Science.gov

Sample records for complex software specifications

  1. 77 FR 50726 - Software Requirement Specifications for Digital Computer Software and Complex Electronics Used in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-22

    ...The U.S. Nuclear Regulatory Commission (NRC or the Commission) is issuing for public comment draft regulatory guide (DG), DG-1209, ``Software Requirement Specifications for Digital Computer Software and Complex Electronics used in Safety Systems of Nuclear Power Plants.'' The DG-1209 is proposed Revision 1 of RG 1.172, dated September 1997. This revision endorses, with clarifications, the......

  2. Master Software Requirements Specification

    NASA Technical Reports Server (NTRS)

    Hu, Chaumin

    2003-01-01

    A basic function of a computational grid such as the NASA Information Power Grid (IPG) is to allow users to execute applications on remote computer systems. The Globus Resource Allocation Manager (GRAM) provides this functionality in the IPG and many other grids at this time. While the functionality provided by GRAM clients is adequate, GRAM does not support useful features such as staging several sets of files, running more than one executable in a single job submission, and maintaining historical information about execution operations. This specification is intended to provide the environmental and software functional requirements for the IPG Job Manager V2.0 being developed by AMTI for NASA.

  3. Compositional Specification of Software Architecture

    NASA Technical Reports Server (NTRS)

    Penix, John; Lau, Sonie (Technical Monitor)

    1998-01-01

    This paper describes our experience using parameterized algebraic specifications to model properties of software architectures. The goal is to model the decomposition of requirements independent of the style used to implement the architecture. We begin by providing an overview of the role of architecture specification in software development. We then describe how architecture specifications are build up from component and connector specifications and give an overview of insights gained from a case study used to validate the method.

  4. SSL: A software specification language

    NASA Technical Reports Server (NTRS)

    Austin, S. L.; Buckles, B. P.; Ryan, J. P.

    1976-01-01

    SSL (Software Specification Language) is a new formalism for the definition of specifications for software systems. The language provides a linear format for the representation of the information normally displayed in a two-dimensional module inter-dependency diagram. In comparing SSL to FORTRAN or ALGOL, it is found to be largely complementary to the algorithmic (procedural) languages. SSL is capable of representing explicitly module interconnections and global data flow, information which is deeply imbedded in the algorithmic languages. On the other hand, SSL is not designed to depict the control flow within modules. The SSL level of software design explicitly depicts intermodule data flow as a functional specification.

  5. Reflight certification software design specifications

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The PDSS/IMC Software Design Specification for the Payload Development Support System (PDSS)/Image Motion Compensator (IMC) is contained. The PDSS/IMC is to be used for checkout and verification of the IMC flight hardware and software by NASA/MSFC.

  6. Does software design complexity affect maintenance effort?

    NASA Technical Reports Server (NTRS)

    Epping, Andreas; Lott, Christopher M.

    1994-01-01

    The design complexity of a software system may be characterized within a refinement level (e.g., data flow among modules), or between refinement levels (e.g., traceability between the specification and the design). We analyzed an existing set of data from NASA's Software Engineering Laboratory to test whether changing software modules with high design complexity requires more personnel effort than changing modules with low design complexity. By analyzing variables singly, we identified strong correlations between software design complexity and change effort for error corrections performed during the maintenance phase. By analyzing variables in combination, we found patterns which identify modules in which error corrections were costly to perform during the acceptance test phase.

  7. Software Complexity Threatens Performance Portability

    SciTech Connect

    Gamblin, T.

    2015-09-11

    Modern HPC software packages are rarely self-contained. They depend on a large number of external libraries, and many spend large fractions of their runtime in external subroutines. Performance portability depends not only on the effort of application teams, but also on the availability of well-tuned libraries. At most sites, the burden of maintaining libraries is shared by code teams and facilities. Facilities typically provide well-tuned default versions, but code teams frequently build with bleeding-edge compilers to achieve high performance. For this reason, HPC has no “standard” software stack, unlike other domains where performance is not critical. Incompatibilities among compilers and software versions force application teams and facility staff to re-build custom versions of libraries for each new toolchain. Because the number of potential configurations is combinatorial, and because HPC software is notoriously difficult to port to new machines [3, 7, 8], the tuning effort required to support and maintain performance-portable libraries outstrips the available manpower at most sites. Software complexity is a growing obstacle to performance portability for HPC.

  8. Software Performs Complex Design Analysis

    NASA Technical Reports Server (NTRS)

    2008-01-01

    Designers use computational fluid dynamics (CFD) to gain greater understanding of the fluid flow phenomena involved in components being designed. They also use finite element analysis (FEA) as a tool to help gain greater understanding of the structural response of components to loads, stresses and strains, and the prediction of failure modes. Automated CFD and FEA engineering design has centered on shape optimization, which has been hindered by two major problems: 1) inadequate shape parameterization algorithms, and 2) inadequate algorithms for CFD and FEA grid modification. Working with software engineers at Stennis Space Center, a NASA commercial partner, Optimal Solutions Software LLC, was able to utilize its revolutionary, one-of-a-kind arbitrary shape deformation (ASD) capability-a major advancement in solving these two aforementioned problems-to optimize the shapes of complex pipe components that transport highly sensitive fluids. The ASD technology solves the problem of inadequate shape parameterization algorithms by allowing the CFD designers to freely create their own shape parameters, therefore eliminating the restriction of only being able to use the computer-aided design (CAD) parameters. The problem of inadequate algorithms for CFD grid modification is solved by the fact that the new software performs a smooth volumetric deformation. This eliminates the extremely costly process of having to remesh the grid for every shape change desired. The program can perform a design change in a markedly reduced amount of time, a process that would traditionally involve the designer returning to the CAD model to reshape and then remesh the shapes, something that has been known to take hours, days-even weeks or months-depending upon the size of the model.

  9. Software requirements: Guidance and control software development specification

    NASA Technical Reports Server (NTRS)

    Withers, B. Edward; Rich, Don C.; Lowman, Douglas S.; Buckland, R. C.

    1990-01-01

    The software requirements for an implementation of Guidance and Control Software (GCS) are specified. The purpose of the GCS is to provide guidance and engine control to a planetary landing vehicle during its terminal descent onto a planetary surface and to communicate sensory information about that vehicle and its descent to some receiving device. The specification was developed using the structured analysis for real time system specification methodology by Hatley and Pirbhai and was based on a simulation program used to study the probability of success of the 1976 Viking Lander missions to Mars. Three versions of GCS are being generated for use in software error studies.

  10. Propagation and stability in software: A complex network perspective

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Wang, Ping

    2015-09-01

    In this paper, we attempt to understand the propagation and stability feature of large-scale complex software from the perspective of complex networks. Specifically, we introduced the concept of "propagation scope" to investigate the problem of change propagation in complex software. Although many complex software networks exhibit clear "small-world" and "scale-free" features, we found that the propagation scope of complex software networks is much lower than that of small-world networks and scale-free networks. Furthermore, because the design of complex software always obeys the principles of software engineering, we introduced the concept of "edge instability" to quantify the structural difference among complex software networks, small-world networks and scale-free networks. We discovered that the edge instability distribution of complex software networks is different from that of small-world networks and scale-free networks. We also found a typical structure that contributes to the edge instability distribution of complex software networks. Finally, we uncovered the correlation between propagation scope and edge instability in complex networks by eliminating the edges with different instability ranges.

  11. Development of simulation computer complex specification

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The Training Simulation Computer Complex Study was one of three studies contracted in support of preparations for procurement of a shuttle mission simulator for shuttle crew training. The subject study was concerned with definition of the software loads to be imposed on the computer complex to be associated with the shuttle mission simulator and the development of procurement specifications based on the resulting computer requirements. These procurement specifications cover the computer hardware and system software as well as the data conversion equipment required to interface the computer to the simulator hardware. The development of the necessary hardware and software specifications required the execution of a number of related tasks which included, (1) simulation software sizing, (2) computer requirements definition, (3) data conversion equipment requirements definition, (4) system software requirements definition, (5) a simulation management plan, (6) a background survey, and (7) preparation of the specifications.

  12. Bias and design in software specifications

    NASA Technical Reports Server (NTRS)

    Straub, Pablo A.; Zelkowitz, Marvin V.

    1990-01-01

    Implementation bias in a specification is an arbitrary constraint in the solution space. Presented here is a model of bias in software specifications. Bias is defined in terms of the specification process and a classification of the attributes of the software product. Our definition of bias provides insight into both the origin and the consequences of bias. It also shows that bias is relative and essentially unavoidable. Finally, we describe current work on defining a measure of bias, formalizing our model, and relating bias to software defects.

  13. Specifications and programs for computer software validation

    NASA Technical Reports Server (NTRS)

    Browne, J. C.; Kleir, R.; Davis, T.; Henneman, M.; Haller, A.; Lasseter, G. L.

    1973-01-01

    Three software products developed during the study are reported and include: (1) FORTRAN Automatic Code Evaluation System, (2) the Specification Language System, and (3) the Array Index Validation System.

  14. Facing software complexity on large telescopes

    NASA Astrophysics Data System (ADS)

    Swart, Gerhard; Bester, Deon; Brink, Janus; Gumede, Clifford; Schalekamp, Hendrik J.

    2004-09-01

    The successful development of any complex control system requires a blend of good software management, an appropriate computer architecture and good software engineering. Due to the large number of controlled parts, high performance goals and required operational efficiency, the control systems for large telescopes are particularly challenging to develop and maintain. In this paper the authors highlight some of the specific challenges that need to be met by control system developers to meet the requirements within a limited budget and schedule. They share some of the practices applied during the development of the Southern African Large Telescope (SALT) and describe specific aspects of the design that contribute to meeting these challenges. The topics discussed include: development methodology, defining the level of system integration, computer architecture, interface management, software standards, language selection, user interface design and personnel selection. Time will reveal the full truth, but the authors believe that the significant progress achieved in commissioning SALT (now 6 months from telescope completion), can largely be attributed to the combined application of these practices and design concepts.

  15. Software complex for geophysical data visualization

    NASA Astrophysics Data System (ADS)

    Kryukov, Ilya A.; Tyugin, Dmitry Y.; Kurkin, Andrey A.; Kurkina, Oxana E.

    2013-04-01

    The effectiveness of current research in geophysics is largely determined by the degree of implementation of the procedure of data processing and visualization with the use of modern information technology. Realistic and informative visualization of the results of three-dimensional modeling of geophysical processes contributes significantly into the naturalness of physical modeling and detailed view of the phenomena. The main difficulty in this case is to interpret the results of the calculations: it is necessary to be able to observe the various parameters of the three-dimensional models, build sections on different planes to evaluate certain characteristics and make a rapid assessment. Programs for interpretation and visualization of simulations are spread all over the world, for example, software systems such as ParaView, Golden Software Surfer, Voxler, Flow Vision and others. However, it is not always possible to solve the problem of visualization with the help of a single software package. Preprocessing, data transfer between the packages and setting up a uniform visualization style can turn into a long and routine work. In addition to this, sometimes special display modes for specific data are required and existing products tend to have more common features and are not always fully applicable to certain special cases. Rendering of dynamic data may require scripting languages that does not relieve the user from writing code. Therefore, the task was to develop a new and original software complex for the visualization of simulation results. Let us briefly list of the primary features that are developed. Software complex is a graphical application with a convenient and simple user interface that displays the results of the simulation. Complex is also able to interactively manage the image, resize the image without loss of quality, apply a two-dimensional and three-dimensional regular grid, set the coordinate axes with data labels and perform slice of data. The

  16. Domain and Specification Models for Software Engineering

    NASA Technical Reports Server (NTRS)

    Iscoe, Neil; Liu, Zheng-Yang; Feng, Guohui

    1992-01-01

    This paper discusses our approach to representing application domain knowledge for specific software engineering tasks. Application domain knowledge is embodied in a domain model. Domain models are used to assist in the creation of specification models. Although many different specification models can be created from any particular domain model, each specification model is consistent and correct with respect to the domain model. One aspect of the system-hierarchical organization is described in detail.

  17. Domain specific software design for decision aiding

    NASA Technical Reports Server (NTRS)

    Keller, Kirby; Stanley, Kevin

    1992-01-01

    McDonnell Aircraft Company (MCAIR) is involved in many large multi-discipline design and development efforts of tactical aircraft. These involve a number of design disciplines that must be coordinated to produce an integrated design and a successful product. Our interpretation of a domain specific software design (DSSD) is that of a representation or framework that is specialized to support a limited problem domain. A DSSD is an abstract software design that is shaped by the problem characteristics. This parallels the theme of object-oriented analysis and design of letting the problem model directly drive the design. The DSSD concept extends the notion of software reusability to include representations or frameworks. It supports the entire software life cycle and specifically leads to improved prototyping capability, supports system integration, and promotes reuse of software designs and supporting frameworks. The example presented in this paper is the task network architecture or design which was developed for the MCAIR Pilot's Associate program. The task network concept supported both module development and system integration within the domain of operator decision aiding. It is presented as an instance where a software design exhibited many of the attributes associated with DSSD concept.

  18. 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.

  19. Reducing the complexity of software systems - A strategic software perspective

    NASA Technical Reports Server (NTRS)

    Hornstein, Rhoda S.

    1992-01-01

    The results of a combined management and technical initiative aimed at reducing the size and complexity associated with developing operations planning, scheduling, and resource management software systems are presented. The initiative has produced operations concepts, functional requirements, system architectures, a comprehensive lexicon, and software tools to revolutionize the traditional software technology and development practices for planning, scheduling, and resource management systems used in space operations control centers. Examples of technology and practices to reduce complexity include a method for projecting design consequences from an operations concept, a universal architecture for heuristic algorithms, an object-oriented framework for describing large classes of problems that parametrically adapt to all domain peculiarities, the identification of general approaches which respond to changes with minimum impact on systems implementations, and a management structure for prototyping to minimize the risks of ill-conceived designs.

  20. Software errors and complexity: An empirical investigation

    NASA Technical Reports Server (NTRS)

    Basili, Victor R.; Perricone, Berry T.

    1983-01-01

    The distributions and relationships derived from the change data collected during the development of a medium scale satellite software project show that meaningful results can be obtained which allow an insight into software traits and the environment in which it is developed. Modified and new modules were shown to behave similarly. An abstract classification scheme for errors which allows a better understanding of the overall traits of a software project is also shown. Finally, various size and complexity metrics are examined with respect to errors detected within the software yielding some interesting results.

  1. Domain-specific functional software testing: A progress report

    NASA Technical Reports Server (NTRS)

    Nonnenmann, Uwe

    1992-01-01

    Software Engineering is a knowledge intensive activity that involves defining, designing, developing, and maintaining software systems. In order to build effective systems to support Software Engineering activities, Artificial Intelligence techniques are needed. The application of Artificial Intelligence technology to Software Engineering is called Knowledge-based Software Engineering (KBSE). The goal of KBSE is to change the software life cycle such that software maintenance and evolution occur by modifying the specifications and then rederiving the implementation rather than by directly modifying the implementation. The use of domain knowledge in developing KBSE systems is crucial. Our work is mainly related to one area of KBSE that is called automatic specification acquisition. One example is the WATSON prototype on which our current work is based. WATSON is an automatic programming system for formalizing specifications for telephone switching software mainly restricted to POTS, i.e., plain old telephone service. Our current approach differentiates itself from other approaches in two antagonistic ways. On the one hand, we address a large and complex real-world problem instead of a 'toy domain' as in many research prototypes. On the other hand, to allow such scaling, we had to relax the ambitious goal of complete automatic programming, to the easier task of automatic testing.

  2. Incubator Display Software Cost Reduction Toolset Software Requirements Specification

    NASA Technical Reports Server (NTRS)

    Moran, Susanne; Jeffords, Ralph

    2005-01-01

    The Incubator Display Software Requirements Specification was initially developed by Intrinsyx Technologies Corporation (Intrinsyx) under subcontract to Lockheed Martin, Contract Number NAS2-02090, for the National Aeronautics and Space Administration (NASA) Ames Research Center (ARC) Space Station Biological Research Project (SSBRP). The Incubator Display is a User Payload Application (UPA) used to control an Incubator subrack payload for the SSBRP. The Incubator Display functions on-orbit as part of the subrack payload laptop, on the ground as part of the Communication and Data System (CDS) ground control system, and also as part of the crew training environment.

  3. 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.

  4. Scheduling Software for Complex Scenarios

    NASA Technical Reports Server (NTRS)

    2006-01-01

    Preparing a vehicle and its payload for a single launch is a complex process that involves thousands of operations. Because the equipment and facilities required to carry out these operations are extremely expensive and limited in number, optimal assignment and efficient use are critically important. Overlapping missions that compete for the same resources, ground rules, safety requirements, and the unique needs of processing vehicles and payloads destined for space impose numerous constraints that, when combined, require advanced scheduling. Traditional scheduling systems use simple algorithms and criteria when selecting activities and assigning resources and times to each activity. Schedules generated by these simple decision rules are, however, frequently far from optimal. To resolve mission-critical scheduling issues and predict possible problem areas, NASA historically relied upon expert human schedulers who used their judgment and experience to determine where things should happen, whether they will happen on time, and whether the requested resources are truly necessary.

  5. Software Accelerates Computing Time for Complex Math

    NASA Technical Reports Server (NTRS)

    2014-01-01

    Ames Research Center awarded Newark, Delaware-based EM Photonics Inc. SBIR funding to utilize graphic processing unit (GPU) technology- traditionally used for computer video games-to develop high-computing software called CULA. The software gives users the ability to run complex algorithms on personal computers with greater speed. As a result of the NASA collaboration, the number of employees at the company has increased 10 percent.

  6. Software analysis handbook: Software complexity analysis and software reliability estimation and prediction

    NASA Technical Reports Server (NTRS)

    Lee, Alice T.; Gunn, Todd; Pham, Tuan; Ricaldi, Ron

    1994-01-01

    This handbook documents the three software analysis processes the Space Station Software Analysis team uses to assess space station software, including their backgrounds, theories, tools, and analysis procedures. Potential applications of these analysis results are also presented. The first section describes how software complexity analysis provides quantitative information on code, such as code structure and risk areas, throughout the software life cycle. Software complexity analysis allows an analyst to understand the software structure, identify critical software components, assess risk areas within a software system, identify testing deficiencies, and recommend program improvements. Performing this type of analysis during the early design phases of software development can positively affect the process, and may prevent later, much larger, difficulties. The second section describes how software reliability estimation and prediction analysis, or software reliability, provides a quantitative means to measure the probability of failure-free operation of a computer program, and describes the two tools used by JSC to determine failure rates and design tradeoffs between reliability, costs, performance, and schedule.

  7. Software Process Assurance for Complex Electronics (SPACE)

    NASA Technical Reports Server (NTRS)

    Plastow, Richard A.

    2007-01-01

    Complex Electronics (CE) are now programmed to perform tasks that were previously handled in software, such as communication protocols. Many of the methods used to develop software bare a close resemblance to CE development. For instance, Field Programmable Gate Arrays (FPGAs) can have over a million logic gates while system-on-chip (SOC) devices can combine a microprocessor, input and output channels, and sometimes an FPGA for programmability. With this increased intricacy, the possibility of software-like bugs such as incorrect design, logic, and unexpected interactions within the logic is great. Since CE devices are obscuring the hardware/software boundary, we propose that mature software methodologies may be utilized with slight modifications in the development of these devices. Software Process Assurance for Complex Electronics (SPACE) is a research project that looks at using standardized S/W Assurance/Engineering practices to provide an assurance framework for development activities. Tools such as checklists, best practices and techniques can be used to detect missing requirements and bugs earlier in the development cycle creating a development process for CE that will be more easily maintained, consistent and configurable based on the device used.

  8. Software Process Assurance for Complex Electronics

    NASA Technical Reports Server (NTRS)

    Plastow, Richard A.

    2007-01-01

    Complex Electronics (CE) now perform tasks that were previously handled in software, such as communication protocols. Many methods used to develop software bare a close resemblance to CE development. Field Programmable Gate Arrays (FPGAs) can have over a million logic gates while system-on-chip (SOC) devices can combine a microprocessor, input and output channels, and sometimes an FPGA for programmability. With this increased intricacy, the possibility of software-like bugs such as incorrect design, logic, and unexpected interactions within the logic is great. With CE devices obscuring the hardware/software boundary, we propose that mature software methodologies may be utilized with slight modifications in the development of these devices. Software Process Assurance for Complex Electronics (SPACE) is a research project that used standardized S/W Assurance/Engineering practices to provide an assurance framework for development activities. Tools such as checklists, best practices and techniques were used to detect missing requirements and bugs earlier in the development cycle creating a development process for CE that was more easily maintained, consistent and configurable based on the device used.

  9. Domain specific software architectures: Command and control

    NASA Technical Reports Server (NTRS)

    Braun, Christine; Hatch, William; Ruegsegger, Theodore; Balzer, Bob; Feather, Martin; Goldman, Neil; Wile, Dave

    1992-01-01

    GTE is the Command and Control contractor for the Domain Specific Software Architectures program. The objective of this program is to develop and demonstrate an architecture-driven, component-based capability for the automated generation of command and control (C2) applications. Such a capability will significantly reduce the cost of C2 applications development and will lead to improved system quality and reliability through the use of proven architectures and components. A major focus of GTE's approach is the automated generation of application components in particular subdomains. Our initial work in this area has concentrated in the message handling subdomain; we have defined and prototyped an approach that can automate one of the most software-intensive parts of C2 systems development. This paper provides an overview of the GTE team's DSSA approach and then presents our work on automated support for message processing.

  10. Requirements management system browser software requirements specification

    SciTech Connect

    Frank, D.D.

    1996-10-01

    The purpose of this document is to define the essential user requirements for the Requirements Management System Browser (RMSB) application. This includes specifications for the Graphical User Interface (GUI) and the supporting database structures. The RMSB application is needed to provide an easy to use PC-based interface to browse system engineering data stored and managed in a UNIX software application. The system engineering data include functions, requirements, and architectures that make up the Tank Waste Remediation System (TWRS) technical baseline. This document also covers the requirements for a software application titled ``RMSB Data Loader (RMSB- DL)``, referred to as the ``Parser.`` The Parser is needed to read and parse a data file and load the data structure supporting the Browser.

  11. Orbital flight simulation utility software unit specifications

    NASA Technical Reports Server (NTRS)

    Wilson, S. W.

    1986-01-01

    The HP PASCAL source code contained in pages 6 through 104 was developed for the Mission Planning and Analysis Division (MPAD) and takes the place of detailed flow charts defining the specifications for a Utility Software Unit designed to support orbital flight simulators such as MANHANDLE and GREAS (General Research and Engineering Analysis Simulator). Besides providing basic input/output, mathematical, vector, matrix, quaternion, and statistical routines for such simulators, one of the primary functions of the Utility Software Unit is to isolate all system-dependent code in one well-defined compartment, thereby facilitating transportation of the simulations from one computer to another. Directives to the PASCAL compilers of the HP-9000 Series 200 PASCAL 3.0 operating system and the HP-9000 Series 500 HP-UX 5.0 operations systems are also provided.

  12. Light duty utility arm software requirements specification

    SciTech Connect

    Kiebel, G.R.

    1995-12-18

    This document defines the software requirements for the integrated control and data acquisition system of the Light Duty Utility Arm (LDUA) System. It is intended to be used to guide the design of the application software, to be a basis for assessing the application software design, and to establish what is to be tested in the finished application software product.

  13. Working Notes from the 1992 AAAI Workshop on Automating Software Design. Theme: Domain Specific Software Design

    NASA Technical Reports Server (NTRS)

    Keller, Richard M. (Editor); Barstow, David; Lowry, Michael R.; Tong, Christopher H.

    1992-01-01

    The goal of this workshop is to identify different architectural approaches to building domain-specific software design systems and to explore issues unique to domain-specific (vs. general-purpose) software design. Some general issues that cut across the particular software design domain include: (1) knowledge representation, acquisition, and maintenance; (2) specialized software design techniques; and (3) user interaction and user interface.

  14. 78 FR 47015 - Software Requirement Specifications for Digital Computer Software Used in Safety Systems of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-02

    ... issued with a temporary identification as Draft Regulatory Guide, DG-1209 on August 22, 2012 (77 FR 50726... COMMISSION Software Requirement Specifications for Digital Computer Software Used in Safety Systems of... 1 of RG 1.172, ``Software Requirement Specifications for Digital Computer Software used in...

  15. Software Analyzes Complex Systems in Real Time

    NASA Technical Reports Server (NTRS)

    2008-01-01

    Expert system software programs, also known as knowledge-based systems, are computer programs that emulate the knowledge and analytical skills of one or more human experts, related to a specific subject. SHINE (Spacecraft Health Inference Engine) is one such program, a software inference engine (expert system) designed by NASA for the purpose of monitoring, analyzing, and diagnosing both real-time and non-real-time systems. It was developed to meet many of the Agency s demanding and rigorous artificial intelligence goals for current and future needs. NASA developed the sophisticated and reusable software based on the experience and requirements of its Jet Propulsion Laboratory s (JPL) Artificial Intelligence Research Group in developing expert systems for space flight operations specifically, the diagnosis of spacecraft health. It was designed to be efficient enough to operate in demanding real time and in limited hardware environments, and to be utilized by non-expert systems applications written in conventional programming languages. The technology is currently used in several ongoing NASA applications, including the Mars Exploration Rovers and the Spacecraft Health Automatic Reasoning Pilot (SHARP) program for the diagnosis of telecommunication anomalies during the Neptune Voyager Encounter. It is also finding applications outside of the Space Agency.

  16. Software for Simulating a Complex Robot

    NASA Technical Reports Server (NTRS)

    Goza, S. Michael

    2003-01-01

    RoboSim (Robot Simulation) is a computer program that simulates the poses and motions of the Robonaut a developmental anthropomorphic robot that has a complex system of joints with 43 degrees of freedom and multiple modes of operation and control. RoboSim performs a full kinematic simulation of all degrees of freedom. It also includes interface components that duplicate the functionality of the real Robonaut interface with control software and human operators. Basically, users see no difference between the real Robonaut and the simulation. Consequently, new control algorithms can be tested by computational simulation, without risk to the Robonaut hardware, and without using excessive Robonaut-hardware experimental time, which is always at a premium. Previously developed software incorporated into RoboSim includes Enigma (for graphical displays), OSCAR (for kinematical computations), and NDDS (for communication between the Robonaut and external software). In addition, RoboSim incorporates unique inverse-kinematical algorithms for chains of joints that have fewer than six degrees of freedom (e.g., finger joints). In comparison with the algorithms of OSCAR, these algorithms are more readily adaptable and provide better results when using equivalent sets of data.

  17. Salvo: Seismic imaging software for complex geologies

    SciTech Connect

    OBER,CURTIS C.; GJERTSEN,ROB; WOMBLE,DAVID E.

    2000-03-01

    This report describes Salvo, a three-dimensional seismic-imaging software for complex geologies. Regions of complex geology, such as overthrusts and salt structures, can cause difficulties for many seismic-imaging algorithms used in production today. The paraxial wave equation and finite-difference methods used within Salvo can produce high-quality seismic images in these difficult regions. However this approach comes with higher computational costs which have been too expensive for standard production. Salvo uses improved numerical algorithms and methods, along with parallel computing, to produce high-quality images and to reduce the computational and the data input/output (I/O) costs. This report documents the numerical algorithms implemented for the paraxial wave equation, including absorbing boundary conditions, phase corrections, imaging conditions, phase encoding, and reduced-source migration. This report also describes I/O algorithms for large seismic data sets and images and parallelization methods used to obtain high efficiencies for both the computations and the I/O of seismic data sets. Finally, this report describes the required steps to compile, port and optimize the Salvo software, and describes the validation data sets used to help verify a working copy of Salvo.

  18. NASA software specification and evaluation system design, part 1

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The research to develop methods for reducing the effort expended in software and verification is reported. The development of a formal software requirements methodology, a formal specifications language, a programming language, a language preprocessor, and code analysis tools are discussed.

  19. Formalization and visualization of domain-specific software architectures

    NASA Technical Reports Server (NTRS)

    Bailor, Paul D.; Luginbuhl, David R.; Robinson, John S.

    1992-01-01

    This paper describes a domain-specific software design system based on the concepts of software architectures engineering and domain-specific models and languages. In this system, software architectures are used as high level abstractions to formulate a domain-specific software design. The software architecture serves as a framework for composing architectural fragments (e.g., domain objects, system components, and hardware interfaces) that make up the knowledge (or model) base for solving a problem in a particular application area. A corresponding software design is generated by analyzing and describing a system in the context of the software architecture. While the software architecture serves as the framework for the design, this concept is insufficient by itself for supplying the additional details required for a specific design. Additional domain knowledge is still needed to instantiate components of the architecture and develop optimized algorithms for the problem domain. One possible way to obtain the additional details is through the use of domain-specific languages. Thus, the general concept of a software architecture and the specific design details provided by domain-specific languages are combined to create what can be termed a domain-specific software architecture (DSSA).

  20. NASA software specification and evaluation system design, part 2

    NASA Technical Reports Server (NTRS)

    1976-01-01

    A survey and analysis of the existing methods, tools and techniques employed in the development of software are presented along with recommendations for the construction of reliable software. Functional designs for software specification language, and the data base verifier are presented.

  1. NASA software specification and evaluation system: Software verification/validation techniques

    NASA Technical Reports Server (NTRS)

    1977-01-01

    NASA software requirement specifications were used in the development of a system for validating and verifying computer programs. The software specification and evaluation system (SSES) provides for the effective and efficient specification, implementation, and testing of computer software programs. The system as implemented will produce structured FORTRAN or ANSI FORTRAN programs, but the principles upon which SSES is designed allow it to be easily adapted to other high order languages.

  2. Preparation guide for class B software specification documents

    NASA Technical Reports Server (NTRS)

    Tausworthe, R. C.

    1979-01-01

    General conceptual requirements and specific application rules and procedures are provided for the production of software specification documents in conformance with deep space network software standards and class B standards. Class B documentation is identified as the appropriate level applicable to implementation, sustaining engineering, and operational uses by qualified personnel. Special characteristics of class B documents are defined.

  3. Industrial Source Complex (ISC) dispersion model. Software

    SciTech Connect

    Schewe, G.; Sieurin, E.

    1980-01-01

    The model updates various EPA dispersion model algorithms and combines them in two computer programs that can be used to assess the air quality impact of emissions from the wide variety of source types associated with an industrial source complex. The ISC Model short-term program ISCST, an updated version of the EPA Single Source (CRSTER) Model uses sequential hourly meteorological data to calculate values of average concentration or total dry deposition for time periods of 1, 2, 3, 4, 6, 8, 12 and 24 hours. Additionally, ISCST may be used to calculate 'N' is 366 days. The ISC Model long-term computer program ISCLT, a sector-averaged model that updates and combines basic features of the EPA Air Quality Display Model (AQDM) and the EPA Climatological Dispersion Model (CDM), uses STAR Summaries to calculate seasonal and/or annual average concentration or total deposition values. Both the ISCST and ISCLT programs make the same basic dispersion-model assumptions. Additionally, both the ISCST and ISCLT programs use either a polar or a Cartesian receptor grid...Software Description: The programs are written in the FORTRAN IV programming language for implementation on a UNIVAC 1110 computer and also on medium-to-large IBM or CDC systems. 65,000k words of core storage are required to operate the model.

  4. SEPAC flight software detailed design specifications, volume 1

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The detailed design specifications (as built) for the SEPAC Flight Software are defined. The design includes a description of the total software system and of each individual module within the system. The design specifications describe the decomposition of the software system into its major components. The system structure is expressed in the following forms: the control-flow hierarchy of the system, the data-flow structure of the system, the task hierarchy, the memory structure, and the software to hardware configuration mapping. The component design description includes details on the following elements: register conventions, module (subroutines) invocaton, module functions, interrupt servicing, data definitions, and database structure.

  5. Tips on Creating Complex Geometry Using Solid Modeling Software

    ERIC Educational Resources Information Center

    Gow, George

    2008-01-01

    Three-dimensional computer-aided drafting (CAD) software, sometimes referred to as "solid modeling" software, is easy to learn, fun to use, and becoming the standard in industry. However, many users have difficulty creating complex geometry with the solid modeling software. And the problem is not entirely a student problem. Even some teachers and…

  6. Reasoning about software specifications - A case study

    NASA Technical Reports Server (NTRS)

    Wild, Chris; Chen, JI; Eckhardt, Dave

    1989-01-01

    The launch intercept condition (LIC) problem was analyzed to better understand the complexity of the automated reasoning process and the nature and role of background knowledge. An extension to resolution-based logic processing systems, called constraint logic programming, is described. Consideration is also given to a knowledge-driven incremental reasoning architecture which integrates a generic constraint logic programming system with a knowledge base of the domain.

  7. Early Childhood Educational Software: Specific Features and Issues of Localization

    ERIC Educational Resources Information Center

    Nikolopoulou, Kleopatra

    2007-01-01

    The computer has now become a recognized tool in the education of young children and when used appropriately can reinforce their learning experiences. This paper reviews specific features (relating to pedagogic design, software content and user-interface design) of early childhood educational software and discusses issues in favor of its…

  8. Analyzing Software Specifications for Mode Confusion Potential

    NASA Technical Reports Server (NTRS)

    Leveson, Nancy G.; Pinnel, L. Denise; Sandys, Sean David; Koga, Shuichi; Reese, Jon Damon

    1998-01-01

    Increased automation in complex systems has led to changes in the human controller's role and to new types of technology-induced human error. Attempts to mitigate these errors have primarily involved giving more authority to the automation, enhancing operator training, or changing the interface. While these responses may be reasonable under many circumstances, an alternative is to redesign the automation in ways that do not reduce necessary or desirable functionality or to change functionality where the tradeoffs are judged to be acceptable. This paper describes an approach to detecting error-prone automation features early in the development process while significant changes can still be made to the conceptual design of the system. The information about such error-prone features can also be useful in the design of the operator interface, operational procedures, or operator training.

  9. 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.

  10. Independent verification and validation of large software requirement specification databases

    SciTech Connect

    Twitchell, K.E.

    1992-04-01

    To enhance quality, an independent verification and validation (IV V) review is conducted as software requirements are defined. Requirements are inspected for consistency and completeness. IV V strives to detect defects early in the software development life cycle and to prevent problems before they occur. The IV V review process of a massive software requirements specification, the Reserve Component Automation System (RCAS) Functional Description (FD) is explored. Analysis of the RCAS FD error history determined that there are no predictors of errors. The size of the FD mandates electronic analysis of the databases. Software which successfully performs automated consistency and completeness checks is discussed. The process of verifying the quality of analysis software is described. The use of intuitive ad hoc techniques, in addition to the automatic analysis of the databases, is required because of the varying content of the requirements databases. The ad hoc investigation process is discussed. Case studies are provided to illustrate how the process works. This thesis demonstrates that it is possible to perform an IV V review on a massive software requirements specification. Automatic analysis enables inspecting for completeness and consistency. The work with the RCAS FD clearly indicates that the IV V review process is not static; it must continually grow, adapt, and change as conditions warrant. The ad hoc investigation process provides this required flexibility This process also analyzes errors discovered by manual review and automatic processing. The analysis results in the development of new algorithms and the addition of new programs to the automatic inspection software.

  11. AM, administrative software ease complex Maryland job

    SciTech Connect

    Troch, S.J.; Agnes, D.C.; Catonzaro, J.S.; Oberlechner, L.E.

    1995-06-01

    A gas distribution looping project, in three segments that traversed a complete range of installation and alignment issues, recently was completed by Baltimore Gas and Electric Co. (BG and E) in northern Maryland. The major projects unit in the company`s gas system engineering and design section was responsible for total oversight of the three projects. This included design, engineering, permitting, right-of-way acquisition, construction, testing and restoration, as well as liaison with other company divisions. A specially selected subcontractor team was organized to provide the latest technology. A project management system, comprised mainly of personal computer applications, was implemented to provide: engineering and design coordination; accurate interface among easement, real estate acquisition data, plats, surveys, permitting and design documents; accurate right-of-way identification; data storage and accessibility of all real estate information for use in design and budgeting; an interface of environmental conditions with topography and design; a computer database that is compatible with existing computer libraries and industry-available software, for producing drawings. Controls for projects costs, budget and schedule were provided by the project management system. This was accomplished by interaction of four data systems: real estate, accounting/budget, geographical information system (GIS), global positioning system (GPS). Construction progress was monitored with a scheduling application that ultimately provided justification for contractor progress payments. The amount of pipe laid in any given time span, as documented by field inspector reports, was entered into the scheduling application. The scheduling software calculated the percent completed and provided information for monitoring progress.

  12. Psychosocial Risks Generated By Assets Specific Design Software

    NASA Astrophysics Data System (ADS)

    Remus, Furtună; Angela, Domnariu; Petru, Lazăr

    2015-07-01

    The human activity concerning an occupation is resultant from the interaction between the psycho-biological, socio-cultural and organizational-occupational factors. Tehnological development, automation and computerization that are to be found in all the branches of activity, the level of speed in which things develop, as well as reaching their complexity, require less and less physical aptitudes and more cognitive qualifications. The person included in the work process is bound in most of the cases to come in line with the organizational-occupational situations that are specific to the demands of the job. The role of the programmer is essencial in the process of execution of ordered softwares, thus the truly brilliant ideas can only come from well-rested minds, concentrated on their tasks. The actual requirements of the jobs, besides the high number of benefits and opportunities, also create a series of psycho-social risks, which can increase the level of stress during work activity, especially for those who work under pressure.

  13. Software Requirements Specification Verifiable Fuel Cycle Simulation (VISION) Model

    SciTech Connect

    D. E. Shropshire; W. H. West

    2005-11-01

    The purpose of this Software Requirements Specification (SRS) is to define the top-level requirements for a Verifiable Fuel Cycle Simulation Model (VISION) of the Advanced Fuel Cycle (AFC). This simulation model is intended to serve a broad systems analysis and study tool applicable to work conducted as part of the AFCI (including costs estimates) and Generation IV reactor development studies.

  14. The KASE approach to domain-specific software systems

    NASA Technical Reports Server (NTRS)

    Bhansali, Sanjay; Nii, H. Penny

    1992-01-01

    Designing software systems, like all design activities, is a knowledge-intensive task. Several studies have found that the predominant cause of failures among system designers is lack of knowledge: knowledge about the application domain, knowledge about design schemes, knowledge about design processes, etc. The goal of domain-specific software design systems is to explicitly represent knowledge relevant to a class of applications and use it to partially or completely automate various aspects of the designing systems within that domain. The hope is that this would reduce the intellectual burden on the human designers and lead to more efficient software development. In this paper, we present a domain-specific system built on top of KASE, a knowledge-assisted software engineering environment being developed at the Stanford Knowledge Systems Laboratory. We introduce the main ideas underlying the construction of domain specific systems within KASE, illustrate the application of the idea in the synthesis of a system for tracking aircraft from radar signals, and discuss some of the issues in constructing domain-specific systems.

  15. Complexity for Artificial Substrates (CASU): Software for Creating and Visualising Habitat Complexity

    PubMed Central

    Loke, Lynette H. L.; Jachowski, Nicholas R.; Bouma, Tjeerd J.; Ladle, Richard J.; Todd, Peter A.

    2014-01-01

    Physical habitat complexity regulates the structure and function of biological communities, although the mechanisms underlying this relationship remain unclear. Urbanisation, pollution, unsustainable resource exploitation and climate change have resulted in the widespread simplification (and loss) of habitats worldwide. One way to restore physical complexity to anthropogenically simplified habitats is through the use of artificial substrates, which also offer excellent opportunities to explore the effects of different components (variables) of complexity on biodiversity and community structure that would be difficult to separate in natural systems. Here, we describe a software program (CASU) that enables users to visualise static, physical complexity. CASU also provides output files that can be used to create artificial substrates for experimental and/or restoration studies. It has two different operational modes: simple and advanced. In simple mode, users can adjust the five main variables of informational complexity (i.e. the number of object types, relative abundance of object types, density of objects, variability and range in the objects’ dimensions, and their spatial arrangement) and visualise the changes as they do so. The advanced mode allows users to design artificial substrates by fine-tuning the complexity variables as well as alter object-specific parameters. We illustrate how CASU can be used to create tiles of different designs for application in a marine environment. Such an ability to systematically influence physical complexity could greatly facilitate ecological restoration by allowing conservationists to rebuild complexity in degraded and simplified habitats. PMID:24551074

  16. Computer Software Configuration Item-Specific Flight Software Image Transfer Script Generator

    NASA Technical Reports Server (NTRS)

    Bolen, Kenny; Greenlaw, Ronald

    2010-01-01

    A K-shell UNIX script enables the International Space Station (ISS) Flight Control Team (FCT) operators in NASA s Mission Control Center (MCC) in Houston to transfer an entire or partial computer software configuration item (CSCI) from a flight software compact disk (CD) to the onboard Portable Computer System (PCS). The tool is designed to read the content stored on a flight software CD and generate individual CSCI transfer scripts that are capable of transferring the flight software content in a given subdirectory on the CD to the scratch directory on the PCS. The flight control team can then transfer the flight software from the PCS scratch directory to the Electronically Erasable Programmable Read Only Memory (EEPROM) of an ISS Multiplexer/ Demultiplexer (MDM) via the Indirect File Transfer capability. The individual CSCI scripts and the CSCI Specific Flight Software Image Transfer Script Generator (CFITSG), when executed a second time, will remove all components from their original execution. The tool will identify errors in the transfer process and create logs of the transferred software for the purposes of configuration management.

  17. Independent verification and validation of large software requirement specification databases

    SciTech Connect

    Twitchell, K.E.

    1992-04-01

    To enhance quality, an independent verification and validation (IV&V) review is conducted as software requirements are defined. Requirements are inspected for consistency and completeness. IV&V strives to detect defects early in the software development life cycle and to prevent problems before they occur. The IV&V review process of a massive software requirements specification, the Reserve Component Automation System (RCAS) Functional Description (FD) is explored. Analysis of the RCAS FD error history determined that there are no predictors of errors. The size of the FD mandates electronic analysis of the databases. Software which successfully performs automated consistency and completeness checks is discussed. The process of verifying the quality of analysis software is described. The use of intuitive ad hoc techniques, in addition to the automatic analysis of the databases, is required because of the varying content of the requirements databases. The ad hoc investigation process is discussed. Case studies are provided to illustrate how the process works. This thesis demonstrates that it is possible to perform an IV&V review on a massive software requirements specification. Automatic analysis enables inspecting for completeness and consistency. The work with the RCAS FD clearly indicates that the IV&V review process is not static; it must continually grow, adapt, and change as conditions warrant. The ad hoc investigation process provides this required flexibility This process also analyzes errors discovered by manual review and automatic processing. The analysis results in the development of new algorithms and the addition of new programs to the automatic inspection software.

  18. Towards a Domain Specific Software Architecture for Scientific Data Distribution

    NASA Astrophysics Data System (ADS)

    Wilson, A.; Lindholm, D. M.

    2011-12-01

    A reference architecture is a "design that satisfies a clearly distinguished subset of the functional capabilities identified in the reference requirements within the boundaries of certain design and implementation constraints, also identified in reference requirements." [Tracz, 1995] Recognizing the value of a reference architecture, NASA's ESDSWG's Standards Process Group (SPG) is introducing a multi-disciplinary science data systems (SDS) reference architecture in order to provide an implementation neutral, template solution for an architecture to support scientific data systems in general [Burnett, et al, 2011]. This reference architecture describes common features and patterns in scientific data systems, and can thus provide guidelines in building and improving such systems. But, guidelines alone may not be sufficient to actually build a system. A domain specific software architecture (DSSA) is "an assemblage of software components, specialized for a particular type of task (domain), generalized for effective use across that domain, composed in a standardized structure (topology) effective for building successful applications." [Tracz, 1995]. It can be thought of as relatively specific reference architecture. The "DSSA Process" is a software life cycle developed at Carnegie Melon's Software Engineering Institute that is based on the development and use of domain-specific software architectures, components, and tools. The process has four distinct activities: 1) develop a domain specific base/model, 2) populate and maintain the library, 3) build applications, 4) operate and maintain applications [Armitage, 1993]. The DSSA process may provide the missing link between guidelines and actual system construction. In this presentation we focus specifically on the realm of scientific data access and distribution. Assuming the role of domain experts in building data access systems, we report the results of creating a DSSA for scientific data distribution. We describe

  19. Observation-Driven Configuration of Complex Software Systems

    NASA Astrophysics Data System (ADS)

    Sage, Aled

    2010-06-01

    The ever-increasing complexity of software systems makes them hard to comprehend, predict and tune due to emergent properties and non-deterministic behaviour. Complexity arises from the size of software systems and the wide variety of possible operating environments: the increasing choice of platforms and communication policies leads to ever more complex performance characteristics. In addition, software systems exhibit different behaviour under different workloads. Many software systems are designed to be configurable so that policies can be chosen to meet the needs of various stakeholders. For complex software systems it can be difficult to accurately predict the effects of a change and to know which configuration is most appropriate. This thesis demonstrates that it is useful to run automated experiments that measure a selection of system configurations. Experiments can find configurations that meet the stakeholders' needs, find interesting behavioural characteristics, and help produce predictive models of the system's behaviour. The design and use of ACT (Automated Configuration Tool) for running such experiments is described, in combination a number of search strategies for deciding on the configurations to measure. Design Of Experiments (DOE) is discussed, with emphasis on Taguchi Methods. These statistical methods have been used extensively in manufacturing, but have not previously been used for configuring software systems. The novel contribution here is an industrial case study, applying the combination of ACT and Taguchi Methods to DC-Directory, a product from Data Connection Ltd (DCL). The case study investigated the applicability of Taguchi Methods for configuring complex software systems. Taguchi Methods were found to be useful for modelling and configuring DC- Directory, making them a valuable addition to the techniques available to system administrators and developers.

  20. Solid Waste Information and Tracking System (SWITS) Software Requirements Specification

    SciTech Connect

    MAY, D.L.

    2000-03-22

    This document is the primary document establishing requirements for the Solid Waste Information and Tracking System (SWITS) as it is converted to a client-server architecture. The purpose is to provide the customer and the performing organizations with the requirements for the SWITS in the new environment. This Software Requirement Specification (SRS) describes the system requirements for the SWITS Project, and follows the PHMC Engineering Requirements, HNF-PRO-1819, and Computer Software Qualify Assurance Requirements, HNF-PRO-309, policies. This SRS includes sections on general description, specific requirements, references, appendices, and index. The SWITS system defined in this document stores information about the solid waste inventory on the Hanford site. Waste is tracked as it is generated, analyzed, shipped, stored, and treated. In addition to inventory reports a number of reports for regulatory agencies are produced.

  1. The Influence of Software Complexity on the Maintenance Effort: Case Study on Software Developed within Educational Process

    ERIC Educational Resources Information Center

    Radulescu, Iulian Ionut

    2006-01-01

    Software complexity is the most important software quality attribute and a very useful instrument in the study of software quality. Is one of the factors that affect most of the software quality characteristics, including maintainability. It is very important to quantity this influence and identify the means to keep it under control; by using…

  2. Engine structures analysis software: Component Specific Modeling (COSMO)

    NASA Astrophysics Data System (ADS)

    McKnight, R. L.; Maffeo, R. J.; Schwartz, S.

    1994-08-01

    A component specific modeling software program has been developed for propulsion systems. This expert program is capable of formulating the component geometry as finite element meshes for structural analysis which, in the future, can be spun off as NURB geometry for manufacturing. COSMO currently has geometry recipes for combustors, turbine blades, vanes, and disks. Component geometry recipes for nozzles, inlets, frames, shafts, and ducts are being added. COSMO uses component recipes that work through neutral files with the Technology Benefit Estimator (T/BEST) program which provides the necessary base parameters and loadings. This report contains the users manual for combustors, turbine blades, vanes, and disks.

  3. Engine Structures Analysis Software: Component Specific Modeling (COSMO)

    NASA Technical Reports Server (NTRS)

    Mcknight, R. L.; Maffeo, R. J.; Schwartz, S.

    1994-01-01

    A component specific modeling software program has been developed for propulsion systems. This expert program is capable of formulating the component geometry as finite element meshes for structural analysis which, in the future, can be spun off as NURB geometry for manufacturing. COSMO currently has geometry recipes for combustors, turbine blades, vanes, and disks. Component geometry recipes for nozzles, inlets, frames, shafts, and ducts are being added. COSMO uses component recipes that work through neutral files with the Technology Benefit Estimator (T/BEST) program which provides the necessary base parameters and loadings. This report contains the users manual for combustors, turbine blades, vanes, and disks.

  4. Managing scientific software complexity with Bocca and CCA

    SciTech Connect

    Benjamin, Allan A.; Norris, Boyana; Elwasif, Wael R; Armstrong, Robert C.

    2008-01-01

    In high-performance scientific software development, the emphasis is often on short time to first solution. Even when the development of new components mostly reuses existing components or libraries and only small amounts of new code must be created, dealing with the component glue code and software build processes to obtain complete applications is still tedious and error-prone. Component-based software meant to reduce complexity at the application level increases complexity to the extent that the user must learn and remember the interfaces and conventions of the component model itself. To address these needs, we introduce Bocca, the first tool to enable application developers to perform rapid component prototyping while maintaining robust software-engineering practices suitable to HPC environments. Bocca provides project management and a comprehensive build environment for creating and managing applications composed of Common Component Architecture components. Of critical importance for high-performance computing (HPC) applications, Bocca is designed to operate in a language-agnostic way, simultaneously handling components written in any of the languages commonly used in scientific applications: C, C++, Fortran, Python and Java. Bocca automates the tasks related to the component glue code, freeing the user to focus on the scientific aspects of the application. Bocca embraces the philosophy pioneered by Ruby on Rails for web applications: start with something that works, and evolve it to the user's purpose.

  5. Managing Scientific Software Complexity with Bocca and CCA

    DOE PAGESBeta

    Allan, Benjamin A.; Norris, Boyana; Elwasif, Wael R.; Armstrong, Robert C.

    2008-01-01

    In high-performance scientific software development, the emphasis is often on short time to first solution. Even when the development of new components mostly reuses existing components or libraries and only small amounts of new code must be created, dealing with the component glue code and software build processes to obtain complete applications is still tedious and error-prone. Component-based software meant to reduce complexity at the application level increases complexity to the extent that the user must learn and remember the interfaces and conventions of the component model itself. To address these needs, we introduce Bocca, the first tool to enablemore » application developers to perform rapid component prototyping while maintaining robust software-engineering practices suitable to HPC environments. Bocca provides project management and a comprehensive build environment for creating and managing applications composed of Common Component Architecture components. Of critical importance for high-performance computing (HPC) applications, Bocca is designed to operate in a language-agnostic way, simultaneously handling components written in any of the languages commonly used in scientific applications: C, C++, Fortran, Python and Java. Bocca automates the tasks related to the component glue code, freeing the user to focus on the scientific aspects of the application. Bocca embraces the philosophy pioneered by Ruby on Rails for web applications: start with something that works, and evolve it to the user's purpose.« less

  6. Air Traffic Complexity Measurement Environment (ACME): Software User's Guide

    NASA Technical Reports Server (NTRS)

    1996-01-01

    A user's guide for the Air Traffic Complexity Measurement Environment (ACME) software is presented. The ACME consists of two major components, a complexity analysis tool and user interface. The Complexity Analysis Tool (CAT) analyzes complexity off-line, producing data files which may be examined interactively via the Complexity Data Analysis Tool (CDAT). The Complexity Analysis Tool is composed of three independently executing processes that communicate via PVM (Parallel Virtual Machine) and Unix sockets. The Runtime Data Management and Control process (RUNDMC) extracts flight plan and track information from a SAR input file, and sends the information to GARP (Generate Aircraft Routes Process) and CAT (Complexity Analysis Task). GARP in turn generates aircraft trajectories, which are utilized by CAT to calculate sector complexity. CAT writes flight plan, track and complexity data to an output file, which can be examined interactively. The Complexity Data Analysis Tool (CDAT) provides an interactive graphic environment for examining the complexity data produced by the Complexity Analysis Tool (CAT). CDAT can also play back track data extracted from System Analysis Recording (SAR) tapes. The CDAT user interface consists of a primary window, a controls window, and miscellaneous pop-ups. Aircraft track and position data is displayed in the main viewing area of the primary window. The controls window contains miscellaneous control and display items. Complexity data is displayed in pop-up windows. CDAT plays back sector complexity and aircraft track and position data as a function of time. Controls are provided to start and stop playback, adjust the playback rate, and reposition the display to a specified time.

  7. Fuzzy complexes: Specific binding without complete folding.

    PubMed

    Sharma, Rashmi; Raduly, Zsolt; Miskei, Marton; Fuxreiter, Monika

    2015-09-14

    Specific molecular recognition is assumed to require a well-defined set of contacts and devoid of conformational and interaction ambiguities. Growing experimental evidence demonstrates however, that structural multiplicity or dynamic disorder can be retained in protein complexes, termed as fuzziness. Fuzzy regions establish alternative contacts between specific partners usually via transient interactions. Nature often tailors the dynamic properties of these segments via post-translational modifications or alternative splicing to fine-tune affinity. Most experimentally characterized fuzzy complexes are involved in regulation of gene-expression, signal transduction and cell-cycle regulation. Fuzziness is also characteristic to viral protein complexes, cytoskeleton structure, and surprisingly in a few metabolic enzymes. A plausible role of fuzzy complexes in increasing half-life of intrinsically disordered proteins is also discussed. PMID:26226339

  8. Applications of Formal Methods to Specification and Safety of Avionics Software

    NASA Technical Reports Server (NTRS)

    Hoover, D. N.; Guaspari, David; Humenn, Polar

    1996-01-01

    This report treats several topics in applications of formal methods to avionics software development. Most of these topics concern decision tables, an orderly, easy-to-understand format for formally specifying complex choices among alternative courses of action. The topics relating to decision tables include: generalizations fo decision tables that are more concise and support the use of decision tables in a refinement-based formal software development process; a formalism for systems of decision tables with behaviors; an exposition of Parnas tables for users of decision tables; and test coverage criteria and decision tables. We outline features of a revised version of ORA's decision table tool, Tablewise, which will support many of the new ideas described in this report. We also survey formal safety analysis of specifications and software.

  9. Specific Language Impairment at Adolescence: Avoiding Complexity

    ERIC Educational Resources Information Center

    Tuller, Laurice; Henry, Celia; Sizaret, Eva; Barthez, Marie-Anne

    2012-01-01

    This study explores complex language in adolescents with specific language impairment (SLI) with the aim of finding out how aspects of language characteristic of typical syntactic development after childhood fare and, in particular, whether there is evidence that individuals with SLI avoid using structures whose syntactic derivation involves…

  10. Software programs that address site-specific inventory characteristics issues.

    SciTech Connect

    Dare, J. H.; Cournoyer, M. E.

    2001-01-01

    The proper characterization of Hazardous, Mixed Low-Level, and Mixed Transuranic waste enhances productivity and safety. Hazardous material criteria that need to be considered include physical and health hazards inherent to the waste stream. Other factors that may influence characterization include: particulate diameter, complexing or chelating agent properties, lead, and mercury content, pressurized containers, and P-listed wastes. To meet these requirements are only a simple matter of generating a database with the proper fields. Manufactures and institutional databases bank huge sources of information, such as, work control documents, substance identification, container types, components of mixtures, physical property data, and regulatory data. In this report, utilization of commercially available software programs to take advantage of these resources in addressing waste characterization issues are presented. The application of user-friendly programs eliminates part of the tediousness associated with the complex requirements of certifying to general waste acceptance criteria with minimal impact on programmatic work. In other words, tapping into manufacturer and institutional database provides a way to take advantage of the combined expertise of these resources in managing a cost effective waste certification program as well as adding a quality assurance element to the program.

  11. Specificity, promiscuity, and the structure of complex information processing networks

    NASA Astrophysics Data System (ADS)

    Myers, Christopher

    2006-03-01

    Both the top-down designs of engineered systems and the bottom-up serendipities of biological evolution must negotiate tradeoffs between specificity and control: overly specific interactions between components can make systems brittle and unevolvable, while more generic interactions can require elaborate control in order to aggregate specificity from distributed pieces. Complex information processing systems reveal network organizations that navigate this landscape of constraints: regulatory and signaling networks in cells involve the coordination of molecular interactions that are surprisingly promiscuous, and object-oriented design in software systems emphasizes the polymorphic composition of objects of minimal necessary specificity [C.R. Myers, Phys Rev E 68, 046116 (2003)]. Models of information processing arising both in systems biology and engineered computation are explored to better understand how particular network organizations can coordinate the activity of promiscuous components to achieve robust and evolvable function.

  12. SIM_EXPLORE: Software for Directed Exploration of Complex Systems

    NASA Technical Reports Server (NTRS)

    Burl, Michael; Wang, Esther; Enke, Brian; Merline, William J.

    2013-01-01

    Physics-based numerical simulation codes are widely used in science and engineering to model complex systems that would be infeasible to study otherwise. While such codes may provide the highest- fidelity representation of system behavior, they are often so slow to run that insight into the system is limited. Trying to understand the effects of inputs on outputs by conducting an exhaustive grid-based sweep over the input parameter space is simply too time-consuming. An alternative approach called "directed exploration" has been developed to harvest information from numerical simulators more efficiently. The basic idea is to employ active learning and supervised machine learning to choose cleverly at each step which simulation trials to run next based on the results of previous trials. SIM_EXPLORE is a new computer program that uses directed exploration to explore efficiently complex systems represented by numerical simulations. The software sequentially identifies and runs simulation trials that it believes will be most informative given the results of previous trials. The results of new trials are incorporated into the software's model of the system behavior. The updated model is then used to pick the next round of new trials. This process, implemented as a closed-loop system wrapped around existing simulation code, provides a means to improve the speed and efficiency with which a set of simulations can yield scientifically useful results. The software focuses on the case in which the feedback from the simulation trials is binary-valued, i.e., the learner is only informed of the success or failure of the simulation trial to produce a desired output. The software offers a number of choices for the supervised learning algorithm (the method used to model the system behavior given the results so far) and a number of choices for the active learning strategy (the method used to choose which new simulation trials to run given the current behavior model). The software

  13. Orbital flight simulation utility software unit specifications, revision 1

    NASA Technical Reports Server (NTRS)

    Wilson, S. W.

    1986-01-01

    The HP PASCAL source code defines the specifications for a Utility Software Unit (USU) designed to support orbital flight simulators such as MANHANDLE and GREAS (General Research and Engineering Analysis Simulator). Besides providing basic input/output, mathematical, matrix, quaternion, and statistical routines for such simulators, one of the primary functions of the USU is to isolate all system-dependent codes in one well-defined compartment, thereby facilitating transportation of the simulations from one computer to another. Directives are given for the PASCAL compilers of the HP-9000 Series 200 Pascal 3.0 and the HP-9000 Series 500 HP-UX 5.0 operating systems that produce a single file of relocatable code from four separate files of source code. Three of the source code files are common to both operating systems. The fourth source code file (utilspif.I) contains all of the system-dependent PASCAL code for the USU. A fifth file of source code written in C is required to interface utilspif.I with the HP-UX I/O package. The Pascal 3.0 compiler directives and the driver source code for a unit rest program and counterparts for the HP-UX 5.0 operating system are given. The major portion of the unit test program source code is common to both operating systems. Unit test results from the Pascal 3.0 operating system and results from the HP-UX operating system are given.

  14. Computer software requirements specification for the world model light duty utility arm system

    SciTech Connect

    Ellis, J.E.

    1996-02-01

    This Computer Software Requirements Specification defines the software requirements for the world model of the Light Duty Utility Arm (LDUA) System. It is intended to be used to guide the design of the application software, to be a basis for assessing the application software design, and to establish what is to be tested in the finished application software product. (This deploys end effectors into underground storage tanks by means of robotic arm on end of telescoping mast.)

  15. 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.

  16. CarbBuilder: Software for building molecular models of complex oligo- and polysaccharide structures.

    PubMed

    Kuttel, Michelle M; Ståhle, Jonas; Widmalm, Göran

    2016-08-15

    CarbBuilder is a portable software tool for producing three-dimensional molecular models of carbohydrates from the simple text specification of a primary structure. CarbBuilder can generate a wide variety of carbohydrate structures, ranging from monosaccharides to large, branched polysaccharides. Version 2.0 of the software, described in this article, supports monosaccharides of both mammalian and bacterial origin and a range of substituents for derivatization of individual sugar residues. This improved version has a sophisticated building algorithm to explore the range of possible conformations for a specified carbohydrate molecule. Illustrative examples of models of complex polysaccharides produced by CarbBuilder demonstrate the capabilities of the software. CarbBuilder is freely available under the Artistic License 2.0 from https://people.cs.uct.ac.za/~mkuttel/Downloads.html. © 2016 Wiley Periodicals, Inc. PMID:27317625

  17. CHSSI Software for Geometrically Complex Unsteady Aerodynamic Applications

    NASA Technical Reports Server (NTRS)

    Chan, William M.; Meakin, Robert L.; Potsdam, Mark A.

    2001-01-01

    A comprehensive package of scalable overset grid CFD software is reviewed. The software facilitates accurate simulation of complete aircraft aerodynamics, including viscous effects, unsteadiness, and relative motion between component parts. The software significantly lowers the manpower and computer costs normally associated with such efforts. The software is discussed in terms of current capabilities and planned future enhancements.

  18. HSCT4.0 Application: Software Requirements Specification

    NASA Technical Reports Server (NTRS)

    Salas, A. O.; Walsh, J. L.; Mason, B. H.; Weston, R. P.; Townsend, J. C.; Samareh, J. A.; Green, L. L.

    2001-01-01

    The software requirements for the High Performance Computing and Communication Program High Speed Civil Transport application project, referred to as HSCT4.0, are described. The objective of the HSCT4.0 application project is to demonstrate the application of high-performance computing techniques to the problem of multidisciplinary design optimization of a supersonic transport configuration, using high-fidelity analysis simulations. Descriptions of the various functions (and the relationships among them) that make up the multidisciplinary application as well as the constraints on the software design arc provided. This document serves to establish an agreement between the suppliers and the customer as to what the HSCT4.0 application should do and provides to the software developers the information necessary to design and implement the system.

  19. 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…

  20. Acquiring Software Project Specifications in a Virtual World

    ERIC Educational Resources Information Center

    Ng, Vincent; Tang, Zoe

    2012-01-01

    In teaching software engineering, it is often interesting to introduce real life scenarios for students to experience and to learn how to collect information from respective clients. The ideal arrangement is to have some real clients willing to spend time to provide their ideas of a target system through interviews. However, this arrangement…

  1. Assessment of the integration capability of system architectures from a complex and distributed software systems perspective

    NASA Astrophysics Data System (ADS)

    Leuchter, S.; Reinert, F.; Müller, W.

    2014-06-01

    Procurement and design of system architectures capable of network centric operations demand for an assessment scheme in order to compare different alternative realizations. In this contribution an assessment method for system architectures targeted at the C4ISR domain is presented. The method addresses the integration capability of software systems from a complex and distributed software system perspective focusing communication, interfaces and software. The aim is to evaluate the capability to integrate a system or its functions within a system-of-systems network. This method uses approaches from software architecture quality assessment and applies them on the system architecture level. It features a specific goal tree of several dimensions that are relevant for enterprise integration. These dimensions have to be weighed against each other and totalized using methods from the normative decision theory in order to reflect the intention of the particular enterprise integration effort. The indicators and measurements for many of the considered quality features rely on a model based view on systems, networks, and the enterprise. That means it is applicable to System-of-System specifications based on enterprise architectural frameworks relying on defined meta-models or domain ontologies for defining views and viewpoints. In the defense context we use the NATO Architecture Framework (NAF) to ground respective system models. The proposed assessment method allows evaluating and comparing competing system designs regarding their future integration potential. It is a contribution to the system-of-systems engineering methodology.

