy systems in regards to their trajectory prediction software. The first case describes the issues with integrating a new decision support tool with a legacy operational system which overlap in domain space. These tools perform similar functions but are driven by different requirements. The difference in the resulting trajectories can lead to conflicting advisories. The second case looks at integrating this same new tool with a legacy system originally developed as an integrated system, but diverged many years ago. Both cases illustrate how the lack of common architecture concepts for the trajectory predictors added cost and complexity to the integration efforts.

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

PubMed

Lin, Zi-Li; Kim, Nam-Hyung

2015-06-01

Ataxia-telangiectasia mutated (ATM) is critical for the DNA damage response, cell cycle checkpoints, and apoptosis. Significant effort has focused on elucidating the relationship between ATM and other nuclear signal transducers; however, little is known about the connection between ATM and oocyte meiotic maturation. We investigated the function of ATM in porcine oocytes. ATM was expressed at all stages of oocyte maturation and localized predominantly in the nucleus. Furthermore, the ATM-specific inhibitor KU-55933 blocked porcine oocyte maturation, reducing the percentages of oocytes that underwent germinal vesicle breakdown (GVBD) and first polar body extrusion. KU-55933 also decreased the expression of DNA damage-related genes (breast cancer 1, budding uninhibited by benzimidazoles 1, and P53) and reduced the mRNA and protein levels of AKT and other cell cycle-regulated genes that are predominantly expressed during G2/M phase, including bone morphogenetic protein 15, growth differentiation factor 9, cell division cycle protein 2, cyclinB1, and AKT. KU-55933 treatment decreased the developmental potential of blastocysts following parthenogenetic activation and increased the level of apoptosis. Together, these data suggested that ATM influenced the meiotic and cytoplasmic maturation of porcine oocytes, potentially by decreasing their sensitivity to DNA strand breaks, stimulating the AKT pathway, and/or altering the expression of other maternal genes. © 2015 International Federation for Cell Biology.

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.

Dual inhibition of ATR and ATM potentiates the activity of trabectedin and lurbinectedin by perturbing the DNA damage response and homologous recombination repair.

PubMed

Lima, Michelle; Bouzid, Hana; Soares, Daniele G; Selle, Frédéric; Morel, Claire; Galmarini, Carlos M; Henriques, João A P; Larsen, Annette K; Escargueil, Alexandre E

2016-05-03

Trabectedin (Yondelis®, ecteinascidin-743, ET-743) is a marine-derived natural product approved for treatment of advanced soft tissue sarcoma and relapsed platinum-sensitive ovarian cancer. Lurbinectedin is a novel anticancer agent structurally related to trabectedin. Both ecteinascidins generate DNA double-strand breaks that are processed through homologous recombination repair (HRR), thereby rendering HRR-deficient cells particularly sensitive. We here characterize the DNA damage response (DDR) to trabectedin and lurbinectedin in HeLa cells. Our results show that both compounds activate the ATM/Chk2 (ataxia-telangiectasia mutated/checkpoint kinase 2) and ATR/Chk1 (ATM and RAD3-related/checkpoint kinase 1) pathways. Interestingly, pharmacological inhibition of Chk1/2, ATR or ATM is not accompanied by any significant improvement of the cytotoxic activity of the ecteinascidins while dual inhibition of ATM and ATR strongly potentiates it. Accordingly, concomitant inhibition of both ATR and ATM is an absolute requirement to efficiently block the formation of γ-H2AX, MDC1, BRCA1 and Rad51 foci following exposure to the ecteinascidins. These results are not restricted to HeLa cells, but are shared by cisplatin-sensitive and -resistant ovarian carcinoma cells. Together, our data identify ATR and ATM as central coordinators of the DDR to ecteinascidins and provide a mechanistic rationale for combining these compounds with ATR and ATM inhibitors.

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.

Availability of software services for a hospital information system.

PubMed

Sakamoto, N

1998-03-01

Hospital information systems (HISs) are becoming more important and covering more parts in daily hospital operations as order-entry systems become popular and electronic charts are introduced. Thus, HISs today need to be able to provide necessary services for hospital operations for a 24-h day, 365 days a year. The provision of services discussed here does not simply mean the availability of computers, in which all that matters is that the computer is functioning. It means the provision of necessary information for hospital operations by the computer software, and we will call it the availability of software services. HISs these days are mostly client-server systems. To increase availability of software services in these systems, it is not enough to just use system structures that are highly reliable in existing host-centred systems. Four main components which support availability of software services are network systems, client computers, server computers, and application software. In this paper, we suggest how to structure these four components to provide the minimum requested software services even if a part of the system stops to function. The network system should be double-protected in stratus using Asynchronous Transfer Mode (ATM) as its base network. Client computers should be fat clients with as much application logic as possible, and reference information which do not require frequent updates (master files, for example) should be replicated in clients. It would be best if all server computers could be double-protected. However, if that is physically impossible, one database file should be made accessible by several server computers. Still, at least the basic patients' information and the latest clinical records should be double-protected physically. Application software should be tested carefully before introduction. Different versions of the application software should always be kept and managed in case the new version has problems. If a hospital information system is designed and developed with these points in mind, it's availability of software services should increase greatly.

Defect measurement and analysis of JPL ground software: a case study

NASA Technical Reports Server (NTRS)

Powell, John D.; Spagnuolo, John N., Jr.

2004-01-01

Ground software systems at JPL must meet high assurance standards while remaining on schedule due to relatively immovable launch dates for spacecraft that will be controlled by such systems. Toward this end, the Software Quality Improvement (SQI) project's Measurement and Benchmarking (M&B) team is collecting and analyzing defect data of JPL ground system software projects to build software defect prediction models. The aim of these models is to improve predictability with regard to software quality activities. Predictive models will quantitatively define typical trends for JPL ground systems as well as Critical Discriminators (CDs) to provide explanations for atypical deviations from the norm at JPL. CDs are software characteristics that can be estimated or foreseen early in a software project's planning. Thus, these CDs will assist in planning for the predicted degree to which software quality activities for a project are likely to deviation from the normal JPL ground system based on pasted experience across the lab.

Manager's handbook for software development, revision 1

NASA Technical Reports Server (NTRS)

1990-01-01

Methods and aids for the management of software development projects are presented. The recommendations are based on analyses and experiences of the Software Engineering Laboratory (SEL) with flight dynamics software development. The management aspects of the following subjects are described: organizing the project, producing a development plan, estimating costs, scheduling, staffing, preparing deliverable documents, using management tools, monitoring the project, conducting reviews, auditing, testing, and certifying.

Conceptions of Software Development by Project Managers: A Study of Managing the Outsourced Development of Software Applications for United States Federal Government Agencies

ERIC Educational Resources Information Center

Eisen, Daniel

2013-01-01

This study explores how project managers, working for private federal IT contractors, experience and understand managing the development of software applications for U.S. federal government agencies. Very little is known about how they manage their projects in this challenging environment. Software development is a complex task and only grows in…

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)

Nuclear factor erythroid 2-related factor 2-antioxidant activation through the action of ataxia telangiectasia-mutated serine/threonine kinase is essential to counteract oxidative stress in bovine mammary epithelial cells.

PubMed

Ma, Y F; Wu, Z H; Gao, M; Loor, J J

2018-06-01

Nuclear factor (erythroid-derived 2)-like factor 2 (NFE2L2, formerly Nrf2) is a transcription factor that binds to the antioxidant response element (ARE) in the upstream promoter region of various antioxidant-responsive genes. Hence, at least in nonruminants, the NFE2L2-ARE signaling pathway plays an important role in the cellular antioxidant defense system. Whether oxidative stress in bovine mammary epithelial cells alters NFE2L2 or the NFE2L2-ARE pathway is unclear. Therefore, the objective of this study was to examine the response in NFE2L2- and NFE2L2-ARE-related components in bovine mammary epithelial cells (BMEC) under oxidative stress. An in silico analysis to identify potential phosphorylation sites on NFE2L2 and the protein kinases was performed with Netphos 3.1 (http://www.cbs.dtu.dk/services/NetPhos/) and Scansite (http://scansite.mit.edu) software. Isolated BMEC were exposed to H 2 O 2 (600 μM) for 6 h to induce oxidative stress. In silico analysis revealed ataxia telangiectasia-mutated (ATM) serine/threonine kinase as a key kinase responsible for the phosphorylation of NFE2L2. Thus, after the 6 h incubation with H 2 O 2 , BMEC were transiently transfected with ATM-small interfering RNA (siRNA) 1, 2, or 3. Compared with the control, transfection with ATM-siRNA3 resulted in proliferation rates that were 60.7 and 36.2% lower with or without H 2 O 2 . In addition, production of reactive oxygen species and malondialdehyde increased markedly, but activities of superoxide dismutase, glutathione peroxidase, catalase, and glutathione-S-transferase decreased markedly in transfected cells without or with H 2 O 2 compared with the control. Transfected cells had markedly lower protein and mRNA expression of NFE2L2 without or with H 2 O 2 compared with the control. In addition, fluorescent activity of the ARE in transfected BMEC indicated that NFE2L2-driven transcriptional activation decreased under oxidative stress. Overall, results indicate that ATM is a physiologically relevant NFE2L2 kinase. Furthermore, inhibition of ATM activity can cause marked alterations in oxidative stress leading to cell death as a result of diminished capacity of BMEC to cope with H 2 O 2 -induced cytotoxicity. The relevance of this kinase in vivo merits further study. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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.

Software-Engineering Process Simulation (SEPS) model

NASA Technical Reports Server (NTRS)

Lin, C. Y.; Abdel-Hamid, T.; Sherif, J. S.

1992-01-01

The Software Engineering Process Simulation (SEPS) model is described which was developed at JPL. SEPS is a dynamic simulation model of the software project development process. It uses the feedback principles of system dynamics to simulate the dynamic interactions among various software life cycle development activities and management decision making processes. The model is designed to be a planning tool to examine tradeoffs of cost, schedule, and functionality, and to test the implications of different managerial policies on a project's outcome. Furthermore, SEPS will enable software managers to gain a better understanding of the dynamics of software project development and perform postmodern assessments.

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.

Nbn and atm cooperate in a tissue and developmental stage-specific manner to prevent double strand breaks and apoptosis in developing brain and eye.

PubMed

Rodrigues, Paulo M G; Grigaravicius, Paulius; Remus, Martina; Cavalheiro, Gabriel R; Gomes, Anielle L; Rocha-Martins, Maurício; Martins, Mauricio R; Frappart, Lucien; Reuss, David; McKinnon, Peter J; von Deimling, Andreas; Martins, Rodrigo A P; Frappart, Pierre-Olivier

2013-01-01

Nibrin (NBN or NBS1) and ATM are key factors for DNA Double Strand Break (DSB) signaling and repair. Mutations in NBN or ATM result in Nijmegen Breakage Syndrome and Ataxia telangiectasia. These syndromes share common features such as radiosensitivity, neurological developmental defects and cancer predisposition. However, the functional synergy of Nbn and Atm in different tissues and developmental stages is not yet understood. Here, we show in vivo consequences of conditional inactivation of both genes in neural stem/progenitor cells using Nestin-Cre mice. Genetic inactivation of Atm in the central nervous system of Nbn-deficient mice led to reduced life span and increased DSBs, resulting in increased apoptosis during neural development. Surprisingly, the increase of DSBs and apoptosis was found only in few tissues including cerebellum, ganglionic eminences and lens. In sharp contrast, we showed that apoptosis associated with Nbn deletion was prevented by simultaneous inactivation of Atm in developing retina. Therefore, we propose that Nbn and Atm collaborate to prevent DSB accumulation and apoptosis during development in a tissue- and developmental stage-specific manner.

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

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%.

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.

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

PubMed

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

2015-10-23

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

The role of the ataxia telangiectasia mutated gene in lung cancer: recent advances in research.

PubMed

Xu, Yanling; Gao, Peng; Lv, Xuejiao; Zhang, Lin; Zhang, Jie

2017-09-01

Lung cancer is the leading cause of death due to cancer worldwide. It is estimated that approximately 1.2 million new cases of lung cancer are diagnosed each year. Early detection and treatment are crucial for improvements in both prognosis and quality of life of lung cancer patients. The ataxia telangiectasia mutated (ATM) gene is a cancer-susceptibility gene that encodes a key apical kinase in the DNA damage response pathway. It has recently been shown to play an important role in the development of lung cancer. The main functions of the ATM gene and protein includes participation in cell cycle regulation, and identification and repair of DNA damage. ATM gene mutation can lead to multiple system dysfunctions as well as a concomitant increase in tumor tendency. In recent years, many studies have indicated that single nucleotide polymorphism of the ATM gene is associated with increased incidence of lung cancer. At the same time, the ATM gene and its encoding product ATM protein predicts the response to radiotherapy, chemotherapy, and prognosis of lung cancer, thus suggesting that the ATM gene may be a new potential target for the diagnosis and treatment of lung cancer.

Project management in the development of scientific software

NASA Astrophysics Data System (ADS)

Platz, Jochen

1986-08-01

This contribution is a rough outline of a comprehensive project management model for the development of software for scientific applications. The model was tested in the unique environment of the Siemens AG Corporate Research and Technology Division. Its focal points are the structuring of project content - the so-called phase organization, the project organization and the planning model used, and its particular applicability to innovative projects. The outline focuses largely on actual project management aspects rather than associated software engineering measures.

Process Acceptance and Adoption by IT Software Project Practitioners

ERIC Educational Resources Information Center

Guardado, Deana R.

2012-01-01

This study addresses the question of what factors determine acceptance and adoption of processes in the context of Information Technology (IT) software development projects. This specific context was selected because processes required for managing software development projects are less prescriptive than in other, more straightforward, IT…

Organizational Stresses and Practices Impeding Quality Software Development in Government Procurements

ERIC Educational Resources Information Center

Holcomb, Glenda S.

2010-01-01

This qualitative, phenomenological doctoral dissertation research study explored the software project team members perceptions of changing organizational cultures based on management decisions made at project deviation points. The research study provided a view into challenged or failing government software projects through the lived experiences…

Proceedings of the 14th Annual Software Engineering Workshop

NASA Technical Reports Server (NTRS)

1989-01-01

Several software related topics are presented. Topics covered include studies and experiment at the Software Engineering Laboratory at the Goddard Space Flight Center, predicting project success from the Software Project Management Process, software environments, testing in a reuse environment, domain directed reuse, and classification tree analysis using the Amadeus measurement and empirical analysis.

Shotgun proteomics reveals physiological response to ocean acidification in Crassostrea gigas.

