Sample records for functional design specification

  1. Functional design specification for the problem data system. [space shuttle

    NASA Technical Reports Server (NTRS)

    Boatman, T. W.

    1975-01-01

    The purpose of the Functional Design Specification is to outline the design for the Problem Data System. The Problem Data System is a computer-based data management system designed to track the status of problems and corrective actions pertinent to space shuttle hardware.

  2. 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.

  3. Feasibility study of an Integrated Program for Aerospace vehicle Design (IPAD). Volume 4: IPAD system design

    NASA Technical Reports Server (NTRS)

    Goldfarb, W.; Carpenter, L. C.; Redhed, D. D.; Hansen, S. D.; Anderson, L. O.; Kawaguchi, A. S.

    1973-01-01

    The computing system design of IPAD is described and the requirements which form the basis for the system design are discussed. The system is presented in terms of a functional design description and technical design specifications. The functional design specifications give the detailed description of the system design using top-down structured programming methodology. Human behavioral characteristics, which specify the system design at the user interface, security considerations, and standards for system design, implementation, and maintenance are also part of the technical design specifications. Detailed specifications of the two most common computing system types in use by the major aerospace companies which could support the IPAD system design are presented. The report of a study to investigate migration of IPAD software between the two candidate 3rd generation host computing systems and from these systems to a 4th generation system is included.

  4. 76 FR 36231 - American Society of Mechanical Engineers (ASME) Codes and New and Revised ASME Code Cases

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ... exceed the test facility limits and reduces the number of functional tests for specific valve designs... addresses reducing the number of functional tests for specific valve designs. The NRC has identified no... the required test pressure for the new Class 1 incompressible-fluid, pressure-relief valve designs...

  5. Towards a behavioral-matching based compilation of synthetic biology functions.

    PubMed

    Basso-Blandin, Adrien; Delaplace, Franck

    2015-09-01

    The field of synthetic biology is looking forward engineering framework for safely designing reliable de-novo biological functions. In this undertaking, Computer-Aided-Design (CAD) environments should play a central role for facilitating the design. Although, CAD environment is widely used to engineer artificial systems the application in synthetic biology is still in its infancy. In this article we address the problem of the design of a high level language which at the core of CAD environment. More specifically the Gubs (Genomic Unified Behavioural Specification) language is a specification language used to describe the observations of the expected behaviour. The compiler appropriately selects components such that the observation of the synthetic biological function resulting to their assembly complies to the programmed behaviour.

  6. Functional design specification for Stowage List And Hardware Tracking System (SLAHTS). [space shuttles

    NASA Technical Reports Server (NTRS)

    Keltner, D. J.

    1975-01-01

    This functional design specification defines the total systems approach to meeting the requirements stated in the Detailed Requirements Document for Stowage List and Hardware Tracking System for the space shuttle program. The stowage list and hardware tracking system is identified at the system and subsystem level with each subsystem defined as a function of the total system.

  7. NASIS data base management system - IBM 360/370 OS MVT implementation. 4: Program design specifications

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The design specifications for the programs and modules within the NASA Aerospace Safety Information System (NASIS) are presented. The purpose of the design specifications is to standardize the preparation of the specifications and to guide the program design. Each major functional module within the system is a separate entity for documentation purposes. The design specifications contain a description of, and specifications for, all detail processing which occurs in the module. Sub-modules, reference tables, and data sets which are common to several modules are documented separately.

  8. NASIS data base management system: IBM 360 TSS implementation. Volume 4: Program design specifications

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The design specifications for the programs and modules within the NASA Aerospace Safety Information System (NASIS) are presented. The purpose of the design specifications is to standardize the preparation of the specifications and to guide the program design. Each major functional module within the system is a separate entity for documentation purposes. The design specifications contain a description of, and specifications for, all detail processing which occurs in the module. Sub-models, reference tables, and data sets which are common to several modules are documented separately.

  9. Spaceborne computer executive routine functional design specification. Volume 2: Computer executive design for space station/base

    NASA Technical Reports Server (NTRS)

    Kennedy, J. R.; Fitzpatrick, W. S.

    1971-01-01

    The computer executive functional system design concepts derived from study of the Space Station/Base are presented. Information Management System hardware configuration as directly influencing the executive design is reviewed. The hardware configuration and generic executive design requirements are considered in detail in a previous report (System Configuration and Executive Requirements Specifications for Reusable Shuttle and Space Station/Base, 9/25/70). This report defines basic system primitives and delineates processes and process control. Supervisor states are considered for describing basic multiprogramming and multiprocessing systems. A high-level computer executive including control of scheduling, allocation of resources, system interactions, and real-time supervisory functions is defined. The description is oriented to provide a baseline for a functional simulation of the computer executive system.

  10. Design and Development of "The Reading Biographer": An Application of Function Specific Assessment.

    ERIC Educational Resources Information Center

    Hanson, Ralph A.; Siegel, Donna Farrell

    The general features of function-specific assessment are described and illustrated via a discussion of the design and development of "The Reading Biographer," an instrument for assessing experiences and activities of students (from early childhood through high school) that affect their reading achievement as high school seniors. The…

  11. Establishing Semantic Interoperability, Under Denied, Disconnected, Intermittant, and Limited Telecommunications Conditions

    DTIC Science & Technology

    2014-06-01

    functionalities and capabilities of DDS. We present a middleware design based on the DDS specifications as developed by the Object Management Group . The...functionalities and capabilities of DDS. We present a middleware design based on the DDS specifications as developed by the Object Management Group ...32 c. History .....................................................................................33 d

  12. Specification and Design of Electrical Flight System Architectures with SysML

    NASA Technical Reports Server (NTRS)

    McKelvin, Mark L., Jr.; Jimenez, Alejandro

    2012-01-01

    Modern space flight systems are required to perform more complex functions than previous generations to support space missions. This demand is driving the trend to deploy more electronics to realize system functionality. The traditional approach for the specification, design, and deployment of electrical system architectures in space flight systems includes the use of informal definitions and descriptions that are often embedded within loosely coupled but highly interdependent design documents. Traditional methods become inefficient to cope with increasing system complexity, evolving requirements, and the ability to meet project budget and time constraints. Thus, there is a need for more rigorous methods to capture the relevant information about the electrical system architecture as the design evolves. In this work, we propose a model-centric approach to support the specification and design of electrical flight system architectures using the System Modeling Language (SysML). In our approach, we develop a domain specific language for specifying electrical system architectures, and we propose a design flow for the specification and design of electrical interfaces. Our approach is applied to a practical flight system.

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

    Goltz, G.; Weiner, H.

    A computer program has been developed for designing and analyzing the performance of solar array/battery power systems for the U. S. Coast Guard Navigational Aids. This program is called the Design Synthesis/Performance Analysis (DSPA) Computer Program. The basic function of the Design Synthesis portion of the DSPA program is to evaluate functional and economic criteria to provide specifications for viable solar array/battery power systems. The basic function of the Performance Analysis portion of the DSPA program is to simulate the operation of solar array/battery power systems under specific loads and environmental conditions. This document provides all the information necessary tomore » access the DSPA programs, to input required data and to generate appropriate Design Synthesis or Performance Analysis Output.« less

  14. Computerized Adaptive Testing System Design: Preliminary Design Considerations.

    ERIC Educational Resources Information Center

    Croll, Paul R.

    A functional design model for a computerized adaptive testing (CAT) system was developed and presented through a series of hierarchy plus input-process-output (HIPO) diagrams. System functions were translated into system structure: specifically, into 34 software components. Implementation of the design in a physical system was addressed through…

  15. Bio-Inspired Multi-Functional Drug Transport Design Concept and Simulations.

    PubMed

    Pidaparti, Ramana M; Cartin, Charles; Su, Guoguang

    2017-04-25

    In this study, we developed a microdevice concept for drug/fluidic transport taking an inspiration from supramolecular motor found in biological cells. Specifically, idealized multi-functional design geometry (nozzle/diffuser/nozzle) was developed for (i) fluidic/particle transport; (ii) particle separation; and (iii) droplet generation. Several design simulations were conducted to demonstrate the working principles of the multi-functional device. The design simulations illustrate that the proposed design concept is feasible for multi-functionality. However, further experimentation and optimization studies are needed to fully evaluate the multifunctional device concept for multiple applications.

  16. Methodology for the systems engineering process. Volume 1: System functional activities

    NASA Technical Reports Server (NTRS)

    Nelson, J. H.

    1972-01-01

    Systems engineering is examined in terms of functional activities that are performed in the conduct of a system definition/design, and system development is described in a parametric analysis that combines functions, performance, and design variables. Emphasis is placed on identification of activities performed by design organizations, design specialty groups, as well as a central systems engineering organizational element. Identification of specific roles and responsibilities for doing functions, and monitoring and controlling activities within the system development operation are also emphasized.

  17. 49 CFR 107.503 - Registration statement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Inspector” or “Design Certifying Engineer”. The following language may be used. I certify that all Registered Inspectors and Design Certifying Engineers used in performance of the prescribed functions meet... requirements applicable to the functions to be performed. (5) A description of the specific functions to be...

  18. Dramatic Arts Facilities.

    ERIC Educational Resources Information Center

    Ontario Dept. of Education, Toronto. School Planning and Building Research Section.

    This booklet begins by explaining the function, the common planning errors, some location specifications, and the general requirements for any dramatic arts area. Facilities for (1) a single classroom, (2) a double classroom, (3) a specifically designed studio, and (4) a specifically designed studio complex are then described and illustrated.…

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

    Bull, Diana L.; Costello, Ronan; Babarit, Aurelien

    Capabilities and functions are hierarchical structures (i.e. taxonomies) that are used in a systems engineering framework to identify complimentary requirements for the system: what the system must do to achieve what it must be. In the case of capabilities, the taxonomy embodies the list of characteristics that are desired, from the perspective of the stakeholders, for the system to be successful. In terms of the functions, the hierarchy represents the solution agnostic (i.e. independent of specific design embodiments) elements that are needed to meet the stakeholder requirements. This paper will focus on the development of the functions. The functions definemore » the fundamental elements of the solution that must be provided in order to achieve the mission and deliver the capabilities. They identify the behaviors the farm must possess, i.e. the farm must be able to generate and deliver electricity from wave power. High-level functions are independent of the technology or design used to implement the function. However, detailed functions may begin to border on specific design choices. Hence a strong effort has been made to maintain functions that are design agnostic.« less

  20. CANES Contracting Strategies for Full Deployment

    DTIC Science & Technology

    2012-01-01

    9 CANES Program Functions in Full Deployment...contractors will design CANES, identifying specific hardware and developing the integration software necessary to consolidate existing C4I functions . At...would be responsible for execut- ing the purchased design and assembling the systems, ensuring that the integration software is functioning . An

  1. Educational Specifications: Linking Design of School Facilities to Educational Program.

    ERIC Educational Resources Information Center

    California State Dept. of Education, Sacramento. Div. of School Facilities Planning.

    The California Department of Education, directed to formalize regulations governing standards for new school design and construction, has prepared a guide to help school districts develop specifications based on the architectural principle that form follows function. This guide discusses the meaning of educational specifications and their…

  2. Design of agricultural product quality safety retrospective supervision system of Jiangsu province

    NASA Astrophysics Data System (ADS)

    Wang, Kun

    2017-08-01

    In store and supermarkets to consumers can trace back agricultural products through the electronic province card to query their origin, planting, processing, packaging, testing and other important information and found that the problems. Quality and safety issues can identify the responsibility of the problem. This paper designs a retroactive supervision system for the quality and safety of agricultural products in Jiangsu Province. Based on the analysis of agricultural production and business process, the goal of Jiangsu agricultural product quality safety traceability system construction is established, and the specific functional requirements and non-functioning requirements of the retroactive system are analyzed, and the target is specified for the specific construction of the retroactive system. The design of the quality and safety traceability system in Jiangsu province contains the design of the overall design, the trace code design and the system function module.

  3. 40 CFR 720.3 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... specific shape or design during manufacture, (2) which has end use function(s) dependent in whole or in part upon its shape or design during end use, and (3) which has either no change of chemical... particles are not considered articles regardless of shape or design. (d) Byproduct means a chemical...

  4. 40 CFR 720.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... specific shape or design during manufacture, (2) which has end use function(s) dependent in whole or in part upon its shape or design during end use, and (3) which has either no change of chemical... particles are not considered articles regardless of shape or design. (d) Byproduct means a chemical...

  5. 40 CFR 720.3 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... specific shape or design during manufacture, (2) which has end use function(s) dependent in whole or in part upon its shape or design during end use, and (3) which has either no change of chemical... particles are not considered articles regardless of shape or design. (d) Byproduct means a chemical...

  6. Specific Language Impairment and Executive Functioning: Parent and Teacher Ratings of Behavior

    ERIC Educational Resources Information Center

    Wittke, Kacie; Spaulding, Tammie J.; Schechtman, Calli J.

