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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

    ... COMMISSION Software Requirement Specifications for Digital Computer Software and Complex Electronics Used in... Digital Computer Software and Complex Electronics used in Safety Systems of Nuclear Power Plants.'' The DG... Requirement Specifications for Digital Computer Software and Complex Electronics used in Safety Systems...

  2. Master Software Requirements Specification

    NASA Technical Reports Server (NTRS)

    Hu, Chaumin

    2003-01-01

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

  3. 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.

  4. SSL: A software specification language

    NASA Technical Reports Server (NTRS)

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

    1976-01-01

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

  5. Reflight certification software design specifications

    NASA Technical Reports Server (NTRS)

    1984-01-01

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

  6. Does software design complexity affect maintenance effort?

    NASA Technical Reports Server (NTRS)

    Epping, Andreas; Lott, Christopher M.

    1994-01-01

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

  7. Software Complexity Threatens Performance Portability

    SciTech Connect

    Gamblin, T.

    2015-09-11

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

  8. Software Performs Complex Design Analysis

    NASA Technical Reports Server (NTRS)

    2008-01-01

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

  9. Software requirements: Guidance and control software development specification

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

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

  10. Bias and design in software specifications

    NASA Technical Reports Server (NTRS)

    Straub, Pablo A.; Zelkowitz, Marvin V.

    1990-01-01

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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Software errors and complexity: An empirical investigation

    NASA Technical Reports Server (NTRS)

    Basili, Victor R.; Perricone, Berry T.

    1983-01-01

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

  17. Methodology of decreasing software complexity using ontology

    NASA Astrophysics Data System (ADS)

    DÄ browska-Kubik, Katarzyna

    2015-09-01

    In this paper a model of web application`s source code, based on the OSD ontology (Ontology for Software Development), is proposed. This model is applied to implementation and maintenance phase of software development process through the DevOntoCreator tool [5]. The aim of this solution is decreasing software complexity of that source code, using many different maintenance techniques, like creation of documentation, elimination dead code, cloned code or bugs, which were known before [1][2]. Due to this approach saving on software maintenance costs of web applications will be possible.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Khoros software specification format and interoperability

    NASA Technical Reports Server (NTRS)

    Rots, A. H.

    1992-01-01

    Khoros defines formats for User Interface Specification (UIS) and Program Specification (PS) files. From such files, its code generator, Ghostwriter, creates source files and documentation. The great advantage of the system is that the code fragments that make up part of the PS file are purely generic. All Khoros-related code is created by the code generator; this includes all user interface code. As a matter of fact, both specification files are very generic in nature. Thus, one could imagine using it as the basis for other software systems. A case is made that writing a code generator that would create IRAF-compatible code from the Khoros UIS and PS files is fairly trivial. Another aspect of the Khoros system conventions concerns the way execution commands are generated by the user interface and the actual syntax of those commands. The protocols are such that interoperability at the level of executable modules is readily possible.

  8. Light duty utility arm software requirements specification

    SciTech Connect

    Kiebel, G.R.

    1995-12-18

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

  9. 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.

  10. 78 FR 47015 - Software Requirement Specifications for Digital Computer Software Used in Safety Systems of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-02

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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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…

  19. 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…

  20. Structural visualization of complex software systems

    SciTech Connect

    Vemuri, V.; Smart, J.C. |

    1991-08-01

    The design outline of an automatic, computer-based Abstract Visualization Utility (A-Vu) is presented. Although A-Vu is a general purpose tool, emphasis here is on its ability to visualize structural aspects of software design. Starting from a system definition, an Ada program library, or a directed graph definition, A-Vu proceeds to develop a variety of ``nice`` linear graphs, revealing different visual representations of the design. Formally, given a linear graph G=(V,E), A-Vu searches for a configuration C such that a suitably defined ``energy`` function J(C) is minimized. The definition of the energy function includes software engineering considerations such as layering, modularity as well as aesthetic considerations like visual appeal, cognitive correctness, and so on. Simulated annealing techniques are applied to linear graph representations of software structures to obtain the ``minimum energy`` configurations.

  1. Structural visualization of complex software systems

    SciTech Connect

    Vemuri, V.; Smart, J.C. . Dept. of Applied Science Lawrence Livermore National Lab., CA )

    1991-08-01

    The design outline of an automatic, computer-based Abstract Visualization Utility (A-Vu) is presented. Although A-Vu is a general purpose tool, emphasis here is on its ability to visualize structural aspects of software design. Starting from a system definition, an Ada program library, or a directed graph definition, A-Vu proceeds to develop a variety of nice'' linear graphs, revealing different visual representations of the design. Formally, given a linear graph G=(V,E), A-Vu searches for a configuration C such that a suitably defined energy'' function J(C) is minimized. The definition of the energy function includes software engineering considerations such as layering, modularity as well as aesthetic considerations like visual appeal, cognitive correctness, and so on. Simulated annealing techniques are applied to linear graph representations of software structures to obtain the minimum energy'' configurations.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

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

    NASA Astrophysics Data System (ADS)

    Wilson, A.; Lindholm, D. M.

    2011-12-01

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

  11. 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.

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

    ERIC Educational Resources Information Center

    Radulescu, Iulian Ionut

    2006-01-01

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

  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. 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.

  16. Managing Scientific Software Complexity with Bocca and CCA

    DOE PAGESBeta

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

    2008-01-01

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

  17. 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.

  18. SWEPP assay system version 2.0 software requirements specification

    SciTech Connect

    Matthews, S.D.; East, L.V.; Marwil, E.S.; Ferguson, J.J.

    1996-06-01

    The INEL Stored Waste Examination Pilot Plant (SWEPP) operations staff use nondestructive analysis methods to characterize the radiological contents of contact-handled radioactive waste containers. Containers of waste from Rocky Flats Environmental Technology Site and other DOE sites are currently stored at SWEPP. Before these containers can be shipped to WIPP, SWEPP must verify compliance with storage, shipping, and disposal requirements. One part of the SWEPP program measures neutron emissions from the containers and estimates the mass of Pu and other transuranic isotopes present. The code NEUT2 was originally used to perform data acquisition and reduction; the SWEPP Assay System (SAS) code replaced NEUT2 in early 1994. This document specifies the requirements for the SAS software as installed at INEL and was written to comply with RWMC (INEL Radioactive Waste Management Complex) quality requirements.

  19. 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.

  20. 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

  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. 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.

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

    PubMed

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

    2016-08-15

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

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

    PubMed

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

    2016-08-15

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

  5. 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.

  6. 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…

  7. 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…

  8. 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.

  9. 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.

  10. 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).

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

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

    ERIC Educational Resources Information Center

    Lounesto, Pertti; And Others

    1990-01-01

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

  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. 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.

  3. 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.

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

    NASA Astrophysics Data System (ADS)

    Ford, Teresa O.

    1994-03-01

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

  5. 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.'

  6. 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.

  7. 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

  8. Rubella-specific immune complexes after congenital infection and vaccination.

    PubMed

    Coyle, P K; Wolinsky, J S; Buimovici-Klein, E; Moucha, R; Cooper, L Z

    1982-05-01

    Circulating immune complexes which contained rubella-specific immunoglobulins were detected in 21 out of 63 subjects with congenital rubella and in 39 out of 65 subjects vaccinated with attenuated rubella virus, but in none of 43 subjects susceptible to rubella or 87 subjects with remote naturally acquired immunity to rubella. The presence or level of circulating immune complexes and the presence of rubella-specific complexes did not correlate with conventional serum rubella hemagglutination inhibition antibody titers. In the group with congenital infection, the presence of specific complexes many years after birth was associated with late-emerging clinical problems involving several organ systems. In vaccinates, the presence of specific complexes was associated with a higher incidence of side reactions. Two-thirds of the vaccinates and all of those revaccinated showed specific immune complexes as late as 8 months after immunization.

  9. Rubella-specific immune complexes after congenital infection and vaccination.

    PubMed Central

    Coyle, P K; Wolinsky, J S; Buimovici-Klein, E; Moucha, R; Cooper, L Z

    1982-01-01

    Circulating immune complexes which contained rubella-specific immunoglobulins were detected in 21 out of 63 subjects with congenital rubella and in 39 out of 65 subjects vaccinated with attenuated rubella virus, but in none of 43 subjects susceptible to rubella or 87 subjects with remote naturally acquired immunity to rubella. The presence or level of circulating immune complexes and the presence of rubella-specific complexes did not correlate with conventional serum rubella hemagglutination inhibition antibody titers. In the group with congenital infection, the presence of specific complexes many years after birth was associated with late-emerging clinical problems involving several organ systems. In vaccinates, the presence of specific complexes was associated with a higher incidence of side reactions. Two-thirds of the vaccinates and all of those revaccinated showed specific immune complexes as late as 8 months after immunization. PMID:7085069

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Specificity of software cooperating with an optoelectronic sensor in the pulse oximeter system

    NASA Astrophysics Data System (ADS)

    Cysewska-Sobusiak, Anna; Wiczynski, Grzegorz; Jedwabny, Tomasz

    1995-06-01

    Specificity of a software package composed of two parts which control an optoelectronic sensor of the computer-aided system made to realize the noninvasive measurements of the arterial blood oxygen saturation as well as some parameters of the peripheral pulse waveform, has been described. Principles of the transmission variant of the one and only noninvasive measurement method, so-called pulse oximetry, has been utilized. The software co-ordinates the suitable cooperation of an IBM PC compatible microcomputer with the sensor and one specialized card. This novel card is a key part of the whole measuring system which some application fields are extended in comparison to pulse oximeters commonly attainable. The user-friendly MS Windows graphical environment which creates the system to be multitask and non-preemptive, has been used to design the specific part of the programming presented here. With this environment, sophisticated tasks of the software package can be performed without excessive complication.

  17. 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.

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

    SciTech Connect

    Graf, F.A. Jr.

    1994-06-03

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

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

    NASA Astrophysics Data System (ADS)

    Roiser, S.

    2011-12-01

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

  20. Software requirements specification for the GIS-T/ISTEA pooled fund study phase C linear referencing engine

    SciTech Connect

    Amai, W.; Espinoza, J. Jr.; Fletcher, D.R.

    1997-06-01

    This Software Requirements Specification (SRS) describes the features to be provided by the software for the GIS-T/ISTEA Pooled Fund Study Phase C Linear Referencing Engine project. This document conforms to the recommendations of IEEE Standard 830-1984, IEEE Guide to Software Requirements Specification (Institute of Electrical and Electronics Engineers, Inc., 1984). The software specified in this SRS is a proof-of-concept implementation of the Linear Referencing Engine as described in the GIS-T/ISTEA pooled Fund Study Phase B Summary, specifically Sheet 13 of the Phase B object model. The software allows an operator to convert between two linear referencing methods and a datum network.

  1. 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.

  2. 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.

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

    PubMed

    Messer-Misak, Karin; Egger, Rudolf

    2016-01-01

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

  4. 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.

  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. 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.

  7. 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.

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

    NASA Astrophysics Data System (ADS)

    Miksa, Krzysztof; Sabina, Pawel; Kasztelnik, Marek

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  12. 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.

  13. 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.

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

    SciTech Connect

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

    2011-04-15

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

  15. 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.

  16. 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.

  17. 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.

  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. 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.

  20. A flexible object-oriented software framework for developing complex multimedia simulations.

    SciTech Connect

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

    2002-05-03

    Decision makers involved in brownfields redevelopment and long-term stewardship must consider environmental conditions, future-use potential, site ownership, area infrastructure, funding resources, cost recovery, regulations, risk and liability management, community relations, and expected return on investment in a comprehensive and integrated fashion to achieve desired results. Successful brownfields redevelopment requires the ability to assess the impacts of redevelopment options on multiple interrelated aspects of the ecosystem, both natural and societal. Computer-based tools, such as simulation models, databases, and geographical information systems (GISs) can be used to address brownfields planning and project execution. The transparent integration of these tools into a comprehensive and dynamic decision support system would greatly enhance the brownfields assessment process. Such a system needs to be able to adapt to shifting and expanding analytical requirements and contexts. The Dynamic Information Architecture System (DIAS) is a flexible, extensible, object-oriented framework for developing and maintaining complex multidisciplinary simulations of a wide variety of application domains. The modeling domain of a specific DIAS-based simulation is determined by (1) software objects that represent the real-world entities that comprise the problem space (atmosphere, watershed, human), and (2) simulation models and other data processing applications that express the dynamic behaviors of the domain entities. Models and applications used to express dynamic behaviors can be either internal or external to DIAS, including existing legacy models written in various languages (FORTRAN, C, etc.). The flexible design framework of DIAS makes the objects adjustable to the context of the problem without a great deal of recoding. The DIAS Spatial Data Set facility allows parameters to vary spatially depending on the simulation context according to any of a number of 1-D, 2-D

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-04-01

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

  3. 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.

  4. Termination of aquired and natural immunological tolerance with specific complexes

    PubMed Central

    1975-01-01

    It was possible to terminate the induced unresponsive state to bovine serum albumin (BSA) and the natural unresponsive state to autologous thyroglobulin in rabbits (RTg) by immunization with complexes composed of heterologous cross-reacting antibody and the tolerated antigens. The unresponsive state was terminated in rabbits made unresponsive by neonatal injections of BSA and then 3 mo later injected with complexes composed of BSA and guinea pig antihuman serum albumin. This termination was manifested by the presence of anti-BSA plaque-forming cells. Similarly, the natural unresponsive state was terminated in adult rabbits injected with complexes between RTg and guinea pig antibovine thyroglobulin (BTg) in that thyroid lesions and circulating anti-RTg were produced. The results can be best explained by the presence of unresponsive T cells and competent B cells, where the guinea pig gamma globulin (antibody) activates T cells specific for the guinea pig gamma globulin portion of the complexes and thus permits stimulation of B cells competent to the exposed determinants of the tolerated (BSA or RTg) portion of the complexes. The detailed mechanism for the activation of B cells in tolerant animals is discussed. PMID:1095680

  5. 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

  6. 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.

  7. High-Level software requirements specification for the TWRS controlled baseline database system

    SciTech Connect

    Spencer, S.G.

    1998-09-23

    This Software Requirements Specification (SRS) is an as-built document that presents the Tank Waste Remediation System (TWRS) Controlled Baseline Database (TCBD) in its current state. It was originally known as the Performance Measurement Control System (PMCS). Conversion to the new system name has not occurred within the current production system. Therefore, for simplicity, all references to TCBD are equivalent to PMCS references. This SRS will reference the PMCS designator from this point forward to capture the as-built SRS. This SRS is written at a high-level and is intended to provide the design basis for the PMCS. The PMCS was first released as the electronic data repository for cost, schedule, and technical administrative baseline information for the TAAS Program. During its initial development, the PMCS was accepted by the customer, TARS Business Management, with no formal documentation to capture the initial requirements.

  8. 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

  9. 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.

  10. 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…

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 75 FR 16817 - Meeting for Software Developers on the Technical Specifications for Common Formats for Patient...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-02

    ... Safety Rule), published in the Federal Register on November 21, 2008: 73 FR 70731- 70814. As authorized... 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...

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

    PubMed Central

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

    2015-01-01

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

  18. A Recombinant Antibody with the Antigen-Specific, Major Histocompatibility Complex-Restricted Specificity of T Cells

    NASA Astrophysics Data System (ADS)

    Andersen, Peter S.; Stryhn, Anette; Hansen, Bjarke E.; Fugger, Lars; Engberg, Jan; Buus, Soren

    1996-03-01

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

  19. [Design of software and hardware complex of automated systems for the management of the State Sanitary and Epidemiological Surveillance].

    PubMed

    Mel'nichenko, P I; Muzychenko, F V; Malinovskiĭ, A A; Leont'ev, L Iu; Ustiukhin, N V

    2005-05-01

    A new information system (IS) - the software and hardware complex for controlling the state sanitary-and-epidemiological inspection (SSEI) was created. The system represents the aggregate of automated working places of RF MD chief state sanitary physician arid specialists from the department of state sanitary-and-epidemiological inspection of the Main Military Medical Headquarters. They interact through communications with working places of specialists from SSEI Main Center, chief state sanitary physicians from the Armed Forces, military districts (fleets) and RFAF CSSEI. The special software provides automation of the following technological processes: operative sanitary-and epidemiological and epidemiological monitoring; the epidemiological analysis of infectious diseases; the evaluation of quality and efficiency of sanitary-and epidemiological work. At present the complex works in the regime of experimental exploitation when the adjustment of communications and special software is performed.

  20. 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.

  1. The practical approach to the reliability analysis of the software architecture of a complex company control system

    NASA Astrophysics Data System (ADS)

    Kovalev, I. V.; Zelenkov, P. V.; Ognerubov, S.

    2015-10-01

    The practical aspects of the implementation of reliability analysis of the architecture of a complex control system of a company are considered in this article. The comparative analysis for two variants of software architecture using different factors is presented, the relations between the reliability characteristics and the amount of system architecture components and their connections with each other are defined.

  2. 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.

  3. 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 ).

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

    PubMed

    Oberortner, Ernst; Densmore, Douglas

    2015-06-19

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

  5. 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.

  6. 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.

  7. Scheduling Software

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Advanced Scheduling Environment is a software product designed and marketed by AVYX, Inc. to provide scheduling solutions for complex manufacturing environments. It can be adapted to specific scheduling and manufacturing processes and has led to substantial cost savings. The system was originally developed for NASA use in scheduling Space Shuttle flights and satellite activities. AVYX, Inc. is an offshoot of a company formed to provide computer-related services to NASA. TREES-plus, the company's initial product became the programming language for the advanced scheduling environment system.

  8. 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.

  9. 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.

  10. 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

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

    PubMed

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

    2016-01-01

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

  12. 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.

  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. 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.

  18. Software requirements specification for the program analysis and control system risk management module

    SciTech Connect

    SCHAEFER, J.C.

    1999-06-02

    TWR Program Analysis and Control System Risk Module is used to facilitate specific data processes surrounding the Risk Management program of the Tank Waste Retrieval environment. This document contains the Risk Management system requirements of the database system.

  19. 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.

  20. 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…

  1. 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

  2. Differential assembly of GPCR signaling complexes determines signaling specificity.

    PubMed

    Maurice, Pascal; Benleulmi-Chaachoua, Abla; Jockers, Ralf

    2012-01-01

    Recent proteomic and biochemical evidence indicates that cellular -signaling is organized in protein modules. G protein-coupled receptors (GPCRs) are privileged entry points for extracellular signals that are transmitted through the plasma membrane into the cell. The adequate cellular response and signaling specificity is regulated by GPCR-associated protein modules. The composition of these modules is dynamic and might depend on receptor stimulation, the proteome of a given cellular context, the subcellular localization of receptor-associated modules, the formation of GPCR oligomers and the variation of expression levels of components of these modules under physiological, for example circadian rhythm, or pathological conditions. The current article will highlight the importance of GPCR-associated protein modules as a biochemical basis for signaling specificity.

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

    PubMed Central

    Krishnaraj, Arun; Alkasab, Tarik K

    2014-01-01

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

  4. 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.

  5. 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

  6. JETSPIN: A specific-purpose open-source software for simulations of nanofiber electrospinning

    NASA Astrophysics Data System (ADS)

    Lauricella, Marco; Pontrelli, Giuseppe; Coluzza, Ivan; Pisignano, Dario; Succi, Sauro

    2015-12-01

    We present the open-source computer program JETSPIN, specifically designed to simulate the electrospinning process of nanofibers. Its capabilities are shown with proper reference to the underlying model, as well as a description of the relevant input variables and associated test-case simulations. The various interactions included in the electrospinning model implemented in JETSPIN are discussed in detail. The code is designed to exploit different computational architectures, from single to parallel processor workstations. This paper provides an overview of JETSPIN, focusing primarily on its structure, parallel implementations, functionality, performance, and availability.

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  8. 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…

  9. 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.

  10. 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).

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

    SciTech Connect

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

    2011-03-17

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

  12. 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.

  13. Exploring the potential relevance of human-specific genes to complex disease

    PubMed Central

    2011-01-01

    Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org) revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease. PMID:21296743

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

    PubMed

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

    2015-05-01

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

  15. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  17. 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.

  18. 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.

  19. Modeling software systems by domains

    NASA Technical Reports Server (NTRS)

    Dippolito, Richard; Lee, Kenneth

    1992-01-01

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

  20. 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.

  1. 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.

  2. Complex Syntax Acquisition: A Longitudinal Case Study of a Child with Specific Language Impairment

    ERIC Educational Resources Information Center

    Schuele, Melanie C.; Dykes, Julianna C.

    2005-01-01

    Although there is extensive documentation of the morphological limitations of children with specific language impairment (SLI), few studies have reported on complex syntax acquisition in children with SLI. This case study examined the development of complex syntax in a child with SLI between 3 and 7 years. Twelve conversational samples were…

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Specificity is complex and time consuming: mutual exclusivity in tyrosine kinase-mediated signaling.

    PubMed

    O'Rourke, Lisa; Ladbury, John E

    2003-06-01

    Most fundamental cellular processes are transduced through tyrosine kinase (TK)-mediated pathways. For transduction without corruption, the protein-protein interactions involved have to be mutually exclusive. Many of these proteins bind via homologous domains whose binding characteristics suggest that their innate specificity is not sufficiently high to account for the integrity of signal transduction. Stimulation of TK-mediated signals is often accompanied by recruitment of a precise, multimolecular protein complex that is itself capable of imposing specificity. Furthermore, this complex provides protection against phosphatase activity, controlling the longevity of the active signaling complex, and thus influencing outcomes in subsequent downstream events.

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

    PubMed

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

    2015-11-01

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

  9. Activity of site-specific endonucleases on complexes of plasmid DNA with multiwalled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Egorova, V. P.; Krylova, H. V.; Lipnevich, I. V.; Veligura, A. A.; Shulitsky, B. G.; Asayonok, A. A.; Vaskovtsev, E. V.

    2016-08-01

    We have synthesized and investigated structural and functional properties of plasmid DNA complexes with multi-walled carbon nanotubes (MWCNTs) for detection of changes in structural state of the plasmid DNA at its recognition by site-specific endonuclease. It has been also established that the site-specific endonuclease is functionally active on the surface of MWCNTs.

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

    NASA Technical Reports Server (NTRS)

    Berg, Melanie D.; Label, Kenneth 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.

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

    NASA Technical Reports Server (NTRS)

    Berg, Melanie D.; Label, Kenneth

    2016-01-01

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

  12. A Reduced-Complexity Fast Algorithm for Software Implementation of the IFFT/FFT in DMT Systems

    NASA Astrophysics Data System (ADS)

    Chan, Tsun-Shan; Kuo, Jen-Chih; Wu, An-Yeu (Andy)

    2002-12-01

    The discrete multitone (DMT) modulation/demodulation scheme is the standard transmission technique in the application of asymmetric digital subscriber lines (ADSL) and very-high-speed digital subscriber lines (VDSL). Although the DMT can achieve higher data rate compared with other modulation/demodulation schemes, its computational complexity is too high for cost-efficient implementations. For example, it requires 512-point IFFT/FFT as the modulation/demodulation kernel in the ADSL systems and even higher in the VDSL systems. The large block size results in heavy computational load in running programmable digital signal processors (DSPs). In this paper, we derive computationally efficient fast algorithm for the IFFT/FFT. The proposed algorithm can avoid complex-domain operations that are inevitable in conventional IFFT/FFT computation. The resulting software function requires less computational complexity. We show that it acquires only 17% number of multiplications to compute the IFFT and FFT compared with the Cooly-Tukey algorithm. Hence, the proposed fast algorithm is very suitable for firmware development in reducing the MIPS count in programmable DSPs.

  13. 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.

  14. 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.

  15. 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.

  16. Specific antibody against the Aujeszky's disease virus in the complex cumulus oophorus-oocyte of sows.

    PubMed

    Jerábek, J; Horký, D; Trávník, P; Rodák, L

    1989-01-01

    Oocytes collected from sows vaccinated and revaccinated with an inactivated vaccine against Aujeszky's disease (AD) were examined for the presence of specific antibodies of the IgG class against AD virus in the complex cumulus oophorus-oocyte by means of immunocytochemical methods. No specific antibody of the IgG class was detected in the cumulus-oocyte complexes collected from sows before vaccination. On the other hand, the specific IgG antibody was found in all immunocytochemically examined complexes cumulus-oocyte collected from revaccinated sows. The specific antibody of the IgG class against AD virus and the porcine IgG were immunocytochemically visualized under both light and electron microscopes as a fine granular product disseminated in oocytes and follicular cells.

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

    PubMed

    Zhang, Wen-Wei; Matlashewski, Greg

    2015-01-01

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

  18. Highly specific transgene expression mediated by a complex adenovirus vector incorporating a prostate-specific amplification feedback loop

    PubMed Central

    Woraratanadharm, Jan; Rubinchik, Semyon; Yu, Hong; Fan, Fan; Morrow, Scotty M.; Dong., John Y.