  2. As-built design specification for proportion estimate software subsystem

    NASA Technical Reports Server (NTRS)

    Obrien, S. (Principal Investigator)

    1980-01-01

    The Proportion Estimate Processor evaluates four estimation techniques in order to get an improved estimate of the proportion of a scene that is planted in a selected crop. The four techniques to be evaluated were provided by the techniques development section and are: (1) random sampling; (2) proportional allocation, relative count estimate; (3) proportional allocation, Bayesian estimate; and (4) sequential Bayesian allocation. The user is given two options for computation of the estimated mean square error. These are referred to as the cluster calculation option and the segment calculation option. The software for the Proportion Estimate Processor is operational on the IBM 3031 computer.

  3. Modeling Complex Cross-Systems Software Interfaces Using SysML

    NASA Technical Reports Server (NTRS)

    Mandutianu, Sanda; Morillo, Ron; Simpson, Kim; Liepack, Otfrid; Bonanne, Kevin

    2013-01-01

    The complex flight and ground systems for NASA human space exploration are designed, built, operated and managed as separate programs and projects. However, each system relies on one or more of the other systems in order to accomplish specific mission objectives, creating a complex, tightly coupled architecture. Thus, there is a fundamental need to understand how each system interacts with the other. To determine if a model-based system engineering approach could be utilized to assist with understanding the complex system interactions, the NASA Engineering and Safety Center (NESC) sponsored a task to develop an approach for performing cross-system behavior modeling. This paper presents the results of applying Model Based Systems Engineering (MBSE) principles using the System Modeling Language (SysML) to define cross-system behaviors and how they map to crosssystem software interfaces documented in system-level Interface Control Documents (ICDs).

  4. On the nature of bias and defects in the software specification process

    NASA Technical Reports Server (NTRS)

    Straub, Pablo A.; Zelkowitz, Marvin V.

    1992-01-01

    Implementation bias in a specification is an arbitrary constraint in the solution space. This paper describes the problem of bias. Additionally, this paper presents a model of the specification and design processes describing individual subprocesses in terms of precision/detail diagrams and a model of bias in multi-attribute software specifications. While studying how bias is introduced into a specification we realized that software defects and bias are dual problems of a single phenomenon. This was used to explain the large proportion of faults found during the coding phase at the Software Engineering Laboratory at NASA/GSFC.

  5. A requirements specification for a software design support system

    NASA Technical Reports Server (NTRS)

    Noonan, Robert E.

    1988-01-01

    Most existing software design systems (SDSS) support the use of only a single design methodology. A good SDSS should support a wide variety of design methods and languages including structured design, object-oriented design, and finite state machines. It might seem that a multiparadigm SDSS would be expensive in both time and money to construct. However, it is proposed that instead an extensible SDSS that directly implements only minimal database and graphical facilities be constructed. In particular, it should not directly implement tools to faciliate language definition and analysis. It is believed that such a system could be rapidly developed and put into limited production use, with the experience gained used to refine and evolve the systems over time.

  6. The optimal community detection of software based on complex networks

    NASA Astrophysics Data System (ADS)

    Huang, Guoyan; Zhang, Peng; Zhang, Bing; Yin, Tengteng; Ren, Jiadong

    2016-02-01

    The community structure is important for software in terms of understanding the design patterns, controlling the development and the maintenance process. In order to detect the optimal community structure in the software network, a method Optimal Partition Software Network (OPSN) is proposed based on the dependency relationship among the software functions. First, by analyzing the information of multiple execution traces of one software, we construct Software Execution Dependency Network (SEDN). Second, based on the relationship among the function nodes in the network, we define Fault Accumulation (FA) to measure the importance of the function node and sort the nodes with measure results. Third, we select the top K(K=1,2,…) nodes as the core of the primal communities (only exist one core node). By comparing the dependency relationships between each node and the K communities, we put the node into the existing community which has the most close relationship. Finally, we calculate the modularity with different initial K to obtain the optimal division. With experiments, the method OPSN is verified to be efficient to detect the optimal community in various softwares.

  7. Application of software quality assurance to a specific scientific code development task

    SciTech Connect

    Dronkers, J.J.

    1986-03-01

    This paper describes an application of software quality assurance to a specific scientific code development program. The software quality assurance program consists of three major components: administrative control, configuration management, and user documentation. The program attempts to be consistent with existing local traditions of scientific code development while at the same time providing a controlled process of development.

  8. The development and application of composite complexity models and a relative complexity metric in a software maintenance environment

    NASA Technical Reports Server (NTRS)

    Hops, J. M.; Sherif, J. S.

    1994-01-01

    A great deal of effort is now being devoted to the study, analysis, prediction, and minimization of software maintenance expected cost, long before software is delivered to users or customers. It has been estimated that, on the average, the effort spent on software maintenance is as costly as the effort spent on all other software costs. Software design methods should be the starting point to aid in alleviating the problems of software maintenance complexity and high costs. Two aspects of maintenance deserve attention: (1) protocols for locating and rectifying defects, and for ensuring that noe new defects are introduced in the development phase of the software process; and (2) protocols for modification, enhancement, and upgrading. This article focuses primarily on the second aspect, the development of protocols to help increase the quality and reduce the costs associated with modifications, enhancements, and upgrades of existing software. This study developed parsimonious models and a relative complexity metric for complexity measurement of software that were used to rank the modules in the system relative to one another. Some success was achieved in using the models and the relative metric to identify maintenance-prone modules.

  9. The Development and Application of Composite Complexity Models and a Relative Complexity Metric in a Software Maintenance Environment

    NASA Astrophysics Data System (ADS)

    Hops, J. M.; Sherif, J. S.

    1994-01-01

    A great deal of effort is now being devoted to the study, analysis, prediction, and minimization of software maintenance expected cost, long before software is delivered to users or customers. It has been estimated that, on the average, the effort spent on software maintenance is as costly as the effort spent on all other software costs. Software design methods should be the starting point to aid in alleviating the problems of software maintenance complexity and high costs. Two aspects of maintenance deserve attention: (1) protocols for locating and rectifying defects, and for ensuring that no new defects are introduced in the development phase of the software process, and (2) protocols for modification, enhancement, and upgrading. This article focuses primarily on the second aspect, the development of protocols to help increase the quality and reduce the costs associated with modi fications, enhancements, and upgrades of existing software. This study developed parsimonious models and a relative complexity metric for complexity measurement of software that were used to rank the modules in the system relative to one another. Some success was achieved in using the models and the relative metric to identify maintenance-prone modules.

  10. Reference and PDF-manager software: complexities, support and workflow.

    PubMed

    Mead, Thomas L; Berryman, Donna R

    2010-10-01

    In the past, librarians taught reference management by training library users to use established software programs such as RefWorks or EndNote. In today's environment, there is a proliferation of Web-based programs that are being used by library clientele that offer a new twist on the well-known reference management programs. Basically, these new programs are PDF-manager software (e.g., Mendeley or Papers). Librarians are faced with new questions, issues, and concerns, given the new workflows and pathways that these PDF-manager programs present. This article takes a look at some of those. PMID:21058181

  11. Core Community Specifications for Electron Microprobe Operating Systems: Software, Quality Control, and Data Management Issues

    NASA Technical Reports Server (NTRS)

    Fournelle, John; Carpenter, Paul

    2006-01-01

    Modem electron microprobe systems have become increasingly sophisticated. These systems utilize either UNIX or PC computer systems for measurement, automation, and data reduction. These systems have undergone major improvements in processing, storage, display, and communications, due to increased capabilities of hardware and software. Instrument specifications are typically utilized at the time of purchase and concentrate on hardware performance. The microanalysis community includes analysts, researchers, software developers, and manufacturers, who could benefit from exchange of ideas and the ultimate development of core community specifications (CCS) for hardware and software components of microprobe instrumentation and operating systems.

  12. Generating Safety-Critical PLC Code From a High-Level Application Software Specification

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The benefits of automatic-application code generation are widely accepted within the software engineering community. These benefits include raised abstraction level of application programming, shorter product development time, lower maintenance costs, and increased code quality and consistency. Surprisingly, code generation concepts have not yet found wide acceptance and use in the field of programmable logic controller (PLC) software development. Software engineers at Kennedy Space Center recognized the need for PLC code generation while developing the new ground checkout and launch processing system, called the Launch Control System (LCS). Engineers developed a process and a prototype software tool that automatically translates a high-level representation or specification of application software into ladder logic that executes on a PLC. All the computer hardware in the LCS is planned to be commercial off the shelf (COTS), including industrial controllers or PLCs that are connected to the sensors and end items out in the field. Most of the software in LCS is also planned to be COTS, with only small adapter software modules that must be developed in order to interface between the various COTS software products. A domain-specific language (DSL) is a programming language designed to perform tasks and to solve problems in a particular domain, such as ground processing of launch vehicles. The LCS engineers created a DSL for developing test sequences of ground checkout and launch operations of future launch vehicle and spacecraft elements, and they are developing a tabular specification format that uses the DSL keywords and functions familiar to the ground and flight system users. The tabular specification format, or tabular spec, allows most ground and flight system users to document how the application software is intended to function and requires little or no software programming knowledge or experience. A small sample from a prototype tabular spec application is

  13. Controlling Combinatorial Complexity in Software and Malware Behavior Computation

    SciTech Connect

    Pleszkoch, Mark G; Linger, Richard C

    2015-01-01

    Virtually all software is out of intellectual control in that no one knows its full behavior. Software Behavior Computation (SBC) is a new technology for understanding everything software does. SBC applies the mathematics of denotational semantics implemented by function composition in Functional Trace Tables (FTTs) to compute the behavior of programs, expressed as disjoint cases of conditional concurrent assignments. In some circumstances, combinatorial explosions in the number of cases can occur when calculating the behavior of sequences of multiple branching structures. This paper describes computational methods that avoid combinatorial explosions. The predicates that control branching structures such as ifthenelses can be organized into three categories: 1) Independent, resulting in no behavior case explosion, 2) Coordinated, resulting in two behavior cases, or 3) Goaloriented, with potential exponential growth in the number of cases. Traditional FTT-based behavior computation can be augmented by two additional computational methods, namely, Single-Value Function Abstractions (SVFAs) and, introduced in this paper, Relational Trace Tables (RTTs). These methods can be applied to the three predicate categories to avoid combinatorial growth in behavior cases while maintaining mathematical correctness.

  14. Managing Complexity in the MSL/Curiosity Entry, Descent, and Landing Flight Software and Avionics Verification and Validation Campaign

    NASA Technical Reports Server (NTRS)

    Stehura, Aaron; Rozek, Matthew

    2013-01-01

    The complexity of the Mars Science Laboratory (MSL) mission presented the Entry, Descent, and Landing systems engineering team with many challenges in its Verification and Validation (V&V) campaign. This paper describes some of the logistical hurdles related to managing a complex set of requirements, test venues, test objectives, and analysis products in the implementation of a specific portion of the overall V&V program to test the interaction of flight software with the MSL avionics suite. Application-specific solutions to these problems are presented herein, which can be generalized to other space missions and to similar formidable systems engineering problems.

  15. Geometric Algebra Software for Teaching Complex Numbers, Vectors and Spinors.

    ERIC Educational Resources Information Center

    Lounesto, Pertti; And Others

    1990-01-01

    Presents a calculator-type computer program, CLICAL, in conjunction with complex number, vector, and other geometric algebra computations. Compares the CLICAL with other symbolic programs for algebra. (Author/YP)

  16. Preliminary flight software specification for the petite amateur Navy satellite (PANSAT)

    NASA Astrophysics Data System (ADS)

    Ford, Teresa O.

    1994-03-01

    PANSAT is a small, spread-spectrum, communications satellite under design at the Naval Postgraduate School. It will support a store and forward bulletin board system for use by the amateur radio community. The flight software is responsible for the autonomous telemetry collection and hardware control operations of the satellite, communications and file transfer protocols allowing access to the bulletin board system, and command interpretation and response to ground control commands. in this thesis, the complete flight software architecture and module interfaces are specified using the Estelle Format Description Technique. The module bodies dealing with communications and file transfer protocols are specified in detail in Estelle. The current design goat for the remainder of the flight software modules are discussed. Appendices include the preliminary flight software specification itself, a data flow diagram interpretation of the specification, and a summary of the Estelle syntax used.

  17. 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.

  18. Specific features of technetium mononuclear octahedral oxo complexes: A review

    SciTech Connect

    Sergienko, V. S. Churakov, A. V.

    2013-01-15

    The specific structural features of technetium mononuclear octahedral oxo complexes have been considered. The structures of d{sup 2}-Tc(V) mono- and dioxo complexes, d{sup 2}-Tc(V) pseudodioxo compounds (Tc(V) mono-oxo complexes with an additional multiply bonded RO{sup -} ligand), and d{sup 0}-Tc(VII) trioxo compounds are analyzed.

  19. Mathematical model and software complex for computer simulation of field emission electron sources

    SciTech Connect

    Nikiforov, Konstantin

    2015-03-10

    The software complex developed in MATLAB allows modelling of function of diode and triode structures based on field emission electron sources with complex sub-micron geometry, their volt-ampere characteristics, calculating distribution of electric field for educational and research needs. The goal of this paper is describing the physical-mathematical model, calculation methods and algorithms the software complex is based on, demonstrating the principles of its function and showing results of its work. For getting to know the complex, a demo version with graphical user interface is presented.

  20. Surveillance Analysis Computer System (SACS): Software requirements specification (SRS). Revision 2

    SciTech Connect

    Glasscock, J.A.

    1995-03-08

    This document is the primary document establishing requirements for the Surveillance Analysis Computer System (SACS) database, an Impact Level 3Q system. SACS stores information on tank temperatures, surface levels, and interstitial liquid levels. This information is retrieved by the customer through a PC-based interface and is then available to a number of other software tools. The software requirements specification (SRS) describes the system requirements for the SACS Project, and follows the Standard Engineering Practices (WHC-CM-6-1), Software Practices (WHC-CM-3-10) and Quality Assurance (WHC-CM-4-2, QR 19.0) policies.

  1. CARDS: A blueprint and environment for domain-specific software reuse

    NASA Technical Reports Server (NTRS)

    Wallnau, Kurt C.; Solderitsch, Anne Costa; Smotherman, Catherine

    1992-01-01

    CARDS (Central Archive for Reusable Defense Software) exploits advances in domain analysis and domain modeling to identify, specify, develop, archive, retrieve, understand, and reuse domain-specific software components. An important element of CARDS is to provide visibility into the domain model artifacts produced by, and services provided by, commercial computer-aided software engineering (CASE) technology. The use of commercial CASE technology is important to provide rich, robust support for the varied roles involved in a reuse process. We refer to this kind of use of knowledge representation systems as supporting 'knowledge-based integration.'

  2. Demontration of Integrated Optimization Software at the Baldwin Energy Complex

    SciTech Connect

    Rob James; John McDermott; Sanjay Patnaik; Steve Piche`

    2009-01-07

    This project encompassed the design, development, and demonstration of integrated online optimization systems at Dynegy Midwest Generation's Baldwin Energy Complex (BEC) located in Baldwin, Illinois. The overall project objective was to improve coal-based generation's emission profile, efficiency, maintenance requirements and plant asset life in order to enhance the long-term viability of the United States abundant coal resources. Five separate but integrated optimization products were developed, addressing combustion, sootblowing, SCR operations, overall unit thermal performance, and plant-wide availability optimization. Optimization results are inherently unit-specific and cannot be known for a particular generating unit in advance. However, NeuCo believed that the following were reasonable targets for the completed, integrated set of products: Furnace NOx reduction improvement by 5%, Heat rate improvement by 1.5%, Increase of annual Available MWh by 1.5%, Commensurate reductions in greenhouse gases, mercury, and particulates; and Commensurate increases in profitability from lower costs, improved reliability, and greater commercial availability. The goal during Phase I was to establish each system and demonstrate their integration in unified plant optimization. Efforts during Phase I focused on: (1) developing, deploying, integrating, and testing prototypes for each of the five products; (2) identifying and addressing issues required for the products to integrate with plant operations; and (3) systematically collecting and assimilating feedback to improve subsequent product releases. As described in the Phase II continuation application NeuCo successfully achieved the goal for Phase I. The goal of Phase II was to improve upon the products installed and tested in Phase I and to quantify the benefits of the integrated system. As this report documents, NeuCo has also successfully achieved the goal for Phase II. The overall results of the project, compared with the

  3. Forecast and restoration of geomagnetic activity indices by using the software-computational neural network complex

    NASA Astrophysics Data System (ADS)

    Barkhatov, Nikolay; Revunov, Sergey

    2010-05-01

    It is known that currently used indices of geomagnetic activity to some extent reflect the physical processes occurring in the interaction of the perturbed solar wind with Earth's magnetosphere. Therefore, they are connected to each other and with the parameters of near-Earth space. The establishment of such nonlinear connections is interest. For such purposes when the physical problem is complex or has many parameters the technology of artificial neural networks is applied. Such approach for development of the automated forecast and restoration method of geomagnetic activity indices with the establishment of creative software-computational neural network complex is used. Each neural network experiments were carried out at this complex aims to search for a specific nonlinear relation between the analyzed indices and parameters. At the core of the algorithm work program a complex scheme of the functioning of artificial neural networks (ANN) of different types is contained: back propagation Elman network, feed forward network, fuzzy logic network and Kohonen layer classification network. Tools of the main window of the complex (the application) the settings used by neural networks allow you to change: the number of hidden layers, the number of neurons in the layer, the input and target data, the number of cycles of training. Process and the quality of training the ANN is a dynamic plot of changing training error. Plot of comparison of network response with the test sequence is result of the network training. The last-trained neural network with established nonlinear connection for repeated numerical experiments can be run. At the same time additional training is not executed and the previously trained network as a filter input parameters get through and output parameters with the test event are compared. At statement of the large number of different experiments provided the ability to run the program in a "batch" mode is stipulated. For this purpose the user a

  4. Automated Translation of Safety Critical Application Software Specifications into PLC Ladder Logic

    NASA Technical Reports Server (NTRS)

    Leucht, Kurt W.; Semmel, Glenn S.

    2008-01-01

    The numerous benefits of automatic application code generation are widely accepted within the software engineering community. A few of these benefits include raising the abstraction level of application programming, shorter product development time, lower maintenance costs, and increased code quality and consistency. Surprisingly, code generation concepts have not yet found wide acceptance and use in the field of programmable logic controller (PLC) software development. Software engineers at the NASA Kennedy Space Center (KSC) recognized the need for PLC code generation while developing their new ground checkout and launch processing system. They developed a process and a prototype software tool that automatically translates a high-level representation or specification of safety critical application software into ladder logic that executes on a PLC. This process and tool are expected to increase the reliability of the PLC code over that which is written manually, and may even lower life-cycle costs and shorten the development schedule of the new control system at KSC. This paper examines the problem domain and discusses the process and software tool that were prototyped by the KSC software engineers.

  5. End-to-end observatory software modeling using domain specific languages

    NASA Astrophysics Data System (ADS)

    Filgueira, José M.; Bec, Matthieu; Liu, Ning; Peng, Chien; Soto, José

    2014-07-01

    The Giant Magellan Telescope (GMT) is a 25-meter extremely large telescope that is being built by an international consortium of universities and research institutions. Its software and control system is being developed using a set of Domain Specific Languages (DSL) that supports a model driven development methodology integrated with an Agile management process. This approach promotes the use of standardized models that capture the component architecture of the system, that facilitate the construction of technical specifications in a uniform way, that facilitate communication between developers and domain experts and that provide a framework to ensure the successful integration of the software subsystems developed by the GMT partner institutions.

  6. An algorithm to find critical execution paths of software based on complex network

    NASA Astrophysics Data System (ADS)

    Huang, Guoyan; Zhang, Bing; Ren, Rong; Ren, Jiadong

    2015-01-01

    The critical execution paths play an important role in software system in terms of reducing the numbers of test date, detecting the vulnerabilities of software structure and analyzing software reliability. However, there are no efficient methods to discover them so far. Thus in this paper, a complex network-based software algorithm is put forward to find critical execution paths (FCEP) in software execution network. First, by analyzing the number of sources and sinks in FCEP, software execution network is divided into AOE subgraphs, and meanwhile, a Software Execution Network Serialization (SENS) approach is designed to generate execution path set in each AOE subgraph, which not only reduces ring structure's influence on path generation, but also guarantees the nodes' integrity in network. Second, according to a novel path similarity metric, similarity matrix is created to calculate the similarity among sets of path sequences. Third, an efficient method is taken to cluster paths through similarity matrices, and the maximum-length path in each cluster is extracted as the critical execution path. At last, a set of critical execution paths is derived. The experimental results show that the FCEP algorithm is efficient in mining critical execution path under software complex network.

  7. Specification-based software sizing: An empirical investigation of function metrics

    NASA Technical Reports Server (NTRS)

    Jeffery, Ross; Stathis, John

    1993-01-01

    For some time the software industry has espoused the need for improved specification-based software size metrics. This paper reports on a study of nineteen recently developed systems in a variety of application domains. The systems were developed by a single software services corporation using a variety of languages. The study investigated several metric characteristics. It shows that: earlier research into inter-item correlation within the overall function count is partially supported; a priori function counts, in themself, do not explain the majority of the effort variation in software development in the organization studied; documentation quality is critical to accurate function identification; and rater error is substantial in manual function counting. The implication of these findings for organizations using function based metrics are explored.

  8. Computer software.

    PubMed

    Rosenthal, L E

    1986-10-01

    Software is the component in a computer system that permits the hardware to perform the various functions that a computer system is capable of doing. The history of software and its development can be traced to the early nineteenth century. All computer systems are designed to utilize the "stored program concept" as first developed by Charles Babbage in the 1850s. The concept was lost until the mid-1940s, when modern computers made their appearance. Today, because of the complex and myriad tasks that a computer system can perform, there has been a differentiation of types of software. There is software designed to perform specific business applications. There is software that controls the overall operation of a computer system. And there is software that is designed to carry out specialized tasks. Regardless of types, software is the most critical component of any computer system. Without it, all one has is a collection of circuits, transistors, and silicone chips. PMID:3536223

  9. The role of reliability graph models in assuring dependable operation of complex hardware/software systems

    NASA Technical Reports Server (NTRS)

    Patterson-Hine, F. A.; Davis, Gloria J.; Pedar, A.

    1991-01-01

    The complexity of computer systems currently being designed for critical applications in the scientific, commercial, and military arenas requires the development of new techniques for utilizing models of system behavior in order to assure 'ultra-dependability'. The complexity of these systems, such as Space Station Freedom and the Air Traffic Control System, stems from their highly integrated designs containing both hardware and software as critical components. Reliability graph models, such as fault trees and digraphs, are used frequently to model hardware systems. Their applicability for software systems has also been demonstrated for software safety analysis and the analysis of software fault tolerance. This paper discusses further uses of graph models in the design and implementation of fault management systems for safety critical applications.

  10. Counselor Cognitions: General and Domain-Specific Complexity

    ERIC Educational Resources Information Center

    Welfare, Laura E.; Borders, L. DiAnne

    2010-01-01

    Counselor cognitive complexity is an important factor in counseling efficacy. The Counselor Cognitions Questionnaire (L. E. Welfare, 2006) and the Washington University Sentence Completion Test (J. Loevinger & R. Wessler, 1970) were used to explore the nature of general and domain-specific cognitive complexity. Counseling experience, supervisory…

  11. Treated effluent disposal system process control computer software requirements and specification

    SciTech Connect

    Graf, F.A. Jr.

    1994-06-03

    The software requirements for the monitor and control system that will be associated with the effluent collection pipeline system known as the 200 Area Treated Effluent Disposal System is covered. The control logic for the two pump stations and specific requirements for the graphic displays are detailed.

  12. Managing Complexity in Next Generation Robotic Spacecraft: From a Software Perspective

    NASA Technical Reports Server (NTRS)

    Reinholtz, Kirk

    2008-01-01

    This presentation highlights the challenges in the design of software to support robotic spacecraft. Robotic spacecraft offer a higher degree of autonomy, however currently more capabilities are required, primarily in the software, while providing the same or higher degree of reliability. The complexity of designing such an autonomous system is great, particularly while attempting to address the needs for increased capabilities and high reliability without increased needs for time or money. The efforts to develop programming models for the new hardware and the integration of software architecture are highlighted.

  13. Hepsoft - an approach for up to date multi-platform deployment of HEP specific software

    NASA Astrophysics Data System (ADS)

    Roiser, S.

    2011-12-01

    LHC experiments are depending on a rich palette of software components to build their specific applications. These underlying software components include the ROOT analysis framework, the Geant4 simulation toolkit, monte carlo generators, grid middle-ware, graphics libraries, scripting languages, databases, tools, etc. which are provided centrally in up to date versions on multiple platforms (Linux, Mac, Windows). Until recently this set of packages has been tested and released in a tree like structure as a consistent set of versions across operating systems, architectures and compilers for LHC experiments only. Because of the tree like deployment these releases were only usable in connection with a configuration management tool which provided the proper build and run-time environments and was hindering other parties outside LHC from easily using this palette of packages. In a new approach the releases will be grouped in "flat structure" such that interested parties can start using it without configuration management, retaining all the above mentioned advantages. In addition to an increased usability the software shall also be distributed via system provided package deployment systems (rpm, apt, etc.). The approach of software deployment is following the ideas of providing a wide range of HEP specific software packages and tools in a coherent, up to date and modular way on multiple platforms. The target audience for such software deployments are individual developers or smaller development groups / experiments who don't have the resources to maintain this kind of infrastructure. This new software deployment strategy has already been successfully implemented for groups at CERN.

  14. Using Colored Stochastic Petri Net (CS-PN) software for protocol specification, validation, and evaluation

    NASA Technical Reports Server (NTRS)

    Zenie, Alexandre; Luguern, Jean-Pierre

    1987-01-01

    The specification, verification, validation, and evaluation, which make up the different steps of the CS-PN software are outlined. The colored stochastic Petri net software is applied to a Wound/Wait protocol decomposable into two principal modules: request or couple (transaction, granule) treatment module and wound treatment module. Each module is specified, verified, validated, and then evaluated separately, to deduce a verification, validation and evaluation of the complete protocol. The colored stochastic Petri nets tool is shown to be a natural extension of the stochastic tool, adapted to distributed systems and protocols, because the color conveniently takes into account the numerous sites, transactions, granules and messages.

  15. Formal Methods Specification and Verification Guidebook for Software and Computer Systems. Volume 1; Planning and Technology Insertion

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The Formal Methods Specification and Verification Guidebook for Software and Computer Systems describes a set of techniques called Formal Methods (FM), and outlines their use in the specification and verification of computer systems and software. Development of increasingly complex systems has created a need for improved specification and verification techniques. NASA's Safety and Mission Quality Office has supported the investigation of techniques such as FM, which are now an accepted method for enhancing the quality of aerospace applications. The guidebook provides information for managers and practitioners who are interested in integrating FM into an existing systems development process. Information includes technical and administrative considerations that must be addressed when establishing the use of FM on a specific project. The guidebook is intended to aid decision makers in the successful application of FM to the development of high-quality systems at reasonable cost. This is the first volume of a planned two-volume set. The current volume focuses on administrative and planning considerations for the successful application of FM.

  16. Specific Requirements of Physiotherapists on the Practical Use of Software in the Therapeutical Process.

    PubMed

    Messer-Misak, Karin; Egger, Rudolf

    2016-01-01

    The current healthcare system requires more effective management. New media and technology are supposed to support the demands of the current healthcare system. By the example of physiotherapy, the primary objective of this study was to define the specific requirements of therapists on the practical use of software which cover the administration, documentation and evaluation of the entire therapy process, including a database with pictures/videos about exercises which can be adapted individually by the therapists. Another objective was to show what conditions for a successful implementation of advanced applications during the entire treatment process have to be fulfilled. The approach of mixed-methods designs was chosen. In the first part a two-stage qualitative study was carried out, followed by a quantitative survey. The results show that the use of the software regarding the therapy-related part is dependent on how adaptable the software is to the special needs of the therapists, that the whole treatment process is mapped on the software and that an additional training during the professional practice must be implemented in order to deploy the use of the software successfully in the therapeutic process. PMID:27139399

  17. Ethical education in software engineering: responsibility in the production of complex systems.

    PubMed

    Génova, Gonzalo; González, M Rosario; Fraga, Anabel

    2007-12-01

    Among the various contemporary schools of moral thinking, consequence-based ethics, as opposed to rule-based, seems to have a good acceptance among professionals such as software engineers. But naïve consequentialism is intellectually too weak to serve as a practical guide in the profession. Besides, the complexity of software systems makes it very hard to know in advance the consequences that will derive from professional activities in the production of software. Therefore, following the spirit of well-known codes of ethics such as the ACM/IEEE's, we advocate for a more solid position in the ethical education of software engineers, which we call 'moderate deontologism', that takes into account both rules and consequences to assess the goodness of actions, and at the same time pays an adequate consideration to the absolute values of human dignity. In order to educate responsible professionals, however, this position should be complemented with a pedagogical approach to virtue ethics. PMID:18066681

  18. On the recognition of complex structures: Computer software using artificial intelligence applied to pattern recognition

    NASA Technical Reports Server (NTRS)

    Yakimovsky, Y.

    1974-01-01

    An approach to simultaneous interpretation of objects in complex structures so as to maximize a combined utility function is presented. Results of the application of a computer software system to assign meaning to regions in a segmented image based on the principles described in this paper and on a special interactive sequential classification learning system, which is referenced, are demonstrated.

  19. Combining Ontologies with Domain Specific Languages: A Case Study from Network Configuration Software

    NASA Astrophysics Data System (ADS)

    Miksa, Krzysztof; Sabina, Pawel; Kasztelnik, Marek

    One of the important aspects of Model-Driven Engineering (MDE) is to consider application-domain variability, which leads to creation of Domain Specific Languages (DSL). As with DSLs models are concise, easy to understand and maintain, this approach greatly increases the productivity and software quality. Usually, the DSLs in MDE are described with a metamodel and a concrete syntax definition. The models expressed in the DSL are linguistic instantiations of the language concepts found in the metamodel.

  20. Tools to aid the specification and design of flight software, appendix B

    NASA Technical Reports Server (NTRS)

    Bristow, G.

    1980-01-01

    The tasks that are normally performed during the specification and architecture design stages of software development are identified. Ways that tools could perform, or aid the performance, of such tasks are also identified. Much of the verification and analysis that is suggested is currently rarely performed during these early stages, but it is believed that this analysis should be done as early as possible so as to detect errors as early as possible.

  1. Host computer software specifications for a zero-g payload manhandling simulator

    NASA Technical Reports Server (NTRS)

    Wilson, S. W.

    1986-01-01

    The HP PASCAL source code was developed for the Mission Planning and Analysis Division (MPAD) of NASA/JSC, and takes the place of detailed flow charts defining the host computer software specifications for MANHANDLE, a digital/graphical simulator that can be used to analyze the dynamics of onorbit (zero-g) payload manhandling operations. Input and output data for representative test cases are contained.

  2. METU-SNP: an integrated software system for SNP-complex disease association analysis.

    PubMed

    Ustünkar, Gürkan; Aydın Son, Yeşim

    2011-01-01

    Recently, there has been increasing research to discover genomic biomarkers, haplotypes, and potentially other variables that together contribute to the development of diseases. Single Nucleotide Polymorphisms (SNPs) are the most common form of genomic variations and they can represent an individual’s genetic variability in greatest detail. Genome-wide association studies (GWAS) of SNPs, high-dimensional case-control studies, are among the most promising approaches for identifying disease causing variants. METU-SNP software is a Java based integrated desktop application specifically designed for the prioritization of SNP biomarkers and the discovery of genes and pathways related to diseases via analysis of the GWAS case-control data. Outputs of METU-SNP can easily be utilized for the downstream biomarkers research to allow the prediction and the diagnosis of diseases and other personalized medical approaches. Here, we introduce and describe the system functionality and architecture of the METU-SNP. We believe that the METU-SNP will help researchers with the reliable identification of SNPs that are involved in the etiology of complex diseases, ultimately supporting the development of personalized medicine approaches and targeted drug discoveries. PMID:22156365

  3. A discussion of higher order software concepts as they apply to functional requirements and specifications. [space shuttles and guidance

    NASA Technical Reports Server (NTRS)

    Hamilton, M.

    1973-01-01

    The entry guidance software functional requirements (requirements design phase), its architectural requirements (specifications design phase), and the entry guidance software verified code are discussed. It was found that the proper integration of designs at both the requirements and specifications levels are of high priority consideration.

  4. An Automated Method for Identifying Inconsistencies within Diagrammatic Software Requirements Specifications

    NASA Technical Reports Server (NTRS)

    Zhang, Zhong

    1997-01-01

    The development of large-scale, composite software in a geographically distributed environment is an evolutionary process. Often, in such evolving systems, striving for consistency is complicated by many factors, because development participants have various locations, skills, responsibilities, roles, opinions, languages, terminology and different degrees of abstraction they employ. This naturally leads to many partial specifications or viewpoints. These multiple views on the system being developed usually overlap. From another aspect, these multiple views give rise to the potential for inconsistency. Existing CASE tools do not efficiently manage inconsistencies in distributed development environment for a large-scale project. Based on the ViewPoints framework the WHERE (Web-Based Hypertext Environment for requirements Evolution) toolkit aims to tackle inconsistency management issues within geographically distributed software development projects. Consequently, WHERE project helps make more robust software and support software assurance process. The long term goal of WHERE tools aims to the inconsistency analysis and management in requirements specifications. A framework based on Graph Grammar theory and TCMJAVA toolkit is proposed to detect inconsistencies among viewpoints. This systematic approach uses three basic operations (UNION, DIFFERENCE, INTERSECTION) to study the static behaviors of graphic and tabular notations. From these operations, subgraphs Query, Selection, Merge, Replacement operations can be derived. This approach uses graph PRODUCTIONS (rewriting rules) to study the dynamic transformations of graphs. We discuss the feasibility of implementation these operations. Also, We present the process of porting original TCM (Toolkit for Conceptual Modeling) project from C++ to Java programming language in this thesis. A scenario based on NASA International Space Station Specification is discussed to show the applicability of our approach. Finally

  5. siRNA Design Software for a Target Gene-Specific RNA Interference

    PubMed Central

    Naito, Yuki; Ui-Tei, Kumiko

    2012-01-01

    RNA interference (RNAi) is a mechanism through which small interfering RNA (siRNA) induces sequence-specific posttranscriptional gene silencing. RNAi is commonly recognized as a powerful tool not only for functional genomics but also for therapeutic applications. Twenty-one-nucleotide-long siRNA suppresses the expression of the intended gene whose transcript possesses perfect complementarity to the siRNA guide strand. Hence, its silencing effect has been assumed to be extremely specific. However, accumulated evidences revealed that siRNA could downregulate unintended genes with partial complementarities mainly to the seven-nucleotide seed region of siRNA. This phenomenon is referred to as off-target effect. We have revealed that the capability to induce off-target effect is strongly correlated to the thermodynamic stability in siRNA seed-target duplex. For understanding accurate target gene function and successful therapeutic application, it may be critical to select a target gene-specific siRNA with minimized off-target effect. Here we present our siRNA design software for a target-specific RNAi. In addition, we also introduce the software programs open to the public for designing functional siRNAs. PMID:22701467

  6. siRNA Design Software for a Target Gene-Specific RNA Interference.

    PubMed

    Naito, Yuki; Ui-Tei, Kumiko

    2012-01-01

    RNA interference (RNAi) is a mechanism through which small interfering RNA (siRNA) induces sequence-specific posttranscriptional gene silencing. RNAi is commonly recognized as a powerful tool not only for functional genomics but also for therapeutic applications. Twenty-one-nucleotide-long siRNA suppresses the expression of the intended gene whose transcript possesses perfect complementarity to the siRNA guide strand. Hence, its silencing effect has been assumed to be extremely specific. However, accumulated evidences revealed that siRNA could downregulate unintended genes with partial complementarities mainly to the seven-nucleotide seed region of siRNA. This phenomenon is referred to as off-target effect. We have revealed that the capability to induce off-target effect is strongly correlated to the thermodynamic stability in siRNA seed-target duplex. For understanding accurate target gene function and successful therapeutic application, it may be critical to select a target gene-specific siRNA with minimized off-target effect. Here we present our siRNA design software for a target-specific RNAi. In addition, we also introduce the software programs open to the public for designing functional siRNAs. PMID:22701467

  7. UQLab - A Software Platform for Uncertainty Quantification of Complex System Models

    NASA Astrophysics Data System (ADS)

    Wang, C.; Duan, Q.; Gong, W.

    2014-12-01

    UQLab (Uncertainty quantification Laboratory) is a flexible, user-friendly software platform that integrates different kinds of UQ methods including experimental design, sensitivity analysis, uncertainty analysis, surrogate modeling and optimization methods to characterize uncertainty of complex system models. It is written in Python language and can run on all common operating systems. UQLab has a graphic user interface (GUI) that allows users to enter commands and output analysis results via pull-down menus. It is equipped with a model driver generator that allows any system model to be linked with the software. The only requirement is to make sure the executable code, control file and output file of interest of a model accessible by the software. Through two geophysics models: the Sacramento Soil Moisture Accounting Model (SAC-SMA) and Common Land Model (CoLM), this presentation intends to demonstrate that UQLab is an effective and easy UQ tool to use, and can be applied to a wide range of applications.

  8. Using formal specification in the Guidance and Control Software (GCS) experiment. Formal design and verification technology for life critical systems

    NASA Technical Reports Server (NTRS)

    Weber, Doug; Jamsek, Damir

    1994-01-01

    The goal of this task was to investigate how formal methods could be incorporated into a software engineering process for flight-control systems under DO-178B and to demonstrate that process by developing a formal specification for NASA's Guidance and Controls Software (GCS) Experiment. GCS is software to control the descent of a spacecraft onto a planet's surface. The GCS example is simplified from a real example spacecraft, but exhibits the characteristics of realistic spacecraft control software. The formal specification is written in Larch.

  9. Managing Complexity - Developing the Node Control Software For The International Space Station

    NASA Technical Reports Server (NTRS)

    Wood, Donald B.

    2000-01-01

    On December 4th, 1998 at 3:36 AM STS-88 (the space shuttle Endeavor) was launched with the "Node 1 Unity Module" in its payload bay. After working on the Space Station program for a very long time, that launch was one of the most beautiful sights I had ever seen! As the Shuttle proceeded to rendezvous with the Russian American module know as Zarya, I returned to Houston quickly to start monitoring the activation of the software I had spent the last 3 years working on. The FGB module (also known as "Zarya"), was grappled by the shuttle robotic arm, and connected to the Unity module. Crewmembers then hooked up the power and data connections between Zarya and Unity. On December 7th, 1998 at 9:49 PM CST the Node Control Software was activated. On December 15th, 1998, the Node-l/Zarya "cornerstone" of the International Space Station was left on-orbit. The Node Control Software (NCS) is the first software flown by NASA for the International Space Station (ISS). The ISS Program is considered the most complex international engineering effort ever undertaken. At last count some 18 countries are active partners in this global venture. NCS has performed all of its intended functions on orbit, over 200 miles above us. I'll be describing how we built the NCS software.

  10. Practical Findings from Applying the PSD Model for Evaluating Software Design Specifications

    NASA Astrophysics Data System (ADS)

    Räisänen, Teppo; Lehto, Tuomas; Oinas-Kukkonen, Harri

    This paper presents practical findings from applying the PSD model to evaluating the support for persuasive features in software design specifications for a mobile Internet device. On the one hand, our experiences suggest that the PSD model fits relatively well for evaluating design specifications. On the other hand, the model would benefit from more specific heuristics for evaluating each technique to avoid unnecessary subjectivity. Better distinction between the design principles in the social support category would also make the model easier to use. Practitioners who have no theoretical background can apply the PSD model to increase the persuasiveness of the systems they design. The greatest benefit of the PSD model for researchers designing new systems may be achieved when it is applied together with a sound theory, such as the Elaboration Likelihood Model. Using the ELM together with the PSD model, one may increase the chances for attitude change.

  11. Assessing software upgrades, plan properties and patient geometry using intensity modulated radiation therapy (IMRT) complexity metrics

    SciTech Connect

    McGarry, Conor K.; Chinneck, Candice D.; O'Toole, Monica M.; O'Sullivan, Joe M; Prise, Kevin M.; Hounsell, Alan R.

    2011-04-15

    Purpose: The aim of this study is to compare the sensitivity of different metrics to detect differences in complexity of intensity modulated radiation therapy (IMRT) plans following upgrades, changes to planning parameters, and patient geometry. Correlations between complexity metrics are also assessed. Method: A program was developed to calculate a series of metrics used to describe the complexity of IMRT fields using monitor units (MUs) and multileaf collimator files: Modulation index (MI), modulation complexity score (MCS), and plan intensity map variation (PIMV). Each metric, including the MUs, was used to assess changes in beam complexity for six prostate patients, following upgrades in the inverse planning optimization software designed to incorporate direct aperture optimization (DAO). All beams were delivered to a 2D ionization chamber array and compared to those calculated using gamma analysis. Each complexity metric was then calculated for all beams, on a different set of six prostate IMRT patients, to assess differences between plans calculated using different minimum field sizes and different maximum segment numbers. Different geometries, including CShape, prostate, and head and neck phantoms, were also assessed using the metrics. Correlations between complexity metrics were calculated for 20 prostate IMRT patients. Results: MU, MCS, MI, and PIMV could all detect reduced complexity following an upgrade to the optimization leaf sequencer, although only MI and MCS could detect a reduction in complexity when one-step optimization (DAO) was employed rather than two-step optimization. All metrics detected a reduction in complexity when the minimum field size was increased from 1 to 4 cm and all apart from PIMV detected reduced complexity when the number of segments was significantly reduced. All metrics apart from MI showed differences in complexity depending on the treatment site. Significant correlations exist between all metrics apart from MI and PIMV for

  12. Hardware-Software Complex for a Study of High-Power Microwave Pulse Parameters

    NASA Astrophysics Data System (ADS)

    Gal'chenko, V. G.; Gladkova, T. A.

    2016-06-01

    An instrumental complex is developed for a study of high-power microwave pulse parameters. The complex includes a bench for calibrating detectors and a measuring instrument for evaluating the microwave pulse parameters. The calibration of the measurement channels of microwave pulses propagating through different elements of the experimental setup is an important problem of experimental research. The available software for calibration of the measuring channels has a significant disadvantage related with the necessity of input of a number of additional parameters directly into the program. The software realized in the Qt 4.5 C++ medium is presented, which significantly simplifies the process of calibration data input in the dialog mode of setting the parameters of the medium of microwave pulse propagation.

  13. Reducing the complexity of the software design process with object-oriented design

    NASA Technical Reports Server (NTRS)

    Schuler, M. P.

    1991-01-01

    Designing software is a complex process. How object-oriented design (OOD), coupled with formalized documentation and tailored object diagraming techniques, can reduce the complexity of the software design process is described and illustrated. The described OOD methodology uses a hierarchical decomposition approach in which parent objects are decomposed into layers of lower level child objects. A method of tracking the assignment of requirements to design components is also included. Increases in the reusability, portability, and maintainability of the resulting products are also discussed. This method was built on a combination of existing technology, teaching experience, consulting experience, and feedback from design method users. The discussed concepts are applicable to hierarchal OOD processes in general. Emphasis is placed on improving the design process by documenting the details of the procedures involved and incorporating improvements into those procedures as they are developed.

  14. Hardware-software complex for chlorophyll estimation in phytocenoses under field conditions

    NASA Astrophysics Data System (ADS)

    Yatsenko, V.; Kochubey, S.; Donets, V.; Kazantsev, T.

    2005-10-01

    Vegetation is a sensitive indicator suitable for testing of ecological stresses and natural anomalies of the technogenic character. First, it is determined by the prompt response of photosynthetic apparatus to changes of environmental conditions, mainly by change of green pigment (chlorophyll) content in leaves. Second, the specific kind of a reflectance spectrum of leaves is due to chlorophyll presence in them, and the area in the range of 500-80 nm is extremely sensitive to variations of its pigment content. Thirdly, there are interesting results now concerning spectral properties of leaves and crops canopies obtaining with high-resolution spectroscopy. The data are high informative in relation to content of chlorophyll and some other biochemical constituents of a cell. The high resistance to various types of noises is inherent to methods developed on the basis of such spectral data. We have developed a method for chlorophyll estimation using the 1-st derivative plots of reflectance spectral curves. The method gives good results for plant-soil systems with both for 100% and incomplete projective covering as our simulation models show. Field measurements of chlorophyll content in closed and open canopies crops confirm the results. A hardware-software complex has been produced by us for chlorophyll determining under field conditions. It consists of spectral and computing blocks. First of them is a two-beam spectrometer of high resolution supplied by a system to visualize of measured object. The irradiance and temperature sensors are included to the spectral block as well as GPS-receiver. The following technical characteristics are inherent to the block: spectral range 500-800 nm, band-pass 1.5 nm, field of view 16x16o, scanning time 0.1-1.0 s, dynamic range of signal 1:1024 (10 bit), signal/noise ratio 400, amount of pixels in image 1240, range of estimated chlorophyll concentrations 1.5-8.0 mg/dm2, supply voltage 12 V, weight 8 kg. Computing block is intended for

  15. Specificity and complexity in bacterial quorum-sensing systems

    PubMed Central

    Hawver, Lisa A.; Jung, Sarah A.; Ng, Wai-Leung

    2016-01-01

    Quorum sensing (QS) is a microbial cell-to-cell communication process that relies on the production and detection of chemical signals called autoinducers (AIs) to monitor cell density and species complexity in the population. QS allows bacteria to behave as a cohesive group and coordinate collective behaviors. While most QS receptors display high specificity to their AI ligands, others are quite promiscuous in signal detection. How do specific QS receptors respond to their cognate signals with high fidelity? Why do some receptors maintain low signal recognition specificity? In addition, many QS systems are composed of multiple intersecting signaling pathways: what are the benefits of preserving such a complex signaling network when a simple linear ‘one-to-one’ regulatory pathway seems sufficient to monitor cell density? Here, we will discuss different molecular mechanisms employed by various QS systems that ensure productive and specific QS responses. Moreover, the network architectures of some well-characterized QS circuits will be reviewed to understand how the wiring of different regulatory components achieves different biological goals. PMID:27354348

  16. Complex software dedicated for design and simulation of LPCE process for heavy water detritiation

    SciTech Connect

    Bornea, A.; Petrutiu, C.; Zamfirache, M.

    2015-03-15

    The main purpose of this paper is to present a comprehensive software, SICA, designed to be used in water-hydrogen liquid phase catalytic exchange process (LPCE). The software calculates the water-gas catalytic isotopic exchange process, following the transfer of any H, D or T isotope from water to gas and vice versa. This software is useful for both design and laboratory-based research; the type of the catalytic filling (ordered or random) can be defined for any of these 2 cases, the isotopic calculation being specific to the package type. For the laboratory-based research, the performance of a catalytic packing can be determined by knowing the type and by using experimental results. Performance of the mixed catalytic packing is defined by mass transfer constants for each catalytic and hydrophilic package in that specific arrangement, and also for the isotope whose transfer is studied from one phase to another. Also, it has been established a link between these constants and commonly used parameters for the fillings performance defined by HETP (Height Equivalent of Theoretical Plate). To demonstrate the performance of the software, we present a comparative analysis of water-gas catalytic isotopic exchange on a column equipped with 3 types of filling: successive layers, random and structured (ordered package filled with catalyst). The program can be used for the LPCE process calculation, process used at detritiation facilities for CANDU reactors or fusion reactors. (authors)

  17. A frame-based domain-specific language for rapid prototyping of FPGA-based software-defined radios

    NASA Astrophysics Data System (ADS)

    Ouedraogo, Ganda Stephane; Gautier, Matthieu; Sentieys, Olivier

    2014-12-01

    The field-programmable gate array (FPGA) technology is expected to play a key role in the development of software-defined radio (SDR) platforms. As this technology evolves, low-level designing methods for prototyping FPGA-based applications did not change throughout the decades. In the outstanding context of SDR, it is important to rapidly implement new waveforms to fulfill such a stringent flexibility paradigm. At the current time, different proposals have defined, through software-based approaches, some efficient methods to prototype SDR waveforms in a processor-based running environment. This paper describes a novel design flow for FPGA-based SDR applications. This flow relies upon high-level synthesis (HLS) principles and leverages the nascent HLS tools. Its entry point is a domain-specific language (DSL) which handles the complexity of programming an FPGA and integrates some SDR features so as to enable automatic waveform control generation from a data frame model. Two waveforms (IEEE 802.15.4 and IEEE 802.11a) have been designed and explored via this new methodology, and the results are highlighted in this paper.

  18. FACET: A simulation software framework for modeling complex societal processes and interactions

    SciTech Connect

    Christiansen, J. H.

    2000-06-02

    FACET, the Framework for Addressing Cooperative Extended Transactions, was developed at Argonne National Laboratory to address the need for a simulation software architecture in the style of an agent-based approach, but with sufficient robustness, expressiveness, and flexibility to be able to deal with the levels of complexity seen in real-world social situations. FACET is an object-oriented software framework for building models of complex, cooperative behaviors of agents. It can be used to implement simulation models of societal processes such as the complex interplay of participating individuals and organizations engaged in multiple concurrent transactions in pursuit of their various goals. These transactions can be patterned on, for example, clinical guidelines and procedures, business practices, government and corporate policies, etc. FACET can also address other complex behaviors such as biological life cycles or manufacturing processes. To date, for example, FACET has been applied to such areas as land management, health care delivery, avian social behavior, and interactions between natural and social processes in ancient Mesopotamia.

  19. Immunogenetic Management Software: a new tool for visualization and analysis of complex immunogenetic datasets

    PubMed Central

    Johnson, Z. P.; Eady, R. D.; Ahmad, S. F.; Agravat, S.; Morris, T; Else, J; Lank, S. M.; Wiseman, R. W.; O’Connor, D. H.; Penedo, M. C. T.; Larsen, C. P.

    2012-01-01

    Here we describe the Immunogenetic Management Software (IMS) system, a novel web-based application that permitsmultiplexed analysis of complex immunogenetic traits that are necessary for the accurate planning and execution of experiments involving large animal models, including nonhuman primates. IMS is capable of housing complex pedigree relationships, microsatellite-based MHC typing data, as well as MHC pyrosequencing expression analysis of class I alleles. It includes a novel, automated MHC haplotype naming algorithm and has accomplished an innovative visualization protocol that allows users to view multiple familial and MHC haplotype relationships through a single, interactive graphical interface. Detailed DNA and RNA-based data can also be queried and analyzed in a highly accessible fashion, and flexible search capabilities allow experimental choices to be made based on multiple, individualized and expandable immunogenetic factors. This web application is implemented in Java, MySQL, Tomcat, and Apache, with supported browsers including Internet Explorer and Firefox onWindows and Safari on Mac OS. The software is freely available for distribution to noncommercial users by contacting Leslie. kean@emory.edu. A demonstration site for the software is available at http://typing.emory.edu/typing_demo, user name: imsdemo7@gmail.com and password: imsdemo. PMID:22080300

  20. Immunogenetic Management Software: a new tool for visualization and analysis of complex immunogenetic datasets.

    PubMed

    Johnson, Z P; Eady, R D; Ahmad, S F; Agravat, S; Morris, T; Else, J; Lank, S M; Wiseman, R W; O'Connor, D H; Penedo, M C T; Larsen, C P; Kean, L S

    2012-04-01

    Here we describe the Immunogenetic Management Software (IMS) system, a novel web-based application that permits multiplexed analysis of complex immunogenetic traits that are necessary for the accurate planning and execution of experiments involving large animal models, including nonhuman primates. IMS is capable of housing complex pedigree relationships, microsatellite-based MHC typing data, as well as MHC pyrosequencing expression analysis of class I alleles. It includes a novel, automated MHC haplotype naming algorithm and has accomplished an innovative visualization protocol that allows users to view multiple familial and MHC haplotype relationships through a single, interactive graphical interface. Detailed DNA and RNA-based data can also be queried and analyzed in a highly accessible fashion, and flexible search capabilities allow experimental choices to be made based on multiple, individualized and expandable immunogenetic factors. This web application is implemented in Java, MySQL, Tomcat, and Apache, with supported browsers including Internet Explorer and Firefox on Windows and Safari on Mac OS. The software is freely available for distribution to noncommercial users by contacting Leslie.kean@emory.edu. A demonstration site for the software is available at http://typing.emory.edu/typing_demo , user name: imsdemo7@gmail.com and password: imsdemo. PMID:22080300

  1. Actinide-specific complexing agents: their structural and solution chemistry

    SciTech Connect

    Raymond, K.N.; Freeman, G.E.; Kappel, M.J.

    1983-07-01

    The synthesis of a series of tetracatecholate ligands designed to be specific for Pu(IV) and other actinide(IV) ions has been achieved. Although these compounds are very effective as in vivo plutonium removal agents, potentiometric and voltammetric data indicate that at neutral pH full complexation of the Pu(IV) ion by all four catecholate groups does not occur. Spectroscopic results indicate that the tetracatecholates, 3,4,3-LICAMS and 3,4,3-LICAMC, complex Am(III). The Am(IV)/(III)-catecholate couple (where catecholate = 3,4,3-LICAMS or 3,4,3-LICAMC) is not observed, but may not be observable due to the large currents associated with ligand oxidation. However, within the potential range where ligand oxidation does not occur, these experiments indicate that the reduction potential of free Am(IV)/(III) is probably greater than or equal to + 2.6 V vs NHE or higher. Proof of the complexation of americium in the trivalent oxidation state by 3,4,3-LICAMS and 3,4,3-LICAMC elimates the possibility of tetracatholates stabilizing Am(IV) in vivo.

  2. CellProfiler Analyst: data exploration and analysis software for complex image-based screens

    PubMed Central

    Jones, Thouis R; Kang, In Han; Wheeler, Douglas B; Lindquist, Robert A; Papallo, Adam; Sabatini, David M; Golland, Polina; Carpenter, Anne E

    2008-01-01

    Background Image-based screens can produce hundreds of measured features for each of hundreds of millions of individual cells in a single experiment. Results Here, we describe CellProfiler Analyst, open-source software for the interactive exploration and analysis of multidimensional data, particularly data from high-throughput, image-based experiments. Conclusion The system enables interactive data exploration for image-based screens and automated scoring of complex phenotypes that require combinations of multiple measured features per cell. PMID:19014601

  3. Project evaluates POSC specifications for infill drilling. [Petrochemical Open Software Corp

    SciTech Connect

    Zahniser, D.L. ); Merritt, R.W. ); Chan, C.K. )

    1994-05-16

    A project is under way to build data-loading tools and create an integrated oil and gas production data base using specifications developed during the last 3 years by the Petrotechnical Open Software Corp. (POSC). The Industry Pilot Project (IPP) Phase 1 is a collaborative effort between seven oil companies. The participating oil companies have provided a large set of data from a producing North American oil and gas field and money, hardware, and personnel. Many companies have already streamlined their infill drilling processes and receive significant incremental benefits. But current information technology can often be a stumbling block. Cross-disciplinary use of information is the key goal of these streamlining efforts, but much time is lost in finding, reformatting, accessing, and determining the quality of data. This project sets out to prove how POSC specifications can help reduce the cost and time for developing a field, improved the quality of the decision-making process, minimize the number of communication barriers and, most importantly, change technology from a hurdle to a seamless step. The project demonstrates that POSC specifications are an enabling technology that can dramatically improve the way oil companies and suppliers operate.

  4. Would Boys and Girls Benefit from Gender-Specific Educational Software?

    ERIC Educational Resources Information Center

    Luik, Piret

    2011-01-01

    Most boys and girls interact differently with educational software and have different preferences for the design of educational software. The question is whether the usage of educational software has the same consequences for both genders. This paper investigates the characteristics of drill-and-practice programmes or drills that are efficient for…

  5. Increasing quality and managing complexity in neuroinformatics software development with continuous integration

    PubMed Central

    Zaytsev, Yury V.; Morrison, Abigail

    2013-01-01

    High quality neuroscience research requires accurate, reliable and well maintained neuroinformatics applications. As software projects become larger, offering more functionality and developing a denser web of interdependence between their component parts, we need more sophisticated methods to manage their complexity. If complexity is allowed to get out of hand, either the quality of the software or the speed of development suffer, and in many cases both. To address this issue, here we develop a scalable, low-cost and open source solution for continuous integration (CI), a technique which ensures the quality of changes to the code base during the development procedure, rather than relying on a pre-release integration phase. We demonstrate that a CI-based workflow, due to rapid feedback about code integration problems and tracking of code health measures, enabled substantial increases in productivity for a major neuroinformatics project and additional benefits for three further projects. Beyond the scope of the current study, we identify multiple areas in which CI can be employed to further increase the quality of neuroinformatics projects by improving development practices and incorporating appropriate development tools. Finally, we discuss what measures can be taken to lower the barrier for developers of neuroinformatics applications to adopt this useful technique. PMID:23316158

  6. The Evolution of Software and Its Impact on Complex System Design in Robotic Spacecraft Embedded Systems

    NASA Technical Reports Server (NTRS)

    Butler, Roy

    2013-01-01

    The growth in computer hardware performance, coupled with reduced energy requirements, has led to a rapid expansion of the resources available to software systems, driving them towards greater logical abstraction, flexibility, and complexity. This shift in focus from compacting functionality into a limited field towards developing layered, multi-state architectures in a grand field has both driven and been driven by the history of embedded processor design in the robotic spacecraft industry.The combinatorial growth of interprocess conditions is accompanied by benefits (concurrent development, situational autonomy, and evolution of goals) and drawbacks (late integration, non-deterministic interactions, and multifaceted anomalies) in achieving mission success, as illustrated by the case of the Mars Reconnaissance Orbiter. Approaches to optimizing the benefits while mitigating the drawbacks have taken the form of the formalization of requirements, modular design practices, extensive system simulation, and spacecraft data trend analysis. The growth of hardware capability and software complexity can be expected to continue, with future directions including stackable commodity subsystems, computer-generated algorithms, runtime reconfigurable processors, and greater autonomy.

  7. A recombinant antibody with the antigen-specific, major histocompatibility complex-restricted specificity of T cells.

    PubMed Central

    Andersen, P S; Stryhn, A; Hansen, B E; Fugger, L; Engberg, J; Buus, S

    1996-01-01

    Specific recognition of peptide/major histocompatibility complex (MHC) molecule complexes by the T-cell receptor is a key reaction in the specific immune response. Antibodies against peptide/MHC complexes would therefore be valuable tools in studying MHC function and T-cell recognition and might lead to novel approaches in immunotherapy. However, it has proven difficult to generate antibodies with the specificity of T cells by conventional hybridoma techniques. Here we report that the phage display technology is a feasible alternative to generate antibodies recognizing specific, predetermined peptide/MHC complexes. Images Fig. 2 PMID:8700842

  8. Modeling of the competition life cycle using the software complex of cellular automata PyCAlab

    NASA Astrophysics Data System (ADS)

    Berg, D. B.; Beklemishev, K. A.; Medvedev, A. N.; Medvedeva, M. A.

    2015-11-01

    The aim of the work is to develop a numerical model of the life cycle of competition on the basis of software complex cellular automata PyCAlab. The model is based on the general patterns of growth of various systems in resource-limited settings. At examples it is shown that the period of transition from an unlimited growth of the market agents to the stage of competitive growth takes quite a long time and may be characterized as monotonic. During this period two main strategies of competitive selection coexist: 1) capture of maximum market space with any reasonable costs; 2) saving by reducing costs. The obtained results allow concluding that the competitive strategies of companies must combine two mentioned types of behavior, and this issue needs to be given adequate attention in the academic literature on management. The created numerical model may be used for market research when developing of the strategies for promotion of new goods and services.

  9. 77 FR 9252 - Meeting for Software Developers on the Technical Specifications for Common Formats for Patient...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-16

    ... events as announced in the Federal Register on November 1, 2011: 76 FR 67456-67457. The Software... Rule), published in the Federal Register on November 21, 2008: 73 FR 70731-70814. AHRQ coordinates the... HUMAN SERVICES Agency for Healthcare Research and Quality Meeting for Software Developers on...

  10. Software/firmware design specification for 10-MWe solar-thermal central-receiver pilot plant

    SciTech Connect

    Ladewig, T.D.

    1981-03-01

    The software and firmware employed for the operation of the Barstow Solar Pilot Plant are completely described. The systems allow operator control of up to 2048 heliostats, and include the capability of operator-commanded control, graphic displays, status displays, alarm generation, system redundancy, and interfaces to the Operational Control System, the Data Acquisition System, and the Beam Characterization System. The requirements are decomposed into eleven software modules for execution in the Heliostat Array Controller computer, one firmware module for execution in the Heliostat Field Controller microprocessor, and one firmware module for execution in the Heliostat Controller microprocessor. The design of the modules to satisfy requirements, the interfaces between the computers, the software system structure, and the computers in which the software and firmware will execute are detailed. The testing sequence for validation of the software/firmware is described. (LEW)

  11. Exploring the specificities of glycan-binding proteins using glycan array data and the GlycoSearch software

    PubMed Central

    Kletter, Doron; Curnutte, Bryan; Maupin, Kevin; Bern, Marshall; Haab, Brian B.

    2015-01-01

    Summary The glycan array is a powerful tool for investigating the specificities of glycan-binding proteins. By incubating a glycan-binding protein on a glycan array, the relative binding to hundreds of different oligosaccharides can be quantified in parallel. Based on these data, much information can be obtained about the preference of a glycan-binding protein for specific subcomponents of oligosaccharides, or motifs. In many cases the analysis and interpretation of glycan array data can be time consuming and imprecise if done manually. Recently we developed software, called GlycoSearch, to facilitate the analysis and interpretation of glycan array data based on the previously developed methods called Motif Segregation and Outlier Motif Analysis. Here we describe the principles behind the software, the use of the software, and an example application. The automated, objective, and precise analysis of glycan array data should enhance the value of the data for a broad range of research applications. PMID:25753713

  12. Software design specification. Part 2: Orbital Flight Test (OFT) detailed design specification. Volume 3: Applications. Book 2: System management

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The functions performed by the systems management (SM) application software are described along with the design employed to accomplish these functions. The operational sequences (OPS) control segments and the cyclic processes they control are defined. The SM specialist function control (SPEC) segments and the display controlled 'on-demand' processes that are invoked by either an OPS or SPEC control segment as a direct result of an item entry to a display are included. Each processing element in the SM application is described including an input/output table and a structured control flow diagram. The flow through the module and other information pertinent to that process and its interfaces to other processes are included.

  13. Network, system, and status software enhancements for the autonomously managed electrical power system breadboard. Volume 3: Commands specification

    NASA Technical Reports Server (NTRS)

    Mckee, James W.

    1990-01-01

    This volume (3 of 4) contains the specification for the command language for the AMPS system. The volume contains a requirements specification for the operating system and commands and a design specification for the operating system and command. The operating system and commands sits on top of the protocol. The commands are an extension of the present set of AMPS commands in that the commands are more compact, allow multiple sub-commands to be bundled into one command, and have provisions for identifying the sender and the intended receiver. The commands make no change to the actual software that implement the commands.