PubMed

Timmins-Schiffman, Emma; Coffey, William D; Hua, Wilber; Nunn, Brook L; Dickinson, Gary H; Roberts, Steven B

2014-11-03

Ocean acidification as a result of increased anthropogenic CO2 emissions is occurring in marine and estuarine environments worldwide. The coastal ocean experiences additional daily and seasonal fluctuations in pH that can be lower than projected end-of-century open ocean pH reductions. In order to assess the impact of ocean acidification on marine invertebrates, Pacific oysters (Crassostrea gigas) were exposed to one of four different p CO2 levels for four weeks: 400 μatm (pH 8.0), 800 μatm (pH 7.7), 1000 μatm (pH 7.6), or 2800 μatm (pH 7.3). At the end of the four week exposure period, oysters in all four p CO2 environments deposited new shell, but growth rate was not different among the treatments. However, micromechanical properties of the new shell were compromised by elevated p CO2. Elevated p CO2 affected neither whole body fatty acid composition, nor glycogen content, nor mortality rate associated with acute heat shock. Shotgun proteomics revealed that several physiological pathways were significantly affected by ocean acidification, including antioxidant response, carbohydrate metabolism, and transcription and translation. Additionally, the proteomic response to a second stress differed with p CO2, with numerous processes significantly affected by mechanical stimulation at high versus low p CO2 (all proteomics data are available in the ProteomeXchange under the identifier PXD000835). Oyster physiology is significantly altered by exposure to elevated p CO2, indicating changes in energy resource use. This is especially apparent in the assessment of the effects of p CO2 on the proteomic response to a second stress. The altered stress response illustrates that ocean acidification may impact how oysters respond to other changes in their environment. These data contribute to an integrative view of the effects of ocean acidification on oysters as well as physiological trade-offs during environmental stress.

Pilot Performance on New ATM Operations: Maintaining In-Trail Separation and Arrival Sequencing

NASA Technical Reports Server (NTRS)

Pritchett, Amy R.; Yankosky, L. J.; Johnson, Walter (Technical Monitor)

1999-01-01

Cockpit Display of Traffic Information (CDTI) may enable new Air Traffic Management (ATM) operations. However, CDTI is not the only source of traffic information in the cockpit; ATM procedures may provide information, implicitly and explicitly, about other aircraft. An experiment investigated pilot ability to perform two new ATM operations - maintaining in-trail separation from another aircraft and sequencing into an arrival stream. In the experiment, pilots were provided different amounts of information from displays and procedures. The results are described.

n/a

NASA Image and Video Library

1971-08-01

The Apollo Telescope Mount (ATM), designed and developed by the Marshall Space Flight Center, was one of four major components comprising the Skylab (1973-1979). The ATM housed the first manned scientific telescope in space. This photograph is of the ATM thermal systems unit undergoing testing in the Space Environment Simulation Laboratory of the Manned Spacecraft Center (MSC). The ATM thermal systems unit was used to control the temperatures of space instrument's subsystems during a mission. The MSC was renamed the Johnson Space Center (JSC) in early 1973.

Large Eddy Simulation Modeling of Flashback and Flame Stabilization in Hydrogen-Rich Gas Turbines Using a Hierarchical Validation Approach

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

Clemens, Noel

This project was a combined computational and experimental effort to improve predictive capability for boundary layer flashback of premixed swirl flames relevant to gas-turbine power plants operating with high-hydrogen-content fuels. During the course of this project, significant progress in modeling was made on four major fronts: 1) use of direct numerical simulation of turbulent flames to understand the coupling between the flame and the turbulent boundary layer; 2) improved modeling capability for flame propagation in stratified pre-mixtures; 3) improved portability of computer codes using the OpenFOAM platform to facilitate transfer to industry and other researchers; and 4) application of LESmore » to flashback in swirl combustors, and a detailed assessment of its capabilities and limitations for predictive purposes. A major component of the project was an experimental program that focused on developing a rich experimental database of boundary layer flashback in swirl flames. Both methane and high-hydrogen fuels, including effects of elevated pressure (1 to 5 atm), were explored. For this project, a new model swirl combustor was developed. Kilohertz-rate stereoscopic PIV and chemiluminescence imaging were used to investigate the flame propagation dynamics. In addition to the planar measurements, a technique capable of detecting the instantaneous, time-resolved 3D flame front topography was developed and applied successfully to investigate the flow-flame interaction. The UT measurements and legacy data were used in a hierarchical validation approach where flows with increasingly complex physics were used for validation. First component models were validated with DNS and literature data in simplified configurations, and this was followed by validation with the UT 1-atm flashback cases, and then the UT high-pressure flashback cases. The new models and portable code represent a major improvement over what was available before this project was initiated.« less

p38 MAPK-Mediated Bmi-1 Down-Regulation and Defective Proliferation in ATM-Deficient Neural Stem Cells Can Be Restored by Akt Activation

PubMed Central

Kim, Jeesun; Hwangbo, Jeon; Wong, Paul K. Y.

2011-01-01

A-T (ataxia telangiectasia) is a genetic disease caused by a mutation in the Atm (A-T mutated) gene that leads to neurodegeneration. Despite an increase in the numbers of studies in this area in recent years, the mechanisms underlying neurodegeneration in human A-T are still poorly understood. Previous studies demonstrated that neural stem cells (NSCs) isolated from the subventricular zone (SVZ) of Atm -/- mouse brains show defective self-renewal and proliferation, which is accompanied by activation of chronic p38 mitogen-activated protein kinase (MAPK) and a lower level of the polycomb protein Bmi-1. However, the mechanism underlying Bmi-1 down-regulation and its relevance to defective proliferation in Atm-/- NSCs remained unclear. Here, we show that over-expression of Bmi-1 increases self-renewal and proliferation of Atm-/- NSCs to normal, indicating that defective proliferation in Atm-/- NSCs is a consequence of down-regulation of Bmi-1. We also demonstrate that epidermal growth factor (EGF)-induced Akt phosphorylation renders Bmi-1 resistant to the proteasomal degradation, leading to its stabilization and accumulation in the nucleus. However, inhibition of the Akt-dependent Bmi-1 stabilizing process by p38 MAPK signaling reduces the levels of Bmi-1. Treatment of the Atm-/- NSCs with a specific p38 MAPK inhibitor SB203580 extended Bmi-1 posttranscriptional turnover and H2A ubiquitination in Atm-/- NSCs. Our observations demonstrate the molecular basis underlying the impairment of self-renewal and proliferation in Atm-/- NSCs through the p38 MAPK-Akt-Bmi-1-p21 signaling pathway. PMID:21305053

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 heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts

PubMed Central

Worgul, Basil V.; Smilenov, Lubomir; Brenner, David J.; Junk, Anna; Zhou, Wei; Hall, Eric J.

2002-01-01

It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM+/−) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM+/− cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage. PMID:12119422

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.

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.

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

PubMed

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

2016-11-04

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

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.

Nickel-cadium batteries for Apollo telescope mount

NASA Technical Reports Server (NTRS)

Kirsch, W. W.; Shikoh, A. E.

1974-01-01

The operational testing and evaluation program is presented which was conducted on 20-ampere-hour nickel-cadmium (Ni-Cd) batteries for use on the Apollo telescope mount (ATM). The test program was initiated in 1967 to determine if the batteries could meet ATM mission requirements and to determine operating characteristics and methods. The ATM system power and charging power for the Ni-Cd secondary batteries is provided by a solar array during the 58-minute daylight portion of the orbit; during the 36-minute night portion of the orbit, the Ni-Cd secondary batteries will supply ATM system power. The test results reflect battery operating characteristics and parameters relative to simulated ATM orbital test conditions. Maximum voltage, charge requirements, capacity, temperature, and cyclic characteristics are presented.

Project SYNERGY: Software Support for Underprepared Students. Software Implementation Report.

ERIC Educational Resources Information Center

Anandam, Kamala; And Others

Miami-Dade Community College's (MDCC's) implementation and assessment of computer software as a part of Project SYNERGY, a multi-institutional project funded by the International Business Machines (IBM) Corporation designed to seek technological solutions for helping students underprepared in reading, writing and mathematics, is described in this…

The dynamics of software development project management: An integrative systems dynamic perspective

NASA Technical Reports Server (NTRS)

Vandervelde, W. E.; Abdel-Hamid, T.

1984-01-01

Rather than continuing to focus on software development projects per se, the system dynamics modeling approach outlined is extended to investigate a broader set of issues pertaining to the software development organization. Rather than trace the life cycle(s) of one or more software projects, the focus is on the operations of a software development department as a continuous stream of software products are developed, placed into operation, and maintained. A number of research questions are ""ripe'' for investigating including: (1) the efficacy of different organizational structures in different software development environments, (2) personnel turnover, (3) impact of management approaches such as management by objectives, and (4) the organizational/environmental determinants of productivity.

A Study of Clinically Related Open Source Software Projects

PubMed Central

Hogarth, Michael A.; Turner, Stuart

2005-01-01

Open source software development has recently gained significant interest due to several successful mainstream open source projects. This methodology has been proposed as being similarly viable and beneficial in the clinical application domain as well. However, the clinical software development venue differs significantly from the mainstream software venue. Existing clinical open source projects have not been well characterized nor formally studied so the ‘fit’ of open source in this domain is largely unknown. In order to better understand the open source movement in the clinical application domain, we undertook a study of existing open source clinical projects. In this study we sought to characterize and classify existing clinical open source projects and to determine metrics for their viability. This study revealed several findings which we believe could guide the healthcare community in its quest for successful open source clinical software projects. PMID:16779056

Skylab

NASA Image and Video Library

1972-02-01

The Apollo Telescope Mount (ATM) was one of four major components of Skylab (1973-1979) that were designed and developed at the Marshall Space Flight Center. In this picture, an ATM solar wing prototype is shown during assembly. A total of four solar wings were required to provide power to the ATM.

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…

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)

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

PubMed Central

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

2018-01-01

Chromosomal translocations are hallmarks of various types of cancers and leukemias. However, the molecular mechanisms of chromosome translocations remain largely unknown. The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. Previously, we showed that ATM deficiency led to the 11q23 chromosome translocation, the most frequent chromosome abnormalities in secondary leukemia. Here, we show that ARP8, a subunit of the INO80 chromatin remodeling complex, is phosphorylated after etoposide treatment. The etoposide-induced phosphorylation of ARP8 is regulated by ATM and ATR, and attenuates its interaction with INO80. The ATM-regulated phosphorylation of ARP8 reduces the excessive loading of INO80 and RAD51 onto the breakpoint cluster region. These findings suggest that the phosphorylation of ARP8, regulated by ATM, plays an important role in maintaining the fidelity of DNA repair to prevent the etoposide-induced 11q23 abnormalities. PMID:29759113

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

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.

Involvement of Atm and Trp53 in neural cell loss due to Terf2 inactivation during mouse brain development.

PubMed

Kim, Jusik; Choi, Inseo; Lee, Youngsoo

2017-11-01

Maintenance of genomic integrity is one of the critical features for proper neurodevelopment and inhibition of neurological diseases. The signals from both ATM and ATR to TP53 are well-known mechanisms to remove neural cells with DNA damage during neurogenesis. Here we examined the involvement of Atm and Atr in genomic instability due to Terf2 inactivation during mouse brain development. Selective inactivation of Terf2 in neural progenitors induced apoptosis, resulting in a complete loss of the brain structure. This neural loss was rescued partially in both Atm and Trp53 deficiency, but not in an Atr-deficient background in the mouse. Atm inactivation resulted in incomplete brain structures, whereas p53 deficiency led to the formation of multinucleated giant neural cells and the disruption of the brain structure. These giant neural cells disappeared in Lig4 deficiency. These data demonstrate ATM and TP53 are important for the maintenance of telomere homeostasis and the surveillance of telomere dysfunction during neurogenesis.

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

PubMed

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

2018-05-08

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

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

PubMed Central

2014-01-01

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

A toolbox for developing bioinformatics software

PubMed Central

Potrzebowski, Wojciech; Puton, Tomasz; Rother, Magdalena; Wywial, Ewa; Bujnicki, Janusz M.

2012-01-01

Creating useful software is a major activity of many scientists, including bioinformaticians. Nevertheless, software development in an academic setting is often unsystematic, which can lead to problems associated with maintenance and long-term availibility. Unfortunately, well-documented software development methodology is difficult to adopt, and technical measures that directly improve bioinformatic programming have not been described comprehensively. We have examined 22 software projects and have identified a set of practices for software development in an academic environment. We found them useful to plan a project, support the involvement of experts (e.g. experimentalists), and to promote higher quality and maintainability of the resulting programs. This article describes 12 techniques that facilitate a quick start into software engineering. We describe 3 of the 22 projects in detail and give many examples to illustrate the usage of particular techniques. We expect this toolbox to be useful for many bioinformatics programming projects and to the training of scientific programmers. PMID:21803787

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

PubMed

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

2017-01-01

The aim of this study was to evaluate the effect of chronic smoking on the expression profile of the repair genes MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers and never smokers. The sample consisted of thirty exfoliative cytology smears per group obtained from Smokers and Never Smokers. Total RNA was extracted and expression of the MLH1, MSH2 and ATM genes were evaluated by quantitative real-time and immunocytochemistry. The gene and protein expression data were correlated to the clinical data. Gene expression was analyzed statistically using the Student t-test and Pearson's correlation coefficient, with p<0.05. MLH1, MSH2 and ATM genes were downregulated in the smoking group compared to the control with significant values for MLH1 (p=0.006), MSH2 (p=0.0001) and ATM (p=0.0001). Immunocytochemical staining for anti-MLH1, anti-MSH2 and anti-ATM was negative in Never Smokers; in Smokers it was rarely positive. No significant correlation was observed among the expression of MLH1, MSH2, ATM and age, number of cigarettes consumed per day, time of smoking during life, smoking history or levels of CO in expired air. The expression of genes and proteins related to DNA repair mechanism MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers was reduced. Copyright © 2016 Elsevier Ltd. All rights reserved.