    2007-01-01

    Summary Development of novel therapeutic agents is needed to address the problems of locally recurrent, metastatic, and advanced hormone-refractory prostate cancer. We have constructed a novel complex adenovirus (Ad) vector regulation system that incorporates both the prostate-specific ARR2PB promoter and a positive feedback loop using the TRE promoter to enhance gene expression. This regulation strategy involves the incorporation of the TRE upstream of the prostate-specific ARR2PB promoter to enhance its activity with Tet-regulation. The expressions of both GFP and tTA were placed under the control of these TRE-ARR2PB promoters, so that in the cells of prostate origin, a positive feedback loop would be generated. This design greatly enhanced GFP reporter expression in prostate cancer cells, while retaining tight control of expression in non-prostate cancer cells, even at MOI as high as 1000. This novel positive feedback loop with prostate specificity (PFLPS) regulation system we have developed may have broad applications for expressing not only high levels of toxic proteins in cancer cells but alternatively could be manipulated to regulate essential genes in a highly efficient conditionally replicative adenovirus (CRAd) vector specifically directed to prostate cancer cells. The PFLPS regulation system, therefore, serves as a promising new approach in the development of both a specific and effective vector for cancer gene therapy. PMID:15229631

  19. 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.

  20. Sequence-specific targeting of MSL complex regulates transcription of the roX RNA genes

    PubMed Central

    Bai, Xiaoying; Alekseyenko, Artyom A; Kuroda, Mitzi I

    2004-01-01

    In Drosophila, dosage compensation is controlled by the male-specific lethal (MSL) complex consisting of at least five proteins and two noncoding RNAs, roX1 and roX2. The roX RNAs function in targeting MSL complex to the X chromosome, and roX transgenes can nucleate spreading of the MSL complex into flanking chromatin when inserted on an autosome. An MSL-binding site (DHS, DNaseI hypersensitive site) has been identified in each roX gene. Here, we investigate the functions of the DHS using transgenic deletion analyses and reporter assays. We find that MSL interaction with the DHS counteracts constitutive repression at roX1, resulting in male-specific expression of roX1 RNA. Surprisingly, the DHS is not required for initiation of cis spreading of MSL complex, instead local transcription of roX RNAs correlates with extensive spreading. PMID:15229655

  1. Complex Oncogenic Translocations with Gene Amplification are Initiated by Specific DNA Breaks in Lymphocytes

    PubMed Central

    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.

    2009-01-01

    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. While 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 demonstrate 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 Eμ 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. PMID:19435904

  2. 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.

  3. Grammaticality and complexity of sentences in monolingual Spanish-speaking children with specific language impairment.

    PubMed

    Coloma, Carmen Julia; Araya, Claudia; Quezada, Camilo; Pavez, Maria Mercedes; Maggiolo, Mariangela

    2016-01-01

    This study examined grammaticality and complexity of sentences in monolingual Spanish-speaking children with specific language impairment (SLI). A group of SLI children (n = 13), mean age 6, was compared to a control group (CCG) matched by age (n = 11), and a younger control group (LCG) with similar linguistic development (n = 13). Grammaticality and complexity of sentences were analysed including identification and counting of: a) simple and complex sentences, b) grammatical and ungrammatical sentences, and c) types of grammatical errors. SLI children were found to be more ungrammatical than CCG in both simple and complex sentences. Considering the number of errors in all sentences produced, SLI children commit more errors than both control groups. Complexity of sentences did not show statistical differences among groups. Future research should explore in further detail the types of errors made by monolingual Spanish-speaking SLI children. PMID:27128985

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

    PubMed Central

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

    1995-01-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  6. Joint analysis of band-specific functional connectivity and signal complexity in autism.

    PubMed

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

    2015-02-01

    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.

  7. 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

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

    ERIC Educational Resources Information Center

    Pizzioli, Fabrizio; Schelstraete, Marie-Anne

    2011-01-01

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

  9. 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.

  10. 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

  11. 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.

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

    PubMed

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

    2016-01-01

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

  13. Specificity of the Anaphase Promoting Complex: a single-molecule study

    PubMed Central

    Lu, Ying; Wang, Weiping; Kirschner, Marc W.

    2015-01-01

    Summary Biological processes require specific enzymatic reactions, paradoxically involving short recognition sequences. As an example, cell-cycle timing depends on a sequence of ubiquitylation events mediated by the Anaphase Promoting Complex (APC) based on short redundant motifs. To understand the origin of specificity we designed single-molecule fluorescence assays that capture transient ubiquitylation reactions. We find that the APC-mediated ubiquitylation involves a highly-processive initial reaction on the substrate, followed by multiple encounters and reactions at a slower rate. The initial ubiquitylation greatly enhances substrate’s binding affinity in subsequent reactions, by both increasing the on-rate and decreasing the off-rate. We postulate that these cycles of positive feedback enable high specificity for substrates with short recognition motifs in a complex cellular environment. PMID:25859049

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Choi, Sungmoon; Yu, Junhua

    2016-08-26

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

  16. 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.

  17. Complexity metric as a complement to measurement based IMRT/VMAT patient-specific QA

    NASA Astrophysics Data System (ADS)

    Götstedt, J.; Karlsson Hauer, A.; Bäck, A.

    2015-01-01

    IMRT/VMAT treatment plans contain treatment fields with MLC openings of various size and shape. Clinical dose calculation algorithms show limitations in calculating the correct dose in small and irregular parts of a MLC opening which leads to differences between the planned and delivered dose distributions. The patient-specific IMRT QA is often designed to compare planned and measured dose distributions and is therefore heavily dependent on the measurement equipment and the evaluation method. The purpose of this study is to develop a complexity metric based on shape and size of MLC openings that correlates to the dose differences between planned and delivered 3D dose distributions. Different MLC openings are measured and evaluated and used to determine a penalty function to steer the complexity metric and make the complexity scores correlate to dose difference pass rates. Results of this initial study show that a correlation was found between complexity scores and dose difference pass rates for static fields with varied complexity. Preliminary results also show that the complexity metric can distinguish clinical IMRT fields with higher complexity.

  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. Specific interactions in the inclusion complexes of pyronines Y and B with beta-cyclodextrin.

    PubMed

    Reija, Belén; Al-Soufi, Wajih; Novo, Mercedes; Vazquez Tato, José

    2005-02-01

    The aim of this work is to analyze the role of specific interactions in host-guest association processes. The formation of inclusion complexes between pyronines Y and B and beta-cyclodextrin and the nature of the interactions involved have been studied using absorption, steady-state fluorescence, and time-resolved fluorescence spectroscopies. The two pyronines form 1:1 complexes with beta-cyclodextrin, with the association equilibrium constant being much higher in the case of pyronine B. Complexation causes a slight red shift of the emission spectra of the pyronines but decreases significantly their fluorescence quantum yields and lifetimes. To explain this atypical behavior, the photophysical properties of the pyronines in different solvents were determined and compared with those of the complexes. The similarities observed between the pyronines in dioxane and in the interior of the cyclodextrin cavity suggest that there are important specific interactions of the pyronines with the electron-rich oxygens present in these media. A possible explanation for the increase in the nonradiative rate constants in these media involves the existence of a charge-transfer excited state with the location of the positive charge at the xanthene moiety, which would be stabilized by the mentioned interactions. The observed differences between pyronine Y and B can be understood on the basis of these specific interactions.

  20. 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.

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

    PubMed

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

    2015-02-25

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

  2. 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.

  3. Dissecting signaling through activation of specific Src-effector complexes in vivo

    PubMed Central

    Karginov, A.V.; Tsygankov, D.; Berginski, M.; Chu, P.-H.; Trudeau, E.D.; Yi, J.J.; Gomez, S.; Elston, T.C.; Hahn, K.M.

    2014-01-01

    We describe an approach to selectively activate a kinase in a specific protein complex or at a specific subcellular location within living cells, and within minutes. This reveals the effects of specific kinase pathways without time for genetic compensation. The new technique, dubbed RapRTAP (rapamycin regulated targeted activation of pathways) was used to dissect the role of Src kinase interactions with FAK and p130Cas in cell motility and morphodynamics. The overall effects of Src activation on cell morphology and adhesion dynamics were first quantified, without restricting effector access. Subsets of Src induced behaviors were then attributed to specific interactions between Src and the two downstream proteins. Activation of Src in the cytoplasm versus at the cell membrane also produced distinct phenotypes. The conserved nature of the kinase site modified for RapRTAP indicates that the technique can be applied to many kinases. PMID:24609359

  4. SREM (Software Requirements Engineering Methodology) evaluation. Volume 2. Specifications and technical data. Final technical report 1 October 1980-15 November 1983

    SciTech Connect

    Stone, A.; Hartschuh, D.; Castor, B.

    1984-02-01

    In the fall of 1980, the Rome Air Development Center contracted Martin Marietta Denver Aerospace to perform a comprehensive evaluation of the Software Requirements Engineering Methodology (SREM). The objectives of the evaluation were to assess the capabilities of SERM for specifying the software requirements of large, embedded computer systems and to recommend improvements which would enhance its effectiveness. Specific evaluation criteria were developed to judge the effectiveness of the methodology, support tools and user training. The approach included attending a SERM training course and using SERM to specify the software requirements for two Air Force systems. In general, it was found that the SERM was an effective vehicle for specifying and analyzing the software requirements of large embedded computer systems, especially descriptions of real work objects, data requirements and message processing. However, deficiencies were noted in the specification language, particularly in describing parallel and distributed processing requirements, in the friendliness of the user interfaces to the analysis (consistency/completeness) and simulation tools, in the performance of these tools and in the effectiveness of the training. Appropriate improvements to all of the functional deficiencies are recommended.

  5. Significance of Lipid-Derived Reactive Aldehyde-Specific Immune Complexes in Systemic Lupus Erythematosus

    PubMed Central

    Wang, Gangduo; Pierangeli, Silvia S.; Willis, Rohan; Gonzalez, Emilio B.; Petri, Michelle; Khan, M. Firoze

    2016-01-01

    Even though systemic lupus erythematosus (SLE) is associated with high morbidity and mortality rates among young and middle-aged women, the molecular mechanisms of disease pathogenesis are not fully understood. Previous studies from our laboratory suggested an association between oxidative stress and SLE disease activity (SLEDAI). To further assess the role of reactive oxygen species (ROS) in SLE, we examined the contribution of lipid-derived reactive aldehydes (LDRAs)-specific immune complexes in SLE. Sera from 60 SLE patients with varying SLEDAI and 32 age- and gender- matched healthy controls were analyzed for oxidative stress and related markers. Patients were divided into two groups based on their SLEDAI scores (<6 and ≥ 6). Both SLEDAI groups showed higher serum 4-hydroxynonenal (HNE)-/malondialdehyde (MDA)-protein adducts and their specific immune complexes (HNE-/MDA-specific ICs) together with IL-17 than the controls, but the levels were significantly greater in the high SLEDAI (≥ 6) group. Moreover, the serum levels of anti-oxidant enzymes Cu/Zn superoxide dismutase (SOD) and catalase (CAT) were significantly reduced in both patient groups compared to controls. Remarkably, for the first time, our data show that increased HNE-/MDA-specific ICs are positively associated with SLEDAI and elevated circulating immune complexes (CICs), suggesting a possible causal relationship among oxidative stress, LDRA-specific ICs and the development of SLE. Our findings, apart from providing firm support to an association between oxidative stress and SLE, also suggest that these oxidative stress markers, especially the HNE-/MDA-specific ICs, may be useful in evaluating the prognosis of SLE as well as in elucidating the mechanisms of disease pathogenesis. PMID:27749917

  6. 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.

  7. 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.

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

    PubMed

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

    2014-08-01

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

  9. 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.

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

    PubMed

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

    2011-12-06

    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.

  11. 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

  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.

  13. 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

  14. Temporal and Tissue-Specific Disruption Of LINC Complexes In Vivo

    PubMed Central

    Razafsky, David; Hodzic, Didier

    2014-01-01

    Migration and anchorage of nuclei within developing and adult tissues rely on Linkers of the Nucleoskeleton to the Cytoskeleton (LINC complexes). These macromolecular assemblies span the nuclear envelope and physically couple chromatin and nuclear lamina to cytoplasmic cytoskeletal networks. LINC complexes assemble within the perinuclear space through direct interactions between the respective evolutionary-conserved SUN and KASH domains of Sun proteins, which reside within the inner nuclear membrane, and Nesprins, which reside within the outer nuclear membrane. Here, we describe and validate a dominant-negative transgenic strategy allowing for the disruption of endogenous SUN/KASH interactions through the inducible expression of a recombinant KASH domain. Our approach, which is based on the Cre/Lox system, allows for the targeted disruption of LINC complexes in a wide array of mouse tissues or specific cell types thereof and bypasses the perinatal lethality and potential cell nonautonomous effects of current mouse models based on germline inactivation of genes encoding Sun proteins and Nesprins. For these reasons, this mouse model provides a useful tool to evaluate the physiological relevance of LINC complexes integrity during development and homeostasis in a wide array of mammalian tissues. PMID:24550182

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

    PubMed Central

    Chappell, Cynthia; Gonzales, Christopher; Okhuysen, Pablo

    2015-01-01

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

  16. 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

    2014-10-01

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

  17. [Dynamic model of protein behavior in water. Possible mechanism of association and dissociation of specific complexes].

    PubMed

    Kiaiviariainen, A I

    1979-01-01

    The proposed mechanism of association and dissociation of specific protein complex with ligands is based on the assumption that thermal fluctuations in the non-polar cavities of protein are interrelated due to the co-operative properties of macromolecules. The non-polar cavities, representing the active centres and clefts in the globule jump from the "open" state to the "closed" one with a certain amount of water being removed to the external medium. It is assumed that the association of ligand with the active centre is accompanied by stabilization of the chest state and destibilization of the open one, dissociation being a reverse process. A rapid change in the state of the active centre under the influence of ligand induces a slow relaxation process resulting in similar alterations in the state of the auxiliary non-polar cavities of protein. As a result, the binding constant of ligand increases, while the free energy of protein decreases. Expressions have been obtained which relate the rate constants of association, dissociation and the binding constant to the rate-constant of the nonpolar cavities transitions from the closed state to the open one, and vice versa. They gave a possibility for a qualitative interpretation of the effect of some specific and non-specific agents upon the stability of immunoglobulins, on the influence of salts upon the association and dissociation of antibody-antigene complexes and on the increase in the constant of binding between antibodies and haptens in the course of prolonged immunisation.

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

    PubMed

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

    2015-07-01

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

  19. 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.

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

    PubMed Central

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

    2015-01-01

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

  1. 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

  2. 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

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

    PubMed

    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

  4. 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.

  5. 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.

  6. Structural analysis of human dual-specificity phosphatase 22 complexed with a phosphotyrosine-like substrate.

    PubMed

    Lountos, George T; Cherry, Scott; Tropea, Joseph E; Waugh, David S

    2015-02-01

    4-Nitrophenyl phosphate (p-nitrophenyl phosphate, pNPP) is widely used as a small molecule phosphotyrosine-like substrate in activity assays for protein tyrosine phosphatases. It is a colorless substrate that upon hydrolysis is converted to a yellow 4-nitrophenolate ion that can be monitored by absorbance at 405 nm. Therefore, the pNPP assay has been widely adopted as a quick and simple method to assess phosphatase activity and is also commonly used in assays to screen for inhibitors. Here, the first crystal structure is presented of a dual-specificity phosphatase, human dual-specificity phosphatase 22 (DUSP22), in complex with pNPP. The structure illuminates the molecular basis for substrate binding and may also facilitate the structure-assisted development of DUSP22 inhibitors.

  7. 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

  8. 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

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

    PubMed

    Gao, X L; Patel, D J

    1990-12-11

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

  10. Specificity of CTL interactions with peptide-MHC class I tetrameric complexes is temperature dependent.

    PubMed

    Whelan, J A; Dunbar, P R; Price, D A; Purbhoo, M A; Lechner, F; Ogg, G S; Griffiths, G; Phillips, R E; Cerundolo, V; Sewell, A K

    1999-10-15

    Tetrameric peptide-MHC class I complexes ("tetramers") are proving invaluable as reagents for characterizing immune responses involving CTLs. However, because the TCR can exhibit a degree of promiscuity for binding peptide-MHC class I ligands, there is potential for cross-reactivity. Recent reports showing that the TCR/peptide-MHC interaction is dramatically dependent upon temperature led us to investigate the effects of incubation temperature on tetramer staining. We find that tetramers rapidly stain CTLs with high intensity at 37 degrees C. We examine the fine specificity of tetramer staining using a well-characterized set of natural epitope variants. Peptide variants that elicit little or no functional cellular response from CTLs can stain these cells at 4 degrees C but not at 37 degrees C when incorporated into tetramers. These results suggest that some studies reporting tetramer incubations at 4 degrees C could detect cross-reactive populations of CTLs with minimal avidity for the tetramer peptide, especially in the tetramer-low population. For identifying specific CTLs among polyclonal cell populations such as PBLs, incubation with tetramers at 37 degrees C improves the staining intensity of specific CTLs, resulting in improved separation of tetramer-high CD8+ cells. Confocal microscopy reveals that tetramers incubated at 37 degrees C can be rapidly internalized by specific CTLs into vesicles that overlap with the early endocytic compartment. This TCR-specific internalization suggests that coupling of tetramers or analogues with toxins, which are activated only after receptor internalization, may create immunotoxins capable of killing CTLs of single specificities.

  11. 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.

  12. Genus-specific recruitment of filovirus ribonucleoprotein complexes into budding particles

    PubMed Central

    Spiegelberg, Larissa; Wahl-Jensen, Victoria; Kolesnikova, Larissa; Feldmann, Heinz; Hoenen, Thomas

    2011-01-01

    The filoviral matrix protein VP40 orchestrates virus morphogenesis and budding. To do this it interacts with both the glycoprotein (GP1,2) and the ribonucleoprotein (RNP) complex components; however, these interactions are still not well understood. Here we show that for efficient VP40-driven formation of transcription and replication-competent virus-like particles (trVLPs), which contain both an RNP complex and GP1,2, the RNP components and VP40, but not GP1,2 and VP40, must be from the same genus. trVLP preparations contained both spherical and filamentous particles, but only the latter were able to infect target cells and to lead to genome replication and transcription. Interestingly, the genus specificity of the VP40–RNP interactions was specific to the formation of filamentous trVLPs, but not to spherical particles. These results not only further our understanding of VP40 interactions, but also suggest that special care is required when using trVLP or VLP systems to model virus morphogenesis. PMID:21900424

  13. Interaction between HMGA1a and the origin recognition complex creates site-specific replication origins

    PubMed Central

    Thomae, Andreas W.; Pich, Dagmar; Brocher, Jan; Spindler, Mark-Peter; Berens, Christian; Hock, Robert; Hammerschmidt, Wolfgang; Schepers, Aloys

    2008-01-01

    In all eukaryotic cells, origins of DNA replication are characterized by the binding of the origin recognition complex (ORC). How ORC is positioned to sites where replication initiates is unknown, because metazoan ORC binds DNA without apparent sequence specificity. Thus, additional factors might be involved in ORC positioning. Our experiments indicate that a family member of the high-mobility group proteins, HMGA1a, can specifically target ORC to DNA. Coimmunoprecipitations and imaging studies demonstrate that HMGA1a interacts with different ORC subunits in vitro and in vivo. This interaction occurs mainly in AT-rich heterochromatic regions to which HMGA1a localizes. Fusion proteins of HMGA1a and the DNA-binding domain of the viral factor EBNA1 or the prokaryotic tetracycline repressor, TetR, can recruit ORC to cognate operator sites forming functional origins of DNA replication. When HMGA1a is targeted to plasmid DNA, the prereplicative complex is assembled during G1 and the amount of ORC correlates with the local concentration of HMGA1a. Nascent-strand abundance assays demonstrate that DNA replication initiates at or near HMGA1a-rich sites. Our experiments indicate that chromatin proteins can target ORC to DNA, suggesting they might specify origins of DNA replication in metazoan cells. PMID:18234858

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. 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.

  17. Software for SARA

    SciTech Connect

    Quinn, P.

    1991-10-01

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

  18. 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)

  19. 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.

  20. 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.

  1. Subunit Composition and Substrate Specificity of a MOF-containing Histone Acetyltransferase Distinct from the Male-specific Lethal (MSL) Complex*

    PubMed Central

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

    2010-01-01

    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. PMID:20018852

  2. 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.

  3. 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.

  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. 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.

  6. 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

  7. Modular Software Performance Monitoring

    NASA Astrophysics Data System (ADS)

    Kruse, Daniele Francesco; Kruzelecki, Karol

    2011-12-01

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

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

    PubMed Central

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

    2012-01-01

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

  9. Identification of proteins that form specific complexes with the highly conserved protein Translin in Schizosaccharomyces pombe.

    PubMed

    Eliahoo, Elad; Litovco, Phyana; Ben Yosef, Ron; Bendalak, Keren; Ziv, Tamar; Manor, Haim

    2014-04-01

    Translin is a single-stranded DNA and RNA binding protein that has a high affinity for G-rich sequences. TRAX is a Translin paralog that associates with Translin. Both Translin and TRAX were highly conserved in eukaryotes. The nucleic acid binding form of Translin is a barrel-shaped homo-octamer. A Translin-TRAX hetero-octamer having a similar structure also binds nucleic acids. Previous reports suggested that Translin may be involved in chromosomal translocations, telomere metabolism and the control of mRNA transport and translation. More recent studies have indicated that Translin-TRAX hetero-octamers are involved in RNA silencing. To gain a further insight into the functions of Translin, we have undertaken to systematically search for proteins with which it forms specific complexes in living cells. Here we report the results of such a search conducted in the fission yeast Schizosaccharomyces pombe, a suitable model system. This search was carried out by affinity purification and immuno-precipitation techniques, combined with differential labeling of the intracellular proteins with the stable isotopes ¹⁵N and ¹⁴N. We identified for the first time two proteins containing an RNA Recognition Motif (RRM), which are specifically associated with the yeast Translin: (1) the pre-mRNA-splicing factor srp1 that belongs to the highly conserved SR family of proteins and (2) vip1, a protein conserved in fungi. Our data also support the presence of RNA in these intracellular complexes. Our experimental approach should be generally applicable to studies of weak intracellular protein-protein interactions and provides a clear distinction between false positive vs. truly interacting proteins.

  10. Crystal structure of human prostate-specific antigen in a sandwich antibody complex.

    PubMed

    Stura, Enrico A; Muller, Bruno H; Bossus, Marc; Michel, Sandrine; Jolivet-Reynaud, Colette; Ducancel, Frédéric

    2011-12-01

    Human prostate-specific antigen (PSA or human kallikrein-related peptidase 3) present in small quantities in the sera of healthy men becomes elevated in prostate cancer (PCa) and other prostate disorders. The ability to identify the free PSA fraction associated with PCa could increase the reliability of the PSA diagnostic test. Here we present the crystal structure of human PSA from seminal fluid in a sandwich complex with two monoclonal antibodies (mAbs). MAb 5D5A5 captures total PSA with exceptionally high affinity, and mAb 5D3D11 selectively discriminates between free PSA subforms that are more abundant in sera from patients with PCa. Although the antigen is not of seric origin, several insights into cancer diagnosis can be discerned from this complex. MAb 5D3D11 recognizes a PSA conformation different from that previously reported. Interacting with the kallikrein loop, the PSA N-linked glycan attached to asparagine 61 is an uncommonly complex sialated triantennary chain. O-linked glycosylation is observed at threonine 125. The description of how PSA subforms in prostatic fluid can be discriminated using pairs of antibodies is a first step in the design of new strategies that are capable of real discrimination among PSA subforms, which will lead to the formulation of more reliable diagnostic tests. In a companion article [Muller, B. H., Savatier, A., L'Hostis, G., Costa, N., Bossus, M., Michel, S., et al. (2011). In vitro affinity maturation of an anti-PSA antibody for prostate cancer diagnostic assay. J. Mol. Biol.], we describe engineering efforts to improve the affinity of mAb 5D3D11, a first step towards such goal. PMID:22037582

  11. 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.

  12. 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

  13. Distinct isoform-specific complexes of TANGO1 cooperatively facilitate collagen secretion from the endoplasmic reticulum.

    PubMed

    Maeda, Miharu; Saito, Kota; Katada, Toshiaki

    2016-09-01

    Collagens synthesized within the endoplasmic reticulum (ER) are too large to fit in conventional COPII-coated transport vesicles; thus their export from the ER requires specialized factors. TANGO1 (L) is an integral membrane protein that binds to collagen and the coatomer of vesicles and is necessary for collagen secretion from the ER. Here we characterized the short isoform of TANGO1 (TANGO1S), lacking the collagen-binding domain, and found that it was independently required for collagen export from the ER. Moreover, we found that each of the TANGO1 isoforms forms a stable protein complex with factors involved in collagen secretion: TANGO1L/cTAGE5/Sec12 (900 kDa) and TANGO1S/cTAGE5/Sec12 (700 kDa). Of interest, TANGO1S and TANGO1L seemed to be interchangeable in exporting collagen from the ER. Our results suggest that mammalian ER exit sites possess two different-sized membrane-bound macromolecular complexes that specifically function in large-cargo export from the ER. PMID:27413011

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-10-01

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

  16. Global Software Engineering: A Software Process Approach

    NASA Astrophysics Data System (ADS)

    Richardson, Ita; Casey, Valentine; Burton, John; McCaffery, Fergal

    Our research has shown that many companies are struggling with the successful implementation of global software engineering, due to temporal, cultural and geographical distance, which causes a range of factors to come into play. For example, cultural, project managementproject management and communication difficulties continually cause problems for software engineers and project managers. While the implementation of efficient software processes can be used to improve the quality of the software product, published software process models do not cater explicitly for the recent growth in global software engineering. Our thesis is that global software engineering factors should be included in software process models to ensure their continued usefulness in global organisations. Based on extensive global software engineering research, we have developed a software process, Global Teaming, which includes specific practices and sub-practices. The purpose is to ensure that requirements for successful global software engineering are stipulated so that organisations can ensure successful implementation of global software engineering.