  14. Data verification of a hardware-software complex of sounding an ionosphere and ionosonde DPS-4

    NASA Astrophysics Data System (ADS)

    Smirnov, Vladimir; Ruzhin, Yuri; Smirnova, Elena; Skobelkin, Vladimir; Tynyankin, Sergey

    Appeared in recent years, opportunities to use as a source of signals used to determine the parameters of the ionosphere, the spacecraft global navigation satellite systems GLONASS and GPS are not currently in widespread use practices ionospheric wave frequency and radio centers and dispatch services. Given the urgency of the discussed areas of research, long experiment whose purpose is to conduct a comparative analysis of the results of determining the critical frequency of F2-layer of the ionosphere in two ways - vertical sounding (ionosonde DPS-4) and radio translucence track "satellite-the Earth" with signals using GLONASS satellites and GPS was started in 2013. For a comparative analysis of the results the hardware-software complex ionospheric soundings (HSCIS) was located at territory of the Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation of the Russian Academy of Sciences. HSCIS product includes a personal computer with it specialized software, a dual-frequency navigation receiver and small receiving antenna. Used in the product receiver developed by NovAtel allows us to receive the signals of the navigation systems GPS/GLONASS and maintain their processing in real time. Location receiver determined autonomously: antenna position - 55.76o N, 37.94o E, coordinates ionosonde DPS-4 - 55.5o N, 37.3o E. In fact, both devices were in close proximity, which it allows for the identity conditions of observation. Both devices operate in real time. Ionosonde DPS- 4 gave the ionosphere parameters every 15 minutes, HSCIS - every minute. Information from both instruments displayed on the screen monitors, and recorded in the memory used by computers. Along with the numerical parameters on the monitor products HSCIS displayed time course of the critical frequency F2- layer of the ionosphere obtained from observations of the nearest navigation satellite. When limiting elevation observations 15o simultaneous use of navigation satellites can

  15. Web-based software tool for constraint-based design specification of synthetic biological systems.

    PubMed

    Oberortner, Ernst; Densmore, Douglas

    2015-06-19

    miniEugene provides computational support for solving combinatorial design problems, enabling users to specify and enumerate designs for novel biological systems based on sets of biological constraints. This technical note presents a brief tutorial for biologists and software engineers in the field of synthetic biology on how to use miniEugene. After reading this technical note, users should know which biological constraints are available in miniEugene, understand the syntax and semantics of these constraints, and be able to follow a step-by-step guide to specify the design of a classical synthetic biological system-the genetic toggle switch.1 We also provide links and references to more information on the miniEugene web application and the integration of the miniEugene software library into sophisticated Computer-Aided Design (CAD) tools for synthetic biology ( www.eugenecad.org ). PMID:25426642

  16. Waste Receiving and Processing Facility Module 1 Data Management System Software Requirements Specification

    SciTech Connect

    Brann, E.C. II

    1994-09-09

    This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-026). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal.

  17. Waste Receiving and Processing Facility Module 1 Data Management System software requirements specification

    SciTech Connect

    Rosnick, C.K.

    1996-04-19

    This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-0126). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal.

  18. Datgan, a reusable software system for facile interrogation and visualization of complex transcription profiling data

    PubMed Central

    2011-01-01

    Background We introduce Glaucoma Discovery Platform (GDP), an online environment for facile visualization and interrogation of complex transcription profiling datasets for glaucoma. We also report the availability of Datgan, the suite of scripts that was developed to construct GDP. This reusable software system complements existing repositories such as NCBI GEO or EBI ArrayExpress as it allows the construction of searchable databases to maximize understanding of user-selected transcription profiling datasets. Description Datgan scripts were used to construct both the underlying data tables and the web interface that form GDP. GDP is populated using data from a mouse model of glaucoma. The data was generated using the DBA/2J strain, a widely used mouse model of glaucoma. The DBA/2J-Gpnmb+ strain provided a genetically matched control strain that does not develop glaucoma. We separately assessed both the retina and the optic nerve head, important tissues in glaucoma. We used hierarchical clustering to identify early molecular stages of glaucoma that could not be identified using morphological assessment of disease. GDP has two components. First, an interactive search and retrieve component provides the ability to assess gene(s) of interest in all identified stages of disease in both the retina and optic nerve head. The output is returned in graphical and tabular format with statistically significant differences highlighted for easy visual analysis. Second, a bulk download component allows lists of differentially expressed genes to be retrieved as a series of files compatible with Excel. To facilitate access to additional information available for genes of interest, GDP is linked to selected external resources including Mouse Genome Informatics and Online Medelian Inheritance in Man (OMIM). Conclusion Datgan-constructed databases allow user-friendly access to datasets that involve temporally ordered stages of disease or developmental stages. Datgan and GDP are

  19. STATIC AND KINETIC SITE-SPECIFIC PROTEIN-DNA PHOTOCROSSLINKING: ANALYSIS OF BACTERIAL TRANSCRIPTION INITIATION COMPLEXES

    PubMed Central

    Naryshkin, Nikolai; Druzhinin, Sergei; Revyakin, Andrei; Kim, Younggyu; Mekler, Vladimir; Ebright, Richard H.

    2009-01-01

    Static site-specific protein-DNA photocrosslinking permits identification of protein-DNA interactions within multiprotein-DNA complexes. Kinetic site-specific protein-DNA photocrosslinking--involving rapid-quench-flow mixing and pulsed-laser irradiation--permits elucidation of pathways and kinetics of formation of protein-DNA interactions within multiprotein-DNA complexes. We present detailed protocols for application of static and kinetic site-specific protein-DNA photocrosslinking to bacterial transcription initiation complexes. PMID:19378179

  20. A theory for graph-based language specification, analysis, and mapping with application to the development of parallel software

    SciTech Connect

    Bailor, P.D.

    1989-01-01

    This investigation develops a generalized formal language theory model and associated theorems for the specification, analysis, and mapping of graphs and graph-based languages. The developed model is defined as a graph generative system, and the model is analyzed from a set theoretic, formal language, algebraic, and abstract automata perspective. As a result of the analysis, numerous theorems pertaining to the properties of the model, graphs, and graph-based languages are derived. Additionally, the graph generative system model serves as the basis for applying graph-based languages to areas such as the specification and design of software and visual programming. The specific application area emphasized is the use of graph-based languages as user friendly interfaces for wide-spectrum languages that include structures for representing parallelism. The goal of this approach is to provide an effective, efficient, and formal method for the specification, design, and rapid prototyping of parallel software. To demonstrate the utility of the theory and the feasibility of the application, two models of parallel computation are chosen. The widely used Petri net model of parallel computation is formalized as a graph-based language. The Petri net syntax is formally mapped into the corresponding syntax of a Communicating Sequential Processes (CSP) model of parallel computation where CSP is used as the formalism for extended wide-spectrum languages. Finally, the Petri net to CSP mapping is analyzed from a behavioral perspective to demonstrate that the CSP specification formally behaves in a manner equivalent to the Petri net model.

  1. Theory for graph-based language specification, analysis, and mapping with application to the development of parallel software. Doctoral thesis

    SciTech Connect

    Bailor, P.D.

    1989-09-01

    Ageneralized formal language theory model and associated theorems were developed for the specification, analysis, and mapping of graphs and graph-based languages. The developed model, defined as a graph-generative system, is analyzed from a set theoretic, formal language, algebraic, and abstract automata perspective. As a result of the analysis, numerous theorems pertaining to the properties of the model, graphs, and graph-based languages are derived. The graph generative system model also serves as the basis for applying graph based languages to areas such as the specification and design of software and visual programming. The specific application area emphasized is the use of graph-based languages as user-friendly interfaces for wide-spectrum languages that include structures for representing parallelism. The goal of this approach is to provide an effective, efficient, and formal method for the specification, design, and rapid prototyping of parallel software. To demonstrate the theory's utility and the feasibility of the application, two models of parallel computation are chosen. The widely used Petri net model of parallel computation is formalized as a graph-based language. The Petri net syntax is formally mapped into the corresponding syntax of a Communicating Sequential Processes(CSP) model of parallel computation where CSP is used as the formalism for extended wide-spectrum languages. Finally, the Petri net to CSP mapping is analyzed to demonstrate that the CSP specification formally behaves in a manner equivalent to the Petri net model.

  2. Tissue specificity in the nuclear envelope supports its functional complexity

    PubMed Central

    de las Heras, Jose I; Meinke, Peter; Batrakou, Dzmitry G; Srsen, Vlastimil; Zuleger, Nikolaj; Kerr, Alastair RW; Schirmer, Eric C

    2013-01-01

    Nuclear envelope links to inherited disease gave the conundrum of how mutations in near-ubiquitous proteins can yield many distinct pathologies, each focused in different tissues. One conundrum-resolving hypothesis is that tissue-specific partner proteins mediate these pathologies. Such partner proteins may have now been identified with recent proteome studies determining nuclear envelope composition in different tissues. These studies revealed that the majority of the total nuclear envelope proteins are tissue restricted in their expression. Moreover, functions have been found for a number these tissue-restricted nuclear envelope proteins that fit with mechanisms proposed to explain how the nuclear envelope could mediate disease, including defects in mechanical stability, cell cycle regulation, signaling, genome organization, gene expression, nucleocytoplasmic transport, and differentiation. The wide range of functions to which these proteins contribute is consistent with not only their involvement in tissue-specific nuclear envelope disease pathologies, but also tissue evolution. PMID:24213376

  3. Onco-Regulon: an integrated database and software suite for site specific targeting of transcription factors of cancer genes

    PubMed Central

    Tomar, Navneet; Mishra, Akhilesh; Mrinal, Nirotpal; Jayaram, B.

    2016-01-01

    Transcription factors (TFs) bind at multiple sites in the genome and regulate expression of many genes. Regulating TF binding in a gene specific manner remains a formidable challenge in drug discovery because the same binding motif may be present at multiple locations in the genome. Here, we present Onco-Regulon (http://www.scfbio-iitd.res.in/software/onco/NavSite/index.htm), an integrated database of regulatory motifs of cancer genes clubbed with Unique Sequence-Predictor (USP) a software suite that identifies unique sequences for each of these regulatory DNA motifs at the specified position in the genome. USP works by extending a given DNA motif, in 5′→3′, 3′ →5′ or both directions by adding one nucleotide at each step, and calculates the frequency of each extended motif in the genome by Frequency Counter programme. This step is iterated till the frequency of the extended motif becomes unity in the genome. Thus, for each given motif, we get three possible unique sequences. Closest Sequence Finder program predicts off-target drug binding in the genome. Inclusion of DNA-Protein structural information further makes Onco-Regulon a highly informative repository for gene specific drug development. We believe that Onco-Regulon will help researchers to design drugs which will bind to an exclusive site in the genome with no off-target effects, theoretically. Database URL: http://www.scfbio-iitd.res.in/software/onco/NavSite/index.htm PMID:27515825

  4. Onco-Regulon: an integrated database and software suite for site specific targeting of transcription factors of cancer genes.

    PubMed

    Tomar, Navneet; Mishra, Akhilesh; Mrinal, Nirotpal; Jayaram, B

    2016-01-01

    Transcription factors (TFs) bind at multiple sites in the genome and regulate expression of many genes. Regulating TF binding in a gene specific manner remains a formidable challenge in drug discovery because the same binding motif may be present at multiple locations in the genome. Here, we present Onco-Regulon (http://www.scfbio-iitd.res.in/software/onco/NavSite/index.htm), an integrated database of regulatory motifs of cancer genes clubbed with Unique Sequence-Predictor (USP) a software suite that identifies unique sequences for each of these regulatory DNA motifs at the specified position in the genome. USP works by extending a given DNA motif, in 5'→3', 3' →5' or both directions by adding one nucleotide at each step, and calculates the frequency of each extended motif in the genome by Frequency Counter programme. This step is iterated till the frequency of the extended motif becomes unity in the genome. Thus, for each given motif, we get three possible unique sequences. Closest Sequence Finder program predicts off-target drug binding in the genome. Inclusion of DNA-Protein structural information further makes Onco-Regulon a highly informative repository for gene specific drug development. We believe that Onco-Regulon will help researchers to design drugs which will bind to an exclusive site in the genome with no off-target effects, theoretically.Database URL: http://www.scfbio-iitd.res.in/software/onco/NavSite/index.htm. PMID:27515825

  5. Simplifying the construction of domain-specific automatic programming systems: The NASA automated software development workstation project

    NASA Technical Reports Server (NTRS)

    Allen, Bradley P.; Holtzman, Peter L.

    1987-01-01

    An overview is presented of the Automated Software Development Workstation Project, an effort to explore knowledge-based approaches to increasing software productivity. The project focuses on applying the concept of domain specific automatic programming systems (D-SAPSs) to application domains at NASA's Johnson Space Center. A version of a D-SAPS developed in Phase 1 of the project for the domain of space station momentum management is described. How problems encountered during its implementation led researchers to concentrate on simplifying the process of building and extending such systems is discussed. Researchers propose to do this by attacking three observed bottlenecks in the D-SAPS development process through the increased automation of the acquisition of programming knowledge and the use of an object oriented development methodology at all stages of the program design. How these ideas are being implemented in the Bauhaus, a prototype workstation for D-SAPS development is discussed.

  6. siDirect: highly effective, target-specific siRNA design software for mammalian RNA interference

    PubMed Central

    Naito, Yuki; Yamada, Tomoyuki; Ui-Tei, Kumiko; Morishita, Shinichi; Saigo, Kaoru

    2004-01-01

    siDirect (http://design.RNAi.jp/) is a web-based online software system for computing highly effective small interfering RNA (siRNA) sequences with maximum target-specificity for mammalian RNA interference (RNAi). Highly effective siRNA sequences are selected using novel guidelines that were established through an extensive study of the relationship between siRNA sequences and RNAi activity. Our efficient software avoids off-target gene silencing to enumerate potential cross-hybridization candidates that the widely used BLAST search may overlook. The website accepts an arbitrary sequence as input and quickly returns siRNA candidates, providing a wide scope of applications in mammalian RNAi, including systematic functional genomics and therapeutic gene silencing. PMID:15215364

  7. Simplifying the construction of domain-specific automatic programming systems: The NASA automated software development workstation project

    NASA Technical Reports Server (NTRS)

    Allen, Bradley P.; Holtzman, Peter L.

    1988-01-01

    An overview is presented of the Automated Software Development Workstation Project, an effort to explore knowledge-based approaches to increasing software productivity. The project focuses on applying the concept of domain specific automatic programming systems (D-SAPSs) to application domains at NASA's Johnson Space Flight Center. A version of a D-SAPS developed in Phase 1 of the project for the domain of space station momentum management is described. How problems encountered during its implementation led researchers to concentrate on simplifying the process of building and extending such systems is discussed. Researchers propose to do this by attacking three observed bottlenecks in the D-SAPS development process through the increased automation of the acquisition of programming knowledge and the use of an object oriented development methodology at all stages of the program design. How these ideas are being implemented in the Bauhaus, a prototype workstation for D-SAPS development is discussed.

  8. Data systems and computer science: Software Engineering Program

    NASA Technical Reports Server (NTRS)

    Zygielbaum, Arthur I.

    1991-01-01

    An external review of the Integrated Technology Plan for the Civil Space Program is presented. This review is specifically concerned with the Software Engineering Program. The goals of the Software Engineering Program are as follows: (1) improve NASA's ability to manage development, operation, and maintenance of complex software systems; (2) decrease NASA's cost and risk in engineering complex software systems; and (3) provide technology to assure safety and reliability of software in mission critical applications.

  9. The definitive analysis of the Bendandi's methodology performed with a specific software

    NASA Astrophysics Data System (ADS)

    Ballabene, Adriano; Pescerelli Lagorio, Paola; Georgiadis, Teodoro

    2015-04-01

    The presentation aims to clarify the "Method Bendandi" supposed, in the past, to be able to forecast earthquakes and never let expressly resolved by the geophysicist from Faenza to posterity. The geoethics implications of the Bendandi's forecasts, and those that arise around the speculation of possible earthquakes inferred from suppositories "Bendandiane" methodologies, rose up in previous years caused by social alarms during supposed occurrences of earthquakes which never happened but where widely spread by media following some 'well informed' non conventional scientists. The analysis was conducted through an extensive literature search of the archive 'Raffaele Bendandi' at Geophy sical Observatory of Faenza and the forecasts analyzed utilising a specially developed software, called "Bendandiano Dashboard", that can reproduce the planetary configurations reported in the graphs made by Italian geophysicist. This analysis should serve to clarify 'definitively' what are the basis of the Bendandi's calculations as well as to prevent future unwarranted warnings issued on the basis of supposed prophecies and illusory legacy documents.

  10. As-built design specification for P1A software system modified display subsystem

    NASA Technical Reports Server (NTRS)

    Horton, C. L.; Story, A. S. (Principal Investigator)

    1980-01-01

    This document contains the design of the proportional estimate processor which was written to satisfy the software requirement of Part A of the P1A experiment. The purposes of the project are: (1) to select the dots to be labelled; (2) to create tables of green numbers and brightness values for all selected dots per acquisition; (3) to create scatter plots of green numbers vs brightness for each acquisition for all selected dots. If labels have been provided then scatter plots of only categories of interest can be optionally produced; and (4) to produce trajectory plots of green number vs brightness at differing acquisition times for each dot. These plots need to be in the same order as the list of selected dots. When labels are provided only plots of dots of categories of interest are to be produced.

  11. Hydrological mofelling of large river basins using the ECOMAG software complex

    NASA Astrophysics Data System (ADS)

    Motovilov, Yuri

    2014-05-01

    According to some hydrologists, the characteristic scale of river basins when using traditional physically based models of runoff formation is limited to the size of a small (elementary) river basin. Within its limits, these models can describe hydrological processes on the different parts of the slopes and in the river network in great detail. For hydrological simulation of large river basins, it is reasonable to use greater calculated cells of hundreds and even thousands square kilometers. The problem is to find a new (compared to the point) computational elements of a certain scale, generalization (filtering) of micro-scale fluctuations of the characteristics that are of secondary importance at this level of consideration and parameterization of hydrological processes models at the meso- and macroscale levels. In this case, such a spatial refinement as in detailed physically based models is not longer needed to describe hydrological processes, since aggregate models operate with flows averaged over the elementary catchments. In particular, such an ideology is adopted in a hydrological semi-distributed model ECOMAG, where a major river basin is covered with a grid of elementary catchments, for each of which a physically based model with lumped parameters is described by a system of ordinary differential equations, most of which obtained by integrating the basic equations of detailed physically based models over space. For solving practical and research tasks with the help of up-to-date informational and technological background, a software complex (SC) was developed on the basis of the ECOMAG model with a daily time step resolution, which included a specialized geographical information system (GIS), databases of archival and operational data on hydrological, meteorological and water management monitoring for the whole Russia, watershed characteristics, as well as the command shell. An ability of hydrological simulation of large river basins using SC ECOMAG is

  12. The Differential Effects of Task Complexity on Domain-Specific and Peer Assessment Skills

    ERIC Educational Resources Information Center

    van Zundert, Marjo J.; Sluijsmans, Dominique M. A.; Konings, Karen D.; van Merrienboer, Jeroen J. G.

    2012-01-01

    In this study the relationship between domain-specific skills and peer assessment skills as a function of task complexity is investigated. We hypothesised that peer assessment skills were superposed on domain-specific skills and will therefore suffer more when higher cognitive load is induced by increased task complexity. In a mixed factorial…

  13. The Decision-Adoption of Software Currency and Specificity Levels: A Quantitative Study of Information Technology (IT) Training

    ERIC Educational Resources Information Center

    Somsen, W. Randy

    2009-01-01

    IT educators and learners are continually challenged to adapt to software changes and remain current in software applications. This study researched if it is necessary for IT educators to prepare IT students in the most current software releases--i.e., at the highest software currency preparation level and in the same software application that the…

  14. A Software System to Collect Expert Relevance Ratings of Medical Record Items for Specific Clinical Tasks

    PubMed Central

    Krishnaraj, Arun; Alkasab, Tarik K

    2014-01-01

    Development of task-specific electronic medical record (EMR) searches and user interfaces has the potential to improve the efficiency and safety of health care while curbing rising costs. The development of such tools must be data-driven and guided by a strong understanding of practitioner information requirements with respect to specific clinical tasks or scenarios. To acquire this important data, this paper describes a model by which expert practitioners are leveraged to identify which components of the medical record are most relevant to a specific clinical task. We also describe the computer system that was created to efficiently implement this model of data gathering. The system extracts medical record data from the EMR of patients matching a given clinical scenario, de-identifies the data, breaks the data up into separate medical record items (eg, radiology reports, operative notes, laboratory results, etc), presents each individual medical record item to experts under the hypothetical of the given clinical scenario, and records the experts’ ratings regarding the relevance of each medical record item to that specific clinical scenario or task. After an iterative process of data collection, these expert relevance ratings can then be pooled and used to design point-of-care EMR searches and user interfaces tailored to the task-specific needs of practitioners. PMID:25600925

  15. Software system safety

    NASA Technical Reports Server (NTRS)

    Uber, James G.

    1988-01-01

    Software itself is not hazardous, but since software and hardware share common interfaces there is an opportunity for software to create hazards. Further, these software systems are complex, and proven methods for the design, analysis, and measurement of software safety are not yet available. Some past software failures, future NASA software trends, software engineering methods, and tools and techniques for various software safety analyses are reviewed. Recommendations to NASA are made based on this review.

  16. Software Design for Wireless Sensor-based Site-specific Irrigation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In-field sensor-based site-specific irrigation management is of benefit to producers for efficient water management. Integration of the decision making process with the controls is a viable option for determining when and where to irrigate, and how much water to apply. This research presents the des...

  17. Technical Specifications for Hardware and Software, and Maintenance in Support of Computer Literacy Program. Volume II.

    ERIC Educational Resources Information Center

    District of Columbia Public Schools, Washington, DC.

    Designed for use by vendors, this guide provides an overview of the objectives for the 5-year computer literacy program to be implemented in the District of Columbia Public Schools; outlines requirements which are mandatory elements of vendors' bids unless explicitly designated "desirable"; and details specifications for computing equipment,…

  18. 75 FR 16817 - Meeting for Software Developers on the Technical Specifications for Common Formats for Patient...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-02

    ... Safety Rule), published in the Federal Register on November 21, 2008: 73 FR 70731- 70814. As authorized... reporting formats (Common Formats) Version 1.1 that allow for reporting of patient safety information to... information on the Common Formats Version 1.1, including the technical specifications, can be obtained...

  19. Software for Managing Complex Learning: Examples from an Educational Psychology Course.

    ERIC Educational Resources Information Center

    Schwartz, Daniel L.; Brophy, Sean; Lin, Xiaodong; Bransford, John D.

    1999-01-01

    Describes a software shell, STAR.Legacy, designed to guide attempts to help students learn from case, problem, and project-based learning. STAR.Legacy supports the integration of four types of learning environments: learner-centered, knowledge-centered, assessment-centered, and community-centered. Describes how a STAR.Legacy constructed for an…

  20. 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.

  1. The Effect of Software Features on Software Adoption and Training in the Audit Profession

    ERIC Educational Resources Information Center

    Kim, Hyo-Jeong

    2012-01-01

    Although software has been studied with technology adoption and training research, the study of specific software features for professional groups has been limited. To address this gap, I researched the impact of software features of varying complexity on internal audit (IA) professionals. Two studies along with the development of training…

  2. Scientific Software Component Technology

    SciTech Connect

    Kohn, S.; Dykman, N.; Kumfert, G.; Smolinski, B.

    2000-02-16

    We are developing new software component technology for high-performance parallel scientific computing to address issues of complexity, re-use, and interoperability for laboratory software. Component technology enables cross-project code re-use, reduces software development costs, and provides additional simulation capabilities for massively parallel laboratory application codes. The success of our approach will be measured by its impact on DOE mathematical and scientific software efforts. Thus, we are collaborating closely with library developers and application scientists in the Common Component Architecture forum, the Equation Solver Interface forum, and other DOE mathematical software groups to gather requirements, write and adopt a variety of design specifications, and develop demonstration projects to validate our approach. Numerical simulation is essential to the science mission at the laboratory. However, it is becoming increasingly difficult to manage the complexity of modern simulation software. Computational scientists develop complex, three-dimensional, massively parallel, full-physics simulations that require the integration of diverse software packages written by outside development teams. Currently, the integration of a new software package, such as a new linear solver library, can require several months of effort. Current industry component technologies such as CORBA, JavaBeans, and COM have all been used successfully in the business domain to reduce software development costs and increase software quality. However, these existing industry component infrastructures will not scale to support massively parallel applications in science and engineering. In particular, they do not address issues related to high-performance parallel computing on ASCI-class machines, such as fast in-process connections between components, language interoperability for scientific languages such as Fortran, parallel data redistribution between components, and massively

  3. Space Shuttle Main Engine Quantitative Risk Assessment: Illustrating Modeling of a Complex System with a New QRA Software Package

    NASA Technical Reports Server (NTRS)

    Smart, Christian

    1998-01-01

    During 1997, a team from Hernandez Engineering, MSFC, Rocketdyne, Thiokol, Pratt & Whitney, and USBI completed the first phase of a two year Quantitative Risk Assessment (QRA) of the Space Shuttle. The models for the Shuttle systems were entered and analyzed by a new QRA software package. This system, termed the Quantitative Risk Assessment System(QRAS), was designed by NASA and programmed by the University of Maryland. The software is a groundbreaking PC-based risk assessment package that allows the user to model complex systems in a hierarchical fashion. Features of the software include the ability to easily select quantifications of failure modes, draw Event Sequence Diagrams(ESDs) interactively, perform uncertainty and sensitivity analysis, and document the modeling. This paper illustrates both the approach used in modeling and the particular features of the software package. The software is general and can be used in a QRA of any complex engineered system. The author is the project lead for the modeling of the Space Shuttle Main Engines (SSMEs), and this paper focuses on the modeling completed for the SSMEs during 1997. In particular, the groundrules for the study, the databases used, the way in which ESDs were used to model catastrophic failure of the SSMES, the methods used to quantify the failure rates, and how QRAS was used in the modeling effort are discussed. Groundrules were necessary to limit the scope of such a complex study, especially with regard to a liquid rocket engine such as the SSME, which can be shut down after ignition either on the pad or in flight. The SSME was divided into its constituent components and subsystems. These were ranked on the basis of the possibility of being upgraded and risk of catastrophic failure. Once this was done the Shuttle program Hazard Analysis and Failure Modes and Effects Analysis (FMEA) were used to create a list of potential failure modes to be modeled. The groundrules and other criteria were used to screen

  4. Software engineering methodologies and tools

    NASA Technical Reports Server (NTRS)

    Wilcox, Lawrence M.

    1993-01-01

    Over the years many engineering disciplines have developed, including chemical, electronic, etc. Common to all engineering disciplines is the use of rigor, models, metrics, and predefined methodologies. Recently, a new engineering discipline has appeared on the scene, called software engineering. For over thirty years computer software has been developed and the track record has not been good. Software development projects often miss schedules, are over budget, do not give the user what is wanted, and produce defects. One estimate is there are one to three defects per 1000 lines of deployed code. More and more systems are requiring larger and more complex software for support. As this requirement grows, the software development problems grow exponentially. It is believed that software quality can be improved by applying engineering principles. Another compelling reason to bring the engineering disciplines to software development is productivity. It has been estimated that productivity of producing software has only increased one to two percent a year in the last thirty years. Ironically, the computer and its software have contributed significantly to the industry-wide productivity, but computer professionals have done a poor job of using the computer to do their job. Engineering disciplines and methodologies are now emerging supported by software tools that address the problems of software development. This paper addresses some of the current software engineering methodologies as a backdrop for the general evaluation of computer assisted software engineering (CASE) tools from actual installation of and experimentation with some specific tools.

  5. Specificity of IS6110-based amplification assays for Mycobacterium tuberculosis complex.

    PubMed Central

    Hellyer, T J; DesJardin, L E; Assaf, M K; Bates, J H; Cave, M D; Eisenach, K D

    1996-01-01

    The specificity of IS6110 for the Mycobacterium tuberculosis complex has recently been questioned. We observed no cross-reaction with 27 nontuberculous mycobacteria using strand displacement- and PCR-based amplification of the nucleotide 970 to 1026 and 762 to 865 regions of IS6110. These data support use of selected regions of IS6110 as M. tuberculosis complex-specific targets. PMID:8897197

  6. Specific antibody for pesticide residue determination produced by antibody-pesticide complex

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A new method for specific antibody production was developed using antibody (Ab)-pesticide complex as a unique immunogen. Parathion (PA) was the targeted pesticide, and rabbit polyclonal antibody (Pab) and mouse monoclonal antibody (Mab) were used as carrier proteins. The Ab-PA complexes were genera...

  7. Three-dimensional representations of complex carbohydrates and polysaccharides--SweetUnityMol: a video game-based computer graphic software.

    PubMed

    Pérez, Serge; Tubiana, Thibault; Imberty, Anne; Baaden, Marc

    2015-05-01

    A molecular visualization program tailored to deal with the range of 3D structures of complex carbohydrates and polysaccharides, either alone or in their interactions with other biomacromolecules, has been developed using advanced technologies elaborated by the video games industry. All the specific structural features displayed by the simplest to the most complex carbohydrate molecules have been considered and can be depicted. This concerns the monosaccharide identification and classification, conformations, location in single or multiple branched chains, depiction of secondary structural elements and the essential constituting elements in very complex structures. Particular attention was given to cope with the accepted nomenclature and pictorial representation used in glycoscience. This achievement provides a continuum between the most popular ways to depict the primary structures of complex carbohydrates to visualizing their 3D structures while giving the users many options to select the most appropriate modes of representations including new features such as those provided by the use of textures to depict some molecular properties. These developments are incorporated in a stand-alone viewer capable of displaying molecular structures, biomacromolecule surfaces and complex interactions of biomacromolecules, with powerful, artistic and illustrative rendering methods. They result in an open source software compatible with multiple platforms, i.e., Windows, MacOS and Linux operating systems, web pages, and producing publication-quality figures. The algorithms and visualization enhancements are demonstrated using a variety of carbohydrate molecules, from glycan determinants to glycoproteins and complex protein-carbohydrate interactions, as well as very complex mega-oligosaccharides and bacterial polysaccharides and multi-stranded polysaccharide architectures. PMID:25475093

  8. A Software System for Filling Complex Holes in 3D Meshes by Flexible Interacting Particles

    NASA Astrophysics Data System (ADS)

    Yamazaki, Daisuke; Savchenko, Vladimir

    3D meshes generated by acquisition devices such as laser range scanners often contain holes due to occlusion, etc. In practice, these holes are extremely geometrically and topologically complex. We propose a heuristic hole filling technique using particle systems to fill complex holes with arbitrary topology in 3D meshes. Our approach includes the following steps: hole identification, base surface creation, particle distribution, triangulation, and mesh refinement. We demonstrate the functionality of the proposed surface retouching system on synthetic and real data.

  9. Detailed analysis of complex single molecule FRET data with the software MASH

    NASA Astrophysics Data System (ADS)

    Hadzic, Mélodie C. A. S.; Kowerko, Danny; Börner, Richard; Zelger-Paulus, Susann; Sigel, Roland K. O.

    2016-04-01

    The processing and analysis of surface-immobilized single molecule FRET (Förster resonance energy transfer) data follows systematic steps (e.g. single molecule localization, clearance of different sources of noise, selection of the conformational and kinetic model, etc.) that require a solid knowledge in optics, photophysics, signal processing and statistics. The present proceeding aims at standardizing and facilitating procedures for single molecule detection by guiding the reader through an optimization protocol for a particular experimental data set. Relevant features were determined from single molecule movies (SMM) imaging Cy3- and Cy5-labeled Sc.ai5γ group II intron molecules synthetically recreated, to test the performances of four different detection algorithms. Up to 120 different parameterizations per method were routinely evaluated to finally establish an optimum detection procedure. The present protocol is adaptable to any movie displaying surface-immobilized molecules, and can be easily reproduced with our home-written software MASH (multifunctional analysis software for heterogeneous data) and script routines (both available in the download section of www.chem.uzh.ch/rna).

  10. Application of the Software as a Service Model to the Control of Complex Building Systems

    SciTech Connect

    Stadler, Michael; Donadee, Jon; Marnay, Chris; Lai, Judy; Mendes, Goncalo; Appen, Jan von; Mégel, Oliver; Bhattacharya, Prajesh; DeForest, Nicholas; Lai, Judy

    2011-03-18

    In an effort to create broad access to its optimization software, Lawrence Berkeley National Laboratory (LBNL), in collaboration with the University of California at Davis (UC Davis) and OSISoft, has recently developed a Software as a Service (SaaS) Model for reducing energy costs, cutting peak power demand, and reducing carbon emissions for multipurpose buildings. UC Davis currently collects and stores energy usage data from buildings on its campus. Researchers at LBNL sought to demonstrate that a SaaS application architecture could be built on top of this data system to optimize the scheduling of electricity and heat delivery in the building. The SaaS interface, known as WebOpt, consists of two major parts: a) the investment& planning and b) the operations module, which builds on the investment& planning module. The operational scheduling and load shifting optimization models within the operations module use data from load prediction and electrical grid emissions models to create an optimal operating schedule for the next week, reducing peak electricity consumption while maintaining quality of energy services. LBNL's application also provides facility managers with suggested energy infrastructure investments for achieving their energy cost and emission goals based on historical data collected with OSISoft's system. This paper describes these models as well as the SaaS architecture employed by LBNL researchers to provide asset scheduling services to UC Davis. The peak demand, emissions, and cost implications of the asset operation schedule and investments suggested by this optimization model are analyzed.

  11. Application of the Software as a Service Model to the Control of Complex Building Systems

    SciTech Connect

    Stadler, Michael; Donadee, Jonathan; Marnay, Chris; Mendes, Goncalo; Appen, Jan von; Megel, Oliver; Bhattacharya, Prajesh; DeForest, Nicholas; Lai, Judy

    2011-03-17

    In an effort to create broad access to its optimization software, Lawrence Berkeley National Laboratory (LBNL), in collaboration with the University of California at Davis (UC Davis) and OSISoft, has recently developed a Software as a Service (SaaS) Model for reducing energy costs, cutting peak power demand, and reducing carbon emissions for multipurpose buildings. UC Davis currently collects and stores energy usage data from buildings on its campus. Researchers at LBNL sought to demonstrate that a SaaS application architecture could be built on top of this data system to optimize the scheduling of electricity and heat delivery in the building. The SaaS interface, known as WebOpt, consists of two major parts: a) the investment& planning and b) the operations module, which builds on the investment& planning module. The operational scheduling and load shifting optimization models within the operations module use data from load prediction and electrical grid emissions models to create an optimal operating schedule for the next week, reducing peak electricity consumption while maintaining quality of energy services. LBNL's application also provides facility managers with suggested energy infrastructure investments for achieving their energy cost and emission goals based on historical data collected with OSISoft's system. This paper describes these models as well as the SaaS architecture employed by LBNL researchers to provide asset scheduling services to UC Davis. The peak demand, emissions, and cost implications of the asset operation schedule and investments suggested by this optimization model are analysed.

  12. Single Event Testing on Complex Devices: Test Like You Fly Versus Test-Specific Design Structures

    NASA Technical Reports Server (NTRS)

    Berg, Melanie D.; Label, Kenneth

    2016-01-01

    We present a mechanism for evaluating complex digital systems targeted for harsh radiation environments such as space. Focus is limited to analyzing the single event upset (SEU) susceptibility of designs implemented inside Field Programmable Gate Array (FPGA) devices. Tradeoffs are provided between application-specific versus test-specific test structures.

  13. GenoMatrix: A Software Package for Pedigree-Based and Genomic Prediction Analyses on Complex Traits.

    PubMed

    Nazarian, Alireza; Gezan, Salvador Alejandro

    2016-07-01

    Genomic and pedigree-based best linear unbiased prediction methodologies (G-BLUP and P-BLUP) have proven themselves efficient for partitioning the phenotypic variance of complex traits into its components, estimating the individuals' genetic merits, and predicting unobserved (or yet-to-be observed) phenotypes in many species and fields of study. The GenoMatrix software, presented here, is a user-friendly package to facilitate the process of using genome-wide marker data and parentage information for G-BLUP and P-BLUP analyses on complex traits. It provides users with a collection of applications which help them on a set of tasks from performing quality control on data to constructing and manipulating the genomic and pedigree-based relationship matrices and obtaining their inverses. Such matrices will be then used in downstream analyses by other statistical packages. The package also enables users to obtain predicted values for unobserved individuals based on the genetic values of observed related individuals. GenoMatrix is available to the research community as a Windows 64bit executable and can be downloaded free of charge at: http://compbio.ufl.edu/software/genomatrix/. PMID:27025440

  14. Software Measurement Guidebook

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This Software Measurement Guidebook is based on the extensive experience of several organizations that have each developed and applied significant measurement programs over a period of at least 10 years. The lessons derived from those experiences reflect not only successes but also failures. By applying those lessons, an organization can minimize, or at least reduce, the time, effort, and frustration of introducing a software measurement program. The Software Measurement Guidebook is aimed at helping organizations to begin or improve a measurement program. It does not provide guidance for the extensive application of specific measures (such as how to estimate software cost or analyze software complexity) other than by providing examples to clarify points. It does contain advice for establishing and using an effective software measurement program and for understanding some of the key lessons that other organizations have learned. Some of that advice will appear counterintuitive, but it is all based on actual experience. Although all of the information presented in this guidebook is derived from specific experiences of mature measurement programs, the reader must keep in mind that the characteristics of every organization are unique. Some degree of measurement is critical for all software development and maintenance organizations, and most of the key rules captured in this report will be generally applicable. Nevertheless, each organization must strive to understand its own environment so that the measurement program can be tailored to suit its characteristics and needs.

  15. Use of checkpoint-restart for complex HEP software on traditional architectures and Intel MIC

    NASA Astrophysics Data System (ADS)

    Arya, Kapil; Cooperman, Gene; Dotti, Andrea; Elmer, Peter

    2014-06-01

    Process checkpoint-restart is a technology with great potential for use in HEP workflows. Use cases include debugging, reducing the startup time of applications both in offline batch jobs and the High Level Trigger, permitting job preemption in environments where spare CPU cycles are being used opportunistically and efficient scheduling of a mix of multicore and single-threaded jobs. We report on tests of checkpoint-restart technology using CMS software, Geant4-MT (multi-threaded Geant4), and the DMTCP (Distributed Multithreaded Checkpointing) package. We analyze both single- and multi-threaded applications and test on both standard Intel x86 architectures and on Intel MIC. The tests with multi-threaded applications on Intel MIC are used to consider scalability and performance. These are considered an indicator of what the future may hold for many-core computing.

  16. Effect of formal specifications on program complexity and reliability: An experimental study

    NASA Technical Reports Server (NTRS)

    Goel, Amrit L.; Sahoo, Swarupa N.

    1990-01-01

    The results are presented of an experimental study undertaken to assess the improvement in program quality by using formal specifications. Specifications in the Z notation were developed for a simple but realistic antimissile system. These specifications were then used to develop 2 versions in C by 2 programmers. Another set of 3 versions in Ada were independently developed from informal specifications in English. A comparison of the reliability and complexity of the resulting programs suggests the advantages of using formal specifications in terms of number of errors detected and fault avoidance.

  17. TASSEL: Software for Association Mapping of Complex Traits in Diverse Samples

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The association mapping of complex traits is becoming the method of choice in plant and animal genetics. In most samples, researchers have to deal with both population and family structure. TASSEL (Trait Analysis by aSSociation, Evolution and Linkage) implements general linear model and mixed line...

  18. Software safety

    NASA Technical Reports Server (NTRS)

    Leveson, Nancy

    1987-01-01

    Software safety and its relationship to other qualities are discussed. It is shown that standard reliability and fault tolerance techniques will not solve the safety problem for the present. A new attitude requires: looking at what you do NOT want software to do along with what you want it to do; and assuming things will go wrong. New procedures and changes to entire software development process are necessary: special software safety analysis techniques are needed; and design techniques, especially eliminating complexity, can be very helpful.

  19. Modeling software systems by domains

    NASA Technical Reports Server (NTRS)

    Dippolito, Richard; Lee, Kenneth

    1992-01-01

    The Software Architectures Engineering (SAE) Project at the Software Engineering Institute (SEI) has developed engineering modeling techniques that both reduce the complexity of software for domain-specific computer systems and result in systems that are easier to build and maintain. These techniques allow maximum freedom for system developers to apply their domain expertise to software. We have applied these techniques to several types of applications, including training simulators operating in real time, engineering simulators operating in non-real time, and real-time embedded computer systems. Our modeling techniques result in software that mirrors both the complexity of the application and the domain knowledge requirements. We submit that the proper measure of software complexity reflects neither the number of software component units nor the code count, but the locus of and amount of domain knowledge. As a result of using these techniques, domain knowledge is isolated by fields of engineering expertise and removed from the concern of the software engineer. In this paper, we will describe kinds of domain expertise, describe engineering by domains, and provide relevant examples of software developed for simulator applications using the techniques.

  20. RT-Syn: A real-time software system generator

    NASA Technical Reports Server (NTRS)

    Setliff, Dorothy E.

    1992-01-01

    This paper presents research into providing highly reusable and maintainable components by using automatic software synthesis techniques. This proposal uses domain knowledge combined with automatic software synthesis techniques to engineer large-scale mission-critical real-time software. The hypothesis centers on a software synthesis architecture that specifically incorporates application-specific (in this case real-time) knowledge. This architecture synthesizes complex system software to meet a behavioral specification and external interaction design constraints. Some examples of these external constraints are communication protocols, precisions, timing, and space limitations. The incorporation of application-specific knowledge facilitates the generation of mathematical software metrics which are used to narrow the design space, thereby making software synthesis tractable. Success has the potential to dramatically reduce mission-critical system life-cycle costs not only by reducing development time, but more importantly facilitating maintenance, modifications, and extensions of complex mission-critical software systems, which are currently dominating life cycle costs.

  1. Screening Leishmania donovani complex-specific genes required for visceral disease.

    PubMed

    Zhang, Wen-Wei; Matlashewski, Greg

    2015-01-01

    Leishmania protozoan parasites are the causing agent of leishmaniasis. Depending on the infecting species, Leishmania infection can causes a wide variety of diseases such as self-healing cutaneous lesions by L. major and fatal visceral leishmaniasis by L. donovani and L. infantum. Comparison of the visceral disease causing L. infantum genome with cutaneous disease causing L. major and L. braziliensis genomes has identified 25 L. infantum (L. donovani complex) species-specific genes that are absent or pseudogenes in L. major and L. braziliensis. To investigate whether these L. donovani complex species-specific genes are involved in visceral infection, we cloned these genes from L. donovani and introduced them into L. major and then determined whether the transgenic L. major had an increased ability to survive in liver and spleen of BALB/c mice. Several of these L. donovani complex specific genes were found to significantly increase L. major survival in visceral organs in BALB/c mice including the A2 and Ld2834 genes, while down regulation of these genes in L. donovani by either antisense RNA or gene knockout dramatically reduced L. donovani virulence in BALB/c mice. This demonstrated that L. donovani complex species-specific genes play important roles in visceral infection. In this chapter, we describe procedures to screen L. donovani complex specific genes required for visceral infection by cross species transgenic expression, gene deletion targeting and measuring infection levels in mice. PMID:25388124

  2. freeQuant: A Mass Spectrometry Label-Free Quantification Software Tool for Complex Proteome Analysis

    PubMed Central

    Li, Zhenye; Pan, Chao; Duan, Huilong

    2015-01-01

    Study of complex proteome brings forward higher request for the quantification method using mass spectrometry technology. In this paper, we present a mass spectrometry label-free quantification tool for complex proteomes, called freeQuant, which integrated quantification with functional analysis effectively. freeQuant consists of two well-integrated modules: label-free quantification and functional analysis with biomedical knowledge. freeQuant supports label-free quantitative analysis which makes full use of tandem mass spectrometry (MS/MS) spectral count, protein sequence length, shared peptides, and ion intensity. It adopts spectral count for quantitative analysis and builds a new method for shared peptides to accurately evaluate abundance of isoforms. For proteins with low abundance, MS/MS total ion count coupled with spectral count is included to ensure accurate protein quantification. Furthermore, freeQuant supports the large-scale functional annotations for complex proteomes. Mitochondrial proteomes from the mouse heart, the mouse liver, and the human heart were used to evaluate the usability and performance of freeQuant. The evaluation showed that the quantitative algorithms implemented in freeQuant can improve accuracy of quantification with better dynamic range. PMID:26665161

  3. FACET: an object-oriented software framework for modeling complex social behavior patterns

    SciTech Connect

    Dolph, J. E.; Christiansen, J. H.; Sydelko, P. J.

    2000-06-30

    The Framework for Addressing Cooperative Extended Transactions (FACET) is a flexible, object-oriented architecture for implementing models of dynamic behavior of multiple individuals, or agents, in a simulation. These agents can be human (individuals or organizations) or animal and may exhibit any type of organized social behavior that can be logically articulated. FACET was developed by Argonne National Laboratory's (ANL) Decision and Information Sciences Division (DIS) out of the need to integrate societal processes into natural system simulations. The FACET architecture includes generic software components that provide the agents with various mechanisms for interaction, such as step sequencing and logic, resource management, conflict resolution, and preemptive event handling. FACET components provide a rich environment within which patterns of behavior can be captured in a highly expressive manner. Interactions among agents in FACET are represented by Course of Action (COA) object-based models. Each COA contains a directed graph of individual actions, which represents any known pattern of social behavior. The agents' behavior in a FACET COA, in turn, influences the natural landscape objects in a simulation (i.e., vegetation, soil, and habitat) by updating their states. The modular design of the FACET architecture provides the flexibility to create multiple and varied simulation scenarios by changing social behavior patterns, without disrupting the natural process models. This paper describes the FACET architecture and presents several examples of FACET models that have been developed to assess the effects of anthropogenic influences on the dynamics of the natural environment.

  4. Complex modeling: a strategy and software program for combining multiple information sources to solve ill posed structure and nanostructure inverse problems.

    PubMed

    Juhás, Pavol; Farrow, Christopher L; Yang, Xiaohao; Knox, Kevin R; Billinge, Simon J L

    2015-11-01

    A strategy is described for regularizing ill posed structure and nanostructure scattering inverse problems (i.e. structure solution) from complex material structures. This paper describes both the philosophy and strategy of the approach, and a software implementation, DiffPy Complex Modeling Infrastructure (DiffPy-CMI). PMID:26522405

  5. THREE-DIMENSIONAL RADIO AND X-RAY MODELING AND DATA ANALYSIS SOFTWARE: REVEALING FLARE COMPLEXITY

    SciTech Connect

    Nita, Gelu M.; Fleishman, Gregory D.; Gary, Dale E.; Kuznetsov, Alexey A.; Kontar, Eduard P.

    2015-02-01

    Many problems in solar physics require analysis of imaging data obtained in multiple wavelength domains with differing spatial resolution in a framework supplied by advanced three-dimensional (3D) physical models. To facilitate this goal, we have undertaken a major enhancement of our IDL-based simulation tools developed earlier for modeling microwave and X-ray emission. The enhanced software architecture allows the user to (1) import photospheric magnetic field maps and perform magnetic field extrapolations to generate 3D magnetic field models; (2) investigate the magnetic topology by interactively creating field lines and associated flux tubes; (3) populate the flux tubes with user-defined nonuniform thermal plasma and anisotropic, nonuniform, nonthermal electron distributions; (4) investigate the spatial and spectral properties of radio and X-ray emission calculated from the model; and (5) compare the model-derived images and spectra with observational data. The package integrates shared-object libraries containing fast gyrosynchrotron emission codes, IDL-based soft and hard X-ray codes, and potential and linear force-free field extrapolation routines. The package accepts user-defined radiation and magnetic field extrapolation plug-ins. We use this tool to analyze a relatively simple single-loop flare and use the model to constrain the magnetic 3D structure and spatial distribution of the fast electrons inside this loop. We iteratively compute multi-frequency microwave and multi-energy X-ray images from realistic magnetic flux tubes obtained from pre-flare extrapolations, and compare them with imaging data obtained by SDO, NoRH, and RHESSI. We use this event to illustrate the tool's use for the general interpretation of solar flares to address disparate problems in solar physics.

  6. Three-dimensional Radio and X-Ray Modeling and Data Analysis Software: Revealing Flare Complexity

    NASA Astrophysics Data System (ADS)

    Nita, Gelu M.; Fleishman, Gregory D.; Kuznetsov, Alexey A.; Kontar, Eduard P.; Gary, Dale E.

    2015-02-01

    Many problems in solar physics require analysis of imaging data obtained in multiple wavelength domains with differing spatial resolution in a framework supplied by advanced three-dimensional (3D) physical models. To facilitate this goal, we have undertaken a major enhancement of our IDL-based simulation tools developed earlier for modeling microwave and X-ray emission. The enhanced software architecture allows the user to (1) import photospheric magnetic field maps and perform magnetic field extrapolations to generate 3D magnetic field models; (2) investigate the magnetic topology by interactively creating field lines and associated flux tubes; (3) populate the flux tubes with user-defined nonuniform thermal plasma and anisotropic, nonuniform, nonthermal electron distributions; (4) investigate the spatial and spectral properties of radio and X-ray emission calculated from the model; and (5) compare the model-derived images and spectra with observational data. The package integrates shared-object libraries containing fast gyrosynchrotron emission codes, IDL-based soft and hard X-ray codes, and potential and linear force-free field extrapolation routines. The package accepts user-defined radiation and magnetic field extrapolation plug-ins. We use this tool to analyze a relatively simple single-loop flare and use the model to constrain the magnetic 3D structure and spatial distribution of the fast electrons inside this loop. We iteratively compute multi-frequency microwave and multi-energy X-ray images from realistic magnetic flux tubes obtained from pre-flare extrapolations, and compare them with imaging data obtained by SDO, NoRH, and RHESSI. We use this event to illustrate the tool's use for the general interpretation of solar flares to address disparate problems in solar physics.

  7. An empirical comparison of a dynamic software testability metric to static cyclomatic complexity

    NASA Technical Reports Server (NTRS)

    Voas, Jeffrey M.; Miller, Keith W.; Payne, Jeffrey E.

    1993-01-01

    This paper compares the dynamic testability prediction technique termed 'sensitivity analysis' to the static testability technique termed cyclomatic complexity. The application that we chose in this empirical study is a CASE generated version of a B-737 autoland system. For the B-737 system we analyzed, we isolated those functions that we predict are more prone to hide errors during system/reliability testing. We also analyzed the code with several other well-known static metrics. This paper compares and contrasts the results of sensitivity analysis to the results of the static metrics.

  8. Software packager user's guide

    NASA Technical Reports Server (NTRS)

    Callahan, John R.

    1995-01-01

    Software integration is a growing area of concern for many programmers and software managers because the need to build new programs quickly from existing components is greater than ever. This includes building versions of software products for multiple hardware platforms and operating systems, building programs from components written in different languages, and building systems from components that must execute on different machines in a distributed network. The goal of software integration is to make building new programs from existing components more seamless -- programmers should pay minimal attention to the underlying configuration issues involved. Libraries of reusable components and classes are important tools but only partial solutions to software development problems. Even though software components may have compatible interfaces, there may be other reasons, such as differences between execution environments, why they cannot be integrated. Often, components must be adapted or reimplemented to fit into another application because of implementation differences -- they are implemented in different programming languages, dependent on different operating system resources, or must execute on different physical machines. The software packager is a tool that allows programmers to deal with interfaces between software components and ignore complex integration details. The packager takes modular descriptions of the structure of a software system written in the package specification language and produces an integration program in the form of a makefile. If complex integration tools are needed to integrate a set of components, such as remote procedure call stubs, their use is implied by the packager automatically and stub generation tools are invoked in the corresponding makefile. The programmer deals only with the components themselves and not the details of how to build the system on any given platform.

  9. New Rust Resistance Specificities Associated with Recombination in the Rp1 Complex in Maize

    PubMed Central

    Richter, T. E.; Pryor, T. J.; Bennetzen, J. L.; Hulbert, S. H.

    1995-01-01

    We address the question of whether genetic reassortment events, including unequal crossing over and gene conversion, at the Rp1 complex are capable of generating novel resistance specificities that were not present in the parents. Some 176 events involving genetic reassortment within the Rp1 complex were screened for novel resistance specificities with a set of 11 different rust biotypes. Most (150/176) of the events were susceptible to all tested rust biotypes, providing no evidence for new specificities. Eleven events selected as double-resistant recombinants, when screened with the 11 test biotypes, showed the combined resistance of the two parental types consistent with a simple recombination and pyramiding of the parental resistances. Nine events selected either as having partial resistance or complete susceptibility to a single biotype possessed resistance to a subset of the biotypes that the parents were resistant to, suggesting segregation of resistance genes present in the parental Rp1 complex. Four events gave rise to novel specificities being resistant to at least one rust biotype to which both parents were susceptible. All four had flanking marker exchange, demonstrating that crossing over within the Rp1 complex is associated with the appearance of new rust resistance specificities. PMID:8536984

  10. An unstructured-grid software system for solving complex aerodynamic problems

    NASA Technical Reports Server (NTRS)

    Frink, Neal T.; Pirzadeh, Shahyar; Parikh, Paresh

    1995-01-01

    A coordinated effort has been underway over the past four years to elevate unstructured-grid methodology to a mature level. The goal of this endeavor is to provide a validated capability to non-expert users for performing rapid aerodynamic analysis and design of complex configurations. The Euler component of the system is well developed, and is impacting a broad spectrum of engineering needs with capabilities such as rapid grid generation and inviscid flow analysis, inverse design, interactive boundary layers, and propulsion effects. Progress is also being made in the more tenuous Navier-Stokes component of the system. A robust grid generator is under development for constructing quality thin-layer tetrahedral grids, along with a companion Navier-Stokes flow solver. This paper presents an overview of this effort, along with a perspective on the present and future status of the methodology.

  11. Children with Specific Language Impairment: The Effect of Argument-Structure Complexity on Auditory Sentence Comprehension

    ERIC Educational Resources Information Center

    Pizzioli, Fabrizio; Schelstraete, Marie-Anne

    2011-01-01

    Children with specific language impairment (SLI) demonstrate consistent comprehension problems. The present study investigated whether these problems are driven primarily by structural complexity or length. A picture-sentence matching task was presented to 30 children: (1) 10 children with SLI, (2) 10 comprehension-matched children with typical…

  12. Rapid and Specific Method for Evaluating Streptomyces Competitive Dynamics in Complex Soil Communities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Quantifying target microbial populations in complex communities remains a barrier to studying species interactions in soil environments. Quantitative real-time PCR (qPCR) offers a rapid and specific means to assess populations of target microorganisms. SYBR Green and TaqMan-based qPCR assays were de...

  13. A flexible object-based software framework for modeling complex systems with interacting natural and societal processes.

    SciTech Connect

    Christiansen, J. H.

    2000-06-15

    The Dynamic Information Architecture System (DIAS) is a flexible, extensible, object-based framework for developing and maintaining complex multidisciplinary simulations. The DIAS infrastructure makes it feasible to build and manipulate complex simulation scenarios in which many thousands of objects can interact via dozens to hundreds of concurrent dynamic processes. The flexibility and extensibility of the DIAS software infrastructure stem mainly from (1) the abstraction of object behaviors, (2) the encapsulation and formalization of model functionality, and (3) the mutability of domain object contents. DIAS simulation objects are inherently capable of highly flexible and heterogeneous spatial realizations. Geospatial graphical representation of DIAS simulation objects is addressed via the GeoViewer, an object-based GIS toolkit application developed at ANL. DIAS simulation capabilities have been extended by inclusion of societal process models generated by the Framework for Addressing Cooperative Extended Transactions (FACET), another object-based framework developed at Argonne National Laboratory. By using FACET models to implement societal behaviors of individuals and organizations within larger DIAS-based natural systems simulations, it has become possible to conveniently address a broad range of issues involving interaction and feedback among natural and societal processes. Example DIAS application areas discussed in this paper include a dynamic virtual oceanic environment, detailed simulation of clinical, physiological, and logistical aspects of health care delivery, and studies of agricultural sustainability of urban centers under environmental stress in ancient Mesopotamia.

  14. 26-10 Fab-digoxin complex: affinity and specificity due to surface complementarity.

    PubMed Central

    Jeffrey, P D; Strong, R K; Sieker, L C; Chang, C Y; Campbell, R L; Petsko, G A; Haber, E; Margolies, M N; Sheriff, S

    1993-01-01

    We have determined the three-dimensional structures of the antigen-binding fragment of the anti-digoxin monoclonal antibody 26-10 in the uncomplexed state at 2.7 A resolution and as a complex with digoxin at 2.5 A resolution. Neither the antibody nor digoxin undergoes any significant conformational changes upon forming the complex. Digoxin interacts primarily with the antibody heavy chain and is oriented such that the carbohydrate groups are exposed to solvent and the lactone ring is buried in a deep pocket at the bottom of the combining site. Despite extensive interactions between antibody and antigen, no hydrogen bonds or salt links are formed between 26-10 and digoxin. Thus the 26-10-digoxin complex is unique among the known three-dimensional structures of antibody-antigen complexes in that specificity and high affinity arise primarily from shape complementarity. Images Fig. 1 PMID:8234291

  15. Complexity and Specificity of the Neutrophil Transcriptomes in Juvenile Idiopathic Arthritis.

    PubMed

    Hu, Zihua; Jiang, Kaiyu; Frank, Mark Barton; Chen, Yanmin; Jarvis, James N

    2016-01-01

    NIH projects such as ENCODE and Roadmap Epigenomics have revealed surprising complexity in the transcriptomes of mammalian cells. In this study, we explored transcriptional complexity in human neutrophils, cells generally regarded as nonspecific in their functions and responses. We studied distinct human disease phenotypes and found that, at the gene, gene isoform, and miRNA level, neutrophils exhibit considerable specificity in their transcriptomes. Thus, even cells whose responses are considered non-specific show tailoring of their transcriptional repertoire toward specific physiologic or pathologic contexts. We also found that miRNAs had a global impact on neutrophil transcriptome and are associated with innate immunity in juvenile idiopathic arthritis (JIA). These findings have important implications for our understanding of the link between genes, non-coding transcripts and disease phenotypes. PMID:27271962

  16. Understanding Interactions between Cellular Matrices and Metal Complexes: Methods To Improve Silver Nanodot-Specific Staining.

    PubMed

    Choi, Sungmoon; Yu, Junhua

    2016-08-26

    Metal complexes are frequently used for biological applications due to their special photophysical and chemical characteristics. Due to strong interactions between metals and biomacromolecules, a random staining of cytoplasm or nucleoplasm by the complexes results in a low signal-to-background ratio. In this study, we used luminescent silver nanodots as a model to investigate the major driving force for non-specific staining in cellular matrices. Even though some silver nanodot emitters exhibited excellent specific staining of nucleoli, labeling with nanodots was problematic owing to severe non-specific staining. Binding between silver and sulfhydryl group of proteins appeared to be the major factor that enforced the silver staining. The oxidation of thiol groups in cells with hexacyanoferrate(III) dramatically weakened the silver-cell interaction and consequently significantly improved the efficiency of targeted staining. PMID:27380586

  17. Complexity and Specificity of the Neutrophil Transcriptomes in Juvenile Idiopathic Arthritis

    PubMed Central

    Hu, Zihua; Jiang, Kaiyu; Frank, Mark Barton; Chen, Yanmin; Jarvis, James N.

    2016-01-01

    NIH projects such as ENCODE and Roadmap Epigenomics have revealed surprising complexity in the transcriptomes of mammalian cells. In this study, we explored transcriptional complexity in human neutrophils, cells generally regarded as nonspecific in their functions and responses. We studied distinct human disease phenotypes and found that, at the gene, gene isoform, and miRNA level, neutrophils exhibit considerable specificity in their transcriptomes. Thus, even cells whose responses are considered non-specific show tailoring of their transcriptional repertoire toward specific physiologic or pathologic contexts. We also found that miRNAs had a global impact on neutrophil transcriptome and are associated with innate immunity in juvenile idiopathic arthritis (JIA). These findings have important implications for our understanding of the link between genes, non-coding transcripts and disease phenotypes. PMID:27271962

  18. Automated Software Development Workstation (ASDW)

    NASA Technical Reports Server (NTRS)

    Fridge, Ernie

    1990-01-01

    Software development is a serious bottleneck in the construction of complex automated systems. An increase of the reuse of software designs and components has been viewed as a way to relieve this bottleneck. One approach to achieving software reusability is through the development and use of software parts composition systems. A software parts composition system is a software development environment comprised of a parts description language for modeling parts and their interfaces, a catalog of existing parts, a composition editor that aids a user in the specification of a new application from existing parts, and a code generator that takes a specification and generates an implementation of a new application in a target language. The Automated Software Development Workstation (ASDW) is an expert system shell that provides the capabilities required to develop and manipulate these software parts composition systems. The ASDW is now in Beta testing at the Johnson Space Center. Future work centers on responding to user feedback for capability and usability enhancement, expanding the scope of the software lifecycle that is covered, and in providing solutions to handling very large libraries of reusable components.

  19. Using protein-binding microarrays to study transcription factor specificity: homologs, isoforms and complexes

    PubMed Central

    Andrilenas, Kellen K.; Penvose, Ashley

    2015-01-01

    Protein–DNA binding is central to specificity in gene regulation, and methods for characterizing transcription factor (TF)–DNA binding remain crucial to studies of regulatory specificity. High-throughput (HT) technologies have revolutionized our ability to characterize protein–DNA binding by significantly increasing the number of binding measurements that can be performed. Protein-binding microarrays (PBMs) are a robust and powerful HT platform for studying DNA-binding specificity of TFs. Analysis of PBM-determined DNA-binding profiles has provided new insight into the scope and mechanisms of TF binding diversity. In this review, we focus specifically on the PBM technique and discuss its application to the study of TF specificity, in particular, the binding diversity of TF homologs and multi-protein complexes. PMID:25431149

  20. A cryptobiosis-specific 19S protein complex of Artemia salina gastrulae.

    PubMed

    De Herdt, E; De Voeght, F; Clauwaert, J; Kondo, M; Slegers, H

    1981-01-15

    The postribosomal supernatant of Artemia salina cryptobiotic embryos contains a large quantity of a 19S protein complex. An amount of 3.6 mg/g of cysts is measured by immunoprecipitation with anti-(19S protein complex) antibody. The quantity of this complex decreases during further development to nauplius larvae to only 15% of the quantity present in cryptobiotic embryos. The complex was no longer detectable after 7 days of growth. The 27000-Mr protein subunit of the 19S complex is not synthesized by mRNA isolated from cryptobiotic embryos. The cryptobiosis-specific complex has Mr 573000 and 610000 as calculated from light-scattering and sedimentation-diffusion measurements respectively. The 19S homocomplex contains 20-23 27000-Mr proteins and has no function in the translation of homologous mRNA. From hydrodynamic data a hydration of 1.25 g of water/g of protein is calculated. The abundant presence of the 19S protein complex in cryptobiotic embryos and the absence of synthesis during development to nauplius larvae indicate a functional role during the cryptobiotic process in early embryogenesis. A role in maintaining the water content of the cytoplasm above a critical threshold during desiccation is suggested. PMID:7305995

  1. Use of Kidspiration[C] Software to Enhance the Reading Comprehension of Story Grammar Components for Elementary-Age Students with Specific Learning Disabilities

    ERIC Educational Resources Information Center

    Wade, Erin; Boon, Richard T.; Spencer, Vicky G.