Simulated leakage of high pCO2 water negatively impacts bivalve dominated infaunal communities from the Western Baltic Sea

NASA Astrophysics Data System (ADS)

Schade, Hanna; Mevenkamp, Lisa; Guilini, Katja; Meyer, Stefanie; Gorb, Stanislav N.; Abele, Doris; Vanreusel, Ann; Melzner, Frank

2016-08-01

Carbon capture and storage is promoted as a mitigation method counteracting the increase of atmospheric CO2 levels. However, at this stage, environmental consequences of potential CO2 leakage from sub-seabed storage sites are still largely unknown. In a 3-month-long mesocosm experiment, this study assessed the impact of elevated pCO2 levels (1,500 to 24,400 μatm) on Cerastoderma edule dominated benthic communities from the Baltic Sea. Mortality of C. edule was significantly increased in the highest treatment (24,400 μatm) and exceeded 50%. Furthermore, mortality of small size classes (0-1 cm) was significantly increased in treatment levels ≥6,600 μatm. First signs of external shell dissolution became visible at ≥1,500 μatm, holes were observed at >6,600 μatm. C. edule body condition decreased significantly at all treatment levels (1,500-24,400 μatm). Dominant meiofauna taxa remained unaffected in abundance. Densities of calcifying meiofauna taxa (i.e. Gastropoda and Ostracoda) decreased in high CO2 treatments (>6,600 μatm), while the non - calcifying Gastrotricha significantly increased in abundance at 24,400 μatm. In addition, microbial community composition was altered at the highest pCO2 level. We conclude that strong CO2 leakage can alter benthic infauna community composition at multiple trophic levels, likely due to high mortality of the dominant macrofauna species C. edule.

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.

Simulated leakage of high pCO2 water negatively impacts bivalve dominated infaunal communities from the Western Baltic Sea.

PubMed

Schade, Hanna; Mevenkamp, Lisa; Guilini, Katja; Meyer, Stefanie; Gorb, Stanislav N; Abele, Doris; Vanreusel, Ann; Melzner, Frank

2016-08-19

Carbon capture and storage is promoted as a mitigation method counteracting the increase of atmospheric CO2 levels. However, at this stage, environmental consequences of potential CO2 leakage from sub-seabed storage sites are still largely unknown. In a 3-month-long mesocosm experiment, this study assessed the impact of elevated pCO2 levels (1,500 to 24,400 μatm) on Cerastoderma edule dominated benthic communities from the Baltic Sea. Mortality of C. edule was significantly increased in the highest treatment (24,400 μatm) and exceeded 50%. Furthermore, mortality of small size classes (0-1 cm) was significantly increased in treatment levels ≥6,600 μatm. First signs of external shell dissolution became visible at ≥1,500 μatm, holes were observed at >6,600 μatm. C. edule body condition decreased significantly at all treatment levels (1,500-24,400 μatm). Dominant meiofauna taxa remained unaffected in abundance. Densities of calcifying meiofauna taxa (i.e. Gastropoda and Ostracoda) decreased in high CO2 treatments (>6,600 μatm), while the non - calcifying Gastrotricha significantly increased in abundance at 24,400 μatm. In addition, microbial community composition was altered at the highest pCO2 level. We conclude that strong CO2 leakage can alter benthic infauna community composition at multiple trophic levels, likely due to high mortality of the dominant macrofauna species C. edule.

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.

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.

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.

Software Transition Project Retrospectives and the Application of SEL Effort Estimation Model and Boehm's COCOMO to Complex Software Transition Projects

NASA Technical Reports Server (NTRS)

McNeill, Justin

1995-01-01

The Multimission Image Processing Subsystem (MIPS) at the Jet Propulsion Laboratory (JPL) has managed transitions of application software sets from one operating system and hardware platform to multiple operating systems and hardware platforms. As a part of these transitions, cost estimates were generated from the personal experience of in-house developers and managers to calculate the total effort required for such projects. Productivity measures have been collected for two such transitions, one very large and the other relatively small in terms of source lines of code. These estimates used a cost estimation model similar to the Software Engineering Laboratory (SEL) Effort Estimation Model. Experience in transitioning software within JPL MIPS have uncovered a high incidence of interface complexity. Interfaces, both internal and external to individual software applications, have contributed to software transition project complexity, and thus to scheduling difficulties and larger than anticipated design work on software to be ported.

Projecting manpower to attain quality

NASA Technical Reports Server (NTRS)

Rone, K. Y.

1983-01-01

The resulting model is useful as a projection tool but must be validated in order to be used as an on-going software cost engineering tool. A procedure is developed to facilitate the tracking of model projections and actual data to allow the model to be tuned. Finally, since the model must be used in an environment of overlapping development activities on a progression of software elements in development and maintenance, a manpower allocation model is developed for use in a steady state development/maintenance environment. In these days of soaring software costs it becomes increasingly important to properly manage a software development project. One element of the management task is the projection and tracking of manpower required to perform the task. In addition, since the total cost of the task is directly related to the initial quality built into the software, it becomes a necessity to project the development manpower in a way to attain that quality. An approach to projecting and tracking manpower with quality in mind is described.

Software metrics: The key to quality software on the NCC project

NASA Technical Reports Server (NTRS)

Burns, Patricia J.

1993-01-01

Network Control Center (NCC) Project metrics are captured during the implementation and testing phases of the NCCDS software development lifecycle. The metrics data collection and reporting function has interfaces with all elements of the NCC project. Close collaboration with all project elements has resulted in the development of a defined and repeatable set of metrics processes. The resulting data are used to plan and monitor release activities on a weekly basis. The use of graphical outputs facilitates the interpretation of progress and status. The successful application of metrics throughout the NCC project has been instrumental in the delivery of quality software. The use of metrics on the NCC Project supports the needs of the technical and managerial staff. This paper describes the project, the functions supported by metrics, the data that are collected and reported, how the data are used, and the improvements in the quality of deliverable software since the metrics processes and products have been in use.

On the Prospects and Concerns of Integrating Open Source Software Environment in Software Engineering Education

ERIC Educational Resources Information Center

Kamthan, Pankaj

2007-01-01

Open Source Software (OSS) has introduced a new dimension in software community. As the development and use of OSS becomes prominent, the question of its integration in education arises. In this paper, the following practices fundamental to projects and processes in software engineering are examined from an OSS perspective: project management;…

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…

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…

SeisCode: A seismological software repository for discovery and collaboration

NASA Astrophysics Data System (ADS)

Trabant, C.; Reyes, C. G.; Clark, A.; Karstens, R.

2012-12-01

SeisCode is a community repository for software used in seismological and related fields. The repository is intended to increase discoverability of such software and to provide a long-term home for software projects. Other places exist where seismological software may be found, but none meet the requirements necessary for an always current, easy to search, well documented, and citable resource for projects. Organizations such as IRIS, ORFEUS, and the USGS have websites with lists of available or contributed seismological software. Since the authors themselves do often not maintain these lists, the documentation often consists of a sentence or paragraph, and the available software may be outdated. Repositories such as GoogleCode and SourceForge, which are directly maintained by the authors, provide version control and issue tracking but do not provide a unified way of locating geophysical software scattered in and among countless unrelated projects. Additionally, projects are hosted at language-specific sites such as Mathworks and PyPI, in FTP directories, and in websites strewn across the Web. Search engines are only partially effective discovery tools, as the desired software is often hidden deep within the results. SeisCode provides software authors a place to present their software, codes, scripts, tutorials, and examples to the seismological community. Authors can choose their own level of involvement. At one end of the spectrum, the author might simply create a web page that points to an existing site. At the other extreme, an author may choose to leverage the many tools provided by SeisCode, such as a source code management tool with integrated issue tracking, forums, news feeds, downloads, wikis, and more. For software development projects with multiple authors, SeisCode can also be used as a central site for collaboration. SeisCode provides the community with an easy way to discover software, while providing authors a way to build a community around their software packages. IRIS invites the seismological community to browse and to submit projects to https://seiscode.iris.washington.edu/

Computer-aided software development process design

NASA Technical Reports Server (NTRS)

Lin, Chi Y.; Levary, Reuven R.

1989-01-01

The authors describe an intelligent tool designed to aid managers of software development projects in planning, managing, and controlling the development process of medium- to large-scale software projects. Its purpose is to reduce uncertainties in the budget, personnel, and schedule planning of software development projects. It is based on dynamic model for the software development and maintenance life-cycle process. This dynamic process is composed of a number of time-varying, interacting developmental phases, each characterized by its intended functions and requirements. System dynamics is used as a modeling methodology. The resulting Software LIfe-Cycle Simulator (SLICS) and the hybrid expert simulation system of which it is a subsystem are described.

How the NWC handles software as product

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

Vinson, D.

1997-11-01

This tutorial provides a hands-on view of how the Nuclear Weapons Complex project should be handling (or planning to handle) software as a product in response to Engineering Procedure 401099. The SQAS has published the document SQAS96-002, Guidelines for NWC Processes for Handling Software Product, that will be the basis for the tutorial. The primary scope of the tutorial is on software products that result from weapons and weapons-related projects, although the information presented is applicable to many software projects. Processes that involve the exchange, review, or evaluation of software product between or among NWC sites, DOE, and external customersmore » will be described.« less

ATD-1 Avionics Phase 2 Flight Test: Flight Test Operations and Saftey Report (FTOSR)

NASA Technical Reports Server (NTRS)

Boyle, Dan; Rein-Weston, Karl; Berckefeldt, Rick; Eggling, Helmuth; Stankiewicz, Craig; Silverman, George

2017-01-01

The Air Traffic Management Technology Demonstration-1 (ATD-1) is a major applied research and development activity of NASA's Airspace Operations and Safety Program (AOSP). The demonstration is the first of an envisioned series of Air Traffic Management (ATM) Technology Demonstration sub-projects that will demonstrate innovative NASA technologies that have attained a sufficient level of maturity to merit more in-depth research and evaluation at the system level in relevant environments.

The TAME Project: Towards improvement-oriented software environments

NASA Technical Reports Server (NTRS)

Basili, Victor R.; Rombach, H. Dieter

1988-01-01

Experience from a dozen years of analyzing software engineering processes and products is summarized as a set of software engineering and measurement principles that argue for software engineering process models that integrate sound planning and analysis into the construction process. In the TAME (Tailoring A Measurement Environment) project at the University of Maryland, such an improvement-oriented software engineering process model was developed that uses the goal/question/metric paradigm to integrate the constructive and analytic aspects of software development. The model provides a mechanism for formalizing the characterization and planning tasks, controlling and improving projects based on quantitative analysis, learning in a deeper and more systematic way about the software process and product, and feeding the appropriate experience back into the current and future projects. The TAME system is an instantiation of the TAME software engineering process model as an ISEE (integrated software engineering environment). The first in a series of TAME system prototypes has been developed. An assessment of experience with this first limited prototype is presented including a reassessment of its initial architecture.

Empirical studies of software design: Implications for SSEs

NASA Technical Reports Server (NTRS)

Krasner, Herb

1988-01-01

Implications for Software Engineering Environments (SEEs) are presented in viewgraph format for characteristics of projects studied; significant problems and crucial problem areas in software design for large systems; layered behavioral model of software processes; implications of field study results; software project as an ecological system; results of the LIFT study; information model of design exploration; software design strategies; results of the team design study; and a list of publications.

Software-Enabled Project Management Techniques and Their Relationship to the Triple Constraints

ERIC Educational Resources Information Center

Elleh, Festus U.

2013-01-01

This study investigated the relationship between software-enabled project management techniques and the triple constraints (time, cost, and scope). There was the dearth of academic literature that focused on the relationship between software-enabled project management techniques and the triple constraints (time, cost, and scope). Based on the gap…

Managers Handbook for Software Development

NASA Technical Reports Server (NTRS)

Agresti, W.; Mcgarry, F.; Card, D.; Page, J.; Church, V.; Werking, R.

1984-01-01

Methods and aids for the management of software development projects are presented. The recommendations are based on analyses and experiences with flight dynamics software development. The management aspects of organizing the project, producing a development plan, estimation costs, scheduling, staffing, preparing deliverable documents, using management tools, monitoring the project, conducting reviews, auditing, testing, and certifying are described.

An Agile Constructionist Mentoring Methodology for Software Projects in the High School

ERIC Educational Resources Information Center

Meerbaum-Salant, Orni; Hazzan, Orit

2010-01-01

This article describes the construction process and evaluation of the Agile Constructionist Mentoring Methodology (ACMM), a mentoring method for guiding software development projects in the high school. The need for such a methodology has arisen due to the complexity of mentoring software project development in the high school. We introduce the…

Extensive Evaluation of Using a Game Project in a Software Architecture Course

ERIC Educational Resources Information Center

Wang, Alf Inge

2011-01-01

This article describes an extensive evaluation of introducing a game project to a software architecture course. In this project, university students have to construct and design a type of software architecture, evaluate the architecture, implement an application based on the architecture, and test this implementation. In previous years, the domain…

Designing for Change: Minimizing the Impact of Changing Requirements in the Later Stages of a Spaceflight Software Project

NASA Technical Reports Server (NTRS)

Allen, B. Danette

1998-01-01

In the traditional 'waterfall' model of the software project life cycle, the Requirements Phase ends and flows into the Design Phase, which ends and flows into the Development Phase. Unfortunately, the process rarely, if ever, works so smoothly in practice. Instead, software developers often receive new requirements, or modifications to the original requirements, well after the earlier project phases have been completed. In particular, projects with shorter than ideal schedules are highly susceptible to frequent requirements changes, as the software requirements analysis phase is often forced to begin before the overall system requirements and top-level design are complete. This results in later modifications to the software requirements, even though the software design and development phases may be complete. Requirements changes received in the later stages of a software project inevitably lead to modification of existing developed software. Presented here is a series of software design techniques that can greatly reduce the impact of last-minute requirements changes. These techniques were successfully used to add built-in flexibility to two complex software systems in which the requirements were expected to (and did) change frequently. These large, real-time systems were developed at NASA Langley Research Center (LaRC) to test and control the Lidar In-Space Technology Experiment (LITE) instrument which flew aboard the space shuttle Discovery as the primary payload on the STS-64 mission.

Skylab

NASA Image and Video Library

1971-10-01

The Apollo Telescope Mount (ATM) was designed and developed by the Marshall Space Flight Center (MSFC) 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. This image is of the ATM flight unit sun end canister in MSFC's building 4755.

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...

Skylab

NASA Image and Video Library

1970-03-01

The Apollo Telescope Mount (ATM) was designed and developed by the Marshall Space Flight Center (MSFC) 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. This image is of the ATM thermal unit being tested in MSFC's building 4619. The thermal unit consisted of an active fluid-cooling system of water and methanol that was circulated to radiators on the outside of the canister. The thermal unit provided temperature stability to the ultrahigh resolution optical instruments that were part of the ATM.

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

NASA Technical Reports Server (NTRS)

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

1997-01-01

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

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 kinase inhibition in glial cells activates the innate immune response and causes neurodegeneration in Drosophila.