  17. 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.

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

    PubMed

    Adams, P

    1994-01-01

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

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

    PubMed

    Adams, P

    1994-01-01

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

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

    PubMed

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

    2009-06-01

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

  1. 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.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Ehrler, Frederic; Lovis, Christian; Blondon, Katherine

    2016-01-01

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

  5. 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.

  6. 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.

  7. A computational model for sex-specific genetic architecture of complex traits in humans: Implications for mapping pain sensitivity

    PubMed Central

    Wang, Chenguang; Cheng, Yun; Liu, Tian; Li, Qin; Fillingim, Roger B; Wallace, Margaret R; Staud, Roland; Kaplan, Lee; Wu, Rongling

    2008-01-01

    Understanding differences in the genetic architecture of complex traits between the two sexes has significant implications for evolutionary studies and clinical diagnosis. However, our knowledge about sex-specific genetic architecture is limited largely because of a lack of analytical models that can detect and quantify the effects of sex on the complexity of quantitative genetic variation. Here, we derived a statistical model for mapping DNA sequence variants that contribute to sex-specific differences in allele frequencies, linkage disequilibria, and additive and dominance genetic effects due to haplotype diversity. This model allows a genome-wide search for functional haplotypes and the estimation and test of haplotype by sex interactions and sex-specific heritability. The model, validated by simulation studies, was used to detect sex-specific functional haplotypes that encode a pain sensitivity trait in humans. The model could have important implications for mapping complex trait genes and studying the detailed genetic architecture of sex-specific differences. PMID:18416828

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. 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

    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 (R (2) > 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Specificity in protein-protein interactions: the structural basis for dual recognition in endonuclease colicin-immunity protein complexes.

    PubMed

    Kühlmann, U C; Pommer, A J; Moore, G R; James, R; Kleanthous, C

    2000-09-01

    Bacteria producing endonuclease colicins are protected against their cytotoxic activity by virtue of a small immunity protein that binds with high affinity and specificity to inactivate the endonuclease. DNase binding by the immunity protein occurs through a "dual recognition" mechanism in which conserved residues from helix III act as the binding-site anchor, while variable residues from helix II define specificity. We now report the 1.7 A crystal structure of the 24.5 kDa complex formed between the endonuclease domain of colicin E9 and its cognate immunity protein Im9, which provides a molecular rationale for this mechanism. Conserved residues of Im9 form a binding-energy hotspot through a combination of backbone hydrogen bonds to the endonuclease, many via buried solvent molecules, and hydrophobic interactions at the core of the interface, while the specificity-determining residues interact with corresponding specificity side-chains on the enzyme. Comparison between the present structure and that reported recently for the colicin E7 endonuclease domain in complex with Im7 highlights how specificity is achieved by very different interactions in the two complexes, predominantly hydrophobic in nature in the E9-Im9 complex but charged in the E7-Im7 complex. A key feature of both complexes is the contact between a conserved tyrosine residue from the immunity proteins (Im9 Tyr54) with a specificity residue on the endonuclease directing it toward the specificity sites of the immunity protein. Remarkably, this tyrosine residue and its neighbour (Im9 Tyr55) are the pivots of a 19 degrees rigid-body rotation that relates the positions of Im7 and Im9 in the two complexes. This rotation does not affect conserved immunity protein interactions with the endonuclease but results in different regions of the specificity helix being presented to the enzyme.

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

    PubMed Central

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

    2007-01-01

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

  17. Streptococcus pneumoniae clonal complex 199: genetic diversity and tissue-specific virulence.

    PubMed

    Thomas, Jonathan C; Figueira, Marisol; Fennie, Kristopher P; Laufer, Alison S; Kong, Yong; Pichichero, Michael E; Pelton, Stephen I; Pettigrew, Melinda M

    2011-01-01

    Streptococcus pneumoniae is an important cause of otitis media and invasive disease. Since introduction of the heptavalent pneumococcal conjugate vaccine, there has been an increase in replacement disease due to serotype 19A clonal complex (CC)199 isolates. The goals of this study were to 1) describe genetic diversity among nineteen CC199 isolates from carriage, middle ear, blood, and cerebrospinal fluid, 2) compare CC199 19A (n = 3) and 15B/C (n = 2) isolates in the chinchilla model for pneumococcal disease, and 3) identify accessory genes associated with tissue-specific disease among a larger collection of S. pneumoniae isolates. CC199 isolates were analyzed by comparative genome hybridization. One hundred and twenty-seven genes were variably present. The CC199 phylogeny split into two main clades, one comprised predominantly of carriage isolates and another of disease isolates. Ability to colonize and cause disease did not differ by serotype in the chinchilla model. However, isolates from the disease clade were associated with faster time to bacteremia compared to carriage clade isolates. One 19A isolate exhibited hypervirulence. Twelve tissue-specific genes/regions were identified by correspondence analysis. After screening a diverse collection of 326 isolates, spr0282 was associated with carriage. Four genes/regions, SP0163, SP0463, SPN05002 and RD8a were associated with middle ear isolates. SPN05002 also associated with blood and CSF, while RD8a associated with blood isolates. The hypervirulent isolate's genome was sequenced using the Solexa paired-end sequencing platform and compared to that of a reference serotype 19A isolate, revealing the presence of a novel 20 kb region with sequence similarity to bacteriophage genes. Genetic factors other than serotype may modulate virulence potential in CC199. These studies have implications for the long-term effectiveness of conjugate vaccines. Ideally, future vaccines would target common proteins to

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

    DOE PAGESBeta

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

    2012-01-01

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

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

    DOE PAGESBeta

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

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-02-01

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

  3. Paired receptor specificity explained by structures of signal regulatory proteins alone and complexed with CD47.

    PubMed

    Hatherley, Deborah; Graham, Stephen C; Turner, Jessie; Harlos, Karl; Stuart, David I; Barclay, A Neil

    2008-07-25

    CD47 is a widely distributed cell-surface protein that acts a marker of self through interactions of myeloid and neural cells. We describe the high-resolution X-ray crystallographic structures of the immunoglobulin superfamily domain of CD47 alone and in complex with the N-terminal ligand-binding domain of signal regulatory protein alpha (SIRPalpha). The unusual and convoluted interacting face of CD47, comprising the N terminus and loops at the end of the domain, intercalates with the corresponding regions in SIRPalpha. We have also determined structures of the N-terminal domains of SIRPbeta, SIRPbeta(2), and SIRPgamma; proteins that are closely related to SIRPalpha but bind CD47 with negligible or reduced affinity. These results explain the specificity of CD47 for the SIRP family of paired receptors in atomic detail. Analysis of SIRPalpha polymorphisms suggests that these, as well as the activating SIRPs, may have evolved to counteract pathogen binding to the inhibitory SIRPalpha receptor.

  4. 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

  5. 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

  6. 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.

  7. 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.

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

    PubMed

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

    2016-04-15

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

  9. Are we there yet? Initial targeting of the Male-Specific Lethal and Polycomb group chromatin complexes in Drosophila

    PubMed Central

    McElroy, Kyle A.; Kang, Hyuckjoon; Kuroda, Mitzi I.

    2014-01-01

    Chromatin-binding proteins must navigate the complex nuclear milieu to find their sites of action, and a constellation of protein factors and other properties are likely to influence targeting specificity. Despite considerable progress, the precise rules by which binding specificity is achieved have remained elusive. Here, we consider early targeting events for two groups of chromatin-binding complexes in Drosophila: the Male-Specific Lethal (MSL) and the Polycomb group (PcG) complexes. These two serve as models for understanding targeting, because they have been extensively studied and play vital roles in Drosophila, and their targets have been documented at high resolution. Furthermore, the proteins and biochemical properties of both complexes are largely conserved in multicellular organisms, including humans. While the MSL complex increases gene expression and PcG members repress genes, the two groups share many similarities such as the ability to modify their chromatin environment to create active or repressive domains, respectively. With legacies of in-depth genetic, biochemical and now genomic approaches, the MSL and PcG complexes will continue to provide tractable systems for understanding the recruitment of multiprotein chromatin complexes to their target loci. PMID:24671948

  10. Selecting Software.

    ERIC Educational Resources Information Center

    Pereus, Steven C.

    2002-01-01

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

  11. 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

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

    PubMed

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

    2012-12-28

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

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

    PubMed Central

    Chakrabarti, Lisa

    2016-01-01

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

  14. 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

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

    NASA Technical Reports Server (NTRS)

    Mcgarry, F.

    1980-01-01

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

  16. 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

  17. 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.

  18. 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.

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

    PubMed

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

    2015-02-21

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

  20. 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

  1. 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.…

  2. Complexes between C1q and C3 or C4: novel and specific markers for classical complement pathway activation.

    PubMed

    Wouters, Diana; Wiessenberg, Hans D; Hart, Margreet; Bruins, Peter; Voskuyl, Alexandre; Daha, Mohamed R; Hack, C Erik

    2005-03-01

    Classical pathway activation is often assessed by measuring circulating levels of activated C4. However, this parameter does not discriminate between activation through the classical or the lectin pathway. We hypothesized that during classical pathway activation, complexes are formed between C1q and activated C4 or C3. Using ELISA, we investigated whether such complexes constitute specific markers for classical pathway activation. In vitro, C1q-C3d/C4d complexes were generated upon incubation of normal recalcified plasma with aggregated IgG or an anti-C1q mAb that activates C1 (mAb anti-C1q-130). In contrast, during incubation with C1s or trypsin, C1q-C3d/C4d complexes were not generated, which excludes an innocent bystander effect. Additionally, C1q-C3d/C4d complexes were not generated during activation of the alternative or the lectin pathway. Repeated freezing and thawing did not influence levels of C1q-C3d/C4d complexes in recalcified plasma. To measure C1q-complement complexes in plasma samples, we separated unbound complement proteins from C1q-C3d/C4d complexes in the samples prior to testing with ELISA. In samples from patients undergoing cardiopulmonary bypass surgery or suffering from rheumatoid arthritis, we found higher levels of C1q-C4 complexes than in samples from healthy individuals. We conclude that complexes between C1q and C4 or C3 are specific markers of classical complement pathway activation.

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

    PubMed Central

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

    2013-01-01

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

  5. 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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2015-01-01

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

  8. High-resolution and specific detection of bacteria on complex surfaces using nanoparticle probes and electron microscopy.

    PubMed

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

    2015-01-01

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

  9. 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.

  10. Functional Characterization and Metal Ion Specificity of the Metal-Citrate Complex Transporter from Streptomyces coelicolor▿

    PubMed Central

    Lensbouer, Joshua J.; Patel, Ami; Sirianni, Joseph P.; Doyle, Robert P.

    2008-01-01

    Secondary transporters of citrate in complex with metal ions belong to the bacterial CitMHS family, about which little is known. The transport of metal-citrate complexes in Streptomyces coelicolor has been investigated. The best cofactor for citrate uptake in Streptomyces coelicolor is Fe3+, but uptake was also noted for Ca2+, Pb2+, Ba2+, and Mn2+. Uptake was not observed with the Mg2+, Ni2+, or Co2+ cofactor. The transportation of iron- and calcium-citrate makes these systems unique among the CitMHS family members reported to date. No complementary uptake akin to that observed for the CitH (Ca2+, Ba2+, Sr2+) and CitM (Mg2+, Ni2+, Mn2+, Co2+, Zn2+) systems of Bacillus subtilis was noted. Competitive experiments using EGTA confirmed that metal-citrate complex formation promoted citrate uptake. Uptake of free citrate was not observed. The open reading frame postulated as being responsible for the metal-citrate transport observed in Streptomyces coelicolor was cloned and overexpressed in Escherichia coli strains with the primary Fe3+-citrate transport system (fecABCDE) removed. Functional expression was successful, with uptake of Ca2+-citrate, Fe3+-citrate, and Pb2+-citrate observed. No free-citrate transport was observed in IPTG (isopropyl-β-d-thiogalactopyranoside)-induced or -uninduced E. coli. Metabolism of the Fe3+-citrate and Ca2+-citrate complexes, but not the Pb2+-citrate complex, was observed. Rationalization is based on the difference in metal-complex coordination upon binding of the metal by citrate. PMID:18556792

  11. Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.

    PubMed

    Lu, Chenggang; Fuller, Margaret T

    2015-12-01

    Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s). In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC), a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs), spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages. PMID:26624996

  12. 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)

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

    PubMed

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

    2008-05-15

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

  15. 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

  16. Model-Based Software Testing for Object-Oriented Software

    ERIC Educational Resources Information Center

    Biju, Soly Mathew

    2008-01-01

    Model-based testing is one of the best solutions for testing object-oriented software. It has a better test coverage than other testing styles. Model-based testing takes into consideration behavioural aspects of a class, which are usually unchecked in other testing methods. An increase in the complexity of software has forced the software industry…

  17. Software Reviews.

    ERIC Educational Resources Information Center

    Smith, Richard L., Ed.

    1985-01-01

    Reviews software packages by providing extensive descriptions and discussions of their strengths and weaknesses. Software reviewed include (1) "VISIFROG: Vertebrate Anatomy" (grade seven-adult); (2) "Fraction Bars Computer Program" (grades three to six) and (3) four telecommunications utilities. (JN)

  18. Tissue-specific function of Patj in regulating the Crumbs complex and epithelial polarity.

    PubMed

    Pénalva, Clothilde; Mirouse, Vincent

    2012-12-01

    Patj is described as a core component of the Crumbs complex. Along with the other components, Crumbs and Stardust, Patj has been proposed as essential for epithelial polarity. However, no proper in vivo genetic analysis of Patj function has been performed in any organism. We have generated the first null mutants for Drosophila Patj. These mutants are lethal. However, Patj is not required in all epithelia where the Crumbs complex is essential. Patj is dispensable for ectoderm polarity and embryonic development, whereas more severe defects are observed in the adult follicular epithelium, including mislocalisation of the Crumbs complex from the apical domain, as well as morphogenetic defects. These defects are similar to those observed with crumbs and stardust mutants, although weaker and less frequent. Also, gain-of-function of Crumbs and Patj mutation genetically suppress each other in follicular cells. We also show that the first PDZ domain of Patj associated with the Stardust-binding domain are sufficient to fully rescue both Drosophila viability and Crumbs localisation. We propose that the only crucial function of Patj hinges on the ability of its first two domains to positively regulate the Crumbs complex, defining a new developmental level of regulation of its dynamics.

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

    ERIC Educational Resources Information Center

    Vyatkina, Nina

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2016-01-01

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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Structure of Crumbs tail in complex with the PALS1 PDZ-SH3-GK tandem reveals a highly specific assembly mechanism for the apical Crumbs complex.

    PubMed

    Li, Youjun; Wei, Zhiyi; Yan, Yan; Wan, Qingwen; Du, Quansheng; Zhang, Mingjie

    2014-12-01

    The Crumbs (Crb) complex, formed by Crb, PALS1, and PATJ, is evolutionarily conserved in metazoans and acts as a master cell-growth and -polarity regulator at the apical membranes in polarized epithelia. Crb intracellular functions, including its direct binding to PALS1, are mediated by Crb's highly conserved 37-residue cytoplasmic tail. However, the mechanistic basis governing the highly specific Crb-PALS1 complex formation is unclear, as reported interaction between the Crb tail (Crb-CT) and PALS1 PSD-95/DLG/ZO-1 (PDZ) domain is weak and promiscuous. Here we have discovered that the PDZ-Src homolgy 3 (SH3)-Guanylate kinase (GK) tandem of PALS1 binds to Crb-CT with a dissociation constant of 70 nM, which is ∼ 100-fold stronger than the PALS1 PDZ-Crb-CT interaction. The crystal structure of the PALS1 PDZ-SH3-GK-Crb-CT complex reveals that PDZ-SH3-GK forms a structural supramodule with all three domains contributing to the tight binding to Crb. Mutations disrupting the tertiary interactions of the PDZ-SH3-GK supramodule weaken the PALS1-Crb interaction and compromise PALS1-mediated polarity establishment in Madin-Darby canine kidney (MDCK) cysts. We further show that specific target binding of other members of membrane-associated guanylate kinases (MAGUKs) (e.g., CASK binding to neurexin) also requires the presence of their PDZ-SH3-GK tandems.

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

    NASA Astrophysics Data System (ADS)

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

    2011-02-01

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

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

    PubMed

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

    1997-02-01

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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Specific Photocrosslinking of DNA-Protein Complexes: Identification of Contacts Between Integration Host Factor and Its Target DNA

    NASA Astrophysics Data System (ADS)

    Yang, Shu-Wei; Nash, Howard A.

    1994-12-01

    Azide moieties have been specifically placed in the backbone of DNA by chemical coupling between azidophenacyl bromide and uniquely positioned phosphorothioate residues. The derivatized DNA forms specific complexes with a DNA-binding protein and, following irradiation with 302-nm light, makes specific crosslinks to the protein. Isolation of this covalent complex, followed by tryptic digestion and Edman degradation of the resulting crosslinked peptide, identifies the portion of the protein that is near the derivatized segment of the target DNA. We use this method to probe the interaction between a specific DNA sequence and integration host factor (IHF) protein. A single IHF heterodimer is known to contact >25 bp of DNA and thereby introduce a sharp bend. Two segments of a typical IHF site were derivatized with aryl azide. Although the segments were separated by only 5 bp, they crosslinked to different subunits of IHF. The locations of the crosslinks support our current view for the way IHF protein binds to and bends its specific targets.

  16. Tool Use Within NASA Software Quality Assurance

    NASA Technical Reports Server (NTRS)

    Shigeta, Denise; Port, Dan; Nikora, Allen P.; Wilf, Joel

    2013-01-01

    As space mission software systems become larger and more complex, it is increasingly important for the software assurance effort to have the ability to effectively assess both the artifacts produced during software system development and the development process itself. Conceptually, assurance is a straightforward idea - it is the result of activities carried out by an organization independent of the software developers to better inform project management of potential technical and programmatic risks, and thus increase management's confidence in the decisions they ultimately make. In practice, effective assurance for large, complex systems often entails assessing large, complex software artifacts (e.g., requirements specifications, architectural descriptions) as well as substantial amounts of unstructured information (e.g., anomaly reports resulting from testing activities during development). In such an environment, assurance engineers can benefit greatly from appropriate tool support. In order to do so, an assurance organization will need accurate and timely information on the tool support available for various types of assurance activities. In this paper, we investigate the current use of tool support for assurance organizations within NASA, and describe on-going work at JPL for providing assurance organizations with the information about tools they need to use them effectively.

  17. Distinguishing Complex Ideas about Climate Change: Knowledge Integration vs. Specific Guidance

    ERIC Educational Resources Information Center

    Vitale, Jonathan M.; McBride, Elizabeth; Linn, Marcia C.

    2016-01-01

    We compared two forms of automated guidance to support students' understanding of climate change in an online inquiry science unit. For "specific" guidance, we directly communicated ideas that were missing or misrepresented in student responses. For "knowledge integration" guidance, we provided hints or suggestions to motivate…

  18. Reconstitution of multivalent PDZ domain binding to the scaffold protein PSD-95 reveals ternary-complex specificity of combinatorial inhibition

    PubMed Central

    McCann, James J.; Choi, Ucheor B.; Bowen, Mark E.

    2014-01-01

    Summary Multi-domain scaffold proteins serve as hubs in the signal transduction network. By physically colocalizing sequential steps in a transduction pathway, scaffolds catalyze and direct incoming signals. Much is known about binary interactions with individual domains but it is unknown whether “scaffolding activity” is predictable from pairwise affinities. Here, we characterized multivalent binding to PSD-95, a scaffold protein containing three PDZ domains connected in series by disordered linkers. We used single molecule fluorescence to watch soluble PSD-95 recruit diffusing proteins to a surface-attached receptor cytoplasmic domain. Different ternary complexes showed unique concentration dependence for scaffolding despite similar pairwise affinity. The concentration dependence of scaffolding activity was not predictable based on binary interactions. PSD-95 did not stabilize specific complexes, but rather increased the frequency of transient binding events. Our results suggest that PSD-95 maintains a loosely-connected pleomorphic ensemble rather than forming a stereospecific complex containing all components. PMID:25220472

  19. 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.

  20. Tissue-specific compartmental analysis for dynamic contrast-enhanced MR imaging of complex tumors.

    PubMed

    Chen, Li; Choyke, Peter L; Chan, Tsung-Han; Chi, Chong-Yung; Wang, Ge; Wang, Yue

    2011-12-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides a noninvasive method for evaluating tumor vasculature patterns based on contrast accumulation and washout. However, due to limited imaging resolution and tumor tissue heterogeneity, tracer concentrations at many pixels often represent a mixture of more than one distinct compartment. This pixel-wise partial volume effect (PVE) would have profound impact on the accuracy of pharmacokinetics studies using existing compartmental modeling (CM) methods. We, therefore, propose a convex analysis of mixtures (CAM) algorithm to explicitly mitigate PVE by expressing the kinetics in each pixel as a nonnegative combination of underlying compartments and subsequently identifying pure volume pixels at the corners of the clustered pixel time series scatter plot simplex. The algorithm is supported theoretically by a well-grounded mathematical framework and practically by plug-in noise filtering and normalization preprocessing. We demonstrate the principle and feasibility of the CAM-CM approach on realistic synthetic data involving two functional tissue compartments, and compare the accuracy of parameter estimates obtained with and without PVE elimination using CAM or other relevant techniques. Experimental results show that CAM-CM achieves a significant improvement in the accuracy of kinetic parameter estimation. We apply the algorithm to real DCE-MRI breast cancer data and observe improved pharmacokinetic parameter estimation, separating tumor tissue into regions with differential tracer kinetics on a pixel-by-pixel basis and revealing biologically plausible tumor tissue heterogeneity patterns. This method combines the advantages of multivariate clustering, convex geometry analysis, and compartmental modeling approaches. The open-source MATLAB software of CAM-CM is publicly available from the Web. PMID:21708498

  1. 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.

  2. Factors associated with Culicoides Obsoletus complex spp.-specific IgE reactivity in Icelandic horses and Shetland ponies.

    PubMed

    Schurink, Anouk; van der Meide, Nathalie M A; Savelkoul, Huub F J; Ducro, Bart J; Tijhaar, Edwin

    2014-09-01

    Insect bite hypersensitivity (IBH) is a common allergic skin disease in horses, caused by biting insects of the Culicoides spp. In The Netherlands, Culicoides spp. of the Obsoletus complex are the most important midges involved in IBH. The aim of the present study was to identify and quantify associations between several endogenous (host) and exogenous (environmental) factors and immunoglobulin E (IgE) reactivity against Obsoletus complex-derived whole body extract or seven recombinant allergens, measured by ELISA. Data from 143 Icelandic horses and 177 Shetland ponies were analysed using multivariable models. In addition, the relationship between IgE reactivity and severity of clinical signs in IBH-affected horses was examined. Positive correlations were found between Obsoletus complex-specific IgE and severity of clinical signs. Disease status (IBH affected or control), breed and the interaction between IBH status and breed were significantly associated with IgE reactivity against several Obsoletus complex allergens. Significantly greater IgE reactivity was seen in IBH-affected horses compared to controls. The differences in IgE values between cases and controls were most pronounced in Icelandic horses. Shetland pony controls had significantly greater IgE reactivity compared to Icelandic horse controls, while differences in IgE values comparing Shetland pony cases and Icelandic horse cases were not significant. Severity of clinical signs and IgE reactivity in IBH-affected horses against several Obsoletus complex allergens appeared to be related. Consideration of the factors associated with Obsoletus complex-specific IgE in horses might further improve interpretation and accuracy of IgE ELISA test results within these breeds, although further research is required.

  3. Choosing a software design method for real-time Ada applications: JSD process inversion as a means to tailor a design specification to the performance requirements and target machine

    NASA Technical Reports Server (NTRS)

    Withey, James V.

    1986-01-01

    The validity of real-time software is determined by its ability to execute on a computer within the time constraints of the physical system it is modeling. In many applications the time constraints are so critical that the details of process scheduling are elevated to the requirements analysis phase of the software development cycle. It is not uncommon to find specifications for a real-time cyclic executive program included to assumed in such requirements. It was found that prelininary designs structured around this implementation abscure the data flow of the real world system that is modeled and that it is consequently difficult and costly to maintain, update and reuse the resulting software. A cyclic executive is a software component that schedules and implicitly synchronizes the real-time software through periodic and repetitive subroutine calls. Therefore a design method is sought that allows the deferral of process scheduling to the later stages of design. The appropriate scheduling paradigm must be chosen given the performance constraints, the largest environment and the software's lifecycle. The concept of process inversion is explored with respect to the cyclic executive.

  4. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia.

