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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

    ... National Standards Institute and Institute of Electrical and Electronics Engineers (ANSI/IEEE) Standard 830-1998, ``IEEE Recommended Practice for Software Requirements Specifications.'' DATES: Submit comments by... Systems Of Nuclear Power Plants,'' dated September 1997. This RG endorses IEEE Standard 830-1998 with...

  2. Specifications for Thesaurus Software.

    ERIC Educational Resources Information Center

    Milstead, Jessica L.

    1991-01-01

    Presents specifications for software that is designed to support manual development and maintenance of information retrieval thesauri. Evaluation of existing software and design of custom software is discussed, requirements for integration with larger systems and for the user interface are described, and relationships among terms are discussed.…

  3. Complexity, Systems, and Software

    DTIC Science & Technology

    2014-08-14

    2014 Carnegie Mellon University Complexity, Systems, and Software Software Engineering Institute Carnegie Mellon University Pittsburgh, PA...NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Software Engineering Institute Carnegie Mellon University Pittsburgh, PA 15213 8...for the operation of the Software Engineering Institute, a federally funded research and development center sponsored by the United States

  4. Modeling complex workflow in molecular diagnostics: design specifications of laboratory software for support of personalized medicine.

    PubMed

    Gomah, Mohamed E; Turley, James P; Lu, Huimin; Jones, Dan

    2010-01-01

    One of the hurdles to achieving personalized medicine has been implementing the laboratory processes for performing and reporting complex molecular tests. The rapidly changing test rosters and complex analysis platforms in molecular diagnostics have meant that many clinical laboratories still use labor-intensive manual processing and testing without the level of automation seen in high-volume chemistry and hematology testing. We provide here a discussion of design requirements and the results of implementation of a suite of lab management tools that incorporate the many elements required for use of molecular diagnostics in personalized medicine, particularly in cancer. These applications provide the functionality required for sample accessioning and tracking, material generation, and testing that are particular to the evolving needs of individualized molecular diagnostics. On implementation, the applications described here resulted in improvements in the turn-around time for reporting of more complex molecular test sets, and significant changes in the workflow. Therefore, careful mapping of workflow can permit design of software applications that simplify even the complex demands of specialized molecular testing. By incorporating design features for order review, software tools can permit a more personalized approach to sample handling and test selection without compromising efficiency.

  5. 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.

  6. Classification of Software Projects' Complexity

    NASA Astrophysics Data System (ADS)

    Fitsilis, P.; Kameas, A.; Anthopoulos, L.

    Software project complexity is a subject that has not received detailed attention. The purpose of this chapter is to present a systematic way for studying and modeling software project complexity. The proposed model is based on the widely known and accepted Project Management Body of Knowledge and it uses a typology for modeling complexity based on complexity of faith, fact, and interaction.

  7. 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.

  8. 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.

  9. RMACS software requirements specification

    SciTech Connect

    Gneiting, B.C.

    1996-10-01

    This document defines the essential user (or functional) requirements of the Requirements Management and Assured Compliance System (RMACS), which is used by the Tank Waste Remediation System program (TWRS). RMACS provides a computer-based environment that TWRS management and systems engineers can use to identify, define, and document requirements. The intent of the system is to manage information supporting definition of the TWRS technical baseline using a structured systems engineering process. RMACS has the capability to effectively manage a complete set of complex requirements and relationships in a manner that satisfactorily assures compliance to the program requirements over the TWRS life-cycle.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Specification Matching of Software Components.

    DTIC Science & Technology

    1995-03-01

    Information Retrieval . McGraw-Hill, 1983. [VLP94] Mary Vernon, Edward Lazowsk, and Stewart Personick, editors. R&D for the Nil: Technical...Signature matching for Ada software reuse. Master’s thesis, University of York, 1994. [SM83] G. Salton and M. J. McGill. Introduction to Modern

  15. 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.

  16. 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

  17. 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.

  18. Formal specification and verification of Ada software

    NASA Technical Reports Server (NTRS)

    Hird, Geoffrey R.

    1991-01-01

    The use of formal methods in software development achieves levels of quality assurance unobtainable by other means. The Larch approach to specification is described, and the specification of avionics software designed to implement the logic of a flight control system is given as an example. Penelope is described which is an Ada-verification environment. The Penelope user inputs mathematical definitions, Larch-style specifications and Ada code and performs machine-assisted proofs that the code obeys its specifications. As an example, the verification of a binary search function is considered. Emphasis is given to techniques assisting the reuse of a verification effort on modified code.

  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. 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.

  1. 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.

  2. In Situ Vitrification software requirements specification

    SciTech Connect

    Grush, W.H.; Marwil, E.S.

    1990-09-01

    This report describes the Software Requirements Specification for the Electrical Resistance Heating and Thermal Energy Transport models of the In-Situ Vitrification (ISV) process. It contains the Data Flow Diagrams, Process Specifications, Data Structure Diagrams, and the Data Dictionary. 5 refs.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

    ... 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 Safety... well as the software elements of those systems. This RG is one of six RG revisions addressing computer...

  17. Metadata specification in a dynamic geometry software

    NASA Astrophysics Data System (ADS)

    Radaković, Davorka; Herceg, Äńorde

    2017-07-01

    Attributes in C# are a mechanism that provides association of declarative information with C# code such as classes, types, methods, properties, namespaces etc. Once defined and associated with a program entity, an attribute can be queried at run time. However, the attributes have certain restrictions which limit their application to representing complex metadata necessary for development of dynamic geometry software (DGS). We have devised a solution, independent of attributes, which was developed to overcome the limitations, while maintaining the functionality of attributes. Our solution covers a wide range of uses, from providing extensibility to a functional programming language and declaring new data types and operations, to being a foundation for runtime optimizations of expression tree evaluation, and helpful user interface features, such as code completion.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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).

  4. Software Requirements Specifications of a Proposed Plant Property Management System.

    DTIC Science & Technology

    1983-06-01

    RD-li32 176 SOFTWARE REQUIREMENTS SPECIFICATIONS OF R PROPOSED 1/2 PLANT PROPERTY MANAGEMENT SYSTEM(U) NAVAL POSTGRRDUATE SCHOOL MONTEREY CA E J...1983J THESIS SOFTWARE REQUIREMENTS SPECIFICATIONS OF A PROPOSED PLANT PROPERTY MANAGEMENT SY’STEM by Edward J. Buselt June 1983 C)Thesis Advisor: R.W...Subtitle) s. TYPE OF REPORT & PERIOD COVERED Software Requirements Specifications Master’s Thesis; of a (June 1983) * Proposed Plant Property Management

  5. 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.

  6. 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.

  7. 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.

  8. 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…

  9. 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…

  10. 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.

  11. The Domain-Specific Software Architecture Program

    DTIC Science & Technology

    1992-06-01

    Department of Electrical Engineering and Computer Science MIT Cambridge, MA DAM @WHEATIES.AI.MIT.EDUMIT Rick Selby and Richard Taylor Department of Computer...situation assessment ([Lesser 80], [Steeb 81]). Intelligent control has been a focus of investigations in both manufacturing ([Murdock 90], [ Pardee 90...Assn. ( Pardee 90] Pardee , W.J., Shaff, M.A., and Hayes-Roth, B. "Intelligent control of complex materials processes", Artificial Intelligence in

  12. 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…

  13. 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.

  14. 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.

  15. Investigation of specification measures for the Software Engineering Laboratory (SEL)

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Requirements specification measures are investigated for potential application in the Software Engineering Laboratory. Eighty-seven candidate measures are defined; sixteen are recommended for use. Most measures are derived from a new representation, the Composite Specification Model, which is introduced. The results of extracting the specification measures from the requirements of a real system are described.

  16. 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.

  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. Software Requirements Specification for Lunar IceCube

    NASA Astrophysics Data System (ADS)

    Glaser-Garbrick, Michael R.

    Lunar IceCube is a 6U satellite that will orbit the moon to measure water volatiles as a function of position, altitude, and time, and measure in its various phases. Lunar IceCube, is a collaboration between Morehead State University, Vermont Technical University, Busek, and NASA. The Software Requirements Specification will serve as contract between the overall team and the developers of the flight software. It will provide a system's overview of the software that will be developed for Lunar IceCube, in that it will detail all of the interconnects and protocols for each subsystem's that Lunar IceCube will utilize. The flight software will be written in SPARK to the fullest extent, due to SPARK's unique ability to make software free of any errors. The LIC flight software does make use of a general purpose, reusable application framework called CubedOS. This framework imposes some structuring requirements on the architecture and design of the flight software, but it does not impose any high level requirements. It will also detail the tools that we will be using for Lunar IceCube, such as why we will be utilizing VxWorks.

  19. 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.

  20. 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.

  1. Complexity for artificial substrates (CASU): software for creating and visualising habitat complexity.

    PubMed

    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.

  2. 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

  3. 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.

  4. 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.

  5. Reusable Software Component Retrieval via Normalized Algebraic Specifications

    DTIC Science & Technology

    1991-12-01

    SOFTWARE COMPONENT RETRIEVAL VIA NORMALUZED ALGEBRAIC SPECIFICATIONS by Robert Allen Steigerwald Captain , United States Air Force B.S., United States...requirements. Aooession For NTIS GRA&I DTIC TAB 0 Unannounced fl Justifitatio By Avat lability Codes avail ead/or DLllt |Speblal iii TABLE OF CONTENTS

  6. 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.

  7. Lysine-specific chemical cross-linking of protein complexes and identification of cross-linking sites using LC-MS/MS and the xQuest/xProphet software pipeline.

    PubMed

    Leitner, Alexander; Walzthoeni, Thomas; Aebersold, Ruedi

    2014-01-01

    Chemical cross-linking in combination with LC-MS/MS (XL-MS) is an emerging technology to obtain low-resolution structural (distance) restraints of proteins and protein complexes. These restraints can also be used to characterize protein complexes by integrative modeling of the XL-MS data, either in combination with other types of structural information or by themselves, to establish spatial relationships of subunits in protein complexes. Here we present a protocol that has been successfully used to generate XL-MS data from a multitude of native proteins and protein complexes. It includes the experimental steps for performing the cross-linking reaction using disuccinimidyl suberate (a homobifunctional, lysine-reactive cross-linking reagent), the enrichment of cross-linked peptides by peptide size-exclusion chromatography (SEC; to remove smaller, non-cross-linked peptides), instructions for tandem MS analysis and the analysis of MS data via the open-source computational software pipeline xQuest and xProphet (available from http://proteomics.ethz.ch). Once established, this robust protocol should take ∼4 d to complete, and it is generally applicable to purified proteins and protein complexes.

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

    SciTech Connect

    Twitchell, Kevin 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.

  9. 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.

  10. 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.

  11. Managing Scientific Software Complexity with Bocca and CCA

    DOE PAGES

    Allan, Benjamin A.; Norris, Boyana; Elwasif, Wael R.; ...

    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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Reproducibility of BMD measurements in the prosthetic knee comparing knee-specific software to traditional DXA software: a clinical validation.

    PubMed

    Tjørnild, Michael; Søballe, Kjeld; Bender, Thomas; Stilling, Maiken

    2011-01-01

    The aim of this study was to validate new knee-specific dual X-ray absorptiometry (DXA) software for cemented total knee arthroplasty (TKA) before initiation of a randomized controlled trial. Firstly, in a phantom study, we evaluated if cementation influenced the measured BMD (g/cm²), the scan reproducibility with the new knee-specific software, and the consequences of leg rotation around a vertical axis. Secondly, in a clinical study, we assessed the clinical reproducibility in repetitive scans performed with the new knee-specific software and with traditional spine-mode DXA software, and further compared the 2 softwares' ability to point type implant and bone edges correctly. Cementation increased the measured bone mineral density (BMD) (p < 0.01). For reproducibility, the coefficient of variation (CV) was 0.52-0.70% in vitro. Leg rotation around a vertical axis significantly changed the measured BMD in most scans. Automatic point typing of implant and bone edge was of varying quality with frequent need of manual correction for both softwares. CVs of clinical reproducibility ranged from 2.78% to 6.19% for knee-specific software and from 1.45% to 6.06% for spine-mode software. We found the new knee-specific software valid for BMD measurement of the bone in proximity of cemented TKA and with clinical reproducibility and corrections of point typing similar to traditional spine-mode software. Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  19. 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.

  20. Revisiting software specification and design for large astronomy projects

    NASA Astrophysics Data System (ADS)

    Wiant, Scott; Berukoff, Steven

    2016-07-01

    The separation of science and engineering in the delivery of software systems overlooks the true nature of the problem being solved and the organization that will solve it. Use of a systems engineering approach to managing the requirements flow between these two groups as between a customer and contractor has been used with varying degrees of success by well-known entities such as the U.S. Department of Defense. However, treating science as the customer and engineering as the contractor fosters unfavorable consequences that can be avoided and opportunities that are missed. For example, the "problem" being solved is only partially specified through the requirements generation process since it focuses on detailed specification guiding the parties to a technical solution. Equally important is the portion of the problem that will be solved through the definition of processes and staff interacting through them. This interchange between people and processes is often underrepresented and under appreciated. By concentrating on the full problem and collaborating on a strategy for its solution a science-implementing organization can realize the benefits of driving towards common goals (not just requirements) and a cohesive solution to the entire problem. The initial phase of any project when well executed is often the most difficult yet most critical and thus it is essential to employ a methodology that reinforces collaboration and leverages the full suite of capabilities within the team. This paper describes an integrated approach to specifying the needs induced by a problem and the design of its solution.

  1. 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.

  2. MOVIE - A Software Environment For Modeling Complex Adaptive Systems

    NASA Astrophysics Data System (ADS)

    Furmanski, Wojtek; Fox, Geoffrey J.

    1990-02-01

    We discuss here the basic elements of the new software system for large scale computation -MOVIE- (Metashell based Object oriented Visual Interactive Environment), recently designed and implemented at Caltech within the Caltech Concurrent Computation Program. From the research perspective, the goal of the MOVIE project is to create a simulation environment for modeling complex systems, with the focus on computational structures capable to adapt and act "intelligently", such as ensembles of image processing, early vision, neural network and Artificial Intelligence modules, integrated in the form of "neural robots". The high level MOVIE model, based on portable communication and computation protocol is suitable for large scale "intelligence engineering" by modeling such systems in distributed heterogeneous multicomputer environment and porting successful implementations to dedicated massively parallel hardware. From the software engineering point of view, the MOVIE model offers a platform for unifying elements of contemporary computing such as networking, windowing, parallelism, number crunching and symbolic processing. The basic idea, borrowed from Sun NeWS, is to use an appropriately extended PostScript as the unifying language. The MOVIE extension aims at promoting PostScript to a general purpose high level object oriented language with a high performance user expandable computational sector, fully compatible with the Adobe model for 2D graphics and the Sun X11 /NeWS model for windowing and multitasking.

  3. 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

    ... HUMAN SERVICES Agency for Healthcare Research and Quality Meeting for Software Developers on the... interactive forum where PSOs and software developers can provide input on these technical specifications. AHRQ... clinical meaning. The technical specifications also provide direction to software developers, so that...

  4. 76 FR 16785 - Meeting for Software Developers on the Technical Specifications for Common Formats for Patient...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-25

    ... HUMAN SERVICES Agency for Healthcare Research and Quality Meeting for Software Developers on the... where PSOs and software developers can provide input on these technical ] specifications for the Common... specifications for software developers. As an update to this release, AHRQ developed the beta version of an...

  5. 78 FR 12063 - Meeting for Software Developers on the Technical Specifications for Common Formats for Patient...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-21

    ... HUMAN SERVICES Agency for Healthcare Research and Quality Meeting for Software Developers on the... interactive forum where PSOs and software developers can provide input on these technical specifications. AHRQ... clinical meaning. The technical specifications also provide direction to software developers, so that...

  6. The 3-D General Geometry PIC Software for Distributed Memory MIMD Computers; EM Software Specification

    DTIC Science & Technology

    1994-09-01

    GENERAL GEOMETRY PIC SOFTWARE FOR DISTRIBUTED MEMORY MIMD COMPUTERS : TASK 1 FINAL REPORT J W Eastwood, W... GENERAL GEOMETRY PIC SOFTWARE FOR DISTRIBUTED MEMORY MIMD COMPUTERS : TASK 1 FINAL REPORT J W Eastwood, W Arter, N J Brealey, R W Hockney September 1994... General geometry PIC for MIMD computers : Final report . Report RFFX(93)56,

  7. Towards an integration of software-ergonomic aspects in formal specifications of graphical user interfaces

    SciTech Connect

    Sucrow, B.E.

    1996-12-31

    Well functioning graphical user interfaces today represent an important part of every interactive system. However, achieving a really good graphical user interface involves quite complex tasks. One of the most important points is to think about the requirements how the interface has to appear and how to behave. Due to the importance of user-friendliness of graphical user interfaces and easy-to-use interfaces these requirements highly concern software-ergonomic aspects, and are mostly non-functional. Thus, the design of a graphical user interface has to arise in an application specific and as well as for the user comfortable manner. In this paper we will investigate how such software-ergonomic aspects can be integrated in the specification process of graphical user interfaces. More precisely, we consider, how the process of specifying software-ergonomic features of graphical user interfaces can be carried out continuously within a constructive interplay between the requirements stage and the design stage. This continuity can be achieved by using a flexible and powerful specification method. We use graph grammars as a means to specify intuitively and at the same time formally as well.

  8. 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…

  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. 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.

  11. 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…

  12. 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…

  13. 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.

  14. 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…

  15. Specification of Software Quality Attributes. Volume 3. Software Quality Evaluation Guidebook

    DTIC Science & Technology

    1985-02-01

    of Defense software quality standard ESD Electronic Systems Division FCA functional configuration audit FSD full-scale development HOL high order...device errors? _NN/A_ AM.6(l) Are there requirements for recovery from all communication transmission errors? FN7 N/A AM.7(I) Are there requirements

  16. Specification of Software Quality Attributes. Volume 1. Final Report.

    DTIC Science & Technology

    1985-02-01

    of Defense software quality standard DRC Dynamics Research Corporation ESD Electronic Systems Division FCA functional configuration audit FSD full...part of the STARS measurement DIDs and being prepared by Dynamics Research Corporation 1-7 ........................... -. aA.A.&..,.°AA.. ~. .... SYSTEM...ACCURACY AC x c ANOMALY MANAIEVIENT AM x x * R AUTONOMY ALIU F ,S-R;BuTE0NESS DI x EP-ECTIVENESS COMMUNICATON E: x MY EFFECTIVE NESS -PROCESSNG ED x A

  17. 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.

  18. 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).

  19. 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).

  20. 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.

  1. Practical Issues in Having a Usable Library of Software Specifications.

    DTIC Science & Technology

    1981-03-01

    Peter Wegner, Jack Dennis , Michael Hammer, and DanielTichrnew (eds.), 1977. Lisknv, B. H. and S. N. Zilles , "Specification Techniques for Data...specifications for others to use in their system design. j , UNCLASSIFIED SgCURITY CLASSIFICATION OF , & G (WhOn Data E*1oo) d’ ’ -*.--;’ Abstract Though...it deemed correct? Liskov and Zilles (1975) views the specification process as a translation from the concept in someone’s mind of what a module should

  2. 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.

  3. Specification and Verification of Secure Concurrent and Distributed Software Systems

    DTIC Science & Technology

    1992-02-01

    143 6.1.2 General Observations ...... ............................... 144 6.2 An OBJ3 Specification of A Simple Operating...their obsevable behavior. Here, observable behavior means operations that. permit one object to be distinguished from another. Furthermore, the...Lisp pro- grams that exercise specifications. Additionally, FASE allows the user to move between specifica- tions and implementations, thus

  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. Automatic derivation of formal software specifications from informal descriptions

    NASA Technical Reports Server (NTRS)

    Miriyala, Kanth; Harandi, Mehdi T.

    1991-01-01

    SPECIFIER, an interactive system which derives formal specifications of data types and programs from their informal descriptions, is described. The process of deriving formal specifications is viewed as a problem-solving process. The system uses common problem-solving techniques such as schemas, analogy, and difference-based reasoning to derive formal specifications. If an informal description is a commonly occurring operation for which the system has a schema, then the formal specification is derived by instantiating the schema. If there is no such schema, SPECIFIER tries to find a previously solved problem which is analogous to the current problem. If the problem found is directly analogous to the current problem, it applies an analogy mapping to obtain a formal specification. On the other hand, if the analogy found is only approximate, it solves the directly analogous part of the problem by analogy and performs difference-based reasoning using the remaining (unmatched) parts to transform the formal specification obtained by analogy to a formal specification for the entire original problem.

  6. 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.

  7. CT-based patient-specific simulation software for pedicle screw insertion.

    PubMed

    Klein, Shawn; Whyne, Cari M; Rush, Raphael; Ginsberg, Howard J

    2009-10-01

    Development of a 3-dimensional, patient-specific simulator for pedicle screw insertion. To allow the user to practice the insertion of pedicle screws into a 3-dimensional model of a patient-specific spine, and have both visual and quantitative feedback provided to the user. The goal is to better prepare surgeons to perform pedicle screw insertion surgery and help reduce the risk of pedicle screw misplacement. Pedicle screw insertion is particularly challenging to carry out on patients with abnormal spine morphology. Currently, preoperative planning for pedicle screw insertion is carried out using patient computed tomography and magnetic resonance imaging scans. In addition, once screws are inserted, there are no quantitative metrics against which to measure the results. The simulator was developed in the TCL scripting language as a graphical plug-in for the commercial visualization software AmiraDev 3.11. Surgical simulation uses a 3-dimensional model of patient's spine developed from the patient's computed tomography scan. Pedicle screw insertion can be practiced using pedicle screws of various sizes and analyzed in both 2-dimension and 3-dimension. Quantitative feedback is provided to the user in the form of anatomic lengths and angles, relative purchase of inserted screws, and a screw placement grading system. The software allows the user to adjust the translucency of a patient's spine to develop a better sense of the trajectories and depths involved with performing pedicle screw insertion on a patient. The simulator offers many helpful features to the surgeon with respect to complex cases and to the surgical trainee learning the basic technique of pedicle screw insertion. A study is currently underway to evaluate the efficacy of the simulator as a teaching tool for surgical trainees in placing pedicle screws. Future work will focus on the transfer of the software to a stand-alone platform.

  8. LLNL Site Specific ASCI Software Quality Engineering Recommended Practices Overview Version 1.0

    SciTech Connect

    Peck, T; Sparkman, D; Storch, N

    2002-02-01

    ''The LLNL Site-Specific Advanced Simulation and Computing (ASCI) Software Quality Engineering Recommended Practices VI.I'' document describes a set of recommended software quality engineering (SQE) practices for ASCI code projects at Lawrence Livermore National Laboratory (LLNL). In this context, SQE is defined as the process of building quality into software products by applying the appropriate guiding principles and management practices. Continual code improvement and ongoing process improvement are expected benefits. Certain practices are recommended, although projects may select the specific activities they wish to improve, and the appropriate time lines for such actions. Additionally, projects can rely on the guidance of this document when generating ASCI Verification and Validation (VSrV) deliverables. ASCI program managers will gather information about their software engineering practices and improvement. This information can be shared to leverage the best SQE practices among development organizations. It will further be used to ensure the currency and vitality of the recommended practices. This Overview is intended to provide basic information to the LLNL ASCI software management and development staff from the ''LLNL Site-Specific ASCI Software Quality Engineering Recommended Practices VI.I'' document. Additionally the Overview provides steps to using the ''LLNL Site-Specific ASCI Software Quality Engineering Recommended Practices VI.I'' document. For definitions of terminology and acronyms, refer to the Glossary and Acronyms sections in the ''LLNL Site-Specific ASCI Software Quality Engineering Recommended Practices VI.I''.

  9. Specification Improvement Through Analysis of Proof Structure (SITAPS): High Assurance Software Development

    DTIC Science & Technology

    2016-02-01

    SPECIFICATION IMPROVEMENT THROUGH ANALYSIS OF PROOF STRUCTURE (SITAPS): HIGH ASSURANCE SOFTWARE DEVELOPMENT BAE SYSTEMS FEBRUARY...ANALYSIS OF PROOF STRUCTURE (SITAPS): HIGH ASSURANCE SOFTWARE DEVELOPMENT 5a. CONTRACT NUMBER FA8750-13-C-0240 5b. GRANT NUMBER N/A 5c. PROGRAM...Release; Distribution Unlimited. PA# 88ABW-2016-0232 Date Cleared: 22 JAN 2016 13. SUPPLEMENTARY NOTES 14. ABSTRACT Formal software verification

  10. Airborne Systems Software Acquisition Engineering Guidebook for Requirements Analysis and Specification.

    DTIC Science & Technology

    1978-09-01

    documented in the pre- liminary system specification. This guidebook does not, however, describe how to produce a complete Computer Program Part I... Part I Development Specification. Software testing is discussed in the SAE Guidebook for Software Quality Assurance and in the SAE Guidebook for...Verification, Validation, and Certification. This guidebook does address -1- all the requirements that would appear in Section 3 of a Part I specification

  11. 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.

  12. 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

    ... HUMAN SERVICES Agency for Healthcare Research and Quality Meeting for Software Developers on the... comparable. This meeting is designed as an interactive forum where PSOs and software developers can provide... presentation and discussion of these new technical specifications, which provide direction to...

  13. Instrument-specific features within the observation preparation software for LINC-NIRVANA

    NASA Astrophysics Data System (ADS)

    Pavlov, Alexey; Trowitzsch, Jan

    2010-07-01

    The LINC-NIRVANA (LN) Observation Preparation Software (LOPS) supports an observer during the complex process of preparing the observations for LINC-NIRVANA (LN). LN is a German-Italian beam combiner for the Large Binocular Telescope. The instrument exploits its full capability by means of Multi-Conjugated Adaptive Optics and an IR Fringe and Flexure Tracker. These sub-systems of the LN instrument and the fixed geometry of the telescope put specific constraints on the observation and scheduling process. LOPS is committed to a generic approach which allows to easily include new features on the so called procedure-plug-in level (low level). Considering specific aspects of the LN instrument the implementation on the generic procedure level is not adequate enough, because an user/observer needs to deal with a lot of instrument-specific parameters when preparing an observation program (OP). For this reason, LOPS provides a high-level application plug-in system which allows to maintain the features of an OP also as separate application in order to benefit from the more advanced GUI. In this paper we present the Guide Star Buffer concept as an exemplary feature-specific application in the framework of LOPS. It is dedicated to search, select and organize guide stars in the corresponding groups needed for LN observations.

  14. 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.

  15. 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

  16. 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.

  17. Evaluating the Software Design of a Complex System of Systems

    DTIC Science & Technology

    2010-01-01

    Architecture ( LCA ) milestone conducted at the SoS level might be the answer. According to the Rational Unified Process, the LCA marks the conclusion of...an SoS is not merely a roll-up of its constituent systems, so it is that an SoS- level LCA is more than a roll-up of lower level LCA anchor points. A...for individual software packages and another for integrated builds. Although LCAs were conducted regularly at constituent systems levels , the focus

  18. Software.

    ERIC Educational Resources Information Center

    Journal of Chemical Education, 1989

    1989-01-01

    Presented are reviews of two computer software packages for Apple II computers; "Organic Spectroscopy," and "Videodisc Display Program" for use with "The Periodic Table Videodisc." A sample spectrograph from "Organic Spectroscopy" is included. (CW)

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.'

  7. 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.

  8. A Software Framework for the Analysis of Complex Microscopy Image Data

    PubMed Central

    Chao, Jerry; Ward, E. Sally

    2012-01-01

    Technological advances in both hardware and software have made possible the realization of sophisticated biological imaging experiments using the optical microscope. As a result, modern microscopy experiments are capable of producing complex image data sets. For a given data analysis task, the images in a set are arranged, based on the requirements of the task, by attributes such as the time and focus levels at which they were acquired. Importantly, different tasks performed over the course of an analysis are often facilitated by the use of different arrangements of the images. We present a software framework which supports the use of different logical image arrangements to analyze a physical set of images. Called the Microscopy Image Analysis Tool (MIATool), this framework realizes the logical arrangements using arrays of pointers to the images, thereby removing the need to replicate and manipulate the actual images in their storage medium. In order that they may be tailored to the specific requirements of disparate analysis tasks, these logical arrangements may differ in size and dimensionality, with no restrictions placed on the number of dimensions and the meaning of each dimension. MIATool additionally supports processing flexibility, extensible image processing capabilities, and data storage management. PMID:20423810

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Intervendor variability of two-dimensional strain using vendor-specific and vendor-independent software.

    PubMed

    Nagata, Yasufumi; Takeuchi, Masaaki; Mizukoshi, Kei; Wu, Victor Chien-Chia; Lin, Fen-Chiung; Negishi, Kazuaki; Nakatani, Satoshi; Otsuji, Yutaka

    2015-06-01

    Although two-dimensional (2D) strain is widely used to assess left ventricular mechanics, the strain values derived from vendor-specific 2D speckle-tracking software are different even for the same subjects and are therefore not interchangeable. The aim of this study was to test the hypothesis that vendor-independent software would produce lower intervendor variability between 2D strain measurements and overcome this limitation. Two sets of three apical images were acquired using two of three types of ultrasound machines (GE, Philips, and Toshiba) in 81 healthy volunteers (GE vs Philips in 26 subjects, Philips vs Toshiba in 31 subjects, and GE vs Toshiba in 24 subjects). Two-dimensional global longitudinal strain (GLS) was measured using vendor-specific software and two vendor-independent software packages (TomTec and Epsilon) in each set of apical images, and GLS values were directly compared with one another. The upgrades of vendor-specific software yielded different values of GLS compared with the previous versions of the software. The correlations between the GLS values determined using vendor-specific software exhibited a wide range of r values (r = 0.23, r = 0.42, and r = 0.72), with significant bias, with the exception of one comparison. The vendor-independent software provided modest degrees of correlation (TomTec: r = 0.65, r = 0.65, and r = 0.77; Epsilon: r = 0.65, r = 0.74, and r = 0.77), with limits of agreement (range, ±3% to ±4.5%) that were not negligible. Although the vendor-independent 2D strain software provided moderate correlations between the GLS values of the ultrasound images obtained from the same subjects using different vendors, relatively large limits of agreement remain a relevant problem. These results suggest that the same ultrasound machine and the same 2D speckle-tracking software should be used for longitudinal analysis of strain values in the same subjects and for cross-sectional studies. Copyright © 2015 American

  15. 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.

  16. 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.

  17. Measuring Software Test Verification for Complex Workpieces based on Virtual Gear Measuring Instrument

    NASA Astrophysics Data System (ADS)

    Yin, Peili; Wang, Jianhua; Lu, Chunxia

    2017-08-01

    Validity and correctness test verification of the measuring software has been a thorny issue hindering the development of Gear Measuring Instrument (GMI). The main reason is that the software itself is difficult to separate from the rest of the measurement system for independent evaluation. This paper presents a Virtual Gear Measuring Instrument (VGMI) to independently validate the measuring software. The triangular patch model with accurately controlled precision was taken as the virtual workpiece and a universal collision detection model was established. The whole process simulation of workpiece measurement is implemented by VGMI replacing GMI and the measuring software is tested in the proposed virtual environment. Taking involute profile measurement procedure as an example, the validity of the software is evaluated based on the simulation results; meanwhile, experiments using the same measuring software are carried out on the involute master in a GMI. The experiment results indicate a consistency of tooth profile deviation and calibration results, thus verifying the accuracy of gear measuring system which includes the measurement procedures. It is shown that the VGMI presented can be applied in the validation of measuring software, providing a new ideal platform for testing of complex workpiece-measuring software without calibrated artifacts.

  18. The optimal approach for the processes of verification and validation of NPP software and hardware complexes

    NASA Astrophysics Data System (ADS)

    Korolev, S.; Tolokonsky, A.; Rogov, V.

    2017-01-01

    Nowadays the task of increasing the quality of software and hardware complex development has not lost its urgency. The problem mentioned has still been solving by the search of an optimal structure, stage content and life cycle processes. The current system of international standards has been developed on the basis of advanced software complexes for aviation, space and defense industries being designed during the second half of the 20th century. However, it lacks a holistic approach for verification and validation. The paper presents the analysis of Russian and international regulatory framework and current verification and validation methods in the context of the life cycle of NPP software and hardware complexes. Basing on the data obtained, a new approach for verification and validation methods has been introduced.