    2010-01-01

    The aim of this research brief was to explore the efficacy of story mapping, with the integration of Kidspiration[C] software, to enhance the reading comprehension skills of story grammar components for elementary-age students. Three students served as the participants, two in third grade and one in fourth, with specific learning disabilities…

  2. Effects of Text-to-Speech Software on the Reading Rate and Comprehension Skills of High School Students with Specific Learning Disabilities

    ERIC Educational Resources Information Center

    Moorman, Amanda; Boon, Richard T.; Keller-Bell, Yolanda; Stagliano, Christina; Jeffs, Tara

    2010-01-01

    The purpose of this study was to examine the effects of a text-to-speech software program known as "Read Please" on the reading rate and reading comprehension accuracy of two high school students with specific learning disabilities (SLD) in reading. A single-subject A-B-A-B "withdrawal" research design (Alberto & Troutman, 2009) was used to…

  3. Characterization of the Mammalian CORVET and HOPS Complexes and Their Modular Restructuring for Endosome Specificity.

    PubMed

    van der Kant, Rik; Jonker, Caspar T H; Wijdeven, Ruud H; Bakker, Jeroen; Janssen, Lennert; Klumperman, Judith; Neefjes, Jacques

    2015-12-18

    Trafficking of cargo through the endosomal system depends on endosomal fusion events mediated by SNARE proteins, Rab-GTPases, and multisubunit tethering complexes. The CORVET and HOPS tethering complexes, respectively, regulate early and late endosomal tethering and have been characterized in detail in yeast where their sequential membrane targeting and assembly is well understood. Mammalian CORVET and HOPS subunits significantly differ from their yeast homologues, and novel proteins with high homology to CORVET/HOPS subunits have evolved. However, an analysis of the molecular interactions between these subunits in mammals is lacking. Here, we provide a detailed analysis of interactions within the mammalian CORVET and HOPS as well as an additional endosomal-targeting complex (VIPAS39-VPS33B) that does not exist in yeast. We show that core interactions within CORVET and HOPS are largely conserved but that the membrane-targeting module in HOPS has significantly changed to accommodate binding to mammalian-specific RAB7 interacting lysosomal protein (RILP). Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome-associated mutations in VPS33B selectively disrupt recruitment to late endosomes by RILP or binding to its partner VIPAS39. Within the shared core of CORVET/HOPS, we find that VPS11 acts as a molecular switch that binds either CORVET-specific TGFBRAP1 or HOPS-specific VPS39/RILP thereby allowing selective targeting of these tethering complexes to early or late endosomes to time fusion events in the endo/lysosomal pathway. PMID:26463206

  4. Characterization of a novel meiosis-specific protein within the central element of the synaptonemal complex.

    PubMed

    Hamer, Geert; Gell, Katarina; Kouznetsova, Anna; Novak, Ivana; Benavente, Ricardo; Höög, Christer

    2006-10-01

    During the first meiotic prophase, alignment and synapsis of the homologous chromosomes are mediated by the synaptonemal complex. Incorrect assembly of this complex results in cell death, impaired meiotic recombination and formation of aneuploid germ cells. We have identified a novel mouse meiosis-specific protein, TEX12, and shown it to be a component of the central element structure of the synaptonemal complex at synapsed homologous chromosomes. Only two other central element proteins, SYCE1 and SYCE2, have been identified to date and, using several mouse knockout models, we show that these proteins and TEX12 specifically depend on the synaptonemal transverse filament protein SYCP1 for localization to the meiotic chromosomes. Additionally, we show that TEX12 exactly co-localized with SYCE2, having the same, often punctate, localization pattern. SYCE1, on the other hand, co-localized with SYCP1 and these proteins displayed the same more continuous expression pattern. These co-localization studies were confirmed by co-immunoprecipitation experiments that showed that TEX12 specifically co-precipitated with SYCE2. Our results suggest a molecular network within the central elements, in which TEX12 and SYCE2 form a complex that interacts with SYCE1. SYCE1 interacts more directly with SYCP1 and could thus anchor the central element proteins to the transverse filaments. PMID:16968740

  5. Spectroscopic investigation on the interaction of ruthenium complexes with tumor specific lectin, jacalin.

    PubMed

    Ayaz Ahmed, Khan Behlol; Reshma, Elamvazhuthi; Mariappan, Mariappan; Anbazhagan, Veerappan

    2015-02-25

    Several ruthenium complexes are regarded as anticancer agents and considered as an alternative to the widely used platinum complexes. Owing to the preferential interaction of jacalin with tumor-associated T-antigen, we report the interaction of jacalin with four ruthenium complex namely, tris(1,10-phenanthroline)ruthenium(II)chloride, bis(1,10-phenanthroline)(N-[1,10]phenanthrolin-5-yl-pyrenylmethanimine)ruthenium(II)chloride, bis(1,10-phenanthroline)(dipyrido[3,2-a:2',3'-c]-phenazine)ruthenium(II)chloride, bis(1,10-phenanthroline)(11-(9-acridinyl)dipyrido[3,2-a:2',3'-c]phenazine)ruthenium(II) chloride. Fluorescence spectroscopic analysis revealed that the ruthenium complexes strongly quenched the intrinsic fluorescence of jacalin through a static quenching procedure, and a non-radiative energy transfer occurred within the molecules. Association constants obtained for the interaction of different ruthenium complexes with jacalin are in the order of 10(5) M(-1), which is in the same range as those obtained for the interaction of lectin with carbohydrate and hydrophobic ligand. Each subunit of the tetrameric jacalin binds one ruthenium complex, and the stoichiometry is found to be unaffected by the presence of the specific sugar, galactose. In addition, agglutination activity of jacalin is largely unaffected by the presence of the ruthenium complexes, indicating that the binding sites for the carbohydrate and the ruthenium complexes are different. These results suggest that the development of lectin-ruthenium complex conjugate would be feasible to target malignant cells in chemo-therapeutics. PMID:25306128

  6. Spectroscopic investigation on the interaction of ruthenium complexes with tumor specific lectin, jacalin

    NASA Astrophysics Data System (ADS)

    Ayaz Ahmed, Khan Behlol; Reshma, Elamvazhuthi; Mariappan, Mariappan; Anbazhagan, Veerappan

    2015-02-01

    Several ruthenium complexes are regarded as anticancer agents and considered as an alternative to the widely used platinum complexes. Owing to the preferential interaction of jacalin with tumor-associated T-antigen, we report the interaction of jacalin with four ruthenium complex namely, tris(1,10-phenanthroline)ruthenium(II)chloride, bis(1,10-phenanthroline)(N-[1,10]phenanthrolin-5-yl-pyrenylmethanimine)ruthenium(II)chloride, bis(1,10-phenanthroline)(dipyrido[3,2-a:2‧,3‧-c]-phenazine)ruthenium(II)chloride, bis(1,10-phenanthroline)(11-(9-acridinyl)dipyrido[3,2-a:2‧,3‧-c]phenazine)ruthenium(II) chloride. Fluorescence spectroscopic analysis revealed that the ruthenium complexes strongly quenched the intrinsic fluorescence of jacalin through a static quenching procedure, and a non-radiative energy transfer occurred within the molecules. Association constants obtained for the interaction of different ruthenium complexes with jacalin are in the order of 105 M-1, which is in the same range as those obtained for the interaction of lectin with carbohydrate and hydrophobic ligand. Each subunit of the tetrameric jacalin binds one ruthenium complex, and the stoichiometry is found to be unaffected by the presence of the specific sugar, galactose. In addition, agglutination activity of jacalin is largely unaffected by the presence of the ruthenium complexes, indicating that the binding sites for the carbohydrate and the ruthenium complexes are different. These results suggest that the development of lectin-ruthenium complex conjugate would be feasible to target malignant cells in chemo-therapeutics.

  7. Dissociation free-energy profiles of specific and nonspecific DNA-protein complexes.

    PubMed

    Yonetani, Yoshiteru; Kono, Hidetoshi

    2013-06-27

    DNA-binding proteins recognize DNA sequences with at least two different binding modes: specific and nonspecific. Experimental structures of such complexes provide us a static view of the bindings. However, it is difficult to reveal further mechanisms of their target-site search and recognition only from static information because the transition process between the bound and unbound states is not clarified by static information. What is the difference between specific and nonspecific bindings? Here we performed adaptive biasing force molecular dynamics simulations with the specific and nonspecific structures of DNA-Lac repressor complexes to investigate the dissociation process. The resultant free-energy profiles showed that the specific complex has a sharp, deep well consistent with tight binding, whereas the nonspecific complex has a broad, shallow well consistent with loose binding. The difference in the well depth, ~5 kcal/mol, was in fair agreement with the experimentally obtained value and was found to mainly come from the protein conformational difference, particularly in the C-terminal tail. Also, the free-energy profiles were found to be correlated with changes in the number of protein-DNA contacts and that of surface water molecules. The derived protein spatial distributions around the DNA indicate that any large dissociation occurs rarely, regardless of the specific and nonspecific sites. Comparison of the free-energy barrier for sliding [~8.7 kcal/mol; Furini J. Phys. Chem. B 2010, 114, 2238] and that for dissociation (at least ~16 kcal/mol) calculated in this study suggests that sliding is much preferred to dissociation. PMID:23713479

  8. Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases.

    PubMed

    Marbach, Daniel; Lamparter, David; Quon, Gerald; Kellis, Manolis; Kutalik, Zoltán; Bergmann, Sven

    2016-04-01

    Mapping perturbed molecular circuits that underlie complex diseases remains a great challenge. We developed a comprehensive resource of 394 cell type- and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) showed that disease-associated genetic variants-including variants that do not reach genome-wide significance-often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissues (http://regulatorycircuits.org). PMID:26950747

  9. Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen

    PubMed Central

    Tsouchnikas, Georgios; Zlatkovic, Juergen; Jarmer, Johanna; Strauß, Judith; Vratskikh, Oksana; Kundi, Michael; Stiasny, Karin

    2015-01-01

    ABSTRACT The antibody response to proteins may be modulated by the presence of preexisting antigen-specific antibodies and the formation of immune complexes (ICs). Effects such as a general increase or decrease of the response as well as epitope-specific phenomena have been described. In this study, we investigated influences of IC immunization on the fine specificity of antibody responses in a structurally well-defined system, using the envelope (E) protein of tick-borne encephalitis (TBE) virus as an immunogen. TBE virus occurs in Europe and Asia and—together with the yellow fever, dengue, West Nile, and Japanese encephalitis viruses—represents one of the major human-pathogenic flaviviruses. Mice were immunized with a dimeric soluble form of E (sE) alone or in complex with monoclonal antibodies specific for each of the three domains of E, and the antibody response induced by these ICs was compared to that seen after immunization with sE alone. Immunoassays using recombinant domains and domain combinations of TBE virus sE as well as the distantly related West Nile virus sE allowed the dissection and quantification of antibody subsets present in postimmunization sera, thus generating fine-specificity patterns of the polyclonal responses. There were substantially different responses with two of the ICs, and the differences could be mechanistically related to (i) epitope shielding and (ii) antibody-mediated structural changes leading to dissociation of the sE dimer. The phenomena described may also be relevant for polyclonal responses upon secondary infections and/or booster immunizations and may affect antibody responses in an individual-specific way. IMPORTANCE Infections with flaviviruses such as yellow fever, dengue, Japanese encephalitis, West Nile, and tick-borne encephalitis (TBE) viruses pose substantial public health problems in different parts of the world. Antibodies to viral envelope protein E induced by natural infection or vaccination were shown to

  10. Modern Tools for Modern Software

    SciTech Connect

    Kumfert, G; Epperly, T

    2001-10-31

    This is a proposal for a new software configure/build tool for building, maintaining, deploying, and installing software. At its completion, this new tool will replace current standard tool suites such as ''autoconf'', ''automake'', ''libtool'', and the de facto standard build tool, ''make''. This ambitious project is born out of the realization that as scientific software has grown in size and complexity over the years, the difficulty of configuring and building software has increased as well. For high performance scientific software, additional complexities often arises from the need for portability to multiple platforms (including many one-of-a-kind platforms), multilanguage implementations, use of third party libraries, and a need to adapt algorithms to the specific features of the hardware. Development of scientific software is being hampered by the quality of configuration and build tools commonly available. Inordinate amounts of time and expertise are required to develop and maintain the configure and build system for a moderately complex project. Better build and configure tools will increase developer productivity. This proposal is a first step in a process of shoring up the foundation upon which DOE software is created and used.

  11. Energy conservation and analysis and evaluation. [specifically at Slidell Computer Complex

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The survey assembled and made recommendations directed at conserving utilities and reducing the use of energy at the Slidell Computer Complex. Specific items included were: (1) scheduling and controlling the use of gas and electricity, (2) building modifications to reduce energy, (3) replacement of old, inefficient equipment, (4) modifications to control systems, (5) evaluations of economizer cycles in HVAC systems, and (6) corrective settings for thermostats, ductstats, and other temperature and pressure control devices.

  12. Characterising the atypical 5'-CG DNA sequence specificity of 9-aminoacridine carboxamide Pt complexes.

    PubMed

    Kava, Hieronimus W; Galea, Anne M; Md Jamil, Farhana; Feng, Yue; Murray, Vincent

    2014-08-01

    In this study, the DNA sequence specificity of four DNA-targeted 9-aminoacridine carboxamide Pt complexes was compared with cisplatin, using two specially constructed plasmid templates. One plasmid contained 5'-CG and 5'-GA insert sequences while the other plasmid contained a G-rich transferrin receptor gene promoter insert sequence. The damage profiles of each compound on the different DNA templates were quantified via a polymerase stop assay with fluorescently labelled primers and capillary electrophoresis. With the plasmid that contained 5'-CG and 5'-GA dinucleotides, the four 9-aminoacridine carboxamide Pt complexes produced distinctly different damage profiles as compared with cisplatin. These 9-aminoacridine complexes had greatly increased levels of DNA damage at CG and GA dinucleotides as compared with cisplatin. It was shown that the presence of a CG or GA dinucleotide was sufficient to reveal the altered DNA sequence selectivity of the 9-aminoacridine carboxamide Pt analogues. The DNA sequence specificity of the Pt complexes was also found to be similarly altered utilising the transferrin receptor DNA sequence. PMID:24827388

  13. Software design and documentation language

    NASA Technical Reports Server (NTRS)

    Kleine, H.

    1977-01-01

    A communications medium to support the design and documentation of complex software applications is studied. The medium also provides the following: (1) a processor which can convert design specifications into an intelligible, informative machine reproducible document; (2) a design and documentation language with forms and syntax that are simple, unrestrictive, and communicative; and (3) methodology for effective use of the language and processor.

  14. Software design and documentation language

    NASA Technical Reports Server (NTRS)

    Kleine, H.

    1980-01-01

    Language supports design and documentation of complex software. Included are: design and documentation language for expressing design concepts; processor that produces intelligble documentation based on design specifications; and methodology for using language and processor to create well-structured top-down programs and documentation. Processor is written in SIMSCRIPT 11.5 programming language for use on UNIVAC, IBM, and CDC machines.

  15. Nuquantus: Machine learning software for the characterization and quantification of cell nuclei in complex immunofluorescent tissue images

    PubMed Central

    Gross, Polina; Honnorat, Nicolas; Varol, Erdem; Wallner, Markus; Trappanese, Danielle M.; Sharp, Thomas E.; Starosta, Timothy; Duran, Jason M.; Koller, Sarah; Davatzikos, Christos; Houser, Steven R.

    2016-01-01

    Determination of fundamental mechanisms of disease often hinges on histopathology visualization and quantitative image analysis. Currently, the analysis of multi-channel fluorescence tissue images is primarily achieved by manual measurements of tissue cellular content and sub-cellular compartments. Since the current manual methodology for image analysis is a tedious and subjective approach, there is clearly a need for an automated analytical technique to process large-scale image datasets. Here, we introduce Nuquantus (Nuclei quantification utility software) - a novel machine learning-based analytical method, which identifies, quantifies and classifies nuclei based on cells of interest in composite fluorescent tissue images, in which cell borders are not visible. Nuquantus is an adaptive framework that learns the morphological attributes of intact tissue in the presence of anatomical variability and pathological processes. Nuquantus allowed us to robustly perform quantitative image analysis on remodeling cardiac tissue after myocardial infarction. Nuquantus reliably classifies cardiomyocyte versus non-cardiomyocyte nuclei and detects cell proliferation, as well as cell death in different cell classes. Broadly, Nuquantus provides innovative computerized methodology to analyze complex tissue images that significantly facilitates image analysis and minimizes human bias. PMID:27005843

  16. Nuquantus: Machine learning software for the characterization and quantification of cell nuclei in complex immunofluorescent tissue images

    NASA Astrophysics Data System (ADS)

    Gross, Polina; Honnorat, Nicolas; Varol, Erdem; Wallner, Markus; Trappanese, Danielle M.; Sharp, Thomas E.; Starosta, Timothy; Duran, Jason M.; Koller, Sarah; Davatzikos, Christos; Houser, Steven R.

    2016-03-01

    Determination of fundamental mechanisms of disease often hinges on histopathology visualization and quantitative image analysis. Currently, the analysis of multi-channel fluorescence tissue images is primarily achieved by manual measurements of tissue cellular content and sub-cellular compartments. Since the current manual methodology for image analysis is a tedious and subjective approach, there is clearly a need for an automated analytical technique to process large-scale image datasets. Here, we introduce Nuquantus (Nuclei quantification utility software) - a novel machine learning-based analytical method, which identifies, quantifies and classifies nuclei based on cells of interest in composite fluorescent tissue images, in which cell borders are not visible. Nuquantus is an adaptive framework that learns the morphological attributes of intact tissue in the presence of anatomical variability and pathological processes. Nuquantus allowed us to robustly perform quantitative image analysis on remodeling cardiac tissue after myocardial infarction. Nuquantus reliably classifies cardiomyocyte versus non-cardiomyocyte nuclei and detects cell proliferation, as well as cell death in different cell classes. Broadly, Nuquantus provides innovative computerized methodology to analyze complex tissue images that significantly facilitates image analysis and minimizes human bias.

  17. Nuquantus: Machine learning software for the characterization and quantification of cell nuclei in complex immunofluorescent tissue images.

    PubMed

    Gross, Polina; Honnorat, Nicolas; Varol, Erdem; Wallner, Markus; Trappanese, Danielle M; Sharp, Thomas E; Starosta, Timothy; Duran, Jason M; Koller, Sarah; Davatzikos, Christos; Houser, Steven R

    2016-01-01

    Determination of fundamental mechanisms of disease often hinges on histopathology visualization and quantitative image analysis. Currently, the analysis of multi-channel fluorescence tissue images is primarily achieved by manual measurements of tissue cellular content and sub-cellular compartments. Since the current manual methodology for image analysis is a tedious and subjective approach, there is clearly a need for an automated analytical technique to process large-scale image datasets. Here, we introduce Nuquantus (Nuclei quantification utility software) - a novel machine learning-based analytical method, which identifies, quantifies and classifies nuclei based on cells of interest in composite fluorescent tissue images, in which cell borders are not visible. Nuquantus is an adaptive framework that learns the morphological attributes of intact tissue in the presence of anatomical variability and pathological processes. Nuquantus allowed us to robustly perform quantitative image analysis on remodeling cardiac tissue after myocardial infarction. Nuquantus reliably classifies cardiomyocyte versus non-cardiomyocyte nuclei and detects cell proliferation, as well as cell death in different cell classes. Broadly, Nuquantus provides innovative computerized methodology to analyze complex tissue images that significantly facilitates image analysis and minimizes human bias. PMID:27005843

  18. Software attribute visualization for high integrity software

    SciTech Connect

    Pollock, G.M.

    1998-03-01

    This report documents a prototype tool developed to investigate the use of visualization and virtual reality technologies for improving software surety confidence. The tool is utilized within the execution phase of the software life cycle. It provides a capability to monitor an executing program against prespecified requirements constraints provided in a program written in the requirements specification language SAGE. The resulting Software Attribute Visual Analysis Tool (SAVAnT) also provides a technique to assess the completeness of a software specification.

  19. A Hybrid Approach to Finding Relevant Social Media Content for Complex Domain Specific Information Needs

    PubMed Central

    Cameron, Delroy; Sheth, Amit P.; Jaykumar, Nishita; Thirunarayan, Krishnaprasad; Anand, Gaurish; Smith, Gary A.

    2015-01-01

    While contemporary semantic search systems offer to improve classical keyword-based search, they are not always adequate for complex domain specific information needs. The domain of prescription drug abuse, for example, requires knowledge of both ontological concepts and “intelligible constructs” not typically modeled in ontologies. These intelligible constructs convey essential information that include notions of intensity, frequency, interval, dosage and sentiments, which could be important to the holistic needs of the information seeker. In this paper, we present a hybrid approach to domain specific information retrieval that integrates ontology-driven query interpretation with synonym-based query expansion and domain specific rules, to facilitate search in social media on prescription drug abuse. Our framework is based on a context-free grammar (CFG) that defines the query language of constructs interpretable by the search system. The grammar provides two levels of semantic interpretation: 1) a top-level CFG that facilitates retrieval of diverse textual patterns, which belong to broad templates and 2) a low-level CFG that enables interpretation of specific expressions belonging to such textual patterns. These low-level expressions occur as concepts from four different categories of data: 1) ontological concepts, 2) concepts in lexicons (such as emotions and sentiments), 3) concepts in lexicons with only partial ontology representation, called lexico-ontology concepts (such as side effects and routes of administration (ROA)), and 4) domain specific expressions (such as date, time, interval, frequency and dosage) derived solely through rules. Our approach is embodied in a novel Semantic Web platform called PREDOSE, which provides search support for complex domain specific information needs in prescription drug abuse epidemiology. When applied to a corpus of over 1 million drug abuse-related web forum posts, our search framework proved effective in retrieving

  20. The Impact of Specific and Complex Trauma on the Mental Health of Homeless Youth.

    PubMed

    Wong, Carolyn F; Clark, Leslie F; Marlotte, Lauren

    2016-03-01

    This study investigates the relative impact of trauma experiences that occurred prior to and since becoming homeless on depressive symptoms, posttraumatic stress disorder (PTSD) symptoms, and self-injurious behaviors among a sample of homeless youth (N = 389). Youth (aged 13 to 25) who had been homeless or precariously housed in the past year completed a survey about housing history, experiences of violence and victimization, mental health, and service utilization. In addition to examining the impact associated with specific trauma types, we also considered the effect of "early-on" poly-victimization (i.e., cumulative number of reported traumas prior to homelessness) and the influence of a compound sexual trauma variable created to represent earlier complex trauma. This created-variable has values ranging from no reported trauma, single trauma, multiple non-sexual traumas, and multiple traumas that co-occurred with sexual abuse. Multivariate analyses revealed that specific traumatic experiences prior to homelessness, including sexual abuse, emotional abuse/neglect, and adverse home environment, predicted greater mental health symptoms. Poly-victimization did not add to the prediction of mental health symptoms after the inclusion of specific traumas. Results with early compound sexual trauma revealed significant differences between lower-order trauma exposures and multiple-trauma exposures. Specifically, experience of multiple traumas that co-occurred with sexual trauma was significantly more detrimental in predicting PTSD symptoms than multiple traumas of non-sexual nature. Findings support the utility of an alternate/novel conceptualization of complex trauma, and support the need to carefully evaluate complex traumatic experiences that occurred prior to homelessness, which can impact the design and implementation of mental health care and services for homeless youth. PMID:25392379

  1. Specific and Rapid Detection of Mycobacterium tuberculosis Complex in Clinical Samples by Polymerase Chain Reaction

    PubMed Central

    Singh, Anamika; Kashyap, Vijendra Kumar

    2012-01-01

    Background. Tuberculosis, a global health problem and highly prevalent in India, has always been a serious problem with respect to definitive diagnosis. Polymerase chain reaction (PCR) techniques are now widely used for early detection and species differentiation of mycobacteria, but mostly with their own limitations. We aim to detect and differentiate Mycobacterium tuberculosis (Mtb) infections by choosing appropriate target sequences, ideally present in all mycobacterial species (MTB complex) and absent in others. Methods. Amplification of three target sequences from unrelated genes, namely, hsp 65 (165 bp), dnaJ (365 bp), and insertion element IS 6110 (541 bp) by PCR was carried out in clinical samples from suspected cases of tuberculosis/ mycobacterioses and healthy controls. Results. The sensitivity of this method ranged from 73.33% to 84.61%, and the specificity was 80%. The PCR method was significantly better (P = 0.03 and P = 0.009) than both smear and culture methods. Conclusion. Our trimarker-based PCR method could specifically detect M. tuberculosis and MTB complex infection from that of major pathogenic NTM and nonpathogenic mycobacteria. This method, by well distinguishing between MTB complex and NTM, presented a fast and accurate method to detect and diagnose mycobacterial infections more efficiently and could thereby help in better patient management particularly considering the increase in mycobacterial infections due to emergence of NTM over the past decades. PMID:23093958

  2. Specific Nucleotide Binding and Rebinding to Individual DNA Polymerase Complexes Captured on a Nanopore

    PubMed Central

    Hurt, Nicholas; Wang, Hongyun; Akeson, Mark; Lieberman, Kate R.

    2009-01-01

    Nanoscale pores are a tool for single molecule analysis of DNA or RNA processing enzymes. Monitoring catalytic activity in real time using this technique requires that these enzymes retain function while held atop a nanopore in an applied electric field. Using an α-hemolysin nanopore, we measured the dwell time for complexes of DNA with the Klenow fragment of Escherichia coli DNA polymerase I (KF) as a function of the concentration of deoxynucleoside triphosphate (dNTP) substrate. We analyzed these dwell time measurements in the framework of a two-state model for captured complexes (DNA-KF binary and DNA-KF-dNTP ternary states). Average nanopore dwell time increased without saturating as a function of correct dNTP concentration across four orders of magnitude. This arises from two factors that are proportional to dNTP concentration: 1) The fraction of complexes that are in the ternary state when initially captured predominantly affects dwell time at low dNTP concentrations; 2) The rate of binding and rebinding of dNTP to captured complexes affects dwell time at higher dNTP concentrations. Thus there are two regimes that display a linear relationship between average dwell time and dNTP concentration. The transition from one linear regime to the other occurs near the equilibrium dissociation constant (Kd) for dNTP binding to KF-DNA complexes in solution. We conclude from the combination of titration experiments and modeling that DNA-KF complexes captured atop the nanopore retain iterative, sequence-specific dNTP binding, as required for catalysis and fidelity in DNA synthesis. PMID:19275265

  3. A Rapid and Specific Method for the Detection of Indole in Complex Biological Samples

    PubMed Central

    Chappell, Cynthia; Gonzales, Christopher; Okhuysen, Pablo

    2015-01-01

    Indole, a bacterial product of tryptophan degradation, has a variety of important applications in the pharmaceutical industry and is a biomarker in biological and clinical specimens. Yet, specific assays to quantitate indole are complex and require expensive equipment and a high level of training. Thus, indole in biological samples is often estimated using the simple and rapid Kovács assay, which nonspecifically detects a variety of commonly occurring indole analogs. We demonstrate here a sensitive, specific, and rapid method for measuring indole in complex biological samples using a specific reaction between unsubstituted indole and hydroxylamine. We compared the hydroxylamine-based indole assay (HIA) to the Kovács assay and confirmed that the two assays are capable of detecting microgram amounts of indole. However, the HIA is specific to indole and does not detect other naturally occurring indole analogs. We further demonstrated the utility of the HIA in measuring indole levels in clinically relevant biological materials, such as fecal samples and bacterial cultures. Mean and median fecal indole concentrations from 53 healthy adults were 2.59 mM and 2.73 mM, respectively, but varied widely (0.30 mM to 6.64 mM) among individuals. We also determined that enterotoxigenic Escherichia coli strain H10407 produces 3.3 ± 0.22 mM indole during a 24-h period in the presence of 5 mM tryptophan. The sensitive and specific HIA should be of value in a variety of settings, such as the evaluation of various clinical samples and the study of indole-producing bacterial species in the gut microbiota. PMID:26386049

  4. Confident Assignment of Site-Specific Glycosylation in Complex Glycoproteins in a Single Step

    PubMed Central

    2015-01-01

    A glycoprotein may contain several sites of glycosylation, each of which is heterogeneous. As a consequence of glycoform diversity and signal suppression from nonglycosylated peptides that ionize more efficiently, typical reversed-phase LC–MS and bottom–up proteomics database searching workflows do not perform well for identification of site-specific glycosylation for complex glycoproteins. We present an LC–MS system for enrichment, separation, and analysis of glycopeptides from complex glycoproteins (>4 N-glycosylation sequons) in a single step. This system uses an online HILIC enrichment trap prior to reversed-phase C18-MS analysis. We demonstrated the effectiveness of the system using a set of glycoproteins including human transferrin (2 sequons), human alpha-1-acid glycoprotein (5 sequons), and influenza A virus hemagglutinin (9 sequons). The online enrichment renders glycopeptides the most abundant ions detected, thereby facilitating the generation of high-quality data-dependent tandem mass spectra. The tandem mass spectra exhibited product ions from both glycan and peptide backbone dissociation for a majority of the glycopeptides tested using collisionally activated dissociation that served to confidently assign site-specific glycosylation. We demonstrated the value of our system to define site-specific glycosylation using a hemagglutinin containing 9 N-glycosylation sequons from a single HILIC-C18-MS acquisition. PMID:25153361

  5. Rapid and specific SPRi detection of L. pneumophila in complex environmental water samples.

    PubMed

    Foudeh, Amir M; Trigui, Hana; Mendis, Nilmini; Faucher, Sebastien P; Veres, Teodor; Tabrizian, Maryam

    2015-07-01

    Legionellosis is a very devastating disease worldwide mainly due to unpredictable outbreaks in man-made water systems. Developing a highly specific and sensitive rapid detection system that detects only metabolically active bacteria is a main priority for water quality assessment. We previously developed a versatile technique for sensitive and specific detection of synthetic RNA. In the present work, we further investigated the performance of the developed biosensor for detection of Legionella pneumophila in complex environmental samples, particularly those containing protozoa. The specificity and sensitivity of the detection system were verified using total RNA extracted from L. pneumophila in spiked water co-cultured with amoebae. We demonstrated that the expression level of ribosomal RNA (rRNA) is extremely dependent on the environmental conditions. The presence of amoebae with L. pneumophila, especially in nutrition-deprived samples, increased the amount of L. pneumophila 15-fold after 1 week as measured through the expression of 16s rRNA. Using the developed surface plasmon resonance imaging (SPRi) detection method, we were also able to successfully detect L. pneumophila within 3 h, both in the presence and absence of amoebae in the complex environmental samples obtained from a cooling water tower. These findings suggest that the developed biosensing system is a viable method for rapid, real-time and effective detection not only for L. pneumophila in environmental samples but also to assess the risk associated with the use of water contaminated with other pathogens. PMID:25935681

  6. Complexity from Specificity: Light Scattering and Colloidal Studies of Dscam Self-Association

    NASA Astrophysics Data System (ADS)

    Collins, Jesse; Arkus, Natalie; Meng, Guangnan; Brenner, Michael; Schmucker, Dietmar; Manoharan, Vinothan

    2008-03-01

    The self-assembly of complex structures from nanometer-sized building blocks is of great technological importance(i.e. for the development of tissue scaffolds and photonic crystals) and is of significant basic scientific interest. Here I present light scattering and colloidal aggregation studies of Dscam, a protein with over 18,000 splice variants which all (or almost all) exhibit exclusively homophilic binding, and which is necessary for the generation of structural complexity in the brain of insects. Static and dynamic light scattering data reveal the statistical mechanical properties of Dscam self-association, including the free energy, second virial coefficient, and oligomer molecular weight. Finally, I demonstrate how to exploit Dscam's unprecedented level of molecular diversity and specificity for the self-assembly of custom nano- and micro-structures out of Dscam-conjugated colloids.

  7. Complex I and complex III inhibition specifically increase cytosolic hydrogen peroxide levels without inducing oxidative stress in HEK293 cells

    PubMed Central

    Forkink, Marleen; Basit, Farhan; Teixeira, José; Swarts, Herman G.; Koopman, Werner J.H.; Willems, Peter H.G.M.

    2015-01-01

    Inhibitor studies with isolated mitochondria demonstrated that complex I (CI) and III (CIII) of the electron transport chain (ETC) can act as relevant sources of mitochondrial reactive oxygen species (ROS). Here we studied ROS generation and oxidative stress induction during chronic (24 h) inhibition of CI and CIII using rotenone (ROT) and antimycin A (AA), respectively, in intact HEK293 cells. Both inhibitors stimulated oxidation of the ROS sensor hydroethidine (HEt) and increased mitochondrial NAD(P)H levels without major effects on cell viability. Integrated analysis of cells stably expressing cytosolic- or mitochondria-targeted variants of the reporter molecules HyPer (H2O2-sensitive and pH-sensitive) and SypHer (H2O2-insensitive and pH-sensitive), revealed that CI- and CIII inhibition increased cytosolic but not mitochondrial H2O2 levels. Total and mitochondria-specific lipid peroxidation was not increased in the inhibited cells as reported by the C11-BODIPY581/591 and MitoPerOx biosensors. Also expression of the superoxide-detoxifying enzymes CuZnSOD (cytosolic) and MnSOD (mitochondrial) was not affected. Oxyblot analysis revealed that protein carbonylation was not stimulated by CI and CIII inhibition. Our findings suggest that chronic inhibition of CI and CIII: (i) increases the levels of HEt-oxidizing ROS and (ii) specifically elevates cytosolic but not mitochondrial H2O2 levels, (iii) does not induce oxidative stress or substantial cell death. We conclude that the increased ROS levels are below the stress-inducing level and might play a role in redox signaling. PMID:26516986

  8. PAF Complex Plays Novel Subunit-Specific Roles in Alternative Cleavage and Polyadenylation

    PubMed Central

    Yang, Yan; Li, Wencheng; Hoque, Mainul; Hou, Liming; Shen, Steven; Tian, Bin; Dynlacht, Brian D.

    2016-01-01

    The PAF complex (Paf1C) has been shown to regulate chromatin modifications, gene transcription, and RNA polymerase II (PolII) elongation. Here, we provide the first genome-wide profiles for the distribution of the entire complex in mammalian cells using chromatin immunoprecipitation and high throughput sequencing. We show that Paf1C is recruited not only to promoters and gene bodies, but also to regions downstream of cleavage/polyadenylation (pA) sites at 3’ ends, a profile that sharply contrasted with the yeast complex. Remarkably, we identified novel, subunit-specific links between Paf1C and regulation of alternative cleavage and polyadenylation (APA) and upstream antisense transcription using RNAi coupled with deep sequencing of the 3’ ends of transcripts. Moreover, we found that depletion of Paf1C subunits resulted in the accumulation of PolII over gene bodies, which coincided with APA. Depletion of specific Paf1C subunits led to global loss of histone H2B ubiquitylation, although there was little impact of Paf1C depletion on other histone modifications, including tri-methylation of histone H3 on lysines 4 and 36 (H3K4me3 and H3K36me3), previously associated with this complex. Our results provide surprising differences with yeast, while unifying observations that link Paf1C with PolII elongation and RNA processing, and indicate that Paf1C subunits could play roles in controlling transcript length through suppression of PolII accumulation at transcription start site (TSS)-proximal pA sites and regulating pA site choice in 3’UTRs. PMID:26765774

  9. Conflict and Reconciliation in Software Design

    NASA Astrophysics Data System (ADS)

    Mandel, Eric

    2014-01-01

    Data analysis software is as open-ended and complex as the research it supports. The written specification is never the full story in an arena where users can’t always know what they want to do next. Requirements often are too vague or too concrete, missing or implicit. They sometimes conflict with one another. How can we design high quality software amidst these variables? In this talk, I will discuss provisional conclusions I have reached concerning software design, based on thirty years of experience developing astronomical software.

  10. Programming Language Software For Graphics Applications

    NASA Technical Reports Server (NTRS)

    Beckman, Brian C.

    1993-01-01

    New approach reduces repetitive development of features common to different applications. High-level programming language and interactive environment with access to graphical hardware and software created by adding graphical commands and other constructs to standardized, general-purpose programming language, "Scheme". Designed for use in developing other software incorporating interactive computer-graphics capabilities into application programs. Provides alternative to programming entire applications in C or FORTRAN, specifically ameliorating design and implementation of complex control and data structures typifying applications with interactive graphics. Enables experimental programming and rapid development of prototype software, and yields high-level programs serving as executable versions of software-design documentation.

  11. An Advanced User Interface Approach for Complex Parameter Study Process Specification in the Information Power Grid

    NASA Technical Reports Server (NTRS)

    Yarrow, Maurice; McCann, Karen M.; Biswas, Rupak; VanderWijngaart, Rob; Yan, Jerry C. (Technical Monitor)

    2000-01-01

    The creation of parameter study suites has recently become a more challenging problem as the parameter studies have now become multi-tiered and the computational environment has become a supercomputer grid. The parameter spaces are vast, the individual problem sizes are getting larger, and researchers are now seeking to combine several successive stages of parameterization and computation. Simultaneously, grid-based computing offers great resource opportunity but at the expense of great difficulty of use. We present an approach to this problem which stresses intuitive visual design tools for parameter study creation and complex process specification, and also offers programming-free access to grid-based supercomputer resources and process automation.

  12. Ascochlorin is a novel, specific inhibitor of the mitochondrial cytochrome bc1 complex

    PubMed Central

    Berry, Edward A.; Huang, Li-shar; Lee, Dong-Woo; Daldal, Fevzi; Nagai, Kazuo; Minagawa, Nobuko

    2009-01-01

    Ascochlorin is an isoprenoid antibiotic that is produced by the phytopathogenic fungus Ascochyta viciae. Similar to ascofuranone, which specifically inhibits trypanosome alternative oxidase by acting at the ubiquinol binding domain, ascochlorin is also structurally related to ubiquinol. When added to the mitochondrial preparations isolated from rat liver, or the yeast Pichia (Hansenula) anomala, ascochlorin inhibited the electron transport via CoQ in a fashion comparable to antimycin A and stigmatellin, indicating that this antibiotic acted on the cytochrome bc1 complex. In contrast to ascochlorin, ascofuranone had much less inhibition on the same activities. On the one hand, like the Qi site inhibitors antimycin A and funiculosin, ascochlorin induced in H. anomala the expression of nuclear-encoded alternative oxidase gene much more strongly than the Qo site inhibitors tested. On the other hand, it suppressed the reduction of cytochrome b and the generation of superoxide anion in the presence of antimycin A3 in a fashion similar to the Qo site inhibitor myxothiazol. These results suggested that ascochlorin might act at both the Qi and the Qo sites of the fungal cytochrome bc1 complex. Indeed, the altered electron paramagnetic resonance (EPR) line shape of the Rieske iron-sulfur protein, and the light-induced time resolved cytochrome b and c reduction kinetics of Rhodobacter capsulatus cytochrome bc1 complex in the presence of ascochlorin demonstrated that this inhibitor can bind to both the Qo and Qi sites of the bacterial enzyme. Additional experiments using purified bovine cytochrome bc1 complex showed that ascochlorin inhibits reduction of cytochrome b by ubiquinone through both Qi and Qo sites. Moreover, crystal structure of chicken cytochrome bc1 complex treated with excess ascochlorin revealed clear electron densities that could be attributed to ascochlorin bound at both the Qi and Qo sites. Overall findings clearly show that ascochlorin is an unusual

  13. Chromomycin dimer-DNA oligomer complexes. Sequence selectivity and divalent cation specificity.

    PubMed

    Gao, X L; Patel, D J

    1990-12-11

    This paper reports on a solution NMR characterization of the sequence selectivity and metal ion specificity in chromomycin-DNA oligomer complexes in the presence of divalent cations. The sequence selectivity studies have focused on chromomycin complexes with the self-complementary d(A1-A2-G3-G4-C5-C6-T7-T8) duplex containing a pair of adjacent (G3-G4).(C5-C6) steps and the self-complementary d(A1-G2-G3-A4-T5-C6-C7-T8) duplex containing a pair of separated (G2-G3).(C6-C7) steps in aqueous solution. The antitumor agent (chromomycin) and nucleic acid protons have been assigned following analysis of distance connectivities in NOESY spectra and coupling connectivities in DQF-COSY spectra for both complexes in H2O and D2O solution. The observed intermolecular NOEs establish that chromomycin binds as a Mg(II)-coordinated dimer [1 Mg(II) per complex] and contacts the minor-groove edge with retention of 2-fold symmetry centered about the (G3-G4-C5-C6).(G3-G4-C5-C6) segment of the d(A2G2C2T2) duplex. By contrast, complex formation is centered about the (G2-G3-A4-T5).(A4-T5-C6-C7) segment and results in removal of the two fold symmetry of the d(AG2ATC2T) duplex. Thus, the binding of one subunit of the chromomycin dimer at its preferred (G-G).(C-C) site assists in the binding of the second subunit to the less preferred adjacent (A-T).(A-T) site. These observations suggest a hierarchy of chromomycin binding sites, with a strong site detected at the (G-G) step due to the hydrogen-bonding potential of acceptor N3 and donor NH2 groups of guanosine that line the minor groove. The divalent cation specificity has been investigated by studies on the symmetric chromomycin-d(A2G2C2T2) complex in the presence of diamagnetic Mg(II), Zn(II), and Cd(II) cations and paramagnetic Ni(II) and Co(II) cations. A comparative NOESY study of the Mg(II) and Ni(II) symmetric complexes suggests that a single tightly bound divalent cation aligns the two chromomycins in the dimer through coordination to

  14. Astrocyte-Specific Overexpression of Nrf2 Protects Striatal Neurons from Mitochondrial Complex II Inhibition

    PubMed Central

    Calkins, Marcus J.; Vargas, Marcelo R.; Johnson, Delinda A.; Johnson, Jeffrey A.

    2010-01-01

    Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that is known to regulate a variety of cytoprotective genes through the antioxidant response element (ARE). This endogenous response is one of the major pathways by which cells are protected from xenobiotic or innate oxidative insults. Furthermore, in neural systems, astrocyte-specific activation of Nrf2 is known to protect neurons. In previous work, our laboratory found that Nrf2 protects from intrastriatal injections of the mitochondrial complex II inhibitor malonate. Here, we extend these results to show that multiple methods of astrocyte-specific Nrf2 overexpression provide protection from neurotoxicity in vivo. GFAP-Nrf2 transgenic mice are significantly more resistant to malonate lesioning. This outcome is associated with an increased basal resistance, but more so, an enhanced Nrf2 response to lesioning that attenuated the ensuing neurotoxicity. Furthermore, striatal transplantation of neuroprogenitor cells overexpressing Nrf2 that differentiate into astrocytes after grafting also significantly reduced malonate toxicity. Overall, these data establish that enhanced astrocytic Nrf2 response and Nrf2 preconditioning are both sufficient to protect from acute lesions from mitochondrial complex II inhibition. PMID:20211941

  15. Sequence-specific interactions of drugs interfering with the topoisomerase-DNA cleavage complex.

    PubMed

    Palumbo, Manlio; Gatto, Barbara; Moro, Stefano; Sissi, Claudia; Zagotto, Giuseppe

    2002-07-18

    DNA-processing enzymes, such as the topoisomerases (tops), represent major targets for potent anticancer (and antibacterial) agents. The drugs kill cells by poisoning the enzymes' catalytic cycle. Understanding the molecular details of top poisoning is a fundamental requisite for the rational development of novel, more effective antineoplastic drugs. In this connection, sequence-specific recognition of the top-DNA complex is a key step to preferentially direct the action of the drugs onto selected genomic sequences. In fact, the (reversible) interference of drugs with the top-DNA complex exhibits well-defined preferences for DNA bases in the proximity of the cleavage site, each drug showing peculiarities connected to its structural features. A second level of selectivity can be observed when chemically reactive groups are present in the structure of the top-directed drug. In this case, the enzyme recognizes or generates a unique site for covalent drug-DNA binding. This will further subtly modulate the drug's efficiency in stimulating DNA damage at selected sites. Finally, drugs can discriminate not only among different types of tops, but also among different isoenzymes, providing an additional level of specific selection. Once the molecular basis for DNA sequence-dependent recognition has been established, the above-mentioned modes to generate selectivity in drug poisoning can be rationally exploited, alone or in combination, to develop tailor-made drugs targeted at defined loci in cancer cells. PMID:12084456

  16. Drosophila homologs of transcriptional mediator complex subunits are required for adult cell and segment identity specification

    PubMed Central

    Boube, Muriel; Faucher, Christian; Joulia, Laurent; Cribbs, David L.; Bourbon, Henri-Marc

    2000-01-01

    The origins of specificity in gene expression are a central concern in understanding developmental control. Mediator protein complexes regulate transcriptional initiation, acting as modular adaptors linking specific transcription factors to core RNA polymerase II. Here, we identified the Drosophila homologs of 23 human mediator genes and mutations of two, dTRAP240 and of dTRAP80 (the putative fly homolog of yeast SRB4). Clonal analysis indicates a general role for dTRAP80 necessary for cell viability. The dTRAP240 gene is also essential, but cells lacking its function are viable and proliferate normally. Clones reveal localized developmental activities including a sex comb cell identity function. This contrasts with the ubiquitous nuclear accumulation of dTRAP240 protein in imaginal discs. Synergistic genetic interactions support shared developmental cell and segment identity functions of dTRAP240 and dTRAP80, potentially within a common complex. Further, they identify the homeotic Sex combs reduced product, required for the same cell/tissue identities, as a functional partner of these mediator proteins. PMID:11090137

  17. Allele-Specific Methylation Occurs at Genetic Variants Associated with Complex Disease

    PubMed Central

    Hutchinson, John N.; Raj, Towfique; Fagerness, Jes; Stahl, Eli; Viloria, Fernando T.; Gimelbrant, Alexander; Seddon, Johanna; Daly, Mark; Chess, Andrew; Plenge, Robert

    2014-01-01

    We hypothesize that the phenomenon of allele-specific methylation (ASM) may underlie the phenotypic effects of multiple variants identified by Genome-Wide Association studies (GWAS). We evaluate ASM in a human population and document its genome-wide patterns in an initial screen at up to 380,678 sites within the genome, or up to 5% of the total genomic CpGs. We show that while substantial inter-individual variation exists, 5% of assessed sites show evidence of ASM in at least six samples; the majority of these events (81%) are under genetic influence. Many of these cis-regulated ASM variants are also eQTLs in peripheral blood mononuclear cells and monocytes and/or in high linkage-disequilibrium with variants linked to complex disease. Finally, focusing on autoimmune phenotypes, we extend this initial screen to confirm the association of cis-regulated ASM with multiple complex disease-associated variants in an independent population using next-generation bisulfite sequencing. These four variants are implicated in complex phenotypes such as ulcerative colitis and AIDS progression disease (rs10491434), Celiac disease (rs2762051), Crohn's disease, IgA nephropathy and early-onset inflammatory bowel disease (rs713875) and height (rs6569648). Our results suggest cis-regulated ASM may provide a mechanistic link between the non-coding genetic changes and phenotypic variation observed in these diseases and further suggests a route to integrating DNA methylation status with GWAS results. PMID:24911414

  18. Structural investigation of the alpha-1-antichymotrypsin: prostate-specific antigen complex by comparative model building.

    PubMed Central

    Villoutreix, B. O.; Lilja, H.; Pettersson, K.; Lövgren, T.; Teleman, O.

    1996-01-01

    Prostate-specific antigen (PSA), produced by prostate cells, provides an excellent serum marker for prostate cancer. It belongs to the human kallikrein family of enzymes, a second prostate-derived member of which is human glandular kallikrein-1 (hK2). Active PSA and hK2 are both 237-residue kallikrein-like proteases, based on sequence homology. An hK2 model structure based on the serine protease fold is presented and compared to PSA and six other serine proteases in order to analyze in depth the role of the surface-accessible loops surrounding the active site. The results show that PSA and hK2 share extensive structural similarity and that most amino acid replacements are centered on the loops surrounding the active site. Furthermore, the electrostatic potential surfaces are very similar for PSA and hK2. PSA interacts with at least two serine protease inhibitors (serpins): alpha-1-antichymotrypsin (ACT) and protein C inhibitor (PCI). Three-dimensional model structures of the uncleaved ACT molecule were developed based upon the recent X-ray structure of uncleaved antithrombin. The serpin was docked both to PSA and hK2. Amino acid replacements and electrostatic complementarities indicate that the overall orientation of the proteins in these complexes is reasonable. In order to investigate PSA's heparin interaction sites, electrostatic computations were carried out on PSA, hK2, protein C, ACT, and PCI. Two heparin binding sites are suggested on the PSA surface and could explain the enhanced complex formation between PSA and PCI, while inhibiting the formation of the ACT-PSA complex, PSA, hK2, and their preliminary complexes with ACT should facilitate the understanding and prediction of structural and functional properties for these important proteins also with respect to prostate diseases. PMID:8732755

  19. The RAVE complex is an isoform-specific V-ATPase assembly factor in yeast

    PubMed Central

    Smardon, Anne M.; Diab, Heba I.; Tarsio, Maureen; Diakov, Theodore T.; Nasab, Negin Dehdar; West, Robert W.; Kane, Patricia M.

    2014-01-01

    The regulator of ATPase of vacuoles and endosomes (RAVE) complex is implicated in vacuolar H+-translocating ATPase (V-ATPase) assembly and activity. In yeast, rav1∆ mutants exhibit a Vma− growth phenotype characteristic of loss of V-ATPase activity only at high temperature. Synthetic genetic analysis identified mutations that exhibit a full, temperature-independent Vma− growth defect when combined with the rav1∆ mutation. These include class E vps mutations, which compromise endosomal sorting. The synthetic Vma− growth defect could not be attributed to loss of vacuolar acidification in the double mutants, as there was no vacuolar acidification in the rav1∆ mutant. The yeast V-ATPase a subunit is present as two isoforms, Stv1p in Golgi and endosomes and Vph1p in vacuoles. Rav1p interacts directly with the N-terminal domain of Vph1p. STV1 overexpression suppressed the growth defects of both rav1∆ and rav1∆vph1∆, and allowed RAVE-independent assembly of active Stv1p-containing V-ATPases in vacuoles. Mutations causing synthetic genetic defects in combination with rav1∆ perturbed the normal localization of Stv1–green fluorescent protein. We propose that RAVE is necessary for assembly of Vph1-containing V-ATPase complexes but not Stv1-containing complexes. Synthetic Vma− phenotypes arise from defects in Vph1p-containing complexes caused by rav1∆, combined with defects in Stv1p-containing V-ATPases caused by the second mutation. Thus RAVE is the first isoform-specific V-ATPase assembly factor. PMID:24307682

  20. Control Software

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Real-Time Innovations, Inc. (RTI) collaborated with Ames Research Center, the Jet Propulsion Laboratory and Stanford University to leverage NASA research to produce ControlShell software. RTI is the first "graduate" of Ames Research Center's Technology Commercialization Center. The ControlShell system was used extensively on a cooperative project to enhance the capabilities of a Russian-built Marsokhod rover being evaluated for eventual flight to Mars. RTI's ControlShell is complex, real-time command and control software, capable of processing information and controlling mechanical devices. One ControlShell tool is StethoScope. As a real-time data collection and display tool, StethoScope allows a user to see how a program is running without changing its execution. RTI has successfully applied its software savvy in other arenas, such as telecommunications, networking, video editing, semiconductor manufacturing, automobile systems, and medical imaging.

  1. Structure of Human Dual Specificity Protein Phosphatase 23, VHZ, Enzyme-Substrate/Product Complex

    SciTech Connect

    Agarwal,R.; Burley, S.; Swaminathan, S.

    2008-01-01

    Protein phosphorylation plays a crucial role in mitogenic signal transduction and regulation of cell growth and differentiation. Dual specificity protein phosphatase 23 (DUSP23) or VHZ mediates dephosphorylation of phospho-tyrosyl (pTyr) and phospho-seryl/threonyl (pSer/pThr) residues in specific proteins. In vitro, it can dephosphorylate p44ERK1 but not p54SAPK-{beta} and enhance activation of c-Jun N-terminal kinase (JNK) and p38. Human VHZ, the smallest of the catalytically active protein-tyrosine phosphatases (PTP) reported to date (150 residues), is a class I Cys-based PTP and bears the distinctive active site signature motif HCXXGXXRS(T). We present the crystal structure of VHZ determined at 1.93 angstrom resolution. The polypeptide chain adopts the typical a{beta}a PTP fold, giving rise to a shallow active site cleft that supports dual phosphorylated substrate specificity. Within our crystals, the Thr-135-Tyr-136 from a symmetry-related molecule bind in the active site with a malate ion, where they mimic the phosphorylated TY motif of the MAPK activation loop in an enzyme-substrate/product complex. Analyses of intermolecular interactions between the enzyme and this pseudo substrate/product along with functional analysis of Phe-66, Leu-97, and Phe-99 residues provide insights into the mechanism of substrate binding and catalysis in VHZ.

  2. Software Configuration Management Guidebook

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The growth in cost and importance of software to NASA has caused NASA to address the improvement of software development across the agency. One of the products of this program is a series of guidebooks that define a NASA concept of the assurance processes which are used in software development. The Software Assurance Guidebook, SMAP-GB-A201, issued in September, 1989, provides an overall picture of the concepts and practices of NASA in software assurance. Lower level guidebooks focus on specific activities that fall within the software assurance discipline, and provide more detailed information for the manager and/or practitioner. This is the Software Configuration Management Guidebook which describes software configuration management in a way that is compatible with practices in industry and at NASA Centers. Software configuration management is a key software development process, and is essential for doing software assurance.

  3. The Integrative Taxonomic Approach Reveals Host Specific Species in an Encyrtid Parasitoid Species Complex

    PubMed Central

    Chesters, Douglas; Wang, Ying; Yu, Fang; Bai, Ming; Zhang, Tong-Xin; Hu, Hao-Yuan; Zhu, Chao-Dong; Li, Cheng-De; Zhang, Yan-Zhou

    2012-01-01

    Integrated taxonomy uses evidence from a number of different character types to delimit species and other natural groupings. While this approach has been advocated recently, and should be of particular utility in the case of diminutive insect parasitoids, there are relatively few examples of its application in these taxa. Here, we use an integrated framework to delimit independent lineages in Encyrtus sasakii (Hymenoptera: Chalcidoidea: Encyrtidae), a parasitoid morphospecies previously considered a host generalist. Sequence variation at the DNA barcode (cytochrome c oxidase I, COI) and nuclear 28S rDNA loci were compared to morphometric recordings and mating compatibility tests, among samples of this species complex collected from its four scale insect hosts, covering a broad geographic range of northern and central China. Our results reveal that Encyrtus sasakii comprises three lineages that, while sharing a similar morphology, are highly divergent at the molecular level. At the barcode locus, the median K2P molecular distance between individuals from three primary populations was found to be 11.3%, well outside the divergence usually observed between Chalcidoidea conspecifics (0.5%). Corroborative evidence that the genetic lineages represent independent species was found from mating tests, where compatibility was observed only within populations, and morphometric analysis, which found that despite apparent morphological homogeneity, populations clustered according to forewing shape. The independent lineages defined by the integrated analysis correspond to the three scale insect hosts, suggesting the presence of host specific cryptic species. The finding of hidden host specificity in this species complex demonstrates the critical role that DNA barcoding will increasingly play in revealing hidden biodiversity in taxa that present difficulties for traditional taxonomic approaches. PMID:22666375

  4. Hybrid QM/MM study of FMO complex with polarized protein-specific charge

    NASA Astrophysics Data System (ADS)

    Jia, Xiangyu; Mei, Ye; Zhang, John Z. H.; Mo, Yan

    2015-11-01

    The Fenna-Matthews-Olson (FMO) light-harvesting complex is now one of the primary model systems for the study of excitation energy transfer (EET). However, the mechanism of the EET in this system is still controversial. In this work, molecular dynamics simulations and the electrostatic-embedding quantum-mechanics/molecular-mechanics single-point calculations have been employed to predict the energy transfer pathways utilizing the polarized protein-specific charge (PPC), which provides a more realistic description of Coulomb interaction potential in the protein than conventional mean-field charge scheme. The recently discovered eighth pigment has also been included in this study. Comparing with the conventional mean-field charges, more stable structures of FMO complex were found under PPC scheme during molecular dynamic simulation. Based on the electronic structure calculations, an exciton model was constructed to consider the couplings during excitation. The results show that pigments 3 and 4 dominate the lowest exciton levels whereas the highest exciton level are mainly constituted of pigments 1 and 6. This observation agrees well with the assumption based on the spatial distribution of the pigments. Moreover, the obtained spectral density in this study gives a reliable description of the diverse local environment embedding each pigment.

  5. Complexes of Thermotoga maritima S-adenosylmethionine decarboxylase provide insights into substrate specificity

    SciTech Connect

    Bale, Shridhar; Baba, Kavita; McCloskey, Diane E.; Pegg, Anthony E.; Ealick, Steven E.

    2010-06-25

    The polyamines putrescine, spermidine and spermine are ubiquitous aliphatic cations and are essential for cellular growth and differentiation. S-Adenosylmethionine decarboxylase (AdoMetDC) is a critical pyruvoyl-dependent enzyme in the polyamine-biosynthetic pathway. The crystal structures of AdoMetDC from humans and plants and of the AdoMetDC proenzyme from Thermotoga maritima have been obtained previously. Here, the crystal structures of activated T. maritima AdoMetDC (TmAdoMetDC) and of its complexes with S-adenosylmethionine methyl ester and 5{prime}-deoxy-5{prime}-dimethylthioadenosine are reported. The results demonstrate for the first time that TmAdoMetDC autoprocesses without the need for additional factors and that the enzyme contains two complete active sites, both of which use residues from both chains of the homodimer. The complexes provide insights into the substrate specificity and ligand binding of AdoMetDC in prokaryotes. The conservation of the ligand-binding mode and the active-site residues between human and T. maritima AdoMetDC provides insight into the evolution of AdoMetDC.

  6. Can pathway-specific LFPs be obtained in cytoarchitectonically complex structures?

    PubMed Central

    Makarova, Julia; Ortuño, Tania; Korovaichuk, Alejandra; Cudeiro, Javier; Makarov, Valeri A.; Rivadulla, Casto; Herreras, Oscar

    2014-01-01

    Deciphering how the brain encodes the continuous flow of information contained in natural stimuli requires understanding the spontaneous activity of functional assemblies in multiple neuronal populations. A promising integrative approach that combines multisite recordings of local field potentials (LFP) with an independent component analysis (ICA) enables continuous readouts of population specific activities of functionally different neuron groups to be obtained. We previously used this technique successfully in the hippocampus, a single-layer neuronal structure. Here we provide numerical evidence that the cytoarchitectonic complexity of other brain structures does not compromise the value of the ICA-separated LFP components, given that spatial sampling of LFP is representative. The spatial distribution of an LFP component may be quite complex due to folded and multilayered structure of the neuronal aggregate. Nevertheless, the time course of each LFP component is still a reliable postsynaptic convolution of spikes fired by a homogeneous afferent population. This claim is supported by preliminary experimental data obtained in the lateral geniculate nucleus of the awake monkey. PMID:24822038

  7. Substrate binding and specificity of rhomboid intramembrane protease revealed by substrate–peptide complex structures

    PubMed Central

    Zoll, Sebastian; Stanchev, Stancho; Began, Jakub; Škerle, Jan; Lepšík, Martin; Peclinovská, Lucie; Majer, Pavel; Strisovsky, Kvido

    2014-01-01

    The mechanisms of intramembrane proteases are incompletely understood due to the lack of structural data on substrate complexes. To gain insight into substrate binding by rhomboid proteases, we have synthesised a series of novel peptidyl-chloromethylketone (CMK) inhibitors and analysed their interactions with Escherichia coli rhomboid GlpG enzymologically and structurally. We show that peptidyl-CMKs derived from the natural rhomboid substrate TatA from bacterium Providencia stuartii bind GlpG in a substrate-like manner, and their co-crystal structures with GlpG reveal the S1 to S4 subsites of the protease. The S1 subsite is prominent and merges into the ‘water retention site’, suggesting intimate interplay between substrate binding, specificity and catalysis. Unexpectedly, the S4 subsite is plastically formed by residues of the L1 loop, an important but hitherto enigmatic feature of the rhomboid fold. We propose that the homologous region of members of the wider rhomboid-like protein superfamily may have similar substrate or client-protein binding function. Finally, using molecular dynamics, we generate a model of the Michaelis complex of the substrate bound in the active site of GlpG. PMID:25216680

  8. LABMAN and LINKMAN: a data management system specifically designed for genome searches of complex diseases.

    PubMed

    Adams, P

    1994-01-01

    Two programs have been developed to manage linkage analysis data. The first program, LABMAN, is a comprehensive laboratory data management system organizing pedigrees, blood DNA samples, DNA markers, Southern blot or polyacrylamide gels, autoradiographs, and marker-allele typings generated from these samples. Output includes mendelization checks for genetic incompatibilities in typings and formatted files ready for linkage analysis. LABMAN can also compress highly polymorphic allele systems into smaller allele systems facilitating analysis of large systems. The second program, LINKMAN, provides data management for lod score output from linkage analyses. It reads linkage analysis output files, calculates lod scores by family, associates lod scores with specific marker and family identifiers, and stores these data in a database where they can be combined with lod scores from previous analyses. LINKMAN easily incorporates any of a wide variety of genetic models. It produces formatted output of lod scores by user-specified criteria for reports or as ASCII files for input to other programs. If desired, tests of homogeneity of linkage across families can be run via the HOMOG program [Ott, 1991] and their output included in reports. The programs include features critical for conducting genome searches of complex diseases: They are easy-to-use, well-tested, and reliable. Data from multicenter investigations can be easily combined for analysis. Moreover, they include extensive error-checking capabilities, and they are specifically set up to protect blindness between laboratory workers and data analysts. LABMAN and LINKMAN are currently available free of charge under DOS. PMID:8013891

  9. Development of a Lactobacillus Specific T-RFLP Method to Determine Lactobacilli Diversity in Complex Samples

    PubMed Central

    Chen, Long; Teasdale, Matt T.; Kaczmarczyk, Melissa M.; Freund, Gregory G.; Miller, Michael J.

    2012-01-01

    Terminal restriction fragment length polymorphism (T-RFLP) analysis has been widely used for studying microbial communities. However, most T-RFLP assays use 16S rDNA as the target and are unable to accurately characterize a microbial subpopulation. In this study, we developed a novel T-RFLP protocol based on Lactobacillus hsp60 to rapidly characterize and compare lactobacilli composition. The theoretical terminal restriction fragment (TRF) profiles were calculated from 769 Lactobacillus hsp60 sequences from online databases. In silico digestion with restriction endonucleases AluI and TacI on hsp60 amplicons generated 83 distinct TRF patterns, of which, 70 were species specific. To validate the assay, five previously sequenced lactobacilli were cultured independently, mixed at known concentrations and subjected to analysis by T-RFLP. All five strains generated the predicted TRFs and a qualitative consistent relationship was revealed. We performed the T-RFLP protocol on fecal samples from mice fed 6 different diets (n=4). Principal component analysis and agglomerative hierarchical clustering revealed that the lactobacilli community was strongly connected to dietary supplementation. Our study demonstrates the potential for using Lactobacillus specific T-RFLP to characterize lactobacilli communities in complex samples. PMID:22981747

  10. Mmi1 RNA surveillance machinery directs RNAi complex RITS to specific meiotic genes in fission yeast

    PubMed Central

    Hiriart, Edwige; Vavasseur, Aurélia; Touat-Todeschini, Leila; Yamashita, Akira; Gilquin, Benoit; Lambert, Emeline; Perot, Jonathan; Shichino, Yuichi; Nazaret, Nicolas; Boyault, Cyril; Lachuer, Joel; Perazza, Daniel; Yamamoto, Masayuki; Verdel, André

    2012-01-01

    RNA interference (RNAi) silences gene expression by acting both at the transcriptional and post-transcriptional levels in a broad range of eukaryotes. In the fission yeast Schizosaccharomyces pombe the RNA-Induced Transcriptional Silencing (RITS) RNAi complex mediates heterochromatin formation at non-coding and repetitive DNA. However, the targeting and role of RITS at other genomic regions, including protein-coding genes, remain unknown. Here we show that RITS localizes to specific meiotic genes and mRNAs. Remarkably, RITS is guided to these meiotic targets by the RNA-binding protein Mmi1 and its associated RNA surveillance machinery that together degrade selective meiotic mRNAs during vegetative growth. Upon sexual differentiation, RITS localization to the meiotic genes and mRNAs is lost. Large-scale identification of Mmi1 RNA targets reveals that RITS subunit Chp1 associates with the vast majority of them. In addition, loss of RNAi affects the effective repression of sexual differentiation mediated by the Mmi1 RNA surveillance machinery. These findings uncover a new mechanism for recruiting RNAi to specific meiotic genes and suggest that RNAi participates in the control of sexual differentiation in fission yeast. PMID:22522705

  11. Effect of compressive force on unbinding specific protein-ligand complexes with force spectroscopy.

    PubMed

    Bowers, Carleen M; Carlson, David A; Rivera, Monica; Clark, Robert L; Toone, Eric J

    2013-05-01

    Atomic force microscopy (AFM) is used extensively for the investigation of noncovalent molecular association. Although the technique is used to derive various types of information, in almost all instances the frequency of complex formation, the magnitude of rupture forces, and the shape of the force-distance curve are used to determine the behavior of the system. We have used AFM to consider the effect of contact force on the unbinding profiles of lactose-galectin-3, as well as the control pairs lactose-KDPG aldolase, and mannose-galectin-3, where the interacting species show negligible solution-phase affinity. Increased contact forces (>250 pN) resulted in increased probabilitites of binding and decreased blocking efficiencies for the cognate ligand-receptor pair lactose-G3. Increased contact force applied to two control systems with no known affinity, mannose-G3 and lactose-KDPG aldolase, resulted in nonspecific ruptures that were indistinguishable from those of specific lactose-G3 interactions. These results demonstrate that careful experimental design is vital to the production of interpretable data, and suggest that contact force minimization is an effective technique for probing the unbinding forces and rupture lengths of only specific ligand-receptor interactions. PMID:23537272

  12. Does the major histocompatibility complex serve as a specific receptor for Semliki Forest virus?

    PubMed Central

    Oldstone, M B; Tishon, A; Dutko, F J; Kennedy, S I; Holland, J J; Lampert, P W

    1980-01-01

    Murine F9 and PCC4 teratoma cells do not express H-2 major transplantation antigens according to virus-specific T-lymphocyte cytotoxic or serological assays. However, such cells can be infected with and readily replicate many types of viruses (coxsackie B 3, mouse hepatitis, Sindbis, Semliki Forest [SFV], lymphocytic choriomeningitis, Pichinde, vesicular stomatitis, herpes simplex type 1) to the same extent as do murine F12 teratoma cells and mouse embryo fibroblasts, all of which express the H-2 determinants. In contrast, F9 and PCC4 cells are not productively infected with murine cytomegalovirus, whereas F12 and mouse embryo fibroblast cells are. In addition to replicating in H-2-negative murine teratoma cells, SFV replicates in H-2-negative murine lymphoblastoid cells. The ability of SFV to infect cells without H-2 antigens and then to effect viral antigenic expression in the cells' cytoplasm and on their surface with similar kinetics and in equivalent amounts as cells with H-2 antigens indicates that the H-2 receptor is not needed for SFV infection. Daudi cells, which lack HLA antigens, block the replication of SFV. This occurs at some point after receptor binding, as demonstrated by diminished viral mRNA. In addition, a possible membrane defect precludes viral exit in Daudi cells transfected with SFV infectious RNA. These results indicate that a cell's possession of H-2 antigens is not a requirement for SFV infection and that major histocompatibility complex antigens are not specific receptors for this virus. Images PMID:7373708

  13. Software for SARA

    SciTech Connect

    Quinn, P.