    PubMed

    Kirov, G; Pocklington, A J; Holmans, P; Ivanov, D; Ikeda, M; Ruderfer, D; Moran, J; Chambert, K; Toncheva, D; Georgieva, L; Grozeva, D; Fjodorova, M; Wollerton, R; Rees, E; Nikolov, I; van de Lagemaat, L N; Bayés, A; Fernandez, E; Olason, P I; Böttcher, Y; Komiyama, N H; Collins, M O; Choudhary, J; Stefansson, K; Stefansson, H; Grant, S G N; Purcell, S; Sklar, P; O'Donovan, M C; Owen, M J

    2012-02-01

    A small number of rare, recurrent genomic copy number variants (CNVs) are known to substantially increase susceptibility to schizophrenia. As a consequence of the low fecundity in people with schizophrenia and other neurodevelopmental phenotypes to which these CNVs contribute, CNVs with large effects on risk are likely to be rapidly removed from the population by natural selection. Accordingly, such CNVs must frequently occur as recurrent de novo mutations. In a sample of 662 schizophrenia proband-parent trios, we found that rare de novo CNV mutations were significantly more frequent in cases (5.1% all cases, 5.5% family history negative) compared with 2.2% among 2623 controls, confirming the involvement of de novo CNVs in the pathogenesis of schizophrenia. Eight de novo CNVs occurred at four known schizophrenia loci (3q29, 15q11.2, 15q13.3 and 16p11.2). De novo CNVs of known pathogenic significance in other genomic disorders were also observed, including deletion at the TAR (thrombocytopenia absent radius) region on 1q21.1 and duplication at the WBS (Williams-Beuren syndrome) region at 7q11.23. Multiple de novos spanned genes encoding members of the DLG (discs large) family of membrane-associated guanylate kinases (MAGUKs) that are components of the postsynaptic density (PSD). Two de novos also affected EHMT1, a histone methyl transferase known to directly regulate DLG family members. Using a systems biology approach and merging novel CNV and proteomics data sets, systematic analysis of synaptic protein complexes showed that, compared with control CNVs, case de novos were significantly enriched for the PSD proteome (P=1.72 × 10⁻⁶. This was largely explained by enrichment for members of the N-methyl-D-aspartate receptor (NMDAR) (P=4.24 × 10⁻⁶) and neuronal activity-regulated cytoskeleton-associated protein (ARC) (P=3.78 × 10⁻⁸) postsynaptic signalling complexes. In an analysis of 18 492 subjects (7907 cases and 10 585 controls), case CNVs were

  5. 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.

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

    PubMed

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

    2005-05-01

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

  7. Determination of specific activity of iron-55 by spectrophotometry and liquid scintillation counting with bathophenanthroline complex

    SciTech Connect

    Yonezawa, C.; Hoshi, M.; Tachikawa, E.

    1985-12-01

    A method for determining the macroscopic amount of iron and its radioactivity (/sup 55/Fe) in radioactive corrosion products was established with a single chemical procedure. The iron was first extracted into a liquid scintillator (2,5-diphenyloxazole-xylene) as an ion associate of iron bathophenanthroline (BPT) complex and perchlorate at pH 3-8, followed by measurement of its radioactivity by a liquid scintillation counter and its absorbance by a spectrophotometer. The absorption maximum and molar absorptivity (epsilon) of the complex were 535 nm and 22,000, respectively. The system conforms to Beer's law at concentrations of up to 30 ..mu..g of iron in 10 mL of organic phase. The counting efficiency of the extracted /sup 55/Fe was found to be 60%. Although /sup 60/Co is extracted into the PPO-xylene together with /sup 5/)2%Fe, it is separated from /sup 55/Fe by back extraction with 0.005 M ethylenediaminetetraacetic acid (pH 6.0) into the aqueous phase. The effects of other foreign elements and radionuclides were also examined. The proposed method was successfully applied to analysis of radioactive corrosion products. 21 references, 6 figures, 3 tables.

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

    PubMed Central

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

    2015-01-01

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

  9. GD1b-specific antibodies may bind to complex of GQ1b and GM1, causing ataxia.

    PubMed

    Yuki, Nobuhiro; Fukami, Yuki; Yanaka, Chiaki; Koike, Saiko; Hirata, Koichi

    2014-08-01

    Monospecific IgG antibodies to GD1b ganglioside (GD1b-specific antibodies) have been found in patients with acute ataxic neuropathy and Guillain-Barré syndrome, but the association of the GD1b-specific antibodies with specific neurological conditions has yet to be established. We tested sera from more than 10,000 patients with various neurological disorders, and found six sera, which contained IgG antibodies to GD1b, but not to LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, GT1b and GQ1b. All six patients who carried GD1b-specific antibodies presented with acute onset of ataxia and monophasic course of the illness, of whom five demonstrated cerebellar-like ataxia. Four patients had antecedent symptoms of upper respiratory tract infection. The six patients demonstrated areflexia, and four complained of distal numbness. All the six patients who had the GD1b-specific antibodies carried IgG antibodies to complex of GQ1b/GM1 and GT1a/GM1. GD1b-specific antibodies were significantly absorbed by GQ1b/GM1 and GT1a/GM1 and anti-GQ1b/GM1 and -GT1a/GM1 antibodies were absorbed by GD1b. In conclusion, the GD1b-specific antibodies, which recognizes GQ1b/GM1 or GT1a/GM1 complex, are associated with acute ataxia.

  10. 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.

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

    SciTech Connect

    1995-09-01

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

  12. Crystal Structure and Substrate Specificity of D-Galactose-6-Phosphate Isomerase Complexed with Substrates

    PubMed Central

    Lee, Jung-Kul; Pan, Cheol-Ho

    2013-01-01

    D-Galactose-6-phosphate isomerase from Lactobacillus rhamnosus (LacAB; EC 5.3.1.26), which is encoded by the tagatose-6-phosphate pathway gene cluster (lacABCD), catalyzes the isomerization of D-galactose-6-phosphate to D-tagatose-6-phosphate during lactose catabolism and is used to produce rare sugars as low-calorie natural sweeteners. The crystal structures of LacAB and its complex with D-tagatose-6-phosphate revealed that LacAB is a homotetramer of LacA and LacB subunits, with a structure similar to that of ribose-5-phosphate isomerase (Rpi). Structurally, LacAB belongs to the RpiB/LacAB superfamily, having a Rossmann-like αβα sandwich fold as has been identified in pentose phosphate isomerase and hexose phosphate isomerase. In contrast to other family members, the LacB subunit also has a unique α7 helix in its C-terminus. One active site is distinctly located at the interface between LacA and LacB, whereas two active sites are present in RpiB. In the structure of the product complex, the phosphate group of D-tagatose-6-phosphate is bound to three arginine residues, including Arg-39, producing a different substrate orientation than that in RpiB, where the substrate binds at Asp-43. Due to the proximity of the Arg-134 residue and backbone Cα of the α6 helix in LacA to the last Asp-172 residue of LacB with a hydrogen bond, a six-carbon sugar-phosphate can bind in the larger pocket of LacAB, compared with RpiB. His-96 in the active site is important for ring opening and substrate orientation, and Cys-65 is essential for the isomerization activity of the enzyme. Two rare sugar substrates, D-psicose and D-ribulose, show optimal binding in the LacAB-substrate complex. These findings were supported by the results of LacA activity assays. PMID:24015281

  13. Crystal structure and substrate specificity of D-galactose-6-phosphate isomerase complexed with substrates.

    PubMed

    Jung, Woo-Suk; Singh, Raushan Kumar; Lee, Jung-Kul; Pan, Cheol-Ho

    2013-01-01

    D-Galactose-6-phosphate isomerase from Lactobacillus rhamnosus (LacAB; EC 5.3.1.26), which is encoded by the tagatose-6-phosphate pathway gene cluster (lacABCD), catalyzes the isomerization of D-galactose-6-phosphate to D-tagatose-6-phosphate during lactose catabolism and is used to produce rare sugars as low-calorie natural sweeteners. The crystal structures of LacAB and its complex with D-tagatose-6-phosphate revealed that LacAB is a homotetramer of LacA and LacB subunits, with a structure similar to that of ribose-5-phosphate isomerase (Rpi). Structurally, LacAB belongs to the RpiB/LacAB superfamily, having a Rossmann-like αβα sandwich fold as has been identified in pentose phosphate isomerase and hexose phosphate isomerase. In contrast to other family members, the LacB subunit also has a unique α7 helix in its C-terminus. One active site is distinctly located at the interface between LacA and LacB, whereas two active sites are present in RpiB. In the structure of the product complex, the phosphate group of D-tagatose-6-phosphate is bound to three arginine residues, including Arg-39, producing a different substrate orientation than that in RpiB, where the substrate binds at Asp-43. Due to the proximity of the Arg-134 residue and backbone Cα of the α6 helix in LacA to the last Asp-172 residue of LacB with a hydrogen bond, a six-carbon sugar-phosphate can bind in the larger pocket of LacAB, compared with RpiB. His-96 in the active site is important for ring opening and substrate orientation, and Cys-65 is essential for the isomerization activity of the enzyme. Two rare sugar substrates, D-psicose and D-ribulose, show optimal binding in the LacAB-substrate complex. These findings were supported by the results of LacA activity assays.

  14. Autonomy Software: V&V Challenges and Characteristics

    NASA Technical Reports Server (NTRS)

    Schumann, Johann; Visser, Willem

    2006-01-01

    The successful operation of unmanned air vehicles requires software with a high degree of autonomy. Only if high level functions can be carried out without human control and intervention, complex missions in a changing and potentially unknown environment can be carried out successfully. Autonomy software is highly mission and safety critical: failures, caused by flaws in the software cannot only jeopardize the mission, but could also endanger human life (e.g., a crash of an UAV in a densely populated area). Due to its large size, high complexity, and use of specialized algorithms (planner, constraint-solver, etc.), autonomy software poses specific challenges for its verification, validation, and certification. -- - we have carried out a survey among researchers aid scientists at NASA to study these issues. In this paper, we will present major results of this study, discussing the broad spectrum. of notions and characteristics of autonomy software and its challenges for design and development. A main focus of this survey was to evaluate verification and validation (V&V) issues and challenges, compared to the development of "traditional" safety-critical software. We will discuss important issues in V&V of autonomous software and advanced V&V tools which can help to mitigate software risks. Results of this survey will help to identify and understand safety concerns in autonomy software and will lead to improved strategies for mitigation of these risks.

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

    PubMed Central

    Girish, Vallerinteavide Mavelli; Kini, R. Manjunatha

    2016-01-01

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

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

    PubMed

    Girish, Vallerinteavide Mavelli; Kini, R Manjunatha

    2016-08-25

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

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

    PubMed

    Girish, Vallerinteavide Mavelli; Kini, R Manjunatha

    2016-01-01

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

  18. Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity.

    PubMed

    Malter, M P; Frisch, C; Schoene-Bake, J C; Helmstaedter, C; Wandinger, K P; Stoecker, W; Urbach, H; Surges, R; Elger, C E; Vincent, A V; Bien, C G

    2014-09-01

    In limbic encephalitis (LE) with antibodies (Abs) to the voltage-gated potassium channel complex (VGKC), the Abs are mainly directed to the VGKC-complex proteins, leucine-rich, glioma inactivated 1 protein (LGI1) or contactin-associated protein-like 2 (CASPR-2) or neither. Here, we relate the outcomes of VGKC-LE patients to the presence of Abs to LGI1, CASPR-2 or neither antigen (LGI1/CASPR-2-Ab(-)). Clinical, neuropsychology and MRI data were obtained from patient records for all LE patients from the Bonn Epilepsy Centre positive for VGKC-Abs by radioimmunoprecipitation assay between 2002 and 2011. Eighteen VGKC-LE patients were identified: nine patients (50 %) had LGI1-Abs, three (16 %) had CASPR-2-Abs; and six (33 %) were negative for both LGI1- and CASPR-2-Abs. At first assessment, the groups did not differ clinically or radiologically, but faciobrachial dystonic seizures were only observed in two LGI1-Ab(+) patients. All patients received monthly intravenous methylprednisolone (MP) pulses. At the most recent follow up (median 26 months), thirteen (72 %) were seizure-free, and seizure-freedom rates did not differ between the Ab groups. Hippocampal atrophy had developed in 7/9 LGI1-Ab(+) patients, but in none of the CASPR-2-Ab(+) or LGI/CASPR-2-Ab(-) patients (p = 0.003). While all subgroups improved, memory scores only normalized in six patients (33 %) and LGI1-Ab(+) patients were left with significantly poorer memory than the other two subgroups. Most VGKC-LE patients become seizure-free with pulsed monthly MP, but memory outcome is less favourable. Hippocampal atrophy and poor memory recovery is common in patients with LGI1-Abs and suggests permanent functional damage. More intense immunotherapies could improve outcomes in LGI1-Ab(+)-LE.

  19. Lamina-specific contribution of glutamatergic and GABAergic potentials to hippocampal sharp wave-ripple complexes.

    PubMed

    Schönberger, Jan; Draguhn, Andreas; Both, Martin

    2014-01-01

    The mammalian hippocampus expresses highly organized patterns of neuronal activity which form a neuronal correlate of spatial memories. These memory-encoding neuronal ensembles form on top of different network oscillations which entrain neurons in a state- and experience-dependent manner. The mechanisms underlying activation, timing and selection of participating neurons are incompletely understood. Here we studied the synaptic mechanisms underlying one prominent network pattern called sharp wave-ripple complexes (SPW-R) which are involved in memory consolidation during sleep. We recorded SPW-R with extracellular electrodes along the different layers of area CA1 in mouse hippocampal slices. Contribution of glutamatergic excitation and GABAergic inhibition, respectively, was probed by local application of receptor antagonists into s. radiatum, pyramidale and oriens. Laminar profiles of field potentials show that GABAergic potentials contribute substantially to sharp waves and superimposed ripple oscillations in s. pyramidale. Inhibitory inputs to s. pyramidale and s. oriens are crucial for action potential timing by ripple oscillations, as revealed by multiunit-recordings in the pyramidal cell layer. Glutamatergic afferents, on the other hand, contribute to sharp waves in s. radiatum where they also evoke a fast oscillation at ~200 Hz. Surprisingly, field ripples in s. radiatum are slightly slower than ripples in s. pyramidale, resulting in a systematic shift between dendritic and somatic oscillations. This complex interplay between dendritic excitation and perisomatic inhibition may be responsible for the precise timing of discharge probability during the time course of SPW-R. Together, our data illustrate a complementary role of spatially confined excitatory and inhibitory transmission during highly ordered network patterns in the hippocampus. PMID:25202239

  20. Crystal structures of artocarpin, a Moraceae lectin with mannose specificity, and its complex with methyl-alpha-D-mannose: implications to the generation of carbohydrate specificity.

    PubMed

    Pratap, J V; Jeyaprakash, A Arockia; Rani, P Geetha; Sekar, K; Surolia, A; Vijayan, M

    2002-03-22

    The seeds of jack fruit (Artocarpus integrifolia) contain two tetrameric lectins, jacalin and artocarpin. Jacalin was the first lectin found to exhibit the beta-prism I fold, which is characteristic of the Moraceae plant lectin family. Jacalin contains two polypeptide chains produced by a post-translational proteolysis which has been shown to be crucial for generating its specificity for galactose. Artocarpin is a single chain protein with considerable sequence similarity with jacalin. It, however, exhibits many properties different from those of jacalin. In particular, it is specific to mannose. The structures of two crystal forms, form I and form II, of the native lectin have been determined at 2.4 and 2.5 A resolution, respectively. The structure of the lectin complexed with methyl-alpha-mannose, has also been determined at 2.9 A resolution. The structure is similar to jacalin, although differences exist in details. The crystal structures and detailed modelling studies indicate that the following differences between the carbohydrate binding sites of artocarpin and jacalin are responsible for the difference in the specificities of the two lectins. Firstly, artocarpin does not contain, unlike jacalin, an N terminus generated by post-translational proteolysis. Secondly, there is no aromatic residue in the binding site of artocarpin whereas there are four in that of jacalin. A comparison with similar lectins of known structures or sequences, suggests that, in general, stacking interactions with aromatic residues are important for the binding of galactose while such interactions are usually absent in the carbohydrate binding sites of mannose-specific lectins with the beta-prism I fold.

  1. Library Software: Directory of Microcomputer Software for Libraries.

    ERIC Educational Resources Information Center

    Walton, Robert A.

    The availability of appropriate software for library applications is a continuing problem, and this directory is designed to reduce the frustration of librarians in their search for library software for a microcomputer by providing profiles of software packages designed specifically for libraries. Each profile describes the purpose of the program,…

  2. NASA Software Documentation Standard

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The NASA Software Documentation Standard (hereinafter referred to as "Standard") is designed to support the documentation of all software developed for NASA; its goal is to provide a framework and model for recording the essential information needed throughout the development life cycle and maintenance of a software system. The NASA Software Documentation Standard can be applied to the documentation of all NASA software. The Standard is limited to documentation format and content requirements. It does not mandate specific management, engineering, or assurance standards or techniques. This Standard defines the format and content of documentation for software acquisition, development, and sustaining engineering. Format requirements address where information shall be recorded and content requirements address what information shall be recorded. This Standard provides a framework to allow consistency of documentation across NASA and visibility into the completeness of project documentation. The basic framework consists of four major sections (or volumes). The Management Plan contains all planning and business aspects of a software project, including engineering and assurance planning. The Product Specification contains all technical engineering information, including software requirements and design. The Assurance and Test Procedures contains all technical assurance information, including Test, Quality Assurance (QA), and Verification and Validation (V&V). The Management, Engineering, and Assurance Reports is the library and/or listing of all project reports.

  3. CNEOST Control Software System

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Zhao, Hai-bin; Xia, Yan; Lu, Hao; Li, Bin

    2016-01-01

    In 2013, CNEOST (China Near Earth Object Survey Telescope) adapted its hardware system for the new CCD camera. Based on the new system architecture, the control software is re-designed and implemented. The software system adopts the messaging mechanism based on the WebSocket protocol, and possesses good flexibility and expansibility. The user interface based on the responsive web design has realized the remote observations under both desktop and mobile devices. The stable operation of the software system has greatly enhanced the operation efficiency while reducing the complexity, and has also made a successful attempt for the future system design of telescope and telescope cloud.

  4. CNEOST Control Software System

    NASA Astrophysics Data System (ADS)

    Wang, X.; Zhao, H. B.; Xia, Y.; Lu, H.; Li, B.

    2015-03-01

    In 2013, CNEOST (China Near Earth Object Survey Telescope) adapted its hardware system for the new CCD camera. Based on the new system architecture, the control software is re-designed and implemented. The software system adopts the message passing mechanism via WebSocket protocol, and improves its flexibility, expansibility, and scalability. The user interface with responsive web design realizes the remote operating under both desktop and mobile devices. The stable operating of software system has greatly enhanced the operation efficiency while reducing the complexity, and has also made a successful attempt for the future system design of telescope and telescope cloud.

  5. Characterization of Fus3 localization: active Fus3 localizes in complexes of varying size and specific activity.

    PubMed

    Choi, K Y; Kranz, J E; Mahanty, S K; Park, K S; Elion, E A

    1999-05-01

    The MAP kinase Fus3 regulates many different signal transduction outputs that govern the ability of Saccharomyces cerevisiae haploid cells to mate. Here we characterize Fus3 localization and association with other proteins. By indirect immunofluorescence, Fus3 localizes in punctate spots throughout the cytoplasm and nucleus, with slightly enhanced nuclear localization after pheromone stimulation. This broad distribution is consistent with the critical role Fus3 plays in mating and contrasts that of Kss1, which concentrates in the nucleus and is not required for mating. The majority of Fus3 is soluble and not bound to any one protein; however, a fraction is stably bound to two proteins of approximately 60 and approximately 70 kDa. Based on fractionation and gradient density centrifugation properties, Fus3 exists in a number of complexes, with its activity critically dependent upon association with other proteins. In the presence of alpha factor, nearly all of the active Fus3 localizes in complexes of varying size and specific activity, whereas monomeric Fus3 has little activity. Fus3 has highest specific activity within a 350- to 500-kDa complex previously shown to contain Ste5, Ste11, and Ste7. Ste5 is required for Fus3 to exist in this complex. Upon alpha factor withdrawal, a pool of Fus3 retains activity for more than one cell cycle. Collectively, these results support Ste5's role as a tether and suggest that association of Fus3 in complexes in the presence of pheromone may prevent inactivation in addition to enhancing activation. PMID:10233162

  6. A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.

    PubMed

    Shah, Meera; Su, Dan; Scheliga, Judith S; Pluskal, Tomáš; Boronat, Susanna; Motamedchaboki, Khatereh; Campos, Alexandre Rosa; Qi, Feng; Hidalgo, Elena; Yanagida, Mitsuhiro; Wolf, Dieter A

    2016-08-16

    The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer. PMID:27477275

  7. Distinguishing complex ideas about climate change: knowledge integration vs. specific guidance

    NASA Astrophysics Data System (ADS)

    Vitale, Jonathan M.; McBride, Elizabeth; Linn, Marcia C.

    2016-06-01

    We compared two forms of automated guidance to support students' understanding of climate change in an online inquiry science unit. For specific guidance, we directly communicated ideas that were missing or misrepresented in student responses. For knowledge integration guidance, we provided hints or suggestions to motivate learners to analyze features of their response and seek more information. We guided both student-constructed energy flow diagrams and short essays at total of five times across an approximately week-long curriculum unit. Our results indicate that while specific guidance typically produced larger accuracy gains on responses within the curriculum unit, knowledge integration guidance produced stronger outcomes on a novel essay at posttest. Closer analysis revealed an association between the time spent revisiting a visualization and posttest scores on this summary essay, only for those students in the knowledge integration condition. We discuss how these gains in knowledge integration extend laboratory results related to 'desirable difficulties' and show how autonomous inquiry can be fostered through automated guidance.

  8. Tissue-Specific Genetic Control of Splicing: Implications for the Study of Complex Traits

    PubMed Central

    Cronin, Kenneth D; Maia, Jessica M; Shianna, Kevin V; Gabriel, Willow N; Welsh-Bohmer, Kathleen A; Hulette, Christine M; Denny, Thomas N; Goldstein, David B

    2008-01-01

    Numerous genome-wide screens for polymorphisms that influence gene expression have provided key insights into the genetic control of transcription. Despite this work, the relevance of specific polymorphisms to in vivo expression and splicing remains unclear. We carried out the first genome-wide screen, to our knowledge, for SNPs that associate with alternative splicing and gene expression in human primary cells, evaluating 93 autopsy-collected cortical brain tissue samples with no defined neuropsychiatric condition and 80 peripheral blood mononucleated cell samples collected from living healthy donors. We identified 23 high confidence associations with total expression and 80 with alternative splicing as reflected by expression levels of specific exons. Fewer than 50% of the implicated SNPs however show effects in both tissue types, reflecting strong evidence for distinct genetic control of splicing and expression in the two tissue types. The data generated here also suggest the possibility that splicing effects may be responsible for up to 13 out of 84 reported genome-wide significant associations with human traits. These results emphasize the importance of establishing a database of polymorphisms affecting splicing and expression in primary tissue types and suggest that splicing effects may be of more phenotypic significance than overall gene expression changes. PMID:19222302

  9. Software Reviews.

    ERIC Educational Resources Information Center

    Beezer, Robert A.; And Others

    1988-01-01

    Reviews for three software packages are given. Those packages are: Linear Algebra Computer Companion; Probability and Statistics Demonstrations and Tutorials; and Math Utilities: CURVES, SURFS, AND DIFFS. (PK)

  10. Promoter-Specific Hypomethylation Correlates with IL-1β Overexpression in Tuberous Sclerosis Complex (TSC).

    PubMed

    Fuso, A; Iyer, A M; van Scheppingen, J; Maccarrone, M; Scholl, T; Hainfellner, J A; Feucht, M; Jansen, F E; Spliet, W G; Krsek, P; Zamecnik, J; Mühlebner, A; Aronica, E

    2016-08-01

    In tuberous sclerosis complex (TSC), overexpression of numerous genes associated with inflammation has been observed. Among different proinflammatory cytokines, interleukin-1β (IL-1β) has been shown to be significantly involved in epileptogenesis and maintenance of seizures. Recent evidence indicates that IL-1β gene expression can be regulated by DNA methylation of its promoter. In the present study, we hypothesized that hypomethylation in the promoter region of the IL-1β gene may underlie its overexpression observed in TSC brain tissue. Bisulfite sequencing was used to study the methylation status of the promoter region of the IL-1β gene in TSC and control samples. We identified hypomethylation in the promoter region of the IL-1β gene in TSC samples. IL-1β is overexpressed in tubers, and gene expression is correlated with promoter hypomethylation at CpG and non-CpG sites. Our results provide the first evidence of epigenetic modulation of the IL-1β signaling in TSC. Thus, strategies that target epigenetic alterations could offer new therapeutic avenues to control the persistent activation of interleukin-1β-mediated inflammatory signaling in TSC brain. PMID:27122151

  11. Camouflaging in a complex environment--octopuses use specific features of their surroundings for background matching.

    PubMed

    Josef, Noam; Amodio, Piero; Fiorito, Graziano; Shashar, Nadav

    2012-01-01

    Living under intense predation pressure, octopuses evolved an effective and impressive camouflaging ability that exploits features of their surroundings to enable them to "blend in." To achieve such background matching, an animal may use general resemblance and reproduce characteristics of its entire surroundings, or it may imitate a specific object in its immediate environment. Using image analysis algorithms, we examined correlations between octopuses and their backgrounds. Field experiments show that when camouflaging, Octopus cyanea and O. vulgaris base their body patterns on selected features of nearby objects rather than attempting to match a large field of view. Such an approach enables the octopus to camouflage in partly occluded environments and to solve the problem of differences in appearance as a function of the viewing inclination of the observer.