  19. 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.

  20. Software Hardware Asset Reuse Enterprise (SHARE) Repository Framework Final Report: Component Specification and Ontology

    DTIC Science & Technology

    2008-09-30

    MDAPs = ^Åèìáëáíáçå=oÉëÉ~êÅÜ=mêçÖê~ã= do^ar^qb=p`elli=lc=_rpfkbpp=C=mr_if`=mlif`v k^s^i=mlpqdo^ar^qb=p`elli= = Human Resources  Learning... resource discovery objectives in the Global Information Grid context. Keywords: Software Reuse, Software repository, Component Specification, Ontology...International Resource Identifier ISO International Organization for Standardization IWS Integrated Warfare Systems KSLOC Thousands of Source Lines of Code

  1. 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.

  2. SU-E-T-76: A Software System to Monitor VMAT Plan Complexity in a Large Radiotherapy Centre

    SciTech Connect

    Arumugam, S; Xing, A; Vial, P; Thwaites, D; Holloway, L

    2015-06-15

    Purpose: To develop a system that analyses and reports the complexity of Volumetric Modulated Arc Therapy (VMAT) plans to aid in the decision making for streamlining patient specific dosimetric quality assurance (QA) tests. Methods: A software system, Delcheck, was developed in-house to calculate VMAT plan and delivery complexity using the treatment delivery file. Delcheck has the functionality to calculate multiple plan complexity metrics including the Li-Xing Modulation Index (LI-MI), multiplicative combination of Leaf Travel and Modulation Complexity Score (LTMCSv), Monitor Units per prescribed dose (MU/D) and the delivery complexity index (MIt) that incorporates the modulation of dose rate, leaf speed and gantry speed. Delcheck includes database functionality to store and compare plan metrics for a specified treatment site. The overall plan and delivery complexity is assessed based on the 95% conformance limit of the complexity metrics as Similar, More or Less complex. The functionality of the software was tested using 42 prostate conventional, 10 prostate SBRT and 15 prostate bed VMAT plans generated for an Elekta linear accelerator. Results: The mean(σ) of LI-MI for conventional, SBRT and prostate bed plans were 1690(486), 3215.4(1294) and 3258(982) respectively. The LTMCSv of the studied categories were 0.334(0.05), 0.325(0.07) and 0.3112(0.09). The MU/D of the studied categories were 2.4(0.4), 2.7(0.7) and 2.5(0.5). The MIt of the studied categories were 21.6(3.4), 18.2(3.0) and 35.9(6.6). The values of the complexity metrics show that LI-MI appeared to resolve the plan complexity better than LTMCSv and MU/D. The MIt value increased as the delivery complexity increased. Conclusion: The developed software was shown to be working as expected. In studied treatment categories Prostate bed plans are more complex in both plan and delivery and SBRT is more complex in plan and less complex in delivery as demonstrated by LI-MI and MIt. This project was funded

  3. 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.

  4. Improving Security in Software Acquisition and Runtime Integration With Data Retention Specifications

    DTIC Science & Technology

    2016-04-30

    qÜáêíÉÉåíÜ=^ååì~ä= ^Åèìáëáíáçå=oÉëÉ~êÅÜ= póãéçëáìã= tÉÇåÉëÇ~ó=pÉëëáçåë= sçäìãÉ=f= = Improving Security in Software Acquisition and Runtime Integration With...University Improving Security in Software Acquisition and Runtime Integration With Data Retention Specifications Daniel Smullen, Research Assistant...Åèìáëáíáçå=oÉëÉ~êÅÜ=mêçÖê~ãW= `êÉ~íáåÖ=póåÉêÖó=Ñçê=fåÑçêãÉÇ=`Ü~åÖÉ= - 322 - Improving Security in Software Acquisition and Runtime

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  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. TChem - A Software Toolkit for the Analysis of Complex Kinetic Models

    SciTech Connect

    Safta, Cosmin; Najm, Habib N.; Knio, Omar

    2011-05-01

    The TChem toolkit is a software library that enables numerical simulations using complex chemistry and facilitates the analysis of detailed kinetic models. The toolkit provide capabilities for thermodynamic properties based on NASA polynomials and species production/consumption rates. It incorporates methods that can selectively modify reaction parameters for sensitivity analysis. The library contains several functions that provide analytically computed Jacobian matrices necessary for the efficient time advancement and analysis of detailed kinetic models.

  15. 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.

  16. A hardware-software complex for modelling and research of near navigation based on pseudolites

    NASA Astrophysics Data System (ADS)

    Gladyshev, A. B.; Dmitriev, D. D.; Veysov, E. A.; Tyapkin, V. N.

    2017-01-01

    The paper considers a hardware-software complex for research of characteristics of accuracy and noise immunity of a near navigation system based on pseudolites. The complex is implemented on the basis of the “National Instruments” hardware platform and “LabView” coding environment. It provides a simulated navigation field, the analysis of the received signals, the determination of the errors of measurement of navigation parameters for pseudolites signals, comparing the measured error with the characteristics of a standard GNSS receiver.

  17. 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.

  18. 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)

  19. ETA: robust software for determination of cell specific rates from extracellular time courses.

    PubMed

    Murphy, Taylor A; Young, Jamey D

    2013-06-01

    Accurate quantification of cell specific rates and their uncertainties is of critical importance for assessing metabolic phenotypes of cultured cells. We applied two different methods of regression and error analysis to estimate specific metabolic rates from time-course measurements obtained in exponentially growing cell cultures. Using simulated data sets to compute specific rates of growth, glucose uptake, and lactate excretion, we found that Gaussian error propagation from prime variables to the final calculated rates was the most accurate method for estimating parameter uncertainty. We incorporated this method into a MATLAB-based software package called Extracellular Time-Course Analysis (ETA), which automates the analysis workflow required to (i) compute cell specific metabolic rates and their uncertainties; (ii) test the goodness-of-fit of the experimental data to the regression model; and (iii) rapidly compare the results across multiple experiments. ETA was used to estimate the uptake or excretion rate of glucose, lactate, and 18 different amino acids in a B-cell model of c-Myc-driven cancer. We found that P493-6 cells with High Myc expression increased their specific uptake of glutamine, arginine, serine, lysine, and branched-chain amino acids by two- to threefold in comparison to low Myc cells, but exhibited only modest increases in glucose uptake and lactate excretion. By making the ETA software package freely available to the scientific community, we expect that it will become an important tool for rigorous estimation of specific rates required for metabolic flux analysis and other quantitative metabolic studies. Copyright © 2013 Wiley Periodicals, Inc.

  20. A preliminary report of designing removable partial denture frameworks using a specifically developed software package.

    PubMed

    Han, Jing; Wang, Yong; Lü, Peijun

    2010-01-01

    This article reports on a method to digitally survey and build virtual patterns for removable partial denture (RPD) frameworks using a new three-dimensional (3D) computer-aided design/computer-assisted manufacturing (CAD/CAM) software package developed specifically for RPD design. The procedure included obtaining 3D data from partially dentate casts, deciding on the path of insertion, and modeling the shape of the components of the frameworks digitally. The completed model data were stored as stereolithography (STL) files, which are commonly used in transferring CAD/CAM models to rapid prototyping technologies. Finally, metal RPD frameworks were fabricated using a selective laser melting technique.

  1. 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.

  2. Application of software complex turbo problem solver to rayleigh-taylor instability modeling

    NASA Astrophysics Data System (ADS)

    Fortova, S. V.; Utkin, P. S.; Shepelev, V. V.

    2016-10-01

    The dynamic processes which take place during high-speed impact of two metal plates with different densities are investigated using three-dimensional numerical simulations. It is shown that as a result of the impact the Rayleigh-Taylor instability forms which leads to the formation of three-dimensional ring-shaped structures on the surface of the metal with smaller density. The comparative analysis of the metals interface deformation process with the use of different equations of state is performed. The numerical study is carried out by means of special software complex Turbo Problem Solver developed by the authors. The software complex Turbo Problem Solver implements generalized approach to the construction of hydrodynamic code for various computational fluid dynamics problems. Turbo Problem Solver provides several numerical schemes and software blocks to set initial, boundary conditions and mass forces. The solution of test problem about Rayleigh-Taylor instability growth and development for the case of very rapid density growth is also presented.

  3. Adaptive, High-Order, and Scalable Software Elements for Dynamic Rupture Simulations in Complex Geometries

    NASA Astrophysics Data System (ADS)

    Kozdon, J. E.; Wilcox, L.; Aranda, A. R.

    2014-12-01

    The goal of this work is to develop a new set of simulation tools for earthquake rupture dynamics based on state-of-the-art high-order, adaptive numerical methods capable of handling complex geometries. High-order methods are ideal for earthquake rupture simulations as the problems are wave-dominated and the waves excited in simulations propagate over distance much larger than their fundamental wavelength. When high-order methods are used for such problems significantly fewer degrees of freedom are required as compared with low-order methods. The base numerical method in our new software elements is a discontinuous Galerkin method based on curved, Kronecker product hexahedral elements. We currently use MPI for off-node parallelism and are in the process of exploring strategies for on-node parallelism. Spatial mesh adaptivity is handled using the p4est library and temporal adaptivity is achieved through an Adams-Bashforth based local time stepping method; we are presently in the process of including dynamic spatial adaptivity which we believe will be valuable for capturing the small-scale features around the propagating rupture front. One of the key features of our software elements is that the method is provably stable, even after the inclusion of the nonlinear frictions laws which govern rupture dynamics. In this presentation we will both outline the structure of the software elements as well as validate the rupture dynamics with SCEC benchmark test problems. We are also presently developing several realistic simulation geometries which may also be reported on. Finally, the software elements that we have designed are fully public domain and have been designed with tightly coupled, wave dominated multiphysics applications in mind. This latter design decisions means the software elements are applicable to many other geophysical and non-geophysical applications.

  4. 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.

  5. LogiKit - assisting complex logic specification and implementation for embedded control systems

    NASA Astrophysics Data System (ADS)

    Diglio, A.; Nicolodi, B.

    2002-07-01

    LogiKit provides an overall lifecycle solution. LogiKit is a powerful software engineering case toolkit for requirements specification, simulation and documentation. LogiKit also provides an automatic ADA software design, code and unit test generator.

  6. Differences in DNA Binding Specificity of Floral Homeotic Protein Complexes Predict Organ-Specific Target Genes.

    PubMed

    Smaczniak, Cezary; Muiño, Jose M; Chen, Dijun; Angenent, Gerco C; Kaufmann, Kerstin

    2017-08-01

    Floral organ identities in plants are specified by the combinatorial action of homeotic master regulatory transcription factors. However, how these factors achieve their regulatory specificities is still largely unclear. Genome-wide in vivo DNA binding data show that homeotic MADS domain proteins recognize partly distinct genomic regions, suggesting that DNA binding specificity contributes to functional differences of homeotic protein complexes. We used in vitro systematic evolution of ligands by exponential enrichment followed by high-throughput DNA sequencing (SELEX-seq) on several floral MADS domain protein homo- and heterodimers to measure their DNA binding specificities. We show that specification of reproductive organs is associated with distinct binding preferences of a complex formed by SEPALLATA3 and AGAMOUS. Binding specificity is further modulated by different binding site spacing preferences. Combination of SELEX-seq and genome-wide DNA binding data allows differentiation between targets in specification of reproductive versus perianth organs in the flower. We validate the importance of DNA binding specificity for organ-specific gene regulation by modulating promoter activity through targeted mutagenesis. Our study shows that intrafamily protein interactions affect DNA binding specificity of floral MADS domain proteins. Differential DNA binding of MADS domain protein complexes plays a role in the specificity of target gene regulation. © 2017 American Society of Plant Biologists. All rights reserved.

  7. U.S. Geological Survey Groundwater Modeling Software: Making Sense of a Complex Natural Resource

    USGS Publications Warehouse

    Provost, Alden M.; Reilly, Thomas E.; Harbaugh, Arlen W.; Pollock, David W.

    2009-01-01

    Computer models of groundwater systems simulate the flow of groundwater, including water levels, and the transport of chemical constituents and thermal energy. Groundwater models afford hydrologists a framework on which to organize their knowledge and understanding of groundwater systems, and they provide insights water-resources managers need to plan effectively for future water demands. Building on decades of experience, the U.S. Geological Survey (USGS) continues to lead in the development and application of computer software that allows groundwater models to address scientific and management questions of increasing complexity.

  8. On the Concept of Trusted Computing and Software Watermarking: A Computational Complexity Treatise

    NASA Astrophysics Data System (ADS)

    Hao, Wu; Guoqing, Wu

    Trusted computing is a new requirement of information security, after the successful modern cryptography. Although there are many developments of methods and techniques to address on the problems of trusted computing, the lack of rigorous theoretic treatment makes it hard to give further mathematical treatment. In this paper, we develop theory and concepts of trusted computing founded on computational complexity, which analogies to modern cryptography and find close connections between trusted computing and one way functions, one of the pillars of the modern cryptography. After that, we reveal that trusted computing has a subtle but deep relation with software watermarking, that concept can be found on the concept of trusted computing.

  9. Netlang: A software for the linguistic analysis of corpora by means of complex networks

    PubMed Central

    Serna Salazar, Diego; Isaza, Gustavo; Castillo Ossa, Luis F.; Bedia, Manuel G.

    2017-01-01

    To date there is no software that directly connects the linguistic analysis of a conversation to a network program. Networks programs are able to extract statistical information from data basis with information about systems of interacting elements. Language has also been conceived and studied as a complex system. However, most proposals do not analyze language according to linguistic theory, but use instead computational systems that should save time at the price of leaving aside many crucial aspects for linguistic theory. Some approaches to network studies on language do apply precise linguistic analyses, made by a linguist. The problem until now has been the lack of interface between the analysis of a sentence and its integration into the network that could be managed by a linguist and that could save the analysis of any language. Previous works have used old software that was not created for these purposes and that often produced problems with some idiosyncrasies of the target language. The desired interface should be able to deal with the syntactic peculiarities of a particular language, the options of linguistic theory preferred by the user and the preservation of morpho-syntactic information (lexical categories and syntactic relations between items). Netlang is the first program able to do that. Recently, a new kind of linguistic analysis has been developed, which is able to extract a complexity pattern from the speaker's linguistic production which is depicted as a network where words are inside nodes, and these nodes connect each other by means of edges or links (the information inside the edge can be syntactic, semantic, etc.). The Netlang software has become the bridge between rough linguistic data and the network program. Netlang has integrated and improved the functions of programs used in the past, namely the DGA annotator and two scripts (ToXML.pl and Xml2Pairs.py) used for transforming and pruning data. Netlang allows the researcher to make accurate

  10. Netlang: A software for the linguistic analysis of corpora by means of complex networks.

    PubMed

    Barceló-Coblijn, Lluís; Serna Salazar, Diego; Isaza, Gustavo; Castillo Ossa, Luis F; Bedia, Manuel G

    2017-01-01

    To date there is no software that directly connects the linguistic analysis of a conversation to a network program. Networks programs are able to extract statistical information from data basis with information about systems of interacting elements. Language has also been conceived and studied as a complex system. However, most proposals do not analyze language according to linguistic theory, but use instead computational systems that should save time at the price of leaving aside many crucial aspects for linguistic theory. Some approaches to network studies on language do apply precise linguistic analyses, made by a linguist. The problem until now has been the lack of interface between the analysis of a sentence and its integration into the network that could be managed by a linguist and that could save the analysis of any language. Previous works have used old software that was not created for these purposes and that often produced problems with some idiosyncrasies of the target language. The desired interface should be able to deal with the syntactic peculiarities of a particular language, the options of linguistic theory preferred by the user and the preservation of morpho-syntactic information (lexical categories and syntactic relations between items). Netlang is the first program able to do that. Recently, a new kind of linguistic analysis has been developed, which is able to extract a complexity pattern from the speaker's linguistic production which is depicted as a network where words are inside nodes, and these nodes connect each other by means of edges or links (the information inside the edge can be syntactic, semantic, etc.). The Netlang software has become the bridge between rough linguistic data and the network program. Netlang has integrated and improved the functions of programs used in the past, namely the DGA annotator and two scripts (ToXML.pl and Xml2Pairs.py) used for transforming and pruning data. Netlang allows the researcher to make accurate

  11. Performance requirements of real-time continuous media computing: specification techniques and hardware/software implications

    NASA Astrophysics Data System (ADS)

    Krishnaswamy, Venkatesh; Subrahmanyam, P. A.

    1996-01-01

    Today's typical multimedia computer consists of a fast CPU and multimedia peripherals such as attached sound and video support hardware. In such a machine, the low-level audio and video handling may be performed by these peripherals while any significant processing on these media requires the intimate involvement of the CPU, main memory system and the operating system. Given that these components are not typically designed to meet the real-time requirements of continuous media, there are a number of constraints on the nature of multimedia applications that can be executed. To get around these constraints, demanding multimedia applications may typically be offloaded to attached peripheral compute engines which are customized to execute the applications. This approach requires dedicating resources to specific applications and suffers from the problem that such applications are not flexible integrated with the main system. We posit that new software and hardware technologies are needed to truly integrate real-time multimedia processing capabilities within a multimedia computer. The design of these technologies must be based on a thorough understanding of the timing and real-time computing requirements of various types of continuous media. Formal mechanisms are needed to express and analyze these requirements in order for multimedia operating systems to efficiently and correctly schedule the use of computing and communication resources. Indeed such mechanisms may be used to guide the specification and design of hardware and software processing component. In this paper, we present a framework for specifying the timing properties and computational requirements of continuous media. We discuss the usefulness of this framework in the context of some common audio and video data formats. We also discuss the impact of this framework on the design of resource scheduling mechanisms. Finally we offer some insights on designing audio/video processing engines based on real

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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…

  17. 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…

  18. Polyamide platinum anticancer complexes designed to target specific DNA sequences.

    PubMed

    Jaramillo, David; Wheate, Nial J; Ralph, Stephen F; Howard, Warren A; Tor, Yitzhak; Aldrich-Wright, Janice R

    2006-07-24

    Two new platinum complexes, trans-chlorodiammine[N-(2-aminoethyl)-4-[4-(N-methylimidazole-2-carboxamido)-N-methylpyrrole-2-carboxamido]-N-methylpyrrole-2-carboxamide]platinum(II) chloride (DJ1953-2) and trans-chlorodiammine[N-(6-aminohexyl)-4-[4-(N-methylimidazole-2-carboxamido)-N-methylpyrrole-2-carboxamido]-N-methylpyrrole-2-carboxamide]platinum(II) chloride (DJ1953-6) have been synthesized as proof-of-concept molecules in the design of agents that can specifically target genes in DNA. Coordinate covalent binding to DNA was demonstrated with electrospray ionization mass spectrometry. Using circular dichroism, these complexes were found to show greater DNA binding affinity to the target sequence: d(CATTGTCAGAC)(2), than toward either d(GTCTGTCAATG)(2,) which contains different flanking sequences, or d(CATTGAGAGAC)(2), which contains a double base pair mismatch sequence. DJ1953-2 unwinds the DNA helix by around 13 degrees , but neither metal complex significantly affects the DNA melting temperature. Unlike simple DNA minor groove binders, DJ1953-2 is able to inhibit, in vitro, RNA synthesis. The cytotoxicity of both metal complexes in the L1210 murine leukaemia cell line was also determined, with DJ1953-6 (34 microM) more active than DJ1953-2 (>50 microM). These results demonstrate the potential of polyamide platinum complexes and provide the structural basis for designer agents that are able to recognize biologically relevant sequences and prevent DNA transcription and replication.

  19. 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

  20. 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.

  1. Hardware-software complex of informing passengers of forecasted route transport arrival at stop

    NASA Astrophysics Data System (ADS)

    Pogrebnoy, V. Yu; Pushkarev, M. I.; Fadeev, A. S.

    2017-02-01

    The paper presents the hardware-software complex of informing the passengers of the forecasted route transport arrival. A client-server architecture of the forecasting information system is represented and an electronic information board prototype is described. The scheme of information transfer and processing, starting with receiving navigating telemetric data from a transport vehicle and up to the time of passenger public transport arrival at the stop, as well as representation of the information on the electronic board is illustrated and described. Methods and algorithms of determination of the transport vehicle current location in the city route network are considered in detail. The description of the proposed forecasting model of transport vehicle arrival time at the stop is given. The obtained result is applied in Tomsk for forecasting and displaying the arrival time information at the stops.

  2. 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)

  3. 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.

  4. Specific DNA recognition by the Antp homeodomain: MD simulations of specific and nonspecific complexes.

    PubMed

    Gutmanas, Aleksandras; Billeter, Martin

    2004-12-01

    Four molecular dynamics simulation trajectories of complexes between the wild-type or a mutant Antennapedia homeodomain and 2 DNA sequences were generated in order to probe the mechanisms governing the specificity of DNA recognition. The starting point was published affinity measurements showing that a single protein mutation combined with a replacement of 2 base pairs yields a new high-affinity complex, whereas the other combinations, with changes on only 1 macromolecule, exhibited lower affinity. The simulations of the 4 complexes yielded fluctuating networks of interaction. On average, these networks differ significantly, explaining the switch of affinity caused by the alterations in the macromolecules. The network of mostly hydrogen-bonding interactions involving several water molecules, which was suggested both by X-ray and NMR structures of the wild-type homeodomain and its DNA operator sequence, could be reproduced in the trajectory. More interestingly, the high-affinity complex with alterations in both the protein and the DNA yielded again a dynamic but very tight network of intermolecular interactions, however, attributing a significantly stronger role to direct hydrophobic interactions at the expense of water bridges. The other 2 homeodomain-DNA complexes, with only 1 molecule altered, show on average over the trajectories a clearly reduced number of protein-DNA interactions. The observations from these simulations suggest specific experiments and thus close the circle formed by biochemical, structural, and computational studies. The shift from a water-dominated to a more "dry" interface may prove important in the design of proteins binding DNA in a specific manner.

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

    PubMed

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

    2015-01-01

    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.

  6. Effects of Using Requirements Catalogs on Effectiveness and Productivity of Requirements Specification in a Software Project Management Course

    ERIC Educational Resources Information Center

    Fernández-Alemán, José Luis; Carrillo-de-Gea, Juan Manuel; Meca, Joaquín Vidal; Ros, Joaquín Nicolás; Toval, Ambrosio; Idri, Ali

    2016-01-01

    This paper presents the results of two educational experiments carried out to determine whether the process of specifying requirements (catalog-based reuse as opposed to conventional specification) has an impact on effectiveness and productivity in co-located and distributed software development environments. The participants in the experiments…

  7. Engineering a root-specific, repressor-operator gene complex.

    PubMed

    Kim, Tehryung; Balish, Rebecca S; Heaton, Andrew C P; McKinney, Elizabeth C; Dhankher, Om Parkash; Meagher, Richard B

    2005-11-01

    Strong, tissue-specific and genetically regulated expression systems are essential tools in plant biotechnology. An expression system tool called a 'repressor-operator gene complex' (ROC) has diverse applications in plant biotechnology fields including phytoremediation, disease resistance, plant nutrition, food safety, and hybrid seed production. To test this concept, we assembled a root-specific ROC using a strategy that could be used to construct almost any gene expression pattern. When a modified E. coli lac repressor with a nuclear localization signal was expressed from a rubisco small subunit expression vector, S1pt::lacIn, LacIn protein was localized to the nuclei of leaf and stem cells, but not to root cells. A LacIn repressible Arabidopsis actin expression vector A2pot was assembled containing upstream bacterial lacO operator sequences, and it was tested for organ and tissue specificity using beta-glucuronidase (GUS) and mercuric ion reductase (merA) gene reporters. Strong GUS enzyme expression was restricted to root tissues of A2pot::GUS/S1pt::lacIn ROC plants, while GUS activity was high in all vegetative tissues of plants lacking the repressor. Repression of shoot GUS expression exceeded 99.9% with no evidence of root repression, among a large percentage of doubly transformed plants. Similarly, MerA was strongly expressed in the roots, but not the shoots of A2pot::merA/S1pt::lacIn plants, while MerA levels remained high in both shoots and roots of plants lacking repressor. Plants with MerA expression restricted to roots were approximately as tolerant to ionic mercury as plants constitutively expressing MerA in roots and shoots. The superiority of this ROC over the previously described root-specific tobacco RB7 promoter is demonstrated.

  8. 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

  9. A library collection of software documentation specific to astronomical data reduction.

    NASA Astrophysics Data System (ADS)

    Rhodes, C.; Kurtz, M.; Rey-Watson, J. M.

    The authors discuss their objectives in establishing such a collection. They present a list of acquired documentation with brief descriptions of the software and the hardware required. The collection will be catalogued and available for interlibrary loan through the Smithsonian Institution Library. Instructions on accessing this collection are included.

  10. Computer Program Development Specification for IDAMST Operational Flight Programs. Addendum 1. Executive Software.

    DTIC Science & Technology

    1976-11-01

    This bit shall be set to logic 1, in Master Mooc onjy, cafer receiving an excepted, valid status word associzeo witn a Remote device in Transmit Mooe...unknown. The additional stora that software can influence are ;;sted below: 16 registers o’ 16 cits eacn (AO tnrougn A15) 4 bits o’f ccciior st.-s fset

  11. 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.

  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. Fast index based algorithms and software for matching position specific scoring matrices

    PubMed Central

    Beckstette, Michael; Homann, Robert; Giegerich, Robert; Kurtz, Stefan

    2006-01-01

    Background In biological sequence analysis, position specific scoring matrices (PSSMs) are widely used to represent sequence motifs in nucleotide as well as amino acid sequences. Searching with PSSMs in complete genomes or large sequence databases is a common, but computationally expensive task. Results We present a new non-heuristic algorithm, called ESAsearch, to efficiently find matches of PSSMs in large databases. Our approach preprocesses the search space, e.g., a complete genome or a set of protein sequences, and builds an enhanced suffix array that is stored on file. This allows the searching of a database with a PSSM in sublinear expected time. Since ESAsearch benefits from small alphabets, we present a variant operating on sequences recoded according to a reduced alphabet. We also address the problem of non-comparable PSSM-scores by developing a method which allows the efficient computation of a matrix similarity threshold for a PSSM, given an E-value or a p-value. Our method is based on dynamic programming and, in contrast to other methods, it employs lazy evaluation of the dynamic programming matrix. We evaluated algorithm ESAsearch with nucleotide PSSMs and with amino acid PSSMs. Compared to the best previous methods, ESAsearch shows speedups of a factor between 17 and 275 for nucleotide PSSMs, and speedups up to factor 1.8 for amino acid PSSMs. Comparisons with the most widely used programs even show speedups by a factor of at least 3.8. Alphabet reduction yields an additional speedup factor of 2 on amino acid sequences compared to results achieved with the 20 symbol standard alphabet. The lazy evaluation method is also much faster than previous methods, with speedups of a factor between 3 and 330. Conclusion Our analysis of ESAsearch reveals sublinear runtime in the expected case, and linear runtime in the worst case for sequences not shorter than |A MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBamrtHrhAL1wy0L2y

  14. 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 ).

  15. Computer-Aided Design for Built-In-Test (CADBIT) - Software Specification. Volume 3

    DTIC Science & Technology

    1989-10-01

    CADD COMAN WIDO IO-CNURET MSL PPLYING~ TET ATEN Figur 3-13- TUTORIA FIGUR PLCMI IN CAD-NVIOMENT ON BOAR SEFTST- 1"os-rnenu, long-tur d nnnih que- list...have software package for reliability calculation A-8 LIBRARY ELEMENT DATA SHE T’" BIT TECHNIQUE: ON-BOARD ROM CATEGORY: L’ONG TUTORIA PAGE ,5 of 14

  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. Implementing a modeling software for animated protein-complex interactions using a physics simulation library.

    PubMed

    Ueno, Yutaka; Ito, Shuntaro; Konagaya, Akihiko

    2014-12-01

    To better understand the behaviors and structural dynamics of proteins within a cell, novel software tools are being developed that can create molecular animations based on the findings of structural biology. This study proposes our method developed based on our prototypes to detect collisions and examine the soft-body dynamics of molecular models. The code was implemented with a software development toolkit for rigid-body dynamics simulation and a three-dimensional graphics library. The essential functions of the target software system included the basic molecular modeling environment, collision detection in the molecular models, and physical simulations of the movement of the model. Taking advantage of recent software technologies such as physics simulation modules and interpreted scripting language, the functions required for accurate and meaningful molecular animation were implemented efficiently.

  19. Major histocompatibility complex conformational epitopes are peptide specific

    PubMed Central

    1992-01-01

    Serologically distinct forms of H-2Kb are stabilized by loading cells expressing "empty" class I major histocompatibility complex (MHC) molecules with different H-2Kb binding peptides. The H-2Kb epitope recognized by monoclonal antibody (mAb) 28.8.6 was stabilized by ovalbumin (OVA) (257-264) and murine cytomegalovirus (MCMV) pp89 (168- 176) peptides, but not by vesicular stomatic virus nucleoprotein (VSV NP) (52-59) and influenza NP (Y345-360) peptides. The H-2Kb epitope recognized by mAb 34.4.20 was stabilized by VSV NP (52-59) peptide but not by OVA (257-264), MCMV pp89 (168-176), or influenza NP (Y345-360) peptides. Immunoprecipitation of H-2Kb molecules from normal cells showed that 28.8.6 and 34.4.20 epitopes were only present on a subset of all conformationally reactive H-2Kb molecules. Using alanine- substituted derivatives of the VSV peptide, the 28.8.6 epitope was completely stabilized by substitution of the first residue and partially stabilized by substitution of the third or the fifth residues in the peptides. These results indicate that distinct conformational MHC epitopes are dependent on the specific peptide that occupies the antigenic peptide binding groove on individual MHC molecules. The changes in MHC epitopes observed may also be important in understanding the diversity of T cell receptors used in an immune response and the influence of peptides on development of the T cell repertoire. PMID:1281212

  20. Complex extracellular matrices promote tissue-specific stem cell differentiation.

    PubMed

    Philp, Deborah; Chen, Silvia S; Fitzgerald, Wendy; Orenstein, Jan; Margolis, Leonid; Kleinman, Hynda K

    2005-02-01

    Most cells in tissues contact an extracellular matrix on at least one surface. These complex mixtures of interacting proteins provide structural support and biological signals that regulate cell differentiation and may be important for stem cell differentiation. In this study, we have grown a rhesus monkey embryonic stem cell line in the presence of various extracellular matrix components in monolayer, in a NASA-developed rotating wall vessel bioreactor in vitro, and subcutaneously in vivo. We find that individual components of the extracellular matrix, such as laminin-1 or collagen I, do not influence the growth or morphology of the cells. In contrast, a basement membrane extract, Matrigel, containing multiple extracellular matrix components, induces the cells within 4 days to form immature glandular- and tubular-like structures, many of which contain a lumen with polarized epithelium and microvilli. Such structures were seen in vitro when the cells were grown in the bioreactor and when the cells were injected into mice. These tubular- and glandular-like structures were polarized epithelia based on immunostaining for laminin and cytokeratin. The cell aggregates and tumors also contained additional mixed populations of cells, including mesenchymal cells and neuronal cells, based on immunostaining with vimentin and neuronal markers. An extract of cartilage, containing multiple cartilage matrix components, promoted chondrogenesis in vivo where alcian blue-stained cartilage nodules could be observed. Some of these nodules stained with von Kossa, indicating that they had formed calcified cartilage. We conclude that extracellular matrices can promote the differentiation of embryonic stem cells into differentiated cells and structures that are similar to the tissue from which the matrix is derived. Such preprogramming of cell differentiation with extracellular matrices may be useful in targeting stem cells to repair specific damaged organs.

  1. 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.

  2. Computer Program Development Specification for IDAMST Operational Flight Program Executive, Software Type B5. Addendum 2.

    DTIC Science & Technology

    1976-07-30

    shall perform a processor self -test and initiate the BCIU self -test. The Processor Control Panel (PCP) discretes shall be read and the processor...Applicable Documents 7 3.0 Requirements 8 3.1 Program Definition 8 3.1.1 Hardware Interfaces 8 * 3.1.1.1 Bus Control Interface Unit (BCIU) 8 3.1.1.1.1...Functions 27 3.1.1.3 Processor Control Panel (PCP) 28 3.1.2 Software Interfaces 30 3.1.2.1 Events 31 3.1.2.2 Tasks 31 3.1.2.3 Comsubs 35 3.1.2.4

  3. 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

  4. Program Requirements and Design Specifications for the Quincy School Complex.

    ERIC Educational Resources Information Center

    Quincy School Community Council, MA.