    1991-10-01

    This paper reports on an increasing number of consulting and software companies that offer PC-based information management programs designed to help companies comply with SARA Title III reporting requirements and the OSHA Hazard Communication Standard (HCS). These are available in a wide range of specific capabilities, from relatively simple systems that enable electronic filing of MSDSs to complex, multi-user systems that track and compute air and water emissions, maintain inventory and manifest records, and generate compliance reports. Prices range from less than $1,000 to more than $20,000.

  14. Assessing the complex sponge microbiota: core, variable and species-specific bacterial communities in marine sponges

    PubMed Central

    Schmitt, Susanne; Tsai, Peter; Bell, James; Fromont, Jane; Ilan, Micha; Lindquist, Niels; Perez, Thierry; Rodrigo, Allen; Schupp, Peter J; Vacelet, Jean; Webster, Nicole; Hentschel, Ute; Taylor, Michael W

    2012-01-01

    Marine sponges are well known for their associations with highly diverse, yet very specific and often highly similar microbiota. The aim of this study was to identify potential bacterial sub-populations in relation to sponge phylogeny and sampling sites and to define the core bacterial community. 16S ribosomal RNA gene amplicon pyrosequencing was applied to 32 sponge species from eight locations around the world's oceans, thereby generating 2567 operational taxonomic units (OTUs at the 97% sequence similarity level) in total and up to 364 different OTUs per sponge species. The taxonomic richness detected in this study comprised 25 bacterial phyla with Proteobacteria, Chloroflexi and Poribacteria being most diverse in sponges. Among these phyla were nine candidate phyla, six of them found for the first time in sponges. Similarity comparison of bacterial communities revealed no correlation with host phylogeny but a tropical sub-population in that tropical sponges have more similar bacterial communities to each other than to subtropical sponges. A minimal core bacterial community consisting of very few OTUs (97%, 95% and 90%) was found. These microbes have a global distribution and are probably acquired via environmental transmission. In contrast, a large species-specific bacterial community was detected, which is represented by OTUs present in only a single sponge species. The species-specific bacterial community is probably mainly vertically transmitted. It is proposed that different sponges contain different bacterial species, however, these bacteria are still closely related to each other explaining the observed similarity of bacterial communities in sponges in this and previous studies. This global analysis represents the most comprehensive study of bacterial symbionts in sponges to date and provides novel insights into the complex structure of these unique associations. PMID:21993395

  15. Formal Methods Specification and Analysis Guidebook for the Verification of Software and Computer Systems. Volume 2; A Practitioner's Companion

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This guidebook, the second of a two-volume series, is intended to facilitate the transfer of formal methods to the avionics and aerospace community. The 1st volume concentrates on administrative and planning issues [NASA-95a], and the second volume focuses on the technical issues involved in applying formal methods to avionics and aerospace software systems. Hereafter, the term "guidebook" refers exclusively to the second volume of the series. The title of this second volume, A Practitioner's Companion, conveys its intent. The guidebook is written primarily for the nonexpert and requires little or no prior experience with formal methods techniques and tools. However, it does attempt to distill some of the more subtle ingredients in the productive application of formal methods. To the extent that it succeeds, those conversant with formal methods will also nd the guidebook useful. The discussion is illustrated through the development of a realistic example, relevant fragments of which appear in each chapter. The guidebook focuses primarily on the use of formal methods for analysis of requirements and high-level design, the stages at which formal methods have been most productively applied. Although much of the discussion applies to low-level design and implementation, the guidebook does not discuss issues involved in the later life cycle application of formal methods.

  16. Shuttle mission simulator software conceptual design

    NASA Technical Reports Server (NTRS)

    Burke, J. F.

    1973-01-01

    Software conceptual designs (SCD) are presented for meeting the simulator requirements for the shuttle missions. The major areas of the SCD discussed include: malfunction insertion, flight software, applications software, systems software, and computer complex.

  17. A software system used for load distribution at a combined heat and power plant with the complex mix of the equipment and complex schemes of heat and electric power supply

    NASA Astrophysics Data System (ADS)

    Makarch'yan, V. A.; Chernyaev, A. N.; Andryushin, A. V.; Pechenkin, S. P.; Lisitsa, V. I.; Logvinov, E. I.; Molchanov, A. Yu.

    2013-05-01

    The authors describe various approaches to construction of an algorithm for the solution of the problem of load distribution at a combined heat and power (CHP) plant with the complex mix of the equipment and complex schemes of heat and electrical energy supply on the basis of which the software system has been developed. Methods of obtaining energy characteristics of the equipment used for solving the problem of load distribution were studied. The results of the implementation of the software system for load distribution at the CHP-23 plant belonging to OAO Mosenergo are given. Realization of recommendations on maintaining an operational mode of the equipment with due regard for its optimal loading makes it possible to obtain fuel savings of up to 1%.

  18. Evolutionary Genomics Reveals Lineage-Specific Gene Loss and Rapid Evolution of a Sperm-Specific Ion Channel Complex: CatSpers and CatSperβ

    PubMed Central

    Cai, Xinjiang; Clapham, David E.

    2008-01-01

    The mammalian CatSper ion channel family consists of four sperm-specific voltage-gated Ca2+ channels that are crucial for sperm hyperactivation and male fertility. All four CatSper subunits are believed to assemble into a heteromultimeric channel complex, together with an auxiliary subunit, CatSperβ. Here, we report a comprehensive comparative genomics study and evolutionary analysis of CatSpers and CatSperβ, with important correlation to physiological significance of molecular evolution of the CatSper channel complex. The development of the CatSper channel complex with four CatSpers and CatSperβ originated as early as primitive metazoans such as the Cnidarian Nematostella vectensis. Comparative genomics revealed extensive lineage-specific gene loss of all four CatSpers and CatSperβ through metazoan evolution, especially in vertebrates. The CatSper channel complex underwent rapid evolution and functional divergence, while distinct evolutionary constraints appear to have acted on different domains and specific sites of the four CatSper genes. These results reveal unique evolutionary characteristics of sperm-specific Ca2+ channels and their adaptation to sperm biology through metazoan evolution. PMID:18974790

  19. Herpesvirus Late Gene Expression: A Viral-Specific Pre-initiation Complex Is Key

    PubMed Central

    Gruffat, Henri; Marchione, Roberta; Manet, Evelyne

    2016-01-01

    During their productive cycle, herpesviruses exhibit a strictly regulated temporal cascade of gene expression that can be divided into three general stages: immediate-early (IE), early (E), and late (L). This expression program is the result of a complex interplay between viral and cellular factors at both the transcriptional and post-transcriptional levels, as well as structural differences within the promoter architecture for each of the three gene classes. Since the cellular enzyme RNA polymerase II (RNAP-II) is responsible for the transcription of herpesvirus genes, most viral promoters contain DNA motifs that are common with those of cellular genes, although promoter complexity decreases from immediate-early to late genes. Immediate-early and early promoters contain numerous cellular and viral cis-regulating sequences upstream of a TATA box, whereas late promoters differ significantly in that they lack cis-acting sequences upstream of the transcription start site (TSS). Moreover, in the case of the β- and γ-herpesviruses, a TATT box motif is frequently found in the position where the consensus TATA box of eukaryotic promoters usually localizes. The mechanisms of transcriptional regulation of the late viral gene promoters appear to be different between α-herpesviruses and the two other herpesvirus subfamilies (β and γ). In this review, we will compare the mechanisms of late gene transcriptional regulation between HSV-1, for which the viral IE transcription factors – especially ICP4 – play an essential role, and the two other subfamilies of herpesviruses, with a particular emphasis on EBV, which has recently been found to code for its own specific TATT-binding protein. PMID:27375590

  20. Towards cancer cell-specific phototoxic organometallic rhenium(I) complexes.

    PubMed

    Leonidova, Anna; Pierroz, Vanessa; Rubbiani, Riccardo; Heier, Jakob; Ferrari, Stefano; Gasser, Gilles

    2014-03-21

    Over the recent years, several Re(I) organometallic compounds have been shown to be toxic to various cancer cell lines. However, these compounds lacked sufficient selectivity towards cancer tissues to be used as novel chemotherapeutic agents. In this study, we probe the potential of two known N,N-bis(quinolinoyl) Re(I) tricarbonyl complex derivatives, namely Re(I) tricarbonyl [N,N-bis(quinolin-2-ylmethyl)amino]-4-butane-1-amine (Re-NH₂) and Re(I) tricarbonyl [N,N-bis(quinolin-2-ylmethyl)amino]-5-valeric acid (Re-COOH), as photodynamic therapy (PDT) photosensitizers. Re-NH₂ and Re-COOH proved to be excellent singlet oxygen generators in a lipophilic environment with quantum yields of about 75%. Furthermore, we envisaged to improve the selectivity of Re-COOH via conjugation to two types of peptides, namely a nuclear localization signal (NLS) and a derivative of the neuropeptide bombesin, to form Re-NLS and Re-Bombesin, respectively. Fluorescent microscopy on cervical cancer cells (HeLa) showed that the conjugation of Re-COOH to NLS significantly enhanced the compound's accumulation into the cell nucleus and more specifically into its nucleoli. Importantly, in view of PDT applications, the cytotoxicity of the Re complexes and their bioconjugates increased significantly upon light irradiation. In particular, Re-Bombesin was found to be at least 20-fold more toxic after light irradiation. DNA photo-cleavage studies demonstrated that all compounds damaged DNA via singlet oxygen and, to a minor extent, superoxide production. PMID:23982882

  1. Serotype-Specific Structural Differences in the Protease-Cofactor Complexes of the Dengue Virus Family

    SciTech Connect

    Chandramouli, Sumana; Joseph, Jeremiah S.; Daudenarde, Sophie; Gatchalian, Jovylyn; Cornillez-Ty, Cromwell; Kuhn, Peter

    2010-03-04

    With an estimated 40% of the world population at risk, dengue poses a significant threat to human health, especially in tropical and subtropical regions. Preventative and curative efforts, such as vaccine development and drug discovery, face additional challenges due to the occurrence of four antigenically distinct serotypes of the causative dengue virus (DEN1 to -4). Complex immune responses resulting from repeat assaults by the different serotypes necessitate simultaneous targeting of all forms of the virus. One of the promising targets for drug development is the highly conserved two-component viral protease NS2B-NS3, which plays an essential role in viral replication by processing the viral precursor polyprotein into functional proteins. In this paper, we report the 2.1-{angstrom} crystal structure of the DEN1 NS2B hydrophilic core (residues 49 to 95) in complex with the NS3 protease domain (residues 1 to 186) carrying an internal deletion in the N terminus (residues 11 to 20). While the overall folds within the protease core are similar to those of DEN2 and DEN4 proteases, the conformation of the cofactor NS2B is dramatically different from those of other flaviviral apoprotease structures. The differences are especially apparent within its C-terminal region, implicated in substrate binding. The structure reveals for the first time serotype-specific structural elements in the dengue virus family, with the reported alternate conformation resulting from a unique metal-binding site within the DEN1 sequence. We also report the identification of a 10-residue stretch within NS3pro that separates the substrate-binding function from the catalytic turnover rate of the enzyme. Implications for broad-spectrum drug discovery are discussed.

  2. The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-seq data analysis

    PubMed Central

    Chung, Betty Y.; Hardcastle, Thomas J.; Jones, Joshua D.; Irigoyen, Nerea; Firth, Andrew E.; Baulcombe, David C.; Brierley, Ian

    2015-01-01

    Ribosome profiling is a technique that permits genome-wide, quantitative analysis of translation and has found broad application in recent years. Here we describe a modified profiling protocol and software package designed to benefit more broadly the translation community in terms of simplicity and utility. The protocol, applicable to diverse organisms, including organelles, is based largely on previously published profiling methodologies, but uses duplex-specific nuclease (DSN) as a convenient, species-independent way to reduce rRNA contamination. We show that DSN-based depletion compares favorably with other commonly used rRNA depletion strategies and introduces little bias. The profiling protocol typically produces high levels of triplet periodicity, facilitating the detection of coding sequences, including upstream, downstream, and overlapping open reading frames (ORFs) and an alternative ribosome conformation evident during termination of protein synthesis. In addition, we provide a software package that presents a set of methods for parsing ribosomal profiling data from multiple samples, aligning reads to coding sequences, inferring alternative ORFs, and plotting average and transcript-specific aspects of the data. Methods are also provided for extracting the data in a form suitable for differential analysis of translation and translational efficiency. PMID:26286745

  3. The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-seq data analysis.

    PubMed

    Chung, Betty Y; Hardcastle, Thomas J; Jones, Joshua D; Irigoyen, Nerea; Firth, Andrew E; Baulcombe, David C; Brierley, Ian

    2015-10-01

    Ribosome profiling is a technique that permits genome-wide, quantitative analysis of translation and has found broad application in recent years. Here we describe a modified profiling protocol and software package designed to benefit more broadly the translation community in terms of simplicity and utility. The protocol, applicable to diverse organisms, including organelles, is based largely on previously published profiling methodologies, but uses duplex-specific nuclease (DSN) as a convenient, species-independent way to reduce rRNA contamination. We show that DSN-based depletion compares favorably with other commonly used rRNA depletion strategies and introduces little bias. The profiling protocol typically produces high levels of triplet periodicity, facilitating the detection of coding sequences, including upstream, downstream, and overlapping open reading frames (ORFs) and an alternative ribosome conformation evident during termination of protein synthesis. In addition, we provide a software package that presents a set of methods for parsing ribosomal profiling data from multiple samples, aligning reads to coding sequences, inferring alternative ORFs, and plotting average and transcript-specific aspects of the data. Methods are also provided for extracting the data in a form suitable for differential analysis of translation and translational efficiency. PMID:26286745

  4. Computer Software.

    ERIC Educational Resources Information Center

    Kay, Alan

    1984-01-01

    Discusses the nature and development of computer software. Programing, programing languages, types of software (including dynamic spreadsheets), and software of the future are among the topics considered. (JN)

  5. Effective Team Support: From Task and Cognitive Modeling to Software Agents for Time-Critical Complex Work Environments

    NASA Technical Reports Server (NTRS)

    Remington, Roger W. (Technical Monitor); John, Bonnie E.; Sycara, Katia

    2005-01-01

    The purpose of this research contract was to perform multidisciplinary research between CMU psychologists, computer scientists and NASA researchers to design a next generation collaborative system to support a team of human experts and intelligent agents. To achieve robust performance enhancement of such a system, we had proposed to perform task and cognitive modeling to thoroughly understand the impact technology makes on the organization and on key individual personnel. Guided by cognitively-inspired requirements, we would then develop software agents that support the human team in decision making, information filtering, information distribution and integration to enhance team situational awareness. During the period covered by this final report, we made substantial progress in completing a system for empirical data collection, cognitive modeling, and the building of software agents to support a team's tasks, and in running experiments for the collection of baseline data.

  6. Structural analysis of specificity: alpha-lytic protease complexes with analogues of reaction intermediates.

    PubMed

    Bone, R; Frank, D; Kettner, C A; Agard, D A

    1989-09-19

    To better understand the structural basis of enzyme specificity, the structures of complexes formed between alpha-lytic protease, an extracellular serine protease of Lysobacter enzymogenes, and five inhibitory peptide boronic acids (R2-boroX, where R2 is methoxysuccinyl-Ala-Ala-Pro- and boroX is the alpha-aminoboronic acid analogue of Ala, Val, Ile, Norleu, or Phe) have been studied at high resolution by X-ray crystallography. The enzyme has primary specificity for Ala in the P1 position of peptide substrates with catalytic efficiency decreasing with increasing side-chain volume. Enzyme affinity for inhibitors with boroVal, boroIle, and boroPhe residues is much higher than expected on the basis of the catalytic efficiencies of homologous substrates. Covalent tetrahedral adducts are formed between the active-site serine and the boronic acid moieties of R2-boroAla, R2-boroVal R2-boroIle, and R2-boroNorleu. Though R2-boroVal is a slowly bound inhibitor and R2-boroAla is rapidly bound [Kettner, C. A., Bone, R., Agard, D. A., & Bachovchin, W. W. (1988) Biochemistry 27, 7682-7688], there appear to be no structural differences that could account for slow binding. The removal from solution of 20% more hydrophobic surface on binding accounts for the improved affinity of alpha-lytic protease for R2-boroVal relative to R2-boroAla. The high affinity of the enzyme for R2-boroIle derives from the selective binding of the L-allo stereoisomer of the boroIle residue, which can avoid bad steric interactions in the binding pocket.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2611204

  7. Conservation of the TRAPPII-specific subunits of a Ypt/Rab exchanger complex

    PubMed Central

    Cox, Randal; Chen, Shu Hui; Yoo, Eunice; Segev, Nava

    2007-01-01

    Background Ypt/Rab GTPases and their GEF activators regulate intra-cellular trafficking in all eukaryotic cells. In S. cerivisiae, the modular TRAPP complex acts as a GEF for the Golgi gatekeepers: Ypt1 and the functional pair Ypt31/32. While TRAPPI, which acts in early Golgi, is conserved from fungi to animals, not much is known about TRAPPII, which acts in late Golgi and consists of TRAPPI plus three additional subunits. Results Here, we show a phylogenetic analysis of the three TRAPPII-specific subunits. One copy of each of the two essential subunits, Trs120 and Trs130, is present in almost every fully sequenced eukaryotic genome. Moreover, the primary, as well as the predicted secondary, structure of the Trs120- and Trs130-related sequences are conserved from fungi to animals. The mammalian orthologs of Trs120 and Trs130, NIBP and TMEM1, respectively, are candidates for human disorders. Currently, NIBP is implicated in signaling, and TMEM1 is suggested to have trans-membrane domains (TMDs) and to function as a membrane channel. However, we show here that the yeast Trs130 does not function as a trans-membrane protein, and the human TMEM1 does not contain putative TMDs. The non-essential subunit, Trs65, is conserved only among many fungi and some unicellular eukaryotes. Multiple alignment analysis of each TRAPPII-specific subunit revealed conserved domains that include highly conserved amino acids. Conclusion We suggest that the function of both NIBP and TMEM1 in the regulation of intra-cellular trafficking is conserved from yeast to man. The conserved domains and amino acids discovered here can be used for functional analysis that should help to resolve the differences in the assigned functions of these proteins in fungi and animals. PMID:17274825

  8. Tissue-specific regulatory network extractor (TS-REX): a database and software resource for the tissue and cell type-specific investigation of transcription factor-gene networks

    PubMed Central

    Colecchia, Federico; Kottwitz, Denise; Wagner, Mandy; Pfenninger, Cosima V.; Thiel, Gerald; Tamm, Ingo; Peterson, Carsten; Nuber, Ulrike A.

    2009-01-01

    The prediction of transcription factor binding sites in genomic sequences is in principle very useful to identify upstream regulatory factors. However, when applying this concept to genomes of multicellular organisms such as mammals, one has to deal with a large number of false positive predictions since many transcription factor genes are only expressed in specific tissues or cell types. We developed TS-REX, a database/software system that supports the analysis of tissue and cell type-specific transcription factor-gene networks based on expressed sequence tag abundance of transcription factor-encoding genes in UniGene EST libraries. The use of expression levels of transcription factor-encoding genes according to hierarchical anatomical classifications covering different tissues and cell types makes it possible to filter out irrelevant binding site predictions and to identify candidates of potential functional importance for further experimental testing. TS-REX covers ESTs from H. sapiens and M. musculus, and allows the characterization of both presence and specificity of transcription factors in user-specified tissues or cell types. The software allows users to interactively visualize transcription factor-gene networks, as well as to export data for further processing. TS-REX was applied to predict regulators of Polycomb group genes in six human tumor tissues and in human embryonic stem cells. PMID:19443447

  9. Tissue-specific regulatory network extractor (TS-REX): a database and software resource for the tissue and cell type-specific investigation of transcription factor-gene networks.

    PubMed

    Colecchia, Federico; Kottwitz, Denise; Wagner, Mandy; Pfenninger, Cosima V; Thiel, Gerald; Tamm, Ingo; Peterson, Carsten; Nuber, Ulrike A

    2009-06-01

    The prediction of transcription factor binding sites in genomic sequences is in principle very useful to identify upstream regulatory factors. However, when applying this concept to genomes of multicellular organisms such as mammals, one has to deal with a large number of false positive predictions since many transcription factor genes are only expressed in specific tissues or cell types. We developed TS-REX, a database/software system that supports the analysis of tissue and cell type-specific transcription factor-gene networks based on expressed sequence tag abundance of transcription factor-encoding genes in UniGene EST libraries. The use of expression levels of transcription factor-encoding genes according to hierarchical anatomical classifications covering different tissues and cell types makes it possible to filter out irrelevant binding site predictions and to identify candidates of potential functional importance for further experimental testing. TS-REX covers ESTs from H. sapiens and M. musculus, and allows the characterization of both presence and specificity of transcription factors in user-specified tissues or cell types. The software allows users to interactively visualize transcription factor-gene networks, as well as to export data for further processing. TS-REX was applied to predict regulators of Polycomb group genes in six human tumor tissues and in human embryonic stem cells. PMID:19443447

  10. Development of a software for control of the Lidar complex at the IAO SB RAS small Lidar station

    NASA Astrophysics Data System (ADS)

    Marichev, V. N.; Bochkovskii, D. A.

    2015-11-01

    The problems are discussed in the wide circles of the scientific community in the end of the last and in the beginning of present century, related with climate change on both global and local scale. The complicated question of changing climatic and ecological systems under the effect of natural and anthropogenic factors requires the development and creation of atmospheric aerosol thermodynamic and spatial-temporal models, development of network of both ground-based and space-based services for monitoring of the atmosphere on a global scale [1, 2]. Measures on collection of great amount of data lead to the need of development of not only technical side of the solution to the problem, but also methodological, algorithmic and software. The last decade is marked by the widespread introduction of computer technology into science and increase of its consumer features, such as speed, volume of RAM and cash memory, as well as the ability of high-quality displaying the data. Therefore, the final item in the development of automation of the experiment and application of mathematical methods is the development of the software tools. Software should carry the main load in the processing and simulation of an experiment, and to be a link between theoreticians, developers of the processing methods and models of physical processes and experimentalists

  11. Modular Software Performance Monitoring

    NASA Astrophysics Data System (ADS)

    Kruse, Daniele Francesco; Kruzelecki, Karol

    2011-12-01

    CPU clock frequency is not likely to be increased significantly in the coming years, and data analysis speed can be improved by using more processors or buying new machines, only if one is willing to change the programming paradigm to a parallel one. Therefore, performance monitoring procedures and tools are needed to help programmers to optimize existing software running on current and future hardware. Low level information from hardware performance counters is vital to spot specific performance problems slowing program execution. HEP software is often huge and complex, and existing tools are unable to give results with the required granularity. We will report on the approach we have chosen to solve this problem that involves decomposing the application into parts and monitoring each one of them separately. Both counting and sampling methods are used to allow an analysis with the required custom granularity: from global level, up to the function level. A set of tools (based on perfmon2 - a software interface to hardware counters) for CMSSW, Gaudi and Geant4 has been developed and deployed. We will show how this type of analysis has been proven useful in spotting specific performance problems and effective in helping with code optimization.

  12. A specific aptamer-cell penetrating peptides complex delivered siRNA efficiently and suppressed prostate tumor growth in vivo.

    PubMed

    Diao, Yanjun; Liu, Jiayun; Ma, Yueyun; Su, Mingquan; Zhang, Hongyi; Hao, Xiaoke

    2016-05-01

    Specific and efficient delivery of siRNA into intended tumor cells remains as a challenge, even though RNAi has been exploited as a new strategy for prostate cancer therapy. This work aims to address both specificity and efficiency of SURVIVIN-siRNA delivery by constructing a therapeutic complex using combinatorial strategies. A fusion protein STD was first expressed to serve as a backbone, consisting of streptavidin, a cell-penetrating peptide called Trans-Activator of Transcription (TAT) and a double-stranded RNA binding domain. A biotinylated Prostate Specific Membrane Antigen (PSMA) specific aptamer A10 and SURVIVIN-siRNA were then linked to STD protein to form the therapeutic complex. This complex could specifically targeted PSMA(+) tumor cells. Compared to lipofectamine and A10-siRNA chimera, it demonstrated higher efficiency in delivering siRNA into target cells by 19.2% and 59.9%, and increased apoptosis by 16.8% and 26.1% respectively. Upon systemic administration, this complex also showed significant efficacy in suppressing tumor growth in athymic mice (p <0.001). We conclude that this therapeutic complex could specifically and efficiently deliver SURVIVIN-siRNA to target cells and suppressed tumor growth in vivo, which indicates its potential to be used as a new strategy in prostate cancer therapy. PMID:26954374

  13. Approach-specific multi-grid anatomical modeling for neurosurgery simulation with public-domain and open-source software

    NASA Astrophysics Data System (ADS)

    Audette, Michel A.; Rivière, Denis; Law, Charles; Ibanez, Luis; Aylward, Stephen R.; Finet, Julien; Wu, Xunlei; Ewend, Matthew G.

    2011-03-01

    We present on-going work on multi-resolution sulcal-separable meshing for approach-specific neurosurgery simulation, in conjunction multi-grid and Total Lagrangian Explicit Dynamics finite elements. Conflicting requirements of interactive nonlinear finite elements and small structures lead to a multi-grid framework. Implications for meshing are explicit control over resolution, and prior knowledge of the intended neurosurgical approach and intended path. This information is used to define a subvolume of clinical interest, within some distance of the path and the target pathology. Restricted to this subvolume are a tetrahedralization of finer resolution, the representation of critical tissues, and sulcal separability constraint for all mesh levels.

  14. Chemistry-specific surface adsorption of the barnacle settlement-inducing protein complex

    PubMed Central

    Petrone, Luigi; Aldred, Nick; Emami, Kaveh; Enander, Karin; Ederth, Thomas; Clare, Anthony S.

    2015-01-01

    Gregarious settlement in barnacle larvae (cyprids) is induced by a contact pheromone, the settlement-inducing protein complex (SIPC). The SIPC has been identified both in the cuticle of adult barnacles and in the temporary adhesive secretion (footprint) of cyprids. Besides acting as a settlement inducer, the presence of the SIPC in footprints points to its additional involvement in the adhesion process. SIPC adsorption behaviour was therefore investigated on a series of self-assembled monolayers (SAMs) by surface plasmon resonance at the pH of seawater (8.3). Fibrinogen and α2-macroglobulin (A2M) (blood complement protease inhibitors with which the SIPC shares 29% sequence homology) were used in the adsorption experiments as positive and negative standards, respectively. The mass uptake of the SIPC was comparable to that of fibrinogen, with adsorption observed even on the protein-resistant oligo(ethylene glycol) surface. Notably, on the positively charged SAM the SIPC showed a kinetic overshoot, indicating a metastable configuration causing the amount of adsorbed protein to temporarily exceed its equilibrium value. A2M adsorption was low or negligible on all SAMs tested, except for the positively charged surface, indicating that A2M adsorption is mainly driven by electrostatics. Evaluation of SIPC non-specific adsorption kinetics revealed that it adsorbed irreversibly and non-cooperatively on all surfaces tested. PMID:25657832

  15. Chemistry-specific surface adsorption of the barnacle settlement-inducing protein complex.

    PubMed

    Petrone, Luigi; Aldred, Nick; Emami, Kaveh; Enander, Karin; Ederth, Thomas; Clare, Anthony S

    2015-02-01

    Gregarious settlement in barnacle larvae (cyprids) is induced by a contact pheromone, the settlement-inducing protein complex (SIPC). The SIPC has been identified both in the cuticle of adult barnacles and in the temporary adhesive secretion (footprint) of cyprids. Besides acting as a settlement inducer, the presence of the SIPC in footprints points to its additional involvement in the adhesion process. SIPC adsorption behaviour was therefore investigated on a series of self-assembled monolayers (SAMs) by surface plasmon resonance at the pH of seawater (8.3). Fibrinogen and α2-macroglobulin (A2M) (blood complement protease inhibitors with which the SIPC shares 29% sequence homology) were used in the adsorption experiments as positive and negative standards, respectively. The mass uptake of the SIPC was comparable to that of fibrinogen, with adsorption observed even on the protein-resistant oligo(ethylene glycol) surface. Notably, on the positively charged SAM the SIPC showed a kinetic overshoot, indicating a metastable configuration causing the amount of adsorbed protein to temporarily exceed its equilibrium value. A2M adsorption was low or negligible on all SAMs tested, except for the positively charged surface, indicating that A2M adsorption is mainly driven by electrostatics. Evaluation of SIPC non-specific adsorption kinetics revealed that it adsorbed irreversibly and non-cooperatively on all surfaces tested. PMID:25657832

  16. Advanced software development workstation project: Engineering scripting language. Graphical editor

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Software development is widely considered to be a bottleneck in the development of complex systems, both in terms of development and in terms of maintenance of deployed systems. Cost of software development and maintenance can also be very high. One approach to reducing costs and relieving this bottleneck is increasing the reuse of software designs and software components. A method for achieving such reuse is a software parts composition system. Such a system consists of a language for modeling software parts and their interfaces, a catalog of existing parts, an editor for combining parts, and a code generator that takes a specification and generates code for that application in the target language. The Advanced Software Development Workstation is intended to be an expert system shell designed to provide the capabilities of a software part composition system.

  17. Quantitative Measures for Software Independent Verification and Validation

    NASA Technical Reports Server (NTRS)

    Lee, Alice

    1996-01-01

    As software is maintained or reused, it undergoes an evolution which tends to increase the overall complexity of the code. To understand the effects of this, we brought in statistics experts and leading researchers in software complexity, reliability, and their interrelationships. These experts' project has resulted in our ability to statistically correlate specific code complexity attributes, in orthogonal domains, to errors found over time in the HAL/S flight software which flies in the Space Shuttle. Although only a prototype-tools experiment, the result of this research appears to be extendable to all other NASA software, given appropriate data similar to that logged for the Shuttle onboard software. Our research has demonstrated that a more complete domain coverage can be mathematically demonstrated with the approach we have applied, thereby ensuring full insight into the cause-and-effects relationship between the complexity of a software system and the fault density of that system. By applying the operational profile we can characterize the dynamic effects of software path complexity under this same approach We now have the ability to measure specific attributes which have been statistically demonstrated to correlate to increased error probability, and to know which actions to take, for each complexity domain. Shuttle software verifiers can now monitor the changes in the software complexity, assess the added or decreased risk of software faults in modified code, and determine necessary corrections. The reports, tool documentation, user's guides, and new approach that have resulted from this research effort represent advances in the state of the art of software quality and reliability assurance. Details describing how to apply this technique to other NASA code are contained in this document.

  18. Java for flight software

    NASA Technical Reports Server (NTRS)

    Benowitz, E.; Niessner, A.

    2003-01-01

    This work involves developing representative mission-critical spacecraft software using the Real-Time Specification for Java (RTSJ). This work currently leverages actual flight software used in the design of actual flight software in the NASA's Deep Space 1 (DSI), which flew in 1998.

  19. Approach-specific multi-grid anatomical modeling for neurosurgery simulation with public-domain and open-source software

    PubMed Central

    Audette, Michel A.; Rivière, Denis; Law, Charles; Ibanez, Luis; Aylward, Stephen R; Finet, Julien; Wu, Xunlei; Ewend, Matthew G.

    2011-01-01

    We present on-going work on multi-resolution sulcal-separable meshing for approach-specific neurosurgery simulation, in conjunction multi-grid and Total Lagrangian Explicit Dynamics finite elements. Conflicting requirements of interactive nonlinear finite elements and small structures lead to a multi-grid framework. Implications for meshing are explicit control over resolution, and prior knowledge of the intended neurosurgical approach and intended path. This information is used to define a subvolume of clinical interest, within some distance of the path and the target pathology. Restricted to this subvolume are a tetrahedralization of finer resolution, the representation of critical tissues, and sulcal separability constraint for all mesh levels. PMID:21666884

  20. Network, system, and status software enhancements for the autonomously managed electrical power system breadboard. Volume 2: Protocol specification

    NASA Technical Reports Server (NTRS)

    Mckee, James W.

    1990-01-01

    This volume (2 of 4) contains the specification, structured flow charts, and code listing for the protocol. The purpose of an autonomous power system on a spacecraft is to relieve humans from having to continuously monitor and control the generation, storage, and distribution of power in the craft. This implies that algorithms will have been developed to monitor and control the power system. The power system will contain computers on which the algorithms run. There should be one control computer system that makes the high level decisions and sends commands to and receive data from the other distributed computers. This will require a communications network and an efficient protocol by which the computers will communicate. One of the major requirements on the protocol is that it be real time because of the need to control the power elements.

  1. Quantification of Alterations in Cortical Bone Geometry Using Site Specificity Software in Mouse models of Aging and the Responses to Ovariectomy and Altered Loading

    PubMed Central

    Galea, Gabriel L.; Hannuna, Sion; Meakin, Lee B.; Delisser, Peter J.; Lanyon, Lance E.; Price, Joanna S.

    2015-01-01

    Investigations into the effect of (re)modeling stimuli on cortical bone in rodents normally rely on analysis of changes in bone mass and architecture at a narrow cross-sectional site. However, it is well established that the effects of axial loading produce site-specific changes throughout bones’ structure. Non-mechanical influences (e.g., hormones) can be additional to or oppose locally controlled adaptive responses and may have more generalized effects. Tools currently available to study site-specific cortical bone adaptation are limited. Here, we applied novel site specificity software to measure bone mass and architecture at each 1% site along the length of the mouse tibia from standard micro-computed tomography (μCT) images. Resulting measures are directly comparable to those obtained through μCT analysis (R2 > 0.96). Site Specificity analysis was used to compare a number of parameters in tibiae from young adult (19-week-old) versus aged (19-month-old) mice; ovariectomized and entire mice; limbs subjected to short periods of axial loading or disuse induced by sciatic neurectomy. Age was associated with uniformly reduced cortical thickness and site-specific decreases in cortical area most apparent in the proximal tibia. Mechanical loading site-specifically increased cortical area and thickness in the proximal tibia. Disuse uniformly decreased cortical thickness and decreased cortical area in the proximal tibia. Ovariectomy uniformly reduced cortical area without altering cortical thickness. Differences in polar moment of inertia between experimental groups were only observed in the proximal tibia. Aging and ovariectomy also altered eccentricity in the distal tibia. In summary, site specificity analysis provides a valuable tool for measuring changes in cortical bone mass and architecture along the entire length of a bone. Changes in the (re)modeling response determined at a single site may not reflect the response at different locations within the same

  2. Self-assembling software generator

    DOEpatents

    Bouchard, Ann M.; Osbourn, Gordon C.

    2011-11-25

    A technique to generate an executable task includes inspecting a task specification data structure to determine what software entities are to be generated to create the executable task, inspecting the task specification data structure to determine how the software entities will be linked after generating the software entities, inspecting the task specification data structure to determine logic to be executed by the software entities, and generating the software entities to create the executable task.

  3. The BAF chromatin remodelling complex is an epigenetic regulator of lineage specification in the early mouse embryo

    PubMed Central

    Panamarova, Maryna; Cox, Andy; Wicher, Krzysztof B.; Butler, Richard; Bulgakova, Natalia; Jeon, Shin; Rosen, Barry; Seong, Rho H.; Skarnes, William; Crabtree, Gerald; Zernicka-Goetz, Magdalena

    2016-01-01

    Dynamic control of gene expression is essential for the development of a totipotent zygote into an embryo with defined cell lineages. The accessibility of genes responsible for cell specification to transcriptional machinery is dependent on chromatin remodelling complexes such as the SWI\\SNF (BAF) complex. However, the role of the BAF complex in early mouse development has remained unclear. Here, we demonstrate that BAF155, a major BAF complex subunit, regulates the assembly of the BAF complex in vivo and regulates lineage specification of the mouse blastocyst. We find that associations of BAF155 with other BAF complex subunits become enriched in extra-embryonic lineages just prior to implantation. This enrichment is attributed to decreased mobility of BAF155 in extra-embryonic compared with embryonic lineages. Downregulation of BAF155 leads to increased expression of the pluripotency marker Nanog and its ectopic expression in extra-embryonic lineages, whereas upregulation of BAF155 leads to the upregulation of differentiation markers. Finally, we show that the arginine methyltransferase CARM1 methylates BAF155, which differentially influences assembly of the BAF complex between the lineages and the expression of pluripotency markers. Together, our results indicate a novel role of BAF-dependent chromatin remodelling in mouse development via regulation of lineage specification. PMID:26952987

  4. Addressing the Complexity of Mobile App Design in Hospital Setting with a Tailored Software Development Life Cycle Model.

    PubMed

    Ehrler, Frederic; Lovis, Christian; Blondon, Katherine

    2016-01-01

    Recent studies on workflow processes in hospital settings have shown that, since the introduction of EHRs, care-providers spend an increasing amount of their time on documentation rather than on bedside patient care. In order to improve the bedside work process and facilitate bedside documentation, we are developing an evidence-based mobile app for healthcare providers. In this paper, we present a tailored software development life cycle model that we created and validated during the design and development of this smartphone application. PMID:27577371

  5. Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration

    PubMed Central

    Chakrabarti, Lisa

    2016-01-01

    Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70–71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions. PMID:27333203

  6. Rescue of PINK1 protein null-specific mitochondrial complex IV deficits by ginsenoside Re activation of nitric oxide signaling.

    PubMed

    Kim, Kyung-Hee; Song, Karen; Yoon, Seung-Hee; Shehzad, Omer; Kim, Yeong-Shik; Son, Jin H

    2012-12-28

    PINK1, linked to familial Parkinson's disease, is known to affect mitochondrial function. Here we identified a novel regulatory role of PINK1 in the maintenance of complex IV activity and characterized a novel mechanism by which NO signaling restored complex IV deficiency in PINK1 null dopaminergic neuronal cells. In PINK1 null cells, levels of specific chaperones, including Hsp60, leucine-rich pentatricopeptide repeat-containing (LRPPRC), and Hsp90, were severely decreased. LRPPRC and Hsp90 were found to act upstream of Hsp60 to regulate complex IV activity. Specifically, knockdown of Hsp60 resulted in a decrease in complex IV activity, whereas antagonistic inhibition of Hsp90 by 17-(allylamino) geldanamycin decreased both Hsp60 and complex IV activity. In contrast, overexpression of the PINK1-interacting factor LRPPRC augmented complex IV activity by up-regulating Hsp60. A similar recovery of complex IV activity was also induced by coexpression of Hsp90 and Hsp60. Drug screening identified ginsenoside Re as a compound capable of reversing the deficit in complex IV activity in PINK1 null cells through specific increases of LRPPRC, Hsp90, and Hsp60 levels. The pharmacological effects of ginsenoside Re could be reversed by treatment of the pan-NOS inhibitor L-NG-Nitroarginine Methyl Ester (L-NAME) and could also be reproduced by low-level NO treatment. These results suggest that PINK1 regulates complex IV activity via interactions with upstream regulators of Hsp60, such as LRPPRC and Hsp90. Furthermore, they demonstrate that treatment with ginsenoside Re enhances functioning of the defective PINK1-Hsp90/LRPPRC-Hsp60-complex IV signaling axis in PINK1 null neurons by restoring NO levels, providing potential for new therapeutics targeting mitochondrial dysfunction in Parkinson's disease. PMID:23144451

  7. xTract: software for characterizing conformational changes of protein complexes by quantitative cross-linking mass spectrometry.

    PubMed

    Walzthoeni, Thomas; Joachimiak, Lukasz A; Rosenberger, George; Röst, Hannes L; Malmström, Lars; Leitner, Alexander; Frydman, Judith; Aebersold, Ruedi

    2015-12-01

    Chemical cross-linking in combination with mass spectrometry generates distance restraints of amino acid pairs in close proximity on the surface of native proteins and protein complexes. In this study we used quantitative mass spectrometry and chemical cross-linking to quantify differences in cross-linked peptides obtained from complexes in spatially discrete states. We describe a generic computational pipeline for quantitative cross-linking mass spectrometry consisting of modules for quantitative data extraction and statistical assessment of the obtained results. We used the method to detect conformational changes in two model systems: firefly luciferase and the bovine TRiC complex. Our method discovers and explains the structural heterogeneity of protein complexes using only sparse structural information. PMID:26501516

  8. xTract: software for characterizing conformational changes of protein complexes by quantitative cross-linking mass spectrometry

    PubMed Central

    Walzthoeni, Thomas; Joachimiak, Lukasz A; Rosenberger, George; Röst, Hannes L; Malmström, Lars; Leitner, Alexander; Frydman, Judith; Aebersold, Ruedi

    2016-01-01

    Chemical cross-linking in combination with mass spectrometry generates distance restraints of amino acid pairs in close proximity on the surface of native proteins and protein complexes. In this study we used quantitative mass spectrometry and chemical cross-linking to quantify differences in cross-linked peptides obtained from complexes in spatially discrete states. We describe a generic computational pipeline for quantitative cross-linking mass spectrometry consisting of modules for quantitative data extraction and statistical assessment of the obtained results. We used the method to detect conformational changes in two model systems: firefly luciferase and the bovine TRiC complex. Our method discovers and explains the structural heterogeneity of protein complexes using only sparse structural information. PMID:26501516

  9. Structure of a Human ASF1a-HIRA Complex and Insights into Specificity of Histone Chaperone Complex Assembly

    SciTech Connect

    Tang,Y.; Poustovoitov, M.; Zhao, K.; Garfinkel, M.; Canutescu, A.; Dunbrack, R.; Adams, P.; Marmorstein, R.

    2006-01-01

    Human HIRA, ASF1a, ASF1b and CAF-1 are evolutionally conserved histone chaperones that form multiple functionally distinct chromatin-assembly complexes, with roles liked to diverse nuclear process, such as DNA replication and formation of heterochromatin in senescent cells. We report the crystal structure of an ASF1a-HIRA heterodimer and a biochemical dissection of ASFA1a's mutually exclusive interactions with HIRA and the p60 subunit of CAF-1. The HIRA B domain forms an antiparallel {beta}-hairpin that binds perpendicular to the strands of the {beta}-sandwich of ASF1a, via {beta}-sheet, salt bridge and van der Waals contacts. the N- and C-terminal regions of ASF1a and ASF1b determine the different affinities of these two proteins for HIRA, by contacting regions outside the HIRA B domain. CAF-1 p60 also uses B domain-like motifs for binding to ASF1a, thereby competing with HIRA. Together, these studies begin to define the molecular determinants of assembly of functionally diverse macromolecular histone chaperone complexes.

  10. Proton MRS and neuropsychological correlates in AIDS dementia complex: evidence of subcortical specificity.

    PubMed

    Paul, Robert H; Yiannoutsos, Constantin T; Miller, Eric N; Chang, Linda; Marra, Christina M; Schifitto, Giovanni; Ernst, Thomas; Singer, Elyse; Richards, Todd; Jarvik, G Jeffrey; Price, Richard; Meyerhoff, Dieter J; Kolson, Dennis; Ellis, Ronald J; Gonzalez, Gilberto; Lenkinski, Robert E; Cohen, Ronald A; Navia, Bradford A

    2007-01-01

    Few studies have described the metabolic substrates underlying neuropsychological performance in HIV infection or examined the specificity of these relationships. The authors performed magnetic resonance spectroscopic and neuropsychological evaluations on 61 patients with AIDS dementia complex (stages 1-3) and 39 HIV-positive neurologically asymptomatic individuals. N-acetylaspartate, a marker of mature neurons, choline and myoinositol, both markers of gliosis, and creatine, a reference marker, were measured in the basal ganglia, frontal white matter, and parietal cortex. The neuropsychological evaluation consisted of tests that measured gross and fine motor skills, psychomotor function, information processing speed, and verbal memory. The authors examined performance on individual subtests and an aggregate Z score based on eight subtests (NPZ-8), adjusted for age and education. The NPZ-8 was significantly higher in subjects with greater N-acetylaspartate/creatine in the frontal white matter and was lower in subjects with higher myoinositol/creatine in the basal ganglia. Particularly strong associations were found between measures of gross and fine motor function, which correlated positively with N-acetylaspartate/creatine in the frontal white matter and negatively with myoinositol/creatine in the basal ganglia. Similarly, cognitive processing speed was negatively correlated with myoinositol/creatine in the basal ganglia. In contrast, there were no statistically significant relationships between brain metabolite levels in the parietal cortex and neuropsychological function. This study provides convincing evidence that neuropsychological impairment is associated with reduced markers of mature neurons and increased markers of gliosis in the basal ganglia and frontal white matter. Neural changes as reflected by these metabolite levels may prove useful in identifying individuals at risk for neuropsychological impairment. Prospective studies are needed to elucidate the

  11. Rapid and accurate tumor-target bio-imaging through specific in vivo biosynthesis of a fluorescent europium complex.

    PubMed

    Ye, Jing; Wang, Jianling; Li, Qiwei; Dong, Xiawei; Ge, Wei; Chen, Yun; Jiang, Xuerui; Liu, Hongde; Jiang, Hui; Wang, Xuemei

    2016-04-22

    A new and facile method for rapidly and accurately achieving tumor targeting fluorescent images has been explored using a specifically biosynthesized europium (Eu) complex in vivo and in vitro. It demonstrated that a fluorescent Eu complex could be bio-synthesized through a spontaneous molecular process in cancerous cells and tumors, but not prepared in normal cells and tissues. In addition, the proteomics analyses show that some biological pathways of metabolism, especially for NADPH production and glutamine metabolism, are remarkably affected during the relevant biosynthesis process, where molecular precursors of europium ions are reduced to fluorescent europium complexes inside cancerous cells or tumor tissues. These results proved that the specific self-biosynthesis of a fluorescent Eu complex by cancer cells or tumor tissues can provide a new strategy for accurate diagnosis and treatment strategies in the early stages of cancers and thus is beneficial for realizing precise surgical intervention based on the relevant cheap and readily available agents. PMID:26810592

  12. The BAF chromatin remodelling complex is an epigenetic regulator of lineage specification in the early mouse embryo.

    PubMed

    Panamarova, Maryna; Cox, Andy; Wicher, Krzysztof B; Butler, Richard; Bulgakova, Natalia; Jeon, Shin; Rosen, Barry; Seong, Rho H; Skarnes, William; Crabtree, Gerald; Zernicka-Goetz, Magdalena

    2016-04-15

    Dynamic control of gene expression is essential for the development of a totipotent zygote into an embryo with defined cell lineages. The accessibility of genes responsible for cell specification to transcriptional machinery is dependent on chromatin remodelling complexes such as the SWI\\SNF (BAF) complex. However, the role of the BAF complex in early mouse development has remained unclear. Here, we demonstrate that BAF155, a major BAF complex subunit, regulates the assembly of the BAF complexin vivoand regulates lineage specification of the mouse blastocyst. We find that associations of BAF155 with other BAF complex subunits become enriched in extra-embryonic lineages just prior to implantation. This enrichment is attributed to decreased mobility of BAF155 in extra-embryonic compared with embryonic lineages. Downregulation of BAF155 leads to increased expression of the pluripotency markerNanogand its ectopic expression in extra-embryonic lineages, whereas upregulation of BAF155 leads to the upregulation of differentiation markers. Finally, we show that the arginine methyltransferase CARM1 methylates BAF155, which differentially influences assembly of the BAF complex between the lineages and the expression of pluripotency markers. Together, our results indicate a novel role of BAF-dependent chromatin remodelling in mouse development via regulation of lineage specification. PMID:26952987

  13. Chemistry specificity of DNA-polycation complex salt response: a simulation study of DNA, polylysine and polyethyleneimine.

    PubMed

    Antila, Hanne S; Härkönen, Marc; Sammalkorpi, Maria

    2015-02-21

    In this work, the chemistry specific stability determining factors of DNA-polycation complexes are examined by performing all-atom molecular dynamics simulations. To this end, we conduct a systematic variation of polycation line charge through polyethyleneimine (PEI) protonation and polycation chemistry via comparison with poly-l-lysine (PLL). Our simulations show that increasing line charge of the polycation alone does not lead to more salt tolerant complexes. Instead, the effective charge compensation by the polycation correlates with the increased stability of the complex against additional salt. The salt stability of PEI-DNA complexes also links to the proton sponge property of weak polycations, commonly assumed to be behind the effectivity of PEI as a gene delivery vector. Examination of the complexes reveals the mechanism behind this behaviour; more Cl(-) ions are attracted by the protonated complexes but, in contrast to the common depiction of the proton sponge behaviour, the ion influx does not cause swelling of the complex structure itself. However, PEI protonation leads to release of PEI while DNA remains tightly bound to the complex. Jointly, these findings shed light on the stability determining factors of DNA-polycation complexes, raise charge distribution as an important stability determining contributor, and indicate that the effectivity of PEI in gene delivery is likely to result from the freed PEI facilitating gene transfection. PMID:25607687

  14. Automating Embedded Analysis Capabilities and Managing Software Complexity in Multiphysics Simulation, Part II: Application to Partial Differential Equations

    DOE PAGESBeta

    Pawlowski, Roger P.; Phipps, Eric T.; Salinger, Andrew G.; Owen, Steven J.; Siefert, Christopher M.; Staten, Matthew L.

    2012-01-01

    A template-based generic programming approach was presented in Part I of this series of papers [Sci. Program. 20 (2012), 197–219] that separates the development effort of programming a physical model from that of computing additional quantities, such as derivatives, needed for embedded analysis algorithms. In this paper, we describe the implementation details for using the template-based generic programming approach for simulation and analysis of partial differential equations (PDEs). We detail several of the hurdles that we have encountered, and some of the software infrastructure developed to overcome them. We end with a demonstration where we present shape optimization and uncertaintymore » quantification results for a 3D PDE application.« less

  15. N-Heterocyclic Carbene-Gold(I) Complexes Conjugated to a Leukemia-Specific DNA Aptamer for Targeted Drug Delivery.

    PubMed

    Niu, Weijia; Chen, Xigao; Tan, Weihong; Veige, Adam S

    2016-07-25

    This report describes the synthesis and characterization of novel N-heterocyclic carbene (NHC)-gold(I) complexes and their bioconjugation to the CCRF-CEM-leukemia-specific aptamer sgc8c. Successful bioconjugation was confirmed by the use of fluorescent tags on both the NHC-Au(I) complex and the aptamer. Cell-viability assays indicated that the NHC-Au(I) -aptamer conjugate was more cytotoxic than the NHC-gold complex alone. A combination of flow cytometry, confocal microscopy, and cell-viability assays provided clear evidence that the NHC-Au(I) -aptamer conjugate was selective for targeted CCRF-CEM leukemia cells. PMID:27311814

  16. Automating Embedded Analysis Capabilities and Managing Software Complexity in Multiphysics Simulation, Part I: Template-Based Generic Programming

    DOE PAGESBeta

    Pawlowski, Roger P.; Phipps, Eric T.; Salinger, Andrew G.

    2012-01-01

    An approach for incorporating embedded simulation and analysis capabilities in complex simulation codes through template-based generic programming is presented. This approach relies on templating and operator overloading within the C++ language to transform a given calculation into one that can compute a variety of additional quantities that are necessary for many state-of-the-art simulation and analysis algorithms. An approach for incorporating these ideas into complex simulation codes through general graph-based assembly is also presented. These ideas have been implemented within a set of packages in the Trilinos framework and are demonstrated on a simple problem from chemical engineering.

  17. Automating Embedded Analysis Capabilities and Managing Software Complexity in Multiphysics Simulation, Part I: Template-Based Generic Programming

    SciTech Connect

    Pawlowski, Roger P.; Phipps, Eric T.; Salinger, Andrew G.

    2012-01-01

    An approach for incorporating embedded simulation and analysis capabilities in complex simulation codes through template-based generic programming is presented. This approach relies on templating and operator overloading within the C++ language to transform a given calculation into one that can compute a variety of additional quantities that are necessary for many state-of-the-art simulation and analysis algorithms. An approach for incorporating these ideas into complex simulation codes through general graph-based assembly is also presented. These ideas have been implemented within a set of packages in the Trilinos framework and are demonstrated on a simple problem from chemical engineering.

  18. Joint Analysis of Band-Specific Functional Connectivity and Signal Complexity in Autism

    ERIC Educational Resources Information Center

    Ghanbari, Yasser; Bloy, Luke; Edgar, J. Christopher; Blaskey, Lisa; Verma, Ragini; Roberts, Timothy P. L.

    2015-01-01

    Examination of resting state brain activity using electrophysiological measures like complexity as well as functional connectivity is of growing interest in the study of autism spectrum disorders (ASD). The present paper jointly examined complexity and connectivity to obtain a more detailed characterization of resting state brain activity in ASD.…

  19. Class diagram based evaluation of software performance

    NASA Astrophysics Data System (ADS)

    Pham, Huong V.; Nguyen, Binh N.

    2013-03-01

    The evaluation of software performance in the early stages of the software life cycle is important and it has been widely studied. In the software model specification, class diagram is the important object-oriented software specification model. The measures based on a class diagram have been widely studied to evaluate quality of software such as complexity, maintainability, reuse capability, etc. However the software performance evaluation based on Class model has not been widely studied, especially for object-oriented design of embedded software. Therefore, in this paper we propose a new approach to directly evaluate the software performance based on class diagrams. From a class diagram, we determine the parameters which are used to evaluate and build formula of the measures such as Size of Class Variables, Size of Class Methods, Size of Instance Variables, Size of Instance Methods, etc. Then, we do analysis of the dependence of performance on these measures and build the performance evaluation function from class diagram. Thereby we can choose the best class diagram based on this evaluation function.

  20. Developing Software to “Track and Catch” Missed Follow-up of Abnormal Test Results in a Complex Sociotechnical Environment

    PubMed Central

    Smith, M.; Murphy, D.; Laxmisan, A.; Sittig, D.; Reis, B.; Esquivel, A.; Singh, H.

    2013-01-01

    Summary Background Abnormal test results do not always receive timely follow-up, even when providers are notified through electronic health record (EHR)-based alerts. High workload, alert fatigue, and other demands on attention disrupt a provider’s prospective memory for tasks required to initiate follow-up. Thus, EHR-based tracking and reminding functionalities are needed to improve follow-up. Objectives The purpose of this study was to develop a decision-support software prototype enabling individual and system-wide tracking of abnormal test result alerts lacking follow-up, and to conduct formative evaluations, including usability testing. Methods We developed a working prototype software system, the Alert Watch And Response Engine (AWARE), to detect abnormal test result alerts lacking documented follow-up, and to present context-specific reminders to providers. Development and testing took place within the VA’s EHR and focused on four cancer-related abnormal test results. Design concepts emphasized mitigating the effects of high workload and alert fatigue while being minimally intrusive. We conducted a multifaceted formative evaluation of the software, addressing fit within the larger socio-technical system. Evaluations included usability testing with the prototype and interview questions about organizational and workflow factors. Participants included 23 physicians, 9 clinical information technology specialists, and 8 quality/safety managers. Results Evaluation results indicated that our software prototype fit within the technical environment and clinical workflow, and physicians were able to use it successfully. Quality/safety managers reported that the tool would be useful in future quality assurance activities to detect patients who lack documented follow-up. Additionally, we successfully installed the software on the local facility’s “test” EHR system, thus demonstrating technical compatibility. Conclusion To address the factors involved in missed

  1. Specific Genetic Immunotherapy Induced by Recombinant Vaccine Alpha-Fetoprotein-Heat Shock Protein 70 Complex

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoping; Lin, Huanping; Wang, Qiaoxia

    Purposes: To construct a recombinant vaccine alpha-fetoprotein (AFP)-heat shock protein (HSP70) complex, and study its ability to induce specific CTL response and its protective effect against AFP-producing tumor. Material/Methods: A recombinant vaccine was constructed by conjugating mouse alpha-fetoprotein to heat shock protein 70. By way of intracutaneous injection, mice were primed and boosted with recombinant vaccine mAFP/HSP70, whereas single mAFP or HSP70 injection as controls. The ELISPOT and ELISA were used to measure the frequency of cells producing the cytokine IFN-γ in splenocytes and the level of anti-AFP antibody of serum from immunized mice respectively. In vivo tumor challenge were carried out to assess the immune effect of the recombinant vaccine. Results: By recombinant mAFP/HSP70 vaccine immunization, the results of ELISPOT and ELISA showed that the number of splenic cells producing IFN-γ and the level of anti-AFP antibody of serum were significantly higher in mAFP/HSP70 group than those in mAFP and HSP70 groups (108.50±11.70 IFN-γ spots/106 cells vs 41.60±10.40 IFN-γ spots/106 cells, 7.32±3.14 IFN-γ spots/106 cells, P<0.01; 156.32±10.42 μg/mL vs 66.52±7.35 μg/mL, 5.73±2.89 μg/mL, P<0.01). The tumor volume in mAFP/HSP70 group was significantly smaller than that in mAFP and HSP70 groups (42.44±7.14 mm3 vs 392.23±12.46 mm3, 838.63±13.84 mm3, P<0.01). Conclusions: The study further confirmed the function of heat shock protein 70's immune adjuvant. Sequential immunization with recombinant mAFP/HSP70 vaccine could generate effective antitumor immunity on AFP-producing tumor. The recombined mAFP/HSP70 vaccine may be suitable for serving as an immunotherapy for hepatocellular carcinoma.

  2. Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity

    PubMed Central

    Araki, Yasuhiro; Ku, Wei-Chi; Akioka, Manami; May, Alexander I.; Hayashi, Yu; Arisaka, Fumio; Ishihama, Yasushi

    2013-01-01

    Autophagy is a conserved eukaryotic process of protein and organelle self-degradation within the vacuole/lysosome. Autophagy is characterized by the formation of an autophagosome, for which Vps34-dervied phosphatidylinositol 3-phosphate (PI3P) is essential. In yeast, Vps34 forms two distinct protein complexes: complex I, which functions in autophagy, and complex II, which is involved in protein sorting to the vacuole. Here we identify and characterize Atg38 as a stably associated subunit of complex I. In atg38Δ cells, autophagic activity was significantly reduced and PI3-kinase complex I dissociated into the Vps15–Vps34 and Atg14–Vps30 subcomplexes. We find that Atg38 physically interacted with Atg14 and Vps34 via its N terminus. Further biochemical analyses revealed that Atg38 homodimerizes through its C terminus and that this homodimer formation is indispensable for the integrity of complex I. These data suggest that the homodimer of Atg38 functions as a physical linkage between the Vps15–Vps34 and Atg14–Vps30 subcomplexes to facilitate complex I formation. PMID:24165940

  3. Software assurance standard

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This standard specifies the software assurance program for the provider of software. It also delineates the assurance activities for the provider and the assurance data that are to be furnished by the provider to the acquirer. In any software development effort, the provider is the entity or individual that actually designs, develops, and implements the software product, while the acquirer is the entity or individual who specifies the requirements and accepts the resulting products. This standard specifies at a high level an overall software assurance program for software developed for and by NASA. Assurance includes the disciplines of quality assurance, quality engineering, verification and validation, nonconformance reporting and corrective action, safety assurance, and security assurance. The application of these disciplines during a software development life cycle is called software assurance. Subsequent lower-level standards will specify the specific processes within these disciplines.

  4. The 73 kD Subunit of the Cleavage and Polyadenylation Specificity Factor (CPSF) Complex Affects Reproductive Development in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cleavage and polyadenylation specificity factor (CPSF) is an important multi-subunit component of the mRNA 3’-end processing apparatus in eukaryotes. We have identified the Arabidopsis CPSF complex that involves five protein subunits named AtCPSF160, AtCPSF100, AtCPSF73-I, AtCPSF73-II and AtCPSF30....

  5. Software productivity improvement through software engineering technology

    NASA Technical Reports Server (NTRS)

    Mcgarry, F. E.

    1985-01-01

    It has been estimated that NASA expends anywhere from 6 to 10 percent of its annual budget on the acquisition, implementation and maintenance of computer software. Although researchers have produced numerous software engineering approaches over the past 5-10 years; each claiming to be more effective than the other, there is very limited quantitative information verifying the measurable impact htat any of these technologies may have in a production environment. At NASA/GSFC, an extended research effort aimed at identifying and measuring software techniques that favorably impact productivity of software development, has been active over the past 8 years. Specific, measurable, software development technologies have been applied and measured in a production environment. Resulting software development approaches have been shown to be effective in both improving quality as well as productivity in this one environment.