  12. Camouflaging in a Complex Environment—Octopuses Use Specific Features of Their Surroundings for Background Matching

    PubMed Central

    Josef, Noam; Amodio, Piero; Fiorito, Graziano; Shashar, Nadav

    2012-01-01

    Living under intense predation pressure, octopuses evolved an effective and impressive camouflaging ability that exploits features of their surroundings to enable them to “blend in.” To achieve such background matching, an animal may use general resemblance and reproduce characteristics of its entire surroundings, or it may imitate a specific object in its immediate environment. Using image analysis algorithms, we examined correlations between octopuses and their backgrounds. Field experiments show that when camouflaging, Octopus cyanea and O. vulgaris base their body patterns on selected features of nearby objects rather than attempting to match a large field of view. Such an approach enables the octopus to camouflage in partly occluded environments and to solve the problem of differences in appearance as a function of the viewing inclination of the observer. PMID:22649542

  13. Structure-Specific nuclease activities of Artemis and the Artemis: DNA-PKcs complex

    PubMed Central

    Chang, Howard H.Y.; Lieber, Michael R.

    2016-01-01

    Artemis is a vertebrate nuclease with both endo- and exonuclease activities that acts on a wide range of nucleic acid substrates. It is the main nuclease in the non-homologous DNA end-joining pathway (NHEJ). Not only is Artemis important for the repair of DNA double-strand breaks (DSBs) in NHEJ, it is essential in opening the DNA hairpin intermediates that are formed during V(D)J recombination. Thus, humans with Artemis deficiencies do not have T- or B-lymphocytes and are diagnosed with severe combined immunodeficiency (SCID). While Artemis is the only vertebrate nuclease capable of opening DNA hairpins, it has also been found to act on other DNA substrates that share common structural features. Here, we discuss the key structural features that all Artemis DNA substrates have in common, thus providing a basis for understanding how this structure-specific nuclease recognizes its DNA targets. PMID:27198222

  14. Antigen nature and complexity influence human antibody light chain usage and specificity.

    PubMed

    Smith, Kenneth; Shah, Hemangi; Muther, Jennifer J; Duke, Angie L; Haley, Kathleen; James, Judith A

    2016-05-27

    Human antibodies consist of a heavy chain and one of two possible light chains, kappa (κ) or lambda (λ). Here we tested how these two possible light chains influence the overall antibody response to polysaccharide and protein antigens by measuring light chain usage in human monoclonal antibodies from antibody secreting cells obtained following vaccination with Pneumovax23. Remarkably, we found that individuals displayed restricted light chain usage to certain serotypes and that lambda antibodies have different specificities and modes of cross-reactivity than kappa antibodies. Thus, at both the monoclonal (7 kappa, no lambda) and serum levels (145μg/mL kappa, 2.82μg/mL lambda), antibodies to cell wall polysaccharide were nearly always kappa. The pneumococcal reference serum 007sp was analyzed for light chain usage to 12 pneumococcal serotypes for which it is well characterized. Similar to results at the monoclonal level, certain serotypes tended to favor one of the light chains (14 and 19A, lambda; 6A and 23F, kappa). We also explored differences in light chain usage at the serum level to a variety of antigens. We examined serum antibodies to diphtheria toxin mutant CRM197 and Epstein-Barr virus protein EBNA-1. These responses tended to be kappa dominant (average kappa-to-lambda ratios of 4.52 and 9.72 respectively). Responses to the influenza vaccine were more balanced with kappa-to-lambda ratio averages having slight strain variations: seasonal H1N1, 1.1; H3N2, 0.96; B, 0.91. We conclude that antigens with limited epitopes tend to produce antibodies with restricted light chain usage and that in most individuals, antibodies with lambda light chains have specificities different and complementary to kappa-containing antibodies.

  15. Antigen nature and complexity influence human antibody light chain usage and specificity.

    PubMed

    Smith, Kenneth; Shah, Hemangi; Muther, Jennifer J; Duke, Angie L; Haley, Kathleen; James, Judith A

    2016-05-27

    Human antibodies consist of a heavy chain and one of two possible light chains, kappa (κ) or lambda (λ). Here we tested how these two possible light chains influence the overall antibody response to polysaccharide and protein antigens by measuring light chain usage in human monoclonal antibodies from antibody secreting cells obtained following vaccination with Pneumovax23. Remarkably, we found that individuals displayed restricted light chain usage to certain serotypes and that lambda antibodies have different specificities and modes of cross-reactivity than kappa antibodies. Thus, at both the monoclonal (7 kappa, no lambda) and serum levels (145μg/mL kappa, 2.82μg/mL lambda), antibodies to cell wall polysaccharide were nearly always kappa. The pneumococcal reference serum 007sp was analyzed for light chain usage to 12 pneumococcal serotypes for which it is well characterized. Similar to results at the monoclonal level, certain serotypes tended to favor one of the light chains (14 and 19A, lambda; 6A and 23F, kappa). We also explored differences in light chain usage at the serum level to a variety of antigens. We examined serum antibodies to diphtheria toxin mutant CRM197 and Epstein-Barr virus protein EBNA-1. These responses tended to be kappa dominant (average kappa-to-lambda ratios of 4.52 and 9.72 respectively). Responses to the influenza vaccine were more balanced with kappa-to-lambda ratio averages having slight strain variations: seasonal H1N1, 1.1; H3N2, 0.96; B, 0.91. We conclude that antigens with limited epitopes tend to produce antibodies with restricted light chain usage and that in most individuals, antibodies with lambda light chains have specificities different and complementary to kappa-containing antibodies. PMID:27113164

  16. Detection of Serotype-Specific Antibodies to the Four Dengue Viruses Using an Immune Complex Binding (ICB) ELISA

    PubMed Central

    Emmerich, Petra; Mika, Angela; Schmitz, Herbert

    2013-01-01

    Background Dengue virus (DENV) infections are preferentially diagnosed by detection of specific IgM antibodies, DENV NS1 antigen assays or by amplification of viral RNA in serum samples of the patients. The type-specific immunity to the four worldwide circulating DENV serotypes can be determined by neutralization assays. An alternative to the complicated neutralization assays would be helpful to study the serotype-specific immune response in people in DENV hyperendemic areas but also in subjects upon DENV vaccination. Methods In consecutive samples of patients with DENV-1- 4 infection type-specific antibodies were detected using an immune complex binding (ICB) ELISA. During incubation of serum samples and enzyme- labeled recombinant envelope domain III (EDIII) antigens immune complexes (ICs) are formed, which are simultaneously bound to a solid phase coated with an Fc–receptor (CD32). After a single washing procedure the bound labeled ICs can be determined. To further improve type-specific reactions high concentrations of competing heterologous unlabeled ED III proteins were added to the labeled antigens. Results Follow-up serum samples of 64 patients with RT-PCR confirmed primary DENV-1, -2, -3 or -4 infections were tested against four enzyme-labeled recombinant DENV EDIII antigens. Antibodies to the EDIII antigens were found in 55 patients (sensitivity 86%). A complete agreement between the serotype detected by PCR in early samples and the serotype-specific antibody in later samples was found. Type-specific anti-EDIII antibodies were first detected 9–20 days after onset of the disease. In 21% of the samples collected from people in Vietnam secondary infections with antibodies to two serotypes could be identified. Conclusions The data obtained with the ICB-ELISA show that after primary DENV infection the corresponding type-specific antibodies are detected in almost all samples collected at least two weeks after onset of the disease. The method will be of value

  17. Specificity of Campylobacter jejuni Adhesin PEB3 for Phosphates and Structural Differences among Its Ligand Complexes

    SciTech Connect

    Min, Tongpil; Vedadi, Masoud; Watson, David C.; Wasney, Gregory A.; Munger, Christine; Cygler, Miroslaw; Matte, Allan; Young, N. Martin

    2009-04-22

    PEB3 is a glycoprotein adhesin from Campylobacter jejuni whose structure suggested a role in transport. We have investigated potential ligands for PEB3 and characterized their binding properties using biophysical methods in solution and by X-ray crystallography. A thermal aggregation assay of PEB3 with a library of physiological compounds identified three possible ligands [3-phosphoglycerate (3-PG), phosphoenolpyruvate (PEP), and aconitate], which stabilized wild-type PEB3 but did not stabilize either a PEB3 form containing two mutations at the ligand-binding site, T138A/S139A, or a second PEB3 mutant, K135E, at a site {approx}14 {angstrom} away. Fluorescence titration experiments and cocrystal structures with various ligands were used to characterize the binding of 3-PG, PEP, and phosphate to PEB3. Further, a C. jejuni growth experiment in minimal medium supplemented with 3-PG showed that this molecule enhances the growth of wild-type C. jejuni, but not of the PEB3 mutants. Crystallographic analysis of PEB3 complexes revealed that the Ser171-Gln180 region in the presence of 3-PG or other phosphates is helical and similar to those of other transport proteins, but it is nonhelical when citrate is bound. The K135E mutation resulted in expression of a more highly glycosylated form of PEB3 in vivo, and its crystal structure showed the conformation of the first two residues of the glycan. On the basis of our findings, we suggest that PEB3 is a transport protein that may function in utilization of 3-PG or other phosphate-containing molecules from the host.

  18. Pan-Specific Prediction of Peptide-MHC Class I Complex Stability, a Correlate of T Cell Immunogenicity.

    PubMed

    Rasmussen, Michael; Fenoy, Emilio; Harndahl, Mikkel; Kristensen, Anne Bregnballe; Nielsen, Ida Kallehauge; Nielsen, Morten; Buus, Søren

    2016-08-15

    Binding of peptides to MHC class I (MHC-I) molecules is the most selective event in the processing and presentation of Ags to CTL, and insights into the mechanisms that govern peptide-MHC-I binding should facilitate our understanding of CTL biology. Peptide-MHC-I interactions have traditionally been quantified by the strength of the interaction, that is, the binding affinity, yet it has been shown that the stability of the peptide-MHC-I complex is a better correlate of immunogenicity compared with binding affinity. In this study, we have experimentally analyzed peptide-MHC-I complex stability of a large panel of human MHC-I allotypes and generated a body of data sufficient to develop a neural network-based pan-specific predictor of peptide-MHC-I complex stability. Integrating the neural network predictors of peptide-MHC-I complex stability with state-of-the-art predictors of peptide-MHC-I binding is shown to significantly improve the prediction of CTL epitopes. The method is publicly available at http://www.cbs.dtu.dk/services/NetMHCstabpan. PMID:27402703

  19. Crystal structure of a 4-thiouridine synthetase–RNA complex reveals specificity of tRNA U8 modification

    PubMed Central

    Neumann, Piotr; Naumann, Peter-Thomas; Erwin, Whitney M.; Lauhon, Charles T.; Ficner, Ralf

    2014-01-01

    In prokaryotes and archaea transfer ribonucleic acid (tRNA) stability as well as cellular UV protection relies on the post-transcriptional modification of uracil at position 8 (U8) of tRNAs by the 4-thiouridine synthetase ThiI. Here, we report three crystal structures of ThiI from Thermotoga maritima in complex with a truncated tRNA. The RNA is mainly bound by the N-terminal ferredoxin-like domain (NFLD) and the THUMP domain of one subunit within the ThiI homo-dimer thereby positioning the U8 close to the catalytic center in the pyrophosphatase domain of the other subunit. The recognition of the 3’-CCA end by the THUMP domain yields a molecular ruler defining the specificity for U8 thiolation. This first structure of a THUMP/NFLD-RNA complex might serve as paradigm for the RNA recognition by THUMP domains of other proteins. The ternary ThiI–RNA–ATP complex shows no significant structural changes due to adenosine triphosphate (ATP) binding, but two different states of active site loops are observed independent of the nucleotide loading state. Thereby conformational changes of the active site are coupled with conformational changes of the bound RNA. The ThiI–RNA complex structures indicate that full-length tRNA has to adopt a non-canonical conformation upon binding to ThiI. PMID:24705700

  20. Domain–domain interactions in full-length p53 and a specific DNA complex probed by methyl NMR spectroscopy

    PubMed Central

    Bista, Michal; Freund, Stefan M.; Fersht, Alan R.

    2012-01-01

    The tumor suppressor p53 is a homotetramer of 4 × 393 residues. Its core domain and tetramerization domain are linked and flanked by intrinsically disordered sequences, which hinder its full structural characterization. There is an outstanding problem of the state of the tetramerization domain. Structural studies on the isolated tetramerization domain show it is in a folded tetrameric conformation, but there are conflicting models from electron microscopy of the full-length protein, one of which proposes that the domain is not tetramerically folded and the tetrameric protein is stabilized by interactions between the N and C termini. Here, we present methyl-transverse relaxation optimized NMR spectroscopy (methyl-TROSY) investigations on the full-length and separate domains of the protein with its methionine residues enriched with 13C to probe its quaternary structure. We obtained high-quality spectra of both the full-length tetrameric p53 and its DNA complex, observing the environment at 11 specific methyl sites. The tetramerization domain was as tetramerically folded in the full-length constructs as in the isolated domain. The N and C termini were intrinsically disordered in both the full-length protein and its complex with a 20-residue specific DNA sequence. Additionally, we detected in the interface of the core (DNA-binding) and N-terminal parts of the protein a slow conformational exchange process that was modulated by specific recognition of DNA, indicating allosteric processes. PMID:22972749

  1. Promoter Complexity and Tissue-Specific Expression of Stress Response Components in Mytilus galloprovincialis, a Sessile Marine Invertebrate Species

    PubMed Central

    Pantzartzi, Chrysa; Drosopoulou, Elena; Yiangou, Minas; Drozdov, Ignat; Tsoka, Sophia; Ouzounis, Christos A.; Scouras, Zacharias G.

    2010-01-01

    The mechanisms of stress tolerance in sessile animals, such as molluscs, can offer fundamental insights into the adaptation of organisms for a wide range of environmental challenges. One of the best studied processes at the molecular level relevant to stress tolerance is the heat shock response in the genus Mytilus. We focus on the upstream region of Mytilus galloprovincialis Hsp90 genes and their structural and functional associations, using comparative genomics and network inference. Sequence comparison of this region provides novel evidence that the transcription of Hsp90 is regulated via a dense region of transcription factor binding sites, also containing a region with similarity to the Gamera family of LINE-like repetitive sequences and a genus-specific element of unknown function. Furthermore, we infer a set of gene networks from tissue-specific expression data, and specifically extract an Hsp class-associated network, with 174 genes and 2,226 associations, exhibiting a complex pattern of expression across multiple tissue types. Our results (i) suggest that the heat shock response in the genus Mytilus is regulated by an unexpectedly complex upstream region, and (ii) provide new directions for the use of the heat shock process as a biosensor system for environmental monitoring. PMID:20628614

  2. Software Bridge

    NASA Technical Reports Server (NTRS)

    1995-01-01

    I-Bridge is a commercial version of software developed by I-Kinetics under a NASA Small Business Innovation Research (SBIR) contract. The software allows users of Windows applications to gain quick, easy access to databases, programs and files on UNIX services. Information goes directly onto spreadsheets and other applications; users need not manually locate, transfer and convert data.

  3. Software Reviews.

    ERIC Educational Resources Information Center

    Miller, Anne, Ed.; Radziemski, Cathy, Ed.

    1988-01-01

    Reviews two software packages for the Macintosh series. "Course Builder 2.0," a courseware authoring system, allows the user to create programs which stand alone and may be used independently in the classroom. "World Builder," an artificial intelligence software package, allows creative thinking, problem-solving, and decision-making. (YP)

  4. Software Reviews.

    ERIC Educational Resources Information Center

    Bitter, Gary G., Ed.

    1990-01-01

    Reviews three computer software: (1) "Elastic Lines: The Electronic Geoboard" on elementary geometry; (2) "Wildlife Adventures: Whales" on environmental science; and (3) "What Do You Do with a Broken Calculator?" on computation and problem solving. Summarizes the descriptions, strengths and weaknesses, and applications of each software. (YP)

  5. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Stephen

    1988-01-01

    Presents reviews of six computer software programs for teaching science. Provides the publisher, grade level, cost, and descriptions of software, including: (1) "Recycling Logic"; (2) "Introduction to Biochemistry"; (3) "Food for Thought"; (4) "Watts in a Home"; (5) "Geology in Action"; and (6) "Biomes." All are for Apple series microcomputers.…

  6. Software Reviews.

    ERIC Educational Resources Information Center

    Science and Children, 1988

    1988-01-01

    Reviews six software packages for the Apple II family. Programs reviewed include "Science Courseware: Earth Science Series"; "Heat and Light"; "In Search of Space: Introduction to Model Rocketry"; "Drug Education Series: Drugs--Their Effects on You'"; "Uncertainties and Measurement"; and "Software Films: Learning about Science Series," which…

  7. NASA software documentation standard software engineering program

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The NASA Software Documentation Standard (hereinafter referred to as Standard) can be applied to the documentation of all NASA software. This Standard is limited to documentation format and content requirements. It does not mandate specific management, engineering, or assurance standards or techniques. This Standard defines the format and content of documentation for software acquisition, development, and sustaining engineering. Format requirements address where information shall be recorded and content requirements address what information shall be recorded. This Standard provides a framework to allow consistency of documentation across NASA and visibility into the completeness of project documentation. This basic framework consists of four major sections (or volumes). The Management Plan contains all planning and business aspects of a software project, including engineering and assurance planning. The Product Specification contains all technical engineering information, including software requirements and design. The Assurance and Test Procedures contains all technical assurance information, including Test, Quality Assurance (QA), and Verification and Validation (V&V). The Management, Engineering, and Assurance Reports is the library and/or listing of all project reports.

  8. Practical Issues with Formal Specifications

    NASA Astrophysics Data System (ADS)

    Altenhofen, Michael; Brucker, Achim D.

    Many software companies still seem to be reluctant to use formal specifications in their development processes. Nevertheless, the trend towards implementing critical business applications in distributed environments makes such applications an attractive target for formal methods. Additionally, the rising complexity also increases the willingness of the development teams to apply formal techniques.

  9. Software Fault Tolerance: A Tutorial

    NASA Technical Reports Server (NTRS)

    Torres-Pomales, Wilfredo

    2000-01-01

    Because of our present inability to produce error-free software, software fault tolerance is and will continue to be an important consideration in software systems. The root cause of software design errors is the complexity of the systems. Compounding the problems in building correct software is the difficulty in assessing the correctness of software for highly complex systems. After a brief overview of the software development processes, we note how hard-to-detect design faults are likely to be introduced during development and how software faults tend to be state-dependent and activated by particular input sequences. Although component reliability is an important quality measure for system level analysis, software reliability is hard to characterize and the use of post-verification reliability estimates remains a controversial issue. For some applications software safety is more important than reliability, and fault tolerance techniques used in those applications are aimed at preventing catastrophes. Single version software fault tolerance techniques discussed include system structuring and closure, atomic actions, inline fault detection, exception handling, and others. Multiversion techniques are based on the assumption that software built differently should fail differently and thus, if one of the redundant versions fails, it is expected that at least one of the other versions will provide an acceptable output. Recovery blocks, N-version programming, and other multiversion techniques are reviewed.

  10. Left atrial electrophysiologic feature specific for the genesis of complex fractionated atrial electrogram during atrial fibrillation.

    PubMed

    Hoshiyama, Tadashi; Yamabe, Hiroshige; Koyama, Junjiroh; Kanazawa, Hisanori; Ogawa, Hisao

    2016-05-01

    Complex fractionated atrial electrogram (CFAE) has been suggested to contribute to the maintenance of atrial fibrillation (AF). However, electrophysiologic characteristics of the left atrial myocardium responsible for genesis of CFAE have not been clarified. Non-contact mapping of the left atrium was performed at 37 AF onset episodes in 24 AF patients. Electrogram amplitude, width, and conduction velocity were measured during sinus rhythm, premature atrial contraction (PAC) with long- (L-PAC), short- (S-PAC) and very short-coupling intervals (VS-PAC). These parameters were compared between CFAE and non-CFAE regions. Unipolar electrogram amplitude was higher in CFAE than non-CFAE during sinus rhythm, L-, S- and VS-PAC (1.82 ± 0.73 vs. 1.13 ± 0.38, p < 0.001; 1.44 ± 0.54 vs. 0.92 ± 0.35, p < 0.001; 1.09 ± 0.40 vs. 0.70 ± 0.27, p < 0.001; 0.76 ± 0.30 vs. 0.53 ± 0.25 mV, p < 0.001). Laplacian bipolar electrogram amplitude was also higher in CFAE than non-CFAE during sinus rhythm, L-, S- and VS-PAC. Unipolar electrogram width was similar in CFAE and non-CFAE. Laplacian bipolar electrogram width was wider in CFAE than non-CFAE during L-, S- and VS-PAC (85.5 ± 6.8 vs. 79.6 ± 4.5, p < 0.001; 96.1 ± 9.7 vs. 84.5 ± 5.9, p < 0.001; 122.4 ± 16.0 vs. 99.6 ± 9.6 ms, p < 0.001), but not during sinus rhythm. The conduction velocity was slower in CFAE during sinus rhythm, L-, S- and VS-PAC than non-CFAE (1.7 ± 0.3 vs. 2.4 ± 0.4, p < 0.001; 1.4 ± 0.3 vs. 2.0 ± 0.5, p < 0.001; 1.2 ± 0.3 vs. 1.7 ± 0.5, p < 0.001; and 0.9 ± 0.3 vs. 1.4 ± 0.4 m/s, p < 0.001). CFAE was generated in the high amplitude atrial myocardium with slow and non-uniform conduction properties which were pronounced associated with premature activation, suggesting that heterogeneous conduction produced in high amplitude region contributes to the genesis of CFAE.

  11. Structure of 5-hydroxymethylcytosine-specific restriction enzyme, AbaSI, in complex with DNA

    SciTech Connect

    Horton, John R.; Borgaro, Janine G.; Griggs, Rose M.; Quimby, Aine; Guan, Shengxi; Zhang, Xing; Wilson, Geoffrey G.; Zheng, Yu; Zhu, Zhenyu; Cheng, Xiaodong

    2014-07-03

    AbaSI, a member of the PvuRts1I-family of modification-dependent restriction endonucleases, cleaves DNA containing 5-hydroxymethylctosine (5hmC) and glucosylated 5hmC (g5hmC), but not DNA containing unmodified cytosine. AbaSI has been used as a tool for mapping the genomic locations of 5hmC, an important epigenetic modification in the DNA of higher organisms. Here we report the crystal structures of AbaSI in the presence and absence of DNA. These structures provide considerable, although incomplete, insight into how this enzyme acts. AbaSI appears to be mainly a homodimer in solution, but interacts with DNA in our structures as a homotetramer. Each AbaSI subunit comprises an N-terminal, Vsr-like, cleavage domain containing a single catalytic site, and a C-terminal, SRA-like, 5hmC-binding domain. Two N-terminal helices mediate most of the homodimer interface. Dimerization brings together the two catalytic sites required for double-strand cleavage, and separates the 5hmC binding-domains by ~ 70 Å, consistent with the known activity of AbaSI which cleaves DNA optimally between symmetrically modified cytosines ~ 22 bp apart. The eukaryotic SET and RING-associated (SRA) domains bind to DNA containing 5-methylcytosine (5mC) in the hemi-methylated CpG sequence. They make contacts in both the major and minor DNA grooves, and flip the modified cytosine out of the helix into a conserved binding pocket. In contrast, the SRA-like domain of AbaSI, which has no sequence specificity, contacts only the minor DNA groove, and in our current structures the 5hmC remains intra-helical. A conserved, binding pocket is nevertheless present in this domain, suitable for accommodating 5hmC and g5hmC. We consider it likely, therefore, that base-flipping is part of the recognition and cleavage mechanism of AbaSI, but that our structures represent an earlier, pre-flipped stage, prior to actual recognition.

  12. Biological evaluation of morin and its new oxovanadium(IV) complex as antioxidant and specific anti-cancer agents.

    PubMed

    Naso, Luciana G; Lezama, Luis; Rojo, Teófilo; Etcheverry, Susana B; Valcarcel, María; Roura, Meritxell; Salado, Clarisa; Ferrer, Evelina G; Williams, Patricia A M

    2013-11-25

    It is known that flavonoids possess, among others, antioxidant and antitumoral properties that depend on their molecular structure. The central objective if this study was to investigate the potential antioxidant and antiproliferative properties of the flavonol morin and its new oxovanadium(IV) complex (VOmor) that was synthesized in order to modify the morin chemical structure. Two osteoblast (UMR106 and MC3T3E1), two breast tumor (T47D and SKBR3) and breast epithelial cell lines in culture were used for the antitumoral determinations. Additionally, a comparative study of their antioxidant capacities using different radicals (DPPH, ABTS(+), OH, O2(-), ROO) was performed. Selected mechanisms of action were studied using the breast cancer cell lines. Results obtained show that morin and its complex behaved as good antioxidant agents for some of the radicals and that the complexation improved the behavior with respect to OH and O2(-) radicals being morin more effective as ROO scavenger. A considerable variation in sensitivity was observed in the breast cancer cells but non-specificity was found for the treatment of osteosarcoma. Moreover, the compounds did not affect the normal proliferation of the breast epithelial mammal cells. The mechanistic studies demonstrated that the complex did not generate reactive oxygen species in the cells (confirming the in vitro studies) and did not produce any damage of DNA. The plasmatic membrane was observed to be damaged only in the SKBR3 cell line. In contrast, the perturbation of the mitochondrial membrane potential and the activation of caspase 3/7 for the breast tumor cells revealed an apoptotic cell death process. All these results collectively suggested that VOmor complex could serve as promising pharmacologically active substance against breast cancer treatment.