    The Quincy School Complex is a unique community facility. A high level of cooperation has led to the planning of this facility whose operation and ownership is divided among several agencies and groups. The introduction to the report on the school complex provides background material for the program itself, and attempts to define the "why" of the…

  5. 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.

  6. The Use of Genetic Algorithms for Flight Test and Evaluation of Artificial Intelligence and Complex Software Systems

    DTIC Science & Technology

    1994-01-01

    8217 Artificial Itelligence and Complex Software! Systemis. D&FL C. Elizabeth Davies E L EC TEJohn McMaster Mary Stark NAWC-AD Patuxenat River MD 20670 F...301) 826-6381 (faxc) Artificial Inteffigence (A!) te:.-no~og~ies ame emerging from :esearh la~boratories into industry, particularly into the field of... artificial intefligence. In particular, the subject of this paper is the develop~ment, of a genetic algorithm (GA) which will automatically find those

  7. 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.

  8. 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

  9. How Precise Are Preinterventional Measurements Using Centerline Analysis Applications? Objective Ground Truth Evaluation Reveals Software-Specific Centerline Characteristics.

    PubMed

    Hoegen, Philipp; Wörz, Stefan; Müller-Eschner, Matthias; Geisbüsch, Philipp; Liao, Wei; Rohr, Karl; Schmitt, Matthias; Rengier, Fabian; Kauczor, Hans-Ulrich; von Tengg-Kobligk, Hendrik

    2017-08-01

    To evaluate different centerline analysis applications using objective ground truth from realistic aortic aneurysm phantoms with precisely defined geometry and centerlines to overcome the lack of unknown true dimensions in previously published in vivo validation studies. Three aortic phantoms were created using computer-aided design (CAD) software and a 3-dimensional (3D) printer. Computed tomography angiograms (CTAs) of phantoms and 3 patients were analyzed with 3 clinically approved and 1 research software application. The 3D centerline coordinates, intraluminal diameters, and lengths were validated against CAD ground truth using a dedicated evaluation software platform. The 3D centerline position mean error ranged from 0.7±0.8 to 2.9±2.5 mm between tested applications. All applications calculated centerlines significantly different from ground truth. Diameter mean errors varied from 0.5±1.2 to 1.1±1.0 mm among 3 applications, but exceeded 8.0±11.0 mm with one application due to an unsteady distortion of luminal dimensions along the centerline. All tested commercially available software tools systematically underestimated centerline total lengths by -4.6±0.9 mm to -10.4±4.3 mm (maximum error -14.6 mm). Applications with the highest 3D centerline accuracy yielded the most precise diameter and length measurements. One clinically approved application did not provide reproducible centerline-based analysis results, while another approved application showed length errors that might influence stent-graft choice and procedure success. The variety and specific characteristics of endovascular aneurysm repair planning software tools require scientific evaluation and user awareness.

  10. 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.

  11. The boot software of the control unit of the near infrared spectrograph of the Euclid space mission: technical specification

    NASA Astrophysics Data System (ADS)

    Gómez-Sáenz-de-Tejada, Jaime; Toledo-Moreo, Rafael; Colodro-Conde, Carlos; Pérez-Lizán, David; Fernández-Conde, Jesús; Sánchez-Prieto, Sebastián.

    2016-07-01

    The Near Infrared Spectrograph and Photometer (NISP) is one of the instruments on board the ESA EUCLID mission. The Boot Software (BSW) is in charge of initialization and communications after a reset occurs at hard- ware level. The Universidad Politecnica de Cartagena and Instituto de Astrofisica de Canarias are responsible of the Instrument Control Unit of the NISP (NI-ICU) in the Euclid Consortium. The NI-ICU BSW is developed by Universidad de Alcaĺa, and its main functions are: communication with the S/C for memory management, self-tests and start of a patchable Application Software (ASW). This paper presents the NI-ICU BSW status of definition and design at the end of the Technical Specification phase.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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…

  18. 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…

  19. 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

  20. STING Millennium Suite: integrated software for extensive analyses of 3d structures of proteins and their complexes

    PubMed Central

    Higa, Roberto H; Togawa, Roberto C; Montagner, Arnaldo J; Palandrani, Juliana CF; Okimoto, Igor KS; Kuser, Paula R; Yamagishi, Michel EB; Mancini, Adauto L; Neshich, Goran

    2004-01-01

    Background The integration of many aspects of protein/DNA structure analysis is an important requirement for software products in general area of structural bioinformatics. In fact, there are too few software packages on the internet which can be described as successful in this respect. We might say that what is still missing is publicly available, web based software for interactive analysis of the sequence/structure/function of proteins and their complexes with DNA and ligands. Some of existing software packages do have certain level of integration and do offer analysis of several structure related parameters, however not to the extent generally demanded by a user. Results We are reporting here about new Sting Millennium Suite (SMS) version which is fully accessible (including for local files at client end), web based software for molecular structure and sequence/structure/function analysis. The new SMS client version is now operational also on Linux boxes and it works with non-public pdb formatted files (structures not deposited at the RCSB/PDB), eliminating earlier requirement for the registration if SMS components were to be used with user's local files. At the same time the new SMS offers some important additions and improvements such as link to ProTherm as well as significant re-engineering of SMS component ConSSeq. Also, we have added 3 new SMS mirror sites to existing network of global SMS servers: Argentina, Japan and Spain. Conclusion SMS is already established software package and many key data base and software servers worldwide, do offer either a link to, or host the SMS. SMS (Sting Millennium Suite) is web-based publicly available software developed to aid researches in their quest for translating information about the structures of macromolecules into knowledge. SMS allows to a user to interactively analyze molecular structures, cross-referencing visualized information with a correlated one, available across the internet. SMS is already used as a

  1. On the Domain Specificity of Cognitive Complexity: An Alternative Approach.

    ERIC Educational Resources Information Center

    Cohen, Harvey S.; Feldman, Jack M.

    This study attempts to assess differences in the three aspects of cognitive complexity--differentiation, discrimination, and integration--as functions of information about and interest in the relevant domain. The two groups of subjects consisted of 20 members of a local sports car club and an equal number from a local garden club. Each group had…

  2. Developing software to "track and catch" missed follow-up of abnormal test results in a complex sociotechnical environment.

    PubMed

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

    2013-01-01

    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. 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. 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. 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. To address the factors involved in missed test results, we developed a software prototype to account for

  3. A software system to collect expert relevance ratings of medical record items for specific clinical tasks.

    PubMed

    Harvey, H Benjamin; Krishnaraj, Arun; Alkasab, Tarik K

    2014-02-28

    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.

  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. Assurance Cases for Design Analysis of Complex System of Systems Software

    DTIC Science & Technology

    2016-06-13

    data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this... data • the designs were not yet complete and would not be complete until after many production decisions had to be made • the need to relate the...software to operational needs • the desire to base conclusions as much as possible on actual data rather than on optimistic plans and confident

  6. 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…

  7. 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…

  8. SecureCore Software Architecture: Trusted Management Layer (TML) Kernel Extension Module Interface Specification

    DTIC Science & Technology

    2008-01-01

    Kernel Extension Module Interface Specification by David J. Shifflett Paul C. Clark Cynthia E. Irvine Thuy D. Nguyen Timothy M. Vidas ...Timothy M. Vidas Timothy E. Levin Research Associate Research Associate...Nguyen, Timothy M. Vidas , and Timothy E. Levin 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval

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

    USDA-ARS?s Scientific Manuscript database

    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...

  10. Software Hardware Asset Reuse Enterprise (SHARE) Repository Framework Final Report: Component Specification and Ontology

    DTIC Science & Technology

    2009-08-19

    component specification and ontology for the repository framework, a brief survey of initiatives and technologies relevant to desired repository... technologies relevant to desired repository capabilities, a development approach, and initial design are described in Johnson & Blais (2008). The...Battle Management Language. His research interests include application of Web-based technologies to improve interoperability of C2 systems and M&S

  11. 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…

  12. Sialidase specificity determined by chemoselective modification of complex sialylated glycans.

    PubMed

    Parker, Randy B; McCombs, Janet E; Kohler, Jennifer J

    2012-09-21

    Sialidases hydrolytically remove sialic acids from sialylated glycoproteins and glycolipids. Sialidases are widely distributed in nature and sialidase-mediated desialylation is implicated in normal and pathological processes. However, mechanisms by which sialidases exert their biological effects remain obscure, in part because sialidase substrate preferences are poorly defined. Here we report the design and implementation of a sialidase substrate specificity assay based on chemoselective labeling of sialosides. We show that this assay identifies components of glycosylated substrates that contribute to sialidase specificity. We demonstrate that specificity of sialidases can depend on structure of the underlying glycan, a characteristic difficult to discern using typical sialidase assays. Moreover, we discovered that Streptococcus pneumoniae sialidase NanC strongly prefers sialosides containing the Neu5Ac form of sialic acid versus those that contain Neu5Gc. We propose using this approach to evaluate sialidase preferences for diverse potential substrates.

  13. A single cognitive heuristic process meets the complexity of domain-specific moral heuristics.

    PubMed

    Dubljević, Veljko; Racine, Eric

    2014-10-01

    The inherence heuristic (a) offers modest insights into the complex nature of both the is-ought tension in moral reasoning and moral reasoning per se, and (b) does not reflect the complexity of domain-specific moral heuristics. Formal and general in nature, we contextualize the process described as "inherence heuristic" in a web of domain-specific heuristics (e.g., agent specific; action specific; consequences specific).

  14. The Development of a Graphical Notation for the Formal Specification of Software

    DTIC Science & Technology

    1990-12-01

    Berztiss is prepared to restrict graphic nota - tions to strictly supporting formal specifications, Ambler and Burnett and Moriconi and Hare describe tools...representation is superior to the latter in terms of clarity and utility. The tuple is Refine’s construction for representing a collection of...then evaluated by the second map. The composition operator is actually a representation of the function composition operator in advanced algebra

  15. Specification Improvement Through Analysis of Proof Structure (SITAPS): High Assurance Software Development

    DTIC Science & Technology

    2016-02-01

    2016 FINAL TECHNICAL REPORT APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED STINFO COPY AIR FORCE RESEARCH...2. REPORT TYPE FINAL TECHNICAL REPORT 3. DATES COVERED (From - To) SEP 2013 – SEP 2015 4. TITLE AND SUBTITLE SPECIFICATION IMPROVEMENT THROUGH...any patented invention that may relate to them. This report was cleared for public release by the 88th ABW, Wright-Patterson AFB Public Affairs

  16. 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

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

    PubMed

    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.

  18. 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

  19. Computer Program Development Specification for IDAMST Operational Flight Programs. Addendum 3. Error Handling and Recovery Software.

    DTIC Science & Technology

    1976-11-01

    LABORATORYDT AIR FORCE SYSTEM COMMAND D I "pUNITED STATES AIR FORCE ELECTE WRIGHT-PATTERSON AFB, OHIO 45PR143903 80 4 15 0 60’ 1 FOREWORD This specification...OF FIGURES vi LIST OF TABLES vii ABBREVIATIONS viii 1.0 SCOPE 1 1.1 IDENTIFICATION 1 1.2 FUNCTIONAL SUMMARY 1 1.2.1 ORGANIZATION 1 2.0 APPLICABLE...LIST OF FIGURES FIGURE NO. TITLE Page 3.1- 1 IDAMST ERROR DETECTION MECHANISMS 6 3.1-2 EHAR PROCESSOR INTERNAL ERROR HANDLING BY

  20. 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

  1. cell type–specific gene expression differences in complex tissues

    PubMed Central

    Shen-Orr, Shai S; Tibshirani, Robert; Khatri, Purvesh; Bodian, Dale L; Staedtler, Frank; Perry, Nicholas M; Hastie, Trevor; Sarwal, Minnie M; Davis, Mark M; Butte, Atul J

    2013-01-01

    We describe cell type–specific significance analysis of microarrays (cssam) for analyzing differential gene expression for each cell type in a biological sample from microarray data and relative cell-type frequencies. first, we validated cssam with predesigned mixtures and then applied it to whole-blood gene expression datasets from stable post-transplant kidney transplant recipients and those experiencing acute transplant rejection, which revealed hundreds of differentially expressed genes that were otherwise undetectable. PMID:20208531

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. Computer Program Development Specification for IDAMST Operational Test Program, Software Type B5. Addendum 4.

    DTIC Science & Technology

    1976-07-30

    UNCLASSIFIED AFAL-TR 76-209ADO- NL " NONhEI/ENl MENhhE 0EIt lllEll/lllllEI AFAL-TR-76-209, Addendum #4 SPECIFICATION NUMBER SD 2043 A b)E r4DOKCODEMIENT PART 1 ...JU/ 7 I/n ¢-2.3. DTIC • E APPROVED FOR PUBLIC RELEASE: DISTRIBUTION UNLIMITED O඘ I i5 06 AIR FORCE AVIONICS LABORATORY AFAL/AAA- 1 WRIGHT-PATTERSON...AFB, OHIO 45433 TABLE OF CONTENTS PARAGRAPH PAGE 1.0 SCOPE 1 1.1 Identification 1 1.2 Functional Summary 1 2.0 APPLICABLE DOCUMENTS 1 3.0 REQUIREMENTS

  7. 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.

  8. Nucleotide Specificity versus Complex Heterogeneity in Exonuclease Activity Measurements

    PubMed Central

    Enderlein, Jörg

    2007-01-01

    A recent publication reported on measurements of Exonuclease I activity using a real-time fluorescence method that measures the time required by molecules of Exonuclease I to hydrolyze single-stranded DNA that was synthesized to have two fluorescently labeled nucleotides. The observed fluorescence-intensity curves were interpreted as a sign of strong heterogeneity of the activity of Exonuclease I. Here, I propose a different model, which assumes that Exonuclease I activity is nucleotide-dependent, and that a fluorescent label bound to a nucleotide significantly slows its cleavage rate. The presented model fits the observed data equally well, but can be used to make specific predictions upon observable sequence dependence of measured fluorescence-intensity curves. PMID:17142274

  9. 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.

  10. 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/. © The American Genetic Association. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. 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.

  12. Subject-specific, multiscale simulation of electrophysiology: a software pipeline for image-based models and application examples

    PubMed Central

    MacLeod, R.S.; Stinstra, J.G.; Lew, S.; Whitaker, R.T.; Swenson, D.J.; Cole, M.J.; Krüger, J.; Brooks, D.H.; Johnson, C.R.

    2009-01-01

    Many simulation studies in biomedicine are based on a similar sequence of processing steps, starting from images and running through geometric model generation, assignment of tissue properties, numerical simulation and visualization of the results—a process known as image-based geometric modelling and simulation. We present an overview of software systems for implementing such a sequence both within highly integrated problem-solving environments and in the form of loosely integrated pipelines. Loose integration in this case indicates that individual programs function largely independently but communicate through files of a common format and support simple scripting, so as to automate multiple executions wherever possible. We then describe three specific applications of such pipelines to translational biomedical research in electrophysiology. PMID:19414456

  13. Subject-specific, multiscale simulation of electrophysiology: a software pipeline for image-based models and application examples.

    PubMed

    MacLeod, R S; Stinstra, J G; Lew, S; Whitaker, R T; Swenson, D J; Cole, M J; Krüger, J; Brooks, D H; Johnson, C R

    2009-06-13

    Many simulation studies in biomedicine are based on a similar sequence of processing steps, starting from images and running through geometric model generation, assignment of tissue properties, numerical simulation and visualization of the results--a process known as image-based geometric modelling and simulation. We present an overview of software systems for implementing such a sequence both within highly integrated problem-solving environments and in the form of loosely integrated pipelines. Loose integration in this case indicates that individual programs function largely independently but communicate through files of a common format and support simple scripting, so as to automate multiple executions wherever possible. We then describe three specific applications of such pipelines to translational biomedical research in electrophysiology.

  14. 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.

  15. 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.

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

    PubMed

    Deng, Ning; 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.

  17. 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.

  18. Analysis of complex physiological systems by information flow: a time scale-specific complexity assessment.

    PubMed

    Hoyer, Dirk; Frank, Birgit; Pompe, Bernd; Schmidt, Hendrik; Werdan, Karl; Müller-Werdan, Ursula; Baranowski, Rafal; Zebrowski, Jan J; Meissner, Winfried; Kletzin, Ulf; Adler, Daniela; Adler, Steffen; Blickhan, Reinhard

    2006-07-01

    In the last two decades conventional linear methods for biosignal analysis have been substantially extended by non-stationary, non-linear, and complexity approaches. So far, complexity is usually assessed with regard to one single time scale, disregarding complex physiology organised on different time scales. This shortcoming was overcome and medically evaluated by information flow functions developed in our research group in collaboration with several theoretical, experimental, and clinical partners. In the present work, the information flow is introduced and typical information flow characteristics are demonstrated. The prognostic value of autonomic information flow (AIF), which reflects communication in the cardiovascular system, was shown in patients with multiple organ dysfunction syndrome and in patients with heart failure. Gait information flow (GIF), which reflects communication in the motor control system during walking, was introduced to discriminate between controls and elderly patients suffering from low back pain. The applications presented for the theoretically based approach of information flow confirm its value for the identification of complex physiological systems. The medical relevance has to be confirmed by comprehensive clinical studies. These information flow measures substantially extend the established linear and complexity measures in biosignal analysis.

  19. 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.

  20. 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.

  1. 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.

  2. CASE: Software design technologies

    SciTech Connect

    Kalyanov, G.N.

    1994-05-01

    CASE (Computer-Aided Software Engineering) is a set of methodologies for software design, development, and maintenance supported by a complex of interconnected automation tools. CASE is a set of tools for the programmer, analyst, and developer for the automation of software design and development. Today, CASE has become an independent discipline in software engineering that has given rise to a powerful CASE industry made up of hundreds of firms and companies of various kinds. They include companies that develop tools for software analysis and design and have a wide network of distributors and dealers, firms that develop specialized tools for narrow subject areas or for individual stages of the software life cycle, firms that organize seminars and courses for specialists, consulting firms, which demonstrate the practical power of CASE toolkits for specific applications, and companies specializing in the publication of periodicals and bulletins on CASE. The principal purchasers of CASE toolkits abroad are military organizations, data-processing centers, and commercial software developers.

  3. Patient-specific IMRT verification using independent fluence-based dose calculation software: experimental benchmarking and initial clinical experience

    NASA Astrophysics Data System (ADS)

    Georg, Dietmar; Stock, Markus; Kroupa, Bernhard; Olofsson, Jörgen; Nyholm, Tufve; Ahnesjö, Anders; Karlsson, Mikael

    2007-08-01

    Experimental methods are commonly used for patient-specific intensity-modulated radiotherapy (IMRT) verification. The purpose of this study was to investigate the accuracy and performance of independent dose calculation software (denoted as 'MUV' (monitor unit verification)) for patient-specific quality assurance (QA). 52 patients receiving step-and-shoot IMRT were considered. IMRT plans were recalculated by the treatment planning systems (TPS) in a dedicated QA phantom, in which an experimental 1D and 2D verification (0.3 cm3 ionization chamber; films) was performed. Additionally, an independent dose calculation was performed. The fluence-based algorithm of MUV accounts for collimator transmission, rounded leaf ends, tongue-and-groove effect, backscatter to the monitor chamber and scatter from the flattening filter. The dose calculation utilizes a pencil beam model based on a beam quality index. DICOM RT files from patient plans, exported from the TPS, were directly used as patient-specific input data in MUV. For composite IMRT plans, average deviations in the high dose region between ionization chamber measurements and point dose calculations performed with the TPS and MUV were 1.6 ± 1.2% and 0.5 ± 1.1% (1 S.D.). The dose deviations between MUV and TPS slightly depended on the distance from the isocentre position. For individual intensity-modulated beams (total 367), an average deviation of 1.1 ± 2.9% was determined between calculations performed with the TPS and with MUV, with maximum deviations up to 14%. However, absolute dose deviations were mostly less than 3 cGy. Based on the current results, we aim to apply a confidence limit of 3% (with respect to the prescribed dose) or 6 cGy for routine IMRT verification. For off-axis points at distances larger than 5 cm and for low dose regions, we consider 5% dose deviation or 10 cGy acceptable. The time needed for an independent calculation compares very favourably with the net time for an experimental approach

  4. 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.

  5. Validation of SmartRank: A likelihood ratio software for searching national DNA databases with complex DNA profiles.

    PubMed

    Benschop, Corina C G; van de Merwe, Linda; de Jong, Jeroen; Vanvooren, Vanessa; Kempenaers, Morgane; Kees van der Beek, C P; Barni, Filippo; Reyes, Eusebio López; Moulin, Léa; Pene, Laurent; Haned, Hinda; Sijen, Titia

    2017-07-01

    Searching a national DNA database with complex and incomplete profiles usually yields very large numbers of possible matches that can present many candidate suspects to be further investigated by the forensic scientist and/or police. Current practice in most forensic laboratories consists of ordering these 'hits' based on the number of matching alleles with the searched profile. Thus, candidate profiles that share the same number of matching alleles are not differentiated and due to the lack of other ranking criteria for the candidate list it may be difficult to discern a true match from the false positives or notice that all candidates are in fact false positives. SmartRank was developed to put forward only relevant candidates and rank them accordingly. The SmartRank software computes a likelihood ratio (LR) for the searched profile and each profile in the DNA database and ranks database entries above a defined LR threshold according to the calculated LR. In this study, we examined for mixed DNA profiles of variable complexity whether the true donors are retrieved, what the number of false positives above an LR threshold is and the ranking position of the true donors. Using 343 mixed DNA profiles over 750 SmartRank searches were performed. In addition, the performance of SmartRank and CODIS were compared regarding DNA database searches and SmartRank was found complementary to CODIS. We also describe the applicable domain of SmartRank and provide guidelines. The SmartRank software is open-source and freely available. Using the best practice guidelines, SmartRank enables obtaining investigative leads in criminal cases lacking a suspect. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. New image-processing and noise-reduction software reduces radiation dose during complex endovascular procedures.

    PubMed

    Kirkwood, Melissa L; Guild, Jeffrey B; Arbique, Gary M; Tsai, Shirling; Modrall, J Gregory; Anderson, Jon A; Rectenwald, John; Timaran, Carlos

    2016-11-01

    A new proprietary image-processing system known as AlluraClarity, developed by Philips Healthcare (Best, The Netherlands) for radiation-based interventional procedures, claims to lower radiation dose while preserving image quality using noise-reduction algorithms. This study determined whether the surgeon and patient radiation dose during complex endovascular procedures (CEPs) is decreased after the implementation of this new operating system. Radiation dose to operators, procedure type, reference air kerma, kerma area product, and patient body mass index were recorded during CEPs on two Philips Allura FD 20 fluoroscopy systems with and without Clarity. Operator dose during CEPs was measured using optically stimulable, luminescent nanoDot (Landauer Inc, Glenwood, Ill) detectors placed outside the lead apron at the left upper chest position. nanoDots were read using a microStar ii (Landauer Inc) medical dosimetry system. For the CEPs in the Clarity group, the radiation dose to surgeons was also measured by the DoseAware (Philips Healthcare) personal dosimetry system. Side-by-side measurements of DoseAware and nanoDots allowed for cross-calibration between systems. Operator effective dose was determined using a modified Niklason algorithm. To control for patient size and case complexity, the average fluoroscopy dose rate and the dose per radiographic frame were adjusted for body mass index differences and then compared between the groups with and without Clarity by procedure. Additional factors, for example, physician practice patterns, that may have affected operator dose were inferred by comparing the ratio of the operator dose to procedural kerma area product with and without Clarity. A one-sided Wilcoxon rank sum test was used to compare groups for radiation doses, reference air kermas, and operating practices for each procedure type. The analysis included 234 CEPs; 95 performed without Clarity and 139 with Clarity. Practice patterns of operators during

  7. Proteoform-specific protein binding of small molecules in complex matrices

    USDA-ARS?s Scientific Manuscript database

    Characterizing the specific binding between protein targets and small molecules is critically important for drug discovery. Conventional assays require isolation and purification of small molecules from complex matrices through multistep chromatographic fractionation, which may alter their original ...

  8. Aloe QDM complex enhances specific cytotoxic T lymphocyte killing in vivo in metabolic disease mice.

    PubMed

    Lee, Youngjoo; Kim, Jiyeon; An, Jinho; Lee, Heetae; Kong, Hyunseok; Song, Youngcheon; Shin, Eunju; Do, Seon-Gil; Lee, Chong-Kil; Kim, Kyungjae

    2017-03-01

    We developed spontaneous diet-induced metabolic disease in mice by feeding them a high-fat diet for 23 weeks and administered Aloe QDM complex for 16 weeks to examine its restorative effect on immune disorders and metabolic syndrome. A series of immune functional assays indicated Aloe QDM complex enhanced lymphocyte proliferation and antigen-specific immunity as determined by the restored functions of cytotoxic T lymphocytes (CTL) and IgG production. The elevated serum TNF-α level was also regulated by Aloe QDM complex treatment, which suggested its complex therapeutic potential. As for metabolic phenotypes, oral administration of Aloe QDM complex significantly improved diabetic symptoms, including high fasting glucose levels and glucose tolerance, and distinctly alleviated lipid accumulation in adipose and hepatic tissue. The simultaneous restoration of Aloe QDM complex on metabolic syndrome and host immune dysfunction, especially on the specific CTL killing was first elucidated in our study.

  9. Web Mapping Architectures Based on Open Specifications and Free and Open Source Software in the Water Domain

    NASA Astrophysics Data System (ADS)

    Arias Muñoz, C.; Brovelli, M. A.; Kilsedar, C. E.; Moreno-Sanchez, R.; Oxoli, D.

    2017-09-01

    The availability of water-related data and information across different geographical and jurisdictional scales is of critical importance for the conservation and management of water resources in the 21st century. Today information assets are often found fragmented across multiple agencies that use incompatible data formats and procedures for data collection, storage, maintenance, analysis, and distribution. The growing adoption of Web mapping systems in the water domain is reducing the gap between data availability and its practical use and accessibility. Nevertheless, more attention must be given to the design and development of these systems to achieve high levels of interoperability and usability while fulfilling different end user informational needs. This paper first presents a brief overview of technologies used in the water domain, and then presents three examples of Web mapping architectures based on free and open source software (FOSS) and the use of open specifications (OS) that address different users' needs for data sharing, visualization, manipulation, scenario simulations, and map production. The purpose of the paper is to illustrate how the latest developments in OS for geospatial and water-related data collection, storage, and sharing, combined with the use of mature FOSS projects facilitate the creation of sophisticated interoperable Web-based information systems in the water domain.

  10. 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.

  11. Reusable Software.

    DTIC Science & Technology

    1984-03-01

    overseeing reusable software, the Reusable Software Organization ( RUSO ). This author does not feel at this time that establishment of such a specific...49] have not been accompanied by establishment of RUSO -like activities. There is need, however, for assurance that functions which a RUSO might be...assurance 6. establishment and maintenance of reuse archival facilities and activities. Actual establishment of a RUSO is best dictated by size of the

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

    NASA Technical Reports Server (NTRS)

    Berg, Melanie; LaBel, Kenneth A.

    2014-01-01

    We present a framework 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. Tissue-specific gene targeting by the multiprotein mammalian DREAM complex.

    PubMed

    Flowers, Stephen; Beck, George R; Moran, Elizabeth

    2011-08-12

    The mammalian DP, RB-like, E2F, and MuvB-like proteins (DREAM) complex, whose key components include p130 and E2F4, plays a fundamental role in repression of cell cycle-specific genes during growth arrest. Mammalian DREAM is well conserved with Drosophila and Caenorhabditis elegans complexes that repress pivotal developmental genes, but the mammalian complex has been thought to exist only in quiescent cells and not to be linked with development. However, new findings here identify tissue-specific promoters repressed by DREAM in proliferating precursors, revealing a new connection between control of growth arrest and terminal differentiation. Mechanistically, tissue-specific promoter occupation by DREAM is dependent on the integrity of a repressor form of the SWI/SNF chromatin-remodeling complex.

  14. 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.

  15. Design and implementation of software for automated quality control and data analysis for a complex LC/MS/MS assay for urine opiates and metabolites.

    PubMed

    Dickerson, Jane A; Schmeling, Michael; Hoofnagle, Andrew N; Hoffman, Noah G

    2013-01-16

    Mass spectrometry provides a powerful platform for performing quantitative, multiplexed assays in the clinical laboratory, but at the cost of increased complexity of analysis and quality assurance calculations compared to other methodologies. Here we describe the design and implementation of a software application that performs quality control calculations for a complex, multiplexed, mass spectrometric analysis of opioids and opioid metabolites. The development and implementation of this application improved our data analysis and quality assurance processes in several ways. First, use of the software significantly improved the procedural consistency for performing quality control calculations. Second, it reduced the amount of time technologists spent preparing and reviewing the data, saving on average over four hours per run, and in some cases improving turnaround time by a day. Third, it provides a mechanism for coupling procedural and software changes with the results of each analysis. We describe several key details of the implementation including the use of version control software and automated unit tests. These generally useful software engineering principles should be considered for any software development project in the clinical lab. Copyright © 2012 Elsevier B.V. All rights reserved.

  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. Understanding the specificity of serpin-protease complexes through interface analysis.

    PubMed

    Rashid, Qudsia; Kapil, Charu; Singh, Poonam; Kumari, Vineeta; Jairajpuri, Mohamad Aman

    2015-01-01

    Serpins such as antithrombin, heparin cofactor II, plasminogen activator inhibitor, antitrypsin, antichymotrypsin, and neuroserpin are involved in important biological processes by inhibiting specific serine proteases. Initially, the protease recognizes the mobile reactive loop of the serpin eliciting conformational changes, where the cleaved loop together with the protease inserts into β-sheet A, translocating the protease to the opposite side of inhibitor leading to its inactivation. Serpin interaction with proteases is governed mainly by the reactive center loop residues (RCL). However, in some inhibitory serpins, exosite residues apart from RCL have been shown to confer protease specificity. Further, this forms the basis of multi-specificity of some serpins, but the residues and their dimension at interface in serpin-protease complexes remain elusive. Here, we present a comprehensive structural analysis of the serpin-protease interfaces using bio COmplexes COntact MAPS (COCOMAPS), PRotein Interface Conservation and Energetics (PRICE), and ProFace programs. We have carried out interface, burial, and evolutionary analysis of different serpin-protease complexes. Among the studied complexes, non-inhibitory serpins exhibit larger interface region with greater number of residue involvement as compared to the inhibitory serpins. On comparing the multi-specific serpins (antithrombin and antitrypsin), a difference in the interface area and residue number was observed, suggestive of a differential mechanism of action of these serpins in regulating their different target proteases. Further, detailed study of these multi-specific serpins listed few essential residues (common in all the complexes) and certain specificity (unique to each complex) determining residues at their interfaces. Structural mapping of interface residues suggested that individual patches with evolutionary conserved residues in specific serpins determine their specificity towards a particular protease.

  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. 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,…

  20. 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…

  1. Identification and evolutionary analysis of tissue-specific isoforms of mitochondrial complex I subunit NDUFV3.

    PubMed

    Guerrero-Castillo, Sergio; Cabrera-Orefice, Alfredo; Huynen, Martijn A; Arnold, Susanne

    2017-03-01

    Mitochondrial complex I is the largest respiratory chain complex. Despite the enormous progress made studying its structure and function in recent years, potential regulatory roles of its accessory subunits remained largely unresolved. Complex I gene NDUFV3, which occurs in metazoa, contains an extra exon that is only present in vertebrates and thereby evolutionary even younger than the rest of the gene. Alternative splicing of this extra exon gives rise to a short NDUFV3-S and a long NDUFV3-L protein isoform. Complexome profiling revealed that the two NDUFV3 isoforms are constituents of the multi-subunit complex I. Further mass spectrometric analyses of complex I from different murine and bovine tissues showed a tissue-specific expression pattern of NDUFV3-S and NDUFV3-L. Hence, NDUFV3-S was identified as the only isoform in heart and skeletal muscle, whereas in liver, brain, and lung NDUFV3-L was expressed as the dominant isoform, together with NDUFV3-S present in all tissues analyzed. Thus, we identified NDUFV3 as the first out of 30 accessory subunits of complex I present in vertebrate- and tissue-specific isoforms. Interestingly, the tissue-specific expression pattern of NDUFV3-S and NDUFV3-L isoforms was paralleled by changes in kinetic parameters, especially the substrate affinity of complex I. This may indicate a regulatory role of the NDUFV3 isoforms in different vertebrate tissues.