    2013-01-01

    Purpose: The current study used the Behavior Rating Inventory of Executive Function--Preschool Version (BRIEF-P; Gioia, Espy, & Isquith, 2003), a rating scale designed to investigate executive behaviors in everyday activities, to examine the executive functioning of preschool children with specific language impairment (SLI) relative to their…

  7. Multiloop Integral System Test (MIST): MIST Facility Functional Specification

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

    Habib, T F; Koksal, C G; Moskal, T E

    1991-04-01

    The Multiloop Integral System Test (MIST) is part of a multiphase program started in 1983 to address small-break loss-of-coolant accidents (SBLOCAs) specific to Babcock and Wilcox designed plants. MIST is sponsored by the US Nuclear Regulatory Commission, the Babcock Wilcox Owners Group, the Electric Power Research Institute, and Babcock and Wilcox. The unique features of the Babcock and Wilcox design, specifically the hot leg U-bends and steam generators, prevented the use of existing integral system data or existing integral facilities to address the thermal-hydraulic SBLOCA questions. MIST was specifically designed and constructed for this program, and an existing facility --more » the Once Through Integral System (OTIS) -- was also used. Data from MIST and OTIS are used to benchmark the adequacy of system codes, such as RELAP5 and TRAC, for predicting abnormal plant transients. The MIST Functional Specification documents as-built design features, dimensions, instrumentation, and test approach. It also presents the scaling basis for the facility and serves to define the scope of work for the facility design and construction. 13 refs., 112 figs., 38 tabs.« less

  8. Designing Homework to Mediate Executive Functioning Deficits in Students with Disabilities

    ERIC Educational Resources Information Center

    Stockall, Nancy

    2017-01-01

    Designing homework to mediate executive functioning disorders of students with disabilities is critical to their future academic success. The article explains and defines different executive functions of the brain and how these impact students' ability to benefit from homework assignments. Specific strategies are provided for designing…

  9. An Analysis of Risk and Function Information in Early Stage Design

    NASA Technical Reports Server (NTRS)

    Barrientos, Francesca; Tumer, Irem; Grantham, Katie; VanWie, Michael; Stone, Robert

    2005-01-01

    The concept of function offers a high potential for thinking and reasoning about designs as well as providing a common thread for relating together other design information. This paper focuses specifically on the relation between function and risk by examining how this information is addressed for a design team conducting early stage design for space missions. Risk information is decomposed into a set of key attributes which are then used to scrutinize the risk information using three approaches from the pragmatics sub-field of linguistics: i) Gricean, ii) Relevance Theory, and Functional Analysis. Results of this linguistics-based approach descriptively account for the context of designer communication with respect to function and risk, and offer prescriptive guidelines for improving designer communication.

  10. Bio-Inspired Multi-Functional Drug Transport Design Concept and Simulations †

    PubMed Central

    Pidaparti, Ramana M.; Cartin, Charles; Su, Guoguang

    2017-01-01

    In this study, we developed a microdevice concept for drug/fluidic transport taking an inspiration from supramolecular motor found in biological cells. Specifically, idealized multi-functional design geometry (nozzle/diffuser/nozzle) was developed for (i) fluidic/particle transport; (ii) particle separation; and (iii) droplet generation. Several design simulations were conducted to demonstrate the working principles of the multi-functional device. The design simulations illustrate that the proposed design concept is feasible for multi-functionality. However, further experimentation and optimization studies are needed to fully evaluate the multifunctional device concept for multiple applications. PMID:28952516

  11. Computer program for design and performance analysis of navigation-aid power systems. Program documentation. Volume 1: Software requirements document

    NASA Technical Reports Server (NTRS)

    Goltz, G.; Kaiser, L. M.; Weiner, H.

    1977-01-01

    A computer program has been developed for designing and analyzing the performance of solar array/battery power systems for the U.S. Coast Guard Navigational Aids. This program is called the Design Synthesis/Performance Analysis (DSPA) Computer Program. The basic function of the Design Synthesis portion of the DSPA program is to evaluate functional and economic criteria to provide specifications for viable solar array/battery power systems. The basic function of the Performance Analysis portion of the DSPA program is to simulate the operation of solar array/battery power systems under specific loads and environmental conditions. This document establishes the software requirements for the DSPA computer program, discusses the processing that occurs within the program, and defines the necessary interfaces for operation.

  12. Spaceborne computer executive routine functional design specification. Volume 1: Functional design of a flight computer executive program for the reusable shuttle

    NASA Technical Reports Server (NTRS)

    Curran, R. T.

    1971-01-01

    A flight computer functional executive design for the reusable shuttle is presented. The design is given in the form of functional flowcharts and prose description. Techniques utilized in the regulation of process flow to accomplish activation, resource allocation, suspension, termination, and error masking based on process primitives are considered. Preliminary estimates of main storage utilization by the Executive are furnished. Conclusions and recommendations for timely, effective software-hardware integration in the reusable shuttle avionics system are proposed.

  13. Design of a recumbent seating system

    NASA Technical Reports Server (NTRS)

    Croyle, Scott; Delarosa, Jose; George, Daren; Hinkle, Cathy; Karas, Stephen

    1993-01-01

    Future space shuttle missions presented by NASA might require the shuttle to rendezvous with the Russian space station Mir for the purpose of transporting astronauts back to earth. Due to the atrophied state of these astronauts, a special seating system must be designed for their transportation. The main functions of this seating system are to support and restrain the astronauts during normal reentry flight and to dampen some of the loading that might occur in a crash situation. Through research, the design team developed many concept variants for these functional requirements. By evaluating each variant, the concepts were eliminated until the four most attractive designs remained. The team used a decision matrix to determine the best concept to carry through embodiment. This concept involved using struts for support during reentry flight and a spring damper/shock absorber system to dampen crash landing loads. The embodiment design process consisted of defining the layout of each of the main functional components, specifically, the seat structure and the strut structure. Through the use of MCS/pal two, the design was refined until it could handle all required loads and dampen to the forces specified. The auxiliary function carriers were then considered. Following the design of these components, the complete final layout could be determined. It is concluded that the final design meets all specifications outlined in the conceptual design. The main advantages of this design are its low weight, simplicity, and large amount of function sharing between different components. The disassembly of this design could potentially present a problem because of time and size constraints involved. Overall, this design meets or exceeds all functional requirements.

  14. Differences in orthotic design for thumb osteoarthritis and its impact on functional outcomes: A scoping review.

    PubMed

    de Almeida, Pedro Henrique Tq; MacDermid, Joy; Pontes, Tatiana Barcelos; Dos Santos-Couto-Paz, Clarissa Cardoso; Matheus, João Paulo Chieregato

    2017-08-01

    Orthoses are a well-known intervention for the treatment of thumb osteoarthritis; however, there is a multitude of orthotic designs and not enough evidence to support the efficacy of specific models. To examine the influence of different orthoses on pain, hand strength, and hand function of patients with thumb osteoarthritis. Literature review. A scoping literature review of 14 publications reporting orthotic interventions for patients with thumb osteoarthritis was conducted. Functional outcomes and measures were extracted and analyzed. In total, 12 studies reported improvements in pain and hand strength after the use of thumb orthoses. Comparisons between different orthotic designs were inconclusive. The use of orthoses can decrease pain and improve hand function of patients with thumb osteoarthritis; however, the effectiveness of different orthoses still needs support through adequate evidence. Clinical relevance Multiple orthoses for thumb osteoarthritis are available. Although current studies support their use to improve pain and hand function, there is no evidence to support the efficacy of specific orthotic designs. Improved functional outcomes can be achieved through the use of short orthoses, providing thumb stabilization without immobilizing adjacent joints.

  15. 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.

  16. Hierarchical specification of the SIFT fault tolerant flight control system

    NASA Technical Reports Server (NTRS)

    Melliar-Smith, P. M.; Schwartz, R. L.

    1981-01-01

    The specification and mechanical verification of the Software Implemented Fault Tolerance (SIFT) flight control system is described. The methodology employed in the verification effort is discussed, and a description of the hierarchical models of the SIFT system is given. To meet the objective of NASA for the reliability of safety critical flight control systems, the SIFT computer must achieve a reliability well beyond the levels at which reliability can be actually measured. The methodology employed to demonstrate rigorously that the SIFT computer meets as reliability requirements is described. The hierarchy of design specifications from very abstract descriptions of system function down to the actual implementation is explained. The most abstract design specifications can be used to verify that the system functions correctly and with the desired reliability since almost all details of the realization were abstracted out. A succession of lower level models refine these specifications to the level of the actual implementation, and can be used to demonstrate that the implementation has the properties claimed of the abstract design specifications.

  17. 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.

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

    Goltz, G.; Weiner, H.

    A computer program has been developed for designing and analyzing the performance of solar array/battery power systems for the U.S. Coast Guard Navigational Aids. This program is called the Design Synthesis/Performance Analysis (DSPA) Computer Program. The basic function of the Design Synthesis portion of the DSPA program is to evaluate functional and economic criteria to provide specifications for viable solar array/battery power systems. The basic function of the Performance Analysis portion of the DSPA program is to simulate the operation of solar array/battery power systems under specific loads and environmental conditions. This document provides a detailed description of the DSPAmore » Computer Program system and its subprograms. This manual will assist the programmer in revising or updating the several subprograms.« less

  19. A Functional-Notional Approach for English for Specific Purposes (ESP) Programs.

    ERIC Educational Resources Information Center

    Kim, Young-Min

    English for Specific Purposes (ESP) programs, characterized by the special needs of the language learners, are described and a review of the literature on a functional-notional approach to the syllabus design of ESP programs is presented. It is suggested that effective ESP programs should teach the language skills necessary to function and perform…

  20. Functional specifications of the annular suspension pointing system, appendix A

    NASA Technical Reports Server (NTRS)

    Edwards, B.

    1980-01-01

    The Annular Suspension Pointing System is described. The Design Realization, Evaluation and Modelling (DREAM) system, and its design description technique, the DREAM Design Notation (DDN) is employed.

  1. Principles for computational design of binding antibodies

    PubMed Central

    Pszolla, M. Gabriele; Lapidoth, Gideon D.; Norn, Christoffer; Dym, Orly; Unger, Tamar; Albeck, Shira; Tyka, Michael D.; Fleishman, Sarel J.

    2017-01-01

    Natural proteins must both fold into a stable conformation and exert their molecular function. To date, computational design has successfully produced stable and atomically accurate proteins by using so-called “ideal” folds rich in regular secondary structures and almost devoid of loops and destabilizing elements, such as cavities. Molecular function, such as binding and catalysis, however, often demands nonideal features, including large and irregular loops and buried polar interaction networks, which have remained challenging for fold design. Through five design/experiment cycles, we learned principles for designing stable and functional antibody variable fragments (Fvs). Specifically, we (i) used sequence-design constraints derived from antibody multiple-sequence alignments, and (ii) during backbone design, maintained stabilizing interactions observed in natural antibodies between the framework and loops of complementarity-determining regions (CDRs) 1 and 2. Designed Fvs bound their ligands with midnanomolar affinities and were as stable as natural antibodies, despite having >30 mutations from mammalian antibody germlines. Furthermore, crystallographic analysis demonstrated atomic accuracy throughout the framework and in four of six CDRs in one design and atomic accuracy in the entire Fv in another. The principles we learned are general, and can be implemented to design other nonideal folds, generating stable, specific, and precise antibodies and enzymes. PMID:28973872

  2. Verification of VLSI designs

    NASA Technical Reports Server (NTRS)

    Windley, P. J.

    1991-01-01

    In this paper we explore the specification and verification of VLSI designs. The paper focuses on abstract specification and verification of functionality using mathematical logic as opposed to low-level boolean equivalence verification such as that done using BDD's and Model Checking. Specification and verification, sometimes called formal methods, is one tool for increasing computer dependability in the face of an exponentially increasing testing effort.

  3. URPD: a specific product primer design tool

    PubMed Central

    2012-01-01

    Background Polymerase chain reaction (PCR) plays an important role in molecular biology. Primer design fundamentally determines its results. Here, we present a currently available software that is not located in analyzing large sequence but used for a rather straight-forward way of visualizing the primer design process for infrequent users. Findings URPD (yoUR Primer Design), a web-based specific product primer design tool, combines the NCBI Reference Sequences (RefSeq), UCSC In-Silico PCR, memetic algorithm (MA) and genetic algorithm (GA) primer design methods to obtain specific primer sets. A friendly user interface is accomplished by built-in parameter settings. The incorporated smooth pipeline operations effectively guide both occasional and advanced users. URPD contains an automated process, which produces feasible primer pairs that satisfy the specific needs of the experimental design with practical PCR amplifications. Visual virtual gel electrophoresis and in silico PCR provide a simulated PCR environment. The comparison of Practical gel electrophoresis comparison to virtual gel electrophoresis facilitates and verifies the PCR experiment. Wet-laboratory validation proved that the system provides feasible primers. Conclusions URPD is a user-friendly tool that provides specific primer design results. The pipeline design path makes it easy to operate for beginners. URPD also provides a high throughput primer design function. Moreover, the advanced parameter settings assist sophisticated researchers in performing experiential PCR. Several novel functions, such as a nucleotide accession number template sequence input, local and global specificity estimation, primer pair redesign, user-interactive sequence scale selection, and virtual and practical PCR gel electrophoresis discrepancies have been developed and integrated into URPD. The URPD program is implemented in JAVA and freely available at http://bio.kuas.edu.tw/urpd/. PMID:22713312

  4. URPD: a specific product primer design tool.

    PubMed

    Chuang, Li-Yeh; Cheng, Yu-Huei; Yang, Cheng-Hong

    2012-06-19

    Polymerase chain reaction (PCR) plays an important role in molecular biology. Primer design fundamentally determines its results. Here, we present a currently available software that is not located in analyzing large sequence but used for a rather straight-forward way of visualizing the primer design process for infrequent users. URPD (yoUR Primer Design), a web-based specific product primer design tool, combines the NCBI Reference Sequences (RefSeq), UCSC In-Silico PCR, memetic algorithm (MA) and genetic algorithm (GA) primer design methods to obtain specific primer sets. A friendly user interface is accomplished by built-in parameter settings. The incorporated smooth pipeline operations effectively guide both occasional and advanced users. URPD contains an automated process, which produces feasible primer pairs that satisfy the specific needs of the experimental design with practical PCR amplifications. Visual virtual gel electrophoresis and in silico PCR provide a simulated PCR environment. The comparison of Practical gel electrophoresis comparison to virtual gel electrophoresis facilitates and verifies the PCR experiment. Wet-laboratory validation proved that the system provides feasible primers. URPD is a user-friendly tool that provides specific primer design results. The pipeline design path makes it easy to operate for beginners. URPD also provides a high throughput primer design function. Moreover, the advanced parameter settings assist sophisticated researchers in performing experiential PCR. Several novel functions, such as a nucleotide accession number template sequence input, local and global specificity estimation, primer pair redesign, user-interactive sequence scale selection, and virtual and practical PCR gel electrophoresis discrepancies have been developed and integrated into URPD. The URPD program is implemented in JAVA and freely available at http://bio.kuas.edu.tw/urpd/.