  6. High-Resolution and Specific Detection of Bacteria on Complex Surfaces Using Nanoparticle Probes and Electron Microscopy

    PubMed Central

    Ye, Jun; Nielsen, Shaun; Joseph, Stephen; Thomas, Torsten

    2015-01-01

    The study of the interaction of bacteria with surfaces requires the detection of specific bacterial groups with high spatial resolution. Here, we describe a method to rapidly and efficiently add nanogold particles to oligonucleotide probes, which target bacterial ribosomal RNA. These nanogold-labeled probes are then used in an in situ hybridization procedure that ensures both cellular integrity and high specificity. Electron microscopy subsequently enables the visualization of specific cells with high local precision on complex surface structures. This method will contribute to an increased understanding of how bacteria interact with surface structures on a sub-micron scale. PMID:26018431

  7. Open Data, Open Specifications and Free and Open Source Software: A powerful mix to create distributed Web-based water information systems

    NASA Astrophysics Data System (ADS)

    Arias, Carolina; Brovelli, Maria Antonia; Moreno, Rafael

    2015-04-01

    We are in an age when water resources are increasingly scarce and the impacts of human activities on them are ubiquitous. These problems don't respect administrative or political boundaries and they must be addressed integrating information from multiple sources at multiple spatial and temporal scales. Communication, coordination and data sharing are critical for addressing the water conservation and management issues of the 21st century. However, different countries, provinces, local authorities and agencies dealing with water resources have diverse organizational, socio-cultural, economic, environmental and information technology (IT) contexts that raise challenges to the creation of information systems capable of integrating and distributing information across their areas of responsibility in an efficient and timely manner. Tight and disparate financial resources, and dissimilar IT infrastructures (data, hardware, software and personnel expertise) further complicate the creation of these systems. There is a pressing need for distributed interoperable water information systems that are user friendly, easily accessible and capable of managing and sharing large volumes of spatial and non-spatial data. In a distributed system, data and processes are created and maintained in different locations each with competitive advantages to carry out specific activities. Open Data (data that can be freely distributed) is available in the water domain, and it should be further promoted across countries and organizations. Compliance with Open Specifications for data collection, storage and distribution is the first step toward the creation of systems that are capable of interacting and exchanging data in a seamlessly (interoperable) way. The features of Free and Open Source Software (FOSS) offer low access cost that facilitate scalability and long-term viability of information systems. The World Wide Web (the Web) will be the platform of choice to deploy and access these systems

  8. Differential reaction kinetics, cleavage complex formation, and nonamer binding domain dependence dictate the structure-specific and sequence-specific nuclease activity of RAGs.

    PubMed

    Naik, Abani Kanta; Raghavan, Sathees C

    2012-01-20

    During V(D)J recombination, RAG (recombination-activating gene) complex cleaves DNA based on sequence specificity. Besides its physiological function, RAG has been shown to act as a structure-specific nuclease. Recently, we showed that the presence of cytosine within the single-stranded region of heteroduplex DNA is important when RAGs cleave on DNA structures. In the present study, we report that heteroduplex DNA containing a bubble region can be cleaved efficiently when present along with a recombination signal sequence (RSS) in cis or trans configuration. The sequence of the bubble region influences RAG cleavage at RSS when present in cis. We also find that the kinetics of RAG cleavage differs between RSS and bubble, wherein RSS cleavage reaches maximum efficiency faster than bubble cleavage. In addition, unlike RSS, RAG cleavage at bubbles does not lead to cleavage complex formation. Finally, we show that the "nonamer binding region," which regulates RAG cleavage on RSS, is not important during RAG activity in non-B DNA structures. Therefore, in the current study, we identify the possible mechanism by which RAG cleavage is regulated when it acts as a structure-specific nuclease. PMID:22119487

  9. Activation Domain-Specific and General Transcription Stimulation by Native Histone Acetyltransferase Complexes

    PubMed Central

    Ikeda, Keiko; Steger, David J.; Eberharter, Anton; Workman, Jerry L.

    1999-01-01

    Recent progress in identifying the catalytic subunits of histone acetyltransferase (HAT) complexes has implicated histone acetylation in the regulation of transcription. Here, we have analyzed the function of two native yeast HAT complexes, SAGA (Spt-Ada-Gcn5 Acetyltransferase) and NuA4 (nucleosome acetyltransferase of H4), in activating transcription from preassembled nucleosomal array templates in vitro. Each complex was tested for the ability to enhance transcription driven by GAL4 derivatives containing either acidic, glutamine-rich, or proline-rich activation domains. On nucleosomal array templates, the SAGA complex selectively stimulates transcription driven by the VP16 acidic activation domain in an acetyl coenzyme A-dependent manner. In contrast, the NuA4 complex facilitates transcription mediated by any of the activation domains tested if allowed to preacetylate the nucleosomal template, indicating a general stimulatory effect of histone H4 acetylation. However, when the extent of acetylation by NuA4 is limited, the complex also preferentially stimulates VP16-driven transcription. SAGA and NuA4 interact directly with the VP16 activation domain but not with a glutamine-rich or proline-rich activation domain. These data suggest that recruitment of the SAGA and NuA4 HAT complexes by the VP16 activation domain contributes to HAT-dependent activation. In addition, extensive H4/H2B acetylation by NuA4 leads to a general activation of transcription, which is independent of activator-NuA4 interactions. PMID:9858608

  10. The software engineering laboratory: An approach to measuring software technology

    NASA Technical Reports Server (NTRS)

    Mcgarry, F.

    1980-01-01

    The investigations of the software evaluation laboratory into the software development process at NASA/Goddard are described. A data collection process for acquiring detailed histories of software development projects is outlined. The application of different sets of software methodologies to specific applications projects is summarized. The effect of the development methodology on productivity is discussed.

  11. Developing Generic Software for Spacecraft Avionics

    NASA Technical Reports Server (NTRS)

    Smith, Joseph

    2003-01-01

    A proposed approach to the development of software for spacecraft avionics is based partly on a concept of generic software that could be tailored to satisfy requirements for specific missions. The proposed approach would stand in contrast to the conventional approach of first defining avionics requirements for a specific mission, then developing software specific to those requirements. The proposed approach might also be adaptable to programming computers that control and monitor other complex equipment systems that range in scale from automobiles to factories. The concept of a spacecraft avionics functional model (SAFM) is a major element of the proposed approach. An SAFM would be, essentially, a systematic and hierarchical description of the functionality required of the avionics software (and hardware) for a given mission. Although the initial input information used to start the construction of an SAFM would typically amount to a high-level description, the SAFM would thereafter be decomposed to a low level. The resulting low-level version of the model would be used to develop a set of generic requirements that could be expected to include a large fraction of all requirements for a large fraction of all missions. The generic requirements would be used to develop software modules that could be included in, or excluded from, the final flight software to satisfy the requirements of a specific mission.

  12. Healthcare Software Assurance

    PubMed Central

    Cooper, Jason G.; Pauley, Keith A.

    2006-01-01

    Software assurance is a rigorous, lifecycle phase-independent set of activities which ensure completeness, safety, and reliability of software processes and products. This is accomplished by guaranteeing conformance to all requirements, standards, procedures, and regulations. These assurance processes are even more important when coupled with healthcare software systems, embedded software in medical instrumentation, and other healthcare-oriented life-critical systems. The current Food and Drug Administration (FDA) regulatory requirements and guidance documentation do not address certain aspects of complete software assurance activities. In addition, the FDA’s software oversight processes require enhancement to include increasingly complex healthcare systems such as Hospital Information Systems (HIS). The importance of complete software assurance is introduced, current regulatory requirements and guidance discussed, and the necessity for enhancements to the current processes shall be highlighted. PMID:17238324

  13. Healthcare software assurance.

    PubMed

    Cooper, Jason G; Pauley, Keith A

    2006-01-01

    Software assurance is a rigorous, lifecycle phase-independent set of activities which ensure completeness, safety, and reliability of software processes and products. This is accomplished by guaranteeing conformance to all requirements, standards, procedures, and regulations. These assurance processes are even more important when coupled with healthcare software systems, embedded software in medical instrumentation, and other healthcare-oriented life-critical systems. The current Food and Drug Administration (FDA) regulatory requirements and guidance documentation do not address certain aspects of complete software assurance activities. In addition, the FDA's software oversight processes require enhancement to include increasingly complex healthcare systems such as Hospital Information Systems (HIS). The importance of complete software assurance is introduced, current regulatory requirements and guidance discussed, and the necessity for enhancements to the current processes shall be highlighted. PMID:17238324

  14. Selecting Software.

    ERIC Educational Resources Information Center

    Pereus, Steven C.

    2002-01-01

    Describes a comprehensive computer software selection and evaluation process, including documenting district needs, evaluating software packages, weighing the alternatives, and making the purchase. (PKP)

  15. New insights into the transition pathway from nonspecific to specific complex of DNA with Escherichia coli integration host factor.

    PubMed

    Vivas, Paula; Kuznetsov, Serguei V; Ansari, Anjum

    2008-05-15

    To elucidate the nature of the transition-state ensemble along the reaction pathway from a nonspecific protein-DNA complex to the specific complex, we have carried out measurements of DNA bending/unbending dynamics on a cognate DNA substrate in complex with integration host factor (IHF), an architectural protein from E. coli that bends its cognate site by approximately 180 degrees . We use a laser temperature jump to perturb the IHF-DNA complex and monitor the relaxation kinetics with time-resolved FRET measurements on DNA substrates end-labeled with a FRET pair. Previously, we showed that spontaneous bending/kinking of DNA, from thermal disruption of base-pairing/-stacking interactions, may be the rate-limiting step in the formation of the specific complex (Kuznetsov, S. V.; Sugimura, S.; Vivas, P.; Crothers, D. M.; Ansari, A. Proc. Natl. Acad. Sci. USA 2006, 103, 18515). Here, we probe the effect of varying [KCl], which affects the stability of the complex, on this rate-limiting step. We find that below approximately 250 mM KCl, the observed relaxation kinetics are from the unimolecular bending/unbending of DNA, and the relaxation rate kr is independent of [KCl]. Above approximately 300 mM KCl, dissociation of the IHF-DNA complex becomes significant, and the observed relaxation process includes contributions from the association/dissociation step, with kr decreasing with increasing [KCl]. The DNA bending step occurs with a positive activation enthalpy, despite the large negative enthalpy change reported for the specific IHF-DNA complex (Holbrook, J. A.; Tsodikov, O. V.; Saecker, R. M.; Record, M. T., Jr. J. Mol. Biol. 2001, 310, 379). Our conclusion from these studies is that in the uphill climb to the transition state, the DNA is kinked, but with no release of ions, as indicated by the salt-independent behavior of k(r) at low [KCl]. Any release of ions in the unimolecular process, together with conformational changes in the protein-DNA complex that facilitate

  16. Technology 84: software

    SciTech Connect

    Wallich, P.

    1984-01-01

    Progress is reported with regard to knowledge systems-artificial intelligence software capable of giving expert advice or analyzing complex information-and their major tasks and applications. A standard military language, ADA, is also discussed along with efforts to standardize software environments.

  17. High resolution bone material property assignment yields robust subject specific finite element models of complex thin bone structures.

    PubMed

    Pakdel, Amirreza; Fialkov, Jeffrey; Whyne, Cari M

    2016-06-14

    Accurate finite element (FE) modeling of complex skeletal anatomy requires high resolution in both meshing and the heterogeneous mapping of material properties onto the generated mesh. This study introduces Node-based elastic Modulus Assignment with Partial-volume correction (NMAP) as a new approach for FE material property assignment to thin bone structures. The NMAP approach incorporates point spread function based deblurring of CT images, partial-volume correction of CT image voxel intensities and anisotropic interpolation and mapping of CT intensity assignment to FE mesh nodes. The NMAP procedure combined with a derived craniomaxillo-facial skeleton (CMFS) specific density-isotropic elastic modulus relationship was applied to produce specimen-specific FE models of 6 cadaveric heads. The NMAP procedure successfully generated models of the complex thin bone structures with surface elastic moduli reflective of cortical bone material properties. The specimen-specific CMFS FE models were able to accurately predict experimental strains measured under in vitro temporalis and masseter muscle loading (r=0.93, slope=1.01, n=5). The strength of this correlation represents a robust validation for CMFS FE modeling that can be used to better understand load transfer in this complex musculoskeletal system. The developed methodology offers a systematic process-flow able to address the complexity of the CMFS that can be further applied to create high-fidelity models of any musculoskeletal anatomy. PMID:27033728

  18. Buyer's Guide to Communications Software.

    ERIC Educational Resources Information Center

    Powell, David B.

    1984-01-01

    In order to help users make informed decisions when buying communications software, this article suggests that buyers consider communications software compatibility; software protocols for data transmission; software products offering compatibility with Telenet, Prestel, and Ethernet/XTEN; specific intended applications; and specialized features…

  19. Ubinuclein-1 confers histone H3.3-specific-binding by the HIRA histone chaperone complex

    PubMed Central

    Daniel Ricketts, M; Frederick, Brian; Hoff, Henry; Tang, Yong; Schultz, David C.; Singh Rai, Taranjit; Grazia Vizioli, Maria; Adams, Peter D.; Marmorstein, Ronen

    2015-01-01

    Histone chaperones bind specific histones to mediate their storage, eviction or deposition from/or into chromatin. The HIRA histone chaperone complex, composed of HIRA, ubinuclein-1 (UBN1) and CABIN1, cooperates with the histone chaperone ASF1a to mediate H3.3-specific binding and chromatin deposition. Here we demonstrate that the conserved UBN1 Hpc2-related domain (HRD) is a novel H3.3-specific-binding domain. Biochemical and biophysical studies show the UBN1-HRD preferentially binds H3.3/H4 over H3.1/H4. X-ray crystallographic and mutational studies reveal that conserved residues within the UBN1-HRD and H3.3 G90 as key determinants of UBN1–H3.3-binding specificity. Comparison of the structure with the unrelated H3.3-specific chaperone DAXX reveals nearly identical points of contact between the chaperone and histone in the proximity of H3.3 G90, although the mechanism for H3.3 G90 recognition appears to be distinct. This study points to UBN1 as the determinant of H3.3-specific binding and deposition by the HIRA complex. PMID:26159857

  20. The Structure-Specific Nicking of Small Heteroduplexes by the RAG Complex: Implications for Lymphoid Chromosomal Translocations

    PubMed Central

    Raghavan, Sathees C.; Gu, Jiafeng; Swanson, Patrick C.; Lieber, Michael R.

    2009-01-01

    During V(D)J recombination, the RAG complex binds at recombination signal sequences and creates double-strand breaks. In addition to this sequence-specific recognition of the RSS, the RAG complex has been shown to be a structure-specific nuclease, cleaving 3′ overhangs and 3′ flaps, and, more recently, 10 nucleotides (nt) bubble (heteroduplex) structures. Here, we assess the smallest size heteroduplex that core and full-length RAGs can cleave. We also test whether bubbles adjacent to a partial RSS are nicked any differently or any more efficiently than bubbles that are surrounded by random sequence. These points are important in considering what types and what size of non-B DNA structure that the RAG complex can nick, and this helps assess the role of the RAG complex in mediating lymphoid chromosomal translocations. We find that the smallest bubble nicked by the RAG complex is 3 nt, and proximity to a partial or full RSS sequence does not affect the nicking by RAGs. RAG nicking efficiency increases with the size of the heteroduplex and is only about two-fold less efficient than an RSS when the bubble is 6 nt. We consider these findings in the context of RAG nicking at non-B DNA structures in lymphoid chromosomal translocations. PMID:17307402

  1. Cohesin-interacting protein WAPL-1 regulates meiotic chromosome structure and cohesion by antagonizing specific cohesin complexes

    PubMed Central

    Crawley, Oliver; Barroso, Consuelo; Testori, Sarah; Ferrandiz, Nuria; Silva, Nicola; Castellano-Pozo, Maikel; Jaso-Tamame, Angel Luis; Martinez-Perez, Enrique

    2016-01-01

    Wapl induces cohesin dissociation from DNA throughout the mitotic cell cycle, modulating sister chromatid cohesion and higher-order chromatin structure. Cohesin complexes containing meiosis-specific kleisin subunits govern most aspects of meiotic chromosome function, but whether Wapl regulates these complexes remains unknown. We show that during C. elegans oogenesis WAPL-1 antagonizes binding of cohesin containing COH-3/4 kleisins, but not REC-8, demonstrating that sensitivity to WAPL-1 is dictated by kleisin identity. By restricting the amount of chromosome-associated COH-3/4 cohesin, WAPL-1 controls chromosome structure throughout meiotic prophase. In the absence of REC-8, WAPL-1 inhibits COH-3/4-mediated cohesion, which requires crossover-fated events formed during meiotic recombination. Thus, WAPL-1 promotes functional specialization of meiotic cohesin: WAPL-1-sensitive COH-3/4 complexes modulate higher-order chromosome structure, while WAPL-1-refractory REC-8 complexes provide stable cohesion. Surprisingly, a WAPL-1-independent mechanism removes cohesin before metaphase I. Our studies provide insight into how meiosis-specific cohesin complexes are regulated to ensure formation of euploid gametes. DOI: http://dx.doi.org/10.7554/eLife.10851.001 PMID:26841696

  2. The structure-specific nicking of small heteroduplexes by the RAG complex: implications for lymphoid chromosomal translocations.

    PubMed

    Raghavan, Sathees C; Gu, Jiafeng; Swanson, Patrick C; Lieber, Michael R

    2007-06-01

    During V(D)J recombination, the RAG complex binds at recombination signal sequences and creates double-strand breaks. In addition to this sequence-specific recognition of the RSS, the RAG complex has been shown to be a structure-specific nuclease, cleaving 3' overhangs and 3' flaps, and, more recently, 10 nucleotides (nt) bubble (heteroduplex) structures. Here, we assess the smallest size heteroduplex that core and full-length RAGs can cleave. We also test whether bubbles adjacent to a partial RSS are nicked any differently or any more efficiently than bubbles that are surrounded by random sequence. These points are important in considering what types and what size of non-B DNA structure that the RAG complex can nick, and this helps assess the role of the RAG complex in mediating lymphoid chromosomal translocations. We find that the smallest bubble nicked by the RAG complex is 3nt, and proximity to a partial or full RSS sequence does not affect the nicking by RAGs. RAG nicking efficiency increases with the size of the heteroduplex and is only about two-fold less efficient than an RSS when the bubble is 6nt. We consider these findings in the context of RAG nicking at non-B DNA structures in lymphoid chromosomal translocations. PMID:17307402

  3. Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In all vertebrate animals, CD8+ cytotoxic T lymphocytes (CTLs) are controlled by major histocompatibility complex class I (MHC-I) molecules, which are highly polymorphic peptide receptors selecting and presenting endogenously derived epitopes to circulating cytotoxic lymphocytes (CTLs). The polymorp...

  4. The Effect of Specific Language Features on the Complexity of Systems for Automated Essay Scoring.

    ERIC Educational Resources Information Center

    Cohen, Yoav; Ben-Simon, Anat; Hovav, Myra

    This paper focuses on the relationship between different aspects of the linguistic structure of a given language and the complexity of the computer program, whether existing or prospective, that is to be used for the scoring of essays in that language. The first part of the paper discusses common scales used to assess writing products, then…

  5. Specific Syntactic Complexity: Developmental Profiling of Individuals Based on an Annotated Learner Corpus

    ERIC Educational Resources Information Center

    Vyatkina, Nina

    2013-01-01

    This study tracks the development of syntactic complexity in the writing of two beginning German as a second language learners with English as a first language over four semesters of collegiate language study by using developmental profiling techniques applied to an annotated learner corpus. The focus of the investigation is on individual…

  6. Learning Human Aspects of Collaborative Software Development

    ERIC Educational Resources Information Center

    Hadar, Irit; Sherman, Sofia; Hazzan, Orit

    2008-01-01

    Collaboration has become increasingly widespread in the software industry as systems have become larger and more complex, adding human complexity to the technological complexity already involved in developing software systems. To deal with this complexity, human-centric software development methods, such as Extreme Programming and other agile…

  7. Specificity of actinomycetal complexes in urbanozems of the city of Kirov

    NASA Astrophysics Data System (ADS)

    Shirokikh, I. G.; Ashikhmina, T. Ya.; Shirokikh, A. A.

    2011-02-01

    The number and composition of the actinomycetal population was studied in urbanozems in the city of Kirov. It was shown that the total population of actinomycetes was an order of magnitude lower than that in the background territories, and the generic structure of the actinomycetal complex and the species composition of the streptomycetes were transformed under the influence of the urbanization factors. The obtained data were compared with the concentrations of the mobile forms of Pb, Zn, Cu, Fe, and Mn in different ecotopes (industrial, traffic, and recreation zones). The increase of the relative portion of micromonosporic actinomycetes in comparison with the background (reference) soils was observed in the complexes of the industrial and transport ecotopes mostly contaminated with heavy metals. It was found that the antibiotic potential of the streptomycetes in the contaminated soils was lower than in the soils of the background territories.

  8. Science Signaling Podcast for 2 August 2016: Patient-specific protein complexes.

    PubMed

    Schrum, Adam G; Neier, Steven C; VanHook, Annalisa M

    2016-01-01

    This Podcast features an interview with Adam Schrum and Steven Neier, authors of a Research Article that appears in the 2 August 2016 issue of Science Signaling, about a method for identifying protein-protein interactions in patient tissue samples. The authors used this method to compare signaling complexes downstream of the T cell receptor in T cells from healthy skin with those in T cells from the skin of patients with the autoimmune disease alopecia areata. The study revealed differences in the relative abundance of some protein complexes between T cells from the control and patient groups. This technique could be adapted for use as a diagnostic tool to stratify patients by molecular phenotype and predict the therapeutic strategy that is likely to work best for each patient.Listen to Podcast. PMID:27485014

  9. The solution structure of a specific GAGA factor-DNA complex reveals a modular binding mode.

    PubMed

    Omichinski, J G; Pedone, P V; Felsenfeld, G; Gronenborn, A M; Clore, G M

    1997-02-01

    The structure of a complex between the DNA binding domain of the GAGA factor (GAGA-DBD) and an oligonucleotide containing its GAGAG consensus binding site has been determined by nuclear magnetic resonance spectroscopy. The GAGA-DBD comprises a single classical Cys2-His2 zinc finger core, and an N-terminal extension containing two highly basic regions, BR1 and BR2. The zinc finger core binds in the major groove and recognizes the first three GAG bases of the consensus in a manner similar to that seen in other classical zinc finger-DNA complexes. Unlike the latter, which require tandem zinc finger repeats with a minimum of two units for high affinity binding, the GAGA-DBD makes use of only a single finger complemented by BR1 and BR2. BR2 forms a helix that interacts in the major groove recognizing the last G of the consensus, while BR1 wraps around the DNA in the minor groove and recognizes the A in the fourth position of the consensus. The implications of the structure of the GAGA-DBD-DNA complex for chromatin remodelling are discussed. PMID:9033593

  10. Rapid Software Evolution

    NASA Astrophysics Data System (ADS)

    Iordanov, Borislav

    The high complexity of modern software systems, described more than twenty years ago in the well-know paper by Fred Brooks [Brooks 1986] has become proverbial amongst practitioners. While the software engineering community has accepted and learned to cope, albeit in a limited way, with what Brooks termed essential difficulties, i.e. intractable obstacles due to the nature of software itself, there is a consensus that the ultra large-scale systems of the future call for a fundamental change in our understanding and practice of software construction [Northrop 2006].

  11. Sentence Repetition in Adolescents with Specific Language Impairments and Autism: An Investigation of Complex Syntax

    ERIC Educational Resources Information Center

    Riches, N. G.; Loucas, T.; Baird, G.; Charman, T.; Simonoff, E.

    2010-01-01

    Background: Recent studies have indicated that many children with autism spectrum disorders present with language difficulties that are similar to those of children with specific language impairments, leading some to argue for similar structural deficits in these two disorders. Aims: Repetition of sentences involving long-distance dependencies was…

  12. Extended intermolecular interactions in a serine protease-canonical inhibitor complex account for strong and highly specific inhibition.

    PubMed

    Fodor, Krisztián; Harmat, Veronika; Hetényi, Csaba; Kardos, József; Antal, József; Perczel, András; Patthy, András; Katona, Gergely; Gráf, László

    2005-07-01

    We have previously shown that a trypsin inhibitor from desert locust Schistocerca gregaria (SGTI) is a taxon-specific inhibitor that inhibits arthropod trypsins, such as crayfish trypsin, five orders of magnitude more effectively than mammalian trypsins. Thermal denaturation experiments, presented here, confirm the inhibition kinetics studies; upon addition of SGTI the melting temperatures of crayfish and bovine trypsins increased 27 degrees C and 4.5 degrees C, respectively. To explore the structural features responsible for this taxon specificity we crystallized natural crayfish trypsin in complex with chemically synthesized SGTI. This is the first X-ray structure of an arthropod trypsin and also the highest resolution (1.2A) structure of a trypsin-protein inhibitor complex reported so far. Structural data show that in addition to the primary binding loop, residues P3-P3' of SGTI, the interactions between SGTI and the crayfish enzyme are also extended over the P12-P4 and P4'-P5' regions. This is partly due to a structural change of region P10-P4 in the SGTI structure induced by binding of the inhibitor to crayfish trypsin. The comparison of SGTI-crayfish trypsin and SGTI-bovine trypsin complexes by structure-based calculations revealed a significant interaction energy surplus for the SGTI-crayfish trypsin complex distributed over the entire binding region. The new regions that account for stronger and more specific binding of SGTI to crayfish than to bovine trypsin offer new inhibitor sites to engineer in order to develop efficient and specific protease inhibitors for practical use. PMID:15922357

  13. IRAS software analysis library

    NASA Technical Reports Server (NTRS)

    Domik, Gitta; Merkle, C. Scott

    1991-01-01

    The goal of this project was to collect 'research software' written in Interactive Data Language (IDL) to support analysis of data from the Infrared Astronomical Satellite (IRAS) and make it available to the larger community. 'Research Software' describes software created by researchers and staff for a specific research goal, but lacks sufficient documentation, easy to use interfaces, and rigorous debugging. Additionally, most of the IDL/IRAS code available needed to be ported to a (largely) hardware independent new version of IDL.

  14. Crystal structure of Pseudomonas fluorescens mannitol 2-dehydrogenase binary and ternary complexes. Specificity and catalytic mechanism.

    PubMed

    Kavanagh, Kathryn L; Klimacek, Mario; Nidetzky, Bernd; Wilson, David K

    2002-11-01

    Long-chain mannitol dehydrogenases are secondary alcohol dehydrogenases that are of wide interest because of their involvement in metabolism and potential applications in agriculture, medicine, and industry. They differ from other alcohol and polyol dehydrogenases because they do not contain a conserved tyrosine and are not dependent on Zn(2+) or other metal cofactors. The structures of the long-chain mannitol 2-dehydrogenase (54 kDa) from Pseudomonas fluorescens in a binary complex with NAD(+) and ternary complex with NAD(+) and d-mannitol have been determined to resolutions of 1.7 and 1.8 A and R-factors of 0.171 and 0.176, respectively. These results show an N-terminal domain that includes a typical Rossmann fold. The C-terminal domain is primarily alpha-helical and mediates mannitol binding. The electron lone pair of Lys-295 is steered by hydrogen-bonding interactions with the amide oxygen of Asn-300 and the main-chain carbonyl oxygen of Val-229 to act as the general base. Asn-191 and Asn-300 are involved in a web of hydrogen bonding, which precisely orients the mannitol O2 proton for abstraction. These residues also aid in stabilizing a negative charge in the intermediate state and in preventing the formation of nonproductive complexes with the substrate. The catalytic lysine may be returned to its unprotonated state using a rectifying proton tunnel driven by Glu-292 oscillating among different environments. Despite low sequence homology, the closest structural neighbors are glycerol-3-phosphate dehydrogenase, N-(1-d-carboxylethyl)-l-norvaline dehydrogenase, UDP-glucose dehydrogenase, and 6-phosphogluconate dehydrogenase, indicating a possible evolutionary relationship among these enzymes. PMID:12196534

  15. The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4

    PubMed Central

    Isabet, Tatiana; Montagnac, Guillaume; Regazzoni, Karine; Raynal, Bertrand; Khadali, Fatima El; England, Patrick; Franco, Michel; Chavrier, Philippe; Houdusse, Anne; Ménétrey, Julie

    2009-01-01

    The JNK-interacting proteins, JIP3 and JIP4, are specific effectors of the small GTP-binding protein ARF6. The interaction of ARF6–GTP with the second leucine zipper (LZII) domains of JIP3/JIP4 regulates the binding of JIPs to kinesin-1 and dynactin. Here, we report the crystal structure of ARF6–GTP bound to the JIP4-LZII at 1.9 Å resolution. The complex is a heterotetramer with dyad symmetry arranged in an ARF6–(JIP4)2–ARF6 configuration. Comparison of the ARF6–JIP4 interface with the equivalent region of ARF1 shows the structural basis of JIP4's specificity for ARF6. Using site-directed mutagenesis and surface plasmon resonance, we further show that non-conserved residues at the switch region borders are the key structural determinants of JIP4 specificity. A structure-derived model of the association of the ARF6–JIP3/JIP4 complex with membranes shows that the JIP4-LZII coiled-coil should lie along the membrane to prevent steric hindrances, resulting in only one ARF6 molecule bound. Such a heterotrimeric complex gives insights to better understand the ARF6-mediated motor switch regulatory function. PMID:19644450

  16. Position-specific adaptation in complex cell receptive fields of the cat striate cortex.

    PubMed

    Marlin, S; Douglas, R; Cynader, M

    1993-06-01

    1. Responses of complex cells in cat striate cortex were studied with flashed light slit stimuli. The responses to slits flashed in different positions in the receptive field were assessed quantitatively before and after periods of prolonged stimulation of one small region of the receptive field. This type of prolonged stimulation resulted in reduced responsivity over a limited zone within the complex cell receptive field. 2. The adaptation-induced responsivity decrement was generally observed in both the ON and OFF response profiles but could also be restricted to one or the other. In general, the magnitude of the response decrements was greatest in the ON response profiles. The adaptation-induced response decrement did not necessarily spread throughout the receptive field but was restricted to a small region surrounding the adapted receptive field position (RFP). Adaptation spread equally widely across the ON and OFF response profiles despite the smaller adaptation effects in the OFF profile. 3. The adaptation effects from repeated stimulation at a single RFP did not spread symmetrically across the receptive field, and a given cell's preferred direction of motion indicated the direction of the asymmetric spread of the adaptation. RFPs that would be stimulated by a light slit originating at the point of adaptation and moving in the preferred direction (preferred side) showed greater adaptation-induced response decrements than did RFPs that would be stimulated by a light slit moving in the opposite direction from the point of adaptation (nonpreferred side). There was significant enhancement of responses at some RFPs on the non-preferred side of the point of adaptation. This asymmetric spread of adaptation could be caused by adaptation of inhibitory connections that contribute to complex cell direction selectivity. 4. The asymmetry of adaptation was significantly different for the ON and OFF response profiles. The asymmetric spread of adaptation for the ON response

  17. Efficacy of species-specific recA PCR tests in the identification of Burkholderia cepacia complex environmental isolates.

    PubMed

    Dalmastri, Claudia; Pirone, Luisa; Tabacchioni, Silvia; Bevivino, Annamaria; Chiarini, Luigi

    2005-05-01

    In this study, we evaluated if recA species-specific PCR assays could be successfully applied to identify environmental isolates of the widespread Burkholderia cepacia complex (Bcc) species. A total of 729 Bcc rhizosphere isolates collected in different samplings were assigned to the species B. cepacia genomovar I (61), B. cenocepacia recA lineage IIIB (514), B. ambifaria (124) and B. pyrrocinia (30), by means of recA (RFLP) analysis, and PCR tests were performed to assess sensitivity and specificity of recA species-specific primers pairs. B. cepacia genomovar I specific primers produced the expected amplicon with all isolates of the corresponding species (sensitivity, 100%), and cross-reacted with all B. pyrrocinia isolates. On the contrary, B. cenocepacia IIIB primers did not give the expected amplicon in 164 B. cenocepacia IIIB isolates (sensitivity, 68.1%), and isolates of distinct populations showed different sensitivity. B. ambifaria primers failed to amplify a recA-specific fragment only in a few isolates of this species (sensitivity, 93.5%). The absence of specific amplification in a high number of B. cenocepacia rhizosphere isolates indicates that recA specific PCR assays can lead to an underestimation of environmental microorganisms belonging to this bacterial species. PMID:15869960

  18. The Staphylococcus aureus lineage-specific markers collagen adhesin and toxic shock syndrome toxin 1 distinguish multilocus sequence typing clonal complexes within spa clonal complexes.

    PubMed

    Deurenberg, Ruud H; Rijnders, Michelle I A; Sebastian, Silvie; Welling, Maaike A; Beisser, Patrick S; Stobberingh, Ellen E

    2009-10-01

    Spa typing/based upon repeat pattern (BURP) sometimes cannot differentiate multilocus sequence typing (MLST) clonal complexes (CCs) within spa-CCs. It has been observed previously that virulence factors, such as collagen adhesin (CNA) and toxic shock syndrome toxin 1 (TSST-1), are associated with certain Staphylococcus aureus lineages. Analysis of methicillin-sensitive and methicillin-resistant S. aureus by spa typing/BURP and detection of CNA and TSST-1 observed an association between CNA and MLST CC1, 12, 22, 30, 45, 51, and 239 and between TSST-1 and MLST CC30. In spa-CC 012, associated with MLST CC7, CC15, and CC30, MLST CC30 could be distinguished from MLST CC7 and CC15 with CNA and TSST-1 as lineage-specific markers. Lineage-specific markers can overcome clustering of nonrelated MLST CCs into 1 spa-CC. PMID:19748421

  19. Product binding enforces the genomic specificity of a yeast Polycomb repressive complex

    PubMed Central

    Dumesic, Phillip A.; Homer, Christina M.; Moresco, James J.; Pack, Lindsey R.; Shanle, Erin K.; Coyle, Scott M.; Strahl, Brian D.; Fujimori, Danica G.; Yates, John R.; Madhani, Hiten D.

    2015-01-01

    SUMMARY We characterize the Polycomb system that assembles repressive subtelomeric domains of H3K27 methylation (H3K27me) in the yeast Cryptococcus neoformans. Purification of this PRC2-like protein complex reveals orthologs of animal PRC2 components as well as a chromodomain-containing subunit, Ccc1, which recognizes H3K27me. Whereas removal of either the EZH or EED ortholog eliminates H3K27me, disruption of mark recognition by Ccc1 causes H3K27me to redistribute. Strikingly, the resulting pattern of H3K27me coincides with domains of heterochromatin marked by H3K9me. Indeed, additional removal of the C. neoformans H3K9 methyltransferase Clr4 results in loss of both H3K9me and the redistributed H3K27me marks. These findings indicate that the anchoring of a chromatin-modifying complex to its product suppresses its attraction to a different chromatin type, explaining how enzymes that act on histones, which often harbor product recognition modules, may deposit distinct chromatin domains despite sharing a highly abundant and largely identical substrate—the nucleosome. PMID:25533783

  20. Solid Waste Operations Complex W-113, Detail Design Report (Title II). Volume 3: Specifications

    SciTech Connect

    1995-09-01

    The Solid Waste Retrieval Facility--Phase 1 (Project W113) will provide the infrastructure and the facility required to retrieve from Trench 04, Burial ground 4C, contact handled (CH) drums and boxes at a rate that supports all retrieved TRU waste batching, treatment, storage, and disposal plans. This includes (1) operations related equipment and facilities, viz., a weather enclosure for the trench, retrieval equipment, weighing, venting, obtaining gas samples, overpacking, NDE, NDA, shipment of waste and (2) operations support related facilities, viz., a general office building, a retrieval staff change facility, and infrastructure upgrades such as supply and routing of water, sewer, electrical power, fire protection, roads, and telecommunication. Title I design for the operations related equipment and facilities was performed by Raytheon/BNFL, and that for the operations support related facilities including infrastructure upgrade was performed by KEH. These two scopes were combined into an integrated W113 Title II scope that was performed by Raytheon/BNFL. Volume 3 is a compilation of the construction specifications that will constitute the Title II materials and performance specifications. This volume contains CSI specifications for non-equipment related construction material type items, performance type items, and facility mechanical equipment items. Data sheets are provided, as necessary, which specify the equipment overall design parameters.

  1. Publishing Platform for Scientific Software - Lessons Learned

    NASA Astrophysics Data System (ADS)

    Hammitzsch, Martin; Fritzsch, Bernadette; Reusser, Dominik; Brembs, Björn; Deinzer, Gernot; Loewe, Peter; Fenner, Martin; van Edig, Xenia; Bertelmann, Roland; Pampel, Heinz; Klump, Jens; Wächter, Joachim

    2015-04-01

    Scientific software has become an indispensable commodity for the production, processing and analysis of empirical data but also for modelling and simulation of complex processes. Software has a significant influence on the quality of research results. For strengthening the recognition of the academic performance of scientific software development, for increasing its visibility and for promoting the reproducibility of research results, concepts for the publication of scientific software have to be developed, tested, evaluated, and then transferred into operations. For this, the publication and citability of scientific software have to fulfil scientific criteria by means of defined processes and the use of persistent identifiers, similar to data publications. The SciForge project is addressing these challenges. Based on interviews a blueprint for a scientific software publishing platform and a systematic implementation plan has been designed. In addition, the potential of journals, software repositories and persistent identifiers have been evaluated to improve the publication and dissemination of reusable software solutions. It is important that procedures for publishing software as well as methods and tools for software engineering are reflected in the architecture of the platform, in order to improve the quality of the software and the results of research. In addition, it is necessary to work continuously on improving specific conditions that promote the adoption and sustainable utilization of scientific software publications. Among others, this would include policies for the development and publication of scientific software in the institutions but also policies for establishing the necessary competencies and skills of scientists and IT personnel. To implement the concepts developed in SciForge a combined bottom-up / top-down approach is considered that will be implemented in parallel in different scientific domains, e.g. in earth sciences, climate research and

  2. Software development methodology for high consequence systems

    SciTech Connect

    Baca, L.S.; Bouchard, J.F.; Collins, E.W.; Eisenhour, M.; Neidigk, D.D.; Shortencarier, M.J.; Trellue, P.A.

    1997-10-01

    This document describes a Software Development Methodology for High Consequence Systems. A High Consequence System is a system whose failure could lead to serious injury, loss of life, destruction of valuable resources, unauthorized use, damaged reputation or loss of credibility or compromise of protected information. This methodology can be scaled for use in projects of any size and complexity and does not prescribe any specific software engineering technology. Tasks are described that ensure software is developed in a controlled environment. The effort needed to complete the tasks will vary according to the size, complexity, and risks of the project. The emphasis of this methodology is on obtaining the desired attributes for each individual High Consequence System.

  3. Exactin: A specific inhibitor of Factor X activation by extrinsic tenase complex from the venom of Hemachatus haemachatus

    PubMed Central

    Girish, Vallerinteavide Mavelli; Kini, R. Manjunatha

    2016-01-01

    Unwanted clots lead to heart attack and stroke that result in a large number of deaths. Currently available anticoagulants have some drawbacks including their non-specific actions. Therefore novel anticoagulants that target specific steps in the coagulation pathway are being sought. Here we describe the identification and characterization of a novel anticoagulant protein from the venom of Hemachatus haemachatus (African Ringhals cobra) that specifically inhibits factor X (FX) activation by the extrinsic tenase complex (ETC) and thus named as exactin. Exactin belongs to the three-finger toxin (3FTx) family, with high sequence identity to neurotoxins and low identity to the well-characterized 3FTx anticoagulants-hemextin and naniproin. It is a mixed-type inhibitor of ETC with the kinetic constants, Ki’ and Ki determined as 30.62 ± 7.73 nM and 153.75 ± 17.96 nM, respectively. Exactin does not bind to the active site of factor VIIa and factor Xa based on its weak inhibition (IC50 ≫ 300 μM) to the amidolytic activities of these proteases. Exactin shows exquisite macromolecular specificity to FX activation as compared to factor IX activation by ETC. Exactin thus displays a distinct mechanism when compared to other anticoagulants targeting ETC, with its selective preference to ETC-FX [ES] complex. PMID:27558950

  4. Exactin: A specific inhibitor of Factor X activation by extrinsic tenase complex from the venom of Hemachatus haemachatus.

    PubMed

    Girish, Vallerinteavide Mavelli; Kini, R Manjunatha

    2016-01-01

    Unwanted clots lead to heart attack and stroke that result in a large number of deaths. Currently available anticoagulants have some drawbacks including their non-specific actions. Therefore novel anticoagulants that target specific steps in the coagulation pathway are being sought. Here we describe the identification and characterization of a novel anticoagulant protein from the venom of Hemachatus haemachatus (African Ringhals cobra) that specifically inhibits factor X (FX) activation by the extrinsic tenase complex (ETC) and thus named as exactin. Exactin belongs to the three-finger toxin (3FTx) family, with high sequence identity to neurotoxins and low identity to the well-characterized 3FTx anticoagulants-hemextin and naniproin. It is a mixed-type inhibitor of ETC with the kinetic constants, Ki' and Ki determined as 30.62 ± 7.73 nM and 153.75 ± 17.96 nM, respectively. Exactin does not bind to the active site of factor VIIa and factor Xa based on its weak inhibition (IC50 ≫ 300 μM) to the amidolytic activities of these proteases. Exactin shows exquisite macromolecular specificity to FX activation as compared to factor IX activation by ETC. Exactin thus displays a distinct mechanism when compared to other anticoagulants targeting ETC, with its selective preference to ETC-FX [ES] complex. PMID:27558950

  5. BCG Vaccination Induces Robust CD4+ T Cell Responses to Mycobacterium tuberculosis Complex-Specific Lipopeptides in Guinea Pigs.

    PubMed

    Kaufmann, Eva; Spohr, Christina; Battenfeld, Sibylle; De Paepe, Diane; Holzhauser, Thomas; Balks, Elisabeth; Homolka, Susanne; Reiling, Norbert; Gilleron, Martine; Bastian, Max

    2016-03-15

    A new class of highly antigenic, MHC-II-restricted mycobacterial lipopeptides that are recognized by CD4-positive T lymphocytes of Mycobacterium tuberculosis-infected humans has recently been described. To investigate the relevance of this novel class of mycobacterial Ags in the context of experimental bacille Calmette-Guérin (BCG) vaccination, Ag-specific T cell responses to mycobacterial lipid and lipopeptide-enriched Ag preparations were analyzed in immunized guinea pigs. Lipid and lipopeptide preparations as well as complex Ag mixtures, such as tuberculin, mycobacterial lysates, and culture supernatants, all induced a similar level of T cell proliferation. The hypothesis that lipopeptide-specific T cells dominate the early BCG-induced T cell response was corroborated in restimulation assays by the observation that Ag-expanded T cells specifically responded to the lipopeptide preparation. A comparative analysis of the responses to Ag preparations from different mycobacterial species revealed that the antigenic lipopeptides are specific for strains of the M. tuberculosis complex. Their intriguing conservation in pathogenic tuberculous bacteria and the fact that these highly immunogenic Ags seem to be actively released during in vitro culture and intracellular infection prompt the urgent question about their role in the fine-tuned interplay between the pathogen and its mammalian host, in particular with regard to BCG vaccination strategies. PMID:26889044

  6. Cooperativity and substrate specificity of an alkaline amylase and neopullulanase complex of Micrococcus halobius OR-1.

    PubMed

    Rajdevi, K P; Yogeeswaran, G

    2001-03-01

    The saccharifying alkaline amylase and neopullulanase complex of Micrococcus halobius OR-1 hydrolyzes both alpha-(1,4)- and alpha-(1,6)-glycosidic linkages of different linear and branched polysaccharides. The following observations were made concerning the analysis of the coexpressed amylase and neopullulanase enzymes. Even though the enzymes were subjected to a rigorous purification protocol, the activities could not be separated, because both the enzymes were found to migrate in a single peak. By contrast, two independent bands of amylolytic activity at 70 kDa and pullulanolytic activity at 53 kDa were evident by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), reducing and nonreducing PAGE, and zymographic analysis on different polysaccharides. Preferential chemical modification of the enzyme and concomitant high-performance thin-layer chromatographic analyses of the saccharides liberated showed that amylase is sensitive to 1-(dimethylamino-propyl)-3-ethyl carbodiimide-HCl and cleaved alpha-(1,4) linkages of starch, amylose, and amylopectin producing predominantly maltotriose. On the other hand, formalin-sensitive neopullulanase acts on both alpha-(1,4) and alpha-(1,6) linkages of pullulan and starch with maltotriose and panose as major products. It is understood that neopullulanase exhibits dual activity and acts in synergy with amylase toward the hydrolysis of alpha-(1,4) linkages, thereby increasing the overall reaction rate; however, such a synergism is not seen in zymograms, in which the enzymes are physically separated during electrophoresis. It is presumed that SDS-protein intercalation dissociated the enzyme complex, without altering the individual active site architecture, with only the synergism lost. The optimum temperature and pH of amylase and neopullulanase were 60 degreesC and 8.0, respectively. The enzymes were found stable in high alkaline pH for 24 h. Therefore, the saccharifying alkaline amylase and neopullulanase of M

  7. Learning from Software Localization.

    ERIC Educational Resources Information Center

    Guo, She-Sen

    2003-01-01

    Localization is the process of adapting a product to meet the language, cultural and other requirements of a specific target environment or market. This article describes ways in which software localization impacts upon curriculum, and discusses what students will learn from software localization. (AEF)

  8. Software measurement guidebook

    NASA Technical Reports Server (NTRS)

    Bassman, Mitchell J.; Mcgarry, Frank; Pajerski, Rose

    1994-01-01

    This software Measurement Guidebook presents information on the purpose and importance of measurement. It discusses the specific procedures and activities of a measurement program and the roles of the people involved. The guidebook also clarifies the roles that measurement can and must play in the goal of continual, sustained improvement for all software production and maintenance efforts.

  9. Flexible Workflow Software enables the Management of an Increased Volume and Heterogeneity of Sensors, and evolves with the Expansion of Complex Ocean Observatory Infrastructures.

    NASA Astrophysics Data System (ADS)

    Tomlin, M. C.; Jenkyns, R.

    2015-12-01

    Ocean Networks Canada (ONC) collects data from observatories in the northeast Pacific, Salish Sea, Arctic Ocean, Atlantic Ocean, and land-based sites in British Columbia. Data are streamed, collected autonomously, or transmitted via satellite from a variety of instruments. The Software Engineering group at ONC develops and maintains Oceans 2.0, an in-house software system that acquires and archives data from sensors, and makes data available to scientists, the public, government and non-government agencies. The Oceans 2.0 workflow tool was developed by ONC to manage a large volume of tasks and processes required for instrument installation, recovery and maintenance activities. Since 2013, the workflow tool has supported 70 expeditions and grown to include 30 different workflow processes for the increasing complexity of infrastructures at ONC. The workflow tool strives to keep pace with an increasing heterogeneity of sensors, connections and environments by supporting versioning of existing workflows, and allowing the creation of new processes and tasks. Despite challenges in training and gaining mutual support from multidisciplinary teams, the workflow tool has become invaluable in project management in an innovative setting. It provides a collective place to contribute to ONC's diverse projects and expeditions and encourages more repeatable processes, while promoting interactions between the multidisciplinary teams who manage various aspects of instrument development and the data they produce. The workflow tool inspires documentation of terminologies and procedures, and effectively links to other tools at ONC such as JIRA, Alfresco and Wiki. Motivated by growing sensor schemes, modes of collecting data, archiving, and data distribution at ONC, the workflow tool ensures that infrastructure is managed completely from instrument purchase to data distribution. It integrates all areas of expertise and helps fulfill ONC's mandate to offer quality data to users.

  10. Model-Based Software Testing for Object-Oriented Software

    ERIC Educational Resources Information Center

    Biju, Soly Mathew

    2008-01-01

    Model-based testing is one of the best solutions for testing object-oriented software. It has a better test coverage than other testing styles. Model-based testing takes into consideration behavioural aspects of a class, which are usually unchecked in other testing methods. An increase in the complexity of software has forced the software industry…

  11. Software Engineering Program: Software Process Improvement Guidebook

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The purpose of this document is to provide experience-based guidance in implementing a software process improvement program in any NASA software development or maintenance community. This guidebook details how to define, operate, and implement a working software process improvement program. It describes the concept of the software process improvement program and its basic organizational components. It then describes the structure, organization, and operation of the software process improvement program, illustrating all these concepts with specific NASA examples. The information presented in the document is derived from the experiences of several NASA software organizations, including the SEL, the SEAL, and the SORCE. Their experiences reflect many of the elements of software process improvement within NASA. This guidebook presents lessons learned in a form usable by anyone considering establishing a software process improvement program within his or her own environment. This guidebook attempts to balance general and detailed information. It provides material general enough to be usable by NASA organizations whose characteristics do not directly match those of the sources of the information and models presented herein. It also keeps the ideas sufficiently close to the sources of the practical experiences that have generated the models and information.

  12. Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity.

    PubMed

    Malter, M P; Frisch, C; Schoene-Bake, J C; Helmstaedter, C; Wandinger, K P; Stoecker, W; Urbach, H; Surges, R; Elger, C E; Vincent, A V; Bien, C G

    2014-09-01

    In limbic encephalitis (LE) with antibodies (Abs) to the voltage-gated potassium channel complex (VGKC), the Abs are mainly directed to the VGKC-complex proteins, leucine-rich, glioma inactivated 1 protein (LGI1) or contactin-associated protein-like 2 (CASPR-2) or neither. Here, we relate the outcomes of VGKC-LE patients to the presence of Abs to LGI1, CASPR-2 or neither antigen (LGI1/CASPR-2-Ab(-)). Clinical, neuropsychology and MRI data were obtained from patient records for all LE patients from the Bonn Epilepsy Centre positive for VGKC-Abs by radioimmunoprecipitation assay between 2002 and 2011. Eighteen VGKC-LE patients were identified: nine patients (50 %) had LGI1-Abs, three (16 %) had CASPR-2-Abs; and six (33 %) were negative for both LGI1- and CASPR-2-Abs. At first assessment, the groups did not differ clinically or radiologically, but faciobrachial dystonic seizures were only observed in two LGI1-Ab(+) patients. All patients received monthly intravenous methylprednisolone (MP) pulses. At the most recent follow up (median 26 months), thirteen (72 %) were seizure-free, and seizure-freedom rates did not differ between the Ab groups. Hippocampal atrophy had developed in 7/9 LGI1-Ab(+) patients, but in none of the CASPR-2-Ab(+) or LGI/CASPR-2-Ab(-) patients (p = 0.003). While all subgroups improved, memory scores only normalized in six patients (33 %) and LGI1-Ab(+) patients were left with significantly poorer memory than the other two subgroups. Most VGKC-LE patients become seizure-free with pulsed monthly MP, but memory outcome is less favourable. Hippocampal atrophy and poor memory recovery is common in patients with LGI1-Abs and suggests permanent functional damage. More intense immunotherapies could improve outcomes in LGI1-Ab(+)-LE. PMID:24935858

  13. Lamina-specific contribution of glutamatergic and GABAergic potentials to hippocampal sharp wave-ripple complexes

    PubMed Central

    Schönberger, Jan; Draguhn, Andreas; Both, Martin

    2014-01-01

    The mammalian hippocampus expresses highly organized patterns of neuronal activity which form a neuronal correlate of spatial memories. These memory-encoding neuronal ensembles form on top of different network oscillations which entrain neurons in a state- and experience-dependent manner. The mechanisms underlying activation, timing and selection of participating neurons are incompletely understood. Here we studied the synaptic mechanisms underlying one prominent network pattern called sharp wave-ripple complexes (SPW-R) which are involved in memory consolidation during sleep. We recorded SPW-R with extracellular electrodes along the different layers of area CA1 in mouse hippocampal slices. Contribution of glutamatergic excitation and GABAergic inhibition, respectively, was probed by local application of receptor antagonists into s. radiatum, pyramidale and oriens. Laminar profiles of field potentials show that GABAergic potentials contribute substantially to sharp waves and superimposed ripple oscillations in s. pyramidale. Inhibitory inputs to s. pyramidale and s. oriens are crucial for action potential timing by ripple oscillations, as revealed by multiunit-recordings in the pyramidal cell layer. Glutamatergic afferents, on the other hand, contribute to sharp waves in s. radiatum where they also evoke a fast oscillation at ~200 Hz. Surprisingly, field ripples in s. radiatum are slightly slower than ripples in s. pyramidale, resulting in a systematic shift between dendritic and somatic oscillations. This complex interplay between dendritic excitation and perisomatic inhibition may be responsible for the precise timing of discharge probability during the time course of SPW-R. Together, our data illustrate a complementary role of spatially confined excitatory and inhibitory transmission during highly ordered network patterns in the hippocampus. PMID:25202239

  14. Portable Medical Laboratory Applications Software

    PubMed Central

    Silbert, Jerome A.

    1983-01-01

    Portability implies that a program can be run on a variety of computers with minimal software revision. The advantages of portability are outlined and design considerations for portable laboratory software are discussed. Specific approaches for achieving this goal are presented.

  15. Methods to Identify Chromatin-Bound Protein Complexes: From Genome-Wide to Locus-Specific Approaches.

    PubMed

    Massie, Charles E

    2016-01-01

    High-throughput sequencing approaches coupled with functional genomics experiments have facilitated a rapid growth in our understanding of chromatin biology, from genome-wide maps of transcription factor binding and histone modifications to insights into higher order chromatin organization under specific cellular conditions. However in most cases these methods require a prior knowledge of the system of interest (e.g., targets for immunoprecipitation or modulation) and therefore are limited in their utility to identify novel components of pathways or for the study of uncharacterized pathways. Several orthologous proteomics approaches have been developed recently that bridge this gap, allowing the identification of protein complexes globally or at specific genomic loci. In this chapter the relative advantages of each approach will be explored and a detailed protocol given for DNA pull-down of a specific androgen receptor (AR) genomic target. PMID:27246338

  16. Conformation specific spectroscopy in the complexity gap: beta-peptides and flexible bichromophores

    NASA Astrophysics Data System (ADS)

    Baquero, Esteban Edwin

    Flexible biomolecules with many degrees of freedom have the ability to sample a great number of structural minima. The intrinsic structural preferences of these molecules are driven by stabilizations due to intramolecular interactions such as hydrogen bonding and interatomic attractive forces. These interactions become increasingly important as the atoms in the molecule come in close proximity to one another. The present work describes the conformational preferences of several model bio-relevant molecules of different sizes where different kinds of intramolecular interactions can occur. Conformation specific ultraviolet and infrared spectroscopies were utilized to obtain the spectroscopic signatures of different conformations of the jet cooled biomolecules. These experiments allowed for the assignment of conformational families and the development of a general protocol to identify the infrared signatures of amide NH stretches, which were found to vary in frequency due to their immediate chemical and structural environment. Specific examples of systems studied include molecules containing unnatural polypeptide chains and a flexible bichromophore. The unnatural polypetides (Ac-beta3-hPhe-NHMe, Ac-beta 3-hTyr-NHMe Ac-beta3-hPhe-beta3-hAla-NHMe and Ac-beta3-hAla-beta3-hPhe-NHMe) were found to have a rich conformational potential energy landscape that contained many kinds of intramolecular hydrogen bonded minima. The flexible bichromophore (HNBPA), containing two spectroscopically distinguishable chromophores (Phenol and Phenyl), was found to be an interesting case study for conformational specific electronic energy transfer and testing how well different theoretical methods manage non-covalent interactions, such as those between side-chain atoms and aromatic pi-clouds.

  17. Software Carpentry In The Hydrological Sciences

    NASA Astrophysics Data System (ADS)

    Ahmadia, A. J.; Kees, C. E.

    2014-12-01

    Scientists are spending an increasing amount of time building and using hydrology software. However, most scientists are never taught how to do this efficiently. As a result, many are unaware of tools and practices that would allow them to write more reliable and maintainable code with less effort. As hydrology models increase in capability and enter use by a growing number of scientists and their communities, it is important that the scientific software development practices scale up to meet the challenges posed by increasing software complexity, lengthening software lifecycles, a growing number of stakeholders and contributers, and a broadened developer base that extends from application domains to high performance computing centers. Many of these challenges in complexity, lifecycles, and developer base have been successfully met by the open source community, and there are many lessons to be learned from their experiences and practices. Additionally, there is much wisdom to be found in the results of research studies conducted on software engineering itself. Software Carpentry aims to bridge the gap between the current state of software development and these known best practices for scientific software development, with a focus on hands-on exercises and practical advice. In 2014, Software Carpentry workshops targeting earth/environmental sciences and hydrological modeling have been organized and run at the Massachusetts Institute of Technology, the US Army Corps of Engineers, the Community Surface Dynamics Modeling System Annual Meeting, and the Earth Science Information Partners Summer Meeting. In this presentation, we will share some of the successes in teaching this material, as well as discuss and present instructional material specific to hydrological modeling.

  18. Powerplant software

    SciTech Connect

    Elliott, T.C.

    1995-07-01

    Powerplants need software to thrive and compete. Covered here are many programs and applications -- an overview of the functions, tasks, and problem-solving software is used for today. Software or, more accurately, software-driven systems are pervasive. Their presence is felt in every nook and cranny of the powerplant -- from design and construction through operation and maintenance, even dismantling and decommissioning -- embracing whole systems but also focusing on individual pieces of equipment. No one software supplier or two or three dominates -- powerplant software is the purview of scores if not hundreds of suppliers ranging from the largest corporations to individual consultants and application developers.

  19. Dynamic Antibody Specificities and Virion Concentrations in Circulating Immune Complexes in Acute to Chronic HIV-1 Infection ▿ †

    PubMed Central

    Liu, Pinghuang; Overman, R. Glenn; Yates, Nicole L.; Alam, S. Munir; Vandergrift, Nathan; Chen, Yue; Graw, Frederik; Freel, Stephanie A.; Kappes, John C.; Ochsenbauer, Christina; Montefiori, David C.; Gao, Feng; Perelson, Alan S.; Cohen, Myron S.; Haynes, Barton F.; Tomaras, Georgia D.

    2011-01-01

    Understanding the interactions between human immunodeficiency virus type 1 (HIV-1) virions and antibodies (Ab) produced during acute HIV-1 infection (AHI) is critical for defining antibody antiviral capabilities. Antibodies that bind virions may prevent transmission by neutralization of virus or mechanically prevent HIV-1 migration through mucosal layers. In this study, we quantified circulating HIV-1 virion-immune complexes (ICs), present in approximately 90% of AHI subjects, and compared the levels and antibody specificity to those in chronic infection. Circulating HIV-1 virions coated with IgG (immune complexes) were in significantly lower levels relative to the viral load in acute infection than in chronic HIV-1 infection. The specificities of the antibodies in the immune complexes differed between acute and chronic infection (anti-gp41 Ab in acute infection and anti-gp120 in chronic infection), potentially suggesting different roles in immunopathogenesis for complexes arising at different stages of infection. We also determined the ability of circulating IgG from AHI to bind infectious versus noninfectious virions. Similar to a nonneutralizing anti-gp41 monoclonal antibody (MAb), purified plasma IgG from acute HIV-1 subjects bound both infectious and noninfectious virions. This was in contrast to the neutralizing antibody 2G12 MAb that bound predominantly infectious virions. Moreover, the initial antibody response captured acute HIV-1 virions without selection for different HIV-1 envelope sequences. In total, this study demonstrates that the composition of immune complexes are dynamic over the course of HIV-1 infection and are comprised initially of antibodies that nonselectively opsonize both infectious and noninfectious virions, likely contributing to the lack of efficacy of the antibody response during acute infection. PMID:21865397

  20. Analyzing Software Requirements Errors in Safety-Critical, Embedded Systems

    NASA Technical Reports Server (NTRS)

    Lutz, Robyn R.

    1993-01-01

    This paper analyzes the root causes of safety-related software errors in safety-critical, embedded systems. The results show that software errors identified as potentially hazardous to the system tend to be produced by different error mechanisms than non- safety-related software errors. Safety-related software errors are shown to arise most commonly from (1) discrepancies between the documented requirements specifications and the requirements needed for correct functioning of the system and (2) misunderstandings of the software's interface with the rest of the system. The paper uses these results to identify methods by which requirements errors can be prevented. The goal is to reduce safety-related software errors and to enhance the safety of complex, embedded systems.

  1. The development model of software product line based AOP

    NASA Astrophysics Data System (ADS)

    Yin, JingHai

    2011-10-01

    In this paper, we proposed a development model of MIS (management information system) software based aspect-oriented programming. MIS software will be the full separation of concerns, and establish corresponding platform-independent model, the dynamic weaving of aspects does not require all the static or fixed in weaver weaving in specific areas and at the same time Optimization, reducing system complexity and improve software development efficiency and speed. While the description and implementation of all aspects of the software industry chain assigned to the various levels of development team to complete, MIS can help resolve the current heavy workload of the software development process, low developing level, low software reuse rate, more duplication work of effort Problems.

  2. A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.

    PubMed

    Shah, Meera; Su, Dan; Scheliga, Judith S; Pluskal, Tomáš; Boronat, Susanna; Motamedchaboki, Khatereh; Campos, Alexandre Rosa; Qi, Feng; Hidalgo, Elena; Yanagida, Mitsuhiro; Wolf, Dieter A

    2016-08-16

    The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer. PMID:27477275

  3. PD5: A General Purpose Library for Primer Design Software

    PubMed Central

    Riley, Michael C.; Aubrey, Wayne; Young, Michael; Clare, Amanda

    2013-01-01

    Background Complex PCR applications for large genome-scale projects require fast, reliable and often highly sophisticated primer design software applications. Presently, such applications use pipelining methods to utilise many third party applications and this involves file parsing, interfacing and data conversion, which is slow and prone to error. A fully integrated suite of software tools for primer design would considerably improve the development time, the processing speed, and the reliability of bespoke primer design software applications. Results The PD5 software library is an open-source collection of classes and utilities, providing a complete collection of software building blocks for primer design and analysis. It is written in object-oriented C++ with an emphasis on classes suitable for efficient and rapid development of bespoke primer design programs. The modular design of the software library simplifies the development of specific applications and also integration with existing third party software where necessary. We demonstrate several applications created using this software library that have already proved to be effective, but we view the project as a dynamic environment for building primer design software and it is open for future development by the bioinformatics community. Therefore, the PD5 software library is published under the terms of the GNU General Public License, which guarantee access to source-code and allow redistribution and modification. Conclusions The PD5 software library is downloadable from Google Code and the accompanying Wiki includes instructions and examples: http://code.google.com/p/primer-design PMID:24278254

  4. Property-Based Software Engineering Measurement

    NASA Technical Reports Server (NTRS)

    Briand, Lionel C.; Morasca, Sandro; Basili, Victor R.

    1997-01-01

    Little theory exists in the field of software system measurement. Concepts such as complexity, coupling, cohesion or even size are very often subject to interpretation and appear to have inconsistent definitions in the literature. As a consequence, there is little guidance provided to the analyst attempting to define proper measures for specific problems. Many controversies in the literature are simply misunderstandings and stem from the fact that some people talk about different measurement concepts under the same label (complexity is the most common case). There is a need to define unambiguously the most important measurement concepts used in the measurement of software products. One way of doing so is to define precisely what mathematical properties characterize these concepts, regardless of the specific software artifacts to which these concepts are applied. Such a mathematical framework could generate a consensus in the software engineering community and provide a means for better communication among researchers, better guidelines for analysts, and better evaluation methods for commercial static analyzers for practitioners. In this paper, we propose a mathematical framework which is generic, because it is not specific to any particular software artifact and rigorous, because it is based on precise mathematical concepts. We use this framework to propose definitions of several important measurement concepts (size, length, complexity, cohesion, coupling). It does not intend to be complete or fully objective; other frameworks could have been proposed and different choices could have been made. However, we believe that the formalisms and properties we introduce are convenient and intuitive. This framework contributes constructively to a firmer theoretical ground of software measurement.

  5. Property-Based Software Engineering Measurement

    NASA Technical Reports Server (NTRS)

    Briand, Lionel; Morasca, Sandro; Basili, Victor R.

    1995-01-01

    Little theory exists in the field of software system measurement. Concepts such as complexity, coupling, cohesion or even size are very often subject to interpretation and appear to have inconsistent definitions in the literature. As a consequence, there is little guidance provided to the analyst attempting to define proper measures for specific problems. Many controversies in the literature are simply misunderstandings and stem from the fact that some people talk about different measurement concepts under the same label (complexity is the most common case). There is a need to define unambiguously the most important measurement concepts used in the measurement of software products. One way of doing so is to define precisely what mathematical properties characterize these concepts regardless of the specific software artifacts to which these concepts are applied. Such a mathematical framework could generate a consensus in the software engineering community and provide a means for better communication among researchers, better guidelines for analysis, and better evaluation methods for commercial static analyzers for practitioners. In this paper, we propose a mathematical framework which is generic, because it is not specific to any particular software artifact, and rigorous, because it is based on precise mathematical concepts. This framework defines several important measurement concepts (size, length, complexity, cohesion, coupling). It is not intended to be complete or fully objective; other frameworks could have been proposed and different choices could have been made. However, we believe that the formalism and properties we introduce are convenient and intuitive. In addition, we have reviewed the literature on this subject and compared it with our work. This framework contributes constructively to a firmer theoretical ground of software measurement.