  13. NASA's Software Safety Standard

    NASA Technical Reports Server (NTRS)

    Ramsay, Christopher M.

    2007-01-01

    NASA relies more and more on software to control, monitor, and verify its safety critical systems, facilities and operations. Since the 1960's there has hardly been a spacecraft launched that does not have a computer on board that will provide command and control services. There have been recent incidents where software has played a role in high-profile mission failures and hazardous incidents. For example, the Mars Orbiter, Mars Polar Lander, the DART (Demonstration of Autonomous Rendezvous Technology), and MER (Mars Exploration Rover) Spirit anomalies were all caused or contributed to by software. The Mission Control Centers for the Shuttle, ISS, and unmanned programs are highly dependant on software for data displays, analysis, and mission planning. Despite this growing dependence on software control and monitoring, there has been little to no consistent application of software safety practices and methodology to NASA's projects with safety critical software. Meanwhile, academia and private industry have been stepping forward with procedures and standards for safety critical systems and software, for example Dr. Nancy Leveson's book Safeware: System Safety and Computers. The NASA Software Safety Standard, originally published in 1997, was widely ignored due to its complexity and poor organization. It also focused on concepts rather than definite procedural requirements organized around a software project lifecycle. Led by NASA Headquarters Office of Safety and Mission Assurance, the NASA Software Safety Standard has recently undergone a significant update. This new standard provides the procedures and guidelines for evaluating a project for safety criticality and then lays out the minimum project lifecycle requirements to assure the software is created, operated, and maintained in the safest possible manner. This update of the standard clearly delineates the minimum set of software safety requirements for a project without detailing the implementation for those

  14. Writing testable software requirements

    SciTech Connect

    Knirk, D.

    1997-11-01

    This tutorial identifies common problems in analyzing requirements in the problem and constructing a written specification of what the software is to do. It deals with two main problem areas: identifying and describing problem requirements, and analyzing and describing behavior specifications.

  15. The Software Architecture of the Upgraded ESA DRAMA Software Suite

    NASA Astrophysics Data System (ADS)

    Kebschull, Christopher; Flegel, Sven; Gelhaus, Johannes; Mockel, Marek; Braun, Vitali; Radtke, Jonas; Wiedemann, Carsten; Vorsmann, Peter; Sanchez-Ortiz, Noelia; Krag, Holger

    2013-08-01

    In the beginnings of man's space flight activities there was the belief that space is so big that everybody could use it without any repercussions. However during the last six decades the increasing use of Earth's orbits has lead to a rapid growth in the space debris environment, which has a big influence on current and future space missions. For this reason ESA issued the "Requirements on Space Debris Mitigation for ESA Projects" [1] in 2008, which apply to all ESA missions henceforth. The DRAMA (Debris Risk Assessment and Mitigation Analysis) software suite had been developed to support the planning of space missions to comply with these requirements. During the last year the DRAMA software suite has been upgraded under ESA contract by TUBS and DEIMOS to include additional tools and increase the performance of existing ones. This paper describes the overall software architecture of the ESA DRAMA software suite. Specifically the new graphical user interface, which manages the five main tools ARES (Assessment of Risk Event Statistics), MIDAS (MASTER-based Impact Flux and Damage Assessment Software), OSCAR (Orbital Spacecraft Active Removal), CROC (Cross Section of Complex Bodies) and SARA (Re-entry Survival and Risk Analysis) is being discussed. The advancements are highlighted as well as the challenges that arise from the integration of the five tool interfaces. A framework had been developed at the ILR and was used for MASTER-2009 and PROOF-2009. The Java based GUI framework, enables the cross-platform deployment, and its underlying model-view-presenter (MVP) software pattern, meet strict design requirements necessary to ensure a robust and reliable method of operation in an environment where the GUI is separated from the processing back-end. While the GUI framework evolved with each project, allowing an increasing degree of integration of services like validators for input fields, it has also increased in complexity. The paper will conclude with an outlook on

  16. LIGA Scanner Control Software

    1999-02-01

    The LIGA Scanner Software is a graphical user interface package that facilitates controlling the scanning operation of x-rays from a synchrotron and sample manipulation for making LIGA parts. The process requires scanning of the LIGA mask and the PMMA resist through a stationary x-ray beam to provide an evenly distributed x-ray exposure over the wafer. This software package has been written specifically to interface with Aerotech motor controllers.

  17. Comparison of peptide-major histocompatibility complex tetramers and dextramers for the identification of antigen-specific T cells.

    PubMed

    Dolton, G; Lissina, A; Skowera, A; Ladell, K; Tungatt, K; Jones, E; Kronenberg-Versteeg, D; Akpovwa, H; Pentier, J M; Holland, C J; Godkin, A J; Cole, D K; Neller, M A; Miles, J J; Price, D A; Peakman, M; Sewell, A K

    2014-07-01

    Fluorochrome-conjugated peptide-major histocompatibility complex (pMHC) multimers are widely used for flow cytometric visualization of antigen-specific T cells. The most common multimers, streptavidin-biotin-based 'tetramers', can be manufactured readily in the laboratory. Unfortunately, there are large differences between the threshold of T cell receptor (TCR) affinity required to capture pMHC tetramers from solution and that which is required for T cell activation. This disparity means that tetramers sometimes fail to stain antigen-specific T cells within a sample, an issue that is particularly problematic when staining tumour-specific, autoimmune or MHC class II-restricted T cells, which often display TCRs of low affinity for pMHC. Here, we compared optimized staining with tetramers and dextramers (dextran-based multimers), with the latter carrying greater numbers of both pMHC and fluorochrome per molecule. Most notably, we find that: (i) dextramers stain more brightly than tetramers; (ii) dextramers outperform tetramers when TCR-pMHC affinity is low; (iii) dextramers outperform tetramers with pMHC class II reagents where there is an absence of co-receptor stabilization; and (iv) dextramer sensitivity is enhanced further by specific protein kinase inhibition. Dextramers are compatible with current state-of-the-art flow cytometry platforms and will probably find particular utility in the fields of autoimmunity and cancer immunology. PMID:24673376

  18. Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B.

    PubMed

    Agop-Nersesian, Carolina; Egarter, Saskia; Langsley, Gordon; Foth, Bernardo J; Ferguson, David J P; Meissner, Markus

    2010-01-01

    Apicomplexan parasites belong to a recently recognised group of protozoa referred to as Alveolata. These protists contain membranous sacs (alveoli) beneath the plasma membrane, termed the Inner Membrane Complex (IMC) in the case of Apicomplexa. During parasite replication the IMC is formed de novo within the mother cell in a process described as internal budding. We hypothesized that an alveolate specific factor is involved in the specific transport of vesicles from the Golgi to the IMC and identified the small GTPase Rab11B as an alveolate specific Rab-GTPase that localises to the growing end of the IMC during replication of Toxoplasma gondii. Conditional interference with Rab11B function leads to a profound defect in IMC biogenesis, indicating that Rab11B is required for the transport of Golgi derived vesicles to the nascent IMC of the daughter cell. Curiously, a block in IMC biogenesis did not affect formation of sub-pellicular microtubules, indicating that IMC biogenesis and formation of sub-pellicular microtubules is not mechanistically linked. We propose a model where Rab11B specifically transports vesicles derived from the Golgi to the immature IMC of the growing daughter parasites.

  19. Annotated bibliography of software engineering laboratory literature

    NASA Technical Reports Server (NTRS)

    Groves, Paula; Valett, Jon

    1990-01-01

    An annotated bibliography of technical papers, documents, and memorandums produced by or related to the Software Engineering Laboratory is given. More than 100 publications are summarized. These publications cover many areas of software engineering and range from research reports to software documentation. This document has been updated and reorganized substantially since the original version (SEL-82-006, November 1982). All materials have been grouped into eight general subject areas for easy reference: the Software Engineering Laboratory; the Software Engineering Laboratory-software development documents; software tools; software models; software measurement; technology evaluations; Ada technology; and data collection. Subject and author indexes further classify these documents by specific topic and individual author.

  20. Annotated bibliography of Software Engineering Laboratory literature

    NASA Technical Reports Server (NTRS)

    Morusiewicz, Linda; Valett, Jon D.

    1991-01-01

    An annotated bibliography of technical papers, documents, and memorandums produced by or related to the Software Engineering Laboratory is given. More than 100 publications are summarized. These publications cover many areas of software engineering and range from research reports to software documentation. All materials have been grouped into eight general subject areas for easy reference: The Software Engineering Laboratory; The Software Engineering Laboratory: Software Development Documents; Software Tools; Software Models; Software Measurement; Technology Evaluations; Ada Technology; and Data Collection. Subject and author indexes further classify these documents by specific topic and individual author.

  1. Software Smarts

    NASA Technical Reports Server (NTRS)

    1998-01-01

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

  2. Software testing

    NASA Astrophysics Data System (ADS)

    Price-Whelan, Adrian M.

    2016-01-01

    Now more than ever, scientific results are dependent on sophisticated software and analysis. Why should we trust code written by others? How do you ensure your own code produces sensible results? How do you make sure it continues to do so as you update, modify, and add functionality? Software testing is an integral part of code validation and writing tests should be a requirement for any software project. I will talk about Python-based tools that make managing and running tests much easier and explore some statistics for projects hosted on GitHub that contain tests.

  3. In Vitro MRV-based Hemodynamic Study of Complex Helical Flow in a Patient-specific Jugular Model

    NASA Astrophysics Data System (ADS)

    Kefayati, Sarah; Acevedo-Bolton, Gabriel; Haraldsson, Henrik; Saloner, David

    2014-11-01

    Neurointerventional Radiologists are frequently requested to evaluate the venous side of the intracranial circulation for a variety of conditions including: Chronic Cerebrospinal Venous Insufficiency thought to play a role in the development of multiple sclerosis; sigmoid sinus diverticulum which has been linked to the presence of pulsatile tinnitus; and jugular vein distension which is related to cardiac dysfunction. Most approaches to evaluating these conditions rely on structural assessment or two dimensional flow analyses. This study was designed to investigate the highly complex jugular flow conditions using magnetic resonance velocimetry (MRV). A jugular phantom was fabricated based on the geometry of the dominant jugular in a tinnitus patient. Volumetric three-component time-resolved velocity fields were obtained using 4D PC-MRI -with the protocol enabling turbulence acquisition- and the patient-specific pulsatile waveform. Flow was highly complex exhibiting regions of jet, high swirling strength, and strong helical pattern with the core originating from the focal point of the jugular bulb. Specifically, flow was analyzed for helicity and the level of turbulence kinetic energy elevated in the core of helix and distally, in the post-narrowing region.

  4. The nucleoporin Seh1 forms a complex with Mio and serves an essential tissue-specific function in Drosophila oogenesis.

    PubMed

    Senger, Stefania; Csokmay, John; Akbar, Tanveer; Tanveer, Akbar; Jones, Takako Iida; Sengupta, Prabuddha; Lilly, Mary A

    2011-05-01

    The nuclear pore complex (NPC) mediates the transport of macromolecules between the nucleus and cytoplasm. Recent evidence indicates that structural nucleoporins, the building blocks of the NPC, have a variety of unanticipated cellular functions. Here, we report an unexpected tissue-specific requirement for the structural nucleoporin Seh1 during Drosophila oogenesis. Seh1 is a component of the Nup107-160 complex, the major structural subcomplex of the NPC. We demonstrate that Seh1 associates with the product of the missing oocyte (mio) gene. In Drosophila, mio regulates nuclear architecture and meiotic progression in early ovarian cysts. Like mio, seh1 has a crucial germline function during oogenesis. In both mio and seh1 mutant ovaries, a fraction of oocytes fail to maintain the meiotic cycle and develop as pseudo-nurse cells. Moreover, the accumulation of Mio protein is greatly diminished in the seh1 mutant background. Surprisingly, our characterization of a seh1 null allele indicates that, although required in the female germline, seh1 is dispensable for the development of somatic tissues. Our work represents the first examination of seh1 function within the context of a multicellular organism. In summary, our studies demonstrate that Mio is a novel interacting partner of the conserved nucleoporin Seh1 and add to the growing body of evidence that structural nucleoporins can have novel tissue-specific roles. PMID:21521741

  5. Structure of a PE–PPE–EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion

    PubMed Central

    Ekiert, Damian C.; Cox, Jeffery S.

    2014-01-01

    Nearly 10% of the coding capacity of the Mycobacterium tuberculosis genome is devoted to two highly expanded and enigmatic protein families called PE and PPE, some of which are important virulence/immunogenicity factors and are secreted during infection via a unique alternative secretory system termed “type VII.” How PE-PPE proteins function during infection and how they are translocated to the bacterial surface through the five distinct type VII secretion systems [ESAT-6 secretion system (ESX)] of M. tuberculosis is poorly understood. Here, we report the crystal structure of a PE-PPE heterodimer bound to ESX secretion-associated protein G (EspG), which adopts a novel fold. This PE-PPE-EspG complex, along with structures of two additional EspGs, suggests that EspG acts as an adaptor that recognizes specific PE–PPE protein complexes via extensive interactions with PPE domains, and delivers them to ESX machinery for secretion. Surprisingly, secretion of most PE-PPE proteins in M. tuberculosis is likely mediated by EspG from the ESX-5 system, underscoring the importance of ESX-5 in mycobacterial pathogenesis. Moreover, our results indicate that PE-PPE domains function as cis-acting targeting sequences that are read out by EspGs, revealing the molecular specificity for secretion through distinct ESX pathways. PMID:25275011

  6. NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1.

    PubMed

    Omichinski, J G; Clore, G M; Schaad, O; Felsenfeld, G; Trainor, C; Appella, E; Stahl, S J; Gronenborn, A M

    1993-07-23

    The three-dimensional solution structure of a complex between the DNA binding domain of the chicken erythroid transcription factor GATA-1 and its cognate DNA site has been determined with multidimensional heteronuclear magnetic resonance spectroscopy. The DNA binding domain consists of a core which contains a zinc coordinated by four cysteines and a carboxyl-terminal tail. The core is composed of two irregular antiparallel beta sheets and an alpha helix, followed by a long loop that leads into the carboxyl-terminal tail. The amino-terminal part of the core, including the helix, is similar in structure, although not in sequence, to the amino-terminal zinc module of the glucocorticoid receptor DNA binding domain. In the other regions, the structures of these two DNA binding domains are entirely different. The DNA target site in contact with the protein spans eight base pairs. The helix and the loop connecting the two antiparallel beta sheets interact with the major groove of the DNA. The carboxyl-terminal tail, which is an essential determinant of specific binding, wraps around into the minor groove. The complex resembles a hand holding a rope with the palm and fingers representing the protein core and the thumb, the carboxyl-terminal tail. The specific interactions between GATA-1 and DNA in the major groove are mainly hydrophobic in nature, which accounts for the preponderance of thymines in the target site. A large number of interactions are observed with the phosphate backbone. PMID:8332909

  7. A facile and versatile methodology for cysteine specific labeling of proteins with octahedral polypyridyl d6 metal complexes

    PubMed Central

    Dwaraknath, Sudharsan; Tran, Ngoc-Han; Dao, Thanh; Colbert, Alexander; Mullen, Sarah; Nguyen, Angelina; Cortez, Alejandro; Cheruzel, Lionel

    2014-01-01

    We have synthesized and characterized four octahedral polypyridyl d6 metal complexes bearing the 5,6-epoxy-5,6-dihydro-[1,10]phenanthroline ligand (L1) as cysteine specific labeling reagents. The proposed synthetic pathways allow the preparation of the metal complexes containing Re(I), Ru(II), Os(II) and Ir(III) while preserving the epoxide functionality. The complexes were characterized by 1H and 13C NMR, mass spectrometry, UV-visible and luminescence spectroscopies as well as cyclic voltammetry. As proof of concept, a set of non-native single cysteine P450 BM3 heme domain mutants previously developed in our laboratory was used to study the labeling reaction. We demonstrate that the proposed labels can selectively react, often in high yield, with cysteine residues of the protein via the nucleophilic thiol ring opening of the epoxide moiety. In addition, under basic conditions, subsequent loss of a water molecule led to the aromatization of the phenanthroline ring on the protein-bound label compounds, as observed by mass spectrometry and luminescence measurements. PMID:24468675

  8. Error-Free Software

    NASA Technical Reports Server (NTRS)

    1989-01-01

    001 is an integrated tool suited for automatically developing ultra reliable models, simulations and software systems. Developed and marketed by Hamilton Technologies, Inc. (HTI), it has been applied in engineering, manufacturing, banking and software tools development. The software provides the ability to simplify the complex. A system developed with 001 can be a prototype or fully developed with production quality code. It is free of interface errors, consistent, logically complete and has no data or control flow errors. Systems can be designed, developed and maintained with maximum productivity. Margaret Hamilton, President of Hamilton Technologies, also directed the research and development of USE.IT, an earlier product which was the first computer aided software engineering product in the industry to concentrate on automatically supporting the development of an ultrareliable system throughout its life cycle. Both products originated in NASA technology developed under a Johnson Space Center contract.

  9. Bioboxes: standardised containers for interchangeable bioinformatics software.

    PubMed

    Belmann, Peter; Dröge, Johannes; Bremges, Andreas; McHardy, Alice C; Sczyrba, Alexander; Barton, Michael D

    2015-01-01

    Software is now both central and essential to modern biology, yet lack of availability, difficult installations, and complex user interfaces make software hard to obtain and use. Containerisation, as exemplified by the Docker platform, has the potential to solve the problems associated with sharing software. We propose bioboxes: containers with standardised interfaces to make bioinformatics software interchangeable.

  10. Bioboxes: standardised containers for interchangeable bioinformatics software.

    PubMed

    Belmann, Peter; Dröge, Johannes; Bremges, Andreas; McHardy, Alice C; Sczyrba, Alexander; Barton, Michael D

    2015-01-01

    Software is now both central and essential to modern biology, yet lack of availability, difficult installations, and complex user interfaces make software hard to obtain and use. Containerisation, as exemplified by the Docker platform, has the potential to solve the problems associated with sharing software. We propose bioboxes: containers with standardised interfaces to make bioinformatics software interchangeable. PMID:26473029

  11. Wildlife software: procedures for publication of computer software

    USGS Publications Warehouse

    Samuel, M.D.

    1990-01-01

    Computers and computer software have become an integral part of the practice of wildlife science. Computers now play an important role in teaching, research, and management applications. Because of the specialized nature of wildlife problems, specific computer software is usually required to address a given problem (e.g., home range analysis). This type of software is not usually available from commercial vendors and therefore must be developed by those wildlife professionals with particular skill in computer programming. Current journal publication practices generally prevent a detailed description of computer software associated with new techniques. In addition, peer review of journal articles does not usually include a review of associated computer software. Thus, many wildlife professionals are usually unaware of computer software that would meet their needs or of major improvements in software they commonly use. Indeed most users of wildlife software learn of new programs or important changes only by word of mouth.

  12. Software Reviews.

    ERIC Educational Resources Information Center

    Dwyer, Donna; And Others

    1989-01-01

    Reviewed are seven software packages for Apple and IBM computers. Included are: "Toxicology"; "Science Corner: Space Probe"; "Alcohol and Pregnancy"; "Science Tool Kit Plus"; Computer Investigations: Plant Growth"; "Climatrolls"; and "Animal Watch: Whales." (CW)

  13. Software Reviews.

    ERIC Educational Resources Information Center

    McGrath, Diane

    1990-01-01

    Reviews two programs: (1) "The Weather Machine" on understanding weather and weather forecasting and (2) "The Mystery of the Hotel Victoria" on problem solving in mathematics. Presents the descriptions, advantages, and weaknesses of the software. (YP)

  14. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Stephen, Ed.

    1990-01-01

    Reviewed are six computer software packages including "Lunar Greenhouse,""Dyno-Quest,""How Weather Works,""Animal Trackers,""Personal Science Laboratory," and "The Skeletal and Muscular Systems." Availability, functional, and hardware requirements are discussed. (CW)

  15. Software Reviews.

    ERIC Educational Resources Information Center

    Classroom Computer Learning, 1990

    1990-01-01

    Reviewed are three computer software packages including "Martin Luther King, Jr.: Instant Replay of History,""Weeds to Trees," and "The New Print Shop, School Edition." Discussed are hardware requirements, costs, grade levels, availability, emphasis, strengths, and weaknesses. (CW)

  16. Software Reviews.

    ERIC Educational Resources Information Center

    Davis, Shelly J., Ed.; Knaupp, Jon, Ed.

    1984-01-01

    Reviewed is computer software on: (1) classification of living things, a tutorial program for grades 5-10; and (2) polynomial practice using tiles, a drill-and-practice program for algebra students. (MNS)

  17. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Stephen, Ed.

    1987-01-01

    Reviews seven computer software programs that can be used in science education programs. Describes courseware which deals with muscles and bones, terminology, classifying animals without backbones, molecular structures, drugs, genetics, and shaping the earth's surface. (TW)

  18. Software Reviews.

    ERIC Educational Resources Information Center

    Mathematics and Computer Education, 1988

    1988-01-01

    Presents reviews of six software packages. Includes (1) "Plain Vanilla Statistics"; (2) "MathCAD 2.0"; (3) "GrFx"; (4) "Trigonometry"; (5) "Algebra II"; (6) "Algebra Drill and Practice I, II, and III." (PK)

  19. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Eugene T., Ed.

    1988-01-01

    Presents reviews by classroom teachers of software for teaching science. Includes material on the work of geologists, genetics, earth science, classification of living things, astronomy, endangered species, skeleton, drugs, and heartbeat. Provides information on availability and equipment needed. (RT)

  20. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Stephen, Ed.

    1987-01-01

    Provides a review of four science software programs. Includes topics such as plate tectonics, laboratory experiment simulations, the human body, and light and temperature. Contains information on ordering and reviewers' comments. (ML)

  1. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Stephen, Ed.

    1987-01-01

    Provides reviews of six computer software programs designed for use in elementary science education programs. Provides the title, publisher, grade level, and descriptions of courseware on ant farms, drugs, genetics, beachcombing, matter, and test generation. (TW)

  2. 3{prime} UTR sequence-specific mRNA-protein complexes and the post-transcriptional regulation of catalase

    SciTech Connect

    Reimer, D.L.; Ott, R.N.; Singh, S.M.

    1994-09-01

    Recently, sequences in the 3{prime} untranslated region (3{prime} UTR) of some genes have been recognized which may play an important role in the post-transcriptional regulation of gene expression. Mutations in this region of the gene are known to cause at least two diseases including myotonic dystrophy and a lysosomal accumulation disease. The mechanism is thought to involve mRNA-protein interactions that affect translation and/or mRNA stability. Reports of this nature are not common and the significance of the often large 3{prime} UTR on the regulation of gene expression remains speculative. Studies on the 3{prime} UTR mRNA-protein interactions in model eukaryotic genes therefore are critical to better understand the molecular mechanisms involved in post-transcriptional gene regulation. Mouse catalase, encoded by Cas-1, was used as a model to characterize the molecular mechanisms of post-transcriptional gene regulation. The 3{prime} UTR (752 bp) of Cas-1 contains three unusual, near repeats [(CA){sub 31}, (U){sub 15} and (TGTGC){sub 7}]. Gel mobility shift assays using {sup 32}P-labelled transcripts which contain these sequences and tissue homogenates from various sources identified mRNA-protein complexes specific to (CA){sub 31} and (U){sub 15} only. In all strains analyzed, a single protein of 69 kDa which was involved in the (CA){sub 31} complex, was observed in most tissues except lung and was localized to the polysomal fraction. Similarly, two proteins involved in the (U){sub 15} complex, 38 and 47 kDa, were observed in all tissues and strains studied. Only the 38 kDa protein was observed in the polysomal fraction. The results argue for a possible role for these 3{prime} UTR mRNA-binding protein complexes in the post-transcriptional regulation of this antioxidant enzyme.

  3. A Feasibility Study of a Field-specific Weather Service for Small-scale Farms in a Topographically Complex Watershed

    NASA Astrophysics Data System (ADS)

    Kim, S. O.; Shim, K. M.; Shin, Y. S.; Yun, J. I.

    2015-12-01

    Adequate downscaling of synoptic forecasts is a prerequisite for improved agrometeorological service to rural areas in South Korea where complex terrain and small farms are common. Geospatial schemes based on topoclimatology were used to scale down the Korea Meteorological Administration (KMA) temperature forecasts to the local scale (~30 m) across a rural catchment. Local temperatures were estimated at 14 validation sites at 0600 and 1500 LST in 2013/2014 using these schemes and were compared with observations. A substantial reduction in the estimation error was found for both 0600 and 1500 temperatures compared with uncorrected KMA products. Improvement was most remarkable at low lying locations for the 0600 temperature and at the locations on west- and south-facing slopes for the 1500 temperature. Using the downscaled real-time temperature data, a pilot service has started to provide field-specific weather information tailored to meet the requirements of small-scale farms. For example, the service system makes a daily outlook on the phenology of crop species grown in a given field using the field-specific temperature data. When the temperature forecast is given for tomorrow morning, a frost risk index is calculated according to a known phenology-frost injury relationship. If the calculated index is higher than a pre-defined threshold, a warning is issued and delivered to the grower's cellular phone with relevant countermeasures to help protect crops against frost damage. The system was implemented for a topographically complex catchment of 350km2with diverse agricultural activities, and more than 400 volunteer farmers are participating in this pilot service to access user-specific weather information.