  5. 33 CFR 157.12f - Workshop functional test requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12f Workshop functional test requirements... the specific design of equipment. A completed workshop certificate including the delivery test... several ppm values on all measurement scales when operated on an oil appropriate for the application of...

  6. 33 CFR 157.12f - Workshop functional test requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12f Workshop functional test requirements... the specific design of equipment. A completed workshop certificate including the delivery test... several ppm values on all measurement scales when operated on an oil appropriate for the application of...

  7. Biomaterials Made from Coiled-Coil Peptides.

    PubMed

    Conticello, Vincent; Hughes, Spencer; Modlin, Charles

    The development of biomaterials designed for specific applications is an important objective in personalized medicine. While the breadth and prominence of biomaterials have increased exponentially over the past decades, critical challenges remain to be addressed, particularly in the development of biomaterials that exhibit highly specific functions. These functional properties are often encoded within the molecular structure of the component molecules. Proteins, as a consequence of their structural specificity, represent useful substrates for the construction of functional biomaterials through rational design. This chapter provides an in-depth survey of biomaterials constructed from coiled-coils, one of the best-understood protein structural motifs. We discuss the utility of this structurally diverse and functionally tunable class of proteins for the creation of novel biomaterials. This discussion illustrates the progress that has been made in the development of coiled-coil biomaterials by showcasing studies that bridge the gap between the academic science and potential technological impact.

  8. Wideband dichroic-filter design for LED-phosphor beam-combining

    DOEpatents

    Falicoff, Waqidi

    2010-12-28

    A general method is disclosed of designing two-component dichroic short-pass filters operable for incidence angle distributions over the 0-30.degree. range, and specific preferred embodiments are listed. The method is based on computer optimization algorithms for an N-layer design, specifically the N-dimensional conjugate-gradient minimization of a merit function based on difference from a target transmission spectrum, as well as subsequent cycles of needle synthesis for increasing N. A key feature of the method is the initial filter design, upon which the algorithm proceeds to iterate successive design candidates with smaller merit functions. This initial design, with high-index material H and low-index L, is (0.75 H, 0.5 L, 0.75 H)^m, denoting m (20-30) repetitions of a three-layer motif, giving rise to a filter with N=2 m+1.

  9. Computational design of a pH stable enzyme: understanding molecular mechanism of penicillin acylase's adaptation to alkaline conditions.

    PubMed

    Suplatov, Dmitry; Panin, Nikolay; Kirilin, Evgeny; Shcherbakova, Tatyana; Kudryavtsev, Pavel; Svedas, Vytas

    2014-01-01

    Protein stability provides advantageous development of novel properties and can be crucial in affording tolerance to mutations that introduce functionally preferential phenotypes. Consequently, understanding the determining factors for protein stability is important for the study of structure-function relationship and design of novel protein functions. Thermal stability has been extensively studied in connection with practical application of biocatalysts. However, little work has been done to explore the mechanism of pH-dependent inactivation. In this study, bioinformatic analysis of the Ntn-hydrolase superfamily was performed to identify functionally important subfamily-specific positions in protein structures. Furthermore, the involvement of these positions in pH-induced inactivation was studied. The conformational mobility of penicillin acylase in Escherichia coli was analyzed through molecular modeling in neutral and alkaline conditions. Two functionally important subfamily-specific residues, Gluβ482 and Aspβ484, were found. Ionization of these residues at alkaline pH promoted the collapse of a buried network of stabilizing interactions that consequently disrupted the functional protein conformation. The subfamily-specific position Aspβ484 was selected as a hotspot for mutation to engineer enzyme variant tolerant to alkaline medium. The corresponding Dβ484N mutant was produced and showed 9-fold increase in stability at alkaline conditions. Bioinformatic analysis of subfamily-specific positions can be further explored to study mechanisms of protein inactivation and to design more stable variants for the engineering of homologous Ntn-hydrolases with improved catalytic properties.

  10. Computational Design of a pH Stable Enzyme: Understanding Molecular Mechanism of Penicillin Acylase's Adaptation to Alkaline Conditions

    PubMed Central

    Suplatov, Dmitry; Panin, Nikolay; Kirilin, Evgeny; Shcherbakova, Tatyana; Kudryavtsev, Pavel; Švedas, Vytas

    2014-01-01

    Protein stability provides advantageous development of novel properties and can be crucial in affording tolerance to mutations that introduce functionally preferential phenotypes. Consequently, understanding the determining factors for protein stability is important for the study of structure-function relationship and design of novel protein functions. Thermal stability has been extensively studied in connection with practical application of biocatalysts. However, little work has been done to explore the mechanism of pH-dependent inactivation. In this study, bioinformatic analysis of the Ntn-hydrolase superfamily was performed to identify functionally important subfamily-specific positions in protein structures. Furthermore, the involvement of these positions in pH-induced inactivation was studied. The conformational mobility of penicillin acylase in Escherichia coli was analyzed through molecular modeling in neutral and alkaline conditions. Two functionally important subfamily-specific residues, Gluβ482 and Aspβ484, were found. Ionization of these residues at alkaline pH promoted the collapse of a buried network of stabilizing interactions that consequently disrupted the functional protein conformation. The subfamily-specific position Aspβ484 was selected as a hotspot for mutation to engineer enzyme variant tolerant to alkaline medium. The corresponding Dβ484N mutant was produced and showed 9-fold increase in stability at alkaline conditions. Bioinformatic analysis of subfamily-specific positions can be further explored to study mechanisms of protein inactivation and to design more stable variants for the engineering of homologous Ntn-hydrolases with improved catalytic properties. PMID:24959852

  11. Earth Observatory Satellite system definition study. Report 5: System design and specifications. Volume 5: Specification for EROS operations control center

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The functional, performance, and design requirements for the Operations Control Center (OCC) of the Earth Observatory Satellite (EOS) system are presented. The OCC controls the operations of the EOS satellite to acquire mission data consisting of: (1) thematic mapper data, (2) multispectral scanner data on EOS-A, or High Resolution Pointable Imager data on EOS-B, and (3) data collection system (DCS) data. The various inputs to the OCC are identified. The functional requirements of the OCC are defined. The specific systems and subsystems of the OCC are described and block diagrams are provided.

  12. Druggable pockets and binding site centric chemical space: a paradigm shift in drug discovery.

    PubMed

    Pérot, Stéphanie; Sperandio, Olivier; Miteva, Maria A; Camproux, Anne-Claude; Villoutreix, Bruno O

    2010-08-01

    Detection, comparison and analyses of binding pockets are pivotal to structure-based drug design endeavors, from hit identification, screening of exosites and de-orphanization of protein functions to the anticipation of specific and non-specific binding to off- and anti-targets. Here, we analyze protein-ligand complexes and discuss methods that assist binding site identification, prediction of druggability and binding site comparison. The full potential of pockets is yet to be harnessed, and we envision that better understanding of the pocket space will have far-reaching implications in the field of drug discovery, such as the design of pocket-specific compound libraries and scoring functions.

  13. Precision control of recombinant gene transcription for CHO cell synthetic biology.

    PubMed

    Brown, Adam J; James, David C

    2016-01-01

    The next generation of mammalian cell factories for biopharmaceutical production will be genetically engineered to possess both generic and product-specific manufacturing capabilities that may not exist naturally. Introduction of entirely new combinations of synthetic functions (e.g. novel metabolic or stress-response pathways), and retro-engineering of existing functional cell modules will drive disruptive change in cellular manufacturing performance. However, before we can apply the core concepts underpinning synthetic biology (design, build, test) to CHO cell engineering we must first develop practical and robust enabling technologies. Fundamentally, we will require the ability to precisely control the relative stoichiometry of numerous functional components we simultaneously introduce into the host cell factory. In this review we discuss how this can be achieved by design of engineered promoters that enable concerted control of recombinant gene transcription. We describe the specific mechanisms of transcriptional regulation that affect promoter function during bioproduction processes, and detail the highly-specific promoter design criteria that are required in the context of CHO cell engineering. The relative applicability of diverse promoter development strategies are discussed, including re-engineering of natural sequences, design of synthetic transcription factor-based systems, and construction of synthetic promoters. This review highlights the potential of promoter engineering to achieve precision transcriptional control for CHO cell synthetic biology. Copyright © 2015. Published by Elsevier Inc.

  14. Executive Functioning and Psychopathology in Psychotherapy for Adolescents with Specific Learning Disorders

    ERIC Educational Resources Information Center

    Kopelman-Rubin, Daphne; Klomek, Anat Brunstein; Al-Yagon, Michal; Mufson, Laura; Apter, Alan; Mikulincer, Mario

    2017-01-01

    This study examined the contribution of executive functioning (EF) to improvements in psychiatric symptomatology following I Can Succeed (ICS; Kopelman-Rubin, 2012) psychotherapy, a skill-enhancement intervention designed to target EF and socio-emotional aspects of specific learning disabilities (SLD). Forty adolescents with SLD underwent ICS in…

  15. Functional Specifications for the OCLC Interlibrary Loan Subsystem.

    ERIC Educational Resources Information Center

    Bova, Phyllis V.

    This report covers functional specifications for the OCLC Interlibrary Loan (ILL) Subsystem, designed to permit participating libraries to increase the availability of library resources to patrons by enabling these libraries to form, transmit, and fulfill loan requests more rapidly and effectively. It will provide rapid access to a large on-line…

  16. 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.

  17. Effectiveness of functional hand splinting and the cognitive orientation to occupational performance (CO-OP) approach in children with cerebral palsy and brain injury: two randomised controlled trial protocols

    PubMed Central

    2014-01-01

    Background Cerebral palsy (CP) and brain injury (BI) are common conditions that have devastating effects on a child’s ability to use their hands. Hand splinting and task-specific training are two interventions that are often used to address deficits in upper limb skills, both in isolation or concurrently. The aim of this paper is to describe the method to be used to conduct two randomised controlled trials (RCT) investigating (a) the immediate effect of functional hand splints, and (b) the effect of functional hand splints used concurrently with task-specific training compared to functional hand splints alone, and to task-specific training alone in children with CP and BI. The Cognitive Orientation to Occupational Performance (CO-OP) approach will be the task-specific training approach used. Methods/Design Two concurrent trials; a two group, parallel design, RCT with a sample size of 30 participants (15 per group); and a three group, parallel design, assessor blinded, RCT with a sample size of 45 participants (15 per group). Inclusion criteria: age 4-15 years; diagnosis of CP or BI; Manual Abilities Classification System (MACS) level I – IV; hand function goals; impaired hand function; the cognitive, language and behavioural ability to participate in CO-OP. Participants will be randomly allocated to one of 3 groups; (1) functional hand splint only (n=15); (2) functional hand splint combined with task-specific training (n=15); (3) task-specific training only (n=15). Allocation concealment will be achieved using sequentially numbered, sealed opaque envelopes opened by an off-site officer after baseline measures. Treatment will be provided for a period of 2 weeks, with outcome measures taken at baseline, 1 hour after randomisation, 2 weeks and 10 weeks. The functional hand splint will be a wrist cock-up splint (+/- thumb support or supination strap). Task-specific training will involve 10 sessions of CO-OP provided in a group of 2-4 children. Primary outcome measures will be the Canadian Occupational Performance Measure (COPM) and the Goal Attainment Scale (GAS). Analysis will be conducted on an intention-to-treat basis. Discussion This paper outlines the protocol for two randomised controlled trials investigating functional hand splints and CO-OP for children with CP and BI. PMID:25023385

  18. Specification and Design Methodologies for High-Speed Fault-Tolerant Array Algorithms and Structures for VLSI.

    DTIC Science & Technology

    1987-06-01

    evaluation and chip layout planning for VLSI digital systems. A high-level applicative (functional) language, implemented at UCLA, allows combining of...operating system. 2.1 Introduction The complexity of VLSI requires the application of CAD tools at all levels of the design process. In order to be...effective, these tools must be adaptive to the specific design. In this project we studied a design method based on the use of applicative languages

  19. In silico design of context-responsive mammalian promoters with user-defined functionality

    PubMed Central

    Gibson, Suzanne J.; Hatton, Diane

    2017-01-01

    Abstract Comprehensive de novo-design of complex mammalian promoters is restricted by unpredictable combinatorial interactions between constituent transcription factor regulatory elements (TFREs). In this study, we show that modular binding sites that do not function cooperatively can be identified by analyzing host cell transcription factor expression profiles, and subsequently testing cognate TFRE activities in varying homotypic and heterotypic promoter architectures. TFREs that displayed position-insensitive, additive function within a specific expression context could be rationally combined together in silico to create promoters with highly predictable activities. As TFRE order and spacing did not affect the performance of these TFRE-combinations, compositions could be specifically arranged to preclude the formation of undesirable sequence features. This facilitated simple in silico-design of promoters with context-required, user-defined functionalities. To demonstrate this, we de novo-created promoters for biopharmaceutical production in CHO cells that exhibited precisely designed activity dynamics and long-term expression-stability, without causing observable retroactive effects on cellular performance. The design process described can be utilized for applications requiring context-responsive, customizable promoter function, particularly where co-expression of synthetic TFs is not suitable. Although the synthetic promoter structure utilized does not closely resemble native mammalian architectures, our findings also provide additional support for a flexible billboard model of promoter regulation. PMID:28977454

  20. HAL/SM system functional design specification. [systems analysis and design analysis of central processing units

    NASA Technical Reports Server (NTRS)

    Ross, C.; Williams, G. P. W., Jr.