  6. Architecture for Verifiable Software

    NASA Technical Reports Server (NTRS)

    Reinholtz, William; Dvorak, Daniel

    2005-01-01

    Verifiable MDS Architecture (VMA) is a software architecture that facilitates the construction of highly verifiable flight software for NASA s Mission Data System (MDS), especially for smaller missions subject to cost constraints. More specifically, the purpose served by VMA is to facilitate aggressive verification and validation of flight software while imposing a minimum of constraints on overall functionality. VMA exploits the state-based architecture of the MDS and partitions verification issues into elements susceptible to independent verification and validation, in such a manner that scaling issues are minimized, so that relatively large software systems can be aggressively verified in a cost-effective manner.

  7. Comprehending Software Architecture using a Single-View Visualization

    SciTech Connect

    Panas, T; Epperly, T W; Quinlan, D J; Saebjoernsen, A; Vuduc, R W

    2007-01-17

    Software is among the most complex human artifacts, and visualization is widely acknowledged as important to understanding software. In this paper, we consider the problem of understanding a software system's architecture through visualization. Whereas traditional visualizations use multiple stakeholder-specific views to present different kinds of task-specific information, we propose an additional visualization technique that unifies the presentation of various kinds of architecture-level information, thereby allowing a variety of stakeholders to quickly see and communicate current development, quality, and costs of a software system. For future empirical evaluation of multi-aspect, single-view architectural visualizations, we have implemented our idea in an existing visualization tool, Vizz3D. Our implementation includes techniques, such as the use of a city metaphor, that reduce visual complexity in order to support single-view visualizations of large-scale programs.

  8. Enhancement of specific biological activity of dipyridamole by complexation with beta-cyclodextrin.

    PubMed

    Fregnan, G B; Bertè, F

    1990-01-01

    Dipyridamole forms an inclusion complex with beta-cyclodextrin (dip-beta-CD) which shows better solubility and bioavailability than the uncomplexed compound. The present studies have demonstrated that dip-beta-CD is more effective than dipyridamole either as base or HCl (dispersed or not in lactose) on some important cardiovascular parameters when orally administered to conscious animals. In particular, dip-beta-CD causes a stronger and prompter coronary and carotid vasodilatation in dogs, at doses which weakly influence the systemic arterial pressure and the heart rate. In addition, platelets collected from treated rabbits at various intervals appear to be protected from sodium adenosine diphosphate-induced aggregation in vitro more effectively and rapidly by dip-beta-CD than by dipyridamole. Studies on tail bleeding time have confirmed that dip-beta-CD is more active than dipyridamole when given orally to mice. These biological findings are fully in agreement with other oral bioavailability studies in dogs and men indicating that dip-beta-CD gives quicker and higher blood levels with smaller interindividual variability than dipyridamole. PMID:2345776

  9. Structure-Specific nuclease activities of Artemis and the Artemis: DNA-PKcs complex

    PubMed Central

    Chang, Howard H.Y.; Lieber, Michael R.

    2016-01-01

    Artemis is a vertebrate nuclease with both endo- and exonuclease activities that acts on a wide range of nucleic acid substrates. It is the main nuclease in the non-homologous DNA end-joining pathway (NHEJ). Not only is Artemis important for the repair of DNA double-strand breaks (DSBs) in NHEJ, it is essential in opening the DNA hairpin intermediates that are formed during V(D)J recombination. Thus, humans with Artemis deficiencies do not have T- or B-lymphocytes and are diagnosed with severe combined immunodeficiency (SCID). While Artemis is the only vertebrate nuclease capable of opening DNA hairpins, it has also been found to act on other DNA substrates that share common structural features. Here, we discuss the key structural features that all Artemis DNA substrates have in common, thus providing a basis for understanding how this structure-specific nuclease recognizes its DNA targets. PMID:27198222

  10. Choosing a software design method for real-time Ada applications: JSD process inversion as a means to tailor a design specification to the performance requirements and target machine

    NASA Technical Reports Server (NTRS)

    Withey, James V.

    1986-01-01

    The validity of real-time software is determined by its ability to execute on a computer within the time constraints of the physical system it is modeling. In many applications the time constraints are so critical that the details of process scheduling are elevated to the requirements analysis phase of the software development cycle. It is not uncommon to find specifications for a real-time cyclic executive program included to assumed in such requirements. It was found that prelininary designs structured around this implementation abscure the data flow of the real world system that is modeled and that it is consequently difficult and costly to maintain, update and reuse the resulting software. A cyclic executive is a software component that schedules and implicitly synchronizes the real-time software through periodic and repetitive subroutine calls. Therefore a design method is sought that allows the deferral of process scheduling to the later stages of design. The appropriate scheduling paradigm must be chosen given the performance constraints, the largest environment and the software's lifecycle. The concept of process inversion is explored with respect to the cyclic executive.

  11. Statistical software for microcomputers-A user's view.

    PubMed

    Averill, D W

    1989-11-01

    The selection of statistical software for use on microcomputers requires a thorough definition of the goal, plus knowledge of the capabilities of the user, the hardware and the software. These factors form a complex, interacting system which is limited by its weakest component. This paper suggests criteria to be used in the selection of software and hardware for statistical applications. Additional sources of information and several examples of statistical software are cited. References to specific hardware and software types and product names are for illustrative purposes only and do not constitute endorsement or recommendation. Any emphasis placed on specific systems reflects the author's experience and/or perception of current market conditions. PMID:24243187

  12. Complex tissue-specific patterns and distribution of multiple RAGE splice variants in different mammals.

    PubMed

    López-Díez, Raquel; Rastrojo, Alberto; Villate, Olatz; Aguado, Begoña

    2013-01-01

    The receptor for advanced glycosylation end products (RAGE) is a multiligand receptor involved in diverse cell signaling pathways. Previous studies show that this gene expresses several splice variants in human, mouse, and dog. Alternative splicing (AS) plays an important role in expanding transcriptomic and proteomic diversity, and it has been related to disease. AS is also one of the main evolutionary mechanisms in mammalian genomes. However, limited information is available regarding the AS of RAGE in a wide context of mammalian tissues. In this study, we examined in detail the different RAGE mRNAs generated by AS from six mammals, including two primates (human and monkey), two artiodactyla (cow and pig), and two rodentia (mouse and rat) in 6-18 different tissues including fetal, adult, and tumor. By nested reverse transcription-polymerase chain reaction (RT-PCR) we identified a high number of splice variants including noncoding transcripts and predicted coding ones with different potential protein modifications affecting mainly the transmembrane and ligand-binding domains that could influence their biological function. However, analysis of RNA-seq data enabled detecting only the most abundant splice variants. More than 80% of the detected RT-PCR variants (87 of 101 transcripts) are novel (different exon/intron structure to the previously described ones), and interestingly, 20-60% of the total transcripts (depending on the species) are noncoding ones that present tissue specificity. Our results suggest that RAGE undergoes extensive AS in mammals, with different expression patterns among adult, fetal, and tumor tissues. Moreover, most splice variants seem to be species specific, especially the noncoding variants, with only two (canonical human Tv1-RAGE, and human N-truncated or Tv10-RAGE) conserved among the six different species. This could indicate a special evolution pattern of this gene at mRNA level. PMID:24273313

  13. Complex Tissue-Specific Patterns and Distribution of Multiple RAGE Splice Variants in Different Mammals

    PubMed Central

    López-Díez, Raquel; Rastrojo, Alberto; Villate, Olatz; Aguado, Begoña

    2013-01-01

    The receptor for advanced glycosylation end products (RAGE) is a multiligand receptor involved in diverse cell signaling pathways. Previous studies show that this gene expresses several splice variants in human, mouse, and dog. Alternative splicing (AS) plays an important role in expanding transcriptomic and proteomic diversity, and it has been related to disease. AS is also one of the main evolutionary mechanisms in mammalian genomes. However, limited information is available regarding the AS of RAGE in a wide context of mammalian tissues. In this study, we examined in detail the different RAGE mRNAs generated by AS from six mammals, including two primates (human and monkey), two artiodactyla (cow and pig), and two rodentia (mouse and rat) in 6–18 different tissues including fetal, adult, and tumor. By nested reverse transcription-polymerase chain reaction (RT-PCR) we identified a high number of splice variants including noncoding transcripts and predicted coding ones with different potential protein modifications affecting mainly the transmembrane and ligand-binding domains that could influence their biological function. However, analysis of RNA-seq data enabled detecting only the most abundant splice variants. More than 80% of the detected RT-PCR variants (87 of 101 transcripts) are novel (different exon/intron structure to the previously described ones), and interestingly, 20–60% of the total transcripts (depending on the species) are noncoding ones that present tissue specificity. Our results suggest that RAGE undergoes extensive AS in mammals, with different expression patterns among adult, fetal, and tumor tissues. Moreover, most splice variants seem to be species specific, especially the noncoding variants, with only two (canonical human Tv1-RAGE, and human N-truncated or Tv10-RAGE) conserved among the six different species. This could indicate a special evolution pattern of this gene at mRNA level. PMID:24273313

  14. Antigen nature and complexity influence human antibody light chain usage and specificity.

    PubMed

    Smith, Kenneth; Shah, Hemangi; Muther, Jennifer J; Duke, Angie L; Haley, Kathleen; James, Judith A

    2016-05-27

    Human antibodies consist of a heavy chain and one of two possible light chains, kappa (κ) or lambda (λ). Here we tested how these two possible light chains influence the overall antibody response to polysaccharide and protein antigens by measuring light chain usage in human monoclonal antibodies from antibody secreting cells obtained following vaccination with Pneumovax23. Remarkably, we found that individuals displayed restricted light chain usage to certain serotypes and that lambda antibodies have different specificities and modes of cross-reactivity than kappa antibodies. Thus, at both the monoclonal (7 kappa, no lambda) and serum levels (145μg/mL kappa, 2.82μg/mL lambda), antibodies to cell wall polysaccharide were nearly always kappa. The pneumococcal reference serum 007sp was analyzed for light chain usage to 12 pneumococcal serotypes for which it is well characterized. Similar to results at the monoclonal level, certain serotypes tended to favor one of the light chains (14 and 19A, lambda; 6A and 23F, kappa). We also explored differences in light chain usage at the serum level to a variety of antigens. We examined serum antibodies to diphtheria toxin mutant CRM197 and Epstein-Barr virus protein EBNA-1. These responses tended to be kappa dominant (average kappa-to-lambda ratios of 4.52 and 9.72 respectively). Responses to the influenza vaccine were more balanced with kappa-to-lambda ratio averages having slight strain variations: seasonal H1N1, 1.1; H3N2, 0.96; B, 0.91. We conclude that antigens with limited epitopes tend to produce antibodies with restricted light chain usage and that in most individuals, antibodies with lambda light chains have specificities different and complementary to kappa-containing antibodies. PMID:27113164

  15. Alternative Splicing of NURF301 Generates Distinct NURF Chromatin Remodeling Complexes with Altered Modified Histone Binding Specificities

    PubMed Central

    Kwon, So Yeon; Xiao, Hua; Wu, Carl; Badenhorst, Paul

    2009-01-01

    Drosophila NURF is an ISWI–containing chromatin remodeling complex that catalyzes ATP–dependent nucleosome sliding. By sliding nucleosomes, NURF can alter chromatin structure and regulate transcription. NURF301/BPTF is the only NURF–specific subunit of NURF and is instrumental in recruiting the complex to target genes. Here we demonstrate that three NURF301 isoforms are expressed and that these encode functionally distinct NURF chromatin remodeling complexes. Full-length NURF301 contains a C-terminal bromodomain and juxtaposed PHD finger that bind histone H3 trimethylated at Lys4 (H3K4me3) and histone H4 acetylated at Lys16 (H4K16Ac) respectively. However, a NURF301 isoform that lacks these C-terminal domains is also detected. This truncated NURF301 isoform assembles a complex containing ISWI, NURF55, and NURF38, indicating that a second class of NURF remodeling complex, deficient in H3K4me3 and H4K16Ac recognition, exists. By comparing microarray expression profiles and phenotypes of null Nurf301 mutants with mutants that remove the C-terminal PHD fingers and bromodomain, we show that full-length NURF301 is not essential for correct expression of the majority of NURF gene targets in larvae. However, full-length NURF301 is required for spermatogenesis. Mutants that lack full-length NURF exhibit a spermatocyte arrest phenotype and fail to express a subset of spermatid differentiation genes. Our data reveal that variants of the NURF ATP–dependent chromatin remodeling complex that recognize post-translational histone modifications are important regulators of primary spermatocyte differentiation in Drosophila. PMID:19629165

  16. Tool Use Within NASA Software Quality Assurance

    NASA Technical Reports Server (NTRS)

    Shigeta, Denise; Port, Dan; Nikora, Allen P.; Wilf, Joel

    2013-01-01

    As space mission software systems become larger and more complex, it is increasingly important for the software assurance effort to have the ability to effectively assess both the artifacts produced during software system development and the development process itself. Conceptually, assurance is a straightforward idea - it is the result of activities carried out by an organization independent of the software developers to better inform project management of potential technical and programmatic risks, and thus increase management's confidence in the decisions they ultimately make. In practice, effective assurance for large, complex systems often entails assessing large, complex software artifacts (e.g., requirements specifications, architectural descriptions) as well as substantial amounts of unstructured information (e.g., anomaly reports resulting from testing activities during development). In such an environment, assurance engineers can benefit greatly from appropriate tool support. In order to do so, an assurance organization will need accurate and timely information on the tool support available for various types of assurance activities. In this paper, we investigate the current use of tool support for assurance organizations within NASA, and describe on-going work at JPL for providing assurance organizations with the information about tools they need to use them effectively.

  17. Pan-Specific Prediction of Peptide-MHC Class I Complex Stability, a Correlate of T Cell Immunogenicity.

    PubMed

    Rasmussen, Michael; Fenoy, Emilio; Harndahl, Mikkel; Kristensen, Anne Bregnballe; Nielsen, Ida Kallehauge; Nielsen, Morten; Buus, Søren

    2016-08-15

    Binding of peptides to MHC class I (MHC-I) molecules is the most selective event in the processing and presentation of Ags to CTL, and insights into the mechanisms that govern peptide-MHC-I binding should facilitate our understanding of CTL biology. Peptide-MHC-I interactions have traditionally been quantified by the strength of the interaction, that is, the binding affinity, yet it has been shown that the stability of the peptide-MHC-I complex is a better correlate of immunogenicity compared with binding affinity. In this study, we have experimentally analyzed peptide-MHC-I complex stability of a large panel of human MHC-I allotypes and generated a body of data sufficient to develop a neural network-based pan-specific predictor of peptide-MHC-I complex stability. Integrating the neural network predictors of peptide-MHC-I complex stability with state-of-the-art predictors of peptide-MHC-I binding is shown to significantly improve the prediction of CTL epitopes. The method is publicly available at http://www.cbs.dtu.dk/services/NetMHCstabpan. PMID:27402703

  18. Limb-specific autonomic dysfunction in complex regional pain syndrome modulated by wearing prism glasses.

    PubMed

    Moseley, G Lorimer; Gallace, Alberto; Di Pietro, Flavia; Spence, Charles; Iannetti, Gian Domenico

    2013-11-01

    In unilateral upper-limb complex regional pain syndrome (CRPS), the temperature of the hands is modulated by where the arms are located relative to the body midline. We hypothesized that this effect depends on the perceived location of the hands, not on their actual location, nor on their anatomical alignment. In 2 separate cross-sectional randomized experiments, 10 (6 female) unilateral CRPS patients wore prism glasses that laterally shifted the visual field by 20°. Skin temperature was measured before and after 9-minute periods in which the position of one hand was changed. Placing the affected hand on the healthy side of the body midline increased its temperature (Δ°C=+0.47 ± 0.14°C), but not if prism glasses made the hand appear to be on the body midline (Δ°C=+0.07 ± 0.06°C). Similarly, when prism glasses made the affected hand appear to be on the healthy side of the body midline, even though it was not, the affected hand warmed up (Δ°C=+0.28 ± 0.14°C). When prism glasses made the healthy hand appear to be on the affected side of the body midline, even though it was not, the healthy hand cooled down (Δ°C=-0.30 ± 0.15°C). Friedman's analysis of variance and Wilcoxon pairs tests upheld the results (P<0.01 for all). We conclude that, in CRPS, cortical mechanisms responsible for encoding the perceived location of the limbs in space modulate the temperature of the hands. PMID:23886518

  19. Site-specific DNA binding of the Schizosaccharomyces pombe origin recognition complex is determined by the Orc4 subunit.

    PubMed

    Kong, D; DePamphilis, M L

    2001-12-01

    The mechanism by which origin recognition complexes (ORCs) identify replication origins was investigated using purified Orc proteins from Schizosaccharomyces pombe. Orc4p alone bound tightly and specifically to several sites within S. pombe replication origins that are genetically required for origin activity. These sites consisted of clusters of A or T residues on one strand but were devoid of either alternating A and T residues or GC-rich sequences. Addition of a complex consisting of Orc1, -2, -3, -5, and -6 proteins (ORC-5) altered neither Orc4p binding to origin DNA nor Orc4p protection of specific sequences. ORC-5 alone bound weakly and nonspecifically to DNA; strong binding required the presence of Orc4p. Under these conditions, all six subunits remained bound to chromatin isolated from each phase of the cell division cycle. These results reveal that the S. pombe ORC binds to multiple, specific sites within replication origins and that site selection, at least in vitro, is determined solely by the Orc4p subunit. PMID:11689699

  20. Generic domain models in software engineering

    NASA Technical Reports Server (NTRS)

    Maiden, Neil

    1992-01-01

    This paper outlines three research directions related to domain-specific software development: (1) reuse of generic models for domain-specific software development; (2) empirical evidence to determine these generic models, namely elicitation of mental knowledge schema possessed by expert software developers; and (3) exploitation of generic domain models to assist modelling of specific applications. It focuses on knowledge acquisition for domain-specific software development, with emphasis on tool support for the most important phases of software development.

  1. Software design and documentation language, revision 1

    NASA Technical Reports Server (NTRS)

    Kleine, H.

    1979-01-01

    The Software Design and Documentation Language (SDDL) developed to provide an effective communications medium to support the design and documentation of complex software applications is described. Features of the system include: (1) a processor which can convert design specifications into an intelligible, informative machine-reproducible document; (2) a design and documentation language with forms and syntax that are simple, unrestrictive, and communicative; and (3) methodology for effective use of the language and processor. The SDDL processor is written in the SIMSCRIPT II programming language and is implemented on the UNIVAC 1108, the IBM 360/370, and Control Data machines.

  2. Proprietary software

    NASA Technical Reports Server (NTRS)

    Marnock, M. J.

    1971-01-01

    The protection of intellectual property by a patent, a copyright, or trade secrets is reviewed. The present and future use of computers and software are discussed, along with the governmental uses of software. The popularity of contractual agreements for sale or lease of computer programs and software services is also summarized.

  3. Generation of monoclonal antibodies to the specific sugar epitopes of Mycobacterium avium complex serovars.

    PubMed Central

    Rivoire, B; Ranchoff, B J; Chatterjee, D; Gaylord, H; Tsang, A Y; Kolk, A H; Aspinall, G O; Brennan, P J

    1989-01-01

    Monoclonal antibodies have been generated to the unique distal sugar epitopes on the oligosaccharide haptens of the glycopeptidolipid antigens of clinically prominent members of the Mycobacterium avium serocomplex. Thus, antibodies are described that recognize the distal O-acetyl-alpha-L-rhamnopyranosyl residue of the specific glycopeptidolipid of M. avium serovar 1, the 4-O-acetyl-2,3-di-O-methyl-alpha-L-fucopyranose of serovar 2, the 4-O-methyl-alpha-L-rhamnopyranosyl-(1----4)-2-O-methyl-alpha-L- fucopyranosyl unit of serovar 4, the 4,6-(1'-carboxyethylidene)-3-O-methyl-beta-D-glucopyranosyl unit of serovar 8 [and the 4,6-(1'-carboxyethylidene)-beta-D-glucopyranosyl residue of serovar 21], and the 4-O-acetyl-2,3-di-O-methyl-alpha-L-fucopyranosyl-(1----4)-beta-D- glucuronopyranosyl unit of serovar 9. Epitope definition was arrived at through use of the pure, chemically defined glycopeptidolipid antigens and neoglycoproteins containing the chemically synthesized distal sugars of some select serovars. These monoclonal antibodies combined with the already published information on the structure of the antigen determinants and the tools used to arrive at these structures provide powerful means for fundamental studies on the role of these antigens in immunopathogenesis and for the precise mapping of the epidemiology of opportunistic infections caused by M. avium. Images PMID:2476400

  4. Collected software engineering papers, volume 2

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Topics addressed include: summaries of the software engineering laboratory (SEL) organization, operation, and research activities; results of specific research projects in the areas of resource models and software measures; and strategies for data collection for software engineering research.

  5. Autonomy Software: V&V Challenges and Characteristics

    NASA Technical Reports Server (NTRS)

    Schumann, Johann; Visser, Willem

    2006-01-01

    The successful operation of unmanned air vehicles requires software with a high degree of autonomy. Only if high level functions can be carried out without human control and intervention, complex missions in a changing and potentially unknown environment can be carried out successfully. Autonomy software is highly mission and safety critical: failures, caused by flaws in the software cannot only jeopardize the mission, but could also endanger human life (e.g., a crash of an UAV in a densely populated area). Due to its large size, high complexity, and use of specialized algorithms (planner, constraint-solver, etc.), autonomy software poses specific challenges for its verification, validation, and certification. -- - we have carried out a survey among researchers aid scientists at NASA to study these issues. In this paper, we will present major results of this study, discussing the broad spectrum. of notions and characteristics of autonomy software and its challenges for design and development. A main focus of this survey was to evaluate verification and validation (V&V) issues and challenges, compared to the development of "traditional" safety-critical software. We will discuss important issues in V&V of autonomous software and advanced V&V tools which can help to mitigate software risks. Results of this survey will help to identify and understand safety concerns in autonomy software and will lead to improved strategies for mitigation of these risks.

  6. Structure of 5-hydroxymethylcytosine-specific restriction enzyme, AbaSI, in complex with DNA

    SciTech Connect

    Horton, John R.; Borgaro, Janine G.; Griggs, Rose M.; Quimby, Aine; Guan, Shengxi; Zhang, Xing; Wilson, Geoffrey G.; Zheng, Yu; Zhu, Zhenyu; Cheng, Xiaodong

    2014-07-03

    AbaSI, a member of the PvuRts1I-family of modification-dependent restriction endonucleases, cleaves DNA containing 5-hydroxymethylctosine (5hmC) and glucosylated 5hmC (g5hmC), but not DNA containing unmodified cytosine. AbaSI has been used as a tool for mapping the genomic locations of 5hmC, an important epigenetic modification in the DNA of higher organisms. Here we report the crystal structures of AbaSI in the presence and absence of DNA. These structures provide considerable, although incomplete, insight into how this enzyme acts. AbaSI appears to be mainly a homodimer in solution, but interacts with DNA in our structures as a homotetramer. Each AbaSI subunit comprises an N-terminal, Vsr-like, cleavage domain containing a single catalytic site, and a C-terminal, SRA-like, 5hmC-binding domain. Two N-terminal helices mediate most of the homodimer interface. Dimerization brings together the two catalytic sites required for double-strand cleavage, and separates the 5hmC binding-domains by ~ 70 Å, consistent with the known activity of AbaSI which cleaves DNA optimally between symmetrically modified cytosines ~ 22 bp apart. The eukaryotic SET and RING-associated (SRA) domains bind to DNA containing 5-methylcytosine (5mC) in the hemi-methylated CpG sequence. They make contacts in both the major and minor DNA grooves, and flip the modified cytosine out of the helix into a conserved binding pocket. In contrast, the SRA-like domain of AbaSI, which has no sequence specificity, contacts only the minor DNA groove, and in our current structures the 5hmC remains intra-helical. A conserved, binding pocket is nevertheless present in this domain, suitable for accommodating 5hmC and g5hmC. We consider it likely, therefore, that base-flipping is part of the recognition and cleavage mechanism of AbaSI, but that our structures represent an earlier, pre-flipped stage, prior to actual recognition.

  7. In Vitro MRV-based Hemodynamic Study of Complex Helical Flow in a Patient-specific Jugular Model

    NASA Astrophysics Data System (ADS)

    Kefayati, Sarah; Acevedo-Bolton, Gabriel; Haraldsson, Henrik; Saloner, David

    2014-11-01

    Neurointerventional Radiologists are frequently requested to evaluate the venous side of the intracranial circulation for a variety of conditions including: Chronic Cerebrospinal Venous Insufficiency thought to play a role in the development of multiple sclerosis; sigmoid sinus diverticulum which has been linked to the presence of pulsatile tinnitus; and jugular vein distension which is related to cardiac dysfunction. Most approaches to evaluating these conditions rely on structural assessment or two dimensional flow analyses. This study was designed to investigate the highly complex jugular flow conditions using magnetic resonance velocimetry (MRV). A jugular phantom was fabricated based on the geometry of the dominant jugular in a tinnitus patient. Volumetric three-component time-resolved velocity fields were obtained using 4D PC-MRI -with the protocol enabling turbulence acquisition- and the patient-specific pulsatile waveform. Flow was highly complex exhibiting regions of jet, high swirling strength, and strong helical pattern with the core originating from the focal point of the jugular bulb. Specifically, flow was analyzed for helicity and the level of turbulence kinetic energy elevated in the core of helix and distally, in the post-narrowing region.

  8. NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1.

    PubMed

    Omichinski, J G; Clore, G M; Schaad, O; Felsenfeld, G; Trainor, C; Appella, E; Stahl, S J; Gronenborn, A M

    1993-07-23

    The three-dimensional solution structure of a complex between the DNA binding domain of the chicken erythroid transcription factor GATA-1 and its cognate DNA site has been determined with multidimensional heteronuclear magnetic resonance spectroscopy. The DNA binding domain consists of a core which contains a zinc coordinated by four cysteines and a carboxyl-terminal tail. The core is composed of two irregular antiparallel beta sheets and an alpha helix, followed by a long loop that leads into the carboxyl-terminal tail. The amino-terminal part of the core, including the helix, is similar in structure, although not in sequence, to the amino-terminal zinc module of the glucocorticoid receptor DNA binding domain. In the other regions, the structures of these two DNA binding domains are entirely different. The DNA target site in contact with the protein spans eight base pairs. The helix and the loop connecting the two antiparallel beta sheets interact with the major groove of the DNA. The carboxyl-terminal tail, which is an essential determinant of specific binding, wraps around into the minor groove. The complex resembles a hand holding a rope with the palm and fingers representing the protein core and the thumb, the carboxyl-terminal tail. The specific interactions between GATA-1 and DNA in the major groove are mainly hydrophobic in nature, which accounts for the preponderance of thymines in the target site. A large number of interactions are observed with the phosphate backbone. PMID:8332909

  9. A facile and versatile methodology for cysteine specific labeling of proteins with octahedral polypyridyl d6 metal complexes

    PubMed Central

    Dwaraknath, Sudharsan; Tran, Ngoc-Han; Dao, Thanh; Colbert, Alexander; Mullen, Sarah; Nguyen, Angelina; Cortez, Alejandro; Cheruzel, Lionel

    2014-01-01

    We have synthesized and characterized four octahedral polypyridyl d6 metal complexes bearing the 5,6-epoxy-5,6-dihydro-[1,10]phenanthroline ligand (L1) as cysteine specific labeling reagents. The proposed synthetic pathways allow the preparation of the metal complexes containing Re(I), Ru(II), Os(II) and Ir(III) while preserving the epoxide functionality. The complexes were characterized by 1H and 13C NMR, mass spectrometry, UV-visible and luminescence spectroscopies as well as cyclic voltammetry. As proof of concept, a set of non-native single cysteine P450 BM3 heme domain mutants previously developed in our laboratory was used to study the labeling reaction. We demonstrate that the proposed labels can selectively react, often in high yield, with cysteine residues of the protein via the nucleophilic thiol ring opening of the epoxide moiety. In addition, under basic conditions, subsequent loss of a water molecule led to the aromatization of the phenanthroline ring on the protein-bound label compounds, as observed by mass spectrometry and luminescence measurements. PMID:24468675

  10. Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability

    SciTech Connect

    Burrows, Scott R.; Chen, Zhenjun; Archbold, Julia K.; Tynan, Fleur E.; Beddoe, Travis; Kjer-Nielsen, Lars; Miles, John J.; Khanna, Rajiv; Moss, Denis J.; Liu, Yu Chih; Gras, Stephanie; Kostenko, Lyudmila; Brennan, Rebekah M.; Clements, Craig S.; Brooks, Andrew G.; Purcell, Anthony W.; McCluskey, James; Rossjohn, Jamie

    2010-07-07

    {alpha}{beta} T cell receptors (TCRs) are genetically restricted to corecognize peptide antigens bound to self-major histocompatibility complex (pMHC) molecules; however, the basis for this MHC specificity remains unclear. Despite the current dogma, evaluation of the TCR-pMHC-I structural database shows that the nongermline-encoded complementarity-determining region (CDR)-3 loops often contact the MHC-I, and the germline-encoded CDR1 and -2 loops frequently participate in peptide-mediated interactions. Nevertheless, different TCRs adopt a roughly conserved docking mode over the pMHC-I, in which three MHC-I residues (65, 69, and 155) are invariably contacted by the TCR in one way or another. Nonetheless, the impact of mutations at these three positions, either individually or together, was not uniformly detrimental to TCR recognition of pHLA-B*0801 or pHLA-B*3508. Moreover, when TCR-pMHC-I recognition was impaired, this could be partially restored by expression of the CD8 coreceptor. The structure of a TCR-pMHC-I complex in which these three (65, 69, and 155) MHC-I positions were all mutated resulted in shifting of the TCR footprint relative to the cognate complex and formation of compensatory interactions. Collectively, our findings reveal the inherent adaptability of the TCR in maintaining peptide recognition while accommodating changes to the central docking site on the pMHC-I.

  11. NASA Software Documentation Standard

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The NASA Software Documentation Standard (hereinafter referred to as "Standard") is designed to support the documentation of all software developed for NASA; its goal is to provide a framework and model for recording the essential information needed throughout the development life cycle and maintenance of a software system. The NASA Software Documentation Standard can be applied to the documentation of all NASA software. The Standard is limited to documentation format and content requirements. It does not mandate specific management, engineering, or assurance standards or techniques. This Standard defines the format and content of documentation for software acquisition, development, and sustaining engineering. Format requirements address where information shall be recorded and content requirements address what information shall be recorded. This Standard provides a framework to allow consistency of documentation across NASA and visibility into the completeness of project documentation. The basic framework consists of four major sections (or volumes). The Management Plan contains all planning and business aspects of a software project, including engineering and assurance planning. The Product Specification contains all technical engineering information, including software requirements and design. The Assurance and Test Procedures contains all technical assurance information, including Test, Quality Assurance (QA), and Verification and Validation (V&V). The Management, Engineering, and Assurance Reports is the library and/or listing of all project reports.

  12. Analysis of the tertiary structure of the ribonuclease P ribozyme-substrate complex by site-specific photoaffinity crosslinking.

    PubMed

    Harris, M E; Kazantsev, A V; Chen, J L; Pace, N R

    1997-06-01

    Bacterial ribonuclease P (RNase P), an endonuclease involved in tRNA maturation, is a ribonucleoprotein containing a catalytic RNA. The secondary structure of this ribozyme is well-established, and a low-resolution model of the three-dimensional structure of the ribozyme-substrate complex has been proposed based on site-specific crosslinking and phylogenetic comparative data [Harris ME et al., 1994 EMBO J 13:3953-3963]. However, several substructures of that model were poorly constrained by the available data. In the present analysis, additional constraints between elements within the Escherichia coli RNase P RNA-pre-tRNA complex were determined by intra- and intermolecular crosslinking experiments. Circularly permuted RNase P RNAs were used to position an azidophenacyl photoactive crosslinking agent specifically at strategic sites within the ribozyme-substrate complex. Crosslink sites were mapped by primer extension and confirmed by analysis of the mobility of the crosslinked RNA lariats on denaturing acrylamide gels relative to circular and linear RNA standards. Crosslinked species generally retained significant catalytic activity, indicating that the results reflect the native ribozyme structure. The crosslinking results support the general configuration of the structure model and predicate new positions and orientations for helices that were previously poorly constrained by the data set. The expanded library of crosslinking constraints was used, together with secondary and tertiary structure identified by phylogenetic sequence comparisons, to refine significantly the model of RNase P RNA with bound substrate pre-tRNA. The crosslinking results and data from chemical-modification and mutational studies are discussed in the context of the current structural perspective on this ribozyme. PMID:9174092

  13. CNEOST Control Software System

    NASA Astrophysics Data System (ADS)

    Wang, X.; Zhao, H. B.; Xia, Y.; Lu, H.; Li, B.

    2015-03-01

    In 2013, CNEOST (China Near Earth Object Survey Telescope) adapted its hardware system for the new CCD camera. Based on the new system architecture, the control software is re-designed and implemented. The software system adopts the message passing mechanism via WebSocket protocol, and improves its flexibility, expansibility, and scalability. The user interface with responsive web design realizes the remote operating under both desktop and mobile devices. The stable operating of software system has greatly enhanced the operation efficiency while reducing the complexity, and has also made a successful attempt for the future system design of telescope and telescope cloud.

  14. CNEOST Control Software System

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Zhao, Hai-bin; Xia, Yan; Lu, Hao; Li, Bin

    2016-01-01

    In 2013, CNEOST (China Near Earth Object Survey Telescope) adapted its hardware system for the new CCD camera. Based on the new system architecture, the control software is re-designed and implemented. The software system adopts the messaging mechanism based on the WebSocket protocol, and possesses good flexibility and expansibility. The user interface based on the responsive web design has realized the remote observations under both desktop and mobile devices. The stable operation of the software system has greatly enhanced the operation efficiency while reducing the complexity, and has also made a successful attempt for the future system design of telescope and telescope cloud.

  15. Designing Educational Software for Tomorrow.

    ERIC Educational Resources Information Center

    Harvey, Wayne

    Designed to address the management and use of computer software in education and training, this paper explores both good and poor software design, calling for improvements in the quality of educational software by attending to design considerations that are based on general principles of learning rather than specific educational objectives. This…

  16. A Feasibility Study of a Field-specific Weather Service for Small-scale Farms in a Topographically Complex Watershed

    NASA Astrophysics Data System (ADS)

    Kim, S. O.; Shim, K. M.; Shin, Y. S.; Yun, J. I.

    2015-12-01

    Adequate downscaling of synoptic forecasts is a prerequisite for improved agrometeorological service to rural areas in South Korea where complex terrain and small farms are common. Geospatial schemes based on topoclimatology were used to scale down the Korea Meteorological Administration (KMA) temperature forecasts to the local scale (~30 m) across a rural catchment. Local temperatures were estimated at 14 validation sites at 0600 and 1500 LST in 2013/2014 using these schemes and were compared with observations. A substantial reduction in the estimation error was found for both 0600 and 1500 temperatures compared with uncorrected KMA products. Improvement was most remarkable at low lying locations for the 0600 temperature and at the locations on west- and south-facing slopes for the 1500 temperature. Using the downscaled real-time temperature data, a pilot service has started to provide field-specific weather information tailored to meet the requirements of small-scale farms. For example, the service system makes a daily outlook on the phenology of crop species grown in a given field using the field-specific temperature data. When the temperature forecast is given for tomorrow morning, a frost risk index is calculated according to a known phenology-frost injury relationship. If the calculated index is higher than a pre-defined threshold, a warning is issued and delivered to the grower's cellular phone with relevant countermeasures to help protect crops against frost damage. The system was implemented for a topographically complex catchment of 350km2with diverse agricultural activities, and more than 400 volunteer farmers are participating in this pilot service to access user-specific weather information.

  17. Characterization of a novel origin recognition complex-like complex: implications for DNA recognition, cell cycle control, and locus-specific gene amplification.

    PubMed

    Mohammad, Mohammad; York, Randall D; Hommel, Jonathan; Kapler, Geoffrey M

    2003-07-01

    The origin recognition complex (ORC) plays a central role in eukaryotic DNA replication. Here we describe a unique ORC-like complex in Tetrahymena thermophila, TIF4, which bound in an ATP-dependent manner to sequences required for cell cycle-controlled replication and gene amplification (ribosomal DNA [rDNA] type I elements). TIF4's mode of DNA recognition was distinct from that of other characterized ORCs, as it bound exclusively to single-stranded DNA. In contrast to yeast ORCs, TIF4 DNA binding activity was cell cycle regulated and peaked during S phase, coincident with the redistribution of the Orc2-related subunit, p69, from the cytoplasm to the macronucleus. Origin-binding activity and nuclear p69 immunoreactivity were further regulated during development, where they distinguished replicating from nonreplicating nuclei. Both activities were lost from germ line micronuclei following the programmed arrest of micronuclear replication. Replicating macronuclei stained with Orc2 antibodies throughout development in wild-type cells but failed to do so in the amplification-defective rmm11 mutant. Collectively, these findings indicate that the regulation of TIF4 is intimately tied to the cell cycle and developmentally programmed replication cycles. They further implicate TIF4 in rDNA gene amplification. As type I elements interact with other sequence-specific single-strand breaks (in vitro and in vivo), the dynamic interplay of Orc-like (TIF4) and non-ORC-like proteins with this replication determinant may provide a novel mechanism for regulation. PMID:12832485

  18. Cleanroom software development

    NASA Technical Reports Server (NTRS)

    Dyer, M.; Mills, H. D.

    1981-01-01

    The 'cleanroom' software development process is a technical and organizational approach to developing software with certifiable reliability. Key ideas behind the process are well structured software specifications, randomized testing methods and the introduction of statistical controls; but the main point is to deny entry for defects during the development of software. This latter point suggests the use of the term 'cleanroom' in analogy to the defect prevention controls used in the manufacturing of high technology hardware. In the 'cleanroom', the entire software development process is embedded within a formal statistical design, in contrast to executing selected tests and appealing to the randomness of operational settings for drawing statistical inferences. Instead, random testing is introduced as a part of the statistical design itself so that when development and testing are completed, statistical inferences are made about the operation of the system.

  19. Tissue-specific splicing of an Ndufs6 gene-trap insertion generates a mitochondrial complex I deficiency-specific cardiomyopathy

    PubMed Central

    Ke, Bi-Xia; Pepe, Salvatore; Grubb, David R.; Komen, Jasper C.; Laskowski, Adrienne; Rodda, Felicity A.; Hardman, Belinda M.; Pitt, James J.; Ryan, Michael T.; Lazarou, Michael; Koleff, Jane; Cheung, Michael M. H.; Smolich, Joseph J.; Thorburn, David R.

    2012-01-01

    Mitochondrial complex I (CI) deficiency is the most common mitochondrial enzyme defect in humans. Treatment of mitochondrial disorders is currently inadequate, emphasizing the need for experimental models. In humans, mutations in the NDUFS6 gene, encoding a CI subunit, cause severe CI deficiency and neonatal death. In this study, we generated a CI-deficient mouse model by knockdown of the Ndufs6 gene using a gene-trap embryonic stem cell line. Ndufs6gt/gt mice have essentially complete knockout of the Ndufs6 subunit in heart, resulting in marked CI deficiency. Small amounts of wild-type Ndufs6 mRNA are present in other tissues, apparently due to tissue-specific mRNA splicing, resulting in milder CI defects. Ndufs6gt/gt mice are born healthy, attain normal weight and maturity, and are fertile. However, after 4 mo in males and 8 mo in females, Ndufs6gt/gt mice are at increased risk of cardiac failure and death. Before overt heart failure, Ndufs6gt/gt hearts show decreased ATP synthesis, accumulation of hydroxyacylcarnitine, but not reactive oxygen species (ROS). Ndufs6gt/gt mice develop biventricular enlargement by 1 mo, most pronounced in males, with scattered fibrosis and abnormal mitochondrial but normal myofibrillar ultrastructure. Ndufs6gt/gt isolated working heart preparations show markedly reduced left ventricular systolic function, cardiac output, and functional work capacity. This reduced energetic and functional capacity is consistent with a known susceptibility of individuals with mitochondrial cardiomyopathy to metabolic crises precipitated by stresses. This model of CI deficiency will facilitate studies of pathogenesis, modifier genes, and testing of therapeutic approaches. PMID:22474353

  20. Tissue-specific splicing of an Ndufs6 gene-trap insertion generates a mitochondrial complex I deficiency-specific cardiomyopathy.

    PubMed

    Ke, Bi-Xia; Pepe, Salvatore; Grubb, David R; Komen, Jasper C; Laskowski, Adrienne; Rodda, Felicity A; Hardman, Belinda M; Pitt, James J; Ryan, Michael T; Lazarou, Michael; Koleff, Jane; Cheung, Michael M H; Smolich, Joseph J; Thorburn, David R

    2012-04-17

    Mitochondrial complex I (CI) deficiency is the most common mitochondrial enzyme defect in humans. Treatment of mitochondrial disorders is currently inadequate, emphasizing the need for experimental models. In humans, mutations in the NDUFS6 gene, encoding a CI subunit, cause severe CI deficiency and neonatal death. In this study, we generated a CI-deficient mouse model by knockdown of the Ndufs6 gene using a gene-trap embryonic stem cell line. Ndufs6(gt/gt) mice have essentially complete knockout of the Ndufs6 subunit in heart, resulting in marked CI deficiency. Small amounts of wild-type Ndufs6 mRNA are present in other tissues, apparently due to tissue-specific mRNA splicing, resulting in milder CI defects. Ndufs6(gt/gt) mice are born healthy, attain normal weight and maturity, and are fertile. However, after 4 mo in males and 8 mo in females, Ndufs6(gt/gt) mice are at increased risk of cardiac failure and death. Before overt heart failure, Ndufs6(gt/gt) hearts show decreased ATP synthesis, accumulation of hydroxyacylcarnitine, but not reactive oxygen species (ROS). Ndufs6(gt/gt) mice develop biventricular enlargement by 1 mo, most pronounced in males, with scattered fibrosis and abnormal mitochondrial but normal myofibrillar ultrastructure. Ndufs6(gt/gt) isolated working heart preparations show markedly reduced left ventricular systolic function, cardiac output, and functional work capacity. This reduced energetic and functional capacity is consistent with a known susceptibility of individuals with mitochondrial cardiomyopathy to metabolic crises precipitated by stresses. This model of CI deficiency will facilitate studies of pathogenesis, modifier genes, and testing of therapeutic approaches. PMID:22474353

  1. NASA software documentation standard software engineering program

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The NASA Software Documentation Standard (hereinafter referred to as Standard) can be applied to the documentation of all NASA software. This Standard is limited to documentation format and content requirements. It does not mandate specific management, engineering, or assurance standards or techniques. This Standard defines the format and content of documentation for software acquisition, development, and sustaining engineering. Format requirements address where information shall be recorded and content requirements address what information shall be recorded. This Standard provides a framework to allow consistency of documentation across NASA and visibility into the completeness of project documentation. This basic framework consists of four major sections (or volumes). The Management Plan contains all planning and business aspects of a software project, including engineering and assurance planning. The Product Specification contains all technical engineering information, including software requirements and design. The Assurance and Test Procedures contains all technical assurance information, including Test, Quality Assurance (QA), and Verification and Validation (V&V). The Management, Engineering, and Assurance Reports is the library and/or listing of all project reports.

  2. Software Fault Tolerance: A Tutorial

    NASA Technical Reports Server (NTRS)

    Torres-Pomales, Wilfredo

    2000-01-01

    Because of our present inability to produce error-free software, software fault tolerance is and will continue to be an important consideration in software systems. The root cause of software design errors is the complexity of the systems. Compounding the problems in building correct software is the difficulty in assessing the correctness of software for highly complex systems. After a brief overview of the software development processes, we note how hard-to-detect design faults are likely to be introduced during development and how software faults tend to be state-dependent and activated by particular input sequences. Although component reliability is an important quality measure for system level analysis, software reliability is hard to characterize and the use of post-verification reliability estimates remains a controversial issue. For some applications software safety is more important than reliability, and fault tolerance techniques used in those applications are aimed at preventing catastrophes. Single version software fault tolerance techniques discussed include system structuring and closure, atomic actions, inline fault detection, exception handling, and others. Multiversion techniques are based on the assumption that software built differently should fail differently and thus, if one of the redundant versions fails, it is expected that at least one of the other versions will provide an acceptable output. Recovery blocks, N-version programming, and other multiversion techniques are reviewed.

  3. Crystal Structures of Complexes of Bacterial DD-Peptidases with Peptidoglycan-mimetic Ligands: The Substrate Specificity Puzzle

    PubMed Central

    Sauvage, Eric; Powell, Ailsa J.; Heilemann, Jason; Josephine, Helen R.; Charlier, Paulette; Davies, Christopher; Pratt, R.F.

    2008-01-01

    Summary The X-ray crystal structures of covalent complexes of the Actinomadura R39 DD-peptidase and Escherichia coli penicillin-binding protein 5 with β-lactams bearing peptidoglycan-mimetic side chains have been determined. The structure of the hydrolysis product of an analogous peptide bound non-covalently to the former enzyme has also been obtained. The R39 DD-peptidase structures reveal the presence of a specific binding site for the D-α-aminopimelyl side chain, characteristic of the stem peptide of Actinomadura R39. This binding site features a hydrophobic cleft for the pimelyl methylene groups and strong hydrogen bonding to the polar terminus. Both of these elements of the site are provided by amino acid side chains from two separate domains of the protein. In contrast, no clear electron density corresponding to the terminus of the peptidoglycan-mimetic side chains is present when these β-lactams are covalently bound to penicillin-binding protein 5. There is, therefore, no indication of a specific side chain binding site in this enzyme. These results are in agreement with those from kinetics studies published earlier and support the general prediction made at the time of a direct correlation between the kinetics and structural evidence. The essential high molecular weight penicillin binding proteins have demonstrated, to date, no specific reactivity with peptidoglycan-mimetic peptide substrates and β-lactam inhibitors and thus probably do not possess a specific substrate binding site of the type demonstrated here with the R39 DD-peptidase. This striking deficiency may represent a sophisticated defense mechanism against low molecular weight substrate-analogue inhibitors/antibiotics; its discovery should focus new inhibitor design. PMID:18602645

  4. A novel T cell receptor single-chain signaling complex mediates antigen-specific T cell activity and tumor control

    PubMed Central

    Stone, Jennifer D.; Harris, Daniel T.; Soto, Carolina M.; Chervin, Adam S.; Aggen, David H.; Roy, Edward J.; Kranz, David M.

    2014-01-01

    Adoptive transfer of genetically modified T cells to treat cancer has shown promise in several clinical trials. Two main strategies have been applied to redirect T cells against cancer: 1) introduction of a full-length T cell receptor (TCR) specific for a tumor-associated peptide-MHC, or 2) introduction of a chimeric antigen receptor (CAR), including an antibody fragment specific for a tumor cell surface antigen, linked intracellularly to T cell signaling domains. Each strategy has advantages and disadvantages for clinical applications. Here, we present data on the in vitro and in vivo effectiveness of a single-chain signaling receptor incorporating a TCR variable fragment as the targeting element (referred to as TCR-SCS). This receptor contained a single-chain TCR (Vβ-linker-Vα) from a high-affinity TCR called m33, linked to the intracellular signaling domains of CD28 and CD3ζ. This format avoided mispairing with endogenous TCR chains, and mediated specific T cell activity when expressed in either CD4 or CD8 T cells. TCR-SCS-transduced CD8-negative cells showed an intriguing sensitivity, compared to full-length TCRs, to higher densities of less stable pepMHC targets. T cells that expressed this peptide-specific receptor persisted in vivo, and exhibited polyfunctional responses. Growth of metastatic antigen-positive tumors was significantly inhibited by T cells that expressed this receptor, and tumor cells that escaped were antigen loss variants. TCR-SCS receptors represent an alternative targeting receptor strategy that combines the advantages of single-chain expression, avoidance of TCR chain mispairing, and targeting of intracellular antigens presented in complex with MHC proteins. PMID:25082071

  5. Defining Binding Efficiency and Specificity of Auxins for SCFTIR1/AFB-Aux/IAA Co-receptor Complex Formation

    PubMed Central

    2013-01-01

    Structure–activity profiles for the phytohormone auxin have been collected for over 70 years, and a number of synthetic auxins are used in agriculture. Auxin classification schemes and binding models followed from understanding auxin structures. However, all of the data came from whole plant bioassays, meaning the output was the integral of many different processes. The discovery of Transport Inhibitor-Response 1 (TIR1) and the Auxin F-Box (AFB) proteins as sites of auxin perception and the role of auxin as molecular glue in the assembly of co-receptor complexes has allowed the development of a definitive quantitative structure–activity relationship for TIR1 and AFB5. Factorial analysis of binding activities offered two uncorrelated factors associated with binding efficiency and binding selectivity. The six maximum-likelihood estimators of Efficiency are changes in the overlap matrixes, inferring that Efficiency is related to the volume of the electronic system. Using the subset of compounds that bound strongly, chemometric analyses based on quantum chemical calculations and similarity and self-similarity indices yielded three classes of Specificity that relate to differential binding. Specificity may not be defined by any one specific atom or position and is influenced by coulomb matrixes, suggesting that it is driven by electrostatic forces. These analyses give the first receptor-specific classification of auxins and indicate that AFB5 is the preferred site for a number of auxinic herbicides by allowing interactions with analogues having van der Waals surfaces larger than that of indole-3-acetic acid. The quality factors are also examined in terms of long-standing models for the mechanism of auxin binding. PMID:24313839

  6. Species-Specific Detection and Identification of Fusarium Species Complex, the Causal Agent of Sugarcane Pokkah Boeng in China

    PubMed Central

    Que, Youxiong; Wang, Jihua; Comstock, Jack C.; Wei, Jinjin; McCord, Per H.; Chen, Baoshan; Chen, Rukai; Zhang, Muqing

    2014-01-01

    Background Pokkah boeng disease caused by the Fusarium species complex results in significant yield losses in sugarcane. Thus, the rapid and accurate detection and identification of the pathogen is urgently required to manage and prevent the spreading of sugarcane pokkah boeng. Methods A total of 101 isolates were recovered from the pokkah boeng samples collected from five major sugarcane production areas in China throughout 2012 and 2013. The causal pathogen was identified by morphological observation, pathogenicity test, and phylogenetic analysis based on the fungus-conserved rDNA-ITS. Species-specific TaqMan real-time PCR and conventional PCR methods were developed for rapid and accurate detection of the causal agent of sugarcane pokkah boeng. The specificity and sensitivity of PCR assay were also evaluated on a total of 84 isolates of Fusarium from China and several isolates from other fungal pathogens of Sporisorium scitamineum and Phoma sp. and sugarcane endophyte of Acremonium sp. Result Two Fusarium species (F. verticillioides and F. proliferatum) that caused sugarcane pokahh boeng were identified by morphological observation, pathogenicity test, and phylogenetic analysis. Species-specific TaqMan PCR and conventional PCR were designed and optimized to target their rDNA-ITS regions. The sensitivity of the TaqMan PCR was approximately 10 pg of fungal DNA input, which was 1,000-fold over conventional PCR, and successfully detected pokkah boeng in the field-grown sugarcane. Conclusions/Significance This study was the first to identify two species, F. verticillioides and F. proliferatum, that were causal pathogens of sugarcane pokkah boeng in China. It also described the development of a species-specific PCR assay to detect and confirm these pathogens in sugarcane plants from mainland China. This method will be very useful for a broad range of research endeavors as well as the regulatory response and management of sugarcane pokkah boeng. PMID:25141192

  7. The Software Architecture of the Upgraded ESA DRAMA Software Suite

    NASA Astrophysics Data System (ADS)

    Kebschull, Christopher; Flegel, Sven; Gelhaus, Johannes; Mockel, Marek; Braun, Vitali; Radtke, Jonas; Wiedemann, Carsten; Vorsmann, Peter; Sanchez-Ortiz, Noelia; Krag, Holger

    2013-08-01

    In the beginnings of man's space flight activities there was the belief that space is so big that everybody could use it without any repercussions. However during the last six decades the increasing use of Earth's orbits has lead to a rapid growth in the space debris environment, which has a big influence on current and future space missions. For this reason ESA issued the "Requirements on Space Debris Mitigation for ESA Projects" [1] in 2008, which apply to all ESA missions henceforth. The DRAMA (Debris Risk Assessment and Mitigation Analysis) software suite had been developed to support the planning of space missions to comply with these requirements. During the last year the DRAMA software suite has been upgraded under ESA contract by TUBS and DEIMOS to include additional tools and increase the performance of existing ones. This paper describes the overall software architecture of the ESA DRAMA software suite. Specifically the new graphical user interface, which manages the five main tools ARES (Assessment of Risk Event Statistics), MIDAS (MASTER-based Impact Flux and Damage Assessment Software), OSCAR (Orbital Spacecraft Active Removal), CROC (Cross Section of Complex Bodies) and SARA (Re-entry Survival and Risk Analysis) is being discussed. The advancements are highlighted as well as the challenges that arise from the integration of the five tool interfaces. A framework had been developed at the ILR and was used for MASTER-2009 and PROOF-2009. The Java based GUI framework, enables the cross-platform deployment, and its underlying model-view-presenter (MVP) software pattern, meet strict design requirements necessary to ensure a robust and reliable method of operation in an environment where the GUI is separated from the processing back-end. While the GUI framework evolved with each project, allowing an increasing degree of integration of services like validators for input fields, it has also increased in complexity. The paper will conclude with an outlook on

  8. Specificity of anti-lymphocyte antibodies in sera from patients with AIDS-related complex (ARC) and healthy homosexuals.

    PubMed Central

    Warren, R Q; Johnson, E A; Donnelly, R P; Lavia, M F; Tsang, K Y

    1988-01-01

    The presence and specificity of anti-lymphocyte antibodies (ALA) was investigated in sera from male homosexuals with AIDS-Related Complex (ARC) as well as healthy homosexuals. Individuals in the healthy homosexual group had no detectable antibodies to human immunodeficiency virus (HIV). Antibodies reactive with normal peripheral blood mononuclear cells were detected by Western blot analysis in sera from both groups of homosexuals. Of those individuals whose sera contained ALA, 71% of ARC patients and 83% of healthy homosexuals had antibodies recognizing a 73 kilodalton (kD) molecule. ALA present in ARC sera reacted with CD3+, CD4+ and CD8+ lymphocytes while little reactivity with B cells was observed. Our results indicate that ALA appear in homosexuals prior to HIV infection and are reactive primarily with T lymphocytes. A 73 kD structure associated with the T cell membrane is frequently the target for these antibodies. Images Fig. 1 Fig. 2 Fig. 3 PMID:3052941

  9. Sensitive and specific detection of pine nut (Pinus spp.) by real-time PCR in complex food products.

    PubMed

    Garino, Cristiano; De Paolis, Angelo; Coïsson, Jean Daniel; Bianchi, Daniela Manila; Decastelli, Lucia; Arlorio, Marco

    2016-03-01

    Pine nuts are a known source of food allergens and several cases of adverse immunological reaction after ingestion have been reported. To protect allergic consumers, methods to unequivocally detect the presence of pine nuts in complex matrices must be developed. A Taqman-based real time PCR method for the detection of Pinus spp. was set up. A homemade pesto spiked at known concentration of pine nut powder was used as model food. Moreover, DNA was purified from commercial foods declaring or not the presence of pine nuts. The method displayed a very high efficiency and specificity for the genus Pinus. The intrinsic LOD was 1pg of DNA, while the practical LOD evaluated on model foods was 0.1ppm of pine nuts powder, the lowest ever registered for the detection of food allergens via real-time PCR. Finally, the declared presence/absence of pine nut in commercial foods was confirmed. PMID:26471643

  10. Ideas for a Cooperative Software Development for Future GGOS Stations

    NASA Astrophysics Data System (ADS)

    Neidhardt, A.; Ettl, M.

    2012-12-01

    The development of software is a creative process, which offers a huge degree of freedom. In scientific fields a lot of researchers develop their own software for specific needs. Everyone has their own preferences and backgrounds regarding the used programming languages, styles, and platforms. This complexity results in software which is not always directly usable by others in the communities. In addition, the software is often error-prone as hidden bugs are not always revealed. Therefore ideas came up to solve these problems at the Geodetic Observatory Wettzell. The results were coding layouts and policies, documentation strategies, the usage of version control, and a consistent process of continuous integration. Within this, the discussed quality factors can define quality metrics which help to quantize code quality. The resulting software is a repository of tested modules that can be used in different programs for the geodetic space techniques. This is one possible contribution to future GGOS stations.

  11. Writing testable software requirements

    SciTech Connect

    Knirk, D.

    1997-11-01

    This tutorial identifies common problems in analyzing requirements in the problem and constructing a written specification of what the software is to do. It deals with two main problem areas: identifying and describing problem requirements, and analyzing and describing behavior specifications.

  12. Software Reviews.

    ERIC Educational Resources Information Center

    Bitter, Gary G., Ed.

    1990-01-01

    Reviews three computer software: (1) "Elastic Lines: The Electronic Geoboard" on elementary geometry; (2) "Wildlife Adventures: Whales" on environmental science; and (3) "What Do You Do with a Broken Calculator?" on computation and problem solving. Summarizes the descriptions, strengths and weaknesses, and applications of each software. (YP)

  13. Software Repository

    NASA Technical Reports Server (NTRS)

    Merwarth, P., D.

    1983-01-01

    The Common Software Module Repository (CSMR) is computerized library system with high product and service visibility to potential users. Online capabilities of system allow both librarian and user to interact with library. Librarian is responsible for maintaining information in CSMR library. User searches library to locate software modules that meet his or her current needs.

  14. Software Reviews.

    ERIC Educational Resources Information Center

    Miller, Anne, Ed.; Radziemski, Cathy, Ed.

    1988-01-01

    Reviews two software packages for the Macintosh series. "Course Builder 2.0," a courseware authoring system, allows the user to create programs which stand alone and may be used independently in the classroom. "World Builder," an artificial intelligence software package, allows creative thinking, problem-solving, and decision-making. (YP)

  15. Software Bridge

    NASA Technical Reports Server (NTRS)

    1995-01-01

    I-Bridge is a commercial version of software developed by I-Kinetics under a NASA Small Business Innovation Research (SBIR) contract. The software allows users of Windows applications to gain quick, easy access to databases, programs and files on UNIX services. Information goes directly onto spreadsheets and other applications; users need not manually locate, transfer and convert data.

  16. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Stephen

    1988-01-01

    Presents reviews of six computer software programs for teaching science. Provides the publisher, grade level, cost, and descriptions of software, including: (1) "Recycling Logic"; (2) "Introduction to Biochemistry"; (3) "Food for Thought"; (4) "Watts in a Home"; (5) "Geology in Action"; and (6) "Biomes." All are for Apple series microcomputers.…

  17. Annotated bibliography of Software Engineering Laboratory literature

    NASA Technical Reports Server (NTRS)

    Morusiewicz, Linda; Valett, Jon D.

    1991-01-01

    An annotated bibliography of technical papers, documents, and memorandums produced by or related to the Software Engineering Laboratory is given. More than 100 publications are summarized. These publications cover many areas of software engineering and range from research reports to software documentation. All materials have been grouped into eight general subject areas for easy reference: The Software Engineering Laboratory; The Software Engineering Laboratory: Software Development Documents; Software Tools; Software Models; Software Measurement; Technology Evaluations; Ada Technology; and Data Collection. Subject and author indexes further classify these documents by specific topic and individual author.

  18. Annotated bibliography of software engineering laboratory literature

    NASA Technical Reports Server (NTRS)

    Groves, Paula; Valett, Jon

    1990-01-01

    An annotated bibliography of technical papers, documents, and memorandums produced by or related to the Software Engineering Laboratory is given. More than 100 publications are summarized. These publications cover many areas of software engineering and range from research reports to software documentation. This document has been updated and reorganized substantially since the original version (SEL-82-006, November 1982). All materials have been grouped into eight general subject areas for easy reference: the Software Engineering Laboratory; the Software Engineering Laboratory-software development documents; software tools; software models; software measurement; technology evaluations; Ada technology; and data collection. Subject and author indexes further classify these documents by specific topic and individual author.

  19. Input-Specific Gain Modulation by Local Sensory Context Shapes Cortical and Thalamic Responses to Complex Sounds.

    PubMed

    Williamson, Ross S; Ahrens, Misha B; Linden, Jennifer F; Sahani, Maneesh

    2016-07-20

    Sensory neurons are customarily characterized by one or more linearly weighted receptive fields describing sensitivity in sensory space and time. We show that in auditory cortical and thalamic neurons, the weight of each receptive field element depends on the pattern of sound falling within a local neighborhood surrounding it in time and frequency. Accounting for this change in effective receptive field with spectrotemporal context improves predictions of both cortical and thalamic responses to stationary complex sounds. Although context dependence varies among neurons and across brain areas, there are strong shared qualitative characteristics. In a spectrotemporally rich soundscape, sound elements modulate neuronal responsiveness more effectively when they coincide with sounds at other frequencies, and less effectively when they are preceded by sounds at similar frequencies. This local-context-driven lability in the representation of complex sounds-a modulation of "input-specific gain" rather than "output gain"-may be a widespread motif in sensory processing. PMID:27346532

  20. 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

  1. LIGA Scanner Control Software

    Energy Science and Technology Software Center (ESTSC)

    1999-02-01

    The LIGA Scanner Software is a graphical user interface package that facilitates controlling the scanning operation of x-rays from a synchrotron and sample manipulation for making LIGA parts. The process requires scanning of the LIGA mask and the PMMA resist through a stationary x-ray beam to provide an evenly distributed x-ray exposure over the wafer. This software package has been written specifically to interface with Aerotech motor controllers.

  2. Nanobodies: site-specific labeling for super-resolution imaging, rapid epitope-mapping and native protein complex isolation

    PubMed Central

    Pleiner, Tino; Bates, Mark; Trakhanov, Sergei; Lee, Chung-Tien; Schliep, Jan Erik; Chug, Hema; Böhning, Marc; Stark, Holger; Urlaub, Henning; Görlich, Dirk

    2015-01-01

    Nanobodies are single-domain antibodies of camelid origin. We generated nanobodies against the vertebrate nuclear pore complex (NPC) and used them in STORM imaging to locate individual NPC proteins with <2 nm epitope-label displacement. For this, we introduced cysteines at specific positions in the nanobody sequence and labeled the resulting proteins with fluorophore-maleimides. As nanobodies are normally stabilized by disulfide-bonded cysteines, this appears counterintuitive. Yet, our analysis showed that this caused no folding problems. Compared to traditional NHS ester-labeling of lysines, the cysteine-maleimide strategy resulted in far less background in fluorescence imaging, it better preserved epitope recognition and it is site-specific. We also devised a rapid epitope-mapping strategy, which relies on crosslinking mass spectrometry and the introduced ectopic cysteines. Finally, we used different anti-nucleoporin nanobodies to purify the major NPC building blocks – each in a single step, with native elution and, as demonstrated, in excellent quality for structural analysis by electron microscopy. The presented strategies are applicable to any nanobody and nanobody-target. DOI: http://dx.doi.org/10.7554/eLife.11349.001 PMID:26633879

  3. Adaptor Protein-3-Mediated Trafficking of TLR2 Ligands Controls Specificity of Inflammatory Responses but Not Adaptor Complex Assembly.