  2. 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.

  3. 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.

  4. 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

    2016-03-23

    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.

  5. 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

  6. Efficient migration of complex off-line computer vision software to real-time system implementation on generic computer hardware.

    PubMed

    Tyrrell, James Alexander; LaPre, Justin M; Carothers, Christopher D; Roysam, Badrinath; Stewart, Charles V

    2004-06-01

    This paper addresses the problem of migrating large and complex computer vision code bases that have been developed off-line, into efficient real-time implementations avoiding the need for rewriting the software, and the associated costs. Creative linking strategies based on Linux loadable kernel modules are presented to create a simultaneous realization of real-time and off-line frame rate computer vision systems from a single code base. In this approach, systemic predictability is achieved by inserting time-critical components of a user-level executable directly into the kernel as a virtual device driver. This effectively emulates a single process space model that is nonpreemptable, nonpageable, and that has direct access to a powerful set of system-level services. This overall approach is shown to provide the basis for building a predictable frame-rate vision system using commercial off-the-shelf hardware and a standard uniprocessor Linux operating system. Experiments on a frame-rate vision system designed for computer-assisted laser retinal surgery show that this method reduces the variance of observed per-frame central processing unit cycle counts by two orders of magnitude. The conclusion is that when predictable application algorithms are used, it is possible to efficiently migrate to a predictable frame-rate computer vision system.

  7. Complex formation between human prostate-specific antigen and protease inhibitors in mouse plasma.

    PubMed

    Hekim, Can; Riipi, Tero; Zhu, Lei; Laakkonen, Pirjo; Stenman, Ulf-Håkan; Koistinen, Hannu

    2010-04-01

    When secreted from the prostate, most of prostate-specific antigen (PSA) is free and enzymatically active. Upon reaching circulation, active PSA is inactivated by complex formation with protease inhibitors. To justify the use of mouse models for evaluation of the function of PSA and for studies on therapeutic modalities based on modulation of PSA activity, it is important to know whether PSA complexation is similar in mouse and man. To characterize the circulating forms of PSA in mouse, we used subcutaneous LNCaP and 22RV1 human prostate cancer cell xenograft tumor models. We also added PSA directly to mouse serum. Free and total PSA were measured by immunoassay, and PSA complexes were extracted by immunopurification followed by SDS-PAGE, in-gel trypsin digestion and identification of signature peptides by mass spectrometry. In mice bearing xenograft tumors, 68% of the immunoreactive PSA occurred in complex, and when added to mouse serum, over 70% of PSA forms complexes that comprises alpha(2)-macroglobulin and members of the alpha(1)-antitrypsin (AAT) family. In mouse plasma, PSA forms complexes similar to those in man, but the major immunoreactive complex contains AAT rather than alpha(1)-antichymotrypsin, which is the main complex forming serpin in man. The complex formation of PSA produced by xenograft tumor models in mice is similar to that of human prostate tumors with respect to the complexation of PSA. (c) 2009 Wiley-Liss, Inc.

  8. In-silico discovery of cancer-specific peptide-HLA complexes for targeted therapy.

    PubMed

    Dhanik, Ankur; Kirshner, Jessica R; MacDonald, Douglas; Thurston, Gavin; Lin, Hsin C; Murphy, Andrew J; Zhang, Wen

    2016-07-20

    Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) Class I molecules bind to peptide fragments of proteins degraded inside the cell and display them on the cell surface. We are interested in peptide-HLA complexes involving peptides that are derived from proteins specifically expressed in cancer cells. Such complexes have been shown to provide an effective means of precisely targeting cancer cells by engineered T-cells and antibodies, which would be an improvement over current chemotherapeutic agents that indiscriminately kill proliferating cells. An important concern with the targeting of peptide-HLA complexes is off-target toxicity that could occur due to the presence of complexes similar to the target complex in cells from essential, normal tissues. We developed a novel computational strategy for identifying potential peptide-HLA cancer targets and evaluating the likelihood of off-target toxicity associated with these targets. Our strategy combines sequence-based and structure-based approaches in a unique way to predict potential off-targets. The focus of our work is on the complexes involving the most frequent HLA class I allele HLA-A*02:01. Using our strategy, we predicted the off-target toxicity observed in past clinical trials. We employed it to perform a first-ever comprehensive exploration of the human peptidome to identify cancer-specific targets utilizing gene expression data from TCGA (The Cancer Genome Atlas) and GTEx (Gene Tissue Expression), and structural data from PDB (Protein Data Bank). We have thus identified a list of 627 peptide-HLA complexes across various TCGA cancer types. Peptide-HLA complexes identified using our novel strategy could enable discovery of cancer-specific targets for engineered T-cells or antibody based therapy with minimal off-target toxicity.

  9. Complex oncogenic translocations with gene amplification are initiated by specific DNA breaks in lymphocytes.

    PubMed

    Wright, Sarah M; Woo, Yong H; Alley, Travis L; Shirley, Bobbi-Jo; Akeson, Ellen C; Snow, Kathy J; Maas, Sarah A; Elwell, Rachel L; Foreman, Oded; Mills, Kevin D

    2009-05-15

    Chromosomal instability is a hallmark of many tumor types. Complex chromosomal rearrangements with associated gene amplification, known as complicons, characterize many hematologic and solid cancers. Whereas chromosomal aberrations, including complicons, are useful diagnostic and prognostic cancer markers, their molecular origins are not known. Although accumulating evidence has implicated DNA double-strand break repair in suppression of oncogenic genome instability, the genomic elements required for chromosome rearrangements, especially complex lesions, have not been elucidated. Using a mouse model of B-lineage lymphoma, characterized by complicon formation involving the immunoglobulin heavy chain (Igh) locus and the c-myc oncogene, we have now investigated the requirement for specific genomic segments as donors for complex rearrangements. We now show that specific DNA double-strand breaks, occurring within a narrow segment of Igh, are necessary to initiate complicon formation. By contrast, neither specific DNA breaks nor the powerful intronic enhancer Emu are required for complicon-independent oncogenesis. This study is the first to delineate mechanisms of complex versus simple instability and the first to identify specific chromosomal elements required for complex chromosomal aberrations. These findings will illuminate genomic cancer susceptibility and risk factors.

  10. Site specific chemoselective labelling of proteins with robust and highly sensitive Ru(II) bathophenanthroline complexes.

    PubMed

    Uzagare, Matthew C; Claussnitzer, Iris; Gerrits, Michael; Bannwarth, Willi

    2012-03-21

    The bioorthogonal and chemoselective fluorescence labelling of several cell-free synthesized proteins containing a site-specifically incorporated azido amino acid was possible using different alkyne-functionalized Ru(II) bathophenanthroline complexes. We were able to achieve a selective labelling even in complex mixtures of proteins despite the fact that ruthenium dyes normally show a high tendency for unspecific interactions with proteins and are commonly used for total staining of proteins. Since the employed Ru complexes are extremely robust, photo-stable and highly sensitive, the approach should be applicable to the production of labelled proteins for single molecule spectroscopy and fluorescence-based interaction studies.

  11. World Workshop on Oral Medicine VI: Utilization of Oral Medicine-specific software for support of clinical care, research, and education: current status and strategy for broader implementation.

    PubMed

    Brailo, Vlaho; Firriolo, Francis John; Tanaka, Takako Imai; Varoni, Elena; Sykes, Rosemary; McCullough, Michael; Hua, Hong; Sklavounou, Alexandra; Jensen, Siri Beier; Lockhart, Peter B; Mattsson, Ulf; Jontell, Mats

    2015-08-01

    To assess the current scope and status of Oral Medicine-specific software (OMSS) utilized to support clinical care, research, and education in Oral Medicine and to propose a strategy for broader implementation of OMSS within the global Oral Medicine community. An invitation letter explaining the objectives was sent to the global Oral Medicine community. Respondents were interviewed to obtain information about different aspects of OMSS functionality. Ten OMSS tools were identified. Four were being used for clinical care, one was being used for research, two were being used for education, and three were multipurpose. Clinical software was being utilized as databases developed to integrate of different type of clinical information. Research software was designed to facilitate multicenter research. Educational software represented interactive, case-orientated technology designed for clinical training in Oral Medicine. Easy access to patient data was the most commonly reported advantage. Difficulty of use and poor integration with other software was the most commonly reported disadvantage. The OMSS presented in this paper demonstrate how information technology (IT) can have an impact on the quality of patient care, research, and education in the field of Oral Medicine. A strategy for broader implementation of OMSS is proposed. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Comparison of the current and a new RTVue OCT software version for detection of ganglion cell complex changes due to cataract surgery.

    PubMed

    Holló, Gábor; Naghizadeh, Farzaneh; Hsu, Sofia; Filkorn, Tamás; Bausz, Mária

    2015-12-01

    The purpose was to compare the current (6.3) and a novel software version (6.12) of the RTVue-100 optical coherence tomograph (RTVue OCT) for ganglion cell complex (GCC) and retinal nerve fibre layer thickness (RNFLT) changes after phacoemulsification in healthy cataract eyes, and to investigate whether version 6.12, in which image segmentation is improved, provides benefits over version 6.3 for RNFLT and GCC imaging via mild cataract. One eye of 22 consecutive healthy cataract patients were imaged before and 1 month after uncomplicated cataract surgery using RTVue-100 OCT software version 6.3. The images were analysed with both software versions. Signal strength index increased significantly after surgery for both RNFLT and the GCC measurements (p ≤ 0.0015). No difference was seen for any RNFLT parameter between the software versions and time points (p ≥ 0.0140). The GCC values did not differ between the versions either before or after surgery (p ≥ 0.4471), but all increased significantly after surgery with software version 6.12 (p < 0.0001). Neither focal loss volume (FLV) nor global loss volume (GLV) differed between the software versions before and after surgery, respectively, but GLV decreased (improved) significantly after surgery (p = 0.010 and <0.001 for versions 6.3 and 6.12, respectively). Cataract surgery induced similar changes with both software versions, but version 6.12 identified the increase of GCC thickness and the decrease of GLV better than the current version. Although no significant difference between software versions was seen before surgery, our results suggest that version 6.12 may be more precise in measuring GCC parameters than the currently available version.

  13. 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.

  14. 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.

  15. 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.

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

    PubMed Central

    Ghanbari, Yasser; Bloy, Luke; Edgar, J. Christopher; Blaskey, Lisa; Verma, Ragini

    2013-01-01

    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. Multi-scale entropy was computed to quantify the signal complexity, and synchronization likelihood was used to evaluate functional connectivity (FC), with node strength values providing a sensor-level measure of connectivity to facilitate comparisons with complexity. Sensor level analysis of complexity and connectivity was performed at different frequency bands computed from resting state MEG from 26 children with ASD and 22 typically developing controls (TD). Analyses revealed band-specific group differences in each measure that agreed with other functional studies in fMRI and EEG: higher complexity in TD than ASD, in frontal regions in the delta band and occipital-parietal regions in the alpha band, and lower complexity in TD than in ASD in delta (parietal regions), theta (central and temporal regions) and gamma (frontal-central boundary regions); increased short-range connectivity in ASD in the frontal lobe in the delta band and long-range connectivity in the temporal, parietal and occipital lobes in the alpha band. Finally, and perhaps most strikingly, group differences between ASD and TD in complexity and FC appear spatially complementary, such that where FC was elevated in ASD, complexity was reduced (and vice versa). The correlation of regional average complexity and connectivity node strength with symptom severity scores of ASD subjects supported the overall complementarity (with opposing sign) of connectivity and complexity measures, pointing to either diminished connectivity leading to elevated entropy due to poor inhibitory regulation or chaotic signals prohibiting effective measure of connectivity. PMID

  17. DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

    PubMed

    Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

    2015-10-01

    The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (p<2.2e-16) than HK gene promoters. The entropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  19. Cas6 specificity and CRISPR RNA loading in a complex CRISPR-Cas system.

    PubMed

    Sokolowski, Richard D; Graham, Shirley; White, Malcolm F

    2014-06-01

    CRISPR-Cas is an adaptive prokaryotic immune system, providing protection against viruses and other mobile genetic elements. In type I and type III CRISPR-Cas systems, CRISPR RNA (crRNA) is generated by cleavage of a primary transcript by the Cas6 endonuclease and loaded into multisubunit surveillance/effector complexes, allowing homology-directed detection and cleavage of invading elements. Highly studied CRISPR-Cas systems such as those in Escherichia coli and Pseudomonas aeruginosa have a single Cas6 enzyme that is an integral subunit of the surveillance complex. By contrast, Sulfolobus solfataricus has a complex CRISPR-Cas system with three types of surveillance complexes (Cascade/type I-A, CSM/type III-A and CMR/type III-B), five Cas6 paralogues and two different CRISPR-repeat families (AB and CD). Here, we investigate the kinetic properties of two different Cas6 paralogues from S. solfataricus. The Cas6-1 subtype is specific for CD-family CRISPR repeats, generating crRNA by multiple turnover catalysis whilst Cas6-3 has a broader specificity and also processes a non-coding RNA with a CRISPR repeat-related sequence. Deep sequencing of crRNA in surveillance complexes reveals a biased distribution of spacers derived from AB and CD loci, suggesting functional coupling between Cas6 paralogues and their downstream effector complexes.

  20. The role of prothrombin complex concentrates in reversal of target specific anticoagulants.

    PubMed

    Babilonia, Katrina; Trujillo, Toby

    2014-01-01

    Over the past several years a new era for patients requiring anticoagulation has arrived. The approval of new target specific oral anticoagulants offers practitioners several advantages over traditionally used vitamin K antagonist agents including predictable pharmacokinetics, rapid onset of action, comparable efficacy and safety, all without the need for routine monitoring. Despite these benefits, hemorrhagic complicates are inevitable with any anticoagulation treatment. One of the major disadvantages of the new oral anticoagulants is lack of specific antidotes or reversal agents for patients with serious bleeding or need for urgent surgery. As use of the new target specific oral anticoagulants continues to increase, practitioners will need to understand both the pharmacodynamics and pharmacokinetic properties of the agents, as well as, the available literature with use of non-specific therapies to reverse anticoagulation. Four factor prothrombin complex concentrates have been available for several years in Europe, and recently became available in the United States with approval of Kcentra. These products have shown efficacy in reversing anticoagulation from vitamin K antagonists, however their usefulness with the new target specific oral anticoagulants is poorly understood. This article will review the properties of dabigatran, rivaroxaban and apixaban, as well as the limited literature available on the effectiveness of prothrombin complex concentrates in reversal of their anticoagulant effects. Additional studies are needed to more accurately define the role of prothrombin complex concentrates in patients with life threatening bleeding or who require emergent surgery, as current data is both limited and conflicting.

  1. The role of prothrombin complex concentrates in reversal of target specific anticoagulants

    PubMed Central

    2014-01-01

    Over the past several years a new era for patients requiring anticoagulation has arrived. The approval of new target specific oral anticoagulants offers practitioners several advantages over traditionally used vitamin K antagonist agents including predictable pharmacokinetics, rapid onset of action, comparable efficacy and safety, all without the need for routine monitoring. Despite these benefits, hemorrhagic complicates are inevitable with any anticoagulation treatment. One of the major disadvantages of the new oral anticoagulants is lack of specific antidotes or reversal agents for patients with serious bleeding or need for urgent surgery. As use of the new target specific oral anticoagulants continues to increase, practitioners will need to understand both the pharmacodynamics and pharmacokinetic properties of the agents, as well as, the available literature with use of non-specific therapies to reverse anticoagulation. Four factor prothrombin complex concentrates have been available for several years in Europe, and recently became available in the United States with approval of Kcentra. These products have shown efficacy in reversing anticoagulation from vitamin K antagonists, however their usefulness with the new target specific oral anticoagulants is poorly understood. This article will review the properties of dabigatran, rivaroxaban and apixaban, as well as the limited literature available on the effectiveness of prothrombin complex concentrates in reversal of their anticoagulant effects. Additional studies are needed to more accurately define the role of prothrombin complex concentrates in patients with life threatening bleeding or who require emergent surgery, as current data is both limited and conflicting. PMID:24742134

  2. The CSSIAR v.1.00 Software: A new tool based on SIAR to assess soil redistribution using Compound Specific Stable Isotopes

    NASA Astrophysics Data System (ADS)

    Sergio, de los Santos-Villalobos; Claudio, Bravo-Linares; dos Anjos Roberto, Meigikos; Renan, Cardoso; Max, Gibbs; Andrew, Swales; Lionel, Mabit; Gerd, Dercon

    Soil erosion is one of the biggest challenges for food production around the world. Many techniques have been used to evaluate and mitigate soil degradation. Nowadays isotopic techniques are becoming a powerful tool to assess soil apportionment. One of the innovative techniques used is the Compound Specific Stable Isotopes (CSSI) analysis, which has been used to track down sediments and specify their sources by the isotopic signature of δ13 C in specific fatty acids. The application of this technique on soil apportionment has been recently developed, however there is a lack of user-friendly Software for data processing and interpretation. The aim of this article is to introduce a new open source tool for working with data sets generated by the use of the CSSI technique to assess soil apportionment, called the CSSIARv1.00 Software

  3. 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

  4. 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.

  5. 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.

  6. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. 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.

  8. Free and complexed prostate-specific antigen (PSA) in the early detection of prostate cancer.

    PubMed

    Tello, F L; Prats, C H; González, M D

    2001-02-01

    We evaluated the analytical performance and diagnostic utility of complexed prostate-specific antigen (CPSA) and their ratios, complexed-to-total PSA (C/T PSA) and free-to-complexed PSA (F/C PSA), in comparison with the total PSA (TPSA) and free-to-total PSA ratio (F/T PSA) as means of diagnosing prostate cancer (PC). Samples (n=101) were drawn from men with no evidence of malignancy (n=80) and from men with PC (n=21) at biopsy. For determination of the F/T PSA ratio, the DPC Immulite-2000 method was used; and the Bayer Immuno-1 CPSA and TPSA assays were used to determine the C/T PSA ratio. The Bayer Immuno-1 CPSA assay provides accurate and precise CPSA values in human serum. The performance of the different forms and ratios was compared using receiver operating characteristic curve analysis. CPSA had the greatest area under the curve (AUC, 0.689) although it was not statistically different from the other parameters. A cut-off value of 4.66 ng/ml for CPSA provided a specificity of 38% and a sensitivity of 93%. The F/C PSA ratio maintained a sensitivity of 93% and had an increased specificity of 41%. The measurement of CPSA provides a slight increase in specificity compared with the use of the TPSA in the early detection of prostate cancer.

  9. Visualization of specific γ-secretase complexes using bimolecular fluorescence complementation.

    PubMed

    Meckler, Xavier; Checler, Frédéric

    2014-01-01

    γ-Secretase is involved in the regulated intramembrane proteolysis of amyloid-β protein precursor (AβPP) and of many other important physiological substrates. γ-secretase is a multiproteic complex made of four main core components, namely presenilin 1 or 2, APH-1, PEN-2, and Nicastrin. Since APH-1 exists as different variants, combinations of these proteins can theoretically yield distinct γ-secretase complexes. Whether γ-secretase complexes trafficking and targeting to either similar or distinct subcellular compartments depend upon their molecular composition remains unknown. A differential complex-specific distribution may drive a narrow specificity for a subset of substrates that would traffic within the same cellular compartments. Here, we generated bigenic expression vectors to co-express untagged nicastrin or presenilin 1 together with either PEN-2 or distinct variants of APH-1 (aL, aS and b) tagged with complementary fragments of the fluorescent protein Venus. We show that these constructs allow the formation of functional γ-secretase complexes and their visualization with bimolecular fluorescence complementation (BiFC). BiFC can be detected at the plasma membrane as well as in endosomes/lysosomes in addition to the endoplasmic reticulum (ER) of COS-7 cells transfected with the different variants of APH-1. However, the majority of cells co-transfected with APH-1b presented BiFC signal only in the ER, suggesting enhanced retention/retrieval of APH-1b-containing γ-secretase complexes. Therefore, the new tools described here should be helpful to decipher the precise subcellular trafficking of γ-secretase complexes and to delineate the distinct variant-linked pathways in various cellular systems.

  10. Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions

    PubMed Central

    Haab, Brian B; Dunham, Maitreya J; Brown, Patrick O

    2001-01-01

    Background: We have developed and tested a method for printing protein microarrays and using these microarrays in a comparative fluorescence assay to measure the abundance of many specific proteins in complex solutions. A robotic device was used to print hundreds of specific antibody or antigen solutions in an array on the surface of derivatized microscope slides. Two complex protein samples, one serving as a standard for comparative quantitation, the other representing an experimental sample in which the protein quantities were to be measured, were labeled by covalent attachment of spectrally resolvable fluorescent dyes. Results: Specific antibody-antigen interactions localized specific components of the complex mixtures to defined cognate spots in the array, where the relative intensity of the fluorescent signal representing the experimental sample and the reference standard provided a measure of each protein's abundance in the experimental sample. To test the specificity, sensitivity and accuracy of this assay, we analyzed the performance of 115 antibody/antigen pairs. 50% of the arrayed antigens and 20% of the arrayed antibodies provided specific and accurate measurements of their cognate ligands at or below concentrations of 0.34 μg/ml and 1.6 μg/ml, respectively. Some of the antibody/antigen pairs allowed detection of the cognate ligands at absolute concentrations below 1 ng/ml, and partial concentrations of 1 part in 106, sensitivities sufficient for measurement of many clinically important proteins in patient blood samples. Conclusions: These results suggest that protein microarrays can provide a practical means to characterize patterns of variation in hundreds of thousands of different proteins in clinical or research applications. PMID:11182887

  11. Milk whey-specific immune complexes in allergic and non-allergic subjects.

    PubMed

    Bell, S J; Potter, P C

    1988-10-01

    We developed an antigen- and isotype-specific ELISA for the rapid detection of native serum immune complexes (IC). It is a sandwich assay, in which a solid phase antigen-specific capture antibody selectively binds the antigen-specific IC via the antigen. The isotype of the bound IC is then identified using an enzyme-labelled indicator antibody. Using this sensitive assay system, we were able to detect native serum milk whey-specific immune complexes (SMIC) of the IgG, IgE and IgA isotypes. Detectable amounts of native serum SMIC of all three isotypes were found in sera of the majority of both atopic and non-atopic subjects. The ELISA was then used to compare the levels of native IgE SMIC in sera of milk RAST positive atopic patients with those found in milk RAST negative atopic patient sera. Milk RAST positive patient sera were found to have significantly higher mean levels (P less than or equal to 0.005) of native IgE SMIC than milk RAST negative sera. Sera of other atopic individuals were also found to contain significantly higher mean levels (P less than or equal to 0.005) of native IgG and IgA SMIC than non-atopic donors. IgE IC may specifically be involved in adverse symptoms seen in milk allergic patients.

  12. Substrate-specific regulation of ubiquitination by the anaphase-promoting complex

    PubMed Central

    Song, Ling

    2011-01-01

    By orchestrating the sequential degradation of a large number of cell cycle regulators, the ubiquitin ligase anaphase-promoting complex (APC/C) is essential for proliferation in all eukaryotes. The correct timing of APC/C-dependent substrate degradation, a critical feature of progression through mitosis, was long known to be controlled by mechanisms targeting the core APC/C-machinery. Recent experiments, however have revealed an important contribution of substrate-specific regulation of the APC/C to achieve accurate cell division. In this perspective, we describe different mechanisms of substrate-specific APC/C-regulation and discuss their importance for cell division. PMID:21191176

  13. 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)

  14. 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.

  15. TU-tagging: cell type specific RNA isolation from intact complex tissues

    PubMed Central

    Miller, Michael R.; Robinson, Kristin J.; Cleary, Michael D.; Doe, Chris Q.

    2009-01-01

    We show that the combination of spatially restricted uracil phosphoribosyltransferase (UPRT) expression with 4-thiouracil (4TU) delivery can be used to label and purify cell type specific RNA from intact complex tissues in Drosophila melanogaster. This method is useful for isolating RNA from cell types that are difficult to isolate by dissection or dissociation methods and should work in many organisms, including mammals and other vertebrates. PMID:19430475

  16. A fast and efficient procedure to produce scFvs specific for large macromolecular complexes.

    PubMed

    Wu, Si; Ke, Ailong; Doudna, Jennifer A

    2007-01-10

    We have expanded the application of antibody phage display to a new type of antigen: ribonucleoprotein (RNP) complexes. We describe a simple and efficient method for screening antibodies specific for large intact RNPs and individual components. We also describe a fast and easy method to overcome the abundance of amber stop codons in the positive phage clones. The resulting antibodies have been used in ELISA and Western blot analysis.

  17. 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.

  18. An Embryonic Stem Cell-Specific NuRD Complex Functions through Interaction with WDR5.

    PubMed

    Ee, Ly-Sha; McCannell, Kurtis N; Tang, Yang; Fernandes, Nancy; Hardy, W Rod; Green, Michael R; Chu, Feixia; Fazzio, Thomas G

    2017-06-06

    The Nucleosome Remodeling and Deacetylase (NuRD) complex is a chromatin regulatory complex that functions as a transcriptional co-repressor in metazoans. The NuRD subunit MBD3 is essential for targeting and assembly of a functional NuRD complex as well as embryonic stem cell (ESC) pluripotency. Three MBD3 isoforms (MBD3A, MBD3B, and MBD3C) are expressed in mouse. Here, we find that the MBD3C isoform contains a unique 50-amino-acid N-terminal region that is necessary for MBD3C to specifically interact with the histone H3 binding protein WDR5. Domain analyses of WDR5 reveal that the H3 binding pocket is required for interaction with MBD3C. We find that while Mbd3c knockout ESCs differentiate normally, MBD3C is redundant with the MBD3A and MBD3B isoforms in regulation of gene expression, with the unique MBD3C N terminus required for this redundancy. Together, our data characterize a unique NuRD complex variant that functions specifically in ESCs. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Discrete promoter elements affect specific properties of RNA polymerase II transcription complexes

    PubMed Central

    Steinke, John W.; Kopytek, Stephan J.; Peterson, David O.

    2000-01-01

    The frequency of transcription initiation at specific RNA polymerase II promoters is, in many cases, related to the ability of the promoter to recruit the transcription machinery to a specific site. However, there may also be functional differences in the properties of assembled transcription complexes that are promoter-specific or regulator-dependent and affect their activity. Transcription complexes formed on variants of the adenovirus major late (AdML) promoter were found to differ in several ways. Mutations in the initiator element increased the sarkosyl sensitivity of the rate of elongation and decreased the rate of early steps in initiation as revealed by a sarkosyl challenge assay that exploited the resistance of RNA synthesis to high concentrations of sarkosyl after formation of one or two phospho­diester bonds. Similar, but clearly distinct, effects were also observed after deletion of the binding site for upstream stimulatory factor from the AdML promoter. In contrast, deletion of binding sites for nuclear factor 1 and Oct-1, as well as mutations in the recognition sequence for initiation site binding protein, were without apparent effect on transcription complexes on templates containing the mouse mammary tumor virus promoter. PMID:10908329

  20. Discrete promoter elements affect specific properties of RNA polymerase II transcription complexes.

    PubMed

    Steinke, J W; Kopytek, S J; Peterson, D O

    2000-07-15

    The frequency of transcription initiation at specific RNA polymerase II promoters is, in many cases, related to the ability of the promoter to recruit the transcription machinery to a specific site. However, there may also be functional differences in the properties of assembled transcription complexes that are promoter-specific or regulator-dependent and affect their activity. Transcription complexes formed on variants of the adenovirus major late (AdML) promoter were found to differ in several ways. Mutations in the initiator element increased the sarkosyl sensitivity of the rate of elongation and decreased the rate of early steps in initiation as revealed by a sarkosyl challenge assay that exploited the resistance of RNA synthesis to high concentrations of sarkosyl after formation of one or two phospho-diester bonds. Similar, but clearly distinct, effects were also observed after deletion of the binding site for upstream stimulatory factor from the AdML promoter. In contrast, deletion of binding sites for nuclear factor 1 and Oct-1, as well as mutations in the recognition sequence for initiation site binding protein, were without apparent effect on transcription complexes on templates containing the mouse mammary tumor virus promoter.

  1. Advanced flight software reconfiguraton

    NASA Technical Reports Server (NTRS)

    Porcher, Bryan

    1991-01-01

    Information is given in viewgraph form on advanced flight software reconfiguration. Reconfiguration is defined as identifying mission and configuration specific requirements, controlling mission and configuration specific data, binding this information to the flight software code to perform specific missions, and the release and distribution of the flight software. The objectives are to develop, demonstrate, and validate advanced software reconfiguration tools and techniques; to demonstrate reconfiguration approaches on Space Station Freedom (SSF) onboard systems displays; and to interactively test onboard systems displays, flight software, and flight data.

  2. Complex Sentence Comprehension and Working Memory in Children With Specific Language Impairment

    PubMed Central

    Montgomery, James W.; Evans, Julia L.

    2015-01-01

    Purpose This study investigated the association of 2 mechanisms of working memory (phonological short-term memory [PSTM], attentional resource capacity/allocation) with the sentence comprehension of school-age children with specific language impairment (SLI) and 2 groups of control children. Method Twenty-four children with SLI, 18 age-matched (CA) children, and 16 language- and memory-matched (LMM) children completed a nonword repetition task (PSTM), the competing language processing task (CLPT; resource capacity/allocation), and a sentence comprehension task comprising complex and simple sentences. Results (1) The SLI group performed worse than the CA group on each memory task; (2) all 3 groups showed comparable simple sentence comprehension, but for complex sentences, the SLI and LMM groups performed worse than the CA group; (3) for the SLI group, (a) CLPT correlated with complex sentence comprehension, and (b) nonword repetition correlated with simple sentence comprehension; (4) for CA children, neither memory variable correlated with either sentence type; and (5) for LMM children, only CLPT correlated with complex sentences. Conclusions Comprehension of both complex and simple grammar by school-age children with SLI is a mentally demanding activity, requiring significant working memory resources. PMID:18723601

  3. 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.

  4. Specific activation of human interleukin-5 depends on de novo synthesis of an AP-1 complex.

    PubMed

    Schwenger, Gretchen T F; Kok, Chee Choy; Arthaningtyas, Estri; Thomas, Marc A; Sanderson, Colin J; Mordvinov, Viatcheslav A

    2002-12-06

    It is clear from the biology of eosinophilia that a specific regulatory mechanism must exist. Because interleukin-5 (IL5) is the key regulatory cytokine, it follows that a gene-specific control of IL5 expression must exist that differs even from closely related cytokines such as IL4. Two features of IL5 induction make it unique compared with other cytokines; first, induction by cyclic adenosine monophosphate (cAMP), which inhibits other T-cell-derived cytokines, and second, sensitivity to protein synthesis inhibitors, which have no effect on other cytokines. This study has utilized the activation of different transcription factors by different stimuli in a human T-cell line to study the role of conserved lymphokine element 0 (CLE0) in the specific induction of IL5. In unstimulated cells the ubiquitous Oct-1 binds to CLE0. Stimulation induces de novo synthesis of the AP-1 members JunD and Fra-2, which bind to CLE0. The amount of IL5 produced correlates with the production of the AP-1 complex, suggesting a key role in IL5 expression. The formation of the AP-1 complex is essential, but the rate-limiting step is the synthesis of AP-1, especially Fra-2. This provides an explanation for the sensitivity of IL5 to protein synthesis inhibitors and a mechanism for the specific induction of IL5 compared with other cytokines.