    1975-01-01

    The functional design of a preprocessor, and subsystems is described. A structure chart and a data flow diagram are included for each subsystem. Also a group of intermodule interface definitions (one definition per module) is included immediately following the structure chart and data flow for a particular subsystem. Each of these intermodule interface definitions consists of the identification of the module, the function the module is to perform, the identification and definition of parameter interfaces to the module, and any design notes associated with the module. Also described are compilers and computer libraries.

  1. Matrix Transfer Function Design for Flexible Structures: An Application

    NASA Technical Reports Server (NTRS)

    Brennan, T. J.; Compito, A. V.; Doran, A. L.; Gustafson, C. L.; Wong, C. L.

    1985-01-01

    The application of matrix transfer function design techniques to the problem of disturbance rejection on a flexible space structure is demonstrated. The design approach is based on parameterizing a class of stabilizing compensators for the plant and formulating the design specifications as a constrained minimization problem in terms of these parameters. The solution yields a matrix transfer function representation of the compensator. A state space realization of the compensator is constructed to investigate performance and stability on the nominal and perturbed models. The application is made to the ACOSSA (Active Control of Space Structures) optical structure.

  2. Toward high-resolution computational design of helical membrane protein structure and function

    PubMed Central

    Barth, Patrick; Senes, Alessandro

    2016-01-01

    The computational design of α-helical membrane proteins is still in its infancy but has made important progress. De novo design has produced stable, specific and active minimalistic oligomeric systems. Computational re-engineering can improve stability and modulate the function of natural membrane proteins. Currently, the major hurdle for the field is not computational, but the experimental characterization of the designs. The emergence of new structural methods for membrane proteins will accelerate progress PMID:27273630

  3. Toward high-resolution computational design of the structure and function of helical membrane proteins.

    PubMed

    Barth, Patrick; Senes, Alessandro

    2016-06-07

    The computational design of α-helical membrane proteins is still in its infancy but has already made great progress. De novo design allows stable, specific and active minimal oligomeric systems to be obtained. Computational reengineering can improve the stability and function of naturally occurring membrane proteins. Currently, the major hurdle for the field is the experimental characterization of the designs. The emergence of new structural methods for membrane proteins will accelerate progress.

  4. DRS: Derivational Reasoning System

    NASA Technical Reports Server (NTRS)

    Bose, Bhaskar

    1995-01-01

    The high reliability requirements for airborne systems requires fault-tolerant architectures to address failures in the presence of physical faults, and the elimination of design flaws during the specification and validation phase of the design cycle. Although much progress has been made in developing methods to address physical faults, design flaws remain a serious problem. Formal methods provides a mathematical basis for removing design flaws from digital systems. DRS (Derivational Reasoning System) is a formal design tool based on advanced research in mathematical modeling and formal synthesis. The system implements a basic design algebra for synthesizing digital circuit descriptions from high level functional specifications. DRS incorporates an executable specification language, a set of correctness preserving transformations, verification interface, and a logic synthesis interface, making it a powerful tool for realizing hardware from abstract specifications. DRS integrates recent advances in transformational reasoning, automated theorem proving and high-level CAD synthesis systems in order to provide enhanced reliability in designs with reduced time and cost.

  5. PET/CT scanners: a hardware approach to image fusion.

    PubMed

    Townsend, David W; Beyer, Thomas; Blodgett, Todd M

    2003-07-01

    New technology that combines positron tomography with x-ray computed tomography (PET/CT) is available from all major vendors of PET imaging equipment: CTI, Siemens, GE, Philips. Although not all vendors have made the same design choices as those described in this review all have in common that their high performance design places a commercial CT scanner in tandem with a commercial PET scanner. The level of physical integration is actually less than that of the original prototype design where the CT and PET components were mounted on the same rotating support. There will undoubtedly be a demand for PET/CT technology with a greater level of integration, and at a reduced cost. This may be achieved through the design of a scanner specifically for combined anatomical and functional imaging, rather than a design combining separate CT and PET scanners, as in the current approaches. By avoiding the duplication of data acquisition and image reconstruction functions, for example, a more integrated design should also allow cost savings over current commercial PET/CT scanners. The goal is then to design and build a device specifically for imaging the function and anatomy of cancer in the most optimal and effective way, without conceptualizing it as combined PET and CT. The development of devices specifically for imaging a particular disease (eg, cancer) differs from the conventional approach of, for example, an all-purpose anatomical imaging device such as a CT scanner. This new concept targets more of a disease management approach rather than the usual division into the medical specialties of radiology (anatomical imaging) and nuclear medicine (functional imaging). Copyright 2003 Elsevier Inc. All rights reserved.

  6. Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.

    PubMed

    Sen, Dilara; Keung, Albert J

    2018-01-01

    The advent of locus-specific protein recruitment technologies has enabled a new class of studies in chromatin biology. Epigenome editors enable biochemical modifications of chromatin at almost any specific endogenous locus. Their locus specificity unlocks unique information including the functional roles of distinct modifications at specific genomic loci. Given the growing interest in using these tools for biological and translational studies, there are many specific design considerations depending on the scientific question or clinical need. Here we present and discuss important design considerations and challenges regarding the biochemical and locus specificities of epigenome editors. These include how to account for the complex biochemical diversity of chromatin; control for potential interdependency of epigenome editors and their resultant modifications; avoid sequestration effects; quantify the locus specificity of epigenome editors; and improve locus specificity by considering concentration, affinity, avidity, and sequestration effects.

  7. Molecular biomimetics: GEPI-based biological routes to technology.

    PubMed

    Tamerler, Candan; Khatayevich, Dmitriy; Gungormus, Mustafa; Kacar, Turgay; Oren, E Emre; Hnilova, Marketa; Sarikaya, Mehmet

    2010-01-01

    In nature, the viability of biological systems is sustained via specific interactions among the tens of thousands of proteins, the major building blocks of organisms from the simplest single-celled to the most complex multicellular species. Biomolecule-material interaction is accomplished with molecular specificity and efficiency leading to the formation of controlled structures and functions at all scales of dimensional hierarchy. Through evolution, Mother Nature developed molecular recognition by successive cycles of mutation and selection. Molecular specificity of probe-target interactions, e.g., ligand-receptor, antigen-antibody, is always based on specific peptide molecular recognition. Using biology as a guide, we can now understand, engineer, and control peptide-material interactions and exploit them as a new design tool for novel materials and systems. We adapted the protocols of combinatorially designed peptide libraries, via both cell surface or phage display methods; using these we select short peptides with specificity to a variety of practical materials. These genetically engineered peptides for inorganics (GEPI) are then studied experimentally to establish their binding kinetics and surface stability. The bound peptide structure and conformations are interrogated both experimentally and via modeling, and self-assembly characteristics are tested via atomic force microscopy. We further engineer the peptide binding and assembly characteristics using a computational biomimetics approach where bioinformatics based peptide-sequence similarity analysis is developed to design higher generation function-specific peptides. The molecular biomimetic approach opens up new avenues for the design and utilization of multifunctional molecular systems in a wide-range of applications from tissue engineering, disease diagnostics, and therapeutics to various areas of nanotechnology where integration is required among inorganic, organic and biological materials. Here, we describe lessons from biology with examples of protein-mediated functional biological materials, explain how novel peptides can be designed with specific affinity to inorganic solids using evolutionary engineering approaches, give examples of their potential utilizations in technology and medicine, and, finally, provide a summary of challenges and future prospects. (c) 2010 Wiley Periodicals, Inc.

  8. Coupling Protein Side-Chain and Backbone Flexibility Improves the Re-design of Protein-Ligand Specificity.

    PubMed

    Ollikainen, Noah; de Jong, René M; Kortemme, Tanja

    2015-01-01

    Interactions between small molecules and proteins play critical roles in regulating and facilitating diverse biological functions, yet our ability to accurately re-engineer the specificity of these interactions using computational approaches has been limited. One main difficulty, in addition to inaccuracies in energy functions, is the exquisite sensitivity of protein-ligand interactions to subtle conformational changes, coupled with the computational problem of sampling the large conformational search space of degrees of freedom of ligands, amino acid side chains, and the protein backbone. Here, we describe two benchmarks for evaluating the accuracy of computational approaches for re-engineering protein-ligand interactions: (i) prediction of enzyme specificity altering mutations and (ii) prediction of sequence tolerance in ligand binding sites. After finding that current state-of-the-art "fixed backbone" design methods perform poorly on these tests, we develop a new "coupled moves" design method in the program Rosetta that couples changes to protein sequence with alterations in both protein side-chain and protein backbone conformations, and allows for changes in ligand rigid-body and torsion degrees of freedom. We show significantly increased accuracy in both predicting ligand specificity altering mutations and binding site sequences. These methodological improvements should be useful for many applications of protein-ligand design. The approach also provides insights into the role of subtle conformational adjustments that enable functional changes not only in engineering applications but also in natural protein evolution.

  9. Structural basis of substrate specificity in the serine proteases.

    PubMed Central

    Perona, J. J.; Craik, C. S.

    1995-01-01

    Structure-based mutational analysis of serine protease specificity has produced a large database of information useful in addressing biological function and in establishing a basis for targeted design efforts. Critical issues examined include the function of water molecules in providing strength and specificity of binding, the extent to which binding subsites are interdependent, and the roles of polypeptide chain flexibility and distal structural elements in contributing to specificity profiles. The studies also provide a foundation for exploring why specificity modification can be either straightforward or complex, depending on the particular system. PMID:7795518

  10. Designated Airworthiness Representatives

    DOT National Transportation Integrated Search

    1985-10-01

    This advisory circular (AC) contains information and guidance concerning the : selection and appointment of Designated Airworthiness Representatives (DAR's) and identifies the specific functions which may be delegated to DAR's as authorized by the Fe...

  11. Putative and unique gene sequence utilization for the design of species specific probes as modeled by Lactobacillus plantarum

    USDA-ARS?s Scientific Manuscript database

    The concept of utilizing putative and unique gene sequences for the design of species specific probes was tested. The abundance profile of assigned functions within the Lactobacillus plantarum genome was used for the identification of the putative and unique gene sequence, csh. The targeted gene (cs...

  12. AMICAL: An aid for architectural synthesis and exploration of control circuits

    NASA Astrophysics Data System (ADS)

    Park, Inhag

    AMICAL is an architectural synthesis system for control flow dominated circuits. A behavioral finite state machine specification, where the scheduling and register allocation were performed, is presented. An abstract architecture specification that may feed existing silicon compilers acting at the logic and register transfer levels is described. AMICAL consists of five main functions allowing automatic, interactive and manual synthesis, as well as the combination of these methods. These functions are a synthesizer, a graphics editor, a verifier, an evaluator, and a documentor. Automatic synthesis is achieved by algorithms that allocate both functional units, stored in an expandable user defined library, and connections. AMICAL also allows the designer to interrupt the synthesis process at any stage and make interactive modifications via a specially designed graphics editor. The user's modifications are verified and evaluated to ensure that no design rules are broken and that any imposed constraints are still met. A documentor provides the designer with status and feedback reports from the synthesis process.

  13. Enhanced Multiobjective Optimization Technique for Comprehensive Aerospace Design. Part A

    NASA Technical Reports Server (NTRS)

    Chattopadhyay, Aditi; Rajadas, John N.