PubMed

Petersen, Andrew J; Rimkus, Stacey A; Wassarman, David A

2012-03-13

To investigate the mechanistic basis for central nervous system (CNS) neurodegeneration in the disease ataxia-telangiectasia (A-T), we analyzed flies mutant for the causative gene A-T mutated (ATM). ATM encodes a protein kinase that functions to monitor the genomic integrity of cells and control cell cycle, DNA repair, and apoptosis programs. Mutation of the C-terminal amino acid in Drosophila ATM inhibited the kinase activity and caused neuron and glial cell death in the adult brain and a reduction in mobility and longevity. These data indicate that reduced ATM kinase activity is sufficient to cause neurodegeneration in A-T. ATM kinase mutant flies also had elevated expression of innate immune response genes in glial cells. ATM knockdown in glial cells, but not neurons, was sufficient to cause neuron and glial cell death, a reduction in mobility and longevity, and elevated expression of innate immune response genes in glial cells, indicating that a non-cell-autonomous mechanism contributes to neurodegeneration in A-T. Taken together, these data suggest that early-onset CNS neurodegeneration in A-T is similar to late-onset CNS neurodegeneration in diseases such as Alzheimer's in which uncontrolled inflammatory response mediated by glial cells drives neurodegeneration.

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

PubMed

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

2017-10-17

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

ATM-Dependent Phosphorylation of MEF2D Promotes Neuronal Survival after DNA Damage

PubMed Central

Chan, Shing Fai; Sances, Sam; Brill, Laurence M.; Okamoto, Shu-ichi; Zaidi, Rameez; McKercher, Scott R.; Akhtar, Mohd W.; Nakanishi, Nobuki

2014-01-01

Mutations in the ataxia telangiectasia mutated (ATM) gene, which encodes a kinase critical for the normal DNA damage response, cause the neurodegenerative disorder ataxia-telangiectasia (AT). The substrates of ATM in the brain are poorly understood. Here we demonstrate that ATM phosphorylates and activates the transcription factor myocyte enhancer factor 2D (MEF2D), which plays a critical role in promoting survival of cerebellar granule cells. ATM associates with MEF2D after DNA damage and phosphorylates the transcription factor at four ATM consensus sites. Knockdown of endogenous MEF2D with a short-hairpin RNA (shRNA) increases sensitivity to etoposide-induced DNA damage and neuronal cell death. Interestingly, substitution of endogenous MEF2D with an shRNA-resistant phosphomimetic MEF2D mutant protects cerebellar granule cells from cell death after DNA damage, whereas an shRNA-resistant nonphosphorylatable MEF2D mutant does not. In vivo, cerebella in Mef2d knock-out mice manifest increased susceptibility to DNA damage. Together, our results show that MEF2D is a substrate for phosphorylation by ATM, thus promoting survival in response to DNA damage. Moreover, dysregulation of the ATM–MEF2D pathway may contribute to neurodegeneration in AT. PMID:24672010

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

PubMed

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

2017-09-02

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

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

PubMed Central

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

2015-01-01

The recognition, signalling and repair of DNA double strand breaks (DSB) involves the participation of a multitude of proteins and post-translational events that ensure maintenance of genome integrity. Amongst the proteins involved are several which when mutated give rise to genetic disorders characterised by chromosomal abnormalities, cancer predisposition, neurodegeneration and other pathologies. ATM (mutated in ataxia-telangiectasia (A-T) and members of the Mre11/Rad50/Nbs1 (MRN complex) play key roles in this process. The MRN complex rapidly recognises and locates to DNA DSB where it acts to recruit and assist in ATM activation. ATM, in the company of several other DNA damage response proteins, in turn phosphorylates all three members of the MRN complex to initiate downstream signalling. While ATM has hundreds of substrates, members of the MRN complex play a pivotal role in mediating the downstream signalling events that give rise to cell cycle control, DNA repair and ultimately cell survival or apoptosis. Here we focus on the interplay between ATM and the MRN complex in initiating signaling of breaks and more specifically on the adaptor role of the MRN complex in mediating ATM signalling to downstream substrates to control different cellular processes. PMID:26512707

The Generalizability of Private Sector Research on Software Project Management in Two USAF Organizations: An Exploratory Study

DTIC Science & Technology

2003-03-01

private sector . Researchers have also identified software acquisitions as one of the major differences between the private sector and public sector MIS. This indicates that the elements for a successful software project in the public sector may be different from the private sector . Private sector project success depends on many elements. Three of them are user interaction with the project’s development, critical success factors, and how the project manager prioritizes the traditional success criteria.

Development and Application of New Quality Model for Software Projects

PubMed Central

Karnavel, K.; Dillibabu, R.

2014-01-01

The IT industry tries to employ a number of models to identify the defects in the construction of software projects. In this paper, we present COQUALMO and its limitations and aim to increase the quality without increasing the cost and time. The computation time, cost, and effort to predict the residual defects are very high; this was overcome by developing an appropriate new quality model named the software testing defect corrective model (STDCM). The STDCM was used to estimate the number of remaining residual defects in the software product; a few assumptions and the detailed steps of the STDCM are highlighted. The application of the STDCM is explored in software projects. The implementation of the model is validated using statistical inference, which shows there is a significant improvement in the quality of the software projects. PMID:25478594

Development and application of new quality model for software projects.

PubMed

Karnavel, K; Dillibabu, R

2014-01-01

The IT industry tries to employ a number of models to identify the defects in the construction of software projects. In this paper, we present COQUALMO and its limitations and aim to increase the quality without increasing the cost and time. The computation time, cost, and effort to predict the residual defects are very high; this was overcome by developing an appropriate new quality model named the software testing defect corrective model (STDCM). The STDCM was used to estimate the number of remaining residual defects in the software product; a few assumptions and the detailed steps of the STDCM are highlighted. The application of the STDCM is explored in software projects. The implementation of the model is validated using statistical inference, which shows there is a significant improvement in the quality of the software projects.

Project W-211, initial tank retrieval systems, retrieval control system software configuration management plan

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

RIECK, C.A.

1999-02-23

This Software Configuration Management Plan (SCMP) provides the instructions for change control of the W-211 Project, Retrieval Control System (RCS) software after initial approval/release but prior to the transfer of custody to the waste tank operations contractor. This plan applies to the W-211 system software developed by the project, consisting of the computer human-machine interface (HMI) and programmable logic controller (PLC) software source and executable code, for production use by the waste tank operations contractor. The plan encompasses that portion of the W-211 RCS software represented on project-specific AUTOCAD drawings that are released as part of the C1 definitive designmore » package (these drawings are identified on the drawing list associated with each C-1 package), and the associated software code. Implementation of the plan is required for formal acceptance testing and production release. The software configuration management plan does not apply to reports and data generated by the software except where specifically identified. Control of information produced by the software once it has been transferred for operation is the responsibility of the receiving organization.« less

WISE: Automated support for software project management and measurement. M.S. Thesis

NASA Technical Reports Server (NTRS)

Ramakrishnan, Sudhakar

1995-01-01

One important aspect of software development and IV&V is measurement. Unless a software development effort is measured in some way, it is difficult to judge the effectiveness of current efforts and predict future performances. Collection of metrics and adherence to a process are difficult tasks in a software project. Change activity is a powerful indicator of project status. Automated systems that can handle change requests, issues, and other process documents provide an excellent platform for tracking the status of the project. A World Wide Web based architecture is developed for (a) making metrics collection an implicit part of the software process, (b) providing metric analysis dynamically, (c) supporting automated tools that can complement current practices of in-process improvement, and (d) overcoming geographical barrier. An operational system (WISE) instantiates this architecture allowing for the improvement of software process in a realistic environment. The tool tracks issues in software development process, provides informal communication between the users with different roles, supports to-do lists (TDL), and helps in software process improvement. WISE minimizes the time devoted to metrics collection, analysis, and captures software change data. Automated tools like WISE focus on understanding and managing the software process. The goal is improvement through measurement.

An Investigation of an Open-Source Software Development Environment in a Software Engineering Graduate Course

ERIC Educational Resources Information Center

Ge, Xun; Huang, Kun; Dong, Yifei

2010-01-01

A semester-long ethnography study was carried out to investigate project-based learning in a graduate software engineering course through the implementation of an Open-Source Software Development (OSSD) learning environment, which featured authentic projects, learning community, cognitive apprenticeship, and technology affordances. The study…

Issues in NASA Program and Project Management: Focus on Project Planning and Scheduling

NASA Technical Reports Server (NTRS)

Hoffman, Edward J. (Editor); Lawbaugh, William M. (Editor)

1997-01-01

Topics addressed include: Planning and scheduling training for working project teams at NASA, overview of project planning and scheduling workshops, project planning at NASA, new approaches to systems engineering, software reliability assessment, and software reuse in wind tunnel control systems.

An Overview of the JPSS Ground Project Algorithm Integration Process

NASA Astrophysics Data System (ADS)

Vicente, G. A.; Williams, R.; Dorman, T. J.; Williamson, R. C.; Shaw, F. J.; Thomas, W. M.; Hung, L.; Griffin, A.; Meade, P.; Steadley, R. S.; Cember, R. P.

2015-12-01

The smooth transition, implementation and operationalization of scientific software's from the National Oceanic and Atmospheric Administration (NOAA) development teams to the Join Polar Satellite System (JPSS) Ground Segment requires a variety of experiences and expertise. This task has been accomplished by a dedicated group of scientist and engineers working in close collaboration with the NOAA Satellite and Information Services (NESDIS) Center for Satellite Applications and Research (STAR) science teams for the JPSS/Suomi-NPOES Preparatory Project (S-NPP) Advanced Technology Microwave Sounder (ATMS), Cross-track Infrared Sounder (CrIS), Visible Infrared Imaging Radiometer Suite (VIIRS) and Ozone Mapping and Profiler Suite (OMPS) instruments. The presentation purpose is to describe the JPSS project process for algorithm implementation from the very early delivering stages by the science teams to the full operationalization into the Interface Processing Segment (IDPS), the processing system that provides Environmental Data Records (EDR's) to NOAA. Special focus is given to the NASA Data Products Engineering and Services (DPES) Algorithm Integration Team (AIT) functional and regression test activities. In the functional testing phase, the AIT uses one or a few specific chunks of data (granules) selected by the NOAA STAR Calibration and Validation (cal/val) Teams to demonstrate that a small change in the code performs properly and does not disrupt the rest of the algorithm chain. In the regression testing phase, the modified code is placed into to the Government Resources for Algorithm Verification, Integration, Test and Evaluation (GRAVITE) Algorithm Development Area (ADA), a simulated and smaller version of the operational IDPS. Baseline files are swapped out, not edited and the whole code package runs in one full orbit of Science Data Records (SDR's) using Calibration Look Up Tables (Cal LUT's) for the time of the orbit. The purpose of the regression test is to identify unintended outcomes. Overall the presentation provides a general and easy to follow overview of the JPSS Algorithm Change Process (ACP) and is intended to facility the audience understanding of a very extensive and complex process.

SAGA: A project to automate the management of software production systems

NASA Technical Reports Server (NTRS)

Campbell, Roy H.; Beckman-Davies, C. S.; Benzinger, L.; Beshers, G.; Laliberte, D.; Render, H.; Sum, R.; Smith, W.; Terwilliger, R.

1986-01-01

Research into software development is required to reduce its production cost and to improve its quality. Modern software systems, such as the embedded software required for NASA's space station initiative, stretch current software engineering techniques. The requirements to build large, reliable, and maintainable software systems increases with time. Much theoretical and practical research is in progress to improve software engineering techniques. One such technique is to build a software system or environment which directly supports the software engineering process, i.e., the SAGA project, comprising the research necessary to design and build a software development which automates the software engineering process. Progress under SAGA is described.

Macrophage infiltration in the omental and subcutaneous adipose tissues of dairy cows with displaced abomasum.

PubMed

Contreras, G Andres; Kabara, Ed; Brester, Jill; Neuder, Louis; Kiupel, Matti

2015-09-01

High concentrations of plasma nonesterified fatty acids (NEFA), a direct measure of lipolysis, are considered a risk factor for displaced abomasum (DA) and other clinical diseases. In nonruminants, uncontrolled lipolysis is commonly associated with adipose tissue macrophage (ATM) infiltration. In dairy cows, recent studies report ATM infiltration in specific adipose depots during the first week of lactation. Depending on their phenotype, ATM can be broadly classified as classically activated (M1) or alternatively activated (M2). The M1 ATM are considered pro-inflammatory, whereas M2 ATM enhance inflammation resolution. Currently, it is not known whether multiparous transition cows with DA have increased ATM infiltration, and the predominant phenotype of these mononuclear cells remains unclear. The objective of this study was to characterize ATM infiltration into different adipose tissue depots in transition cows with DA (days in milk=7.8±4.6 d; body condition score=2.95±0.10; n=6). Serum samples and biopsies from omental (OM) and subcutaneous (SC) fat depots were obtained during corrective surgery for DA. In an effort to compare ATM infiltration in DA cows with that of healthy cows in anabolic state (AS), adipose biopsies and blood samples were collected from nonlactating, nongestating dairy cows at the time of slaughter (body condition score=3.75±0.12; n=6). Adipose tissues were digested and cells from the stromal vascular fraction (SVF) were analyzed using flow cytometry to establish cell surface expression of specific macrophage markers including CD14, CD11c, CD163, and CD172a. Tissue sections were analyzed by immunohistochemistry to assess ATM localization. Cows with DA were ketotic and had plasma NEFA above 1.0 mEq/L. The same group of cows had significant infiltration of ATM in OM characterized by increased numbers of SVF cells expressing CD14 and CD172a. At the same time, expression of CD11c, and CD163 was significantly higher in SVF from OM and SC of DA cows compared with those from AS animals. Expression of M1 macrophage inflammatory phenotype-related genes CCL2, IL6, and TNFα in SVF from cows with DA was significantly higher than that in healthy cows (AS). Significant populations of ATM in OM and SC depots of cows with DA were localized in multiple cellular aggregates that included multinucleated cells. In contrast, ATM in AS cows were fewer and randomly localized in both SC and OM. Together, these results indicate that infiltration of classically activated ATM is a concurrent finding in DA cases and may be associated with metabolic stress around parturition contributing to the pro-inflammatory status of transition dairy cows. Future studies are needed to establish whether ATM infiltration is more pronounced in cows with DA compared with healthy dairy cows at the same lactation stage and if this increased mononuclear immune cell trafficking has any pathophysiological significance. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Software Smarts

NASA Technical Reports Server (NTRS)

1998-01-01

Under an SBIR (Small Business Innovative Research) contract with Johnson Space Center, Knowledge Based Systems Inc. (KBSI) developed an intelligent software environment for modeling and analyzing mission planning activities, simulating behavior, and, using a unique constraint propagation mechanism, updating plans with each change in mission planning activities. KBSI developed this technology into a commercial product, PROJECTLINK, a two-way bridge between PROSIm, KBSI's process modeling and simulation software and leading project management software like Microsoft Project and Primavera's SureTrak Project Manager.