  5. Non-DNA-binding cofactors enhance DNA-binding specificity of a transcriptional regulatory complex

    PubMed Central

    Siggers, Trevor; Duyzend, Michael H; Reddy, Jessica; Khan, Sidra; Bulyk, Martha L

    2011-01-01

    Recruitment of cofactors to specific DNA sites is integral for specificity in gene regulation. As a model system, we examined how targeting and transcriptional control of the sulfur metabolism genes in Saccharomyces cerevisiae is governed by recruitment of the transcriptional co-activator Met4. We developed genome-scale approaches to measure transcription factor (TF) DNA-binding affinities and cofactor recruitment to >1300 genomic binding site sequences. We report that genes responding to the TF Cbf1 and cofactor Met28 contain a novel ‘recruitment motif' (RYAAT), adjacent to Cbf1 binding sites, which enhances the binding of a Met4–Met28–Cbf1 regulatory complex, and that abrogation of this motif significantly reduces gene induction under low-sulfur conditions. Furthermore, we show that correct recognition of this composite motif requires both non-DNA-binding cofactors Met4 and Met28. Finally, we demonstrate that the presence of an RYAAT motif next to a Cbf1 site, rather than Cbf1 binding affinity, specifies Cbf1-dependent sulfur metabolism genes. Our results highlight the need to examine TF/cofactor complexes, as novel specificity can result from cofactors that lack intrinsic DNA-binding specificity. PMID:22146299

  6. Specific heteromeric association of four transmembrane peptides derived from platelet glycoprotein Ib-IX complex

    PubMed Central

    Luo, Shi-Zhong; Li, Renhao

    2008-01-01

    Summary As the receptor on platelet surface for von Willebrand factor, glycoprotein (GP) Ib-IX complex is critically involved in hemostasis and thrombosis. How the complex is assembled from GP Ibα, GP Ibβ and GP IX subunits, all of which are type I transmembrane proteins, is not entirely clear. Genetic and mutational analyses have identified the transmembrane (TM) domains of these subunits as active participants in complex assembly. In this study, peptides containing the transmembrane domain of each subunit have been produced and their interaction with one another characterized. Only the Ibβ TM sequence, not Ibα and IX counterparts, can form homo-oligomers in SDS electrophoresis and TOXCAT assays. Following up on our earlier observation that a Ibβ-Ibα-Ibβ peptide complex (αβ2) linked through native juxtamembrane disulfide bonds could be produced from isolated Ibα and Ibβ TM peptides in detergent micelles, here we show that addition of the IX TM peptide facilitates formation of the native αβ2 complex, reproducing the same effect by the IX subunit in cells expressing GP Ib-IX complex. Specific fluorescence resonance energy transfer was observed between donor-labeled αβ2 peptide complex and acceptor-conjugated IX TM peptide in micelles. Finally, the mutation D135K in the IX TM peptide could hamper both the αβ2 complex formation and the energy transfer, consistent with its reported effect in the full-length complex. Overall, our results have demonstrated directly the native-like heteromeric interaction among the isolated Ibα, Ibβ and IX TM peptides, which provides support for the four-helical bundle model of the TM domains in GP Ib-IX complex and paves the way for further structural analysis. The methods developed in this study may also be applicable to other studies of heteromeric interaction among multiple TM helices. PMID:18674540

  7. Variable motif utilization in homeotic selector (Hox)-cofactor complex formation controls specificity.

    PubMed

    Lelli, Katherine M; Noro, Barbara; Mann, Richard S

    2011-12-27

    Homeotic selector (Hox) proteins often bind DNA cooperatively with cofactors such as Extradenticle (Exd) and Homothorax (Hth) to achieve functional specificity in vivo. Previous studies identified the Hox YPWM motif as an important Exd interaction motif. Using a comparative approach, we characterize the contribution of this and additional conserved sequence motifs to the regulation of specific target genes for three Drosophila Hox proteins. We find that Sex combs reduced (Scr) uses a simple interaction mechanism, where a single tryptophan-containing motif is necessary for Exd-dependent DNA-binding and in vivo functions. Abdominal-A (AbdA) is more complex, using multiple conserved motifs in a context-dependent manner. Lastly, Ultrabithorax (Ubx) is the most flexible, in that it uses multiple conserved motifs that function in parallel to regulate target genes in vivo. We propose that using different binding mechanisms with the same cofactor may be one strategy to achieve functional specificity in vivo.

  8. Specificity-Determining DNA Triplet Code for Positioning of Human Preinitiation Complex

    NASA Astrophysics Data System (ADS)

    Goldshtein, Matan; Lukatsky, David B.

    2017-05-01

    The notion that transcription factors bind DNA only through specific, consensus binding sites has been recently questioned. In a pioneering study by Pugh and Venters no specific consensus motif for the positioning of the human pre-initiation complex (PIC) has been identified. Here, we reveal that nonconsensus, statistical, DNA triplet code provides specificity for the positioning of the human PIC. In particular, we reveal a highly non-random, statistical pattern of repetitive nucleotide triplets that correlates with the genome-wide binding preferences of PIC measured by Chip-exo. We analyze the triplet enrichment and depletion near the transcription start site (TSS) and identify triplets that have the strongest effect on PIC-DNA nonconsensus binding. Our results constitute a proof-of-concept for a new design principle for protein-DNA recognition in the human genome, which can lead to a better mechanistic understanding of transcriptional regulation.

  9. Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment.

    PubMed

    Hodges, Emily; Molaro, Antoine; Dos Santos, Camila O; Thekkat, Pramod; Song, Qiang; Uren, Philip J; Park, Jin; Butler, Jason; Rafii, Shahin; McCombie, W Richard; Smith, Andrew D; Hannon, Gregory J

    2011-10-07

    DNA methylation has been implicated as an epigenetic component of mechanisms that stabilize cell-fate decisions. Here, we have characterized the methylomes of human female hematopoietic stem/progenitor cells (HSPCs) and mature cells from the myeloid and lymphoid lineages. Hypomethylated regions (HMRs) associated with lineage-specific genes were often methylated in the opposing lineage. In HSPCs, these sites tended to show intermediate, complex patterns that resolve to uniformity upon differentiation, by increased or decreased methylation. Promoter HMRs shared across diverse cell types typically display a constitutive core that expands and contracts in a lineage-specific manner to fine-tune the expression of associated genes. Many newly identified intergenic HMRs, both constitutive and lineage specific, were enriched for factor binding sites with an implied role in genome organization and regulation of gene expression, respectively. Overall, our studies represent an important reference data set and provide insights into directional changes in DNA methylation as cells adopt terminal fates.

  10. 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

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

    PubMed

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

    2014-12-01

    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

  12. 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. © The Author(s) 2014.

  13. Distinct Roles of Meiosis-Specific Cohesin Complexes in Mammalian Spermatogenesis.

    PubMed

    Biswas, Uddipta; Hempel, Kai; Llano, Elena; Pendas, Alberto; Jessberger, Rolf

    2016-10-01

    Mammalian meiocytes feature four meiosis-specific cohesin proteins in addition to ubiquitous ones, but the roles of the individual cohesin complexes are incompletely understood. To decipher the functions of the two meiosis-specific kleisins, REC8 or RAD21L, together with the only meiosis-specific SMC protein SMC1β, we generated Smc1β-/-Rec8-/- and Smc1β-/-Rad21L-/- mouse mutants. Analysis of spermatocyte chromosomes revealed that besides SMC1β complexes, SMC1α/RAD21 and to a small extent SMC1α/REC8 contribute to chromosome axis length. Removal of SMC1β and RAD21L almost completely abolishes all chromosome axes. The sex chromosomes do not pair in single or double mutants, and autosomal synapsis is impaired in all mutants. Super resolution microscopy revealed synapsis-associated SYCP1 aberrantly deposited between sister chromatids and on single chromatids in Smc1β-/-Rad21L-/- cells. All mutants show telomere length reduction and structural disruptions, while wild-type telomeres feature a circular TRF2 structure reminiscent of t-loops. There is no loss of centromeric cohesion in both double mutants at leptonema/early zygonema, indicating that, at least in the mutant backgrounds, an SMC1α/RAD21 complex provides centromeric cohesion at this early stage. Thus, in early prophase I the most prominent roles of the meiosis-specific cohesins are in axis-related features such as axis length, synapsis and telomere integrity rather than centromeric cohesion.

  14. Distinct Roles of Meiosis-Specific Cohesin Complexes in Mammalian Spermatogenesis

    PubMed Central

    Biswas, Uddipta; Hempel, Kai; Llano, Elena; Pendas, Alberto; Jessberger, Rolf

    2016-01-01

    Mammalian meiocytes feature four meiosis-specific cohesin proteins in addition to ubiquitous ones, but the roles of the individual cohesin complexes are incompletely understood. To decipher the functions of the two meiosis-specific kleisins, REC8 or RAD21L, together with the only meiosis-specific SMC protein SMC1β, we generated Smc1β-/-Rec8-/- and Smc1β-/-Rad21L-/- mouse mutants. Analysis of spermatocyte chromosomes revealed that besides SMC1β complexes, SMC1α/RAD21 and to a small extent SMC1α/REC8 contribute to chromosome axis length. Removal of SMC1β and RAD21L almost completely abolishes all chromosome axes. The sex chromosomes do not pair in single or double mutants, and autosomal synapsis is impaired in all mutants. Super resolution microscopy revealed synapsis-associated SYCP1 aberrantly deposited between sister chromatids and on single chromatids in Smc1β-/-Rad21L-/- cells. All mutants show telomere length reduction and structural disruptions, while wild-type telomeres feature a circular TRF2 structure reminiscent of t-loops. There is no loss of centromeric cohesion in both double mutants at leptonema/early zygonema, indicating that, at least in the mutant backgrounds, an SMC1α/RAD21 complex provides centromeric cohesion at this early stage. Thus, in early prophase I the most prominent roles of the meiosis-specific cohesins are in axis-related features such as axis length, synapsis and telomere integrity rather than centromeric cohesion. PMID:27792785

  15. How do ncRNAs guide chromatin-modifying complexes to specific locations within the nucleus?

    PubMed

    Scott, Maxwell J; Li, Fang

    2008-01-01

    Transcriptome analyses have led to the realization that eukaryotic cells make a large number of noncoding RNAs (ncRNAs). It appears that some of these are involved in guiding chromatin-modifying complexes to specific locations within the nucleus. How such ncRNAs function is largely unknown but various models have been proposed. Here we briefly discuss the evidence supporting two such models; that ncRNAs function by annealing either with nascent transcripts or with homologous DNA sequences. We then review a third model that is based on our recent work on the role of the noncoding roX RNAs in the localization of the MSL complex to sites on the X chromosome in Drosophila. Our results suggest that the MSL1 and MSL2 proteins bind to chromatin but it is the incorporation of the roX RNAs into the complex that somehow alters the binding specificity of the MSL1/MSL2 proteins to recognize sites on the X chromosome.

  16. Phosphodiester hydrolysis and specific DNA binding and cleavage promoted by guanidinium-functionalized zinc complexes.

    PubMed

    He, Juan; Sun, Jing; Mao, Zong-Wan; Ji, Liang-Nian; Sun, Hongzhe

    2009-05-01

    Two new Zn(II) complexes containing guanidinium groups, [Zn(L(1))Cl(2)](ClO(4))(2).H(2)O.CH(3)OH (1) and [Zn(L(2))Cl(2)](ClO(4))(2).0.5H(2)O (2), were synthesized and characterized (L(1)=5,5'-di[1-(guanidyl)methyl]-2,2'-bipyridyl bication and L(2)=6,6'-di[1-(guanidyl)methyl]-2,2'-bipyridyl bication). Both complexes are able to catalyze bis(p-nitrophenyl) phosphate (BNPP) hydrolysis efficiently. Obtained kinetic data reveal that both 1 and 2 show nearly 300- and 600-fold rate enhancement of BNPP hydrolysis, respectively, compared to their simple analogue without the guanidinium groups [Zn(bpy)Cl(2)] (bpy=2,2'-bipyridy) (3). Enhanced acceleration for cleavage of BNPP could be attributed to cooperative interaction between the Zn(II) ion and the guanidinium groups by electrostatic interaction and H-bonding. Studies on inhibition of sequence-specific endonucleases (DraI and SmaI) by complexes show that 1 and 2 are able to recognize nucleotide sequence, -TTT;AAA-, and highly effectively cleave the plasmid DNA in the presence of hydrogen peroxide, while 3 has no specific binding to the DNA target sequences and only shows low DNA cleavage activity.

  17. A mammalian nervous-system-specific plasma membrane proteasome complex that modulates neuronal function.

    PubMed

    Ramachandran, Kapil V; Margolis, Seth S

    2017-04-01

    In the nervous system, rapidly occurring processes such as neuronal transmission and calcium signaling are affected by short-term inhibition of proteasome function. It is unclear how proteasomes are able to acutely regulate such processes, as this action is inconsistent with their canonical role in proteostasis. Here we describe a mammalian nervous-system-specific membrane proteasome complex that directly and rapidly modulates neuronal function by degrading intracellular proteins into extracellular peptides that can stimulate neuronal signaling. This proteasome complex is closely associated with neuronal plasma membranes, exposed to the extracellular space, and catalytically active. Selective inhibition of the membrane proteasome complex by a cell-impermeable proteasome inhibitor blocked the production of extracellular peptides and attenuated neuronal-activity-induced calcium signaling. Moreover, we observed that membrane-proteasome-derived peptides were sufficient to induce neuronal calcium signaling. Our discoveries challenge the prevailing notion that proteasomes function primarily to maintain proteostasis, and highlight a form of neuronal communication that takes place through a membrane proteasome complex.

  18. The SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers

    PubMed Central

    Alver, Burak H.; Kim, Kimberly H.; Lu, Ping; Wang, Xiaofeng; Manchester, Haley E.; Wang, Weishan; Haswell, Jeffrey R.; Park, Peter J.; Roberts, Charles W. M.

    2017-01-01

    Genes encoding subunits of SWI/SNF (BAF) chromatin remodelling complexes are collectively altered in over 20% of human malignancies, but the mechanisms by which these complexes alter chromatin to modulate transcription and cell fate are poorly understood. Utilizing mouse embryonic fibroblast and cancer cell line models, here we show via ChIP-seq and biochemical assays that SWI/SNF complexes are preferentially targeted to distal lineage specific enhancers and interact with p300 to modulate histone H3 lysine 27 acetylation. We identify a greater requirement for SWI/SNF at typical enhancers than at most super-enhancers and at enhancers in untranscribed regions than in transcribed regions. Our data further demonstrate that SWI/SNF-dependent distal enhancers are essential for controlling expression of genes linked to developmental processes. Our findings thus establish SWI/SNF complexes as regulators of the enhancer landscape and provide insight into the roles of SWI/SNF in cellular fate control. PMID:28262751

  19. CLAVATA2 forms a distinct CLE-binding receptor complex regulating Arabidopsis stem cell specification

    PubMed Central

    Guo, Yongfeng; Han, Linqu; Hymes, Matthew; Denver, Robert; Clark, Steven E.

    2010-01-01

    SUMMARY CLAVATA1 (CLV1), CLV2, CLV3, CORYNE (CRN), BAM1 and BAM2 are key regulators that function at the shoot apical meristem (SAM) of plants to promote differentiation by limiting the size of the organizing center that maintains stem cell identity in neighboring cells. Previous results have indicated that the extracellular domain of the receptor-kinase CLV1 binds to the CLV3-derived CLE ligand. The biochemical role of receptor-like protein CLV2 has remained largely unknown. While genetic analysis suggested that CLV2, together with the membrane kinase CRN, act in parallel with CLV1, recent studies using transient expression indicated that CLV2 and CRN from a complex with CLV1. Here we report evidence for distinct CLV2/CRN heteromultimeric and CLV1/BAM multimeric complexes in transient expression and in Arabidopsis. Weaker interactions between the two complexes were detectable in transient expression. We also find that CLV2 alone generates a membrane-localized CLE binding activity independent of CLV1. CLV2, CLV1 and the CLV1 homologs BAM1 and BAM2 all bind to the CLV3-derived CLE peptide with similar kinetics, but BAM receptors show a broader range of interactions with different CLE peptides. Finally, we show that BAM and CLV1 over-expression can compensate for the loss of CLV2 function in vivo. These results suggest two parallel ligand-binding receptor complexes controlling stem cell specification in Arabidopsis. PMID:20626648

  20. BiQ Analyzer HiMod: an interactive software tool for high-throughput locus-specific analysis of 5-methylcytosine and its oxidized derivatives.

    PubMed

    Becker, Daniel; Lutsik, Pavlo; Ebert, Peter; Bock, Christoph; Lengauer, Thomas; Walter, Jörn

    2014-07-01

    Recent data suggest important biological roles for oxidative modifications of methylated cytosines, specifically hydroxymethylation, formylation and carboxylation. Several assays are now available for profiling these DNA modifications genome-wide as well as in targeted, locus-specific settings. Here we present BiQ Analyzer HiMod, a user-friendly software tool for sequence alignment, quality control and initial analysis of locus-specific DNA modification data. The software supports four different assay types, and it leads the user from raw sequence reads to DNA modification statistics and publication-quality plots. BiQ Analyzer HiMod combines well-established graphical user interface of its predecessor tool, BiQ Analyzer HT, with new and extended analysis modes. BiQ Analyzer HiMod also includes updates of the analysis workspace, an intuitive interface, a custom vector graphics engine and support of additional input and output data formats. The tool is freely available as a stand-alone installation package from http://biq-analyzer-himod.bioinf.mpi-inf.mpg.de/.

  1. The plant-specific CDKB1-CYCB1 complex mediates homologous recombination repair in Arabidopsis.

    PubMed

    Weimer, Annika K; Biedermann, Sascha; Harashima, Hirofumi; Roodbarkelari, Farshad; Takahashi, Naoki; Foreman, Julia; Guan, Yonsheng; Pochon, Gaëtan; Heese, Maren; Van Damme, Daniël; Sugimoto, Keiko; Koncz, Csaba; Doerner, Peter; Umeda, Masaaki; Schnittger, Arp

    2016-10-04

    Upon DNA damage, cyclin-dependent kinases (CDKs) are typically inhibited to block cell division. In many organisms, however, it has been found that CDK activity is required for DNA repair, especially for homology-dependent repair (HR), resulting in the conundrum how mitotic arrest and repair can be reconciled. Here, we show that Arabidopsis thaliana solves this dilemma by a division of labor strategy. We identify the plant-specific B1-type CDKs (CDKB1s) and the class of B1-type cyclins (CYCB1s) as major regulators of HR in plants. We find that RADIATION SENSITIVE 51 (RAD51), a core mediator of HR, is a substrate of CDKB1-CYCB1 complexes. Conversely, mutants in CDKB1 and CYCB1 fail to recruit RAD51 to damaged DNA CYCB1;1 is specifically activated after DNA damage and we show that this activation is directly controlled by SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1), a transcription factor that acts similarly to p53 in animals. Thus, while the major mitotic cell-cycle activity is blocked after DNA damage, CDKB1-CYCB1 complexes are specifically activated to mediate HR. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  2. Confident assignment of site-specific glycosylation in complex glycoproteins in a single step.

    PubMed

    Khatri, Kshitij; Staples, Gregory O; Leymarie, Nancy; Leon, Deborah R; Turiák, Lilla; Huang, Yu; Yip, Shun; Hu, Han; Heckendorf, Christian F; Zaia, Joseph

    2014-10-03

    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.

  3. 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.

  4. 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.

  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. A rapid and specific method for the detection of indole in complex biological samples.

    PubMed

    Darkoh, Charles; Chappell, Cynthia; Gonzales, Christopher; Okhuysen, Pablo

    2015-12-01

    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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. 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.

  8. Diazirine photocrosslinking recruits activated FTO demethylase complexes for specific N(6)-methyladenosine recognition.

    PubMed

    Jeong, Hyun Seok; Hayashi, Gosuke; Okamoto, Akimitsu

    2015-06-19

    N(6)-methyladenosine (m(6)A) is a prevalent modification of RNAs. m(6)A exists in mRNA and plays an important role in RNA biological pathways and in RNA epigenetic regulation. We applied diazirine photocrosslinking to the event of m(6)A recognition mediated by the fat mass and obesity associated (FTO) demethylase. A highly photoreactive diazirine adjacent to m(6)A on the RNA successfully recruited activated FTO complexes with an m(6)A preference. The process of recognition of m(6)A via FTO using diazirine photocrosslinking was controlled by the α-ketoglutarate (α-KG) cosubstrate and the Fe(II) cofactor, which are involved in m(6)A oxidative demethylation. In addition, FTO bound to ssRNAs prior to the m(6)A recognition process. Diazirine photocrosslinking contributes to increasing the chances of capturing activated FTO complexes with specific m(6)A recognition and provides new insights into the dynamic FTO oxidative demethylation process.

  9. 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%.

  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. Development and application of a complex numerical model and software for the computation of dose conversion factors for radon progenies.

    PubMed

    Farkas, Árpád; Balásházy, Imre

    2015-04-01

    A more exact determination of dose conversion factors associated with radon progeny inhalation was possible due to the advancements in epidemiological health risk estimates in the last years. The enhancement of computational power and the development of numerical techniques allow computing dose conversion factors with increasing reliability. The objective of this study was to develop an integrated model and software based on a self-developed airway deposition code, an own bronchial dosimetry model and the computational methods accepted by International Commission on Radiological Protection (ICRP) to calculate dose conversion coefficients for different exposure conditions. The model was tested by its application for exposure and breathing conditions characteristic of mines and homes. The dose conversion factors were 8 and 16 mSv WLM(-1) for homes and mines when applying a stochastic deposition model combined with the ICRP dosimetry model (named PM-A model), and 9 and 17 mSv WLM(-1) when applying the same deposition model combined with authors' bronchial dosimetry model and the ICRP bronchiolar and alveolar-interstitial dosimetry model (called PM-B model). User friendly software for the computation of dose conversion factors has also been developed. The software allows one to compute conversion factors for a large range of exposure and breathing parameters and to perform sensitivity analyses.

  12. Identification of myelin transcription factor 1 (MyT1) as a subunit of the neural cell type-specific lysine-specific demethylase 1 (LSD1) complex.

    PubMed

    Yokoyama, Atsushi; Igarashi, Katsuhide; Sato, Tetsuya; Takagi, Kiyoshi; Otsuka I, Maky; Shishido, Yurina; Baba, Takashi; Ito, Ryo; Kanno, Jun; Ohkawa, Yasuyuki; Morohashi, Ken-Ichirou; Sugawara, Akira

    2014-06-27

    Regulation of spatiotemporal gene expression in higher eukaryotic cells is critical for the precise and orderly development of undifferentiated progenitors into committed cell types of the adult. It is well known that dynamic epigenomic regulation (including chromatin remodeling and histone modifications by transcriptional coregulator complexes) is involved in transcriptional regulation. Precisely how these coregulator complexes exert their cell type and developing stage-specific activity is largely unknown. In this study we aimed to isolate the histone demethylase lysine-specific demethylase 1 (LSD1) complex from neural cells by biochemical purification. In so doing, we identified myelin transcription factor 1 (MyT1) as a novel LSD1 complex component. MyT1 is a neural cell-specific zinc finger factor, and it forms a stable multiprotein complex with LSD1 through direct interaction. Target gene analysis using microarray and ChIP assays revealed that the Pten gene was directly regulated by the LSD1-MyT1 complex. Knockdown of either LSD1 or MyT1 derepressed the expression of endogenous target genes and inhibited cell proliferation of a neuroblastoma cell line, Neuro2a. We propose that formation of tissue-specific combinations of coregulator complexes is a critical mechanism for tissue-specific transcriptional regulation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. 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

  14. Heavy Metal-induced Metallothionein Expression Is Regulated by Specific Protein Phosphatase 2A Complexes*

    PubMed Central

    Chen, Liping; Ma, Lu; Bai, Qing; Zhu, Xiaonian; Zhang, Jinmiao; Wei, Qing; Li, Daochuan; Gao, Chen; Li, Jie; Zhang, Zhengbao; Liu, Caixia; He, Zhini; Zeng, Xiaowen; Zhang, Aihua; Qu, Weidong; Zhuang, Zhixiong; Chen, Wen; Xiao, Yongmei

    2014-01-01

    Induction of metallothionein (MT) expression is involved in metal homeostasis and detoxification. To identify the key pathways that regulate metal-induced cytotoxicity, we investigate how phosphorylated metal-responsive transcription factor-1 (MTF-1) contributed to induction of MT expression. Immortal human embryonic kidney cells (HEK cells) were treated with seven kinds of metals including cadmium chloride (CdCl2), zinc sulfate (ZnSO4), copper sulfate(CuSO4), lead acetate (PbAc), nickel sulfate (NiSO4), sodium arsenite (NaAsO2), and potassium bichromate (K2Cr2O7). The MT expression was induced in a dose-response and time-dependent manner upon various metal treatments. A cycle of phosphorylation and dephosphorylation was required for translocation of MTF-1 from cytoplasm to nucleus, leading to the up-regulation of MTs expression. Protein phosphatase 2A (PP2A) participated in regulating MT expression through dephosphorylation of MTF-1. A loss-of-function screen revealed that the specific PP2A complexes containing PR110 were involved in metal-induced MT expression. Suppression of PP2A PR110 in HEK cells resulted in the persistent MTF-1 phosphorylation and the disturbance of MTF-1 nuclear translocation, which was concomitant with a significant decrease of MT expression and enhanced cytotoxicity in HEK cells. Notably, MTF-1 was found in complex with specific PP2A complexes containing the PR110 subunit upon metal exposure. Furthermore, we identify that the dephosphorylation of MTF-1 at residue Thr-254 is directly regulated by PP2A PR110 complexes and responsible for MTF-1 activation. Taken together, these findings delineate a novel pathway that determines cytotoxicity in response to metal treatments and provide new insight into the role of PP2A in cellular stress response. PMID:24962574

  15. 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.

  16. Femtosecond Element-Specific XUV Spectroscopy of Complex Molecules and Materials

    NASA Astrophysics Data System (ADS)

    Vura-Weis, Josh

    2017-06-01

    Systems with multiple heavy atoms, such as the multimetallic clusters favored by Nature for redox catalysis and emerging photovoltaic materials such as CH_{3}NH_{3}PbI_{3}, pose challenges for traditional spectroscopic techniques. The growing field of high-harmonic extreme ultraviolet spectroscopy combines the element-, oxidation state-, spin state-, and ligand field specificity of XANES spectroscopy with the femtosecond time resolution of tabletop Ti:Sapphire lasers. We will show that this technique can be used to measure the photophysics of transition metal complexes, organohalide perovskites, and even small metalloproteins, extending the technique to mainstream problems in physical and inorganic chemistry.

  17. Complex-specific immunoglobulin M antibody patterns in humans infected with alphaviruses.

    PubMed Central

    Calisher, C H; el-Kafrawi, A O; Al-Deen Mahmud, M I; Travassos da Rosa, A P; Bartz, C R; Brummer-Korvenkontio, M; Haksohusodo, S; Suharyono, W

    1986-01-01

    Sera from humans with serologically confirmed eastern equine encephalitis, western equine encephalitis, Pogosta (Ockelbo), Mayaro, Ross River, and chikungunya virus infections were tested by immunoglobulin M (IgM) antibody capture enzyme immunoassay. Diagnostically useful IgM antibody titers were detected, and selected sera with high IgM antibody titers were tested for IgM antibody with nine heterologous alphaviruses. The results provide evidence for the complex specificity of IgM antibody and indicate the usefulness of this test in both individual cases and epidemic situations. PMID:3009526

  18. Water-soluble mitochondria-specific ytterbium complex with impressive NIR emission.

    PubMed

    Zhang, Tao; Zhu, Xunjin; Cheng, Chopen C W; Kwok, Wai-Ming; Tam, Hoi-Lam; Hao, Jianhua; Kwong, Daniel W J; Wong, Wai-Kwok; Wong, Ka-Leung

    2011-12-21

    A water-soluble porphyrinato ytterbium complex linked with rhodamine B (Yb-2) showed mitochondria-specific subcellular localization and strong two-photon-induced NIR emissions (λ(em) = 650 nm, porphyrinate ligand π → π* transition; λ(em) = 1060 nm, Yb(III) (5)F(5/2) → (5)F(7/2) transitions; σ(2) = 375 GM in DMSO) with an impressive Yb(III) NIR emission quantum yield (1% at λ(ex) = 340 nm; 2.5% at λ(ex) = 430 nm) in aqueous solution.

  19. 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.

  20. Male-specific lethal complex in Drosophila counteracts histone acetylation and does not mediate dosage compensation

    PubMed Central

    Sun, Lin; Fernandez, Harvey R.; Donohue, Ryan C.; Li, Jilong; Cheng, Jianlin; Birchler, James A.

    2013-01-01

    Dosage compensation is achieved in male Drosophila by a twofold up-regulation of the single X chromosome to reach the level of the two X chromosomes in females. A popular hypothesis to explain this phenomenon is that the male-specific lethal (MSL) complex, which is present at high levels on the male X, mediates this modulation of gene expression. One member of the complex, MOF, a histone acetyltransferase, acetylates lysine 16 of histone H4 and another, MSL2, which is only expressed in males, triggers its assembly. Here, we find that when a GAL4-MOF fusion protein is targeted to an upstream-activating sequence linked to a miniwhite reporter, up-regulation occurs in females but down-regulation in males, even though in the latter the whole MSL complex is recruited to the reporter genes and produces an increased histone acetylation. The expression of a GAL4-MSL2 fusion protein does not cause dosage compensation of X and autosomal reporters in females, although its expression causes the organization of the MSL complex on the reporter genes, leading to increased histone acetylation. RNAseq analysis of global endogenous gene expression in females with ectopic expression of MSL2 to coat the X chromosomes shows no evidence of increased expression compared with normal females. These data from multiple approaches indicate that the MSL complex does not mediate dosage compensation directly, but rather its activity overrides the high level of histone acetylation and counteracts the potential overexpression of X-linked genes to achieve the proper twofold up-regulation in males. PMID:23382189

  1. Primary Sex Determination in Drosophila melanogaster Does Not Rely on the Male-Specific Lethal Complex.

    PubMed

    Erickson, James W

    2016-02-01

    It has been proposed that the Male Specific Lethal (MSL) complex is active in Drosophila melanogaster embryos of both sexes prior to the maternal-to-zygotic transition. Elevated gene expression from the two X chromosomes of female embryos is proposed to facilitate the stable establishment of Sex-lethal (Sxl) expression, which determines sex and represses further activity of the MSL complex, leaving it active only in males. Important supporting data included female-lethal genetic interactions between the seven msl genes and either Sxl or scute and sisterlessA, two of the X-signal elements (XSE) that regulate early Sxl expression. Here I report contrary findings that there are no female-lethal genetic interactions between the msl genes and Sxl or its XSE regulators. Fly stocks containing the msl3(1) allele were found to exhibit a maternal-effect interaction with Sxl, scute, and sisterlessA mutations, but genetic complementation experiments showed that msl3 is neither necessary nor sufficient for the female-lethal interactions, which appear to be due to an unidentified maternal regulator of Sxl. Published data cited as evidence for an early function of the MSL complex in females, including a maternal effect of msl2, have been reevaluated and found not to support a maternal, or other effect, of the MSL complex in sex determination. These findings suggest that the MSL complex is not involved in primary sex determination or in X chromosome dosage compensation prior to the maternal-to-zygotic transition. Copyright © 2016 by the Genetics Society of America.

  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. Response latency and verbal complexity: stochastic models of individual differences in children with specific language impairments.

    PubMed

    Evans, J L; Viele, K; Kass, R E

    1997-08-01

    Within-subject statistical modeling techniques were employed to investigate individual differences in the extent to which two possible indicators of processing time predicted changes in utterance complexity during spontaneous discourse for 10 children ages 7;1 to 10;1 with specific language impairments (SLI) who differed in receptive language abilities. The two indicators of processing time that were modeled were response latency and the use of a specific discourse marker (Verbal Pause) that provided children with additional time to respond. Longer response latencies were not a strong predictor of increased utterance length for any of the children. However, results indicated that children with better receptive skills used substantially more verbal pauses than children with both expressive and receptive deficits and that the use of these pauses was a strong predictor of increased utterance length for children with better comprehension skills.