    1997-01-01

    A multidisciplinary design optimization procedure which couples formal multiobjectives based techniques and complex analysis procedures (such as computational fluid dynamics (CFD) codes) developed. The procedure has been demonstrated on a specific high speed flow application involving aerodynamics and acoustics (sonic boom minimization). In order to account for multiple design objectives arising from complex performance requirements, multiobjective formulation techniques are used to formulate the optimization problem. Techniques to enhance the existing Kreisselmeier-Steinhauser (K-S) function multiobjective formulation approach have been developed. The K-S function procedure used in the proposed work transforms a constrained multiple objective functions problem into an unconstrained problem which then is solved using the Broyden-Fletcher-Goldfarb-Shanno (BFGS) algorithm. Weight factors are introduced during the transformation process to each objective function. This enhanced procedure will provide the designer the capability to emphasize specific design objectives during the optimization process. The demonstration of the procedure utilizes a computational Fluid dynamics (CFD) code which solves the three-dimensional parabolized Navier-Stokes (PNS) equations for the flow field along with an appropriate sonic boom evaluation procedure thus introducing both aerodynamic performance as well as sonic boom as the design objectives to be optimized simultaneously. Sensitivity analysis is performed using a discrete differentiation approach. An approximation technique has been used within the optimizer to improve the overall computational efficiency of the procedure in order to make it suitable for design applications in an industrial setting.

  14. 26 CFR 1.263(a)-4 - Amounts paid to acquire or create intangibles.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...). (v) Creation of package design. Amounts paid to develop a package design are treated as amounts that...). For purposes of this section, the term package design means the specific graphic arrangement or design... design of a container with respect to its shape or function. (4) Coordination with other provisions of...

  15. An overview of software design languages. [for Galileo spacecraft Command and Data Subsystems

    NASA Technical Reports Server (NTRS)

    Callender, E. D.

    1980-01-01

    The nature and use of design languages and associated processors that are used in software development are reviewed with reference to development work on the Galileo spacecraft project, a Jupiter orbiter scheduled for launch in 1984. The major design steps are identified (functional design, architectural design, detailed design, coding, and testing), and the purpose, functions and the range of applications of design languages are examined. Then the general character of any design language is analyzed in terms of syntax and semantics. Finally, the differences and similarities between design languages are illustrated by examining two specific design languages: Software Design and Documentation language and Problem Statement Language/Problem Statement Analyzer.

  16. What Do Children with Specific Language Impairment Do with Multiple Forms of "DO"?

    ERIC Educational Resources Information Center

    Rice, Mabel L.; Blossom, Megan

    2013-01-01

    Purpose: This study was designed to examine the early usage patterns of multiple grammatical functions of "DO" in children with and without specific language impairment (SLI). Children's use of this plurifunctional form is informative for evaluation of theoretical accounts of the deficit in SLI. Method: Spontaneous uses of multiple functions of…

  17. RNA Nanostructures – Methods and Protocols | Center for Cancer Research

    Cancer.gov

    RNA nanotechnology is a young field with many potential applications. The goal is to utilize designed RNA strands, such that the obtained constructs have specific properties in terms of shape and functionality. RNA has potential functionalities that are comparable to that of proteins, but possesses (compared to proteins) simpler design principles akin to DNA. The promise is

  18. Adsorptive detoxification of fermentation inhibitors in acid pretreated liquor using functionalized polymer designed by molecular simulation.

    PubMed

    Devendra, Leena P; Pandey, Ashok

    2017-11-01

    Acid pretreatment is the most common method employed in the lignocellulosic biorefinery leading to the separation of pentose and hexose sugar. The liquor obtained after pretreatment (acid pretreatment liquor or APL) needs to be detoxified prior to fermentation. The aim of this study was to design functional groups on a polymer matrix which are selective in their interaction to inhibitors with little or no specificity to sugars. Molecular modeling was used as a tool to design a suitable adsorbent for selective adsorption of inhibitors from a complex mixture of APL. Phenyl glycine-p-sulfonic acid loaded on chloromethylated polystyrene polymer was designed as an adsorbent for selective interaction with inhibitors. Experimental verification of the selectivity was successfully achieved. The current study provides insights on the adsorptive separation processes at the molecular level by design of specific adsorbent which can be tailor made for the better selectivity of the desired component.

  19. Space shuttle configuration accounting functional design specification

    NASA Technical Reports Server (NTRS)

    1974-01-01

    An analysis is presented of the requirements for an on-line automated system which must be capable of tracking the status of requirements and engineering changes and of providing accurate and timely records. The functional design specification provides the definition, description, and character length of the required data elements and the interrelationship of data elements to adequately track, display, and report the status of active configuration changes. As changes to the space shuttle program levels II and III configuration are proposed, evaluated, and dispositioned, it is the function of the configuration management office to maintain records regarding changes to the baseline and to track and report the status of those changes. The configuration accounting system will consist of a combination of computers, computer terminals, software, and procedures, all of which are designed to store, retrieve, display, and process information required to track proposed and proved engineering changes to maintain baseline documentation of the space shuttle program levels II and III.

  20. Graphic design of pinhole cameras

    NASA Technical Reports Server (NTRS)

    Edwards, H. B.; Chu, W. P.

    1979-01-01

    The paper describes a graphic technique for the analysis and optimization of pinhole size and focal length. The technique is based on the use of the transfer function of optical elements described by Scott (1959) to construct the transfer function of a circular pinhole camera. This transfer function is the response of a component or system to a pattern of lines having a sinusoidally varying radiance at varying spatial frequencies. Some specific examples of graphic design are presented.

  1. Mining HIV protease cleavage data using genetic programming with a sum-product function.

    PubMed

    Yang, Zheng Rong; Dalby, Andrew R; Qiu, Jing

    2004-12-12

    In order to design effective HIV inhibitors, studying and understanding the mechanism of HIV protease cleavage specification is critical. Various methods have been developed to explore the specificity of HIV protease cleavage activity. However, success in both extracting discriminant rules and maintaining high prediction accuracy is still challenging. The earlier study had employed genetic programming with a min-max scoring function to extract discriminant rules with success. However, the decision will finally be degenerated to one residue making further improvement of the prediction accuracy difficult. The challenge of revising the min-max scoring function so as to improve the prediction accuracy motivated this study. This paper has designed a new scoring function called a sum-product function for extracting HIV protease cleavage discriminant rules using genetic programming methods. The experiments show that the new scoring function is superior to the min-max scoring function. The software package can be obtained by request to Dr Zheng Rong Yang.

  2. Communications network design and costing model users manual

    NASA Technical Reports Server (NTRS)

    Logan, K. P.; Somes, S. S.; Clark, C. A.

    1983-01-01

    The information and procedures needed to exercise the communications network design and costing model for performing network analysis are presented. Specific procedures are included for executing the model on the NASA Lewis Research Center IBM 3033 computer. The concepts, functions, and data bases relating to the model are described. Model parameters and their format specifications for running the model are detailed.

  3. AN ULTRAVIOLET-VISIBLE SPECTROPHOTOMETER AUTOMATION SYSTEM. PART I: FUNCTIONAL SPECIFICATIONS

    EPA Science Inventory

    This document contains the project definition, the functional requirements, and the functional design for a proposed computer automation system for scanning spectrophotometers. The system will be implemented on a Data General computer using the BASIC language. The system is a rea...

  4. Leveraging advances in biology to design biomaterials

    NASA Astrophysics Data System (ADS)

    Darnell, Max; Mooney, David J.

    2017-12-01

    Biomaterials have dramatically increased in functionality and complexity, allowing unprecedented control over the cells that interact with them. From these engineering advances arises the prospect of improved biomaterial-based therapies, yet practical constraints favour simplicity. Tools from the biology community are enabling high-resolution and high-throughput bioassays that, if incorporated into a biomaterial design framework, could help achieve unprecedented functionality while minimizing the complexity of designs by identifying the most important material parameters and biological outputs. However, to avoid data explosions and to effectively match the information content of an assay with the goal of the experiment, material screens and bioassays must be arranged in specific ways. By borrowing methods to design experiments and workflows from the bioprocess engineering community, we outline a framework for the incorporation of next-generation bioassays into biomaterials design to effectively optimize function while minimizing complexity. This framework can inspire biomaterials designs that maximize functionality and translatability.

  5. Friendly Extensible Transfer Tool Beta Version

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

    Collins, William P.; Gutierrez, Kenneth M.; McRee, Susan R.

    2016-04-15

    Often data transfer software is designed to meet specific requirements or apply to specific environments. Frequently, this requires source code integration for added functionality. An extensible data transfer framework is needed to more easily incorporate new capabilities, in modular fashion. Using FrETT framework, functionality may be incorporated (in many cases without need of source code) to handle new platform capabilities: I/O methods (e.g., platform specific data access), network transport methods, data processing (e.g., data compression.).

  6. In vitro optimization of antisense oligodeoxynucleotide design: an example using the connexin gene family.

    PubMed

    Law, Lee Yong; Zhang, Wei V; Stott, N Susan; Becker, David L; Green, Colin R

    2006-09-01

    The completion of the human and mouse genomes has identified at least 20 connexin isomers in this family of intercellular channel proteins. However, there are no specific gap junction blockers or channel-blocking mimetic peptides available for the study of specific connexins. We designed antisense oligodeoxynucleotides that functionally reduce targeted connexin protein expression and can be used to reveal the biological function of individual connexins in vivo. Connexin mRNA was firstly exposed in vitro to deoxyribozymes complementing the sense coding sequence. Those that cleaved the target connexin mRNA in defined regions were used as the basis to design oligodeoxynucleotides to the accessible sites, thus taking into account tertiary mRNA configurations rather than relying on computed predictions. Antisense oligodeoxynucleotides designed to bind to accessible mRNA sites selectively reduced connexin26 and -43 mRNA expression in a corneal epithelium ex vivo model. Connexin43 protein levels were reduced correlating with the knockdown in mRNA and the protein's rapid turnover; protein levels of connexin26 did not alter, supporting lower turnover rates reported for that protein. We show, for the first time, an inexpensive and empirical approach to the preparation of specific and functional antisense oligodeoxynucleotides against known gene targets in the post-genomic era.

  7. Power Extension Package (PEP) system definition extension, orbital service module systems analysis study. Volume 4: PEP functional specification

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The functional, performance, design, and test requirements for the Orbiter power extension package and its associated ground support equipment are defined. Both government and nongovernment standards and specifications are cited for the following subsystems: electrical power, structural/mechanical, avionics, and thermal control. Quality control assurance provisions and preparation for delivery are also discussed.

  8. Quest for business intelligence in health care.

    PubMed

    Van De Graaff, Joe; Cameron, Austin

    2013-02-01

    In an era of reform, providers are examining more forward-thinking business intelligence strategies, according to a recent study. Enterprise business intelligence tool sets offer a breadth of design and functionality that often are capable of serving the enterprise. One limitation of broader tool sets is that they may lack needed application-specific functionality or prebuilt healthcare content for a specific department.

  9. Multiobjective optimization techniques for structural design

    NASA Technical Reports Server (NTRS)

    Rao, S. S.

    1984-01-01

    The multiobjective programming techniques are important in the design of complex structural systems whose quality depends generally on a number of different and often conflicting objective functions which cannot be combined into a single design objective. The applicability of multiobjective optimization techniques is studied with reference to simple design problems. Specifically, the parameter optimization of a cantilever beam with a tip mass and a three-degree-of-freedom vabration isolation system and the trajectory optimization of a cantilever beam are considered. The solutions of these multicriteria design problems are attempted by using global criterion, utility function, game theory, goal programming, goal attainment, bounded objective function, and lexicographic methods. It has been observed that the game theory approach required the maximum computational effort, but it yielded better optimum solutions with proper balance of the various objective functions in all the cases.

  10. Space station MSFC-DPD-235/DR no. CM-03 specification, modular space station project, Part 1 CEI

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Contract engineering item specifications for the modular space station are presented. These specifications resulted from the development and allocations of requirements which are concise statements of performance or constraints on performance. Specifications contain requirements for functional performance and for the verification of design solutions.

  11. In-vitro engineering of novel bioactivity in the natural enzymes

    NASA Astrophysics Data System (ADS)

    Tiwari, Vishvanath

    2016-10-01

    Enzymes catalyze various biochemical functions with high efficiency and specificity. In-vitro design of the enzyme leads to novel bioactivity in this natural biomolecule that give answers of some vital questions like crucial residues in binding with substrate, molecular evolution, cofactor specificity etc. Enzyme engineering technology involves directed evolution, rational designing, semi-rational designing and structure-based designing using chemical modifications. Similarly, combined computational and in-vitro evolution approaches together help in artificial designing of novel bioactivity in the natural enzyme. DNA shuffling, error prone PCR and staggered extension process are used to artificially redesign active site of enzyme, which can alter its efficiency and specificity. Modifications of the enzyme can lead to the discovery of new path of molecular evolution, designing of efficient enzymes, locating active sites and crucial residues, shift in substrate and cofactor specificity. The methods and thermodynamics of in-vitro designing of the enzyme are also discussed. Similarly, engineered thermophilic and psychrophilic enzymes attain substrate specificity and activity of mesophilic enzymes that may also be beneficial for industry and therapeutics.

  12. Recommended System Design for the Occupational Health Management Information System (OHMIS). Volume 1.

    DTIC Science & Technology

    1983-04-01

    Management Information System (OHMIS). The system design includes: detailed function data flows for each of the core data processing functions of OHMIS, in the form of input/processing/output algorithms; detailed descriptions of the inputs and outputs; performance specifications of OHMIS; resources required to develop and operate OHMIS (Vol II). In addition, the report provides a summary of the rationale used to develop the recommended system design, a description of the methodology used to develop the recommended system design, and a review of existing

  13. Program design by a multidisciplinary team. [for structural finite element analysis on STAR-100 computer

    NASA Technical Reports Server (NTRS)

    Voigt, S.