Removing a barrier to computer-based outbreak and disease surveillance--the RODS Open Source Project.

PubMed

Espino, Jeremy U; Wagner, M; Szczepaniak, C; Tsui, F C; Su, H; Olszewski, R; Liu, Z; Chapman, W; Zeng, X; Ma, L; Lu, Z; Dara, J

2004-09-24

Computer-based outbreak and disease surveillance requires high-quality software that is well-supported and affordable. Developing software in an open-source framework, which entails free distribution and use of software and continuous, community-based software development, can produce software with such characteristics, and can do so rapidly. The objective of the Real-Time Outbreak and Disease Surveillance (RODS) Open Source Project is to accelerate the deployment of computer-based outbreak and disease surveillance systems by writing software and catalyzing the formation of a community of users, developers, consultants, and scientists who support its use. The University of Pittsburgh seeded the Open Source Project by releasing the RODS software under the GNU General Public License. An infrastructure was created, consisting of a website, mailing lists for developers and users, designated software developers, and shared code-development tools. These resources are intended to encourage growth of the Open Source Project community. Progress is measured by assessing website usage, number of software downloads, number of inquiries, number of system deployments, and number of new features or modules added to the code base. During September--November 2003, users generated 5,370 page views of the project website, 59 software downloads, 20 inquiries, one new deployment, and addition of four features. Thus far, health departments and companies have been more interested in using the software as is than in customizing or developing new features. The RODS laboratory anticipates that after initial installation has been completed, health departments and companies will begin to customize the software and contribute their enhancements to the public code base.

Effects of ocean acidification with pCO2 diurnal fluctuations on survival and larval shell formation of Ezo abalone, Haliotis discus hannai.

PubMed

Onitsuka, Toshihiro; Takami, Hideki; Muraoka, Daisuke; Matsumoto, Yukio; Nakatsubo, Ayumi; Kimura, Ryo; Ono, Tsuneo; Nojiri, Yukihiro

2018-03-01

This study assessed the effects of constant and diurnally fluctuating pCO 2 on development and shell formation of larval abalone Haliotis discus hannai. The larvae was exposed to different pCO 2 conditions; constant [450, 800, or 1200 μatm in the first experiment (Exp. I), 450 or 780 μatm in the second experiment (Exp. II)] or diurnally fluctuating pCO 2 (800 ± 400 or 1200 ± 400 μatm in Exp. I, 450 ± 80, 780 ± 200 or 780 ± 400 μatm in Exp. II). Mortality, malformation rates or shell length of larval abalone were not significantly different among the 450, 800, and 800 ± 400 μatm pCO 2 treatments. Meanwhile, significantly higher malformation rates and smaller shells were detected in the 1200 and 1200 ± 400 μatm pCO 2 treatments than in the 450 μatm pCO 2 treatment. The negative impacts were greater in the 1200 ± 400 μatm than in the 1200 μatm. Shell length and malformation rate of larval abalone were related with aragonite saturation state (Ω-aragonite) in experimental seawater, and greatly changed around 1.1 of Ω-aragonite which corresponded to 1000-1300 μatm pCO 2 . These results indicate that there is a pCO 2 threshold associated with Ω-aragonite in the seawater, and that pCO 2 fluctuations produce additional negative impacts on abalone when above the threshold. Clear relationships were detected between abalone fitness and the integrated pCO 2 value over the threshold, indicating that the effects of OA on development and shell formation of larval abalone can be determined by intensity and time of exposure to pCO 2 over the threshold. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-01-01

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

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

Software Engineering Research/Developer Collaborations in 2004 (C104)

NASA Technical Reports Server (NTRS)

Pressburger, Tom; Markosian, Lawrance

2005-01-01

In 2004, six collaborations between software engineering technology providers and NASA software development personnel deployed a total of five software engineering technologies (for references, see Section 7.2) on the NASA projects. The main purposes were to benefit the projects, infuse the technologies if beneficial into NASA, and give feedback to the technology providers to improve the technologies. Each collaboration project produced a final report (for references, see Section 7.1). Section 2 of this report summarizes each project, drawing from the final reports and communications with the software developers and technology providers. Section 3 indicates paths to further infusion of the technologies into NASA practice. Section 4 summarizes some technology transfer lessons learned. Section 6 lists the acronyms used in this report.

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

PubMed

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

1998-03-01

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

miR-181a promotes G1/S transition and cell proliferation in pediatric acute myeloid leukemia by targeting ATM.

PubMed

Liu, Xiaodan; Liao, Wang; Peng, Hongxia; Luo, Xuequn; Luo, Ziyan; Jiang, Hua; Xu, Ling

2016-01-01

Abnormal expression of miRNAs is intimately related to a variety of human cancers. The purpose of this study is to confirm the expression of miR-181a and elucidate its physiological function and mechanism in pediatric acute myeloid leukemia (AML). Pediatric AML patients and healthy controls were enrolled, and the expression of miR-181a and ataxia telangiectasia mutated (ATM) in tissues were examined using quantitative PCR. Moreover, cell proliferation and cell cycle were evaluated in several cell lines (HL60, NB4 and K562) by using flow cytometry after transfected with miR-181a mimics and inhibitors, or ATM siRNA and control siRNA. Finally, ATM as the potential target protein of miR-181a was examined. We found that miR-181a was significantly increased in pediatric AML, which showed an inverse association with ATM expression. Overexpressed miR-181a in cell lines significantly enhanced cell proliferation, as well as increased the ratio of S-phase cells by miR-181a mimics transfection in vitro. Luciferase activity of the reporter construct identified ATM as the direct molecular target of miR-181a. ATM siRNA transfection significantly enhanced cell proliferation and increased the ratio of S-phase cells in vitro. The results revealed novel mechanism through which miR-181a regulates G1/S transition and cell proliferation in pediatric AML by regulating the tumor suppressor ATM, providing insights into the molecular mechanism in pediatric AML.

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

PubMed Central

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

2017-01-01

Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We previously showed that miR-203a is expressed at relatively low levels in GBM patients, and ectopic miR-203a expression in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon (IFN) or temozolomide in vitro, and inhibited GBM tumorigenesis in vivo. Here we show that ectopic expression of miR-203a in GBM cell lines promotes the IFN response pathway as evidenced by increased IFN production and IFN-stimulated gene (ISG) expression, and high basal tyrosine phosphorylation of multiple STAT proteins. Importantly, we identified that miR-203a directly suppressed the protein levels of ataxia-telangiectasia mutated (ATM) kinase that negatively regulates IFN production. We found that high ATM expression in GBM correlates with poor patient survival and that ATM expression is inversely correlated with miR-203a expression. Knockout of ATM expression and inhibition of ATM function in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by therapeutic agents in vitro, and markedly suppressed GBM tumor growth and promoted animal survival. In contrast, restoring ATM levels in GBM cells ectopically expressing miR-203a increased tumorigenicity and decreased animal survival. Our study suggests that low miR-203a expression in GBM suppresses the interferon response through an ATM-dependent pathway. PMID:29348882

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

PubMed

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

2017-12-22

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

Framework for Small-Scale Experiments in Software Engineering: Guidance and Control Software Project: Software Engineering Case Study

NASA Technical Reports Server (NTRS)

Hayhurst, Kelly J.

1998-01-01

Software is becoming increasingly significant in today's critical avionics systems. To achieve safe, reliable software, government regulatory agencies such as the Federal Aviation Administration (FAA) and the Department of Defense mandate the use of certain software development methods. However, little scientific evidence exists to show a correlation between software development methods and product quality. Given this lack of evidence, a series of experiments has been conducted to understand why and how software fails. The Guidance and Control Software (GCS) project is the latest in this series. The GCS project is a case study of the Requirements and Technical Concepts for Aviation RTCA/DO-178B guidelines, Software Considerations in Airborne Systems and Equipment Certification. All civil transport airframe and equipment vendors are expected to comply with these guidelines in building systems to be certified by the FAA for use in commercial aircraft. For the case study, two implementations of a guidance and control application were developed to comply with the DO-178B guidelines for Level A (critical) software. The development included the requirements, design, coding, verification, configuration management, and quality assurance processes. This paper discusses the details of the GCS project and presents the results of the case study.

Impact of Requirements Quality on Project Success or Failure

NASA Astrophysics Data System (ADS)

Tamai, Tetsuo; Kamata, Mayumi Itakura

We are interested in the relationship between the quality of the requirements specifications for software projects and the subsequent outcome of the projects. To examine this relationship, we investigated 32 projects started and completed between 2003 and 2005 by the software development division of a large company in Tokyo. The company has collected reliable data on requirements specification quality, as evaluated by software quality assurance teams, and overall project performance data relating to cost and time overruns. The data for requirements specification quality were first converted into a multiple-dimensional space, with each dimension corresponding to an item of the recommended structure for software requirements specifications (SRS) defined in IEEE Std. 830-1998. We applied various statistical analysis methods to the SRS quality data and project outcomes.

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.

Training survey -- educational profile for Hanford HANDI 2000 project

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

Wilson, D.

Fluor Daniel Hanford, Inc. (FDH) is currently adopting streamlined business processes through integrated software solutions. Replacing the legacy software (current/replacement systems, attached) also avoids significant maintenance required to resolve Year 2000 issues. This initiative is being referred to as `HANDI 2000`. The software being implemented in the first phase of this project includes Indus International`s PASSPORT Software, Peoplesoft and Primavera P3 Software. The project, which encompasses all the system replacements that will occur, has been named `HANDI 2000.` The PASSPORT applications being implemented are Inventory Management, Purchasing, Contract Management, Accounts Payable, and MSDS (Material Safety Data Sheets).

Open source software projects of the caBIG In Vivo Imaging Workspace Software special interest group.

PubMed

Prior, Fred W; Erickson, Bradley J; Tarbox, Lawrence

2007-11-01

The Cancer Bioinformatics Grid (caBIG) program was created by the National Cancer Institute to facilitate sharing of IT infrastructure, data, and applications among the National Cancer Institute-sponsored cancer research centers. The program was launched in February 2004 and now links more than 50 cancer centers. In April 2005, the In Vivo Imaging Workspace was added to promote the use of imaging in cancer clinical trials. At the inaugural meeting, four special interest groups (SIGs) were established. The Software SIG was charged with identifying projects that focus on open-source software for image visualization and analysis. To date, two projects have been defined by the Software SIG. The eXtensible Imaging Platform project has produced a rapid application development environment that researchers may use to create targeted workflows customized for specific research projects. The Algorithm Validation Tools project will provide a set of tools and data structures that will be used to capture measurement information and associated needed to allow a gold standard to be defined for the given database against which change analysis algorithms can be tested. Through these and future efforts, the caBIG In Vivo Imaging Workspace Software SIG endeavors to advance imaging informatics and provide new open-source software tools to advance cancer research.

Estimation and evaluation of COSMIC radio occultation excess phase using undifferenced measurements

NASA Astrophysics Data System (ADS)

Xia, Pengfei; Ye, Shirong; Jiang, Kecai; Chen, Dezhong

2017-05-01

In the GPS radio occultation technique, the atmospheric excess phase (AEP) can be used to derive the refractivity, which is an important quantity in numerical weather prediction. The AEP is conventionally estimated based on GPS double-difference or single-difference techniques. These two techniques, however, rely on the reference data in the data processing, increasing the complexity of computation. In this study, an undifferenced (ND) processing strategy is proposed to estimate the AEP. To begin with, we use PANDA (Positioning and Navigation Data Analyst) software to perform the precise orbit determination (POD) for the purpose of acquiring the position and velocity of the mass centre of the COSMIC (The Constellation Observing System for Meteorology, Ionosphere and Climate) satellites and the corresponding receiver clock offset. The bending angles, refractivity and dry temperature profiles are derived from the estimated AEP using Radio Occultation Processing Package (ROPP) software. The ND method is validated by the COSMIC products in typical rising and setting occultation events. Results indicate that rms (root mean square) errors of relative refractivity differences between undifferenced and atmospheric profiles (atmPrf) provided by UCAR/CDAAC (University Corporation for Atmospheric Research/COSMIC Data Analysis and Archive Centre) are better than 4 and 3 % in rising and setting occultation events respectively. In addition, we also compare the relative refractivity bias between ND-derived methods and atmPrf profiles of globally distributed 200 COSMIC occultation events on 12 December 2013. The statistical results indicate that the average rms relative refractivity deviation between ND-derived and COSMIC profiles is better than 2 % in the rising occultation event and better than 1.7 % in the setting occultation event. Moreover, the observed COSMIC refractivity profiles from ND processing strategy are further validated using European Centre for Medium-Range Weather Forecasts (ECMWF) analysis data, and the results indicate that the undifferenced method reduces the noise level on the excess phase paths in the lower troposphere compared to the single-difference processing strategy.

Skylab

NASA Image and Video Library

1970-05-01

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. In this image, the ATM canister, housing the solar instruments, is mated to the thermal rack that provided thermal stability.

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.

Saturn Apollo Program

NASA Image and Video Library

1967-08-01

The Apollo Telescope Mount (ATM), designed and developed by the Marshall Space Flight Center, served as the primary scientific instrument unit aboard the Skylab. The ATM contained eight complex astronomical instruments designed to observe the Sun over a wide spectrum from visible light to x-rays. This photo depicts a mockup of the ATM contamination monitor camera and photometer.

Saturn Apollo Program

NASA Image and Video Library

1967-08-01

The Apollo Telescope Mount (ATM), designed and developed by the Marshall Space Flight Center, served as the primary scientific instrument unit aboard the Skylab. The ATM contained eight complex astronomical instruments designed to observe the Sun over a wide spectrum from visible light to x-rays. This angle view is of an ATM contamination monitor meter mockup.

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…

Proteomic profiling of ATM kinase proficient and deficient cell lines upon blockage of proteasome activity☆

PubMed Central

Marzano, Valeria; Santini, Simonetta; Rossi, Claudia; Zucchelli, Mirco; D'Alessandro, Annamaria; Marchetti, Carlo; Mingardi, Michele; Stagni, Venturina; Barilà, Daniela; Urbani, Andrea

2012-01-01

Ataxia Telangiectasia Mutated (ATM) protein kinase is a key effector in the modulation of the functionality of some important stress responses, including DNA damage and oxidative stress response, and its deficiency is the hallmark of Ataxia Telangiectasia (A-T), a rare genetic disorder. ATM modulates the activity of hundreds of target proteins, essential for the correct balance between proliferation and cell death. The aim of this study is to evaluate the phenotypic adaptation at the protein level both in basal condition and in presence of proteasome blockage in order to identify the molecules whose level and stability are modulated through ATM expression. We pursued a comparative analysis of ATM deficient and proficient lymphoblastoid cells by label-free shotgun proteomic experiments comparing the panel of proteins differentially expressed. Through a non-supervised comparative bioinformatic analysis these data provided an insight on the functional role of ATM deficiency in cellular carbohydrate metabolism's regulation. This hypothesis has been demonstrated by targeted metabolic fingerprint analysis SRM (Selected Reaction Monitoring) on specific thermodynamic checkpoints of glycolysis. This article is part of a Special Issue entitled: Translational Proteomics. PMID:22641158

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

Tyrosyl-DNA Phosphodiesterase I a critical survival factor for neuronal development and homeostasis.