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

    PubMed Central

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

    2016-01-01

    Mapping the molecular circuits that are perturbed by genetic variants underlying complex traits and diseases remains a great challenge. We present a comprehensive resource of 394 cell type and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity between transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) shows 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. PMID:26950747

  5. Mechanosensing of DNA bending in a single specific protein-DNA complex

    NASA Astrophysics Data System (ADS)

    Le, Shimin; Chen, Hu; Cong, Peiwen; Lin, Jie; Dröge, Peter; Yan, Jie

    2013-12-01

    Many crucial biological processes are regulated by mechanical stimuli. Here, we report new findings that pico-Newton forces can drastically affect the stability of the site-specific DNA binding of a single transcription factor, the E. coli integration host factor (IHF), by stretching a short ~150 nm DNA containing a single IHF binding site. Dynamic binding and unbinding of single IHF were recorded and analyzed for the force-dependent stability of the IHF-DNA complex. Our results demonstrate that the IHF-DNA interaction is fine tuned by force in different salt concentration and temperature over physiological ranges, indicating that, besides other physiological factors, force may play equally important role in transcription regulation. These findings have broad implications with regard to general mechanosensitivity of site-specific DNA bending proteins.

  6. Post-transcription initiation function of the ubiquitous SAGA complex in tissue-specific gene activation

    PubMed Central

    Weake, Vikki M.; Dyer, Jamie O.; Seidel, Christopher; Box, Andrew; Swanson, Selene K.; Peak, Allison; Florens, Laurence; Washburn, Michael P.; Abmayr, Susan M.; Workman, Jerry L.

    2011-01-01

    The Spt–Ada–Gcn5–acetyltransferase (SAGA) complex was discovered from Saccharomyces cerevisiae and has been well characterized as an important transcriptional coactivator that interacts both with sequence-specific transcription factors and the TATA-binding protein TBP. SAGA contains a histone acetyltransferase and a ubiquitin protease. In metazoans, SAGA is essential for development, yet little is known about the function of SAGA in differentiating tissue. We analyzed the composition, interacting proteins, and genomic distribution of SAGA in muscle and neuronal tissue of late stage Drosophila melanogaster embryos. The subunit composition of SAGA was the same in each tissue; however, SAGA was associated with considerably more transcription factors in muscle compared with neurons. Consistent with this finding, SAGA was found to occupy more genes specifically in muscle than in neurons. Strikingly, SAGA occupancy was not limited to enhancers and promoters but primarily colocalized with RNA polymerase II within transcribed sequences. SAGA binding peaks at the site of RNA polymerase pausing at the 5′ end of transcribed sequences. In addition, many tissue-specific SAGA-bound genes required its ubiquitin protease activity for full expression. These data indicate that in metazoans SAGA plays a prominent post-transcription initiation role in tissue-specific gene expression. PMID:21764853

  7. Specificity-Determining DNA Triplet Code for Positioning of Human Preinitiation Complex.

    PubMed

    Goldshtein, Matan; Lukatsky, David B

    2017-05-23

    The notion that transcription factors bind DNA only through specific, consensus binding sites has been recently questioned. No specific consensus motif for the positioning of the human preinitiation complex (PIC) has been identified. Here, we reveal that nonconsensus, statistical, DNA triplet code provides specificity for the positioning of the human PIC. In particular, we reveal a highly nonrandom, statistical pattern of repetitive nucleotide triplets that correlates with the genomewide binding preferences of PIC measured by Chip-exo. We analyze the triplet enrichment and depletion near the transcription start site and identify triplets that have the strongest effect on PIC-DNA nonconsensus binding. Using statistical mechanics, a random-binder model without fitting parameters, with genomic DNA sequence being the only input, we further validate that the nonconsensus nucleotide triplet code constitutes a key signature providing PIC binding specificity in the human genome. Our results constitute a proof-of-concept for, to our knowledge, a new design principle for protein-DNA recognition in the human genome, which can lead to a better mechanistic understanding of transcriptional regulation. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. 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. © 2015 Chung et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  10. 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.

  11. Funding Research Software Development

    NASA Astrophysics Data System (ADS)

    Momcheva, Ivelina G.

    2017-01-01

    Astronomical software is used by each and every member of our scientific community. Purpose-build software is becoming ever more critical as we enter the regime of large datasets and simulations of increasing complexity. However, financial investments in building, maintaining and renovating the software infrastructure have been uneven. In this talk I will summarize past and current funding sources for astronomical software development, discuss other models of funding and introduce a new initiative for supporting community software at STScI. The purpose of this talk is to prompt discussion about how we allocate resources to this vital infrastructure.

  12. 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.

  13. Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivity.

    PubMed

    Sarma, Ganapathy N; Kinderman, Francis S; Kim, Choel; von Daake, Sventja; Chen, Lirong; Wang, Bi-Cheng; Taylor, Susan S

    2010-02-10

    A-kinase anchoring proteins (AKAPs) regulate cyclic AMP-dependent protein kinase (PKA) signaling in space and time. Dual-specific AKAP 2 (D-AKAP2) binds to the dimerization/docking (D/D) domain of both RI and RII regulatory subunits of PKA with high affinity. Here we have determined the structures of the RIalpha D/D domain alone and in complex with D-AKAP2. The D/D domain presents an extensive surface for binding through a well-formed N-terminal helix, and this surface restricts the diversity of AKAPs that can interact. The structures also underscore the importance of a redox-sensitive disulfide in affecting AKAP binding. An unexpected shift in the helical register of D-AKAP2 compared to the RIIalpha:D-AKAP2 complex structure makes the mode of binding to RIalpha novel. Finally, the comparison allows us to deduce a molecular explanation for the sequence and spatial determinants of AKAP specificity.

  14. Structure of D-AKAP2:PKA RI Complex: Insights into AKAP Specificity and Selectivity

    SciTech Connect

    Sarma, Ganapathy N.; Kinderman, Francis S.; Kim, Choel; von Daake, Sventja; Chen, Lirong; Wang, Bi-Cheng; Taylor, Susan S.

    2010-11-22

    A-kinase anchoring proteins (AKAPs) regulate cyclic AMP-dependent protein kinase (PKA) signaling in space and time. Dual-specific AKAP 2 (D-AKAP2) binds to the dimerization/docking (D/D) domain of both RI and RII regulatory subunits of PKA with high affinity. Here we have determined the structures of the RI{alpha} D/D domain alone and in complex with D-AKAP2. The D/D domain presents an extensive surface for binding through a well-formed N-terminal helix, and this surface restricts the diversity of AKAPs that can interact. The structures also underscore the importance of a redox-sensitive disulfide in affecting AKAP binding. An unexpected shift in the helical register of D-AKAP2 compared to the RII{alpha}:D-AKAP2 complex structure makes the mode of binding to RI{alpha} novel. Finally, the comparison allows us to deduce a molecular explanation for the sequence and spatial determinants of AKAP specificity.

  15. Importance of patient-specific intraoperative guides in complex maxillofacial reconstruction.

    PubMed

    Rohner, Dennis; Guijarro-Martínez, Raquel; Bucher, Peter; Hammer, Beat

    2013-07-01

    Conventional maxillofacial reconstruction often leads to suboptimal results due to inaccurate planning or surgical difficulties in adjusting a free flap and osteosynthesis plates into a three-dimensional defect. To justify the importance of patient-specific intraoperative guides in complex maxillofacial reconstruction. CLINICAL EXAMPLE: A 40-year old patient underwent a left hemimaxillectomy for an adenoid cystic carcinoma of the palate. Six years later, massive recurrence required radical resection of the left orbit and reconstruction with cranial bone grafts and a free latissimus dorsi flap. Postoperative radiotherapy resulted in local osteoradionecrosis. Surgical revision and restoration of the maxillary defect with a prefabricated fibula flap was performed. The authors provide ample information on the application of computer-aided design and manufacturing (CAD-CAM) and rapid prototyping at each reconstructive step. Stereolithographic models enable simulation of the resective and reconstructive phases, prebending of reconstruction plates and fabrication of surgical guides. Optimal restitution of complex maxillofacial defects requires meticulous planning of the surgical and prosthetic phases and effective transfer of the plan to the operating room through patient specific guides. CAD-CAM technology and stereolithographic models represent an effective strategy to achieve this. Improved patient outcomes and intraoperative efficiency certainly offset the inherent increase in costs. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  16. Astrocyte-specific overexpression of Nrf2 protects striatal neurons from mitochondrial complex II inhibition.

    PubMed

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

    2010-06-01

    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.

  17. 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

  18. Allele-specific methylation occurs at genetic variants associated with complex disease.

    PubMed

    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.

  19. Centralspindlin and Chromosomal Passenger Complex Behavior During Normal and Rappaport Furrow Specification in Echinoderm Embryos

    PubMed Central

    Argiros, Haroula; Henson, Lauren; Holguin, Christiana; Foe, Victoria; Shuster, Charles Bradley

    2014-01-01

    The chromosomal passenger (CPC) and Centralspindlin complexes are essential for organizing the anaphase central spindle and providing cues that position the cytokinetic furrow between daughter nuclei. However, echinoderm zygotes are also capable of forming “Rappaport furrows” between asters positioned back-to-back without intervening chromosomes. To understand how these complexes contribute to normal and Rappaport furrow formation, we studied the localization patterns of Survivin and mitotic-kinesin-like-protein1 (MKLP1), members respectively of the CPC and the Centralspindlin complex, and the effect of CPC inhibition on cleavage in mono- and binucleate echinoderm zygotes. In zygotes, Survivin initially localized to metaphase chromosomes, upon anaphase onset relocalized to the central spindle and then, together with MKLP1 spread towards the equatorial cortex in an Aurora-dependent manner. Inhibition of Aurora kinase activity resulted in disruption of central spindle organization and furrow regression, although astral microtubule elongation and furrow initiation were normal. In binucleate cells containing two parallel spindles MKLP1 and Survivin localized to the plane of the former metaphase plate, but were not observed in the secondary cleavage plane formed between unrelated spindle poles, except when chromosomes were abnormally present there. However, the secondary furrow was sensitive to Aurora inhibition, indicating that Aurora kinase may still contribute to furrow ingression without chromosomes nearby. Our results provide insights that reconcile classic micromanipulation studies with current molecular understanding of furrow specification in animal cells. PMID:22887753

  20. Centralspindlin and chromosomal passenger complex behavior during normal and Rappaport furrow specification in echinoderm embryos.

    PubMed

    Argiros, Haroula; Henson, Lauren; Holguin, Christiana; Foe, Victoria; Shuster, Charles Bradley

    2012-10-01

    The chromosomal passenger (CPC) and Centralspindlin complexes are essential for organizing the anaphase central spindle and providing cues that position the cytokinetic furrow between daughter nuclei. However, echinoderm zygotes are also capable of forming "Rappaport furrows" between asters positioned back-to-back without intervening chromosomes. To understand how these complexes contribute to normal and Rappaport furrow formation, we studied the localization patterns of Survivin and mitotic-kinesin-like-protein1 (MKLP1), members respectively of the CPC and the Centralspindlin complex, and the effect of CPC inhibition on cleavage in mono- and binucleate echinoderm zygotes. In zygotes, Survivin initially localized to metaphase chromosomes, upon anaphase onset relocalized to the central spindle and then, together with MKLP1 spread towards the equatorial cortex in an Aurora-dependent manner. Inhibition of Aurora kinase activity resulted in disruption of central spindle organization and furrow regression, although astral microtubule elongation and furrow initiation were normal. In binucleate cells containing two parallel spindles MKLP1 and Survivin localized to the plane of the former metaphase plate, but were not observed in the secondary cleavage plane formed between unrelated spindle poles, except when chromosomes were abnormally present there. However, the secondary furrow was sensitive to Aurora inhibition, indicating that Aurora kinase may still contribute to furrow ingression without chromosomes nearby. Our results provide insights that reconcile classic micromanipulation studies with current molecular understanding of furrow specification in animal cells. Copyright © 2012 Wiley Periodicals, Inc.

  1. Phosphorescent iridium(III) complexes as multicolor probes for specific mitochondrial imaging and tracking.

    PubMed

    Chen, Yu; Qiao, Liping; Ji, Liangnian; Chao, Hui

    2014-01-01

    In the present study, four phosphorescent iridium(III) complexes [Ir(C-N)2(PhenSe)](+) (Ir1-Ir4, in which C-N = 2-(2,4-difluorophenyl)pyridine (dfppy), dibenzo[f,h]quinoxaline (dbq), 2-phenylquinoline (2-pq) and 2-phenylpyridine (ppy), PhenSe = 1,10-phenanthrolineselenazole) with tunable emission colors were developed to image mitochondria and track the dynamics of the mitochondrial morphology. In comparison with commercially available mitochondrial trackers, Ir1-Ir4 possess high specificity to mitochondria in live and fixed cells without requiring prior membrane permeabilization or the replacement of the culture medium. Due to the high resistance of Ir1-Ir4 to the loss of mitochondrial membrane potential as well as the appreciable tolerance to environmental changes, these complexes are applicable for the imaging and tracking of the mitochondrial morphological changes over long periods of time. In addition, Ir2-Ir4 exhibited superior photostability compared to the commercially available mitochondrial trackers. These colorful iridium(III) complexes may contribute to the future development of staining agents for organelle-selective imaging in living cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Detection of drug specific circulating immune complexes from in vivo cynomolgus monkey serum samples.

    PubMed

    Pierog, Piotr; Krishna, Murli; Yamniuk, Aaron; Chauhan, Anil; DeSilva, Binodh

    2015-01-01

    Administration of a biotherapeutic can result in the formation of anti-drug antibodies (ADAs). The resulting ADA can potentially form immune complexes (ICs) with the drug leading to altered pharmacokinetic (PK) profiles and/or adverse events. Furthermore the presence of such complexes may interfere with accurate PK assessment, and/or detection of ADA in immunogenicity assays. Here, we present two assays to detect the presence of drug-ADA immune complexes in cynomolgus monkeys. Serum samples were analyzed for IC formation in vivo. 8/8 tested animals were positive for drug specific IC. Depending on the time point tested 4/8 or 7/8 animals tested positive for ADA during drug dosing. All 8 animals were confirmed positive for ADA during the washout phase, indicating drug interference in the bridging assay. Relative amount of IC over time was determined and its correlation with PK and ADA was then assessed. Multivariate data analysis demonstrates good correlation between signals obtained from the anti-drug and FcγRIIIa based capture assays, although due to its biological characteristic FcγRIIIa based assay captured only a subset of drug specific IC. In one animal IC remained in circulation even when the drug levels decreased below detection limit. Results from this study indicate the presence of IC during administration of an immunogenic biotherapeutic. Potential application of these assays includes detection of ADA in an IC during high drug levels. The results on the kinetics of IC formation during ADA response can complement the understanding of PK and ADA profiles. Moreover, the presence of IC indicates possible ADA interference in standard PK assays and potential underestimation of total drug exposure in toxicology studies. In addition this study also highlights the need to understand downstream in vivo consequences of drug-ADA IC as no animals under investigation developed adverse events. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. A Lectin from Platypodium elegans with Unusual Specificity and Affinity for Asymmetric Complex N-Glycans*

    PubMed Central

    Benevides, Raquel Guimarães; Ganne, Géraldine; Simões, Rafael da Conceição; Schubert, Volker; Niemietz, Mathäus; Unverzagt, Carlo; Chazalet, Valérie; Breton, Christelle; Varrot, Annabelle; Cavada, Benildo Sousa; Imberty, Anne

    2012-01-01

    Lectin activity with specificity for mannose and glucose has been detected in the seed of Platypodium elegans, a legume plant from the Dalbergieae tribe. The gene of Platypodium elegans lectin A has been cloned, and the resulting 261-amino acid protein belongs to the legume lectin family with similarity with Pterocarpus angolensis agglutinin from the same tribe. The recombinant lectin has been expressed in Escherichia coli and refolded from inclusion bodies. Analysis of specificity by glycan array evidenced a very unusual preference for complex type N-glycans with asymmetrical branches. A short branch consisting of one mannose residue is preferred on the 6-arm of the N-glycan, whereas extensions by GlcNAc, Gal, and NeuAc are favorable on the 3-arm. Affinities have been obtained by microcalorimetry using symmetrical and asymmetrical Asn-linked heptasaccharides prepared by the semi-synthetic method. Strong affinity with Kd of 4.5 μm was obtained for both ligands. Crystal structures of Platypodium elegans lectin A complexed with branched trimannose and symmetrical complex-type Asn-linked heptasaccharide have been solved at 2.1 and 1.65 Å resolution, respectively. The lectin adopts the canonical dimeric organization of legume lectins. The trimannose bridges the binding sites of two neighboring dimers, resulting in the formation of infinite chains in the crystal. The Asn-linked heptasaccharide binds with the 6-arm in the primary binding site with extensive additional contacts on both arms. The GlcNAc on the 6-arm is bound in a constrained conformation that may rationalize the higher affinity observed on the glycan array for N-glycans with only a mannose on the 6-arm. PMID:22692206

  4. CLAVATA2 forms a distinct CLE-binding receptor complex regulating Arabidopsis stem cell specification.

    PubMed

    Guo, Yongfeng; Han, Linqu; Hymes, Matthew; Denver, Robert; Clark, Steven E

    2010-09-01

    CLAVATA1 (CLV1), CLV2, CLV3, CORYNE (CRN), BAM1 and BAM2 are key regulators that function at the shoot apical meristem (SAM) of plants to promote differentiation by limiting the size of the organizing center that maintains stem cell identity in neighboring cells. Previous results have indicated that the extracellular domain of the receptor kinase CLV1 binds to the CLV3-derived CLE ligand. The biochemical role of the receptor-like protein CLV2 has remained largely unknown. Although genetic analysis suggested that CLV2, together with the membrane kinase CRN, acts in parallel with CLV1, recent studies using transient expression indicated that CLV2 and CRN from a complex with CLV1. Here, we report detection of distinct CLV2-CRN heteromultimeric and CLV1-BAM multimeric complexes in transient expression in tobacco and in Arabidopsis meristems. Weaker interactions between the two complexes were detectable in transient expression. We also find that CLV2 alone generates a membrane-localized CLE binding activity independent of CLV1. CLV2, CLV1 and the CLV1 homologs BAM1 and BAM2 all bind to the CLV3-derived CLE peptide with similar kinetics, but BAM receptors show a broader range of interactions with different CLE peptides. Finally, we show that BAM and CLV1 overexpression can compensate for the loss of CLV2 function in vivo. These results suggest two parallel ligand-binding receptor complexes controlling stem cell specification in Arabidopsis. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

  5. A Novel Software Evolution Model Based on Software Networks

    NASA Astrophysics Data System (ADS)

    Pan, Weifeng; Li, Bing; Ma, Yutao; Liu, Jing

    Many published papers analyzed the forming mechanisms and evolution laws of OO software systems from software reuse, software pattern, etc. There, however, have been fewer models so far merely built on the software components such as methods, classes, etc. and their interactions. In this paper, a novel Software Evolution Model based on Software Networks (called SEM-SN) is proposed. It uses software network at class level to represent software systems, and uses software network’s dynamical generating process to simulate activities in real software development process such as new classes’ dynamical creations and their dynamical interactions with already existing classes. It also introduces the concept of node/edge ageing to describe the decaying of classes with time. Empirical results on eight open-source Object-Oriented (OO) software systems demonstrate that SCM-SN roughly describes the evolution process of software systems and the emergence of their complex network characteristics.

  6. Sex-specific differences in the synaptonemal complex in the genus Oreochromis (Cichlidae).

    PubMed

    Campos-Ramos, Rafael; Harvey, Simon C; Penman, David J

    2009-04-01

    Total synaptonemal complex (SC) lengths were estimated from Oreochromis aureus Steindachner (which has a WZ/ZZ sex determination system), O. mossambicus Peters and O. niloticus L. (both of which have XX/XY sex determination systems). The total SC length in oocytes was greater than that in spermatocytes in all three species (194 +/- 30 microm and 134 +/- 13 microm, 187 +/- 22 microm and 127 +/- 17 microm, 193 +/- 37 microm and 144 +/- 19 microm, respectively). These sex-specific differences did not appear to be influenced by the type of sex determination system (the female/male total SC length ratio was 1.45 in O. aureus, 1.47 in O. mossambicus and 1.34 in O. niloticus) and do not correlate with the lack of any overall sex-specific length differences in the current Oreochromis linkage map. Although based on data from relatively few species, there appears to be no consistent relationship between sex-specific SC lengths and linkage map lengths in fish. Neomale (hormonally masculinized genetic female) O. aureus and O. mossambicus had total SC lengths of 138 +/- 13 microm and 146 +/- 13 microm respectively, more similar to normal males than to normal females. These findings agree with data from other vertebrate species that suggest that phenotypic sex, rather than genotype, determines traits such as total SC length, chiasmata position and recombination pattern, at least for the autosomes.

  7. Protein interaction evolution from promiscuity to specificity with reduced flexibility in an increasingly complex network

    PubMed Central

    Alhindi, T.; Zhang, Z.; Ruelens, P.; Coenen, H.; Degroote, H.; Iraci, N.; Geuten, K.

    2017-01-01

    A key question regarding protein evolution is how proteins adapt to the dynamic environment in which they function and how in turn their evolution shapes the protein interaction network. We used extant and resurrected ancestral plant MADS-domain transcription factors to understand how SEPALLATA3, a protein with hub and glue properties, evolved and takes part in network organization. Although the density of dimeric interactions was saturated in the network, many new interactions became mediated by SEPALLATA3 after a whole genome triplication event. By swapping SEPALLATA3 and its ancestors between dimeric networks of different ages, we found that the protein lost the capacity of promiscuous interaction and acquired specificity in evolution. This was accompanied with constraints on conformations through proline residue accumulation, which made the protein less flexible. SHORT VEGETATIVE PHASE on the other hand (non-hub) was able to gain protein-protein interactions due to a C-terminal domain insertion, allowing for a larger interaction interface. These findings illustrate that protein interaction evolution occurs at the level of conformational dynamics, when the binding mechanism concerns an induced fit or conformational selection. Proteins can evolve towards increased specificity with reduced flexibility when the complexity of the protein interaction network requires specificity. PMID:28337996

  8. Proteoform-Specific Protein Binding of Small Molecules in Complex Matrices.

    PubMed

    Gil, Geuncheol; Mao, Pan; Avula, Bharathi; Ali, Zulfiqar; Chittiboyina, Amar G; Khan, Ikhlas A; Walker, Larry A; Wang, Daojing

    2017-02-17

    Characterizing the specific binding between protein targets and small molecules is critically important for drug discovery. Conventional assays require isolation and purification of small molecules from complex matrices through multistep chromatographic fractionation, which may alter their original bioactivity. Most proteins undergo posttranslational modification, and only certain proteoforms have the right conformation with accessible domains and available residues for small molecule binding. We developed a top-down mass spectrometry (MS) centric workflow for rapid evaluation of the bioactivity of crude botanical extracts after a one-step reaction. Our assay distinguished covalent from noncovalent binding and mapped the residue for covalent binding between bioactive constituents and specific proteoforms of the target protein. We augmented our approach with a nanoflow liquid chromatography-selected reaction monitoring (SRM)-MS assay for simultaneous identification and label-free multiplex quantitation of small molecules in the crude botanical extracts. Our assay was validated for various proteoforms of human serum albumin, which plays a key role in pharmacokinetics of small molecules in vivo. We demonstrated the utility of our proteoform-specific assay for evaluating thymoquinone in crude botanical extracts, studying its pharmacokinetics in human blood, and interpreting its toxicity to human breast cancer cells in tissue culture.

  9. 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.

  10. Gene set analysis for self-contained tests: complex null and specific alternative hypotheses

    PubMed Central

    Rahmatallah, Y.; Glazko, G.

    2012-01-01

    Motivation: The analysis of differentially expressed gene sets became a routine in the analyses of gene expression data. There is a multitude of tests available, ranging from aggregation tests that summarize gene-level statistics for a gene set to true multivariate tests, accounting for intergene correlations. Most of them detect complex departures from the null hypothesis but when the null hypothesis is rejected, the specific alternative leading to the rejection is not easily identifiable. Results: In this article we compare the power and Type I error rates of minimum-spanning tree (MST)-based non-parametric multivariate tests with several multivariate and aggregation tests, which are frequently used for pathway analyses. In our simulation study, we demonstrate that MST-based tests have power that is for many settings comparable with the power of conventional approaches, but outperform them in specific regions of the parameter space corresponding to biologically relevant configurations. Further, we find for simulated and for gene expression data that MST-based tests discriminate well against shift and scale alternatives. As a general result, we suggest a two-step practical analysis strategy that may increase the interpretability of experimental data: first, apply the most powerful multivariate test to find the subset of pathways for which the null hypothesis is rejected and second, apply MST-based tests to these pathways to select those that support specific alternative hypotheses. Contact: gvglazko@uams.edu or yrahmatallah@uams.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23044539

  11. 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.

  12. Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex.

    PubMed

    Cai, Yong; Jin, Jingji; Swanson, Selene K; Cole, Michael D; Choi, Seung Hyuk; Florens, Laurence; Washburn, Michael P; Conaway, Joan W; Conaway, Ronald C

    2010-02-12

    Human MOF (MYST1), a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of histone acetyltransferases (HATs), is the human ortholog of the Drosophila males absent on the first (MOF) protein. MOF is the catalytic subunit of the male-specific lethal (MSL) HAT complex, which plays a key role in dosage compensation in the fly and is responsible for a large fraction of histone H4 lysine 16 (H4K16) acetylation in vivo. MOF was recently reported to be a component of a second HAT complex, designated the non-specific lethal (NSL) complex (Mendjan, S., Taipale, M., Kind, J., Holz, H., Gebhardt, P., Schelder, M., Vermeulen, M., Buscaino, A., Duncan, K., Mueller, J., Wilm, M., Stunnenberg, H. G., Saumweber, H., and Akhtar, A. (2006) Mol. Cell 21, 811-823). Here we report an analysis of the subunit composition and substrate specificity of the NSL complex. Proteomic analyses of complexes purified through multiple candidate subunits reveal that NSL is composed of nine subunits. Two of its subunits, WD repeat domain 5 (WDR5) and host cell factor 1 (HCF1), are shared with members of the MLL/SET family of histone H3 lysine 4 (H3K4) methyltransferase complexes, and a third subunit, MCRS1, is shared with the human INO80 chromatin-remodeling complex. In addition, we show that assembly of the MOF HAT into MSL or NSL complexes controls its substrate specificity. Although MSL-associated MOF acetylates nucleosomal histone H4 almost exclusively on lysine 16, NSL-associated MOF exhibits a relaxed specificity and also acetylates nucleosomal histone H4 on lysines 5 and 8.

  13. BetaMol: A Molecular Modeling, Analysis and Visualization Software Based on the Beta-Complex and the Quasi-Triangulation

    NASA Astrophysics Data System (ADS)

    Cho, Youngsong; Kim, Jae-Kwan; Ryu, Joonghyun; Won, Chung-In; Kim, Chong-Min; Kim, Donguk; Kim, Deok-Soo

    Molecular shape is one of the most critical factors that determines molecular function. Therefore, it is frequently desirable to understand geometric characteristics of a molecule more precisely and efficiently. In this paper, we introduce the BetaMol, a molecular modeling, analysis, and visualization software based on the recent theory of the beta-complex and the quasi-triangulation that are derived from the Voronoi diagram of three-dimensional spherical atoms. The powerful features of the BetaMol are solely based on a unified, single framework of the mathematically rigorous and computationally efficient beta-complex theory. The BetaMol is implemented in the standard C++ language with OpenGL graphics library and freely available at Voronoi Diagram Research Center web site (http://voronoi.hanyang.ac.kr).

  14. 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.

  15. 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.

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

    DOE PAGES

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

    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

  17. 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

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

    DOE PAGES

    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.

  19. 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.

  20. Nuclear pore complex composition: a new regulator of tissue-specific and developmental functions.

    PubMed

    Raices, Marcela; D'Angelo, Maximiliano A

    2012-11-01

    Nuclear pore complexes (NPCs) are multiprotein aqueous channels that penetrate the nuclear envelope connecting the nucleus and the cytoplasm. NPCs consist of multiple copies of roughly 30 different proteins known as nucleoporins (NUPs). Due to their essential role in controlling nucleocytoplasmic transport, NPCs have traditionally been considered as structures of ubiquitous composition. The overall structure of the NPC is indeed conserved in all cells, but new evidence suggests that the protein composition of NPCs varies among cell types and tissues. Moreover, mutations in various nucleoporins result in tissue-specific diseases. These findings point towards a heterogeneity in NPC composition and function. This unexpected heterogeneity suggests that cells use a combination of different nucleoporins to assemble NPCs with distinct properties and specialized functions.

  1. Specificity and temporal dynamics of complex bacteria--sponge symbiotic interactions.

    PubMed

    Björk, Johannes R; Díez-Vives, C; Coma, Rafel; Ribes, Marta; Montoya, José M

    2013-12-01

    Microbes are known to form intricate and intimate relationships with most animal and plant taxa. Microbe--host symbiotic associations are poorly explored in comparison with other species interaction networks. The current paradigm on symbiosis research stems from species-poor systems where pairwise and reciprocally specialized interactions between a single microbe and a single host that coevolve are the norm. These symbioses involving just a few species are fascinating in their own right, but more diverse and complex host-associated microbial communities are increasingly found, with new emerging questions that require new paradigms and approaches. Here we adopt an intermediate complexity approach to study the specificity, phylogenetic community structure, and temporal variability of the subset of the most abundant bacteria associated with different sponge host species with diverse eco-evolutionary characteristics. We do so by using a monthly resolved annual temporal series of host-associated and free-living bacteria. Bacteria are very abundant and diverse within marine sponges, and these symbiotic interactions are hypothesized to have a very ancient origin. We show that host-bacteria reciprocal specialization depends on the temporal scale and level of taxonomic aggregation considered. Sponge hosts with similar eco-evolutionary characteristics (e.g., volume of tissue corresponding to microbes, water filtering rates, and microbial transmission type) have similar bacterial phylogenetic community structure when looking at interactions aggregated over time. In general, sponge hosts hypothesized to form more intricate relationships with bacteria show a remarkably persistent bacterial community over time. Other hosts, however, show a large turnover similar to that observed for free-living bacterioplankton. Our study highlights the importance of exploring temporal variability in host--microbe interaction networks if we aim to determine how specific and persistent these

  2. AMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability

    PubMed Central

    Brechet, Aline; Buchert, Rebecca; Schwenk, Jochen; Boudkkazi, Sami; Zolles, Gerd; Siquier-Pernet, Karine; Schaber, Irene; Bildl, Wolfgang; Saadi, Abdelkrim; Bole-Feysot, Christine; Nitschke, Patrick; Reis, Andre; Sticht, Heinrich; Al-Sanna’a, Nouriya; Rolfs, Arndt; Kulik, Akos; Schulte, Uwe; Colleaux, Laurence; Abou Jamra, Rami; Fakler, Bernd

    2017-01-01

    AMPA-type glutamate receptors (AMPARs), key elements in excitatory neurotransmission in the brain, are macromolecular complexes whose properties and cellular functions are determined by the co-assembled constituents of their proteome. Here we identify AMPAR complexes that transiently form in the endoplasmic reticulum (ER) and lack the core-subunits typical for AMPARs in the plasma membrane. Central components of these ER AMPARs are the proteome constituents FRRS1l (C9orf4) and CPT1c that specifically and cooperatively bind to the pore-forming GluA1-4 proteins of AMPARs. Bi-allelic mutations in the human FRRS1L gene are shown to cause severe intellectual disability with cognitive impairment, speech delay and epileptic activity. Virus-directed deletion or overexpression of FRRS1l strongly impact synaptic transmission in adult rat brain by decreasing or increasing the number of AMPARs in synapses and extra-synaptic sites. Our results provide insight into the early biogenesis of AMPARs and demonstrate its pronounced impact on synaptic transmission and brain function. PMID:28675162

  3. 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.

  4. p38 pathway targets SWI-SNF chromatin-remodeling complex to muscle-specific loci.