    1975-01-01

    The use of software engineering aids in the design of a structural finite-element analysis computer program for the STAR-100 computer is described. Nested functional diagrams to aid in communication among design team members were used, and a standardized specification format to describe modules designed by various members was adopted. This is a report of current work in which use of the functional diagrams provided continuity and helped resolve some of the problems arising in this long-running part-time project.

  14. Designer biomaterials for mechanobiology

    NASA Astrophysics Data System (ADS)

    Li, Linqing; Eyckmans, Jeroen; Chen, Christopher S.

    2017-12-01

    Biomaterials engineered with specific bioactive ligands, tunable mechanical properties and complex architecture have emerged as powerful tools to probe cell sensing and response to physical properties of their material surroundings, and ultimately provide designer approaches to control cell function.

  15. DNA Origami Patterned Colloids for Programmed Design and Chirality

    NASA Astrophysics Data System (ADS)

    Ben Zion, Matan Yah; He, Xiaojin; Maass, Corinna; Sha, Ruojie; Seeman, Ned; Chaikin, Paul

    Micron size colloidal particles are scientifically important as model systems for equilibrium and active systems in physics, chemistry and biology and for technologies ranging from catalysis to photonics. The past decade has seen development of new particles with directional patches, lock and key reactions and specific recognition that guide assembly of structures such as complex crystalline arrays. What remains lacking is the ability to self-assemble structures of arbitrary shape with specific chirality, placement and orientation of neighbors. Here we demonstrate the adaptation of DNA origami nanotechnology to the micron colloidal scale with designed control of neighbor type, placement and dihedral angle. We use DNA origami belts with programmed flexibility, and functionality to pattern colloidal surfaces and bind particles to specific sites at specific angles and make uniquely right handed or left handed structures. The hybrid DNA origami colloid technology should allow the synthesis of designed functional structural and active materials. This work was supported as part of the Center for Bio-Inspired Energy Science, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences under Award # DE-SC0000989.

  16. Development of a Model for Measuring Scientific Processing Skills Based on Brain-Imaging Technology: Focused on the Experimental Design Process

    ERIC Educational Resources Information Center

    Lee, Il-Sun; Byeon, Jung-Ho; Kim, Young-shin; Kwon, Yong-Ju

    2014-01-01

    The purpose of this study was to develop a model for measuring experimental design ability based on functional magnetic resonance imaging (fMRI) during biological inquiry. More specifically, the researchers developed an experimental design task that measures experimental design ability. Using the developed experimental design task, they measured…

  17. Analytical Tools for Functional Assessment of Architectural Layouts

    NASA Astrophysics Data System (ADS)

    Bąkowski, Jarosław

    2017-10-01

    Functional layout of the building, understood as a layout or set of the facility rooms (or groups of rooms) with a system of internal communication, creates an environment and a place of mutual relations between the occupants of the object. Achieving optimal (from the occupants’ point of view) spatial arrangement is possible through activities that often go beyond the stage of architectural design. Adopted in the architectural design, most often during trial and error process or on the basis of previous experience (evidence-based design), functional layout is subject to continuous evaluation and dynamic changing since the beginning of its use. Such verification of the occupancy phase allows to plan future, possible transformations, as well as to develop model solutions for use in other settings. In broader terms, the research hypothesis is to examine whether and how the collected datasets concerning the facility and its utilization can be used to develop methods for assessing functional layout of buildings. In other words, if it is possible to develop an objective method of assessing functional layouts basing on a set of buildings’ parameters: technical, technological and functional ones and whether the method allows developing a set of tools enhancing the design methodology of complex functional objects. By linking the design with the construction phase it is possible to build parametric models of functional layouts, especially in the context of sustainable design or lean design in every aspect: ecological (by reducing the property’s impact on environment), economic (by optimizing its cost) and social (through the implementation of high-performance work environment). Parameterization of size and functional connections of the facility become part of the analyses, as well as the element of model solutions. The “lean” approach means the process of analysis of the existing scheme and consequently - finding weak points as well as means for eliminating these defects. This approach, supplemented by the method of reverse engineering means that already in the design phase there is essential knowledge about the functioning of the facility. It is far beyond intuitive knowledge, based on the standards and specifications. In the scope of reverse engineering methods, the subject of the research is an audit of the product (i.e. architectural design, especially the built spatial layout) in order to determine exactly how it works. Information gained in this way is to help building a system for supporting decisions for preparing design solutions for future investments as well as the functional analysis itself becomes an essential part of the setting up building information process. The data are presented with graphical methods as networks of different factors between rooms. The direct analytical method for the setting is to determine the functional collision between users’ tracks, finding or indication of the shortest paths connecting analyzed rooms and finally to identify the optimal location of these rooms (each according to different factor). The measurement data are supplemented by the results of surveys conducted among users of hospitals, statistics and quantitative medical procedures performed in the test section of the hospital. The results of research are transferred and integrated with BIM system (building information modelling system), and included in the specifications of the IFC (Industry Foundation Classes), especially at the level of information on the relationship between the individual properties associated with elements (in the case of hospitals it may be information about the necessary connections with other rooms, access times from or to specific rooms, rooms utilization conditions, fire safety protection and conditions and many other). At the level of the BIM specification the model data are integrated at the BIM 6D (an extension of the model data with a range of functional analysis) or even BIM 7D (additional integration with systems used at the stage of operation and maintenance of the facility).

  18. Expanding the Scope of Site-Specific Recombinases for Genetic and Metabolic Engineering

    PubMed Central

    Gaj, Thomas; Sirk, Shannon J.; Barbas, Carlos F.

    2014-01-01

    Site-specific recombinases are tremendously valuable tools for basic research and genetic engineering. By promoting high-fidelity DNA modifications, site-specific recombination systems have empowered researchers with unprecedented control over diverse biological functions, enabling countless insights into cellular structure and function. The rigid target specificities of many sites-specific recombinases, however, have limited their adoption in fields that require highly flexible recognition abilities. As a result, intense effort has been directed toward altering the properties of site-specific recombination systems by protein engineering. Here, we review key developments in the rational design and directed molecular evolution of site-specific recombinases, highlighting the numerous applications of these enzymes across diverse fields of study. PMID:23982993

  19. Hercules Single-Stage Reusable Vehicle (HSRV) Operating Base

    NASA Technical Reports Server (NTRS)

    Moon, Michael J.; McCleskey, Carey M.

    2017-01-01

    Conceptual design for the layout of lunar-planetary surface support systems remains an important area needing further master planning. This paper explores a structured approach to organize the layout of a Mars-based site equipped for routinely flying a human-scale reusable taxi system. The proposed Hercules Transportation System requires a surface support capability to sustain its routine, affordable, and dependable operation. The approach organizes a conceptual Hercules operating base through functional station sets. The station set approach will allow follow-on work to trade design approaches and consider technologies for more efficient flow of material, energy, and information at future Mars bases and settlements. The station set requirements at a Mars site point to specific capabilities needed. By drawing from specific Hercules design characteristics, the technology requirements for surface-based systems will come into greater focus. This paper begins a comprehensive process for documenting functional needs, architectural design methods, and analysis techniques necessary for follow-on concept studies.

  20. Compiler writing system detail design specification. Volume 1: Language specification

    NASA Technical Reports Server (NTRS)

    Arthur, W. J.

    1974-01-01

    Construction within the Meta language for both language and target machine specification is reported. The elements of the function language as a meaning and syntax are presented, and the structure of the target language is described which represents the target dependent object text representation of applications programs.

  1. Architecture of autonomous systems

    NASA Technical Reports Server (NTRS)

    Dikshit, Piyush; Guimaraes, Katia; Ramamurthy, Maya; Agrawala, Ashok; Larsen, Ronald L.

    1986-01-01

    Automation of Space Station functions and activities, particularly those involving robotic capabilities with interactive or supervisory human control, is a complex, multi-disciplinary systems design problem. A wide variety of applications using autonomous control can be found in the literature, but none of them seem to address the problem in general. All of them are designed with a specific application in mind. In this report, an abstract model is described which unifies the key concepts underlying the design of automated systems such as those studied by the aerospace contractors. The model has been kept as general as possible. The attempt is to capture all the key components of autonomous systems. With a little effort, it should be possible to map the functions of any specific autonomous system application to the model presented here.

  2. Optimization of affinity, specificity and function of designed influenza inhibitors using deep sequencing

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

    Whitehead, Timothy A.; Chevalier, Aaron; Song, Yifan

    2012-06-19

    We show that comprehensive sequence-function maps obtained by deep sequencing can be used to reprogram interaction specificity and to leapfrog over bottlenecks in affinity maturation by combining many individually small contributions not detectable in conventional approaches. We use this approach to optimize two computationally designed inhibitors against H1N1 influenza hemagglutinin and, in both cases, obtain variants with subnanomolar binding affinity. The most potent of these, a 51-residue protein, is broadly cross-reactive against all influenza group 1 hemagglutinins, including human H2, and neutralizes H1N1 viruses with a potency that rivals that of several human monoclonal antibodies, demonstrating that computational design followedmore » by comprehensive energy landscape mapping can generate proteins with potential therapeutic utility.« less

  3. Small Molecules Targeting the miRNA-Binding Domain of Argonaute 2: From Computer-Aided Molecular Design to RNA Immunoprecipitation.

    PubMed

    Bellissimo, Teresa; Masciarelli, Silvia; Poser, Elena; Genovese, Ilaria; Del Rio, Alberto; Colotti, Gianni; Fazi, Francesco

    2017-01-01

    The development of small-molecule-based target therapy design for human disease and cancer is object of growing attention. Recently, specific microRNA (miRNA) mimicking compounds able to bind the miRNA-binding domain of Argonaute 2 protein (AGO2) to inhibit miRNA loading and its functional activity were described. Computer-aided molecular design techniques and RNA immunoprecipitation represent suitable approaches to identify and experimentally determine if a compound is able to impair the loading of miRNAs on AGO2 protein. Here, we describe these two methodologies that we recently used to select a specific compound able to interfere with the AGO2 functional activity and able to improve the retinoic acid-dependent myeloid differentiation of leukemic cells.

  4. Architecture of autonomous systems

    NASA Technical Reports Server (NTRS)

    Dikshit, Piyush; Guimaraes, Katia; Ramamurthy, Maya; Agrawala, Ashok; Larsen, Ronald L.

    1989-01-01

    Automation of Space Station functions and activities, particularly those involving robotic capabilities with interactive or supervisory human control, is a complex, multi-disciplinary systems design problem. A wide variety of applications using autonomous control can be found in the literature, but none of them seem to address the problem in general. All of them are designed with a specific application in mind. In this report, an abstract model is described which unifies the key concepts underlying the design of automated systems such as those studied by the aerospace contractors. The model has been kept as general as possible. The attempt is to capture all the key components of autonomous systems. With a little effort, it should be possible to map the functions of any specific autonomous system application to the model presented here.

  5. European Design Types for 21st Century Schools: An Overview

    ERIC Educational Resources Information Center

    Rigolon, Alessandro

    2010-01-01

    This article presents a critical overview of European school building design types, based on an analysis of morphologies and spatial layouts. The different design types are evaluated in function of specific didactic and social needs. (Contains 1 figure, 18 footnotes, a bibliography and 2 online resources.)

  6. Laboratory Animal Facilities. Laboratory Design Notes.

    ERIC Educational Resources Information Center

    Jonas, Albert M.

    1965-01-01

    Design of laboratory animal facilities must be functional. Accordingly, the designer should be aware of the complex nature of animal research and specifically the type of animal research which will be conducted in a new facility. The building of animal-care facilities in research institutions requires special knowledge in laboratory animal…

  7. Optimization of digital designs

    NASA Technical Reports Server (NTRS)

    Miles, Lowell H. (Inventor); Whitaker, Sterling R. (Inventor)

    2009-01-01

    An application specific integrated circuit is optimized by translating a first representation of its digital design to a second representation. The second representation includes multiple syntactic expressions that admit a representation of a higher-order function of base Boolean values. The syntactic expressions are manipulated to form a third representation of the digital design.

  8. Multi-function displays : a guide for human factors evaluation.

    DOT National Transportation Integrated Search

    2013-11-01

    This guide is designed to assist aircraft certification personnel and avionics : manufacturers in evaluating the human factors aspects of Multi-function Displays : (MFDs) for FAA certification. The guide focuses specifically on human factors and : do...

  9. Patient specific ankle-foot orthoses using rapid prototyping

    PubMed Central

    2011-01-01

    Background Prefabricated orthotic devices are currently designed to fit a range of patients and therefore they do not provide individualized comfort and function. Custom-fit orthoses are superior to prefabricated orthotic devices from both of the above-mentioned standpoints. However, creating a custom-fit orthosis is a laborious and time-intensive manual process performed by skilled orthotists. Besides, adjustments made to both prefabricated and custom-fit orthoses are carried out in a qualitative manner. So both comfort and function can potentially suffer considerably. A computerized technique for fabricating patient-specific orthotic devices has the potential to provide excellent comfort and allow for changes in the standard design to meet the specific needs of each patient. Methods In this paper, 3D laser scanning is combined with rapid prototyping to create patient-specific orthoses. A novel process was engineered to utilize patient-specific surface data of the patient anatomy as a digital input, manipulate the surface data to an optimal form using Computer Aided Design (CAD) software, and then download the digital output from the CAD software to a rapid prototyping machine for fabrication. Results Two AFOs were rapidly prototyped to demonstrate the proposed process. Gait analysis data of a subject wearing the AFOs indicated that the rapid prototyped AFOs performed comparably to the prefabricated polypropylene design. Conclusions The rapidly prototyped orthoses fabricated in this study provided good fit of the subject's anatomy compared to a prefabricated AFO while delivering comparable function (i.e. mechanical effect on the biomechanics of gait). The rapid fabrication capability is of interest because it has potential for decreasing fabrication time and cost especially when a replacement of the orthosis is required. PMID:21226898

  10. W-026, Waste Receiving and Processing Facility data management system validation and verification report

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

    Palmer, M.E.