  4. Software Quality Assurance Audits Guidebooks

    NASA Technical Reports Server (NTRS)

    1990-01-01

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

  5. Absolute quantification of allergens from complex mixtures: a new sensitive tool for standardization of allergen extracts for specific immunotherapy.

    PubMed

    Seppälä, Ulla; Dauly, Claire; Robinson, Sarah; Hornshaw, Martin; Larsen, Jørgen Nedergaard; Ipsen, Henrik

    2011-04-01

    Products for specific diagnosis and immunotherapy of IgE-mediated allergies are currently based on natural extracts. Quantification of major allergen content is an important aspect of standardization as important allergens particularly impact vaccine potency. The aim of the study was to develop a mass spectrometry (MS) based assay for absolute quantification of Timothy (Phleum pratense) pollen allergens Phl p 1 and Phl p 5 in P. pratense extract. High-resolution and accurate mass (HRAM) MS was selected for its ability to detect peptides with high selectivity and mass accuracy (<3 ppm). Isotope labeled heavy peptides were used for absolute quantification of specific isoallergens of Phl p 1 and Phl p 5 at low femtomole level in P. pratense extract. Robustness and linearity of the method was demonstrated with intra day precision ≤ 5% (n = 3). Phl p 1b was shown to be 5 times less abundant than its variant Phl p 1a and Phl p 5b was shown to be 9 times more abundant than the Phl p 5a. The present study shows that allergen, and/or isoallergen specific, surrogate signature peptides analyzed with HRAM MS is a sensitive and accurate tool for identification and quantification of allergens from complex allergen sources.

  6. Immunogenicity of a Prefusion HIV-1 Envelope Trimer in Complex with a Quaternary-Structure-Specific Antibody

    PubMed Central

    Cheng, Cheng; Pancera, Marie; Bossert, Adam; Schmidt, Stephen D.; Chen, Rita E.; Chen, Xuejun; Druz, Aliaksandr; Narpala, Sandeep; Doria-Rose, Nicole A.; McDermott, Adrian B.

    2015-01-01

    ABSTRACT The HIV-1 envelope trimer (Env) is the target of broadly neutralizing antibodies and is being explored as a vaccine candidate to elicit protective antibodies. One of the most promising antigenic and structural mimics of HIV-1 Env is the SOSIP.664-stabilized soluble trimer from the clade A strain BG505, which is preferentially recognized by broadly neutralizing antibodies. Trimer immunization elicits high-titer neutralization of the autologous tier 2 BG505 strain; however, breadth is limited, and substantial interest has focused on understanding and improving trimer immunogenicity. We sought to improve the antigenic specificity of BG505 SOSIP.664 by reducing recognition of the variable loop 3 (V3) region, which elicits only weakly neutralizing antibodies. To stabilize the trimer in its prefusion closed conformation, we complexed trimeric BG505 SOSIP.664 with the antigen-binding fragment (Fab) of PGT145, a broadly neutralizing quaternary-structure-specific antibody. Compared to the ligand-free trimer, the PGT145 Fab-BG505 SOSIP.664 complex displayed increased melting temperature stability and reduced V3 recognition. In guinea pigs, immunization with the PGT145 Fab-BG505 SOSIP.664 complex elicited ∼100-fold lower V3-directed binding and neutralization titers than those obtained with ligand-free BG505 SOSIP.664. Both complexed and ligand-free BG505 SOSIP.664 elicited comparable neutralization of the autologous BG505 virus, and in both cases, BG505 neutralization mapped to the outer domain of gp120 for some guinea pigs. Our results indicate that it is possible to reduce immune recognition of the V3 region of the trimer while maintaining the antigenic profile needed to induce autologous neutralizing antibodies. These data suggest that appropriate modifications of trimer immunogens could further focus the immune response on key neutralization epitopes. IMPORTANCE HIV-1 Env trimers have been proposed as preferred HIV-1 vaccine immunogens. One version, BG505

  7. Software Formal Inspections Guidebook

    NASA Technical Reports Server (NTRS)

    1993-01-01

    The Software Formal Inspections Guidebook is designed to support the inspection process of software developed by and for NASA. This document provides information on how to implement a recommended and proven method for conducting formal inspections of NASA software. This Guidebook is a companion document to NASA Standard 2202-93, Software Formal Inspections Standard, approved April 1993, which provides the rules, procedures, and specific requirements for conducting software formal inspections. Application of the Formal Inspections Standard is optional to NASA program or project management. In cases where program or project management decide to use the formal inspections method, this Guidebook provides additional information on how to establish and implement the process. The goal of the formal inspections process as documented in the above-mentioned Standard and this Guidebook is to provide a framework and model for an inspection process that will enable the detection and elimination of defects as early as possible in the software life cycle. An ancillary aspect of the formal inspection process incorporates the collection and analysis of inspection data to effect continual improvement in the inspection process and the quality of the software subjected to the process.

  8. NASA PC software evaluation project

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

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

  9. NASA's Approach to Software Assurance

    NASA Technical Reports Server (NTRS)

    Wetherholt, Martha

    2015-01-01

    NASA defines software assurance as: the planned and systematic set of activities that ensure conformance of software life cycle processes and products to requirements, standards, and procedures via quality, safety, reliability, and independent verification and validation. NASA's implementation of this approach to the quality, safety, reliability, security and verification and validation of software is brought together in one discipline, software assurance. Organizationally, NASA has software assurance at each NASA center, a Software Assurance Manager at NASA Headquarters, a Software Assurance Technical Fellow (currently the same person as the SA Manager), and an Independent Verification and Validation Organization with its own facility. An umbrella risk mitigation strategy for safety and mission success assurance of NASA's software, software assurance covers a wide area and is better structured to address the dynamic changes in how software is developed, used, and managed, as well as it's increasingly complex functionality. Being flexible, risk based, and prepared for challenges in software at NASA is essential, especially as much of our software is unique for each mission.

  10. Defining Binding Efficiency and Specificity of Auxins for SCFTIR1/AFB-Aux/IAA Co-receptor Complex Formation

    PubMed Central

    2013-01-01

    Structure–activity profiles for the phytohormone auxin have been collected for over 70 years, and a number of synthetic auxins are used in agriculture. Auxin classification schemes and binding models followed from understanding auxin structures. However, all of the data came from whole plant bioassays, meaning the output was the integral of many different processes. The discovery of Transport Inhibitor-Response 1 (TIR1) and the Auxin F-Box (AFB) proteins as sites of auxin perception and the role of auxin as molecular glue in the assembly of co-receptor complexes has allowed the development of a definitive quantitative structure–activity relationship for TIR1 and AFB5. Factorial analysis of binding activities offered two uncorrelated factors associated with binding efficiency and binding selectivity. The six maximum-likelihood estimators of Efficiency are changes in the overlap matrixes, inferring that Efficiency is related to the volume of the electronic system. Using the subset of compounds that bound strongly, chemometric analyses based on quantum chemical calculations and similarity and self-similarity indices yielded three classes of Specificity that relate to differential binding. Specificity may not be defined by any one specific atom or position and is influenced by coulomb matrixes, suggesting that it is driven by electrostatic forces. These analyses give the first receptor-specific classification of auxins and indicate that AFB5 is the preferred site for a number of auxinic herbicides by allowing interactions with analogues having van der Waals surfaces larger than that of indole-3-acetic acid. The quality factors are also examined in terms of long-standing models for the mechanism of auxin binding. PMID:24313839

  11. Species-Specific Detection and Identification of Fusarium Species Complex, the Causal Agent of Sugarcane Pokkah Boeng in China

    PubMed Central

    Que, Youxiong; Wang, Jihua; Comstock, Jack C.; Wei, Jinjin; McCord, Per H.; Chen, Baoshan; Chen, Rukai; Zhang, Muqing

    2014-01-01

    Background Pokkah boeng disease caused by the Fusarium species complex results in significant yield losses in sugarcane. Thus, the rapid and accurate detection and identification of the pathogen is urgently required to manage and prevent the spreading of sugarcane pokkah boeng. Methods A total of 101 isolates were recovered from the pokkah boeng samples collected from five major sugarcane production areas in China throughout 2012 and 2013. The causal pathogen was identified by morphological observation, pathogenicity test, and phylogenetic analysis based on the fungus-conserved rDNA-ITS. Species-specific TaqMan real-time PCR and conventional PCR methods were developed for rapid and accurate detection of the causal agent of sugarcane pokkah boeng. The specificity and sensitivity of PCR assay were also evaluated on a total of 84 isolates of Fusarium from China and several isolates from other fungal pathogens of Sporisorium scitamineum and Phoma sp. and sugarcane endophyte of Acremonium sp. Result Two Fusarium species (F. verticillioides and F. proliferatum) that caused sugarcane pokahh boeng were identified by morphological observation, pathogenicity test, and phylogenetic analysis. Species-specific TaqMan PCR and conventional PCR were designed and optimized to target their rDNA-ITS regions. The sensitivity of the TaqMan PCR was approximately 10 pg of fungal DNA input, which was 1,000-fold over conventional PCR, and successfully detected pokkah boeng in the field-grown sugarcane. Conclusions/Significance This study was the first to identify two species, F. verticillioides and F. proliferatum, that were causal pathogens of sugarcane pokkah boeng in China. It also described the development of a species-specific PCR assay to detect and confirm these pathogens in sugarcane plants from mainland China. This method will be very useful for a broad range of research endeavors as well as the regulatory response and management of sugarcane pokkah boeng. PMID:25141192

  12. A novel T cell receptor single-chain signaling complex mediates antigen-specific T cell activity and tumor control

    PubMed Central

    Stone, Jennifer D.; Harris, Daniel T.; Soto, Carolina M.; Chervin, Adam S.; Aggen, David H.; Roy, Edward J.; Kranz, David M.

    2014-01-01

    Adoptive transfer of genetically modified T cells to treat cancer has shown promise in several clinical trials. Two main strategies have been applied to redirect T cells against cancer: 1) introduction of a full-length T cell receptor (TCR) specific for a tumor-associated peptide-MHC, or 2) introduction of a chimeric antigen receptor (CAR), including an antibody fragment specific for a tumor cell surface antigen, linked intracellularly to T cell signaling domains. Each strategy has advantages and disadvantages for clinical applications. Here, we present data on the in vitro and in vivo effectiveness of a single-chain signaling receptor incorporating a TCR variable fragment as the targeting element (referred to as TCR-SCS). This receptor contained a single-chain TCR (Vβ-linker-Vα) from a high-affinity TCR called m33, linked to the intracellular signaling domains of CD28 and CD3ζ. This format avoided mispairing with endogenous TCR chains, and mediated specific T cell activity when expressed in either CD4 or CD8 T cells. TCR-SCS-transduced CD8-negative cells showed an intriguing sensitivity, compared to full-length TCRs, to higher densities of less stable pepMHC targets. T cells that expressed this peptide-specific receptor persisted in vivo, and exhibited polyfunctional responses. Growth of metastatic antigen-positive tumors was significantly inhibited by T cells that expressed this receptor, and tumor cells that escaped were antigen loss variants. TCR-SCS receptors represent an alternative targeting receptor strategy that combines the advantages of single-chain expression, avoidance of TCR chain mispairing, and targeting of intracellular antigens presented in complex with MHC proteins. PMID:25082071

  13. Correlation of phantom-based and log file patient-specific QA with complexity scores for VMAT.

    PubMed

    Agnew, Christina E; Irvine, Denise M; McGarry, Conor K

    2014-11-08

    The motivation for this study was to reduce physics workload relating to patient- specific quality assurance (QA). VMAT plan delivery accuracy was determined from analysis of pre- and on-treatment trajectory log files and phantom-based ionization chamber array measurements. The correlation in this combination of measurements for patient-specific QA was investigated. The relationship between delivery errors and plan complexity was investigated as a potential method to further reduce patient-specific QA workload. Thirty VMAT plans from three treatment sites - prostate only, prostate and pelvic node (PPN), and head and neck (H&N) - were retrospectively analyzed in this work. The 2D fluence delivery reconstructed from pretreatment and on-treatment trajectory log files was compared with the planned fluence using gamma analysis. Pretreatment dose delivery verification was also car- ried out using gamma analysis of ionization chamber array measurements compared with calculated doses. Pearson correlations were used to explore any relationship between trajectory log file (pretreatment and on-treatment) and ionization chamber array gamma results (pretreatment). Plan complexity was assessed using the MU/ arc and the modulation complexity score (MCS), with Pearson correlations used to examine any relationships between complexity metrics and plan delivery accu- racy. Trajectory log files were also used to further explore the accuracy of MLC and gantry positions. Pretreatment 1%/1 mm gamma passing rates for trajectory log file analysis were 99.1% (98.7%-99.2%), 99.3% (99.1%-99.5%), and 98.4% (97.3%-98.8%) (median (IQR)) for prostate, PPN, and H&N, respectively, and were significantly correlated to on-treatment trajectory log file gamma results (R = 0.989, p < 0.001). Pretreatment ionization chamber array (2%/2 mm) gamma results were also significantly correlated with on-treatment trajectory log file gamma results (R = 0.623, p < 0.001). Furthermore, all gamma results displayed a

  14. Specificity of anti-lymphocyte antibodies in sera from patients with AIDS-related complex (ARC) and healthy homosexuals.

    PubMed Central

    Warren, R Q; Johnson, E A; Donnelly, R P; Lavia, M F; Tsang, K Y

    1988-01-01

    The presence and specificity of anti-lymphocyte antibodies (ALA) was investigated in sera from male homosexuals with AIDS-Related Complex (ARC) as well as healthy homosexuals. Individuals in the healthy homosexual group had no detectable antibodies to human immunodeficiency virus (HIV). Antibodies reactive with normal peripheral blood mononuclear cells were detected by Western blot analysis in sera from both groups of homosexuals. Of those individuals whose sera contained ALA, 71% of ARC patients and 83% of healthy homosexuals had antibodies recognizing a 73 kilodalton (kD) molecule. ALA present in ARC sera reacted with CD3+, CD4+ and CD8+ lymphocytes while little reactivity with B cells was observed. Our results indicate that ALA appear in homosexuals prior to HIV infection and are reactive primarily with T lymphocytes. A 73 kD structure associated with the T cell membrane is frequently the target for these antibodies. Images Fig. 1 Fig. 2 Fig. 3 PMID:3052941

  15. Use of Specific rRNA Oligonucleotide Probes for Microscopic Detection of Mycobacterium avium Complex Organisms in Tissue

    PubMed Central

    Amand, Allison L. St.; Frank, Daniel N.; De Groote, Mary Ann; Pace, Norman R.

    2005-01-01

    Members of the Mycobacterium avium complex (MAC) are important environmental pathogens that are implicated in several chronic, idiopathic diseases. Diagnosis of MAC-based diseases is compromised by the need to cultivate these fastidious and slowly growing organisms in order to identify which mycobacterial species are present. Detection is particularly difficult when MAC is intracellular or embedded within mammalian tissues. We report on the development of culture-independent, in situ hybridization (ISH) assays for the detection of MAC in culture, sputum, and tissue. This assay includes a highly reliable technique for the permeabilization of mycobacterial cells within culture and tissues. We describe a set of rRNA-based oligonucleotide probes that specifically detect either M. intracellulare, the two M. avium subspecies associated with human disease, or all members of MAC. The results call into question the validity of ISH results derived by the use of other gene loci, such as IS900. PMID:15814959

  16. Sensitive and specific detection of pine nut (Pinus spp.) by real-time PCR in complex food products.

    PubMed

    Garino, Cristiano; De Paolis, Angelo; Coïsson, Jean Daniel; Bianchi, Daniela Manila; Decastelli, Lucia; Arlorio, Marco

    2016-03-01

    Pine nuts are a known source of food allergens and several cases of adverse immunological reaction after ingestion have been reported. To protect allergic consumers, methods to unequivocally detect the presence of pine nuts in complex matrices must be developed. A Taqman-based real time PCR method for the detection of Pinus spp. was set up. A homemade pesto spiked at known concentration of pine nut powder was used as model food. Moreover, DNA was purified from commercial foods declaring or not the presence of pine nuts. The method displayed a very high efficiency and specificity for the genus Pinus. The intrinsic LOD was 1pg of DNA, while the practical LOD evaluated on model foods was 0.1ppm of pine nuts powder, the lowest ever registered for the detection of food allergens via real-time PCR. Finally, the declared presence/absence of pine nut in commercial foods was confirmed.

  17. Software reengineering

    NASA Technical Reports Server (NTRS)

    Fridge, Ernest M., III

    1991-01-01

    Today's software systems generally use obsolete technology, are not integrated properly with other software systems, and are difficult and costly to maintain. The discipline of reverse engineering is becoming prominent as organizations try to move their systems up to more modern and maintainable technology in a cost effective manner. JSC created a significant set of tools to develop and maintain FORTRAN and C code during development of the Space Shuttle. This tool set forms the basis for an integrated environment to re-engineer existing code into modern software engineering structures which are then easier and less costly to maintain and which allow a fairly straightforward translation into other target languages. The environment will support these structures and practices even in areas where the language definition and compilers do not enforce good software engineering. The knowledge and data captured using the reverse engineering tools is passed to standard forward engineering tools to redesign or perform major upgrades to software systems in a much more cost effective manner than using older technologies. A beta vision of the environment was released in Mar. 1991. The commercial potential for such re-engineering tools is very great. CASE TRENDS magazine reported it to be the primary concern of over four hundred of the top MIS executives.

  18. Identification of bovine hibernation-specific protein complex and evidence of its regulation in fasting and aging.

    PubMed

    Fujita, Satoshi; Okamoto, Ryuji; Taniguchi, Masaya; Ban-Tokuda, Tomomi; Konishi, Katsuhisa; Goto, Itaru; Yamamoto, Yasunari; Sugimoto, Kazushi; Takamatsu, Nobuhiko; Nakamura, Mashio; Shiraki, Katsuya; Buechler, Christa; Ito, Masaaki

    2013-05-01

    Hibernation-specific protein (HP) is a plasma protein that regulates hibernation in chipmunks. The HP complex (HP20c) consists of three homologous proteins, HP20, HP25 and HP27, all produced by liver and belonging to the C1q family. To date, HP20c has not been identified in any mammalian species except chipmunk and ground squirrel hibernators. Here, we report a bovine HP20 gene isolated from liver tissue and aortic endothelial cells. Total homology between bovine and chipmunk variants was 63% at the amino acid level. Gene expression was highest in the liver. Western blot revealed HP20 protein in foetal, newborn, calf and adult serum, with highest concentrations in the adult. Similar proteins were detected in sera of other ruminants but not in humans, bears, mice or rats. Bovine HP20 protein was found mainly in ovaries, stomach, heart, kidneys, lungs, testes and prostate, but not in the skeletal muscle. Native HP20 was purified from bovine adult serum as a complex containing 25 and 27 kDa proteins. Mass spectrometry revealed that these proteins are orthologues of chipmunk HP25 and HP27, respectively. Interestingly, bovine HP20 was highly expressed in cattle serum after fasting. Native bovine HP20c may be a useful tool for investigating HP function.

  19. Star Wars software debate

    SciTech Connect

    Myers, W.

    1986-02-01

    David L. Parnas, Landsdowne Professor of Computer Science at the University of Victoria resigned from the SDI Organization's Panel on Computing in Support of Battle Management on June 28, 1985. Parnas, with 20 years of research on software engineering plus 8 years of work on military aircraft real-time software, says the software portion of SDI cannot be built error-free and he doesn't expect the next 20 years of research to change that fact. Since Parnas resigned, there have been several public debates on Star Wars software questions. In November 1985 the SDIO panel from which Parnas resigned released a draft of its report, reflecting its effort to critics of the project. While one might think that errors could be entirely eliminated with enough care and checking, most software professionals believe there will always be some residue of errors in a system of this size and complexity. The general line of the critics' argument is that the larger the amount of software in a single, unified system, the higher the percentage of errors it will contain. Proponents counter that the one very large system can be divided into a number of smaller, relatively independent pieces, thus reducing the proportionate number of errors in each separate piece. This approach is in turn countered by those who point to the intricate relations between these pieces, which themselves contribute to error.

  20. Software Process Assessment (SPA)

    NASA Technical Reports Server (NTRS)

    Rosenberg, Linda H.; Sheppard, Sylvia B.; Butler, Scott A.

    1994-01-01

    NASA's environment mirrors the changes taking place in the nation at large, i.e. workers are being asked to do more work with fewer resources. For software developers at NASA's Goddard Space Flight Center (GSFC), the effects of this change are that we must continue to produce quality code that is maintainable and reusable, but we must learn to produce it more efficiently and less expensively. To accomplish this goal, the Data Systems Technology Division (DSTD) at GSFC is trying a variety of both proven and state-of-the-art techniques for software development (e.g., object-oriented design, prototyping, designing for reuse, etc.). In order to evaluate the effectiveness of these techniques, the Software Process Assessment (SPA) program was initiated. SPA was begun under the assumption that the effects of different software development processes, techniques, and tools, on the resulting product must be evaluated in an objective manner in order to assess any benefits that may have accrued. SPA involves the collection and analysis of software product and process data. These data include metrics such as effort, code changes, size, complexity, and code readability. This paper describes the SPA data collection and analysis methodology and presents examples of benefits realized thus far by DSTD's software developers and managers.

  1. Antiterrorist Software

    NASA Technical Reports Server (NTRS)

    Clark, David A.

    1998-01-01

    In light of the escalation of terrorism, the Department of Defense spearheaded the development of new antiterrorist software for all Government agencies by issuing a Broad Agency Announcement to solicit proposals. This Government-wide competition resulted in a team that includes NASA Lewis Research Center's Computer Services Division, who will develop the graphical user interface (GUI) and test it in their usability lab. The team launched a program entitled Joint Sphere of Security (JSOS), crafted a design architecture (see the following figure), and is testing the interface. This software system has a state-ofthe- art, object-oriented architecture, with a main kernel composed of the Dynamic Information Architecture System (DIAS) developed by Argonne National Laboratory. DIAS will be used as the software "breadboard" for assembling the components of explosions, such as blast and collapse simulations.

  2. Integrating interface slicing into software engineering processes

    NASA Technical Reports Server (NTRS)

    Beck, Jon

    1993-01-01

    Interface slicing is a tool which was developed to facilitate software engineering. As previously presented, it was described in terms of its techniques and mechanisms. The integration of interface slicing into specific software engineering activities is considered by discussing a number of potential applications of interface slicing. The applications discussed specifically address the problems, issues, or concerns raised in a previous project. Because a complete interface slicer is still under development, these applications must be phrased in future tenses. Nonetheless, the interface slicing techniques which were presented can be implemented using current compiler and static analysis technology. Whether implemented as a standalone tool or as a module in an integrated development or reverse engineering environment, they require analysis no more complex than that required for current system development environments. By contrast, conventional slicing is a methodology which, while showing much promise and intuitive appeal, has yet to be fully implemented in a production language environment despite 12 years of development.

  3. Formation and characterization of precise eucaryotic transcription complexes using a semisynthetic DNA template and specific oligoribonucleotide primers.

    PubMed

    Mougey, E B; Dennis, D

    1988-06-01

    An artificial template of defined sequence which supports specific in vitro initiation and elongation by yeast RNA polymerase II has been constructed. This template is a pBR322 derivative which contains a synthetic oligonucleotide inserted into the BamHI cloning site. The sequence of this oligonucleotide is such that when the plasmid is restricted with SacI the two ends obtained are identical. The addition of an oligodeoxycytidylate chain to the 3' hydroxy termini produces a DNA template, (poly dC-p+22), with the sequence: 3'(C)nTCGA-GAGTCTCCTA. . . . The underlined position denotes the beginning of the duplex region. When initiation is primed with the diribonucleotide GpC the predicted sequence of the transcript obtained is: 5'GCUCUCAGAGGAU. . . . Kinetic and product analyses indicate that a ternary complex containing a precise length of transcript can be produced which is subsequently resistant to heparin inactivation. Initiation can also be directed to a specific position dictated by a tri or tetraribonucleotide primer.

  4. Nanobodies: site-specific labeling for super-resolution imaging, rapid epitope-mapping and native protein complex isolation

    PubMed Central

    Pleiner, Tino; Bates, Mark; Trakhanov, Sergei; Lee, Chung-Tien; Schliep, Jan Erik; Chug, Hema; Böhning, Marc; Stark, Holger; Urlaub, Henning; Görlich, Dirk

    2015-01-01

    Nanobodies are single-domain antibodies of camelid origin. We generated nanobodies against the vertebrate nuclear pore complex (NPC) and used them in STORM imaging to locate individual NPC proteins with <2 nm epitope-label displacement. For this, we introduced cysteines at specific positions in the nanobody sequence and labeled the resulting proteins with fluorophore-maleimides. As nanobodies are normally stabilized by disulfide-bonded cysteines, this appears counterintuitive. Yet, our analysis showed that this caused no folding problems. Compared to traditional NHS ester-labeling of lysines, the cysteine-maleimide strategy resulted in far less background in fluorescence imaging, it better preserved epitope recognition and it is site-specific. We also devised a rapid epitope-mapping strategy, which relies on crosslinking mass spectrometry and the introduced ectopic cysteines. Finally, we used different anti-nucleoporin nanobodies to purify the major NPC building blocks – each in a single step, with native elution and, as demonstrated, in excellent quality for structural analysis by electron microscopy. The presented strategies are applicable to any nanobody and nanobody-target. DOI: http://dx.doi.org/10.7554/eLife.11349.001 PMID:26633879

  5. Thrombin activation of human platelets dissociates a complex containing gelsolin and actin from phosphatidylinositide-specific phospholipase Cgamma1.