PubMed

van Waardenburg, Robert C A M

2016-01-01

Tyrosyl-DNA phosphodiesterase I (TDP1), like most DNA repair associated proteins, is not essential for cell viability. However, dysfunctioning TDP1 or ATM (ataxia telangiectasia mutated) results in autosomal recessive neuropathology with similar phenotypes, including cerebellar atrophy. Dual inactivation of TDP1 and ATM causes synthetic lethality. A TDP1H 493 R catalytic mutant is associated with spinocerebellar ataxia with axonal neuropathy (SCAN1), and stabilizes the TDP1 catalytic obligatory enzyme-DNA covalent complex. The ATM kinase activates proteins early on in response to DNA damage. Tdp1-/- and Atm-/- mice exhibit accumulation of DNA topoisomerase I-DNA covalent complexes (TOPO1-cc) explicitly in neuronal tissue during development. TDP1 resolves 3'- and 5'-DNA adducts including trapped TOPO1-cc and TOPO1 protease resistant peptide-DNA complex. ATM appears to regulate the response to TOPO1-cc via a noncanonical function by regulating SUMO/ubiquitin-mediated TOPO1 degradation. In conclusion, TDP1 and ATM are critical factors for neuronal cell viability via two independent but cooperative pathways.

Characterisation of ATM mutations in Slavic Ataxia telangiectasia patients.

PubMed

Soukupova, Jana; Pohlreich, Petr; Seemanova, Eva

2011-09-01

Ataxia telangiectasia (AT) is a genomic instability syndrome characterised, among others, by progressive cerebellar degeneration, oculocutaneous telangiectases, immunodeficiency, elevated serum alpha-phetoprotein level, chromosomal breakage, hypersensitivity to ionising radiation and increased cancer risk. This autosomal recessive disorder is caused by mutations in the ataxia telangiectasia mutated (ATM) gene coding for serine/threonine protein kinase with a crucial role in response to DNA double-strand breaks. We characterised genotype and phenotype of 12 Slavic AT patients from 11 families. Mutation analysis included sequencing of the entire coding sequence, adjacent intron regions, 3'UTR and 5'UTR of the ATM gene and multiplex ligation-dependent probe amplification (MLPA) for the detection of large deletions/duplications at the ATM locus. The high incidence of new and individual mutations demonstrates a marked mutational heterogeneity of AT in the Czech Republic. Our data indicate that sequence analysis of the entire coding region of ATM is sufficient for a high detection rate of mutations in ATM and that MLPA analysis for the detection of deletions/duplications seems to be redundant in the Slavic population.

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.

Structures of closed and open conformations of dimeric human ATM

PubMed Central

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

2017-01-01

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

Analysis of injuries from the Army Ten Miler: A 6-year retrospective review.

PubMed

Pasquina, Paul F; Griffin, Sarah C; Anderson-Barnes, Victoria C; Tsao, Jack W; O'Connor, Francis G

2013-01-01

A number of long-distance running events are held each year in the United States; the Army Ten Miler (ATM) is one such race held annually in Washington, DC. The purpose of the present study was to retrospectively analyze medical encounters for runners participating in the ATM from 1998 to 2004. Of the estimated 91,750 runners over the 6-year period, 73,100 participants finished the race and were included in the data analysis. Demographic and injury data were collected from medical records of participants who received medical care while participating in the ATM, and injury-related factors were assessed. The most common category of injury was musculoskeletal (44%), followed by medical-related problems (27%) and dermatological injuries (27%). Similar to marathon and ironman races, ATM injury rates correlate with race-day temperature and dew point. Overall, however, the injury rates observed at the ATM were relatively low compared to those reported for longer distance events. Finally, we detail the medical coverage provided at the ATM, as this coverage could be used as a guide for similarly distanced races.

Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway

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

Nagane, Masaki; Yasui, Hironobu; Sakai, Yuri

2015-01-02

Highlights: • eNOS activity is increased in BAECs exposed to X-rays. • ATM is involved in this increased eNOS activity. • HSP90 modulates the radiation-induced activation of ATM and eNOS. - Abstract: In this study, the involvement of ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) in endothelial nitric oxide synthase (eNOS) activation was investigated in X-irradiated bovine aortic endothelial cells. The activity of nitric oxide synthase (NOS) and the phosphorylation of serine 1179 of eNOS (eNOS-Ser1179) were significantly increased in irradiated cells. The radiation-induced increases in NOS activity and eNOS-Ser1179 phosphorylation levels were significantly reduced bymore » treatment with either an ATM inhibitor (Ku-60019) or an HSP90 inhibitor (geldanamycin). Geldanamycin was furthermore found to suppress the radiation-induced phosphorylation of ATM-Ser1181. Our results indicate that the radiation-induced eNOS activation in bovine aortic endothelial cells is regulated by ATM and HSP90.« less

Lessons learned in deploying software estimation technology and tools

NASA Technical Reports Server (NTRS)

Panlilio-Yap, Nikki; Ho, Danny

1994-01-01

Developing a software product involves estimating various project parameters. This is typically done in the planning stages of the project when there is much uncertainty and very little information. Coming up with accurate estimates of effort, cost, schedule, and reliability is a critical problem faced by all software project managers. The use of estimation models and commercially available tools in conjunction with the best bottom-up estimates of software-development experts enhances the ability of a product development group to derive reasonable estimates of important project parameters. This paper describes the experience of the IBM Software Solutions (SWS) Toronto Laboratory in selecting software estimation models and tools and deploying their use to the laboratory's product development groups. It introduces the SLIM and COSTAR products, the software estimation tools selected for deployment to the product areas, and discusses the rationale for their selection. The paper also describes the mechanisms used for technology injection and tool deployment, and concludes with a discussion of important lessons learned in the technology and tool insertion process.

Software engineering with application-specific languages

NASA Technical Reports Server (NTRS)

Campbell, David J.; Barker, Linda; Mitchell, Deborah; Pollack, Robert H.

1993-01-01

Application-Specific Languages (ASL's) are small, special-purpose languages that are targeted to solve a specific class of problems. Using ASL's on software development projects can provide considerable cost savings, reduce risk, and enhance quality and reliability. ASL's provide a platform for reuse within a project or across many projects and enable less-experienced programmers to tap into the expertise of application-area experts. ASL's have been used on several software development projects for the Space Shuttle Program. On these projects, the use of ASL's resulted in considerable cost savings over conventional development techniques. Two of these projects are described.

Delivering Software Process-Specific Project Courses in Tertiary Education Environment: Challenges and Solution

ERIC Educational Resources Information Center

Rong, Guoping; Shao, Dong

2012-01-01

The importance of delivering software process courses to software engineering students has been more and more recognized in China in recent years. However, students usually cannot fully appreciate the value of software process courses by only learning methodology and principle in the classroom. Therefore, a process-specific project course was…

Software Size Estimation Using Expert Estimation: A Fuzzy Logic Approach

ERIC Educational Resources Information Center

Stevenson, Glenn A.

2012-01-01

For decades software managers have been using formal methodologies such as the Constructive Cost Model and Function Points to estimate the effort of software projects during the early stages of project development. While some research shows these methodologies to be effective, many software managers feel that they are overly complicated to use and…

Effects of the Meetings-Flow Approach on Quality Teamwork in the Training of Software Capstone Projects

ERIC Educational Resources Information Center

Chen, Chung-Yang; Hong, Ya-Chun; Chen, Pei-Chi

2014-01-01

Software development relies heavily on teamwork; determining how to streamline this collaborative development is an essential training subject in computer and software engineering education. A team process known as the meetings-flow (MF) approach has recently been introduced in software capstone projects in engineering programs at various…

ATM Is Required for the Prolactin-Induced HSP90-Mediated Increase in Cellular Viability and Clonogenic Growth After DNA Damage.

PubMed

Karayazi Atici, Ödül; Urbanska, Anna; Gopinathan, Sesha Gopal; Boutillon, Florence; Goffin, Vincent; Shemanko, Carrie S

2018-02-01

Prolactin (PRL) acts as a survival factor for breast cancer cells, but the PRL signaling pathway and the mechanism are unknown. Previously, we identified the master chaperone, heat shock protein 90 (HSP90) α, as a prolactin-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) target gene involved in survival, and here we investigated the role of HSP90 in the mechanism of PRL-induced viability in response to DNA damage. The ataxia-telangiectasia mutated kinase (ATM) protein plays a critical role in the cellular response to double-strand DNA damage. We observed that PRL increased viability of breast cancer cells treated with doxorubicin or etoposide. The increase in cellular resistance is specific to the PRL receptor, because the PRL receptor antagonist, Δ1-9-G129R-hPRL, prevented the increase in viability. Two different HSP90 inhibitors, 17-allylamino-17-demethoxygeldanamycin and BIIB021, reduced the PRL-mediated increase in cell viability of doxorubicin-treated cells and led to a decrease in JAK2, ATM, and phosphorylated ATM protein levels. Inhibitors of JAK2 (G6) and ATM (KU55933) abolished the PRL-mediated increase in cell viability of DNA-damaged cells, supporting the involvement of each, as well as the crosstalk of ATM with the PRL pathway in the context of DNA damage. Drug synergism was detected between the ATM inhibitor (KU55933) and doxorubicin and between the HSP90 inhibitor (BIIB021) and doxorubicin. Short interfering RNA directed against ATM prevented the PRL-mediated increase in cell survival in two-dimensional cell culture, three-dimensional collagen gel cultures, and clonogenic cell survival, after doxorubicin treatment. Our results indicate that ATM contributes to the PRL-JAK2-STAT5-HSP90 pathway in mediating cellular resistance to DNA-damaging agents. Copyright © 2018 Endocrine Society.

Software Engineering Laboratory (SEL) data and information policy

NASA Technical Reports Server (NTRS)

Mcgarry, Frank

1991-01-01

The policies and overall procedures that are used in distributing and in making available products of the Software Engineering Laboratory (SEL) are discussed. The products include project data and measures, project source code, reports, and software tools.

Software Project Management and Measurement on the World-Wide-Web (WWW)

NASA Technical Reports Server (NTRS)

Callahan, John; Ramakrishnan, Sudhaka

1996-01-01

We briefly describe a system for forms-based, work-flow management that helps members of a software development team overcome geographical barriers to collaboration. Our system, called the Web Integrated Software Environment (WISE), is implemented as a World-Wide-Web service that allows for management and measurement of software development projects based on dynamic analysis of change activity in the workflow. WISE tracks issues in a software development process, provides informal communication between the users with different roles, supports to-do lists, and helps in software process improvement. WISE minimizes the time devoted to metrics collection and analysis by providing implicit delivery of messages between users based on the content of project documents. The use of a database in WISE is hidden from the users who view WISE as maintaining a personal 'to-do list' of tasks related to the many projects on which they may play different roles.

Genetic Programming as Alternative for Predicting Development Effort of Individual Software Projects

PubMed Central

Chavoya, Arturo; Lopez-Martin, Cuauhtemoc; Andalon-Garcia, Irma R.; Meda-Campaña, M. E.

2012-01-01

Statistical and genetic programming techniques have been used to predict the software development effort of large software projects. In this paper, a genetic programming model was used for predicting the effort required in individually developed projects. Accuracy obtained from a genetic programming model was compared against one generated from the application of a statistical regression model. A sample of 219 projects developed by 71 practitioners was used for generating the two models, whereas another sample of 130 projects developed by 38 practitioners was used for validating them. The models used two kinds of lines of code as well as programming language experience as independent variables. Accuracy results from the model obtained with genetic programming suggest that it could be used to predict the software development effort of individual projects when these projects have been developed in a disciplined manner within a development-controlled environment. PMID:23226305

Ensemble Eclipse: A Process for Prefab Development Environment for the Ensemble Project

NASA Technical Reports Server (NTRS)

Wallick, Michael N.; Mittman, David S.; Shams, Khawaja, S.; Bachmann, Andrew G.; Ludowise, Melissa

2013-01-01

This software simplifies the process of having to set up an Eclipse IDE programming environment for the members of the cross-NASA center project, Ensemble. It achieves this by assembling all the necessary add-ons and custom tools/preferences. This software is unique in that it allows developers in the Ensemble Project (approximately 20 to 40 at any time) across multiple NASA centers to set up a development environment almost instantly and work on Ensemble software. The software automatically has the source code repositories and other vital information and settings included. The Eclipse IDE is an open-source development framework. The NASA (Ensemble-specific) version of the software includes Ensemble-specific plug-ins as well as settings for the Ensemble project. This software saves developers the time and hassle of setting up a programming environment, making sure that everything is set up in the correct manner for Ensemble development. Existing software (i.e., standard Eclipse) requires an intensive setup process that is both time-consuming and error prone. This software is built once by a single user and tested, allowing other developers to simply download and use the software

Lessons learned applying CASE methods/tools to Ada software development projects

NASA Technical Reports Server (NTRS)

Blumberg, Maurice H.; Randall, Richard L.

1993-01-01

This paper describes the lessons learned from introducing CASE methods/tools into organizations and applying them to actual Ada software development projects. This paper will be useful to any organization planning to introduce a software engineering environment (SEE) or evolving an existing one. It contains management level lessons learned, as well as lessons learned in using specific SEE tools/methods. The experiences presented are from Alpha Test projects established under the STARS (Software Technology for Adaptable and Reliable Systems) project. They reflect the front end efforts by those projects to understand the tools/methods, initial experiences in their introduction and use, and later experiences in the use of specific tools/methods and the introduction of new ones.

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.

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

PubMed

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

2018-05-01

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

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

PubMed Central

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

2016-01-01

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. PMID:27075534

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.

FAA/NASA UAS Traffic Management Pilot Program (UPP)

NASA Technical Reports Server (NTRS)

Johnson, Ronald D.; Kopardekar, Parimal H.; Rios, Joseph L.

2018-01-01

NASA Ames is leading ATM R&D organization. NASA started working on UTM in 2012, it's come a long way primarily due to close relationship with FAA and industry. We have a research transition team between FAA and NASA for UTM. We have a few other RTTs as well. UTM is a great example of collaborative innovation, and now it's reaching very exciting stage of UTM Pilot Project (UPP). NASA is supporting FAA and industry to make the UPP most productive and successful.