    1997-12-05

    This V and V Report includes analysis of two revisions of the DMS [data management system] System Requirements Specification (SRS) and the Preliminary System Design Document (PSDD); the source code for the DMS Communication Module (DMSCOM) messages; the source code for selected DMS Screens, and the code for the BWAS Simulator. BDM Federal analysts used a series of matrices to: compare the requirements in the System Requirements Specification (SRS) to the specifications found in the System Design Document (SDD), to ensure the design supports the business functions, compare the discreet parts of the SDD with each other, to ensure thatmore » the design is consistent and cohesive, compare the source code of the DMS Communication Module with the specifications, to ensure that the resultant messages will support the design, compare the source code of selected screens to the specifications to ensure that resultant system screens will support the design, compare the source code of the BWAS simulator with the requirements to interface with DMS messages and data transfers relating to the BWAS operations.« less

  11. Flood type specific construction of synthetic design hydrographs

    NASA Astrophysics Data System (ADS)

    Brunner, Manuela I.; Viviroli, Daniel; Sikorska, Anna E.; Vannier, Olivier; Favre, Anne-Catherine; Seibert, Jan

    2017-02-01

    Accurate estimates of flood peaks, corresponding volumes, and hydrographs are required to design safe and cost-effective hydraulic structures. In this paper, we propose a statistical approach for the estimation of the design variables peak and volume by constructing synthetic design hydrographs for different flood types such as flash-floods, short-rain floods, long-rain floods, and rain-on-snow floods. Our approach relies on the fitting of probability density functions to observed flood hydrographs of a certain flood type and accounts for the dependence between peak discharge and flood volume. It makes use of the statistical information contained in the data and retains the process information of the flood type. The method was tested based on data from 39 mesoscale catchments in Switzerland and provides catchment specific and flood type specific synthetic design hydrographs for all of these catchments. We demonstrate that flood type specific synthetic design hydrographs are meaningful in flood-risk management when combined with knowledge on the seasonality and the frequency of different flood types.

  12. Applying User-Centered Design Methods to the Development of an mHealth Application for Use in the Hospital Setting by Patients and Care Partners.

    PubMed

    Couture, Brittany; Lilley, Elizabeth; Chang, Frank; DeBord Smith, Ann; Cleveland, Jessica; Ergai, Awatef; Katsulis, Zachary; Benneyan, James; Gershanik, Esteban; Bates, David W; Collins, Sarah A

    2018-04-01

     Developing an optimized and user-friendly mHealth application for patients and family members in the hospital environment presents unique challenges given the diverse patient population and patients' various states of well-being.  This article describes user-centered design methods and results for developing the patient and family facing user interface and functionality of MySafeCare, a safety reporting tool for hospitalized patients and their family members.  Individual and group usability sessions were conducted with specific testing scenarios for participants to follow to test the usability and functionality of the tool. Participants included patients, family members, and Patient and Family Advisory Council (PFAC) members. Engagement rounds were also conducted on study units and lessons learned provided additional information to the usability work. Usability results were aligned with Nielsen's Usability Heuristics.  Eleven patients and family members and 25 PFAC members participated in usability testing and over 250 patients and family members were engaged during research team rounding. Specific themes resulting from the usability testing sessions influenced the changes made to the user interface design, workflow functionality, and terminology.  User-centered design should focus on workflow functionality, terminology, and user interface issues for mHealth applications. These themes illustrated issues aligned with four of Nielsen's Usability Heuristics: match between system and the real world, consistency and standards, flexibility and efficiency of use, and aesthetic and minimalist design. We identified workflow and terminology issues that may be specific to the use of an mHealth application focused on safety and used by hospitalized patients and their families. Schattauer GmbH Stuttgart.

  13. Biophysical characterization of a de novo elastin

    NASA Astrophysics Data System (ADS)

    Greenland, Kelly Nicole

    Natural human elastin is found in tissue such as the lungs, arteries, and skin. This protein is formed at birth with no mechanism present to repair or supplement the initial quantity formed. As a result, the functionality and durability of elastin's elasticity is critically important. To date, the mechanics of this ability to stretch and recoil is not fully understood. This study utilizes de novo protein design to create a small library of simplistic versions of elastin-like proteins, demonstrate the elastin-like proteins, maintain elastin's functionality, and inquire into its structure using solution nuclear magnetic resonance (NMR). Elastin is formed from cross-linked tropoelastin. Therefore, the first generation of designed proteins consisted of one protein that utilized homogony of interspecies tropoelastin by using three common domains, two hydrophobic and one cross-linking domains. Basic modifications were made to open the hydrophobic region and also to make the protein easier to purify and characterize. The designed protein maintained its functionality, self-aggregating as the temperature increased. Uniquely, the protein remained self-aggregated as the temperature returned below the critical transition temperature. Self-aggregation was additionally induced by increasing salt concentrations and by modifying the pH. The protein appeared to have little secondary structure when studied with solution NMR. These results fueled a second generation of designed elastin-like proteins. This generation contained variations designed to study the cross-linking domain, one specific hydrophobic domain, and the effect of the length of the elastin-like protein. The cross-linking domain in one variation has been significantly modified while the flanking hydrophobic domains have remained unchanged. This characterization of this protein will answer questions regarding the specificity of the homologous nature of the cross-linking domain of tropoelastin across species. A second protein has additional hydrophobic domains flanking the originally designed elastin-like protein. The characterization of this protein will answer questions regarding the functionality of longer or more hydrophobic elastin-like proteins. The final variation designed is one hydrophobic domain and the new cross-linking domain repeating several times. The characterization of this protein will answer questions regarding the specific hydrophobic domain and its functionality.

  14. Charge-transfer-based terbium MOF nanoparticles as fluorescent pH sensor for extreme acidity.

    PubMed

    Qi, Zewan; Chen, Yang

    2017-01-15

    Newly emerged metal organic frameworks (MOFs) have aroused the great interest in designing functional materials by means of its flexible structure and component. In this study, we used lanthanide Tb 3+ ions and small molecular ligands to design and assemble a kind of pH-sensitive MOF nanoparticle based on intramolecular-charge-transfer effect. This kind of made-to-order MOF nanoparticle for H + is highly specific and sensitive and could be used to fluorescently indicate pH value of strong acidic solution via preset mechanism through luminescence of Tb 3+ . The long luminescence lifetime of Tb 3+ allows eliminating concomitant non-specific fluorescence by time-revised fluorescence techniques, processing an advantage in sensing H + in biological media with strong autofluorescence. Our method showed a great potential of MOF structures in designing and constructing sensitive sensing materials for specific analytes directly via the assembly of functional ions/ligands. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Automating software design system DESTA

    NASA Technical Reports Server (NTRS)

    Lovitsky, Vladimir A.; Pearce, Patricia D.

    1992-01-01

    'DESTA' is the acronym for the Dialogue Evolutionary Synthesizer of Turnkey Algorithms by means of a natural language (Russian or English) functional specification of algorithms or software being developed. DESTA represents the computer-aided and/or automatic artificial intelligence 'forgiving' system which provides users with software tools support for algorithm and/or structured program development. The DESTA system is intended to provide support for the higher levels and earlier stages of engineering design of software in contrast to conventional Computer Aided Design (CAD) systems which provide low level tools for use at a stage when the major planning and structuring decisions have already been taken. DESTA is a knowledge-intensive system. The main features of the knowledge are procedures, functions, modules, operating system commands, batch files, their natural language specifications, and their interlinks. The specific domain for the DESTA system is a high level programming language like Turbo Pascal 6.0. The DESTA system is operational and runs on an IBM PC computer.

  16. Customizing Countermeasure Prescriptions using Predictive Measures of Sensorimotor Adaptability

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Miller, C. A.; Batson, C. D.; Wood, S. J.; Guined, J. R.; Cohen, H. S.; Buccello-Stout, R.; DeDios, Y. E.; hide

    2014-01-01

    Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the readapation phase following a return to a gravitational environment. These alterations may lead to disruption in the ability to perform mission critical functional tasks during and after these gravitational transitions. Astronauts show significant inter-subject variation in adaptive capability following gravitational transitions. The ability to predict the manner and degree to which each individual astronaut will be affected would improve the effectiveness of a countermeasure comprised of a training program designed to enhance sensorimotor adaptability. Due to this inherent individual variability we need to develop predictive measures of sensorimotor adaptability that will allow us to predict, before actual space flight, which crewmember will experience challenges in adaptive capacity. Thus, obtaining this information will allow us to design and implement better sensorimotor adaptability training countermeasures that will be customized for each crewmember's unique adaptive capabilities. Therefore the goals of this project are to: 1) develop a set of predictive measures capable of identifying individual differences in sensorimotor adaptability, and 2) use this information to design sensorimotor adaptability training countermeasures that are customized for each crewmember's individual sensorimotor adaptive characteristics. To achieve these goals we are currently pursuing the following specific aims: Aim 1: Determine whether behavioral metrics of individual sensory bias predict sensorimotor adaptability. For this aim, subjects perform tests that delineate individual sensory biases in tests of visual, vestibular, and proprioceptive function. Aim 2: Determine if individual capability for strategic and plastic-adaptive responses predicts sensorimotor adaptability. For this aim, each subject's strategic and plastic-adaptive motor learning abilities are assessed using a test of locomotor function designed specifically to delineate both mechanisms. Aim 3: Develop predictors of sensorimotor adaptability using brain structural and functional metrics. We will measure individual differences in regional brain volumes (structural MRI), white matter integrity (diffusion tensor imaging, or DTI), functional network integrity (resting state functional connectivity MRI), and sensorimotor adaptation task-related functional brain activation (functional MRI). We decided to complete the data collection for Specific Aims 1, 2 and 3 simultaneously on the same subjects to increase data capture. By having the same subjects perform all three specific aims we can enhance our ability to detect how a wider range of factors can predict adaptability in a specific individual. This provides a much richer database and potentially a better understanding of the predictive power of the selected factors. In this presentation I will discuss preliminary data obtained to date.

  17. Functional design to support CDTI/DABS flight experiments

    NASA Technical Reports Server (NTRS)

    Goka, T.

    1982-01-01

    The objectives of this project are to: (1) provide a generalized functional design of CDTI avionics using the FAA developd DABS/ATARS ground system as the 'traffic sensor', (2) specify software modifications and/or additions to the existing DABS/ATARS ground system to support CDTI avionics, (3) assess the existing avionics of a NASA research aircraft in terms of CDTI applications, and (4) apply the generalized functional design to provide research flight experiment capability. DABS Data Link Formats are first specified for CDTI flight experiments. The set of CDTI/DABS Format specifications becomes a vehicle to coordinate the CDTI avionics and ground system designs, and hence, to develop overall system requirements. The report is the first iteration of a system design and development effort to support eventual CDTI flight test experiments.

  18. Development of baked and extruded functional foods from metabolic syndrome specific ingredient mix.

    PubMed

    Miglani, Neetu; Bains, Kiran; Kaur, Harpreet

    2015-09-01

    The study was aimed to develop baked and extruded functional foods from Metabolic Syndrome (MS) specific designed ingredient mixes with optimum amino acid makeup using key food ingredients with functional properties such as whole cereals, legumes, skimmed milk powder, along with flaxseeds and fenugreek seeds. Two cereals viz. barley and oats and four pulses viz. mung bean, cowpea, bengal gram and soybean were blended in different proportions in order to balance the limiting amino acid lysine in the wheat flour. Three products namely bread, extruded snack and noodles prepared from twenty five ingredient mixes. Six ingredient mixes of breads and four ingredient mixes each of extruded snack and noodles specifically designed for MS patients were organoleptically at par with control wheat flour products. The acceptable products had significantly (p ≤ 0.05) higher lysine, crude protein, ash and fibre and low carbohydrates in compare control whole wheat flour products, hence appropriate for MS patients.

  19. Minimization In Digital Design As A Meta-Planning Problem

    NASA Astrophysics Data System (ADS)

    Ho, William P. C.; Wu, Jung-Gen

    1987-05-01

    In our model-based expert system for automatic digital system design, we formalize the design process into three sub-processes - compiling high-level behavioral specifications into primitive behavioral operations, grouping primitive operations into behavioral functions, and grouping functions into modules. Consideration of design minimization explicitly controls decision-making in the last two subprocesses. Design minimization, a key task in the automatic design of digital systems, is complicated by the high degree of interaction among the time sequence and content of design decisions. In this paper, we present an AI approach which directly addresses these interactions and their consequences by modeling the minimization prob-lem as a planning problem, and the management of design decision-making as a meta-planning problem.