    PubMed

    Petnicki-Ocwieja, Tanja; Kern, Aurelie; Killpack, Tess L; Bunnell, Stephen C; Hu, Linden T

    2015-11-01

    Innate immune engagement results in the activation of host defenses that produce microbe-specific inflammatory responses. A long-standing interest in the field of innate immunity is to understand how varied host responses are generated through the signaling of just a limited number of receptors. Recently, intracellular trafficking and compartmental partitioning have been identified as mechanisms that provide signaling specificity for receptors by regulating signaling platform assembly. We show that cytokine activation as a result of TLR2 stimulation occurs at different intracellular locations and is mediated by the phagosomal trafficking molecule adaptor protein-3 (AP-3). AP-3 is required for trafficking TLR2 purified ligands or the Lyme disease causing bacterium, Borrelia burgdorferi, to LAMP-1 lysosomal compartments. The presence of AP-3 is necessary for the activation of cytokines such as IL-6 but not TNF-α or type I IFNs, suggesting induction of these cytokines occurs from a different compartment. Lack of AP-3 does not interfere with the recruitment of TLR signaling adaptors TRAM and MyD88 to the phagosome, indicating that the TLR-MyD88 signaling complex is assembled at a prelysosomal stage and that IL-6 activation depends on proper localization of signaling molecules downstream of MyD88. Finally, infection of AP-3-deficient mice with B. burgdorferi resulted in altered joint inflammation during murine Lyme arthritis. Our studies further elucidate the effects of phagosomal trafficking on tailoring immune responses in vitro and in vivo. PMID:26423153

  4. Wildlife software: procedures for publication of computer software

    USGS Publications Warehouse

    Samuel, M.D.

    1990-01-01

    Computers and computer software have become an integral part of the practice of wildlife science. Computers now play an important role in teaching, research, and management applications. Because of the specialized nature of wildlife problems, specific computer software is usually required to address a given problem (e.g., home range analysis). This type of software is not usually available from commercial vendors and therefore must be developed by those wildlife professionals with particular skill in computer programming. Current journal publication practices generally prevent a detailed description of computer software associated with new techniques. In addition, peer review of journal articles does not usually include a review of associated computer software. Thus, many wildlife professionals are usually unaware of computer software that would meet their needs or of major improvements in software they commonly use. Indeed most users of wildlife software learn of new programs or important changes only by word of mouth.

  5. Error-Free Software

    NASA Technical Reports Server (NTRS)

    1989-01-01

    001 is an integrated tool suited for automatically developing ultra reliable models, simulations and software systems. Developed and marketed by Hamilton Technologies, Inc. (HTI), it has been applied in engineering, manufacturing, banking and software tools development. The software provides the ability to simplify the complex. A system developed with 001 can be a prototype or fully developed with production quality code. It is free of interface errors, consistent, logically complete and has no data or control flow errors. Systems can be designed, developed and maintained with maximum productivity. Margaret Hamilton, President of Hamilton Technologies, also directed the research and development of USE.IT, an earlier product which was the first computer aided software engineering product in the industry to concentrate on automatically supporting the development of an ultrareliable system throughout its life cycle. Both products originated in NASA technology developed under a Johnson Space Center contract.

  6. Crystal structure of the Yersinia protein-tyrosine phosphatase YopH complexed with a specific small molecule inhibitor.

    PubMed

    Sun, Jin-Peng; Wu, Li; Fedorov, Alexander A; Almo, Steven C; Zhang, Zhong-Yin

    2003-08-29

    The pathogenic bacteria Yersinia are causative agents in human diseases ranging from gastrointestinal syndromes to bubonic plague. There is increasing risk of misuse of infectious agents, such as Yersinia pestis, as weapons of terror as well as instruments of warfare for mass destruction. Because the phosphatase activity of the Yersinia protein tyrosine phosphatase, YopH, is essential for virulence in the Yersinia pathogen, potent and selective YopH inhibitors are expected to serve as novel anti-plague agents. We have identified a specific YopH small molecule inhibitor, p-nitrocatechol sulfate (pNCS), which exhibits a Ki value of 25 microM for YopH and displays a 13-60-fold selectivity in favor of YopH against a panel of mammalian PTPs. To facilitate the understanding of the underlying molecular basis for tight binding and specificity, we have determined the crystal structure of YopH in complex with pNCS at a 2.0-A resolution. The structural data are corroborated by results from kinetic analyses of the interactions of YopH and its site-directed mutants with pNCS. The results show that while the interactions of the sulfuryl moiety and the phenyl ring with the YopH active site contribute to pNCS binding affinity, additional interactions of the hydroxyl and nitro groups in pNCS with Asp-356, Gln-357, Arg-404, and Gln-446 are responsible for the increased potency and selectivity. In particular, we note that residues Arg-404, Glu-290, Asp-356, and a bound water (WAT185) participate in a unique H-bonding network with the hydroxyl group ortho to the sulfuryl moiety, which may be exploited to design more potent and specific YopH inhibitors. PMID:12810712

  7. Use of mouse models to understand the molecular basis of tissue-specific tumorigenesis in the Carney complex.

    PubMed

    Kirschner, L S

    2009-07-01

    Carney complex (CNC) is an autosomal dominant, multiple endocrine neoplasia syndrome comprised of spotty skin pigmentation, myxomatosis, endocrine tumours and schwannomas. The majority of cases are due to inactivating mutations in PRKAR1A, the gene encoding the type 1A regulatory subunit of the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase, PKA (protein kinase A). In order to understand the molecular basis for tumorigenesis associated with PRKAR1A mutations, we have developed conventional and conditional Prkar1a knockout (KO) mice as well as primary cell culture models corresponding to these genetic manipulations. At the biochemical level, removal of Prkar1a from cells causes enhanced PKA activity, the same effect which has been observed in tumours isolated from CNC patients. Mice heterozygous for Prkar1a mutations (the exact genetic model for CNC patients) are born at expected frequencies and are tumour prone, developing neoplasms in cAMP-responsive cell types such as Schwann cells, osteoblasts and thyrocytes. In order to understand the basis of tissue-specific tumour formation, we have created tissue-specific KOs of the gene from three different tissues: the neural crest (Schwann cells), the pituitary gland and the heart. In the neural crest and the pituitary, ablation of Prkar1a leads to excess proliferation and tumorigenesis, whereas the same manipulation in developing cardiomyocytes leads to reduced proliferation and embryonic demise. The KO hearts also exhibit myxomatous changes suggesting a connection between PKA activation and myxomagenesis, although the nature of this relationship has not yet been determined. This work confirms the role of Prkar1a as a tissue-specific tumour suppressor, and ongoing work is focused on identifying the key downstream signalling targets affected by dysregulation of PKA. PMID:19522826

  8. Crystal Structures of the Human Doublecortin C- and N-terminal Domains in Complex with Specific Antibodies.

    PubMed

    Burger, Dominique; Stihle, Martine; Sharma, Ashwani; Di Lello, Paola; Benz, Jörg; D'Arcy, Brigitte; Debulpaep, Maja; Fry, David; Huber, Walter; Kremer, Thomas; Laeremans, Toon; Matile, Hugues; Ross, Alfred; Rufer, Arne C; Schoch, Guillaume; Steinmetz, Michel O; Steyaert, Jan; Rudolph, Markus G; Thoma, Ralf; Ruf, Armin

    2016-07-29

    Doublecortin is a microtubule-associated protein produced during neurogenesis. The protein stabilizes microtubules and stimulates their polymerization, which allows migration of immature neurons to their designated location in the brain. Mutations in the gene that impair doublecortin function and cause severe brain formation disorders are located on a tandem repeat of two doublecortin domains. The molecular mechanism of action of doublecortin is only incompletely understood. Anti-doublecortin antibodies, such as the rabbit polyclonal Abcam 18732, are widely used as neurogenesis markers. Here, we report the generation and characterization of antibodies that bind to single doublecortin domains. The antibodies were used as tools to obtain structures of both domains. Four independent crystal structures of the N-terminal domain reveal several distinct open and closed conformations of the peptide linking N- and C-terminal domains, which can be related to doublecortin function. An NMR assignment and a crystal structure in complex with a camelid antibody fragment show that the doublecortin C-terminal domain adopts the same well defined ubiquitin-like fold as the N-terminal domain, despite its reported aggregation and molten globule-like properties. The antibodies' unique domain specificity also renders them ideal research tools to better understand the role of individual domains in doublecortin function. A single chain camelid antibody fragment specific for the C-terminal doublecortin domain affected microtubule binding, whereas a monoclonal mouse antibody specific for the N-terminal domain did not. Together with steric considerations, this suggests that the microtubule-interacting doublecortin domain observed in cryo-electron micrographs is the C-terminal domain rather than the N-terminal one. PMID:27226599

  9. Structure of 'linkerless' hydroxamic acid inhibitor-HDAC8 complex confirms the formation of an isoform-specific subpocket.

    PubMed

    Tabackman, Alexa A; Frankson, Rochelle; Marsan, Eric S; Perry, Kay; Cole, Kathryn E

    2016-09-01

    Histone deacetylases (HDACs) catalyze the hydrolysis of acetylated lysine side chains in histone and non-histone proteins, and play a critical role in the regulation of many biological processes, including cell differentiation, proliferation, senescence, and apoptosis. Aberrant HDAC activity is associated with cancer, making these enzymes important targets for drug design. In general, HDAC inhibitors (HDACi) block the proliferation of tumor cells by inducing cell differentiation, cell cycle arrest, and/or apoptosis, and comprise some of the leading therapies in cancer treatments. To date, four HDACi have been FDA approved for the treatment of cancers: suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza®), romidepsin (FK228, Istodax®), belinostat (Beleodaq®), and panobinostat (Farydak®). Most current inhibitors are pan-HDACi, and non-selectively target a number of HDAC isoforms. Six previously reported HDACi were rationally designed, however, to target a unique sub-pocket found only in HDAC8. While these inhibitors were indeed potent against HDAC8, and even demonstrated specificity for HDAC8 over HDACs 1 and 6, there were no structural data to confirm the mode of binding. Here we report the X-ray crystal structure of Compound 6 complexed with HDAC8 to 1.98Å resolution. We also describe the use of molecular docking studies to explore the binding interactions of the other 5 related HDACi. Our studies confirm that the HDACi induce the formation of and bind in the HDAC8-specific subpocket, offering insights into isoform-specific inhibition. PMID:27374062

  10. 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.

  11. Software testing

    NASA Astrophysics Data System (ADS)

    Price-Whelan, Adrian M.

    2016-01-01

    Now more than ever, scientific results are dependent on sophisticated software and analysis. Why should we trust code written by others? How do you ensure your own code produces sensible results? How do you make sure it continues to do so as you update, modify, and add functionality? Software testing is an integral part of code validation and writing tests should be a requirement for any software project. I will talk about Python-based tools that make managing and running tests much easier and explore some statistics for projects hosted on GitHub that contain tests.

  12. Software Quality Assurance Audits Guidebooks

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The growth in cost and importance of software to NASA has caused NASA to address the improvement of software development across the agency. One of the products of this program is a series of guidebooks that define a NASA concept of the assurance processes that are used in software development. The Software Assurance Guidebook, NASA-GB-A201, issued in September, 1989, provides an overall picture of the NASA concepts and practices in software assurance. Second level guidebooks focus on specific activities that fall within the software assurance discipline, and provide more detailed information for the manager and/or practitioner. This is the second level Software Quality Assurance Audits Guidebook that describes software quality assurance audits in a way that is compatible with practices at NASA Centers.

  13. A novel mouse model of tuberous sclerosis complex (TSC): eye-specific Tsc1-ablation disrupts visual-pathway development

    PubMed Central

    Jones, Iwan; Hägglund, Anna-Carin; Törnqvist, Gunilla; Nord, Christoffer; Ahlgren, Ulf; Carlsson, Leif

    2015-01-01

    ABSTRACT Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome that is best characterised by neurodevelopmental deficits and the presence of benign tumours (called hamartomas) in affected organs. This multi-organ disorder results from inactivating point mutations in either the TSC1 or the TSC2 genes and consequent activation of the canonical mammalian target of rapamycin complex 1 signalling (mTORC1) pathway. Because lesions to the eye are central to TSC diagnosis, we report here the generation and characterisation of the first eye-specific TSC mouse model. We demonstrate that conditional ablation of Tsc1 in eye-committed progenitor cells leads to the accelerated differentiation and subsequent ectopic radial migration of retinal ganglion cells. This results in an increase in retinal ganglion cell apoptosis and consequent regionalised axonal loss within the optic nerve and topographical changes to the contra- and ipsilateral input within the dorsal lateral geniculate nucleus. Eyes from adult mice exhibit aberrant retinal architecture and display all the classic neuropathological hallmarks of TSC, including an increase in organ and cell size, ring heterotopias, hamartomas with retinal detachment, and lamination defects. Our results provide the first major insight into the molecular etiology of TSC within the developing eye and demonstrate a pivotal role for Tsc1 in regulating various aspects of visual-pathway development. Our novel mouse model therefore provides a valuable resource for future studies concerning the molecular mechanisms underlying TSC and also as a platform to evaluate new therapeutic approaches for the treatment of this multi-organ disorder. PMID:26449264

  14. The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels.

    PubMed

    Boulay, Anne-Cécile; Saubaméa, Bruno; Cisternino, Salvatore; Mignon, Virginie; Mazeraud, Aurélien; Jourdren, Laurent; Blugeon, Corinne; Cohen-Salmon, Martine

    2015-01-01

    Astrocytes, the most prominent glial cell type in the brain, send specialized processes called endfeet, around blood vessels and express a large molecular repertoire regulating the cerebrovascular system physiology. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction proteins Connexin 43 and 30 (Cx43 and Cx30) allowing in particular for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. In this study, we addressed the specific role of Cx30 at the gliovascular interface. Using an inactivation mouse model for Cx30 (Cx30(Δ/Δ); Δ means deleted allele) we showed that absence of Cx30 does not affect blood-brain barrier (BBB) organization and permeability. However, it results in the cerebrovascular fraction, in a strong upregulation of Sgcg encoding γ-Sarcoglycan (γ-SG), a member of the Dystrophin-associated protein complex (DAPC) connecting cytoskeleton and the extracellular matrix. The same molecular event occurs in Cx30(T5M/T5M) mutated mice, where Cx30 channels are closed, demonstrating that Sgcg regulation relied on Cx30 channel functions. We further characterized the expression of other Sarcoglycan complex (SGC) molecules in the cerebrovascular system and showed the presence of α-, β-, δ-, γ-, ε- and ζ- SG, as well as Sarcospan. Their expression was however not modified in Cx30(Δ/Δ). These results suggest that a full SGC might be present in the cerebrovascular system, and that expression of one of its member, γ-SG, depends on Cx30 channels. As described in skeletal muscles, the SGC may contribute to membrane stabilization and signal transduction in the cerebrovascular system, which may therefore be regulated by Cx30 channel-mediated functions. PMID:25698924

  15. The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels

    PubMed Central

    Boulay, Anne-Cécile; Saubaméa, Bruno; Cisternino, Salvatore; Mignon, Virginie; Mazeraud, Aurélien; Jourdren, Laurent; Blugeon, Corinne; Cohen-Salmon, Martine

    2015-01-01

    Astrocytes, the most prominent glial cell type in the brain, send specialized processes called endfeet, around blood vessels and express a large molecular repertoire regulating the cerebrovascular system physiology. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction proteins Connexin 43 and 30 (Cx43 and Cx30) allowing in particular for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. In this study, we addressed the specific role of Cx30 at the gliovascular interface. Using an inactivation mouse model for Cx30 (Cx30Δ/Δ; Δ means deleted allele) we showed that absence of Cx30 does not affect blood-brain barrier (BBB) organization and permeability. However, it results in the cerebrovascular fraction, in a strong upregulation of Sgcg encoding γ-Sarcoglycan (γ-SG), a member of the Dystrophin-associated protein complex (DAPC) connecting cytoskeleton and the extracellular matrix. The same molecular event occurs in Cx30T5M/T5M mutated mice, where Cx30 channels are closed, demonstrating that Sgcg regulation relied on Cx30 channel functions. We further characterized the expression of other Sarcoglycan complex (SGC) molecules in the cerebrovascular system and showed the presence of α-, β-, δ-, γ-, ε- and ζ- SG, as well as Sarcospan. Their expression was however not modified in Cx30Δ/Δ. These results suggest that a full SGC might be present in the cerebrovascular system, and that expression of one of its member, γ-SG, depends on Cx30 channels. As described in skeletal muscles, the SGC may contribute to membrane stabilization and signal transduction in the cerebrovascular system, which may therefore be regulated by Cx30 channel-mediated functions. PMID:25698924

  16. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Stephen, Ed.

    1990-01-01

    Reviewed are six computer software packages including "Lunar Greenhouse,""Dyno-Quest,""How Weather Works,""Animal Trackers,""Personal Science Laboratory," and "The Skeletal and Muscular Systems." Availability, functional, and hardware requirements are discussed. (CW)

  17. Software Reviews.

    ERIC Educational Resources Information Center

    McGrath, Diane

    1990-01-01

    Reviews two programs: (1) "The Weather Machine" on understanding weather and weather forecasting and (2) "The Mystery of the Hotel Victoria" on problem solving in mathematics. Presents the descriptions, advantages, and weaknesses of the software. (YP)

  18. Software Reviews.

    ERIC Educational Resources Information Center

    Davis, Shelly J., Ed.; Knaupp, Jon, Ed.

    1984-01-01

    Reviewed is computer software on: (1) classification of living things, a tutorial program for grades 5-10; and (2) polynomial practice using tiles, a drill-and-practice program for algebra students. (MNS)

  19. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Stephen, Ed.

    1987-01-01

    Provides a review of four science software programs. Includes topics such as plate tectonics, laboratory experiment simulations, the human body, and light and temperature. Contains information on ordering and reviewers' comments. (ML)

  20. Software Reviews.

    ERIC Educational Resources Information Center

    Dwyer, Donna; And Others

    1989-01-01

    Reviewed are seven software packages for Apple and IBM computers. Included are: "Toxicology"; "Science Corner: Space Probe"; "Alcohol and Pregnancy"; "Science Tool Kit Plus"; Computer Investigations: Plant Growth"; "Climatrolls"; and "Animal Watch: Whales." (CW)

  1. Software Reviews.

    ERIC Educational Resources Information Center

    Kimball, Jeffrey P.; And Others

    1987-01-01

    Describes a variety of computer software. The packages reviewed include a variety of simulations, a spread sheet, a printer driver and an alternative operating system for DBM.PCs and compatible programs. (BSR)

  2. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Eugene T., Ed.

    1988-01-01

    Presents reviews by classroom teachers of software for teaching science. Includes material on the work of geologists, genetics, earth science, classification of living things, astronomy, endangered species, skeleton, drugs, and heartbeat. Provides information on availability and equipment needed. (RT)

  3. Software Reviews.

    ERIC Educational Resources Information Center

    Classroom Computer Learning, 1990

    1990-01-01

    Reviewed are three computer software packages including "Martin Luther King, Jr.: Instant Replay of History,""Weeds to Trees," and "The New Print Shop, School Edition." Discussed are hardware requirements, costs, grade levels, availability, emphasis, strengths, and weaknesses. (CW)

  4. Software Reviews.

    ERIC Educational Resources Information Center

    Mathematics and Computer Education, 1988

    1988-01-01

    Presents reviews of six software packages. Includes (1) "Plain Vanilla Statistics"; (2) "MathCAD 2.0"; (3) "GrFx"; (4) "Trigonometry"; (5) "Algebra II"; (6) "Algebra Drill and Practice I, II, and III." (PK)

  5. Astronomy Software

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Software Bisque's TheSky, SkyPro and Remote Astronomy Software incorporate technology developed for the Hubble Space Telescope. TheSky and SkyPro work together to orchestrate locating, identifying and acquiring images of deep sky objects. With all three systems, the user can directly control computer-driven telescopes and charge coupled device (CCD) cameras through serial ports. Through the systems, astronomers and students can remotely operate a telescope at the Mount Wilson Observatory Institute.

  6. TALE-Like Effectors Are an Ancestral Feature of the Ralstonia solanacearum Species Complex and Converge in DNA Targeting Specificity.

    PubMed

    Schandry, Niklas; de Lange, Orlando; Prior, Philippe; Lahaye, Thomas

    2016-01-01

    Ralstonia solanacearum, a species complex of bacterial plant pathogens divided into four monophyletic phylotypes, causes plant diseases in tropical climates around the world. Some strains exhibit a broad host range on solanaceous hosts, while others are highly host-specific as for example some banana-pathogenic strains. Previous studies showed that transcription activator-like (TAL) effectors from Ralstonia, termed RipTALs, are capable of activating reporter genes in planta, if these are preceded by a matching effector binding element (EBE). RipTALs target DNA via their central repeat domain (CRD), where one repeat pairs with one DNA-base of the given EBE. The repeat variable diresidue dictates base repeat specificity in a predictable fashion, known as the TALE code. In this work, we analyze RipTALs across all phylotypes of the Ralstonia solanacearum species complex. We find that RipTALs are prevalent in phylotypes I and IV but absent from most phylotype III and II strains (10/12, 8/14, 1/24, and 1/5 strains contained a RipTAL, respectively). RipTALs originating from strains of the same phylotype show high levels of sequence similarity (>98%) in the N-terminal and C-terminal regions, while RipTALs isolated from different phylotypes show 47-91% sequence similarity in those regions, giving rise to four RipTAL classes. We show that, despite sequence divergence, the base preference for guanine, mediated by the N-terminal region, is conserved across RipTALs of all classes. Using the number and order of repeats found in the CRD, we functionally sub-classify RipTALs, introduce a new simple nomenclature, and predict matching EBEs for all seven distinct RipTALs identified. We experimentally study RipTAL EBEs and uncover that some RipTALs are able to target the EBEs of other RipTALs, referred to as cross-reactivity. In particular, RipTALs from strains with a broad host range on solanaceous hosts cross-react on each other's EBEs. Investigation of sequence divergence between

  7. TALE-Like Effectors Are an Ancestral Feature of the Ralstonia solanacearum Species Complex and Converge in DNA Targeting Specificity

    PubMed Central

    Schandry, Niklas; de Lange, Orlando; Prior, Philippe; Lahaye, Thomas

    2016-01-01

    Ralstonia solanacearum, a species complex of bacterial plant pathogens divided into four monophyletic phylotypes, causes plant diseases in tropical climates around the world. Some strains exhibit a broad host range on solanaceous hosts, while others are highly host-specific as for example some banana-pathogenic strains. Previous studies showed that transcription activator-like (TAL) effectors from Ralstonia, termed RipTALs, are capable of activating reporter genes in planta, if these are preceded by a matching effector binding element (EBE). RipTALs target DNA via their central repeat domain (CRD), where one repeat pairs with one DNA-base of the given EBE. The repeat variable diresidue dictates base repeat specificity in a predictable fashion, known as the TALE code. In this work, we analyze RipTALs across all phylotypes of the Ralstonia solanacearum species complex. We find that RipTALs are prevalent in phylotypes I and IV but absent from most phylotype III and II strains (10/12, 8/14, 1/24, and 1/5 strains contained a RipTAL, respectively). RipTALs originating from strains of the same phylotype show high levels of sequence similarity (>98%) in the N-terminal and C-terminal regions, while RipTALs isolated from different phylotypes show 47–91% sequence similarity in those regions, giving rise to four RipTAL classes. We show that, despite sequence divergence, the base preference for guanine, mediated by the N-terminal region, is conserved across RipTALs of all classes. Using the number and order of repeats found in the CRD, we functionally sub-classify RipTALs, introduce a new simple nomenclature, and predict matching EBEs for all seven distinct RipTALs identified. We experimentally study RipTAL EBEs and uncover that some RipTALs are able to target the EBEs of other RipTALs, referred to as cross-reactivity. In particular, RipTALs from strains with a broad host range on solanaceous hosts cross-react on each other’s EBEs. Investigation of sequence divergence

  8. Cardiomyocyte-Specific Ablation of Med1 Subunit of the Mediator Complex Causes Lethal Dilated Cardiomyopathy in Mice

    PubMed Central

    Jia, Yuzhi; Chang, Hsiang-Chun; Schipma, Matthew J.; Liu, Jing; Shete, Varsha; Liu, Ning; Sato, Tatsuya; Thorp, Edward B.; Barger, Philip M.; Zhu, Yi-Jun; Viswakarma, Navin; Kanwar, Yashpal S.; Ardehali, Hossein; Thimmapaya, Bayar; Reddy, Janardan K.

    2016-01-01

    Mediator, an evolutionarily conserved multi-protein complex consisting of about 30 subunits, is a key component of the polymerase II mediated gene transcription. Germline deletion of the Mediator subunit 1 (Med1) of the Mediator in mice results in mid-gestational embryonic lethality with developmental impairment of multiple organs including heart. Here we show that cardiomyocyte-specific deletion of Med1 in mice (csMed1-/-) during late gestational and early postnatal development by intercrossing Med1fl/fl mice to α-MyHC-Cre transgenic mice results in lethality within 10 days after weaning due to dilated cardiomyopathy-related ventricular dilation and heart failure. The csMed1-/- mouse heart manifests mitochondrial damage, increased apoptosis and interstitial fibrosis. Global gene expression analysis revealed that loss of Med1 in heart down-regulates more than 200 genes including Acadm, Cacna1s, Atp2a2, Ryr2, Pde1c, Pln, PGC1α, and PGC1β that are critical for calcium signaling, cardiac muscle contraction, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and peroxisome proliferator-activated receptor regulated energy metabolism. Many genes essential for oxidative phosphorylation and proper mitochondrial function such as genes coding for the succinate dehydrogenase subunits of the mitochondrial complex II are also down-regulated in csMed1-/- heart contributing to myocardial injury. Data also showed up-regulation of about 180 genes including Tgfb2, Ace, Atf3, Ctgf, Angpt14, Col9a2, Wisp2, Nppa, Nppb, and Actn1 that are linked to cardiac muscle contraction, cardiac hypertrophy, cardiac fibrosis and myocardial injury. Furthermore, we demonstrate that cardiac specific deletion of Med1 in adult mice using tamoxifen-inducible Cre approach (TmcsMed1-/-), results in rapid development of cardiomyopathy and death within 4 weeks. We found that the key findings of the csMed1-/- studies described above are highly reproducible in TmcsMed1-/- mouse heart

  9. 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.

  10. Software Formal Inspections Guidebook

    NASA Technical Reports Server (NTRS)

    1993-01-01

    The Software Formal Inspections Guidebook is designed to support the inspection process of software developed by and for NASA. This document provides information on how to implement a recommended and proven method for conducting formal inspections of NASA software. This Guidebook is a companion document to NASA Standard 2202-93, Software Formal Inspections Standard, approved April 1993, which provides the rules, procedures, and specific requirements for conducting software formal inspections. Application of the Formal Inspections Standard is optional to NASA program or project management. In cases where program or project management decide to use the formal inspections method, this Guidebook provides additional information on how to establish and implement the process. The goal of the formal inspections process as documented in the above-mentioned Standard and this Guidebook is to provide a framework and model for an inspection process that will enable the detection and elimination of defects as early as possible in the software life cycle. An ancillary aspect of the formal inspection process incorporates the collection and analysis of inspection data to effect continual improvement in the inspection process and the quality of the software subjected to the process.

  11. Use of DNA melting simulation software for in silico diagnostic assay design: targeting regions with complex melting curves and confirmation by real-time PCR using intercalating dyes

    PubMed Central

    Rasmussen, John P; Saint, Christopher P; Monis, Paul T

    2007-01-01

    Background DNA melting curve analysis using double-stranded DNA-specific dyes such as SYTO9 produce complex and reproducible melting profiles, resulting in the detection of multiple melting peaks from a single amplicon and allowing the discrimination of different species. We compare the melting curves of several Naegleria and Cryptosporidium amplicons generated in vitro with in silico DNA melting simulations using the programs POLAND and MELTSIM., then test the utility of these programs for assay design using a genetic marker for toxin production in cyanobacteria. Results The SYTO9 melting curve profiles of three species of Naegleria and two species of Cryptosporidium were similar to POLAND and MELTSIM melting simulations, excepting some differences in the relative peak heights and the absolute melting temperatures of these peaks. MELTSIM and POLAND were used to screen sequences from a putative toxin gene in two different species of cyanobacteria and identify regions exhibiting diagnostic melting profiles. For one of these diagnostic regions the POLAND and MELTSIM melting simulations were observed to be different, with POLAND more accurately predicting the melting curve generated in vitro. Upon further investigation of this region with MELTSIM, inconsistencies between the melting simulation for forward and reverse complement sequences were observed. The assay was used to accurately type twenty seven cyanobacterial DNA extracts in vitro. Conclusion Whilst neither POLAND nor MELTSIM simulation programs were capable of exactly predicting DNA dissociation in the presence of an intercalating dye, the programs were successfully used as tools to identify regions where melting curve differences could be exploited for diagnostic melting curve assay design. Refinements in the simulation parameters would be required to account for the effect of the intercalating dye and salt concentrations used in real-time PCR. The agreement between the melting curve simulations for

  12. Evolutionary Genomics Suggests That CheV Is an Additional Adaptor for Accommodating Specific Chemoreceptors within the Chemotaxis Signaling Complex

    PubMed Central

    Ortega, Davi R.; Zhulin, Igor B.

    2016-01-01

    Escherichia coli and Salmonella enterica are models for many experiments in molecular biology including chemotaxis, and most of the results obtained with one organism have been generalized to another. While most components of the chemotaxis pathway are strongly conserved between the two species, Salmonella genomes contain some chemoreceptors and an additional protein, CheV, that are not found in E. coli. The role of CheV was examined in distantly related species Bacillus subtilis and Helicobacter pylori, but its role in bacterial chemotaxis is still not well understood. We tested a hypothesis that in enterobacteria CheV functions as an additional adaptor linking the CheA kinase to certain types of chemoreceptors that cannot be effectively accommodated by the universal adaptor CheW. Phylogenetic profiling, genomic context and comparative protein sequence analyses suggested that CheV interacts with specific domains of CheA and chemoreceptors from an orthologous group exemplified by the Salmonella McpC protein. Structural consideration of the conservation patterns suggests that CheV and CheW share the same binding spot on the chemoreceptor structure, but have some affinity bias towards chemoreceptors from different orthologous groups. Finally, published experimental results and data newly obtained via comparative genomics support the idea that CheV functions as a “phosphate sink” possibly to off-set the over-stimulation of the kinase by certain types of chemoreceptors. Overall, our results strongly suggest that CheV is an additional adaptor for accommodating specific chemoreceptors within the chemotaxis signaling complex. PMID:26844549

  13. Dynamic Parameter Identification of Subject-Specific Body Segment Parameters Using Robotics Formalism: Case Study Head Complex.

    PubMed

    Díaz-Rodríguez, Miguel; Valera, Angel; Page, Alvaro; Besa, Antonio; Mata, Vicente

    2016-05-01

    Accurate knowledge of body segment inertia parameters (BSIP) improves the assessment of dynamic analysis based on biomechanical models, which is of paramount importance in fields such as sport activities or impact crash test. Early approaches for BSIP identification rely on the experiments conducted on cadavers or through imaging techniques conducted on living subjects. Recent approaches for BSIP identification rely on inverse dynamic modeling. However, most of the approaches are focused on the entire body, and verification of BSIP for dynamic analysis for distal segment or chain of segments, which has proven to be of significant importance in impact test studies, is rarely established. Previous studies have suggested that BSIP should be obtained by using subject-specific identification techniques. To this end, our paper develops a novel approach for estimating subject-specific BSIP based on static and dynamics identification models (SIM, DIM). We test the validity of SIM and DIM by comparing the results using parameters obtained from a regression model proposed by De Leva (1996, "Adjustments to Zatsiorsky-Seluyanov's Segment Inertia Parameters," J. Biomech., 29(9), pp. 1223-1230). Both SIM and DIM are developed considering robotics formalism. First, the static model allows the mass and center of gravity (COG) to be estimated. Second, the results from the static model are included in the dynamics equation allowing us to estimate the moment of inertia (MOI). As a case study, we applied the approach to evaluate the dynamics modeling of the head complex. Findings provide some insight into the validity not only of the proposed method but also of the application proposed by De Leva (1996, "Adjustments to Zatsiorsky-Seluyanov's Segment Inertia Parameters," J. Biomech., 29(9), pp. 1223-1230) for dynamic modeling of body segments. PMID:26974715

  14. In silico identification and characterization of the ion transport specificity for P-type ATPases in the Mycobacterium tuberculosis complex

    PubMed Central

    2012-01-01

    Background P-type ATPases hydrolyze ATP and release energy that is used in the transport of ions against electrochemical gradients across plasma membranes, making these proteins essential for cell viability. Currently, the distribution and function of these ion transporters in mycobacteria are poorly understood. Results In this study, probabilistic profiles were constructed based on hidden Markov models to identify and classify P-type ATPases in the Mycobacterium tuberculosis complex (MTBC) according to the type of ion transported across the plasma membrane. Topology, hydrophobicity profiles and conserved motifs were analyzed to correlate amino acid sequences of P-type ATPases and ion transport specificity. Twelve candidate P-type ATPases annotated in the M. tuberculosis H37Rv proteome were identified in all members of the MTBC, and probabilistic profiles classified them into one of the following three groups: heavy metal cation transporters, alkaline and alkaline earth metal cation transporters, and the beta subunit of a prokaryotic potassium pump. Interestingly, counterparts of the non-catalytic beta subunits of Hydrogen/Potassium and Sodium/Potassium P-type ATPases were not found. Conclusions The high content of heavy metal transporters found in the MTBC suggests that they could play an important role in the ability of M. tuberculosis to survive inside macrophages, where tubercle bacilli face high levels of toxic metals. Finally, the results obtained in this work provide a starting point for experimental studies that may elucidate the ion specificity of the MTBC P-type ATPases and their role in mycobacterial infections. PMID:23031689

  15. Assessment of clinical analytical sensitivity and specificity of next-generation sequencing for detection of simple and complex mutations

    PubMed Central

    2013-01-01

    Background Detecting mutations in disease genes by full gene sequence analysis is common in clinical diagnostic laboratories. Sanger dideoxy terminator sequencing allows for rapid development and implementation of sequencing assays in the clinical laboratory, but it has limited throughput, and due to cost constraints, only allows analysis of one or at most a few genes in a patient. Next-generation sequencing (NGS), on the other hand, has evolved rapidly, although to date it has mainly been used for large-scale genome sequencing projects and is beginning to be used in the clinical diagnostic testing. One advantage of NGS is that many genes can be analyzed easily at the same time, allowing for mutation detection when there are many possible causative genes for a specific phenotype. In addition, regions of a gene typically not tested for mutations, like deep intronic and promoter mutations, can also be detected. Results Here we use 20 previously characterized Sanger-sequenced positive controls in disease-causing genes to demonstrate the utility of NGS in a clinical setting using standard PCR based amplification to assess the analytical sensitivity and specificity of the technology for detecting all previously characterized changes (mutations and benign SNPs). The positive controls chosen for validation range from simple substitution mutations to complex deletion and insertion mutations occurring in autosomal dominant and recessive disorders. The NGS data was 100% concordant with the Sanger sequencing data identifying all 119 previously identified changes in the 20 samples. Conclusions We have demonstrated that NGS technology is ready to be deployed in clinical laboratories. However, NGS and associated technologies are evolving, and clinical laboratories will need to invest significantly in staff and infrastructure to build the necessary foundation for success. PMID:23418865

  16. Evolutionary Genomics Suggests That CheV Is an Additional Adaptor for Accommodating Specific Chemoreceptors within the Chemotaxis Signaling Complex.

    PubMed

    Ortega, Davi R; Zhulin, Igor B

    2016-02-01

    Escherichia coli and Salmonella enterica are models for many experiments in molecular biology including chemotaxis, and most of the results obtained with one organism have been generalized to another. While most components of the chemotaxis pathway are strongly conserved between the two species, Salmonella genomes contain some chemoreceptors and an additional protein, CheV, that are not found in E. coli. The role of CheV was examined in distantly related species Bacillus subtilis and Helicobacter pylori, but its role in bacterial chemotaxis is still not well understood. We tested a hypothesis that in enterobacteria CheV functions as an additional adaptor linking the CheA kinase to certain types of chemoreceptors that cannot be effectively accommodated by the universal adaptor CheW. Phylogenetic profiling, genomic context and comparative protein sequence analyses suggested that CheV interacts with specific domains of CheA and chemoreceptors from an orthologous group exemplified by the Salmonella McpC protein. Structural consideration of the conservation patterns suggests that CheV and CheW share the same binding spot on the chemoreceptor structure, but have some affinity bias towards chemoreceptors from different orthologous groups. Finally, published experimental results and data newly obtained via comparative genomics support the idea that CheV functions as a "phosphate sink" possibly to off-set the over-stimulation of the kinase by certain types of chemoreceptors. Overall, our results strongly suggest that CheV is an additional adaptor for accommodating specific chemoreceptors within the chemotaxis signaling complex. PMID:26844549

  17. Evaluation of Visualization Software

    NASA Technical Reports Server (NTRS)

    Globus, Al; Uselton, Sam

    1995-01-01

    Visualization software is widely used in scientific and engineering research. But computed visualizations can be very misleading, and the errors are easy to miss. We feel that the software producing the visualizations must be thoroughly evaluated and the evaluation process as well as the results must be made available. Testing and evaluation of visualization software is not a trivial problem. Several methods used in testing other software are helpful, but these methods are (apparently) often not used. When they are used, the description and results are generally not available to the end user. Additional evaluation methods specific to visualization must also be developed. We present several useful approaches to evaluation, ranging from numerical analysis of mathematical portions of algorithms to measurement of human performance while using visualization systems. Along with this brief survey, we present arguments for the importance of evaluations and discussions of appropriate use of some methods.

  18. Integrating interface slicing into software engineering processes

    NASA Technical Reports Server (NTRS)

    Beck, Jon

    1993-01-01

    Interface slicing is a tool which was developed to facilitate software engineering. As previously presented, it was described in terms of its techniques and mechanisms. The integration of interface slicing into specific software engineering activities is considered by discussing a number of potential applications of interface slicing. The applications discussed specifically address the problems, issues, or concerns raised in a previous project. Because a complete interface slicer is still under development, these applications must be phrased in future tenses. Nonetheless, the interface slicing techniques which were presented can be implemented using current compiler and static analysis technology. Whether implemented as a standalone tool or as a module in an integrated development or reverse engineering environment, they require analysis no more complex than that required for current system development environments. By contrast, conventional slicing is a methodology which, while showing much promise and intuitive appeal, has yet to be fully implemented in a production language environment despite 12 years of development.

  19. A technique for incorporating the NASA spacelab payload dedicated experiment processor software into the simulation system for the payload crew training complex

    NASA Technical Reports Server (NTRS)

    Bremmer, D. A.

    1986-01-01

    The feasibility of some off-the-shelf microprocessors and state-of-art software is assessed (1) as a development system for the principle investigator (pi) in the design of the experiment model, (2) as an example of available technology application for future PI's experiments, (3) as a system capable of being interactive in the PCTC's simulation of the dedicated experiment processor (DEP), preferably by bringing the PI's DEP software directly into the simulation model, (4) as a system having bus compatibility with host VAX simulation computers, (5) as a system readily interfaced with mock-up panels and information displays, and (6) as a functional system for post mission data analysis.

  20. Structural characterization of a noncovalent complex between ubiquitin and the transactivation domain of the erythroid-specific factor EKLF.

    PubMed

    Raiola, Luca; Lussier-Price, Mathieu; Gagnon, David; Lafrance-Vanasse, Julien; Mascle, Xavier; Arseneault, Genevieve; Legault, Pascale; Archambault, Jacques; Omichinski, James G

    2013-11-01

    Like other acidic transactivation domains (TAD), the minimal TAD from the erythroid-specific transcription factor EKLF (EKLFTAD) has been shown to contribute both to its transcriptional activity as well as to its ubiquitin(UBI)-mediated degradation. In this article, we examine the activation-degradation role of the acidic TAD of EKLF and demonstrate that the first 40 residues (EKLFTAD1) within this region form a noncovalent interaction with UBI. Nuclear magnetic resonance (NMR) structural studies of an EKLFTAD1-UBI complex show that EKLFTAD1 adopts a 14-residue α helix that forms the recognition interface with UBI in a similar manner as the UBI-interacting helix of Rabex5. We also identify a similar interaction between UBI and the activation-degradation region of SREBP1a, but not with the activation-degradation regions of p53, GAL4, and VP16. These results suggest that select activation-degradation regions like the ones found in EKLF and SREBP1a function in part through their ability to form noncovalent interactions with UBI. PMID:24139988

  1. Thyroid-specific ablation of the Carney complex gene, PRKAR1A, results in hyperthyroidism and follicular thyroid cancer.

    PubMed

    Pringle, Daphne R; Yin, Zhirong; Lee, Audrey A; Manchanda, Parmeet K; Yu, Lianbo; Parlow, Alfred F; Jarjoura, David; La Perle, Krista M D; Kirschner, Lawrence S

    2012-06-01

    Thyroid cancer is the most common endocrine malignancy in the population, and the incidence of this cancer is increasing at a rapid rate. Although genetic analysis of papillary thyroid cancer (PTC) has identified mutations in a large percentage of patients, the genetic basis of follicular thyroid cancer (FTC) is less certain. Thyroid cancer, including both PTC and FTC, has been observed in patients with the inherited tumor predisposition Carney complex, caused by mutations in PRKAR1A. In order to investigate the role of loss of PRKAR1A in thyroid cancer, we generated a tissue-specific knockout of Prkar1a in the thyroid. We report that the resulting mice are hyperthyroid and developed follicular thyroid neoplasms by 1 year of age, including FTC in over 40% of animals. These thyroid tumors showed a signature of pathway activation different from that observed in other models of thyroid cancer. In vitro cultures of the tumor cells indicated that Prkar1a-null thyrocytes exhibited growth factor independence and suggested possible new therapeutic targets. Overall, this work represents the first report of a genetic mutation known to cause human FTC that exhibits a similar phenotype when modeled in the mouse. In addition to our knowledge of the mechanisms of human follicular thyroid tumorigenesis, this model is highly reproducible and may provide a viable mechanism for the further clinical development of therapies aimed at FTC. PMID:22514108

  2. Identification of novel ribonucleo-protein complexes from the brain-specific snoRNA MBII-52.

    PubMed

    Soeno, Yuuichi; Taya, Yuji; Stasyk, Taras; Huber, Lukas A; Aoba, Takaaki; Hüttenhofer, Alexander

    2010-07-01

    Small nucleolar RNAs (snoRNAs) guide nucleotide modifications within ribosomal RNAs or spliceosomal RNAs by base-pairing to complementary regions within their RNA targets. The brain-specific snoRNA MBII-52 lacks such a complementarity to rRNAs or snRNAs, but instead has been reported to target the serotonin receptor 2C pre-mRNA, thereby regulating pre-mRNA editing and/or alternative splicing. To understand how the MBII-52 snoRNA might be involved in these regulatory processes, we isolated the MBII-52 snoRNP from total mouse brain by an antisense RNA affinity purification approach. Surprisingly, by mass spectrometry we identified 17 novel candidates for MBII-52 snoRNA binding proteins, which previously had not been reported to be associated with canonical snoRNAs. Among these, Nucleolin and ELAVL1 proteins were confirmed to independently and directly interact with the MBII-52 snoRNA by coimmunoprecipitation. Our findings suggest that the MBII-52 snoRNA assembles into novel RNA-protein complexes, distinct from canonical snoRNPs. PMID:20484469

  3. Chaperonin containing T-complex polypeptide subunit eta (CCT-eta) is a specific regulator of fibroblast motility and contractility.

    PubMed

    Satish, Latha; Johnson, Sandra; Wang, James H-C; Post, J Christopher; Ehrlich, Garth D; Kathju, Sandeep

    2010-01-01

    Integumentary wounds in mammalian fetuses heal without scar; this scarless wound healing is intrinsic to fetal tissues and is notable for absence of the contraction seen in postnatal (adult) wounds. The precise molecular signals determining the scarless phenotype remain unclear. We have previously reported that the eta subunit of the chaperonin containing T-complex polypeptide (CCT-eta) is specifically reduced in healing fetal wounds in a rabbit model. In this study, we examine the role of CCT-eta in fibroblast motility and contractility, properties essential to wound healing and scar formation. We demonstrate that CCT-eta (but not CCT-beta) is underexpressed in fetal fibroblasts compared to adult fibroblasts. An in vitro wound healing assay demonstrated that adult fibroblasts showed increased cell migration in response to epidermal growth factor (EGF) and platelet derived growth factor (PDGF) stimulation, whereas fetal fibroblasts were unresponsive. Downregulation of CCT-eta in adult fibroblasts with short inhibitory RNA (siRNA) reduced cellular motility, both basal and growth factor-induced; in contrast, siRNA against CCT-beta had no such effect. Adult fibroblasts were more inherently contractile than fetal fibroblasts by cellular traction force microscopy; this contractility was increased by treatment with EGF and PDGF. CCT-eta siRNA inhibited the PDGF-induction of adult fibroblast contractility, whereas CCT-beta siRNA had no such effect. In each of these instances, the effect of downregulating CCT-eta was to modulate the behavior of adult fibroblasts so as to more closely approximate the characteristics of fetal fibroblasts. We next examined the effect of CCT-eta modulation on alpha-smooth muscle actin (alpha-SMA) expression, a gene product well known to play a critical role in adult wound healing. Fetal fibroblasts were found to constitutively express less alpha-SMA than adult cells. Reduction of CCT-eta with siRNA had minimal effect on cellular beta-actin but

  4. Software Reliability 2002

    NASA Technical Reports Server (NTRS)

    Wallace, Dolores R.

    2003-01-01

    In FY01 we learned that hardware reliability models need substantial changes to account for differences in software, thus making software reliability measurements more effective, accurate, and easier to apply. These reliability models are generally based on familiar distributions or parametric methods. An obvious question is 'What new statistical and probability models can be developed using non-parametric and distribution-free methods instead of the traditional parametric method?" Two approaches to software reliability engineering appear somewhat promising. The first study, begin in FY01, is based in hardware reliability, a very well established science that has many aspects that can be applied to software. This research effort has investigated mathematical aspects of hardware reliability and has identified those applicable to software. Currently the research effort is applying and testing these approaches to software reliability measurement, These parametric models require much project data that may be difficult to apply and interpret. Projects at GSFC are often complex in both technology and schedules. Assessing and estimating reliability of the final system is extremely difficult when various subsystems are tested and completed long before others. Parametric and distribution free techniques may offer a new and accurate way of modeling failure time and other project data to provide earlier and more accurate estimates of system reliability.

  5. The LUCIFER control software

    NASA Astrophysics Data System (ADS)

    Jütte, Marcus; Knierim, Volker; Polsterer, Kai; Lehmitz, Michael; Storz, Clemens; Seifert, Walter; Ageorges, Nancy

    2010-07-01

    The successful roll-out of the control software for a complex NIR imager/spectrograph with MOS calls for flexible development strategies due to changing requirements during different phases of the project. A waterfall strategy used in the beginning has to change to a more iterative and agile process in the later stages. The choice of an appropriate program language as well as suitable software layout is crucial. For example the software has to accomplish multiple demands of different user groups, including a high level of flexibility for later changes and extensions. Different access levels to the instrument are mandatory to afford direct control mechanisms for lab operations and inspections of the instrument as well as tools to accomplish efficient science observations. Our hierarchical software structure with four layers of increasing abstract levels and the use of an object oriented language ideally supports these requirements. Here we describe our software architecture, the software development process, the different access levels and our commissioning experiences with LUCIFER 1.

  6. Star Wars software debate

    SciTech Connect

    Myers, W.

    1986-02-01

    David L. Parnas, Landsdowne Professor of Computer Science at the University of Victoria resigned from the SDI Organization's Panel on Computing in Support of Battle Management on June 28, 1985. Parnas, with 20 years of research on software engineering plus 8 years of work on military aircraft real-time software, says the software portion of SDI cannot be built error-free and he doesn't expect the next 20 years of research to change that fact. Since Parnas resigned, there have been several public debates on Star Wars software questions. In November 1985 the SDIO panel from which Parnas resigned released a draft of its report, reflecting its effort to critics of the project. While one might think that errors could be entirely eliminated with enough care and checking, most software professionals believe there will always be some residue of errors in a system of this size and complexity. The general line of the critics' argument is that the larger the amount of software in a single, unified system, the higher the percentage of errors it will contain. Proponents counter that the one very large system can be divided into a number of smaller, relatively independent pieces, thus reducing the proportionate number of errors in each separate piece. This approach is in turn countered by those who point to the intricate relations between these pieces, which themselves contribute to error.

  7. Software Process Assessment (SPA)

    NASA Technical Reports Server (NTRS)

    Rosenberg, Linda H.; Sheppard, Sylvia B.; Butler, Scott A.

    1994-01-01

    NASA's environment mirrors the changes taking place in the nation at large, i.e. workers are being asked to do more work with fewer resources. For software developers at NASA's Goddard Space Flight Center (GSFC), the effects of this change are that we must continue to produce quality code that is maintainable and reusable, but we must learn to produce it more efficiently and less expensively. To accomplish this goal, the Data Systems Technology Division (DSTD) at GSFC is trying a variety of both proven and state-of-the-art techniques for software development (e.g., object-oriented design, prototyping, designing for reuse, etc.). In order to evaluate the effectiveness of these techniques, the Software Process Assessment (SPA) program was initiated. SPA was begun under the assumption that the effects of different software development processes, techniques, and tools, on the resulting product must be evaluated in an objective manner in order to assess any benefits that may have accrued. SPA involves the collection and analysis of software product and process data. These data include metrics such as effort, code changes, size, complexity, and code readability. This paper describes the SPA data collection and analysis methodology and presents examples of benefits realized thus far by DSTD's software developers and managers.

  8. Software engineering

    NASA Technical Reports Server (NTRS)

    Fridge, Ernest M., III; Hiott, Jim; Golej, Jim; Plumb, Allan

    1993-01-01

    Today's software systems generally use obsolete technology, are not integrated properly with other software systems, and are difficult and costly to maintain. The discipline of reverse engineering is becoming prominent as organizations try to move their systems up to more modern and maintainable technology in a cost effective manner. The Johnson Space Center (JSC) created a significant set of tools to develop and maintain FORTRAN and C code during development of the space shuttle. This tool set forms the basis for an integrated environment to reengineer existing code into modern software engineering structures which are then easier and less costly to maintain and which allow a fairly straightforward translation into other target languages. The environment will support these structures and practices even in areas where the language definition and compilers do not enforce good software engineering. The knowledge and data captured using the reverse engineering tools is passed to standard forward engineering tools to redesign or perform major upgrades to software systems in a much more cost effective manner than using older technologies. The latest release of the environment was in Feb. 1992.

  9. Software reengineering

    NASA Technical Reports Server (NTRS)

    Fridge, Ernest M., III

    1991-01-01

    Today's software systems generally use obsolete technology, are not integrated properly with other software systems, and are difficult and costly to maintain. The discipline of reverse engineering is becoming prominent as organizations try to move their systems up to more modern and maintainable technology in a cost effective manner. JSC created a significant set of tools to develop and maintain FORTRAN and C code during development of the Space Shuttle. This tool set forms the basis for an integrated environment to re-engineer existing code into modern software engineering structures which are then easier and less costly to maintain and which allow a fairly straightforward translation into other target languages. The environment will support these structures and practices even in areas where the language definition and compilers do not enforce good software engineering. The knowledge and data captured using the reverse engineering tools is passed to standard forward engineering tools to redesign or perform major upgrades to software systems in a much more cost effective manner than using older technologies. A beta vision of the environment was released in Mar. 1991. The commercial potential for such re-engineering tools is very great. CASE TRENDS magazine reported it to be the primary concern of over four hundred of the top MIS executives.

  10. Automatic generation of conceptual database design tools from data model specifications

    SciTech Connect

    Hong, Shuguang.

    1989-01-01

    The problems faced in the design and implementation of database software systems based on object-oriented data models are similar to that of other software design, i.e., difficult, complex, yet redundant effort. Automatic generation of database software system has been proposed as a solution to the problems. In order to generate database software system for a variety of object-oriented data models, two critical issues: data model specification and software generation, must be addressed. SeaWeed is a software system that automatically generates conceptual database design tools from data model specifications. A meta model has been defined for the specification of a class of object-oriented data models. This meta model provides a set of primitive modeling constructs that can be used to express the semantics, or unique characteristics, of specific data models. Software reusability has been adopted for the software generation. The technique of design reuse is utilized to derive the requirement specification of the software to be generated from data model specifications. The mechanism of code reuse is used to produce the necessary reusable software components. This dissertation presents the research results of SeaWeed including the meta model, data model specification, a formal representation of design reuse and code reuse, and the software generation paradigm.

  11. Chemically-blocked Antibody Microarray for Multiplexed High-throughput Profiling of Specific Protein Glycosylation in Complex Samples

    PubMed Central

    Lu, Chen; Wonsidler, Joshua L.; Li, Jianwei; Du, Yanming; Block, Timothy; Haab, Brian; Chen, Songming

    2012-01-01

    In this study, we describe an effective protocol for use in a multiplexed high-throughput antibody microarray with glycan binding protein detection that allows for the glycosylation profiling of specific proteins. Glycosylation of proteins is the most prevalent post-translational modification found on proteins, and leads diversified modifications of the physical, chemical, and biological properties of proteins. Because the glycosylation machinery is particularly susceptible to disease progression and malignant transformation, aberrant glycosylation has been recognized as early detection biomarkers for cancer and other diseases. However, current methods to study protein glycosylation typically are too complicated or expensive for use in most normal laboratory or clinical settings and a more practical method to study protein glycosylation is needed. The new protocol described in this study makes use of a chemically blocked antibody microarray with glycan-binding protein (GBP) detection and significantly reduces the time, cost, and lab equipment requirements needed to study protein glycosylation. In this method, multiple immobilized glycoprotein-specific antibodies are printed directly onto the microarray slides and the N-glycans on the antibodies are blocked. The blocked, immobilized glycoprotein-specific antibodies are able to capture and isolate glycoproteins from a complex sample that is applied directly onto the microarray slides. Glycan detection then can be performed by the application of biotinylated lectins and other GBPs to the microarray slide, while binding levels can be determined using Dylight 549-Streptavidin. Through the use of an antibody panel and probing with multiple biotinylated lectins, this method allows for an effective glycosylation profile of the different proteins found in a given human or animal sample to be developed. Introduction Glycosylation of protein, which is the most ubiquitous post-translational modification on proteins, modifies

  12. Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer-specific bioluminescence resonance energy transfer-based sensors.

    PubMed

    Giner, Xavier C; Cotnoir-White, David; Mader, Sylvie; Lévesque, Daniel

    2015-10-01

    Retinoid X receptors (RXRs) play a role as master regulators because of their capacity to form heterodimers with other nuclear receptors (NRs). Accordingly, retinoid signaling is involved in multiple biologic processes, including development, cell differentiation, metabolism, and cell death. However, the role and function of RXRs in different heterodimer complexes remain unidentified, mainly because most RXR drugs (called rexinoids) are not selective of specific heterodimer complexes. The lack of selectivity strongly limits the use of rexinoids for specific therapeutic approaches. To better characterize rexinoids at specific NR complexes, we have developed and optimized luciferase (Luc) protein complementation(PCA)-based bioluminescence resonance energy transfer (BRET) assays that can directly measure recruitment of a coactivator (CoA) motif fused to yellow fluorescent protein (YFP) by specific NR dimers. To validate the assays, we compared rexinoid modulation of CoA recruitment by the RXR homodimer and by the heterodimers Nur77/RXR and Nurr1/RXR. Results revealed that some rexinoids display selective CoA recruitment activities with homo- or heterodimer complexes. In particular, SR11237 (BMS649) has stronger potency for recruitment of CoA motif and transcriptional activity with the heterodimer Nur77/RXR than other complexes. This technology should be useful in identifying new compounds with specificity for individual dimeric species formed by NRs. PMID:26148973

  13. Antiterrorist Software

    NASA Technical Reports Server (NTRS)

    Clark, David A.

    1998-01-01

    In light of the escalation of terrorism, the Department of Defense spearheaded the development of new antiterrorist software for all Government agencies by issuing a Broad Agency Announcement to solicit proposals. This Government-wide competition resulted in a team that includes NASA Lewis Research Center's Computer Services Division, who will develop the graphical user interface (GUI) and test it in their usability lab. The team launched a program entitled Joint Sphere of Security (JSOS), crafted a design architecture (see the following figure), and is testing the interface. This software system has a state-ofthe- art, object-oriented architecture, with a main kernel composed of the Dynamic Information Architecture System (DIAS) developed by Argonne National Laboratory. DIAS will be used as the software "breadboard" for assembling the components of explosions, such as blast and collapse simulations.

  14. A Specific Form of Phospho Protein Phosphatase 2 Regulates Anaphase-promoting Complex/Cyclosome Association with Spindle Poles

    PubMed Central

    Ban, Kenneth H.

    2010-01-01

    In early mitosis, the END (Emi1/NuMA/Dynein-dynactin) network anchors the anaphase-promoting complex/cyclosome (APC/C) to the mitotic spindle and poles. Spindle anchoring restricts APC/C activity, thereby limiting the destruction of spindle-associated cyclin B and ensuring maintenance of spindle integrity. Emi1 binds directly to hypophosphorylated APC/C, linking the APC/C to the spindle via NuMA. However, whether the phosphorylation state of the APC/C is important for its association with the spindle and what kinases and phosphatases are necessary for regulating this event remain unknown. Here, we describe the regulation of APC/C-mitotic spindle pole association by phosphorylation. We find that only hypophosphorylated APC/C associates with microtubule asters, suggesting that phosphatases are important. Indeed, a specific form of PPP2 (CA/R1A/R2B) binds APC/C, and PPP2 activity is necessary for Cdc27 dephosphorylation. Screening by RNA interference, we find that inactivation of CA, R1A, or R2B leads to delocalization of APC/C from spindle poles, early mitotic spindle defects, a failure to congress chromosomes, and decreased levels of cyclin B on the spindle. Consistently, inhibition of cyclin B/Cdk1 activity increased APC/C binding to microtubules. Thus, cyclin B/Cdk1 and PPP2 regulate the dynamic association of APC/C with spindle poles in early mitosis, a step necessary for proper spindle formation. PMID:20089842

  15. Human-specific evolution of killer cell immunoglobulin-like receptor recognition of major histocompatibility complex class I molecules.

    PubMed

    Parham, Peter; Norman, Paul J; Abi-Rached, Laurent; Guethlein, Lisbeth A

    2012-03-19

    In placental mammals, natural killer (NK) cells are a population of lymphocytes that make unique contributions to immune defence and reproduction, functions essential for survival of individuals, populations and species. Modulating these functions are conserved and variable NK-cell receptors that recognize epitopes of major histocompatibility complex (MHC) class I molecules. In humans, for example, recognition of human leucocyte antigen (HLA)-E by the CD94:NKG2A receptor is conserved, whereas recognition of HLA-A, B and C by the killer cell immunoglobulin-like receptors (KIRs) is diversified. Competing demands of the immune and reproductive systems, and of T-cell and NK-cell immunity-combined with the segregation on different chromosomes of variable NK-cell receptors and their MHC class I ligands-drive an unusually rapid evolution that has resulted in unprecedented levels of species specificity, as first appreciated from comparison of mice and humans. Counterparts to human KIR are present only in simian primates. Observed in these species is the coevolution of KIR and the four MHC class I epitopes to which human KIR recognition is restricted. Unique to hominids is the emergence of the MHC-C locus as a supplier of specialized and superior ligands for KIR. This evolutionary trend is most highly elaborated in the chimpanzee. Unique to the human KIR locus are two groups of KIR haplotypes that are present in all human populations and subject to balancing selection. Group A KIR haplotypes resemble chimpanzee KIR haplotypes and are enriched for genes encoding KIR that bind HLA class I, whereas group B KIR haplotypes are enriched for genes encoding receptors with diminished capacity to bind HLA class I. Correlating with their balance in human populations, B haplotypes favour reproductive success, whereas A haplotypes favour successful immune defence. Evolution of the B KIR haplotypes is thus unique to the human species. PMID:22312047

  16. Iterative software kernels

    SciTech Connect

    Duff, I.

    1994-12-31

    This workshop focuses on kernels for iterative software packages. Specifically, the three speakers discuss various aspects of sparse BLAS kernels. Their topics are: `Current status of user lever sparse BLAS`; Current status of the sparse BLAS toolkit`; and `Adding matrix-matrix and matrix-matrix-matrix multiply to the sparse BLAS toolkit`.

  17. High-resolution structure of HLA-A*0201 in complex with a tumour-specific antigenic peptide encoded by the MAGE-A4 gene.

    PubMed

    Hillig, R C; Coulie, P G; Stroobant, V; Saenger, W; Ziegler, A; Hülsmeyer, M

    2001-07-27

    The heterotrimeric complex of the human major histocompatibity complex (MHC) molecule HLA-A*0201, beta2-microglobulin and the decameric peptide GVYDGREHTV derived from the melanoma antigen (MAGE-A4 protein has been determined by X-ray crystallography at 1.4 A resolution. MAGE-A4 belongs to a family of genes that are specifically expressed in a variety of tumours. MAGE-A4-derived peptides are presented by MHC molecules at the cell surface to cytotoxic T-lymphocytes. As the HLA-A*0201:MAGE-A4 complex occurs only on tumour cells, it is considered to be an appropriate target for immunotherapy. The structure presented here reveals potential epitopes specific to the complex and indicates which peptide residues could be recognised by T-cell receptors. In addition, as the structure could be refined anisotropically, it was possible to describe the movements of the bound peptide in more detail. PMID:11502003

  18. An expert system based software sizing tool, phase 2

    NASA Technical Reports Server (NTRS)

    Friedlander, David

    1990-01-01

    A software tool was developed for predicting the size of a future computer program at an early stage in its development. The system is intended to enable a user who is not expert in Software Engineering to estimate software size in lines of source code with an accuracy similar to that of an expert, based on the program's functional specifications. The project was planned as a knowledge based system with a field prototype as the goal of Phase 2 and a commercial system planned for Phase 3. The researchers used techniques from Artificial Intelligence and knowledge from human experts and existing software from NASA's COSMIC database. They devised a classification scheme for the software specifications, and a small set of generic software components that represent complexity and apply to large classes of programs. The specifications are converted to generic components by a set of rules and the generic components are input to a nonlinear sizing function which makes the final prediction. The system developed for this project predicted code sizes from the database with a bias factor of 1.06 and a fluctuation factor of 1.77, an accuracy similar to that of human experts but without their significant optimistic bias.

  19. SAR Product Control Software

    NASA Astrophysics Data System (ADS)

    Meadows, P. J.; Hounam, D.; Rye, A. J.; Rosich, B.; Börner, T.; Closa, J.; Schättler, B.; Smith, P. J.; Zink, M.

    2003-03-01

    As SAR instruments and their operating modes become more complex, as new applications place more and more demands on image quality and as our understanding of their imperfections becomes more sophisticated, there is increasing recognition that SAR data quality has to be controlled more completely to keep pace. The SAR product CONtrol software (SARCON) is a comprehensive SAR product control software suite tailored to the latest generation of SAR sensors. SARCON profits from the most up-to-date thinking on SAR image performance derived from other spaceborne and airborne SAR projects and is based on the newest applications. This paper gives an overview of the structure and the features of this new software tool, which is a product of a co-operation between teams at BAE SYSTEMS Advanced Technology Centre and DLR under contract to ESA (ESRIN). Work on SARCON began in 1999 and is continuing.

  20. Software Reviews.

    ERIC Educational Resources Information Center

    Classroom Computer Learning, 1990

    1990-01-01

    Reviewed are two computer software packages: "Super Solvers Midnight Rescue!" a problem-solving program for IBM PCs; and "Interactive Physics," a simulation program for the Macintosh computer. The functions of the package are discussed including strengths and weaknesses and teaching suggestions. (CW)