    PubMed

    Simone, Cristiano; Forcales, Sonia Vanina; Hill, David A; Imbalzano, Anthony N; Latella, Lucia; Puri, Pier Lorenzo

    2004-07-01

    During skeletal myogenesis, genomic reprogramming toward terminal differentiation is achieved by recruiting chromatin-modifying enzymes to muscle-specific loci. The relative contribution of extracellular signaling cascades in targeting these enzymes to individual genes is unknown. Here we show that the differentiation-activated p38 pathway targets the SWI-SNF chromatin-remodeling complex to myogenic loci. Upon differentiation, p38 kinases were recruited to the chromatin of muscle-regulatory elements. Blockade of p38 alpha/beta repressed the transcription of muscle genes by preventing recruitment of the SWI-SNF complex at these elements without affecting chromatin binding of muscle-regulatory factors and acetyltransferases. The SWI-SNF subunit BAF60 could be phosphorylated by p38 alpha-beta in vitro, and forced activation of p38 alpha/beta in myoblasts by expression of a constitutively active MKK6 (refs. 5,6,7) promoted unscheduled SWI-SNF recruitment to the myogenin promoter. Conversely, inactivation of SWI-SNF enzymatic subunits abrogated MKK6-dependent induction of muscle gene expression. These results identify an unexpected function of differentiation-activated p38 in converting external cues into chromatin modifications at discrete loci, by selectively targeting SWI-SNF to muscle-regulatory elements.

  5. Crystal structure of Vigna radiata cytokinin-specific binding protein in complex with zeatin.

    PubMed

    Pasternak, Oliwia; Bujacz, Grzegorz D; Fujimoto, Yasuyuki; Hashimoto, Yuichi; Jelen, Filip; Otlewski, Jacek; Sikorski, Michal M; Jaskolski, Mariusz

    2006-10-01

    The cytosolic fraction of Vigna radiata contains a 17-kD protein that binds plant hormones from the cytokinin group, such as zeatin. Using recombinant protein and isothermal titration calorimetry as well as fluorescence measurements coupled with ligand displacement, we have reexamined the K(d) values and show them to range from approximately 10(-6) M (for 4PU30) to 10(-4) M (for zeatin) for 1:1 stoichiometry complexes. In addition, we have crystallized this cytokinin-specific binding protein (Vr CSBP) in complex with zeatin and refined the structure to 1.2 A resolution. Structurally, Vr CSBP is similar to plant pathogenesis-related class 10 (PR-10) proteins, despite low sequence identity (<20%). This unusual fold conservation reinforces the notion that classic PR-10 proteins have evolved to bind small-molecule ligands. The fold consists of an antiparallel beta-sheet wrapped around a C-terminal alpha-helix, with two short alpha-helices closing a cavity formed within the protein core. In each of the four independent CSBP molecules, there is a zeatin ligand located deep in the cavity with conserved conformation and protein-ligand interactions. In three cases, an additional zeatin molecule is found in variable orientation but with excellent definition in electron density, which plugs the entrance to the binding pocket, sealing the inner molecule from contact with bulk solvent.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26611739

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

    PubMed

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

    2014-10-16

    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.

  8. 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

  9. 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.

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

    PubMed

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

    2015-11-27

    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.

  11. 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

  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. 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

  14. 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

    2013-05-02

    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.

  15. Complex bud architecture and cell-specific chemical patterns enable supercooling of Picea abies bud primordia.

    PubMed

    Kuprian, Edith; Munkler, Caspar; Resnyak, Anna; Zimmermann, Sonja; Tuong, Tan D; Gierlinger, Notburga; Müller, Thomas; Livingston, David P; Neuner, Gilbert

    2017-09-29

    Bud primordia of Picea abies, despite a frozen shoot, stay ice free down to -50°C by a mechanism termed supercooling whose biophysical and biochemical requirements are poorly understood. Bud architecture was assessed by 3D-reconstruction, supercooling and freezing patterns by infrared video thermography, freeze dehydration and extra-organ freezing by water potential measurements and cell-specific chemical patterns by RAMAN microscopy and Mass Spectrometry Imaging. A bowl-like ice barrier tissue insulates primordia from entrance by intrinsic ice. Water repellent and densely packed bud scales prevent extrinsic ice penetration. At -18°C break-down of supercooling was triggered by intrinsic ice nucleators while the ice barrier remained active. Temperature-dependent freeze dehydration (-0.1 MPa/K) caused accumulation of extra-organ ice masses that by rupture of the shoot pith tissue are accommodated in large voids. The barrier tissue has exceptionally pectin-rich cell walls and intercellular spaces and the cell lumina were lined or filled with proteins, especially near the primordium. Primordial cells close to the barrier accumulate di-, tri- and tetrasaccharides. Bud architecture efficiently prevents ice penetration but ice nucleators become active inside the primordium below a temperature threshold. Biochemical patterns indicate a complex cellular interplay enabling supercooling and the necessity for cell-specific biochemical analysis. This article is protected by copyright. All rights reserved.

  16. Development of a Lactobacillus specific T-RFLP method to determine lactobacilli diversity in complex samples.

    PubMed

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

    2012-11-01

    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. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Tissue-Specific and Complex Complementation Patterns in the Punch Locus of DROSOPHILA MELANOGASTER

    PubMed Central

    Mackay, William J.; Reynolds, Elaine R.; O'Donnell, Janis M.

    1985-01-01

    Mutations in the Punch locus result in loss of GTP cyclohydrolase activity, but all mutations do not affect the enzyme in the same way. There are at least three classes of Punch mutations. One class results in a dominant eye color, recessive lethal phenotype. A second class of mutations also causes a recessive lethal phenotype, but heterozygous mutants have normal eye color. They show loss of GTP cyclohydrolase function in all tissues where activity can be measured. Alleles comprising a third class are recessive eye color mutations that are homozygous viable. Individuals with this third type of mutation show loss of enzyme activity in the eye, but show normal or near-normal activity elsewhere. In order to examine the organization and function of this locus further, we have performed interallelic complementation tests on 25 Punch mutations, monitoring viability and enzyme activity in prepupae and adults. Most allele combinations are lethal. Those that complement do so in ways that are tissue-or stage-specific and unpredictable. Tests of mutants with tissue-specific phenotypes and of individuals mutant for complementing Punch lethal alleles lead us to conclude that Punch is a complex locus, both with respect to its organization and to its products. PMID:3934035

  18. Rapid and Specific Detection of the Escherichia coli Sequence Type 648 Complex within Phylogroup F.

    PubMed

    Johnson, James R; Johnston, Brian D; Gordon, David M

    2017-04-01

    The Escherichia coli sequence type 648 complex (STc648) is an emerging lineage within phylogroup F-formerly included within phylogroup D-that is associated with multidrug resistance. Here, we designed and validated a novel multiplex PCR-based assay for STc648 that took advantage of (i) four distinctive single-nucleotide polymorphisms in icd allele 96 and gyrB allele 87, two of the multilocus sequence typing alleles that define ST648; and (ii) the typical absence within STc648 of uidA, an E. coli-specific gene encoding β-glucuronidase. Within a diverse 212-strain validation set that included 109 STs other than STc648, from phylogroups A, B1, B2, C, D, E, and F, the assay exhibited 100% sensitivity (95% confidence interval [CI], 82% to 100%) and specificity (95% CI, 98% to 100%). It functioned similarly well in two distant laboratories that used boiled lysates or DNAzol-purified DNA as the template DNA. Thus, this novel multiplex PCR-based assay should enable any laboratory equipped for diagnostic PCR to rapidly, accurately, and economically screen E. coli isolates for membership in STc648. Copyright © 2017 American Society for Microbiology.

  19. Nuclear mRNA export requires specific FG nucleoporins for translocation through the nuclear pore complex.

    PubMed

    Terry, Laura J; Wente, Susan R

    2007-09-24

    Trafficking of nucleic acids and large proteins through nuclear pore complexes (NPCs) requires interactions with NPC proteins that harbor FG (phenylalanine-glycine) repeat domains. Specialized transport receptors that recognize cargo and bind FG domains facilitate these interactions. Whether different transport receptors utilize preferential FG domains in intact NPCs is not fully resolved. In this study, we use a large-scale deletion strategy in Saccharomyces cerevisiae to generate a new set of more minimal pore (mmp) mutants that lack specific FG domains. A comparison of messenger RNA (mRNA) export versus protein import reveals unique subsets of mmp mutants with functional defects in specific transport receptors. Thus, multiple functionally independent NPC translocation routes exist for different transport receptors. Our global analysis of the FG domain requirements in mRNA export also finds a requirement for two NPC substructures-one on the nuclear NPC face and one in the NPC central core. These results pinpoint distinct steps in the mRNA export mechanism that regulate NPC translocation efficiency.

  20. Bragg Grating Simulation Software

    DTIC Science & Technology

    2008-02-01

    Organisation DSTO-TN-0800 ABSTRACT (U) This document is a user manual for a software application that predicts the complex reflection spectrum of...fibre Bragg gratings, given user defined input parameters. The software is designed primarily to complement the joint DSTO/Swinburne grating writing

  1. Mycobacterium tuberculosis Complex Exhibits Lineage-Specific Variations Affecting Protein Ductility and Epitope Recognition

    PubMed Central

    Yruela, Inmaculada; Contreras-Moreira, Bruno; Magalhães, Carlos; Osório, Nuno S.

    2016-01-01

    Abstract The advent of whole-genome sequencing has provided an unprecedented detail about the evolution and genetic significance of species-specific variations across the whole Mycobacterium tuberculosis Complex. However, little attention has been focused on understanding the functional roles of these variations in the protein coding sequences. In this work, we compare the coding sequences from 74 sequenced mycobacterial species including M. africanum, M. bovis, M. canettii, M. caprae, M. orygis, and M. tuberculosis. Results show that albeit protein variations affect all functional classes, those proteins involved in lipid and intermediary metabolism and respiration have accumulated mutations during evolution. To understand the impact of these mutations on protein functionality, we explored their implications on protein ductility/disorder, a yet unexplored feature of mycobacterial proteomes. In agreement with previous studies, we found that a Gly71Ile substitution in the PhoPR virulence system severely affects the ductility of its nearby region in M. africanum and animal-adapted species. In the same line of evidence, the SmtB transcriptional regulator shows amino acid variations specific to the Beijing lineage, which affects the flexibility of the N-terminal trans-activation domain. Furthermore, despite the fact that MTBC epitopes are evolutionary hyperconserved, we identify strain- and lineage-specific amino acid mutations affecting previously known T-cell epitopes such as EsxH and FbpA (Ag85A). Interestingly, in silico studies reveal that these variations result in differential interaction of epitopes with the main HLA haplogroups. PMID:28062754

  2. Pbx-Hox heterodimers recruit coactivator-corepressor complexes in an isoform-specific manner.

    PubMed

    Asahara, H; Dutta, S; Kao, H Y; Evans, R M; Montminy, M

    1999-12-01

    Homeobox (hox) proteins have been shown to regulate cell fate and segment identity by promoting the expression of specific genetic programs. In contrast to their restricted biological action in vivo, however, most homeodomain factors exhibit promiscuous DNA binding properties in vitro, suggesting a requirement for additional cofactors that enhance target site selectivity. In this regard, the pbx family of homeobox genes has been found to heterodimerize with and thereby augment the DNA binding activity of certain hox proteins on a subset of potential target sites. Here we examine the transcriptional properties of a forced hox-pbx heterodimer containing the pancreas-specific orphan homeobox factor pdx fused to pbx-1a. Compared to the pdx monomer, the forced pdx-pbx1a dimer, displayed 10- to 20-fold-higher affinity for a consensus hox-pbx binding site but was completely unable to bind a hox monomer recognition site. The pdx-pbx dimer stimulated target gene expression via an N-terminal trans-activation domain in pdx that interacts with the coactivator CREB binding protein. The pdx-pbx dimer was also found to repress transcription via a C-terminal domain in pbx-1a that associates with the corepressors SMRT and NCoR. The transcriptional properties of the pdx-pbx1 complex appear to be regulated at the level of alternative splicing; a pdx-pbx polypeptide containing the pbx1b isoform, which lacks the C-terminal extension in pbx1a, was unable to repress target gene expression via NCoR-SMRT. Since pbx1a and pbx1b are differentially expressed in endocrine versus exocrine compartments of the adult pancreas, our results illustrate a novel mechanism by which pbx proteins may modulate the expression of specific genetic programs, either positively or negatively, during development.

  3. Pbx-Hox Heterodimers Recruit Coactivator-Corepressor Complexes in an Isoform-Specific Manner

    PubMed Central

    Asahara, Hiroshi; Dutta, Sanjoy; Kao, Hung-Ying; Evans, Ronald M.; Montminy, Marc

    1999-01-01

    Homeobox (hox) proteins have been shown to regulate cell fate and segment identity by promoting the expression of specific genetic programs. In contrast to their restricted biological action in vivo, however, most homeodomain factors exhibit promiscuous DNA binding properties in vitro, suggesting a requirement for additional cofactors that enhance target site selectivity. In this regard, the pbx family of homeobox genes has been found to heterodimerize with and thereby augment the DNA binding activity of certain hox proteins on a subset of potential target sites. Here we examine the transcriptional properties of a forced hox-pbx heterodimer containing the pancreas-specific orphan homeobox factor pdx fused to pbx-1a. Compared to the pdx monomer, the forced pdx-pbx1a dimer, displayed 10- to 20-fold-higher affinity for a consensus hox-pbx binding site but was completely unable to bind a hox monomer recognition site. The pdx-pbx dimer stimulated target gene expression via an N-terminal trans-activation domain in pdx that interacts with the coactivator CREB binding protein. The pdx-pbx dimer was also found to repress transcription via a C-terminal domain in pbx-1a that associates with the corepressors SMRT and NCoR. The transcriptional properties of the pdx-pbx1 complex appear to be regulated at the level of alternative splicing; a pdx-pbx polypeptide containing the pbx1b isoform, which lacks the C-terminal extension in pbx1a, was unable to repress target gene expression via NCoR-SMRT. Since pbx1a and pbx1b are differentially expressed in endocrine versus exocrine compartments of the adult pancreas, our results illustrate a novel mechanism by which pbx proteins may modulate the expression of specific genetic programs, either positively or negatively, during development. PMID:10567547

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

    PubMed

    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

    2012-03-01

    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.

  5. 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…

  6. 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.

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

    PubMed

    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.

  8. 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

  9. 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.

  10. A nonemissive iridium(III) complex that specifically lights-up the nuclei of living cells.

    PubMed

    Li, Chunyan; Yu, Mengxiao; Sun, Yun; Wu, Yongquan; Huang, Chunhui; Li, Fuyou

    2011-07-27

    A nonemissive cyclometalated iridium(III) solvent complex, without conjugation with a cell-penetrating molecular transporter, [Ir(ppy)(2)(DMSO)(2)](+)PF(6)(-) (LIr1), has been developed as a first reaction-based fluorescence-turn-on agent for the nuclei of living cells. LIr1 can rapidly and selectively light-up the nuclei of living cells over fixed cells, giving rise to a significant luminescence enhancement (200-fold), and shows very low cytotoxicity at the imaging concentration (incubation time <10 min, LIr1 concentration 10 μM). More importantly, in contrast to the reported nuclear stains that are based on luminescence enhancement through interaction with nucleic acids, complex LIr1 as a nuclear stain has a reaction-based mode of action, which relies on its rapid reaction with histidine/histidine-containing proteins. Cellular uptake of LIr1 has been investigated in detail under different conditions, such as at various temperatures, with hypertonic treatment, and in the presence of metabolic and endocytic inhibitors. The results have indicated that LIr1 permeates the outer and nuclear membranes of living cells through an energy-dependent entry pathway within a few minutes. As determined by an inductively coupled plasma atomic emission spectroscopy (ICP-AEC), LIr1 is accumulated in the nuclei of living cells and converted into an intensely emissive adduct. Such novel reaction-based nuclear staining for visualizing exclusively the nuclei of living cells with a significant luminescence enhancement may extend the arsenal of currently available fluorescent stains for specific staining of cellular compartments.

  11. Crystal structure of the histone lysine specific demethylase LSD1 complexed with tetrahydrofolate.

    PubMed

    Luka, Zigmund; Pakhomova, Svetlana; Loukachevitch, Lioudmila V; Calcutt, M Wade; Newcomer, Marcia E; Wagner, Conrad

    2014-07-01

    An important epigenetic modification is the methylation/demethylation of histone lysine residues. The first histone demethylase to be discovered was a lysine-specific demethylase 1, LSD1, a flavin containing enzyme which carries out the demethylation of di- and monomethyllysine 4 in histone H3. The removed methyl groups are oxidized to formaldehyde. This reaction is similar to those performed by dimethylglycine dehydrogenase and sarcosine dehydrogenase, in which protein-bound tetrahydrofolate (THF) was proposed to serve as an acceptor of the generated formaldehyde. We showed earlier that LSD1 binds THF with high affinity which suggests its possible participation in the histone demethylation reaction. In the cell, LSD1 interacts with co-repressor for repressor element 1 silencing transcription factor (CoREST). In order to elucidate the role of folate in the demethylating reaction we solved the crystal structure of the LSD1-CoREST-THF complex. In the complex, the folate-binding site is located in the active center in close proximity to flavin adenine dinucleotide. This position of the folate suggests that the bound THF accepts the formaldehyde generated in the course of histone demethylation to form 5,10-methylene-THF. We also show the formation of 5,10-methylene-THF during the course of the enzymatic reaction in the presence of THF by mass spectrometry. Production of this form of folate could act to prevent accumulation of potentially toxic formaldehyde in the cell. These studies suggest that folate may play a role in the epigenetic control of gene expression in addition to its traditional role in the transfer of one-carbon units in metabolism.

  12. 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.

  13. Software Prototyping

    PubMed Central

    Del Fiol, Guilherme; Hanseler, Haley; Crouch, Barbara Insley; Cummins, Mollie R.

    2016-01-01

    Summary Background Health information exchange (HIE) between Poison Control Centers (PCCs) and Emergency Departments (EDs) could improve care of poisoned patients. However, PCC information systems are not designed to facilitate HIE with EDs; therefore, we are developing specialized software to support HIE within the normal workflow of the PCC using user-centered design and rapid prototyping. Objective To describe the design of an HIE dashboard and the refinement of user requirements through rapid prototyping. Methods Using previously elicited user requirements, we designed low-fidelity sketches of designs on paper with iterative refinement. Next, we designed an interactive high-fidelity prototype and conducted scenario-based usability tests with end users. Users were asked to think aloud while accomplishing tasks related to a case vignette. After testing, the users provided feedback and evaluated the prototype using the System Usability Scale (SUS). Results Survey results from three users provided useful feedback that was then incorporated into the design. After achieving a stable design, we used the prototype itself as the specification for development of the actual software. Benefits of prototyping included having 1) subject-matter experts heavily involved with the design; 2) flexibility to make rapid changes, 3) the ability to minimize software development efforts early in the design stage; 4) rapid finalization of requirements; 5) early visualization of designs; 6) and a powerful vehicle for communication of the design to the programmers. Challenges included 1) time and effort to develop the prototypes and case scenarios; 2) no simulation of system performance; 3) not having all proposed functionality available in the final product; and 4) missing needed data elements in the PCC information system. PMID:27081404

  14. Complex Visual Adaptations in Squid for Specific Tasks in Different Environments

    PubMed Central

    Chung, Wen-Sung; Marshall, N. Justin

    2017-01-01

    In common with their major competitors, the fish, squid are fast moving visual predators that live over a great range of depths in the ocean. Both squid and fish show a variety of adaptations with respect to optical properties, receptors and their underlying neural circuits, and these adaptations are often linked to the light conditions of their specific niche. In contrast to the extensive investigations of adaptive strategies in fish, vision in response to the varying quantity and quality of available light, our knowledge of visual adaptations in squid remains sparse. This study therefore undertook a comparative study of visual adaptations and capabilities in a number of squid species collected between 0 and 1,200 m. Histology, magnetic resonance imagery (MRI), and depth distributions were used to compare brains, eyes, and visual capabilities, revealing that the squid eye designs reflect the lifestyle and the versatility of neural architecture in its visual system. Tubular eyes and two types of regional retinal deformation were identified and these eye modifications are strongly associated with specific directional visual tasks. In addition, a combination of conventional and immuno-histology demonstrated a new form of a complex retina possessing two inner segment layers in two mid-water squid species which they rhythmically move across a broad range of depths (50–1,000 m). In contrast to their relatives with the regular single-layered inner segment retina live in the upper mesopelagic layer (50–400 m), the new form of retinal interneuronal layers suggests that the visual sensitivity of these two long distance vertical migrants may increase in response to dimmer environments. PMID:28286484

  15. Guanine-specific DNA damage photosensitized by the dihydroxo(tetraphenylporphyrinato)antimony(V) complex.

    PubMed

    Hirakawa, Kazutaka; Kawanishi, Shosuke; Matsumoto, Jin; Shiragami, Tsutomu; Yasuda, Masahide

    2006-01-02

    The dihydroxo(tetraphenylporphyrinato)antimony(V) complex (SbTPP) demonstrates bactericidal activity under visible-light irradiation. This phototoxic effect could be caused by photodamage to biomolecules, but the mechanism has not been well understood. In this study, to clarify the mechanism of phototoxicity by SbTPP, DNA damage photosensitized by SbTPP was examined using [(32)P]-5'-end-labeled DNA fragments. SbTPP induced markedly severe photodamage to single-stranded rather than to double-stranded DNA. Photo-irradiated SbTPP frequently caused DNA cleavage at the guanine residue of single-stranded DNA after Escherichia coli formamidopyrimidine-DNA glycosylase or piperidine treatment. HPLC measurement confirmed the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an oxidation product of 2'-deoxyguanosine, and showed that the content of 8-oxodG in single-stranded DNA is larger than that in double-stranded DNA. The effects of scavengers of reactive oxygen species on DNA damage suggested the involvement of singlet oxygen. These results have shown that the mechanism via singlet oxygen formation mainly contributes to the phototoxicity of SbTPP. On the other hand, SbTPP induced DNA damage specifically at the underlined G of 5'-GG, 5'-GGG, and 5'-GGGG in double-stranded DNA. The sequence-specificity of DNA damage is quite similar to that induced by the type I photosensitizers, suggesting that photo-induced electron transfer slightly participates in the phototoxicity of SbTPP. In conclusion, SbTPP induces DNA photodamage via singlet oxygen formation and photo-induced electron transfer. A similar mechanism can damage other biomacromolecules, such as protein and the phospholipid membrane. The damage to biomacromolecules via these mechanisms may participate in the phototoxicity of SbTPP.

  16. Evolution of design considerations in complex craniofacial reconstruction using patient-specific implants.

    PubMed

    Peel, Sean; Bhatia, Satyajeet; Eggbeer, Dominic; Morris, Daniel S; Hayhurst, Caroline

    2016-12-01

    Previously published evidence has established major clinical benefits from using computer-aided design, computer-aided manufacturing, and additive manufacturing to produce patient-specific devices. These include cutting guides, drilling guides, positioning guides, and implants. However, custom devices produced using these methods are still not in routine use, particularly by the UK National Health Service. Oft-cited reasons for this slow uptake include the following: a higher up-front cost than conventionally fabricated devices, material-choice uncertainty, and a lack of long-term follow-up due to their relatively recent introduction. This article identifies a further gap in current knowledge - that of design rules, or key specification considerations for complex computer-aided design/computer-aided manufacturing/additive manufacturing devices. This research begins to address the gap by combining a detailed review of the literature with first-hand experience of interdisciplinary collaboration on five craniofacial patient case studies. In each patient case, bony lesions in the orbito-temporal region were segmented, excised, and reconstructed in the virtual environment. Three cases translated these digital plans into theatre via polymer surgical guides. Four cases utilised additive manufacturing to fabricate titanium implants. One implant was machined from polyether ether ketone. From the literature, articles with relevant abstracts were analysed to extract design considerations. In all, 19 frequently recurring design considerations were extracted from previous publications. Nine new design considerations were extracted from the case studies - on the basis of subjective clinical evaluation. These were synthesised to produce a design considerations framework to assist clinicians with prescribing and design engineers with modelling. Promising avenues for further research are proposed.

  17. 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

  18. Comparison between In-house developed and Diamond commercial software for patient specific independent monitor unit calculation and verification with heterogeneity corrections.

    PubMed

    Kuppusamy, Vijayalakshmi; Nagarajan, Vivekanandan; Jeevanandam, Prakash; Murugan, Lavanya

    2016-02-01

    The study was aimed to compare two different monitor unit (MU) or dose verification software in volumetric modulated arc therapy (VMAT) using modified Clarkson's integration technique for 6 MV photons beams. In-house Excel Spreadsheet based monitor unit verification calculation (MUVC) program and PTW's DIAMOND secondary check software (SCS), version-6 were used as a secondary check to verify the monitor unit (MU) or dose calculated by treatment planning system (TPS). In this study 180 patients were grouped into 61 head and neck, 39 thorax and 80 pelvic sites. Verification plans are created using PTW OCTAVIUS-4D phantom and also measured using 729 detector chamber and array with isocentre as the suitable point of measurement for each field. In the analysis of 154 clinically approved VMAT plans with isocentre at a region above -350 HU, using heterogeneity corrections, In-house Spreadsheet based MUVC program and Diamond SCS showed good agreement TPS. The overall percentage average deviations for all sites were (-0.93% + 1.59%) and (1.37% + 2.72%) for In-house Excel Spreadsheet based MUVC program and Diamond SCS respectively. For 26 clinically approved VMAT plans with isocentre at a region below -350 HU showed higher variations for both In-house Spreadsheet based MUVC program and Diamond SCS. It can be concluded that for patient specific quality assurance (QA), the In-house Excel Spreadsheet based MUVC program and Diamond SCS can be used as a simple and fast accompanying to measurement based verification for plans with isocentre at a region above -350 HU. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  19. 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.

  20. FASTBUS software status

    SciTech Connect

    Gustavson, D.B.

    1980-10-01

    Computer software will be needed in addition to the mechanical, electrical, protocol and timing specifications of the FASTBUS, in order to facilitate the use of this flexible new multiprocessor and multisegment data acquisition and processing system. Software considerations have been important in the FASTBUS design, but standard subroutines and recommended algorithms will be needed as the FASTBUS comes into use. This paper summarizes current FASTBUS software projects, goals and status.

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

    PubMed Central

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

    2016-01-01

    ABSTRACT 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

  2. Recognition of class I major histocompatibility complex molecules by Ly- 49: specificities and domain interactions

    PubMed Central

    1996-01-01

    Ly-49 is a family type II transmembrane proteins encoded by a gene cluster on murine chromosome 6. One member of this family, Ly-49A, is expressed by a natural killer (NK) cell subset, binds to class I major histocompatibility complex (MHC) molecules, and blocks the killing of target cells bearing the appropriate H-2 antigens. Here we show that another member of this family which is expressed by an NK cell subset, Ly-49C, recognizes H-2b and H-2d structures which are distinct from and overlapping with those recognized by Ly-49A. Interactions between Ly- 49A and C and their class I ligands are entirely blocked by the antibodies 5E6, YE1/48, YE1/32, and A1, all of which were found to recognize epitopes contained within the carbohydrate recognition domain (CRD). However, cell-cell binding assays revealed that class I binding specificity is conferred by a combination of sequences within both the CRD and a 19-amino acid adjacent region. We also investigated the question of whether Ly-49A and C form dimers on cells which express both receptors. When coexpressed on COS cells, sequential immunoprecipitation demonstrated that these receptors pair exclusively as homodimers, with no evidence for heterodimeric structures. These observations provide insight into both the biochemical nature of the Ly- 49 family as well as the receptor functions of Ly-49C on NK cells. PMID:8666913

  3. Long-term stability of alpha-1-antichymotrypsin complexed form of prostate specific antigen.

    PubMed

    Brawer, M K; Ferreri, L F; Bankson, D D

    2000-11-01

    PSA complexed with alpha-1-anti-chymotrypsin (cPSA trade mark ) is the moiety in greatest proportion in the serum of men with prostate cancer (CAP). The performance of this analyte has been established primarily in retrospective archival serum. Studies indicate cPSA trade mark provides the specificity enhancement of the free-to-total PSA ratio, yet obviates the need to measure two markers. In the present investigation we sought to establish the stability of cPSA trade mark with long-term storage. Serum from men undergoing ultrasound-guided biopsy was utilized. Serum was assayed soon after collection and 18 months later. All serum was initially aliquotted and stored at -80 degrees C. There was no freeze-thaw. cPSA trade mark was measured utilizing the Bayer Immuno 1 method according to manufacturer's recommendations. The mean (s.d.) PSA was 5.5 (3.8) and 5.6 (3.9) ng/ml at the initial and subsequent testing, respectively. The medians were 4.3 and 4.4 ng/ml, respectively. No significant differences exist between the two determinants (r(2)=1.0, slope=1.01, t-test P=0.9194). These data establish for the first time the long-term stability of cPSA trade mark. Retrospective studies performed on archival material should give meaningful results. Prostate Cancer and Prostatic Diseases (2000) 3, 191-194

  4. Transactivation of the parathyroid hormone promoter by specificity proteins and the nuclear factor Y complex.

    PubMed

    Alimov, Alexander P; Park-Sarge, Ok-Kyong; Sarge, Kevin D; Malluche, Hartmut H; Koszewski, Nicholas J

    2005-08-01

    We previously identified a highly conserved specificity protein 1 (Sp1) DNA element in mammalian PTH promoters that acted as an enhancer of gene transcription and bound Sp1 and Sp3 proteins present in parathyroid gland nuclear extracts. More recently, a nuclear factor (NF)-Y element (NF-Y(prox)) was also described by our group, which was located approximately 30 bp downstream from the Sp1 site in the human PTH (hPTH) promoter and by itself acted as a weak enhancer of gene transcription. We now report that Sp proteins and NF-Y can synergistically enhance transcription of a minimal hPTH promoter construct. Positioning of the Sp1 DNA element appears to be critical for this synergism because deviations of one half of a helical turn caused an approximate 60% decrease in transactivation. Finally, examination of the bovine PTH (bPTH) promoter also revealed Sp1/NF-Y synergism, in conjunction with the identification of an analogous NF-Y binding site similarly positioned downstream from the bPTH Sp1 element. In summary, synergistic transactivation of the hPTH and bPTH promoters is observed by Sp proteins and the NF-Y complex. The conservation of this transactivation in the human and bovine promoters suggests that this may be a principle means of enhancing PTH gene transcription.

  5. What can bibliographic software offer you?

    PubMed

    Ravenscroft, E F

    2000-01-01

    This article provides an introduction to bibliographic software products, common uses for bibliographic software, and some suggestions on how to choose the right software product. The focus of this article is on software for individual, rather than institutional, use. Bibliographic software is designed to allow information to be catalogued and retrieved with ease. Bibliographic software products range from catalogue database software to more specialized bibliographic database and management software products. Each type of product meets the needs of a specific user group.

  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. 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…

  8. Complex, multifocal, individual-specific attention-related cortical functional circuits.

    PubMed

    Basile, Luis F H

    2007-01-01

    Recent studies focusing on the analysis of individual patterns of non-sensory-motor CNS activity may significantly alter our view of CNS functional mapping. We have recently provided evidence for highly variable attention-related Slow Potential (SP) generating cortical areas across individuals (Basile et al., 2003, 2006). In this work, we present new evidence, searching for other physiological indexes of attention by a new use of a well established method, for individual-specific sets of cortical areas active during expecting attention. We applied latency corrected peak averaging to oscillatory bursts, from 124-channel EEG recordings, and modeled their generators by current density reconstruction. We first computed event-related total power, and averaging was based on individual patterns of narrow task-induced band-power. This method is sensitive to activity out of synchrony with stimuli, and may detect task-related changes missed by regular Event-Related Potential (ERP) averaging. We additionally analyzed overall inter-electrode phase-coherence. The main results were (1) the detection of two bands of attention-induced beta range oscillations (around 25 and 21 Hz), whose scalp topography and current density cortical distribution were complex multi-focal, and highly variable across subjects, including prefrontal and posterior cortical areas. Most important, however, was the observation that (2) the generators of task-induced oscillations are largely the same individual-specific sets of cortical areas active during the resting, baseline state. We concluded that attention-related electrical cortical activity is highly individual-specific (significantly different from sensory-related visual evoked potentials or delta and theta induced band-power), and to a great extent already established during mere wakefulness. We discuss the critical implications of those results, in combination with other studies presenting individual data, to functional mapping: the need to

  9. Inferring condition-specific targets of human TF-TF complexes using ChIP-seq data.

    PubMed

    Yang, Chia-Chun; Chen, Min-Hsuan; Lin, Sheng-Yi; Andrews, Erik H; Cheng, Chao; Liu, Chun-Chi; Chen, Jeremy J W

    2017-01-10

    Transcription factors (TFs) often interact with one another to form TF complexes that bind DNA and regulate gene expression. Many databases are created to describe known TF complexes identified by either mammalian two-hybrid experiments or data mining. Lately, a wealth of ChIP-seq data on human TFs under different experiment conditions are available, making it possible to investigate condition-specific (cell type and/or physiologic state) TF complexes and their target genes. Here, we developed a systematic pipeline to infer Condition-Specific Targets of human TF-TF complexes (called the CST pipeline) by integrating ChIP-seq data and TF motifs. In total, we predicted 2,392 TF complexes and 13,504 high-confidence or 127,994 low-confidence regulatory interactions amongst TF complexes and their target genes. We validated our predictions by (i) comparing predicted TF complexes to external TF complex databases, (ii) validating selected target genes of TF complexes using ChIP-qPCR and RT-PCR experiments, and (iii) analysing target genes of select TF complexes using gene ontology enrichment to demonstrate the accuracy of our work. Finally, the predicted results above were integrated and employed to construct a CST database. We built up a methodology to construct the CST database, which contributes to the analysis of transcriptional regulation and the identification of novel TF-TF complex formation in a certain condition. This database also allows users to visualize condition-specific TF regulatory networks through a user-friendly web interface.