    PubMed Central

    Baldassare, J J; Henderson, P A; Tarver, A; Fisher, G J

    1997-01-01

    We have examined the association of two cytoskeleton proteins, gelsolin and actin, with phosphatidylinositide-specific phospholipase Cgamma1 (PLCgamma1) in resting and thrombin-stimulated human platelets. In unstimulated platelets, gelsolin, actin and PLCgamma1 were immunoprecipitated as a complex by a polyclonal antibody to PLCgamma1. The association of gelsolin and actin was specific for PLCgamma1 because immunoprecipitates of PLCs beta2, beta3, gamma2 and delta1, which are also expressed in human platelets, did not contain detectable gelsolin or actin. Activation with thrombin resulted in platelet aggregation and the dissociation of gelsolin and actin from PLCgamma1. Inhibition of thrombin-induced platelet aggregation blocked the dissociation of gelsolin and actin from PLCgamma1. After stimulation with thrombin, PLCgamma1 activity in immunoprecipitates was increased 2-3-fold. This elevation in PLCgamma1 activity in response to thrombin activation was not observed when platelet aggregation was blocked. Although PLCgamma1 is tyrosine phosphorylated in response to many agonists, we could not detect, by Western analysis with anti-phosphotyrosine antibodies, tyrosine phosphorylation of PLCgamma1 immunoprecipitated from thrombin-stimulated platelets. These results demonstrate that PLCgamma1 is associated with gelsolin and actin in resting platelets, and that thrombin-induced platelet aggregation results in the dissociation of PLCgamma1 from gelsolin and actin, and the stimulation of PLCgamma1 activity. PMID:9164868

  6. Rapid, sensitive, and specific detection of Mycobacterium tuberculosis complex by real-time PCR on paraffin-embedded human tissues.

    PubMed

    Lee, Hye Seung; Park, Kyoung Un; Park, Jung Ok; Chang, Ho Eun; Song, Junghan; Choe, Gheeyoung

    2011-07-01

    The detection of Mycobacterium tuberculosis complex (MTB) in clinical specimens is important for diagnosing and caring for patients in whom tuberculosis is clinically suspected. We collected 129 FFPE specimens, including 56 nontuberculosis cases, 63 MTB cases, and 10 nontuberculous mycobacteria (NTM) cases determined by acid-fast bacilli (AFB) culture. We performed AFB staining; nested MTB PCR, targeting the IS6110 gene; and real-time MTB PCR, targeting the senX3-regX3 intergenic region in the 129 FFPE specimens. The sensitivity and specificity of AFB staining were 37.0% and 98.2%, respectively, using AFB culture results as the reference standard. The sensitivity and specificity of detecting MTB were 68.3% and 98.5%, respectively, by nested PCR; and 74.6% and 98.5% by real-time PCR, respectively. Among the 129 specimens, four were positive by AFB staining but negative by nested or real-time PCR. NTM grew in all four of these cases by AFB culture. AFB density in FFPE tissue sections significantly correlated with MTB DNA load. Thus, real-time PCR is a useful diagnostic tool for rapid and sensitive MTB detection in FFPE specimens, whereas NTM should be included in differential diagnoses of cases positive by AFB staining but negative by PCR.

  7. Early detection of dominant Env-specific and subdominant Gag-specific CD8+ lymphocytes in equine infectious anemia virus-infected horses using major histocompatibility complex class I/peptide tetrameric complexes.

    PubMed

    Mealey, Robert H; Sharif, Amin; Ellis, Shirley A; Littke, Matt H; Leib, Steven R; McGuire, Travis C

    2005-08-15

    Cytotoxic T lymphocytes (CTL) are critical for control of lentiviruses, including equine infectious anemia virus (EIAV). Measurement of equine CTL responses has relied on chromium-release assays, which do not allow accurate quantitation. Recently, the equine MHC class I molecule 7-6, associated with the ELA-A1 haplotype, was shown to present both the Gag-GW12 and Env-RW12 EIAV CTL epitopes. In this study, 7-6/Gag-GW12 and 7-6/Env-RW12 MHC class I/peptide tetrameric complexes were constructed and used to analyze Gag-GW12- and Env-RW12-specific CTL responses in two EIAV-infected horses (A2164 and A2171). Gag-GW12 and Env-RW12 tetramer-positive CD8+ cells were identified in nonstimulated peripheral blood mononuclear cells as early as 14 days post-EIAV inoculation, and frequencies of tetramer-positive cells ranged from 0.4% to 6.7% of nonstimulated peripheral blood CD8+ cells during the 127-day study period. Although both horses terminated the initial viremic peak, only horse A2171 effectively controlled viral load. Neutralizing antibody was present during the initial control of viral load in both horses, but the ability to maintain control correlated with Gag-GW12-specific CD8+ cells in A2171. Despite Env-RW12 dominance, Env-RW12 escape viral variants were identified in both horses and there was no correlation between Env-RW12-specific CD8+ cells and control of viral load. Although Gag-GW12 CTL escape did not occur, a Gag-GW12 epitope variant arose in A2164 that was recognized less efficiently than the original epitope. These data indicate that tetramers are useful for identification and quantitation of CTL responses in horses, and suggest that the observed control of EIAV replication and clinical disease was associated with sustained CTL recognition of Gag-specific epitopes. PMID:15979679

  8. Structure of 'linkerless' hydroxamic acid inhibitor-HDAC8 complex confirms the formation of an isoform-specific subpocket.

    PubMed

    Tabackman, Alexa A; Frankson, Rochelle; Marsan, Eric S; Perry, Kay; Cole, Kathryn E

    2016-09-01

    Histone deacetylases (HDACs) catalyze the hydrolysis of acetylated lysine side chains in histone and non-histone proteins, and play a critical role in the regulation of many biological processes, including cell differentiation, proliferation, senescence, and apoptosis. Aberrant HDAC activity is associated with cancer, making these enzymes important targets for drug design. In general, HDAC inhibitors (HDACi) block the proliferation of tumor cells by inducing cell differentiation, cell cycle arrest, and/or apoptosis, and comprise some of the leading therapies in cancer treatments. To date, four HDACi have been FDA approved for the treatment of cancers: suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza®), romidepsin (FK228, Istodax®), belinostat (Beleodaq®), and panobinostat (Farydak®). Most current inhibitors are pan-HDACi, and non-selectively target a number of HDAC isoforms. Six previously reported HDACi were rationally designed, however, to target a unique sub-pocket found only in HDAC8. While these inhibitors were indeed potent against HDAC8, and even demonstrated specificity for HDAC8 over HDACs 1 and 6, there were no structural data to confirm the mode of binding. Here we report the X-ray crystal structure of Compound 6 complexed with HDAC8 to 1.98Å resolution. We also describe the use of molecular docking studies to explore the binding interactions of the other 5 related HDACi. Our studies confirm that the HDACi induce the formation of and bind in the HDAC8-specific subpocket, offering insights into isoform-specific inhibition. PMID:27374062

  9. [Software version and medical device software supervision].

    PubMed

    Peng, Liang; Liu, Xiaoyan

    2015-01-01

    The importance of software version in the medical device software supervision does not cause enough attention at present. First of all, the effect of software version in the medical device software supervision is discussed, and then the necessity of software version in the medical device software supervision is analyzed based on the discussion of the misunderstanding of software version. Finally the concrete suggestions on software version naming rules, software version supervision for the software in medical devices, and software version supervision scheme are proposed.

  10. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Stephen, Ed.

    1990-01-01

    Reviewed are six software packages for Apple and/or IBM computers. Included are "Autograph,""The New Game Show,""Science Probe-Earth Science,""Pollution Patrol,""Investigating Plant Growth," and "AIDS: The Investigation." Discussed are the grade level, function, availability, cost, and hardware requirements of each. (CW)

  11. Software Reviews.

    ERIC Educational Resources Information Center

    Science and Children, 1989

    1989-01-01

    Reviews of seven software packages are presented including "The Environment I: Habitats and EcoSystems; II Cycles and Interactions"; "Super Sign Maker"; "The Great Knowledge Race: Substance Abuse"; "Exploring Science: Temperature"; "Fast Food Calculator and RD Aide"; "The Human Body: Circulation and Respiration" and "Forces in Liquids and Gases."…

  12. Star Software.

    ERIC Educational Resources Information Center

    Kloza, Brad

    2000-01-01

    Presents a collection of computer software programs designed to spark learning enthusiasm at every grade level and across the curriculum. They include Reader Rabbit's Learn to Read, Spelling Power, Mind Twister Math, Community Construction Kit, Breaking the Code, Encarta Africana 2000, Virtual Serengeti, Operation: Frog (Deluxe), and My First…

  13. Software Reviews.

    ERIC Educational Resources Information Center

    Science and Children, 1988

    1988-01-01

    Reviews five software packages for use with school age children. Includes "Science Toolkit Module 2: Earthquake Lab"; "Adaptations and Identification"; "Geoworld"; "Body Systems II Series: The Blood System: A Liquid of Life," all for Apple II, and "Science Courseware: Life Science/Biology" for Apple II and IBM. (CW)

  14. Software Update.

    ERIC Educational Resources Information Center

    Currents, 2000

    2000-01-01

    A chart of 40 alumni-development database systems provides information on vendor/Web site, address, contact/phone, software name, price range, minimum suggested workstation/suggested server, standard reports/reporting tools, minimum/maximum record capacity, and number of installed sites/client type. (DB)

  15. Software Comparison

    NASA Technical Reports Server (NTRS)

    Blanchard, D. C.

    1986-01-01

    Software Comparison Package (SCP) compares similar files. Normally, these are 90-character files produced by CDC UPDATE utility from program libraries that contain FORTRAN source code plus identifier. SCP also used to compare load maps, cross-reference outputs, and UPDATE corrections sets. Helps wherever line-by-line comparison of similarly structured files required.

  16. Software Reviews.

    ERIC Educational Resources Information Center

    Classroom Computer Learning, 1990

    1990-01-01

    Reviewed are two computer software packages: "Super Solvers Midnight Rescue!" a problem-solving program for IBM PCs; and "Interactive Physics," a simulation program for the Macintosh computer. The functions of the package are discussed including strengths and weaknesses and teaching suggestions. (CW)

  17. Software Reviews.

    ERIC Educational Resources Information Center

    Bitter, Gary G., Ed.

    1989-01-01

    Describes three software packages: (1) "MacMendeleev"--database/graphic display for chemistry, grades 10-12, Macintosh; (2) "Geometry One: Foundations"--geometry tutorial, grades 7-12, IBM; (3) "Mathematics Exploration Toolkit"--algebra and calculus tutorial, grades 8-12, IBM. (MVL)

  18. Software reengineering

    NASA Technical Reports Server (NTRS)

    Fridge, Ernest M., III

    1991-01-01

    Programs in use today generally have all of the function and information processing capabilities required to do their specified job. However, older programs usually use obsolete technology, are not integrated properly with other programs, and are difficult to maintain. Reengineering is becoming a prominent discipline as organizations try to move their systems to more modern and maintainable technologies. The Johnson Space Center (JSC) Software Technology Branch (STB) is researching and developing a system to support reengineering older FORTRAN programs into more maintainable forms that can also be more readily translated to a modern languages such as FORTRAN 8x, Ada, or C. This activity has led to the development of maintenance strategies for design recovery and reengineering. These strategies include a set of standards, methodologies, and the concepts for a software environment to support design recovery and reengineering. A brief description of the problem being addressed and the approach that is being taken by the STB toward providing an economic solution to the problem is provided. A statement of the maintenance problems, the benefits and drawbacks of three alternative solutions, and a brief history of the STB experience in software reengineering are followed by the STB new FORTRAN standards, methodology, and the concepts for a software environment.

  19. Software Patents.

    ERIC Educational Resources Information Center

    Burke, Edmund B.

    1994-01-01

    Outlines basic patent law information that pertains to computer software programs. Topics addressed include protection in other countries; how to obtain patents; kinds of patents; duration; classes of patentable subject matter, including machines and processes; patentability searches; experimental use prior to obtaining a patent; and patent…

  20. Software Reviews.

    ERIC Educational Resources Information Center

    Mathematics and Computer Education, 1987

    1987-01-01

    Presented are reviews of several microcomputer software programs. Included are reviews of: (1) Microstat (Zenith); (2) MathCAD (MathSoft); (3) Discrete Mathematics (True Basic); (4) CALCULUS (True Basic); (5) Linear-Kit (John Wiley); and (6) Geometry Sensei (Broderbund). (RH)

  1. Software Reviews.

    ERIC Educational Resources Information Center

    Smith, Richard L., Ed.

    1988-01-01

    Reviews two software packages, "Solutions Unlimited" and "BASIC Data Base System." Provides a description, summary, strengths and weaknesses, availability and costs. Includes reviews of three structured BASIC packages: "True BASIC (2.0)"; "Turbo BASIC (1.0)"; and "QuickBASIC (3.0)." Explains significant features such as graphics, costs,…

  2. Reviews: Software.

    ERIC Educational Resources Information Center

    Mackenzie, Norma N.; And Others

    1988-01-01

    Reviews four computer software packages including: "The Physical Science Series: Sound" which demonstrates making waves, speed of sound, doppler effect, and human hearing; "Andromeda" depicting celestial motions in any direction; "Biology Quiz: Humans" covering chemistry, cells, viruses, and human biology; and "MacStronomy" covering information on…

  3. Reviews, Software.

    ERIC Educational Resources Information Center

    Science Teacher, 1988

    1988-01-01

    Reviews two software programs for Apple series computers. Includes "Orbital Mech," a basic planetary orbital simulation for the Macintosh, and "START: Stimulus and Response Tools for Experiments in Memory, Learning, Cognition, and Perception," a program that demonstrates basic psychological principles and experiments. (CW)

  4. Software Reviews.

    ERIC Educational Resources Information Center

    Teles, Elizabeth, Ed.; And Others

    1990-01-01

    Reviewed are two computer software packages for Macintosh microcomputers including "Phase Portraits," an exploratory graphics tool for studying first-order planar systems; and "MacMath," a set of programs for exploring differential equations, linear algebra, and other mathematical topics. Features, ease of use, cost, availability, and hardware…

  5. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Stephen, Ed.

    1989-01-01

    Six software packages are described in this review. Included are "Molecules and Atoms: Exploring the Essence of Matter"; "Heart Probe"; "GM Sunraycer"; "Six Puzzles"; "Information Laboratory--Life Science"; and "Science Test Builder." Hardware requirements, prices, and a summary of the abilities of each program are presented. (CW)

  6. Software Reviews.

    ERIC Educational Resources Information Center

    Wulfson, Stephen, Ed.

    1989-01-01

    Presents comments by classroom teachers on software for science teaching including topics on: the size of a molecule, matter, leaves, vitamins and minerals, dinosaurs, and collecting and measuring data. Each is an Apple computer series. Availability and costs are included. (RT)

  7. Software Reviews.

    ERIC Educational Resources Information Center

    Smith, Richard L., Ed.

    1987-01-01

    Reviewed are three computer software programs: the Astronomer (astronomy program for middle school students and older); Hands-on-Statistics: Explorations with a Microcomputer (statistics program for secondary school students and older); and CATGEN (a genetics program for secondary school students and older). Each review provides information on:…

  8. Software Review.

    ERIC Educational Resources Information Center

    McGrath, Diane, Ed.

    1989-01-01

    Reviewed is a computer software package entitled "Audubon Wildlife Adventures: Grizzly Bears" for Apple II and IBM microcomputers. Included are availability, hardware requirements, cost, and a description of the program. The murder-mystery flavor of the program is stressed in this program that focuses on illegal hunting and game management. (CW)

  9. Software Reviews.

    ERIC Educational Resources Information Center

    Science and Children, 1990

    1990-01-01

    Reviewed are seven computer software packages for IBM and/or Apple Computers. Included are "Windows on Science: Volume 1--Physical Science"; "Science Probe--Physical Science"; "Wildlife Adventures--Grizzly Bears"; "Science Skills--Development Programs"; "The Clean Machine"; "Rock Doctor"; and "Geology Search." Cost, quality, hardware, and…

  10. Software Reviews.

    ERIC Educational Resources Information Center

    McGrath, Diane, Ed.

    1989-01-01

    Reviewed are two computer software programs for Apple II computers on weather for upper elementary and middle school grades. "Weather" introduces the major factors (temperature, humidity, wind, and air pressure) affecting weather. "How Weather Works" uses simulation and auto-tutorial formats on sun, wind, fronts, clouds, and storms. (YP)

  11. Software Reviews.

    ERIC Educational Resources Information Center

    Bitter, Gary G., Ed.

    1989-01-01

    Reviews three software packages: (1) "The Weather Machine Courseware Kit" for grades 7-12; (2) "Exploring Measurement, Time, and Money--Level I," for primary level mathematics; and (3) "Professor DOS with SmartGuide for DOS" providing an extensive tutorial covering DOS 2.1 to 4.0. Discusses the strengths and weaknesses of each package. (YP)

  12. Software Reviews.

    ERIC Educational Resources Information Center

    Science and Children, 1990

    1990-01-01

    Reviewed are six computer software packages including "Invisible Bugs,""Chaos Plus...,""The Botanist's Apprentice,""A Baby is Born," Storyboard Plus-Version 2.0," and "Weather." Hardware requirements, functions, performance, and use in the classroom are discussed. (CW)

  13. Software Reviews.

    ERIC Educational Resources Information Center

    Science and Children, 1988

    1988-01-01

    Reviews six software packages for use with school age children ranging from grade 3 to grade 12. Includes "The Microcomputer Based Lab Project: Motion, Sound"; "Genetics"; "Geologic History"; "The Microscope Simulator"; and "Wiz Works" all for Apple II and "Reading for Information: Level II" for IBM. (CW)

  14. Software Reviews.

    ERIC Educational Resources Information Center

    Mackenzie, Norma N.; And Others

    1988-01-01

    Describes computer software for use with various age groups. Topics include activities involving temperature, simulations, earth science, the circulatory system, human body, reading in science, and ecology. Provides information on equipment needed, availability, package contents, and price. Comments of reviews are presented by classroom teachers.…

  15. No Fail Software.

    ERIC Educational Resources Information Center

    Buckleitner, Warren

    1996-01-01

    Recommends and describes specific software programs for children based on a review of 1800 titles. Includes recommendations for preschoolers in the areas of language, math, logic, science, art, creativity, and all-purpose. Presents choices for early elementary students including reading, writing, math, logic, science, social studies, creativity,…

  16. Iterative software kernels

    SciTech Connect

    Duff, I.

    1994-12-31

    This workshop focuses on kernels for iterative software packages. Specifically, the three speakers discuss various aspects of sparse BLAS kernels. Their topics are: `Current status of user lever sparse BLAS`; Current status of the sparse BLAS toolkit`; and `Adding matrix-matrix and matrix-matrix-matrix multiply to the sparse BLAS toolkit`.

  17. SAR Product Control Software

    NASA Astrophysics Data System (ADS)

    Meadows, P. J.; Hounam, D.; Rye, A. J.; Rosich, B.; Börner, T.; Closa, J.; Schättler, B.; Smith, P. J.; Zink, M.

    2003-03-01

    As SAR instruments and their operating modes become more complex, as new applications place more and more demands on image quality and as our understanding of their imperfections becomes more sophisticated, there is increasing recognition that SAR data quality has to be controlled more completely to keep pace. The SAR product CONtrol software (SARCON) is a comprehensive SAR product control software suite tailored to the latest generation of SAR sensors. SARCON profits from the most up-to-date thinking on SAR image performance derived from other spaceborne and airborne SAR projects and is based on the newest applications. This paper gives an overview of the structure and the features of this new software tool, which is a product of a co-operation between teams at BAE SYSTEMS Advanced Technology Centre and DLR under contract to ESA (ESRIN). Work on SARCON began in 1999 and is continuing.

  18. A novel mouse model of tuberous sclerosis complex (TSC): eye-specific Tsc1-ablation disrupts visual-pathway development

    PubMed Central

    Jones, Iwan; Hägglund, Anna-Carin; Törnqvist, Gunilla; Nord, Christoffer; Ahlgren, Ulf; Carlsson, Leif

    2015-01-01

    ABSTRACT Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome that is best characterised by neurodevelopmental deficits and the presence of benign tumours (called hamartomas) in affected organs. This multi-organ disorder results from inactivating point mutations in either the TSC1 or the TSC2 genes and consequent activation of the canonical mammalian target of rapamycin complex 1 signalling (mTORC1) pathway. Because lesions to the eye are central to TSC diagnosis, we report here the generation and characterisation of the first eye-specific TSC mouse model. We demonstrate that conditional ablation of Tsc1 in eye-committed progenitor cells leads to the accelerated differentiation and subsequent ectopic radial migration of retinal ganglion cells. This results in an increase in retinal ganglion cell apoptosis and consequent regionalised axonal loss within the optic nerve and topographical changes to the contra- and ipsilateral input within the dorsal lateral geniculate nucleus. Eyes from adult mice exhibit aberrant retinal architecture and display all the classic neuropathological hallmarks of TSC, including an increase in organ and cell size, ring heterotopias, hamartomas with retinal detachment, and lamination defects. Our results provide the first major insight into the molecular etiology of TSC within the developing eye and demonstrate a pivotal role for Tsc1 in regulating various aspects of visual-pathway development. Our novel mouse model therefore provides a valuable resource for future studies concerning the molecular mechanisms underlying TSC and also as a platform to evaluate new therapeutic approaches for the treatment of this multi-organ disorder. PMID:26449264

  19. A novel mouse model of tuberous sclerosis complex (TSC): eye-specific Tsc1-ablation disrupts visual-pathway development.

    PubMed

    Jones, Iwan; Hägglund, Anna-Carin; Törnqvist, Gunilla; Nord, Christoffer; Ahlgren, Ulf; Carlsson, Leif

    2015-12-01

    Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome that is best characterised by neurodevelopmental deficits and the presence of benign tumours (called hamartomas) in affected organs. This multi-organ disorder results from inactivating point mutations in either the TSC1 or the TSC2 genes and consequent activation of the canonical mammalian target of rapamycin complex 1 signalling (mTORC1) pathway. Because lesions to the eye are central to TSC diagnosis, we report here the generation and characterisation of the first eye-specific TSC mouse model. We demonstrate that conditional ablation of Tsc1 in eye-committed progenitor cells leads to the accelerated differentiation and subsequent ectopic radial migration of retinal ganglion cells. This results in an increase in retinal ganglion cell apoptosis and consequent regionalised axonal loss within the optic nerve and topographical changes to the contra- and ipsilateral input within the dorsal lateral geniculate nucleus. Eyes from adult mice exhibit aberrant retinal architecture and display all the classic neuropathological hallmarks of TSC, including an increase in organ and cell size, ring heterotopias, hamartomas with retinal detachment, and lamination defects. Our results provide the first major insight into the molecular etiology of TSC within the developing eye and demonstrate a pivotal role for Tsc1 in regulating various aspects of visual-pathway development. Our novel mouse model therefore provides a valuable resource for future studies concerning the molecular mechanisms underlying TSC and also as a platform to evaluate new therapeutic approaches for the treatment of this multi-organ disorder.

  20. The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels

    PubMed Central

    Boulay, Anne-Cécile; Saubaméa, Bruno; Cisternino, Salvatore; Mignon, Virginie; Mazeraud, Aurélien; Jourdren, Laurent; Blugeon, Corinne; Cohen-Salmon, Martine

    2015-01-01

    Astrocytes, the most prominent glial cell type in the brain, send specialized processes called endfeet, around blood vessels and express a large molecular repertoire regulating the cerebrovascular system physiology. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction proteins Connexin 43 and 30 (Cx43 and Cx30) allowing in particular for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. In this study, we addressed the specific role of Cx30 at the gliovascular interface. Using an inactivation mouse model for Cx30 (Cx30Δ/Δ; Δ means deleted allele) we showed that absence of Cx30 does not affect blood-brain barrier (BBB) organization and permeability. However, it results in the cerebrovascular fraction, in a strong upregulation of Sgcg encoding γ-Sarcoglycan (γ-SG), a member of the Dystrophin-associated protein complex (DAPC) connecting cytoskeleton and the extracellular matrix. The same molecular event occurs in Cx30T5M/T5M mutated mice, where Cx30 channels are closed, demonstrating that Sgcg regulation relied on Cx30 channel functions. We further characterized the expression of other Sarcoglycan complex (SGC) molecules in the cerebrovascular system and showed the presence of α-, β-, δ-, γ-, ε- and ζ- SG, as well as Sarcospan. Their expression was however not modified in Cx30Δ/Δ. These results suggest that a full SGC might be present in the cerebrovascular system, and that expression of one of its member, γ-SG, depends on Cx30 channels. As described in skeletal muscles, the SGC may contribute to membrane stabilization and signal transduction in the cerebrovascular system, which may therefore be regulated by Cx30 channel-mediated functions. PMID:25698924