Incremental development and prototyping in current laboratory software development projects: Preliminary analysis

NASA Technical Reports Server (NTRS)

Griesel, Martha Ann

1988-01-01

Several Laboratory software development projects that followed nonstandard development processes, which were hybrids of incremental development and prototyping, are being studied. Factors in the project environment leading to the decision to use a nonstandard development process and affecting its success are analyzed. A simple characterization of project environment based on this analysis is proposed, together with software development approaches which have been found effective for each category. These approaches include both documentation and review requirements.

Testing Software Development Project Productivity Model

NASA Astrophysics Data System (ADS)

Lipkin, Ilya

Software development is an increasingly influential factor in today's business environment, and a major issue affecting software development is how an organization estimates projects. If the organization underestimates cost, schedule, and quality requirements, the end results will not meet customer needs. On the other hand, if the organization overestimates these criteria, resources that could have been used more profitably will be wasted. There is no accurate model or measure available that can guide an organization in a quest for software development, with existing estimation models often underestimating software development efforts as much as 500 to 600 percent. To address this issue, existing models usually are calibrated using local data with a small sample size, with resulting estimates not offering improved cost analysis. This study presents a conceptual model for accurately estimating software development, based on an extensive literature review and theoretical analysis based on Sociotechnical Systems (STS) theory. The conceptual model serves as a solution to bridge organizational and technological factors and is validated using an empirical dataset provided by the DoD. Practical implications of this study allow for practitioners to concentrate on specific constructs of interest that provide the best value for the least amount of time. This study outlines key contributing constructs that are unique for Software Size E-SLOC, Man-hours Spent, and Quality of the Product, those constructs having the largest contribution to project productivity. This study discusses customer characteristics and provides a framework for a simplified project analysis for source selection evaluation and audit task reviews for the customers and suppliers. Theoretical contributions of this study provide an initial theory-based hypothesized project productivity model that can be used as a generic overall model across several application domains such as IT, Command and Control, Simulation and etc... This research validates findings from previous work concerning software project productivity and leverages said results in this study. The hypothesized project productivity model provides statistical support and validation of expert opinions used by practitioners in the field of software project estimation.

The NCC project: A quality management perspective

NASA Technical Reports Server (NTRS)

Lee, Raymond H.

1993-01-01

The Network Control Center (NCC) Project introduced the concept of total quality management (TQM) in mid-1990. The CSC project team established a program which focused on continuous process improvement in software development methodology and consistent deliveries of high quality software products for the NCC. The vision of the TQM program was to produce error free software. Specific goals were established to allow continuing assessment of the progress toward meeting the overall quality objectives. The total quality environment, now a part of the NCC Project culture, has become the foundation for continuous process improvement and has resulted in the consistent delivery of quality software products over the last three years.

An Empirical Investigation of Pre-Project Partnering Activities on Project Performance in the Software Industry

ERIC Educational Resources Information Center

Proffitt, Curtis K.

2012-01-01

Project failure remains a challenge within the software development field especially during the early stages of the IT project development. Despite the herculean efforts by project managers and organizations to identify and offset problems, projects remain plagued with issues. If these challenges are not mitigated, to a successful degree,…

A measurement system for large, complex software programs

NASA Technical Reports Server (NTRS)

Rone, Kyle Y.; Olson, Kitty M.; Davis, Nathan E.

1994-01-01

This paper describes measurement systems required to forecast, measure, and control activities for large, complex software development and support programs. Initial software cost and quality analysis provides the foundation for meaningful management decisions as a project evolves. In modeling the cost and quality of software systems, the relationship between the functionality, quality, cost, and schedule of the product must be considered. This explicit relationship is dictated by the criticality of the software being developed. This balance between cost and quality is a viable software engineering trade-off throughout the life cycle. Therefore, the ability to accurately estimate the cost and quality of software systems is essential to providing reliable software on time and within budget. Software cost models relate the product error rate to the percent of the project labor that is required for independent verification and validation. The criticality of the software determines which cost model is used to estimate the labor required to develop the software. Software quality models yield an expected error discovery rate based on the software size, criticality, software development environment, and the level of competence of the project and developers with respect to the processes being employed.

Office Computer Software: A Comprehensive Review of Software Programs.

ERIC Educational Resources Information Center

Secretary, 1992

1992-01-01

Describes types of software including system software, application software, spreadsheets, accounting software, graphics packages, desktop publishing software, database, desktop and personal information management software, project and records management software, groupware, and shareware. (JOW)

Skylab

NASA Image and Video Library

1970-03-01

The Apollo Telescope Mount (ATM) was designed and developed by the Marshall Space Flight Center (MSFC) 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. In this image, the thermal unit, that controlled the temperature stability of the ATM, is being installed into a vacuum chamber.

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

DTIC Science & Technology

2015-05-01

mediators of gastric cancer. Br. J. Cancer 94(8):1204-1212. 11. Shen SQ, et al. 2008 Expression and clinical significance of NET-1 and PCNA in...ATM mutations and phenotypes in Ataxia-telangiectasia families in the british isles: Expression of mutant ATM and the risk of Leukemia, Lymphoma

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

Saturn Apollo Program

NASA Image and Video Library

1967-08-01

The Apollo Telescope Mount (ATM), designed and developed by the Marshall Space Flight Center, served as the primary scientific instrument unit aboard the Skylab. The ATM contained eight complex astronomical instruments designed to observe the Sun over a wide spectrum from visible light to x-rays. This photo depicts a side view is of a fully extended ATM contamination monitor mockup.

Saturn Apollo Program

NASA Image and Video Library

1967-08-01

The Apollo Telescope Mount (ATM), designed and developed by the Marshall Space Flight Center, served as the primary scientific instrument unit aboard the Skylab. The ATM contained eight complex astronomical instruments designed to observe the Sun over a wide spectrum from visible light to x-rays. This photo of the ATM contamination monitor mockup offers an extended view of the sunshield interior.

A Prototype for the Support of Integrated Software Process Development and Improvement

NASA Astrophysics Data System (ADS)

Porrawatpreyakorn, Nalinpat; Quirchmayr, Gerald; Chutimaskul, Wichian

An efficient software development process is one of key success factors for quality software. Not only can the appropriate establishment but also the continuous improvement of integrated project management and of the software development process result in efficiency. This paper hence proposes a software process maintenance framework which consists of two core components: an integrated PMBOK-Scrum model describing how to establish a comprehensive set of project management and software engineering processes and a software development maturity model advocating software process improvement. Besides, a prototype tool to support the framework is introduced.

Assessment Environment for Complex Systems Software Guide

NASA Technical Reports Server (NTRS)

2013-01-01

This Software Guide (SG) describes the software developed to test the Assessment Environment for Complex Systems (AECS) by the West Virginia High Technology Consortium (WVHTC) Foundation's Mission Systems Group (MSG) for the National Aeronautics and Space Administration (NASA) Aeronautics Research Mission Directorate (ARMD). This software is referred to as the AECS Test Project throughout the remainder of this document. AECS provides a framework for developing, simulating, testing, and analyzing modern avionics systems within an Integrated Modular Avionics (IMA) architecture. The purpose of the AECS Test Project is twofold. First, it provides a means to test the AECS hardware and system developed by MSG. Second, it provides an example project upon which future AECS research may be based. This Software Guide fully describes building, installing, and executing the AECS Test Project as well as its architecture and design. The design of the AECS hardware is described in the AECS Hardware Guide. Instructions on how to configure, build and use the AECS are described in the User's Guide. Sample AECS software, developed by the WVHTC Foundation, is presented in the AECS Software Guide. The AECS Hardware Guide, AECS User's Guide, and AECS Software Guide are authored by MSG. The requirements set forth for AECS are presented in the Statement of Work for the Assessment Environment for Complex Systems authored by NASA Dryden Flight Research Center (DFRC). The intended audience for this document includes software engineers, hardware engineers, project managers, and quality assurance personnel from WVHTC Foundation (the suppliers of the software), NASA (the customer), and future researchers (users of the software). Readers are assumed to have general knowledge in the field of real-time, embedded computer software development.

ATM-Mediated Transcriptional and Developmental Responses to γ-rays in Arabidopsis

PubMed Central

Renou, Jean-Pierre; Pichon, Olivier; Fochesato, Sylvain; Ortet, Philippe; Montané, Marie-Hélène

2007-01-01

ATM (Ataxia Telangiectasia Mutated) is an essential checkpoint kinase that signals DNA double-strand breaks in eukaryotes. Its depletion causes meiotic and somatic defects in Arabidopsis and progressive motor impairment accompanied by several cell deficiencies in patients with ataxia telangiectasia (AT). To obtain a comprehensive view of the ATM pathway in plants, we performed a time-course analysis of seedling responses by combining confocal laser scanning microscopy studies of root development and genome-wide expression profiling of wild-type (WT) and homozygous ATM-deficient mutants challenged with a dose of γ-rays (IR) that is sublethal for WT plants. Early morphologic defects in meristematic stem cells indicated that AtATM, an Arabidopsis homolog of the human ATM gene, is essential for maintaining the quiescent center and controlling the differentiation of initial cells after exposure to IR. Results of several microarray experiments performed with whole seedlings and roots up to 5 h post-IR were compiled in a single table, which was used to import gene information and extract gene sets. Sequence and function homology searches; import of spatio-temporal, cell cycling, and mutant-constitutive expression characteristics; and a simplified functional classification system were used to identify novel genes in all functional classes. The hundreds of radiomodulated genes identified were not a random collection, but belonged to functional pathways such as those of the cell cycle; cell death and repair; DNA replication, repair, and recombination; and transcription; translation; and signaling, indicating the strong cell reprogramming and double-strand break abrogation functions of ATM checkpoints. Accordingly, genes in all functional classes were either down or up-regulated concomitantly with downregulation of chromatin deacetylases or upregulation of acetylases and methylases, respectively. Determining the early transcriptional indicators of prolonged S-G2 phases that coincided with cell proliferation delay, or an anticipated subsequent auxin increase, accelerated cell differentiation or death, was used to link IR-regulated hallmark functions and tissue phenotypes after IR. The transcription burst was almost exclusively AtATM-dependent or weakly AtATR-dependent, and followed two major trends of expression in atm: (i)-loss or severe attenuation and delay, and (ii)-inverse and/or stochastic, as well as specific, enabling one to distinguish IR/ATM pathway constituents. Our data provide a large resource for studies on the interaction between plant checkpoints of the cell cycle, development, hormone response, and DNA repair functions, because IR-induced transcriptional changes partially overlap with the response to environmental stress. Putative connections of ATM to stem cell maintenance pathways after IR are also discussed. PMID:17487278

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

PubMed

Ricaud, Lilian; Proux, Caroline; Renou, Jean-Pierre; Pichon, Olivier; Fochesato, Sylvain; Ortet, Philippe; Montané, Marie-Hélène

2007-05-09

ATM (Ataxia Telangiectasia Mutated) is an essential checkpoint kinase that signals DNA double-strand breaks in eukaryotes. Its depletion causes meiotic and somatic defects in Arabidopsis and progressive motor impairment accompanied by several cell deficiencies in patients with ataxia telangiectasia (AT). To obtain a comprehensive view of the ATM pathway in plants, we performed a time-course analysis of seedling responses by combining confocal laser scanning microscopy studies of root development and genome-wide expression profiling of wild-type (WT) and homozygous ATM-deficient mutants challenged with a dose of gamma-rays (IR) that is sublethal for WT plants. Early morphologic defects in meristematic stem cells indicated that AtATM, an Arabidopsis homolog of the human ATM gene, is essential for maintaining the quiescent center and controlling the differentiation of initial cells after exposure to IR. Results of several microarray experiments performed with whole seedlings and roots up to 5 h post-IR were compiled in a single table, which was used to import gene information and extract gene sets. Sequence and function homology searches; import of spatio-temporal, cell cycling, and mutant-constitutive expression characteristics; and a simplified functional classification system were used to identify novel genes in all functional classes. The hundreds of radiomodulated genes identified were not a random collection, but belonged to functional pathways such as those of the cell cycle; cell death and repair; DNA replication, repair, and recombination; and transcription; translation; and signaling, indicating the strong cell reprogramming and double-strand break abrogation functions of ATM checkpoints. Accordingly, genes in all functional classes were either down or up-regulated concomitantly with downregulation of chromatin deacetylases or upregulation of acetylases and methylases, respectively. Determining the early transcriptional indicators of prolonged S-G2 phases that coincided with cell proliferation delay, or an anticipated subsequent auxin increase, accelerated cell differentiation or death, was used to link IR-regulated hallmark functions and tissue phenotypes after IR. The transcription burst was almost exclusively AtATM-dependent or weakly AtATR-dependent, and followed two major trends of expression in atm: (i)-loss or severe attenuation and delay, and (ii)-inverse and/or stochastic, as well as specific, enabling one to distinguish IR/ATM pathway constituents. Our data provide a large resource for studies on the interaction between plant checkpoints of the cell cycle, development, hormone response, and DNA repair functions, because IR-induced transcriptional changes partially overlap with the response to environmental stress. Putative connections of ATM to stem cell maintenance pathways after IR are also discussed.

ALDH1A1 Deficiency in Gorlin Syndrome Suggests a Central Role for Retinoic Acid and ATM Deficits in Radiation Carcinogenesis.

PubMed

Weber, Thomas J; Magnaldo, Thierry; Xiong, Yijia

2014-09-11

We hypothesize that aldehyde dehydrogenase 1A1 (ALDH1A1) deficiency will result in impaired ataxia-telangiectasia mutated (ATM) activation in a retinoic acid-sensitive fashion. Data supporting this hypothesis include (1) reduced ATM activation in irradiated primary dermal fibroblasts from ALDH1A1-deficient Gorlin syndrome patients (GDFs), relative to ALDH1A1-positive normal human dermal fibroblasts (NHDFs) and (2) increased ATM activation by X-radiation in GDFs pretreated with retinoic acid, however, the impact of donor variability on ATM activation in fibroblasts was not assessed and is a prudent consideration in future studies. Clonogenic survival of irradiated cells showed differential responses to retinoic acid as a function of treatment time. Long-term (5 Day) retinoic acid treatment functioned as a radiosensitizer and was associated with downregulation of ATM protein levels. Short-term (7 h) retinoic acid treatment showed a trend toward increased survival of irradiated cells and did not downregulate ATM protein levels. Using a newly developed IncubATR technology, which defines changes in bulk chemical bond patterns in live cells, we can discriminate between the NHDF and GDF phenotypes, but treatment of GDFs with retinoic acid does not induce reversion of bulk chemical bond patterns associated with GDFs toward the NHDF phenotype. Collectively, our preliminary investigation of the Gorlin phenotype has identified deficient ALDH1A1 expression associated with deficient ATM activation as a possible susceptibility factor that is consistent with the high incidence of spontaneous and radiation-induced carcinogenesis in these patients. The IncubATR technology exhibits sufficient sensitivity to detect phenotypic differences in live cells that may be relevant to radiation health effects.