  10. 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.

  11. The assembly, activation, and substrate specificity of Cyclin D1/Cdk2 complexes

    PubMed Central

    Jahn, Stephan C.; Law, Mary E.; Corsino, Patrick E.; Rowe, Thomas C.; Davis, Bradley J.; Law, Brian K.

    2013-01-01

    Previous studies have shown conflicting data regarding Cyclin D1/Cdk2 complexes and, considering the widespread overexpression of Cyclin D1 in cancer, it is important to fully understand their relevance. While many have shown Cyclin D1/Cdk2 complexes to form active complexes, others have failed to show activity or association. Here, using a novel p21-PCNA fusion protein as well as p21 mutant proteins, we show that p21 is a required scaffolding protein, with Cyclin D1 and Cdk2 failing to complex in its absence. These p21/Cyclin D1/Cdk2 complexes are active and also bind the trimeric PCNA complex, with each trimer capable of independently binding distinct Cyclin/Cdk complexes. We also show that increased p21 levels due to treatment with chemotherapeutic agents result in increased formation and kinase activity of Cyclin D1/Cdk2 complexes, and that Cyclin D1/Cdk2 complexes are able to phosphorylate a number of substrates in addition to Rb. Nucleophosmin and Cdh1, two proteins important for centrosome replication and implicated in the chromosomal instability of cancer are shown to be phosphorylated by Cyclin D1/Cdk2 complexes. Additionally, PSF is identified as a novel Cdk2 substrate, being phosphorylated by Cdk2 complexed with either Cyclin E or Cyclin D1, and given the many functions of PSF, it could have important implications on cellular activity. PMID:23627734

  12. Software Assurance Competency Model

    DTIC Science & Technology

    2013-03-01

    2010a]: Application of technologies and processes to achieve a required level of confidence that software systems and services function in the...for specific projects. L5: Analyze assurance technologies and contribute to the development of new ones. Assured Software Development L1

  13. 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.

  14. 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)

  15. 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)

  16. 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

  17. Rescue of PINK1 Protein Null-specific Mitochondrial Complex IV Deficits by Ginsenoside Re Activation of Nitric Oxide Signaling*

    PubMed Central

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

    2012-01-01

    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

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

    PubMed

    Pollard, Amelia Kate; Craig, Emma Louise; 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.

  19. 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.

  20. Specificity of recognition of mRNA 5' cap by human nuclear cap-binding complex.

    PubMed

    Worch, Remigiusz; Niedzwiecka, Anna; Stepinski, Janusz; Mazza, Catherine; Jankowska-Anyszka, Marzena; Darzynkiewicz, Edward; Cusack, Stephen; Stolarski, Ryszard

    2005-09-01

    The heterodimeric nuclear cap-binding complex (CBC) binds to the mono-methylated 5' cap of eukaryotic RNA polymerase II transcripts such as mRNA and U snRNA. The binding is important for nuclear maturation of mRNAs and possibly in the first round of translation and nonsense-mediated decay. It is also essential for nuclear export of U snRNAs in metazoans. We report characterization by fluorescence spectroscopy of the recognition of 5' capped RNA by human CBC. The association constants (K(as)) for 17 mono- and dinucleotide cap analogs as well as for the oligomer m7GpppA(m2') pU(m2')pA(m2') cover the range from 1.8 x 10(6) M(-1) to 2.3 x 10(8) M(-1). Higher affinity for CBC is observed for the dinucleotide compared with mononucleotide analogs, especially for those containing a purine nucleoside next to m7G. The mRNA tetramer associates with CBC as tightly as the dinucleotide analogs. Replacement of Tyr138 by alanine in the CBP20 subunit of CBC reduces the cap affinity except for the mononucleotide analogs, consistent with the crystallographic observation of the second base stacking on this residue. Our spectroscopic studies showed that contrary to the other known cap-binding proteins, the first two nucleotides of a capped-RNA are indispensable for its specific recognition by CBC. Differences in the cap binding of CBC compared with the eukaryotic translation initiation factor 4E (eIF4E) are analyzed and discussed regarding replacement of CBC by eIF4E.

  1. Specificity and Membrane Partitioning of Grsp1 Signaling Complexes with Grp1 Family ARF Exchange Factors

    PubMed Central

    DiNitto, Jonathan P.; Lee, Meng-Tse; Malaby, Andrew W.; Lambright, David G.

    2010-01-01

    The Arf exchange factor Grp1 selectively binds phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3), which is required for recruitment to the plasma membrane in stimulated cells. The mechanisms for phosphoinositide recognition by the PH domain, catalysis of nucleotide exchange by the Sec7 domain, and autoinhibition by elements proximal to the PH domain are well characterized. The N-terminal heptad repeats in Grp1 have also been shown to mediate homodimerization in vitro as well as heteromeric interactions with heptad repeats in the FERM domain-containing protein Grsp1 both in vitro and in cells (1). Here, we have characterized the oligomeric state of Grsp1 and Grp1 family proteins (Grp1, ARNO, and Cytohesin-1) as well as the oligomeric state, stoichiometry, and specificity of Grsp1 complexes with Grp1, ARNO and Cytohesin-1. At low micromolar concentrations, Grp1 and ARNO are homodimeric whereas Cytohesin-1 and Grsp1 are monomeric. When mixed with Grsp1, Grp1 homodimers and Cytohesin-1 monomers spontaneously re-equilibrate to form heterodimers whereas approximately 50% of ARNO remains homodimeric under the same conditions. Fluorescence resonance energy transfer experiments suggest that the Grsp1 heterodimers with Grp1 and Cytohesin-1 adopt a largely anti-parallel orientation. Finally, formation of Grsp1-Grp1 heterodimers does not substantially influence Grp1 binding to the head groups of PtdIns(3,4,5)P3 or PtdIns(4,5)P2 nor does it influence partitioning with liposomes containing PtdIns(3,4,5)P3, PtdIns(4,5)P2 and/or phosphatidyl serine. PMID:20527794

  2. 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.

  3. Development and evaluation of the LiSN & learn auditory training software for deficit-specific remediation of binaural processing deficits in children: preliminary findings.

    PubMed

    Cameron, Sharon; Dillon, Harvey

    2011-01-01

    The LiSN & Learn auditory training software was developed specifically to improve binaural processing skills in children with suspected central auditory processing disorder who were diagnosed as having a spatial processing disorder (SPD). SPD is defined here as a condition whereby individuals are deficient in their ability to use binaural cues to selectively attend to sounds arriving from one direction while simultaneously suppressing sounds arriving from another. As a result, children with SPD have difficulty understanding speech in noisy environments, such as in the classroom. To develop and evaluate the LiSN & Learn auditory training software for children diagnosed with the Listening in Spatialized Noise-Sentences Test (LiSN-S) as having an SPD. The LiSN-S is an adaptive speech-in-noise test designed to differentially diagnose spatial and pitch-processing deficits in children with suspected central auditory processing disorder. Participants were nine children (aged between 6 yr, 9 mo, and 11 yr, 4 mo) who performed outside normal limits on the LiSN-S. In a pre-post study of treatment outcomes, participants trained on the LiSN & Learn for 15 min per day for 12 weeks. Participants acted as their own control. Participants were assessed on the LiSN-S, as well as tests of attention and memory and a self-report questionnaire of listening ability. Performance on all tasks was reassessed after 3 mo where no further training occurred. The LiSN & Learn produces a three-dimensional auditory environment under headphones on the user's home computer. The child's task was to identify a word from a target sentence presented in background noise. A weighted up-down adaptive procedure was used to adjust the signal level of the target based on the participant's response. On average, speech reception thresholds on the LiSN & Learn improved by 10 dB over the course of training. As hypothesized, there were significant improvements in posttraining performance on the LiSN-S conditions

  4. 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

    2016-04-01

    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.

  5. 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.

  6. 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.

  7. Does pattern recognition software using the Bahr monitor improve the sensitivity, specificity, and concordance of ambulatory skin conductance monitoring of hot flushes?

    PubMed

    Stefanopoulou, Evgenia; Hunter, Myra Sally

    2013-11-01

    The aim of this study was to validate the performance of a new pattern recognition method for quantifying physiological hot flushes against conventional fixed criterion methods and to explore its suitability for use in ambulatory clinical trials. This study performed a secondary analysis of baseline and outcome sternal skin conductance monitoring data from two recent randomized controlled trials of cognitive-behavioral therapy (CBT) for hot flushes in breast cancer patients (MENOS1) and healthy peri- and postmenopausal women (MENOS2) using a revised pattern recognition method (Bahr monitor; software version 1.1.6). Sensitivity and specificity were recalculated and compared with previous findings, based on conventional criteria, using monitor-defined flushes as "gold standard" and combined baseline data. Outcome data for physiologically measured flushes between the CBT group and the treatment-as-usual group were separately reexamined using the revised method for each trial. Pattern recognition showed higher concordance (36%), sensitivity (0.64), and specificity (0.99) than the standard method. Hot flushes recorded during the day showed slightly higher concordance (39%) and fewer false-negatives than 24-hour recordings. Based on the revised method, well women randomized to CBT (MENOS2) had significantly fewer flushes than those randomized to treatment as usual at posttreatment (P < 0.04), but CBT did not impact on physiologically measured hot flushes for breast cancer patients (MENOS1). Pattern recognition can identify flushes more reliably by detecting the shape of physiological signals rather than by relying solely on the amplitude of their signals (as used in conventional criteria). With application of the revised method, ambulatory sternal skin conductance monitoring detects changes after a CBT intervention in well women but not in breast cancer survivors.

  8. 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.…

  9. Structural basis of pyrimidine specificity in the MS2 RNA hairpin-coat-protein complex.

    PubMed Central

    Grahn, E; Moss, T; Helgstrand, C; Fridborg, K; Sundaram, M; Tars, K; Lago, H; Stonehouse, N J; Davis, D R; Stockley, P G; Liljas, L

    2001-01-01

    We have determined the X-ray structures of six MS2 RNA hairpin-coat-protein complexes having five different substitutions at the hairpin loop base -5. This is a uracil in the wild-type hairpin and contacts the coat protein both by stacking on to a tyrosine side chain and by hydrogen bonding to an asparagine side chain. The RNA consensus sequence derived from coat protein binding studies with natural sequence variants suggested that the -5 base needs to be a pyrimidine for strong binding. The five -5 substituents used in this study were 5-bromouracil, pyrimidin-2-one, 2-thiouracil, adenine, and guanine. The structure of the 5-bromouracil complex was determined to 2.2 A resolution, which is the highest to date for any MS2 RNA-protein complex. All the complexes presented here show very similar conformations, despite variation in affinity in solution. The results suggest that the stacking of the -5 base on to the tyrosine side chain is the most important driving force for complex formation. A number of hydrogen bonds that are present in the wild-type complex are not crucial for binding, as they are missing in one or more of the complexes. The results also reveal the flexibility of this RNA-protein interface, with respect to functional group variation, and may be generally applicable to other RNA-protein complexes. PMID:11720290

  10. 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.…

  11. 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.

  12. PD5: a general purpose library for primer design software.

    PubMed

    Riley, Michael C; Aubrey, Wayne; Young, Michael; Clare, Amanda

    2013-01-01

    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. 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. The PD5 software library is downloadable from Google Code and the accompanying Wiki includes instructions and examples: http://code.google.com/p/primer-design.

  13. 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

  14. Deconvolution method for specific and nonspecific binding of ligand to multi-protein complex by native mass spectrometry

    PubMed Central

    Guan, Shenheng; Trnka, Michael J.; Burlingame, Alma L.; Bushnell, David A.; Robinson, Philip J. J.; Kornberg, Roger D.; Gestwicki, Jason E.; Prusiner, Stanley B.

    2016-01-01

    In native mass spectrometry, it has been difficult to discriminate between specific binding of a ligand to a multi-protein complex from the nonspecific interactions. Here, we present a deconvolution model that consists of two levels of data reduction. At the first level, the apparent association binding constants are extracted from the measured intensities of the target/ligand complexes by varying ligand concentration. At the second level, two functional forms representing the specific- and non-specific binding events are fit to the binding constants obtained from the first level of modeling. Using this approach, we found that an inverse power distribution described nonspecific binding of α-amanitin to yeast RNA polymerase II. Moreover, treating the concentration of the multi-protein complex as a fitting parameter reduced the impact of inaccuracies in this experimental measurement on the apparent association constants. This model provides an improved way of separating specific and non-specific binding to large, multi-protein complexes in native mass spectrometry. PMID:26189511

  15. 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.

  16. 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.

  17. 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.

  18. Development of in vitro PIK3C3/VPS34 complex protein assay for autophagy-specific inhibitor screening.

    PubMed

    Kim, Tae-Mi; Baek, Jong-Hyuk; Kim, Jeong Hee; Oh, Myung Sook; Kim, Joungmok

    2015-07-01

    Autophagy is an important catabolic program to respond to a variety of cellular stresses by forming a double membrane vesicle, autophagosome. Autophagy plays key roles in various cellular functions. Accordingly, dysregulation of autophagy is closely associated with diseases such as diabetes, neurodegenerative diseases, cardiomyopathy, and cancer. In this sense, autophagy is emerging as an important therapeutic target for disease control. Among the autophagy machineries, PIK3C3/VPS34 complex functions as an autophagy-triggering kinase to recruit the subsequent autophagy protein machineries on the phagophore membrane. Accumulating evidence showing that inhibition of PIK3C3/VPS34 complex successfully inhibits autophagy makes the complex an attractive target for developing autophagy inhibitors. However, one concern about PIK3C3/VPS34 complex is that many different PIK3C3/VPS34 complexes have distinct cellular functions. In this study, we have developed an in vitro PIK3C3/VPS34 complex monitoring assay for autophagy inhibitor screening in a high-throughput assay format instead of targeting the catalytic activity of the PIK3C3/VPS34 complex, which shuts down all PIK3C3/VPS34 complexes. We performed in vitro reconstitution of an essential autophagy-promoting PIK3C3/VPS34 complex, Vps34-Beclin1-ATG14L complex, in a microwell plate (96-well format) and successfully monitored the complex formation in many different conditions. This PIK3C3/VPS34 complex protein assay would provide a reliable tool for the screening of autophagy-specific inhibitors.

  19. Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism

    PubMed Central

    Chauhan, Abha; Gu, Feng; Essa, Musthafa M.; Wegiel, Jerzy; Kaur, Kulbir; Brown, William Ted; Chauhan, Ved

    2016-01-01

    Mitochondria play important roles in generation of free radicals, ATP formation, and in apoptosis. We studied the levels of mitochondrial electron transport chain (ETC) complexes, that is, complexes I, II, III, IV, and V, in brain tissue samples from the cerebellum and the frontal, parietal, occipital, and temporal cortices of subjects with autism and age-matched control subjects. The subjects were divided into two groups according to their ages: Group A (children, ages 4–10 years) and Group B (adults, ages 14–39 years). In Group A, we observed significantly lower levels of complexes III and V in the cerebellum (p < 0.05), of complex I in the frontal cortex (p < 0.05), and of complexes II (p < 0.01), III (p<0.01), and V (p < 0.05) in the temporal cortex of children with autism as compared to age-matched control subjects, while none of the five ETC complexes was affected in the parietal and occipital cortices in subjects with autism. In the cerebellum and temporal cortex, no overlap was observed in the levels of these ETC complexes between subjects with autism and control subjects. In the frontal cortex of Group A, a lower level of ETC complexes was observed in a subset of autism cases, that is, 60% (3/5) for complexes I, II, and V, and 40% (2/5) for complexes III and IV. A striking observation was that the levels of ETC complexes were similar in adult subjects with autism and control subjects (Group B). A significant increase in the levels of lipid hydroperoxides, an oxidative stress marker, was also observed in the cerebellum and temporal cortex in the children with autism. These results suggest that the expression of ETC complexes is decreased in the cerebellum and the frontal and temporal regions of the brain in children with autism, which may lead to abnormal energy metabolism and oxidative stress. The deficits observed in the levels of ETC complexes in children with autism may readjust to normal levels by adulthood. PMID:21250997

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Alteration of Skin Wound Healing in Keratinocyte-Specific Mediator Complex Subunit 1 Null Mice

    PubMed Central

    Inui, Shigeki; Reddy, Janardan K.; Itami, Satoshi

    2014-01-01

    MED1 (Mediator complex subunit 1) is a co-activator of various transcription factors that function in multiple transcriptional pathways. We have already established keratinocyte-specific MED1 null mice (Med1epi−/−) that develop epidermal hyperplasia. Herein, to investigate the function(s) of MED1 in skin wound healing, full-thickness skin wounds were generated in Med1epi−/− and age-matched wild-type mice and the healing process was analyzed. Macroscopic wound closure and the re-epithelialization rate were accelerated in 8-week-old Med1epi−/− mice compared with age-matched wild-type mice. Increased lengths of migrating epithelial tongues and numbers of Ki67-positive cells at the wounded epidermis were observed in 8-week-old Med1epi−/− mice, whereas wound contraction and the area of α-SMA-positive myofibroblasts in the granulation tissue were unaffected. Migration was enhanced in Med1epi−/− keratinocytes compared with wild-type keratinocytes in vitro. Immunoblotting revealed that the expression of follistatin was significantly decreased in Med1epi−/− keratinocytes. Moreover, the mitogen-activated protein kinase pathway was enhanced before and after treatment of Med1epi−/− keratinocytes with activin A in vitro. Cell-cycle analysis showed an increased ratio of S phase cells after activin A treatment of Med1epi−/− keratinocytes compared with wild-type keratinocytes. These findings indicate that the activin-follistatin system is involved in this acceleration of skin wound healing in 8-week-old Med1epi−/− mice. On the other hand, skin wound healing in 6-month-old Med1epi−/− mice was significantly delayed with decreased numbers of Ki67-positive cells at the wounded epidermis as well as BrdU-positive label retaining cells in hair follicles compared with age-matched wild-type mice. These results agree with our previous observation that hair follicle bulge stem cells are reduced in older Med1epi−/− mice, indicating a decreased

  5. RADC (Rome Air Development Center) System/Software Requirements Engineering Testbed Research and Development Program

    DTIC Science & Technology

    1988-06-01

    for complex systems and software. Even among software contractors, existing tools and rethods have not been quickly adopted. Air Force users have...great difficulty in recognizing and tracking their mission concerns in requTrements specifications, because they tend to be large, * complex , ard written...provides important capabilities for humans deal ’g with complexity in large system designs. IN S11 -.-. ’," , -,% -, ,,. i ,’jw

  6. 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.

  7. A Staphylococcus aureus Proteome Overview: Shared and Specific Proteins and Protein Complexes from Representative Strains of All Three Clades.

    PubMed

    Liang, Chunguang; Schaack, Dominik; Srivastava, Mugdha; Gupta, Shishir K; Sarukhanyan, Edita; Giese, Anne; Pagels, Martin; Romanov, Natalie; Pané-Farré, Jan; Fuchs, Stephan; Dandekar, Thomas

    2016-02-19

    Staphylococcus aureus is an important model organism and pathogen. This S. aureus proteome overview details shared and specific proteins and selected virulence-relevant protein complexes from representative strains of all three major clades. To determine the strain distribution and major clades we used a refined strain comparison combining ribosomal RNA, MLST markers, and looking at highly-conserved regions shared between strains. This analysis shows three sub-clades (A-C) for S. aureus. As calculations are complex and strain annotation is quite time consuming we compare here key representatives of each clade with each other: model strains COL, USA300, Newman, and HG001 (clade A), model strain N315 and Mu50 (clade B) and ED133 and MRSA252 (clade C). We look at these individual proteomes and compare them to a background of 64 S. aureus strains. There are overall 13,284 S. aureus proteins not part of the core proteome which are involved in different strain-specific or more general complexes requiring detailed annotation and new experimental data to be accurately delineated. By comparison of the eight representative strains, we identify strain-specific proteins (e.g., 18 in COL, 105 in N315 and 44 in Newman) that characterize each strain and analyze pathogenicity islands if they contain such strain-specific proteins. We identify strain-specific protein repertoires involved in virulence, in cell wall metabolism, and phosphorylation. Finally we compare and analyze protein complexes conserved and well-characterized among S. aureus (a total of 103 complexes), as well as predict and analyze several individual protein complexes, including structure modeling in the three clades.

  8. A Staphylococcus aureus Proteome Overview: Shared and Specific Proteins and Protein Complexes from Representative Strains of All Three Clades

    PubMed Central

    Liang, Chunguang; Schaack, Dominik; Srivastava, Mugdha; Gupta, Shishir K.; Sarukhanyan, Edita; Giese, Anne; Pagels, Martin; Romanov, Natalie; Pané-Farré, Jan; Fuchs, Stephan; Dandekar, Thomas

    2016-01-01

    Staphylococcus aureus is an important model organism and pathogen. This S. aureus proteome overview details shared and specific proteins and selected virulence-relevant protein complexes from representative strains of all three major clades. To determine the strain distribution and major clades we used a refined strain comparison combining ribosomal RNA, MLST markers, and looking at highly-conserved regions shared between strains. This analysis shows three sub-clades (A–C) for S. aureus. As calculations are complex and strain annotation is quite time consuming we compare here key representatives of each clade with each other: model strains COL, USA300, Newman, and HG001 (clade A), model strain N315 and Mu50 (clade B) and ED133 and MRSA252 (clade C). We look at these individual proteomes and compare them to a background of 64 S. aureus strains. There are overall 13,284 S. aureus proteins not part of the core proteome which are involved in different strain-specific or more general complexes requiring detailed annotation and new experimental data to be accurately delineated. By comparison of the eight representative strains, we identify strain-specific proteins (e.g., 18 in COL, 105 in N315 and 44 in Newman) that characterize each strain and analyze pathogenicity islands if they contain such strain-specific proteins. We identify strain-specific protein repertoires involved in virulence, in cell wall metabolism, and phosphorylation. Finally we compare and analyze protein complexes conserved and well-characterized among S. aureus (a total of 103 complexes), as well as predict and analyze several individual protein complexes, including structure modeling in the three clades. PMID:28248218

  9. The SWI/SNF chromatin remodeling complex regulates myocardin-induced smooth muscle-specific gene expression

    PubMed Central

    Zhou, Jiliang; Zhang, Min; Fang, Hong; El-Mounayri, Omar; Rodenberg, Jennifer M.; Imbalzano, Anthony N.; Herring, B. Paul

    2009-01-01

    Objective Transcription regulatory complexes comprising myocardin and serum response factor (SRF) are critical for the transcriptional regulation of many smooth muscle-specific genes. However, little is known about the epigenetic mechanisms that regulate the activity of these complexes. In the current study, we investigated the role of SWI/SNF ATP-dependent chromatin remodeling enzymes in regulating the myogenic activity of myocardin. Methods and Results We found that both Brg1 and Brm are required for maintaining expression of several smooth muscle-specific genes in primary cultures of aortic smooth muscle cells. Furthermore, the ability of myocardin to induce expression of smooth muscle-specific genes is abrogated in cells expressing dominant negative Brg1. In SW13 cells, that lack endogenous Brg1 and Brm1, myocardin is unable to induce expression of smooth muscle-specific genes. Whereas, reconstitution of wild type, or bromodomain mutant forms Brg1 or Brm1, into SW13 cells restored their responsiveness to myocardin. SWI/SNF complexes were found to be required for myocardin to increase SRF binding to the promoters of smooth muscle-specific genes. Brg1 and Brm directly bind to the N-terminus of myocardin, in vitro, through their ATPase domains and Brg1 forms a complex with SRF and myocardin in vivo in smooth muscle cells. Conclusion These data demonstrate that the ability of myocardin to induce smooth muscle-specific gene expression is dependent on its interaction with SWI/SNF ATP-dependent chromatin remodeling complexes. PMID:19342595

  10. 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.

  11. Complexity markers in morphosyntactic productions in French-speaking children with specific language impairment (SLI).

    PubMed

    Prigent, Gaïd; Parisse, Christophe; Leclercq, Anne-Lise; Maillart, Christelle

    2015-01-01

    The usage-based theory considers that the morphosyntactic productions of children with SLI are particularly dependent on input frequency. When producing complex syntax, the language of these children is, therefore, predicted to have a lower variability and to contain fewer infrequent morphosyntactic markers than that of younger children matched on morphosyntactic abilities. Using a spontaneous language task, the current study compared the complexity of the morphological and structural productions of 20 children with SLI and 20 language-matched peers (matched on both morphosyntactic comprehension and mean length of utterance). As expected, results showed that although basic structures were produced in the same way in both groups, several complex forms (i.e. tenses such as Imperfect, Future or Conditional and Conjunctions) were less frequent in the productions of children with SLI. Finally, we attempted to highlight complex linguistic forms that could be good clinical markers for these children.

  12. 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.

  13. 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.

  14. 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.

  15. Structure of the NPr:EIN(Ntr) Complex: Mechanism for Specificity in Paralogous Phosphotransferase Systems.

    PubMed

    Strickland, Madeleine; Stanley, Ann Marie; Wang, Guangshun; Botos, Istvan; Schwieters, Charles D; Buchanan, Susan K; Peterkofsky, Alan; Tjandra, Nico

    2016-12-06

    Paralogous enzymes arise from gene duplication events that confer a novel function, although it is unclear how cross-reaction between the original and duplicate protein interaction network is minimized. We investigated HPr:EI(sugar) and NPr:EI(Ntr), the initial complexes of paralogous phosphorylation cascades involved in sugar import and nitrogen regulation in bacteria, respectively. Although the HPr:EI(sugar) interaction has been well characterized, involving multiple complexes and transient interactions, the exact nature of the NPr:EI(Ntr) complex was unknown. We set out to identify the key features of the interaction by performing binding assays and elucidating the structure of NPr in complex with the phosphorylation domain of EI(Ntr) (EIN(Ntr)), using a hybrid approach involving X-ray, homology, and sparse nuclear magnetic resonance. We found that the overall fold and active-site structure of the two complexes are conserved in order to maintain productive phosphorylation, however, the interface surface potential differs between the two complexes, which prevents cross-reaction.

  16. Structure of the NPr:EINNtr Complex: Mechanism for Specificity in Paralogous Phosphotransferase Systems

    SciTech Connect

    Strickland, Madeleine; Stanley, Ann Marie; Wang, Guangshun; Botos, Istvan; Schwieters, Charles D.; Buchanan, Susan K.; Peterkofsky, Alan; Tjandra, Nico

    2016-12-01

    Paralogous enzymes arise from gene duplication events that confer a novel function, although it is unclear how cross-reaction between the original and duplicate protein interaction network is minimized. We investigated HPr:EIsugar and NPr:EINtr, the initial complexes of paralogous phosphorylation cascades involved in sugar import and nitrogen regulation in bacteria, respectively. Although the HPr:EIsugar interaction has been well characterized, involving multiple complexes and transient interactions, the exact nature of the NPr:EINtr complex was unknown. We set out to identify the key features of the interaction by performing binding assays and elucidating the structure of NPr in complex with the phosphorylation domain of EINtr (EINNtr), using a hybrid approach involving X-ray, homology, and sparse nuclear magnetic resonance. We found that the overall fold and active-site structure of the two complexes are conserved in order to maintain productive phosphorylation, however, the interface surface potential differs between the two complexes, which prevents cross-reaction.

  17. Relation of Auditory Attention and Complex Sentence Comprehension in Children with Specific Language Impairment: A Preliminary Study

    ERIC Educational Resources Information Center

    Montgomery, James W.; Evans, Julia L.; Gillam, Ronald B.

    2009-01-01

    We investigated the relation of two dimensions of attentional functioning (sustained auditory attention and resource capacity/allocation) and complex sentence comprehension of children with specific language impairment (SLI) and a group of typically developing (TD) children matched for age. Twenty-six school-age children with SLI and 26 TD peers…

  18. Luminescent oligo(ethylene glycol)-functionalized cyclometalated platinum(II) complexes: cellular characterization and mitochondria-specific localization.

    PubMed

    Guo, Zhengqing; Tong, Wah-Leung; Chan, Michael C W

    2014-02-18

    A readily tunable series of non-planar oligo(ethylene glycol)-substituted phosphorescent Pt(II) complexes has been investigated as live cell imaging agents; suitable structural modifications can give good cellular uptake, traceable mitochondria-specific localization and potent cytotoxic characteristics towards HeLa cells.

  19. Discovery of tMAC: a Drosophila testis-specific meiotic arrest complex paralogous to Myb–Muv B

    PubMed Central

    Beall, Eileen L.; Lewis, Peter W.; Bell, Maren; Rocha, Michael; Jones, D. Leanne; Botchan, Michael R.

    2007-01-01

    The Drosophila Myb–Muv B (MMB)/dREAM complex regulates gene expression and DNA replication site-specifically, but its activities in vivo have not been thoroughly explored. In ovarian amplification-stage follicle cell nuclei, the largest subunit, Mip130, is a negative regulator of replication, whereas another subunit, Myb, is a positive regulator. Here, we identified a mutation in mip40 and generated a mutation in mip120, two additional MMB subunits. Both mutants were viable, but mip120 mutants had many complex phenotypes including shortened longevity and severe eye defects. mip40 mutant females had severely reduced fertility, whereas mip120 mutant females were sterile, substantiating ovarian regulatory role(s) for MMB. Myb accumulation and binding to polytene chromosomes was dependent on the core factors of the MMB complex. In contrast to the documented mip130 mutant phenotypes, both mip40 and mip120 mutant males were sterile. We purified Mip40-containing complexes from testis nuclear extracts and identified tMAC, a new testis-specific meiotic arrest complex that contained Mip40, Caf1/p55, the Mip130 family member, Always early (Aly), and a Mip120 family member, Tombola (Tomb). Together, these data demonstrate that MMB serves diverse roles in different developmental pathways, and members of MMB can be found in alternative, noninteracting complexes in different cell types. PMID:17403774

  20. Complex Osteotomies of Tibial Plateau Malunions Using Computer-Assisted Planning and Patient-Specific Surgical Guides.

    PubMed

    Fürnstahl, Philipp; Vlachopoulos, Lazaros; Schweizer, Andreas; Fucentese, Sandro F; Koch, Peter P

    2015-08-01

    The accurate reduction of tibial plateau malunions can be challenging without guidance. In this work, we report on a novel technique that combines 3-dimensional computer-assisted planning with patient-specific surgical guides for improving reliability and accuracy of complex intraarticular corrective osteotomies. Preoperative planning based on 3-dimensional bone models was performed to simulate fragment mobilization and reduction in 3 cases. Surgical implementation of the preoperative plan using patient-specific cutting and reduction guides was evaluated; benefits and limitations of the approach were identified and discussed. The preliminary results are encouraging and show that complex, intraarticular corrective osteotomies can be accurately performed with this technique. For selective patients with complex malunions around the tibia plateau, this method might be an attractive option, with the potential to facilitate achieving the most accurate correction possible.