A crucial role for ATR in the regulation of deoxycytidine kinase activity.

PubMed

Beyaert, Maxime; Starczewska, Eliza; Van Den Neste, Eric; Bontemps, Françoise

2016-01-15

Deoxycytidine kinase (dCK) (EC 2.7.1.74) is a key enzyme for salvage of deoxynucleosides and activation of numerous anticancer and antiviral nucleoside analogs. dCK activity is enhanced in response to several genotoxic treatments, which has been correlated with an increase of dCK phosphorylation at Ser-74. ATM was recently identified as the kinase responsible for Ser-74 phosphorylation and dCK activation after ionizing radiation (IR). Here, we investigated the role of ATM and the related kinase ATR in dCK activation induced by other types of DNA damage. Using ATM-deficient cells or the ATM inhibitor KU-60019, we found that ATM was not required for dCK activation caused by UV light, aphidicolin, cladribine, and unexpectedly also IR. On the other hand, the selective ATR inhibitor VE-821 significantly reduced up-regulation of dCK activity induced by these genotoxic agents, though not IR, and also down-regulated basal dCK activity. A role for ATR in the control of dCK activity was confirmed by using ATR siRNA and ATR-Seckel cells. ATR was also found to directly phosphorylate dCK at Ser-74 in vitro. Further studies revealed that ATR, which is also activated in response to IR, although later than ATM, was responsible for IR-induced dCK activation in ATM-deficient cells or in the presence of KU-60019. Overall, our results demonstrate that ATR controls basal dCK activity and dCK activation in response to replication stress and indicate that ATR can activate dCK after IR if ATM is lacking or inhibited. Copyright © 2015 Elsevier Inc. All rights reserved.

Dissecting cellular responses to irradiation via targeted disruptions of the ATM-CHK1-PP2A circuit

PubMed Central

Palii, Stela S.; Cui, Yuxia; Innes, Cynthia L.; Paules, Richard S.

2013-01-01

Exposure of proliferating cells to genotoxic stresses activates a cascade of signaling events termed the DNA damage response (DDR). The DDR preserves genetic stability by detecting DNA lesions, activating cell cycle checkpoints and promoting DNA damage repair. The phosphoinositide 3-kinase-related kinases (PIKKs) ataxia telangiectasia-mutated (ATM), ATM and Rad 3-related kinase (ATR) and DNA-dependent protein kinase (DNA-PK) are crucial for sensing lesions and signal transduction. The checkpoint kinase 1 (CHK1) is a traditional ATR target involved in DDR and normal cell cycle progression and represents a pharmacological target for anticancer regimens. This study employed cell lines stably depleted for CHK1, ATM or both for dissecting cross-talk and compensatory effects on G₂/M checkpoint in response to ionizing radiation (IR). We show that a 90% depletion of CHK1 renders cells radiosensitive without abrogating their IR-mediated G₂/M checkpoint arrest. ATM phosphorylation is enhanced in CHK1-deficient cells compared with their wild-type counterparts. This correlates with lower nuclear abundance of the PP2A catalytic subunit in CHK1-depleted cells. Stable depletion of CHK1 in an ATM-deficient background showed only a 50% reduction from wild-type CHK1 protein expression levels and resulted in an additive attenuation of the G₂/M checkpoint response compared with the individual knockdowns. ATM inhibition and 90% CHK1 depletion abrogated the early G₂/M checkpoint and precluded the cells from mounting an efficient compensatory response to IR at later time points. Our data indicates that dual targeting of ATM and CHK1 functionalities disrupts the compensatory response to DNA damage and could be exploited for developing efficient anti-neoplastic treatments. PMID:23462183

Transition in Survival From Low-Dose Hyper-Radiosensitivity to Increased Radioresistance Is Independent of Activation of ATM SER1981 Activity

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

Krueger, Sarah A.; Collis, Spencer J.; Joiner, Michael C.

2007-11-15

Purpose: The molecular basis of low-dose hyper-radiosensitivity (HRS) is only partially understood. The aim of this study was to define the roles of ataxia telangiectasia mutated (ATM) activity and the downstream ATM-dependent G{sub 2}-phase cell cycle checkpoint in overcoming HRS and triggering radiation resistance. Methods and Materials: Survival was measured using a high-resolution clonogenic assay. ATM Ser1981 activation was measured by Western blotting. The role of ATM was determined in survival experiments after molecular (siRNA) and chemical (0.4 mM caffeine) inhibition and chemical (20 {mu}g/mL chloroquine, 15 {mu}M genistein) activation 4-6 h before irradiation. Checkpoint responsiveness was assessed in eightmore » cell lines of differing HRS status using flow cytometry to quantify the progression of irradiated (0-2 Gy) G{sub 2}-phase cells entering mitosis, using histone H3 phosphorylation analysis. Results: The dose-response pattern of ATM activation was concordant with the transition from HRS to radioresistance. However, ATM activation did not play a primary role in initiating increased radioresistance. Rather, a relationship was discovered between the function of the downstream ATM-dependent early G{sub 2}-phase checkpoint and the prevalence and overcoming of HRS. Four cell lines that exhibited HRS failed to show low-dose (<0.3-Gy) checkpoint function. In contrast, four HRS-negative cell lines exhibited immediate cell cycle arrest for the entire 0-2-Gy dose range. Conclusion: Overcoming HRS is reliant on the function of the early G{sub 2}-phase checkpoint. These data suggest that clinical exploitation of HRS could be achieved by combining radiotherapy with chemotherapeutic agents that modulate this cell cycle checkpoint.« less

SV40 Utilizes ATM Kinase Activity to Prevent Non-homologous End Joining of Broken Viral DNA Replication Products

PubMed Central

Sowd, Gregory A.; Mody, Dviti; Eggold, Joshua; Cortez, David; Friedman, Katherine L.; Fanning, Ellen

2014-01-01

Simian virus 40 (SV40) and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PKcs kinase activity, facilitates some aspects of double strand break (DSB) repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR) and do not colocalize with non-homologous end joining (NHEJ) factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PKcs and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5′ to 3′ end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication. PMID:25474690

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.

SAGA: A project to automate the management of software production systems

NASA Technical Reports Server (NTRS)

Campbell, R. H.; Badger, W.; Beckman, C. S.; Beshers, G.; Hammerslag, D.; Kimball, J.; Kirslis, P. A.; Render, H.; Richards, P.; Terwilliger, R.

1984-01-01

The project to automate the management of software production systems is described. The SAGA system is a software environment that is designed to support most of the software development activities that occur in a software lifecycle. The system can be configured to support specific software development applications using given programming languages, tools, and methodologies. Meta-tools are provided to ease configuration. Several major components of the SAGA system are completed to prototype form. The construction methods are described.

Software quality assurance plan for GCS

NASA Technical Reports Server (NTRS)

Duncan, Stephen E.; Bailey, Elizabeth K.

1990-01-01

The software quality assurance (SQA) function for the Guidance and Control Software (GCS) project which is part of a software error studies research program is described. The SQA plan outlines all of the procedures, controls, and audits to be carried out by the SQA organization to ensure adherence to the policies, procedures, and standards for the GCS project.

Data-Driven Decision Making as a Tool to Improve Software Development Productivity

ERIC Educational Resources Information Center

Brown, Mary Erin

2013-01-01

The worldwide software project failure rate, based on a survey of information technology software manager's view of user satisfaction, product quality, and staff productivity, is estimated to be between 24% and 36% and software project success has not kept pace with the advances in hardware. The problem addressed by this study was the limited…

The aquatic animals' transcriptome resource for comparative functional analysis.

PubMed

Chou, Chih-Hung; Huang, Hsi-Yuan; Huang, Wei-Chih; Hsu, Sheng-Da; Hsiao, Chung-Der; Liu, Chia-Yu; Chen, Yu-Hung; Liu, Yu-Chen; Huang, Wei-Yun; Lee, Meng-Lin; Chen, Yi-Chang; Huang, Hsien-Da

2018-05-09

Aquatic animals have great economic and ecological importance. Among them, non-model organisms have been studied regarding eco-toxicity, stress biology, and environmental adaptation. Due to recent advances in next-generation sequencing techniques, large amounts of RNA-seq data for aquatic animals are publicly available. However, currently there is no comprehensive resource exist for the analysis, unification, and integration of these datasets. This study utilizes computational approaches to build a new resource of transcriptomic maps for aquatic animals. This aquatic animal transcriptome map database dbATM provides de novo assembly of transcriptome, gene annotation and comparative analysis of more than twenty aquatic organisms without draft genome. To improve the assembly quality, three computational tools (Trinity, Oases and SOAPdenovo-Trans) were employed to enhance individual transcriptome assembly, and CAP3 and CD-HIT-EST software were then used to merge these three assembled transcriptomes. In addition, functional annotation analysis provides valuable clues to gene characteristics, including full-length transcript coding regions, conserved domains, gene ontology and KEGG pathways. Furthermore, all aquatic animal genes are essential for comparative genomics tasks such as constructing homologous gene groups and blast databases and phylogenetic analysis. In conclusion, we establish a resource for non model organism aquatic animals, which is great economic and ecological importance and provide transcriptomic information including functional annotation and comparative transcriptome analysis. The database is now publically accessible through the URL http://dbATM.mbc.nctu.edu.tw/ .

ATM Card Cloning and Ethical Considerations.

PubMed

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

2018-05-01

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

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

NASA Astrophysics Data System (ADS)

Susanti; Hardini, H. T.

2018-01-01

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

10 CFR 961.11 - Text of the contract.

Code of Federal Regulations, 2014 CFR

2014-01-01

... program including information on cost projections, project plans and progress reports. 5. (a) Beginning on...-type documents or computer software (including computer programs, computer software data bases, and computer software documentation). Examples of technical data include research and engineering data...

10 CFR 961.11 - Text of the contract.

Code of Federal Regulations, 2013 CFR

2013-01-01

... program including information on cost projections, project plans and progress reports. 5. (a) Beginning on...-type documents or computer software (including computer programs, computer software data bases, and computer software documentation). Examples of technical data include research and engineering data...

Software risk management through independent verification and validation

NASA Technical Reports Server (NTRS)

Callahan, John R.; Zhou, Tong C.; Wood, Ralph

1995-01-01

Software project managers need tools to estimate and track project goals in a continuous fashion before, during, and after development of a system. In addition, they need an ability to compare the current project status with past project profiles to validate management intuition, identify problems, and then direct appropriate resources to the sources of problems. This paper describes a measurement-based approach to calculating the risk inherent in meeting project goals that leverages past project metrics and existing estimation and tracking models. We introduce the IV&V Goal/Questions/Metrics model, explain its use in the software development life cycle, and describe our attempts to validate the model through the reverse engineering of existing projects.

NASA's Earth Imagery Service as Open Source Software

NASA Astrophysics Data System (ADS)

De Cesare, C.; Alarcon, C.; Huang, T.; Roberts, J. T.; Rodriguez, J.; Cechini, M. F.; Boller, R. A.; Baynes, K.

2016-12-01

The NASA Global Imagery Browse Service (GIBS) is a software system that provides access to an archive of historical and near-real-time Earth imagery from NASA-supported satellite instruments. The imagery itself is open data, and is accessible via standards such as the Open Geospatial Consortium (OGC)'s Web Map Tile Service (WMTS) protocol. GIBS includes three core software projects: The Imagery Exchange (TIE), OnEarth, and the Meta Raster Format (MRF) project. These projects are developed using a variety of open source software, including: Apache HTTPD, GDAL, Mapserver, Grails, Zookeeper, Eclipse, Maven, git, and Apache Commons. TIE has recently been released for open source, and is now available on GitHub. OnEarth, MRF, and their sub-projects have been on GitHub since 2014, and the MRF project in particular receives many external contributions from the community. Our software has been successful beyond the scope of GIBS: the PO.DAAC State of the Ocean and COVERAGE visualization projects reuse components from OnEarth. The MRF source code has recently been incorporated into GDAL, which is a core library in many widely-used GIS software such as QGIS and GeoServer. This presentation will describe the challenges faced in incorporating open software and open data into GIBS, and also showcase GIBS as a platform on which scientists and the general public can build their own applications.

Analyses of requirements for computer control and data processing experiment subsystems. Volume 2: ATM experiment S-056 image data processing system software development

NASA Technical Reports Server (NTRS)

1972-01-01

The IDAPS (Image Data Processing System) is a user-oriented, computer-based, language and control system, which provides a framework or standard for implementing image data processing applications, simplifies set-up of image processing runs so that the system may be used without a working knowledge of computer programming or operation, streamlines operation of the image processing facility, and allows multiple applications to be run in sequence without operator interaction. The control system loads the operators, interprets the input, constructs the necessary parameters for each application, and cells the application. The overlay feature of the IBSYS loader (IBLDR) provides the means of running multiple operators which would otherwise overflow core storage.

Integrating and Managing Bim in GIS, Software Review

NASA Astrophysics Data System (ADS)

El Meouche, R.; Rezoug, M.; Hijazi, I.

2013-08-01

Since the advent of Computer-Aided Design (CAD) and Geographical Information System (GIS) tools, project participants have been increasingly leveraging these tools throughout the different phases of a civil infrastructure project. In recent years the number of GIS software that provides tools to enable the integration of Building information in geo context has risen sharply. More and more GIS software are added tools for this purposes and other software projects are regularly extending these tools. However, each software has its different strength and weakness and its purpose of use. This paper provides a thorough review to investigate the software capabilities and clarify its purpose. For this study, Autodesk Revit 2012 i.e. BIM editor software was used to create BIMs. In the first step, three building models were created, the resulted models were converted to BIM format and then the software was used to integrate it. For the evaluation of the software, general characteristics was studied such as the user interface, what formats are supported (import/export), and the way building information are imported.

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.

Investigating the Human Computer Interaction Problems with Automated Teller Machine Navigation Menus

ERIC Educational Resources Information Center

Curran, Kevin; King, David

2008-01-01

Purpose: The automated teller machine (ATM) has become an integral part of our society. However, using the ATM can often be a frustrating experience as people frequently reinsert cards to conduct multiple transactions. This has led to the research question of whether ATM menus are designed in an optimal manner. This paper aims to address the…

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.