  20. Biomimicry enhances sequential reactions of tethered glycolytic enzymes, TPI and GAPDHS.

    PubMed

    Mukai, Chinatsu; Gao, Lizeng; Bergkvist, Magnus; Nelson, Jacquelyn L; Hinchman, Meleana M; Travis, Alexander J

    2013-01-01

    Maintaining activity of enzymes tethered to solid interfaces remains a major challenge in developing hybrid organic-inorganic devices. In nature, mammalian spermatozoa have overcome this design challenge by having glycolytic enzymes with specialized targeting domains that enable them to function while tethered to a cytoskeletal element. As a step toward designing a hybrid organic-inorganic ATP-generating system, we implemented a biomimetic site-specific immobilization strategy to tether two glycolytic enzymes representing different functional enzyme families: triose phosphoisomerase (TPI; an isomerase) and glyceraldehyde 3-phosphate dehydrogenase (GAPDHS; an oxidoreductase). We then evaluated the activities of these enzymes in comparison to when they were tethered via classical carboxyl-amine crosslinking. Both enzymes show similar surface binding regardless of immobilization method. Remarkably, specific activities for both enzymes were significantly higher when tethered using the biomimetic, site-specific immobilization approach. Using this biomimetic approach, we tethered both enzymes to a single surface and demonstrated their function in series in both forward and reverse directions. Again, the activities in series were significantly higher in both directions when the enzymes were coupled using this biomimetic approach versus carboxyl-amine binding. Our results suggest that biomimetic, site-specific immobilization can provide important functional advantages over chemically specific, but non-oriented attachment, an important strategic insight given the growing interest in recapitulating entire biological pathways on hybrid organic-inorganic devices.

  1. Biomimicry Enhances Sequential Reactions of Tethered Glycolytic Enzymes, TPI and GAPDHS

    PubMed Central

    Mukai, Chinatsu; Gao, Lizeng; Bergkvist, Magnus; Nelson, Jacquelyn L.; Hinchman, Meleana M.; Travis, Alexander J.

    2013-01-01

    Maintaining activity of enzymes tethered to solid interfaces remains a major challenge in developing hybrid organic-inorganic devices. In nature, mammalian spermatozoa have overcome this design challenge by having glycolytic enzymes with specialized targeting domains that enable them to function while tethered to a cytoskeletal element. As a step toward designing a hybrid organic-inorganic ATP-generating system, we implemented a biomimetic site-specific immobilization strategy to tether two glycolytic enzymes representing different functional enzyme families: triose phosphoisomerase (TPI; an isomerase) and glyceraldehyde 3-phosphate dehydrogenase (GAPDHS; an oxidoreductase). We then evaluated the activities of these enzymes in comparison to when they were tethered via classical carboxyl-amine crosslinking. Both enzymes show similar surface binding regardless of immobilization method. Remarkably, specific activities for both enzymes were significantly higher when tethered using the biomimetic, site-specific immobilization approach. Using this biomimetic approach, we tethered both enzymes to a single surface and demonstrated their function in series in both forward and reverse directions. Again, the activities in series were significantly higher in both directions when the enzymes were coupled using this biomimetic approach versus carboxyl-amine binding. Our results suggest that biomimetic, site-specific immobilization can provide important functional advantages over chemically specific, but non-oriented attachment, an important strategic insight given the growing interest in recapitulating entire biological pathways on hybrid organic-inorganic devices. PMID:23626684

  2. Ligand binding by repeat proteins: natural and designed

    PubMed Central

    Grove, Tijana Z; Cortajarena, Aitziber L; Regan, Lynne

    2012-01-01

    Repeat proteins contain tandem arrays of small structural motifs. As a consequence of this architecture, they adopt non-globular, extended structures that present large, highly specific surfaces for ligand binding. Here we discuss recent advances toward understanding the functional role of this unique modular architecture. We showcase specific examples of natural repeat proteins interacting with diverse ligands and also present examples of designed repeat protein–ligand interactions. PMID:18602006

  3. Volunteering in the Community: Potential Benefits for Cognitive Aging.

    PubMed

    Guiney, Hayley; Machado, Liana

    2018-03-02

    This review aims to advance understanding of the potential benefits of volunteering in the community for older adults' cognitive functioning by taking an in-depth look at the relevant evidence to date. This review describes the main pathways through which volunteering could plausibly benefit cognitive functioning and critically examines research that has specifically investigated links between volunteering and cognition. Fifteen articles that assessed in adults aged ≥ 55 years the relationship between volunteering (predictor) and cognitive functioning (outcome) were identified via literature database searches. On balance, evidence from the small number of relevant studies to date supports the idea that volunteering can protect against cognitive aging with respect to global functioning and at least some specific cognitive domains. Studies that used robust designs and assessed domain-specific cognitive functioning produced the largest effect sizes. To help advance the field, this review puts forward recommendations for future research, with an emphasis on the need for robust study designs and specific investigations into the nature and extent of the cognitive benefits of volunteering. Through that work, researchers can determine how a simple and accessible activity like volunteering can best be used to help reduce the burden of age-related cognitive decline. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Two-Dimensional Hermite Filters Simplify the Description of High-Order Statistics of Natural Images.

    PubMed

    Hu, Qin; Victor, Jonathan D

    2016-09-01

    Natural image statistics play a crucial role in shaping biological visual systems, understanding their function and design principles, and designing effective computer-vision algorithms. High-order statistics are critical for conveying local features, but they are challenging to study - largely because their number and variety is large. Here, via the use of two-dimensional Hermite (TDH) functions, we identify a covert symmetry in high-order statistics of natural images that simplifies this task. This emerges from the structure of TDH functions, which are an orthogonal set of functions that are organized into a hierarchy of ranks. Specifically, we find that the shape (skewness and kurtosis) of the distribution of filter coefficients depends only on the projection of the function onto a 1-dimensional subspace specific to each rank. The characterization of natural image statistics provided by TDH filter coefficients reflects both their phase and amplitude structure, and we suggest an intuitive interpretation for the special subspace within each rank.

  5. Navigating the Requirements Jungle

    NASA Astrophysics Data System (ADS)

    Langer, Boris; Tautschnig, Michael

    Research on validation and verification of requirements specifications has thus far focused on functional properties. Yet, in embedded systems, functional requirements constitute only a small fraction of the properties that must hold to guarantee proper and safe operation of the system under design.

  6. Industrial Design in Aerospace/Role of Aesthetics

    NASA Technical Reports Server (NTRS)

    Bushnell, Dennis M.

    2006-01-01

    Industrial design creates and develops concepts and specifications that seek to simultaneously and synergistically optimize function, production, value and appearance. The inclusion of appearance, or esthetics, as a major design metric represents both an augmentation of conventional engineering design and an intersection with artistic endeavor(s). Report surveys past and current industrial design practices and examples across aerospace including aircraft and spacecraft, both exterior and interior.

  7. Functional Performance of Pyrovalves

    NASA Technical Reports Server (NTRS)

    Bement, Laurence J.

    1996-01-01

    Following several flight and ground test failures of spacecraft systems using single-shot, 'normally closed' pyrotechnically actuated valves (pyrovalves), a government/industry cooperative program was initiated to assess the functional performance of five qualified designs. The goal of the program was to improve performance-based requirements for the procurement of pyrovalves. Specific objectives included the demonstration of performance test methods, the measurement of 'blowby' (the passage of gases from the pyrotechnic energy source around the activating piston into the valve's fluid path), and the quantification of functional margins for each design. Experiments were conducted in-house at NASA on several units each of the five valve designs. The test methods used for this program measured the forces and energies required to actuate the valves, as well as the energies and the pressures (where possible) delivered by the pyrotechnic sources. Functional performance ranged widely among the designs. Blowby cannot be prevented by o-ring seals; metal-to-metal seals were effective. Functional margin was determined by dividing the energy delivered by the pyrotechnic sources in excess to that required to accomplish the function by the energy required for that function. All but two designs had adequate functional margins with the pyrotechnic cartridges evaluated.

  8. Partitioning of functional and taxonomic diversity in surface-associated microbial communities.

    PubMed

    Roth-Schulze, Alexandra J; Zozaya-Valdés, Enrique; Steinberg, Peter D; Thomas, Torsten

    2016-12-01

    Surfaces, including those submerged in the marine environment, are subjected to constant interactions and colonisation by surrounding microorganisms. The principles that determine the assembly of those epibiotic communities are however poorly understood. In this study, we employed a hierarchical design to assess the functionality and diversity of microbial communities on different types of host surfaces (e.g. macroalgae, seagrasses). We found that taxonomic diversity was unique to each type of host, but that the majority of functions (> 95%) could be found in any given surface community, suggesting a high degree of functional redundancy. However, some community functions were enriched on certain surfaces and were related to host-specific properties (e.g. the degradation of specific polysaccharides). Together these observations support a model, whereby communities on surfaces are assembled from guilds of microorganisms with a functionality that is partitioned into general properties for a surface-associated life-style, but also specific features that mediate host-specificity. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  9. Specific Uptake of Lipid-Antibody-Functionalized LbL Microcarriers by Cells.

    PubMed

    Göse, Martin; Scheffler, Kira; Reibetanz, Uta

    2016-11-14

    The modular construction of Layer-by-Layer biopolymer microcarriers facilitates a highly specific design of drug delivery systems. A supported lipid bilayer (SLB) contributes to biocompatibility and protection of sensitive active agents. The addition of a lipid anchor equipped with PEG (shielding from opsonins) and biotin (attachment of exchangeable outer functional molecules) enhances the microcarrier functionality even more. However, a homogeneously assembled supported lipid bilayer is a prerequisite for a specific binding of functional components. Our investigations show that a tightly packed SLB improves the efficiency of functional components attached to the microcarrier's surface, as illustrated with specific antibodies in cellular application. Only a low quantity of antibodies is needed to obtain improved cellular uptake rates independent from cell type as compared to an antibody-functionalized loosely packed lipid bilayer or directly assembled antibody onto the multilayer. A fast disassembly of the lipid bilayer within endolysosomes exposing the underlying drug delivering multilayer structure demonstrates the suitability of LbL-microcarriers as a multifunctional drug delivery system.

  10. Functional categories for future flight deck designs

    NASA Technical Reports Server (NTRS)

    Abbott, Terence S.

    1993-01-01

    With the addition of each new system on the flight deck, the danger of increasing overall operator workload while reducing crew understanding of critical mission information exists. The introduction of more powerful onboard computers, larger databases, and the increased use of electronic display media may lead to a situation of flight deck 'sophistication' at the expense of losses in flight crew capabilities and situational awareness. To counter this potentially negative impact of new technology, research activities are underway to reassess the flight deck design process. The fundamental premise of these activities is that a human-centered, systems-oriented approach to the development of advanced civil aircraft flight decks will be required for future designs to remain ergonomically sound and economically competitive. One of the initial steps in an integrated flight deck process is to define the primary flight deck functions needed to support the mission goals of the vehicle. This would allow the design team to evaluate candidate concepts in relation to their effectiveness in meeting the functional requirements. In addition, this would provide a framework to aid in categorizing and bookkeeping all of the activities that are required to be performed on the flight deck, not just activities of the crew or of a specific system. This could then allow for a better understanding and allocation of activities in the design, an understanding of the impact of a specific system on overall system performance, and an awareness of the total crew performance requirements for the design. One candidate set of functional categories that could be used to guide an advanced flight deck design are described.

  11. Design Method for Numerical Function Generators Based on Polynomial Approximation for FPGA Implementation

    DTIC Science & Technology

    2007-08-01

    with a Design Specification de- scribed by Scilab [26], a MATLAB-like software applica- tion, and ends up with HDL code. The Design Specifica- tion...Conf. on Field Programmable Logic and Applications (FPL’05), Tampere, Finland, pp. 118–123, Aug. 2005. [26] Scilab 3.0, INRIA-ENPC, France, http

  12. The 18th Aerospace Mechanisms Symposium

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Topics concerning aerospace mechanisms, their functional performance, and design specifications are presented. Discussed subjects include the design and development of release mechanisms, actuators, linear driver/rate controllers, antenna and appendage deployment systems, position control systems, and tracking mechanisms for antennas and solar arrays. Engine design, spaceborne experiments, and large space structure technology are also examined.

  13. Formal Functional Test Designs: Bridging the Gap Between Test Requirements and Test Specifications

    NASA Technical Reports Server (NTRS)

    Hops, Jonathan

    1993-01-01

    This presentation describes the testing life cycle, the purpose of the test design phase, and test design methods and gives an example application. Also included is a description of Test Representation Language (TRL), a summary of the language, and an example of an application of TRL. A sample test requirement and sample test design are included.

  14. Integrated flight/propulsion control - Subsystem specifications for performance

    NASA Technical Reports Server (NTRS)

    Neighbors, W. K.; Rock, Stephen M.

    1993-01-01

    A procedure is presented for calculating multiple subsystem specifications given a number of performance requirements on the integrated system. This procedure applies to problems where the control design must be performed in a partitioned manner. It is based on a structured singular value analysis, and generates specifications as magnitude bounds on subsystem uncertainties. The performance requirements should be provided in the form of bounds on transfer functions of the integrated system. This form allows the expression of model following, command tracking, and disturbance rejection requirements. The procedure is demonstrated on a STOVL aircraft design.

  15. Expanding the scope of site-specific recombinases for genetic and metabolic engineering.

    PubMed

    Gaj, Thomas; Sirk, Shannon J; Barbas, Carlos F

    2014-01-01

    Site-specific recombinases are tremendously valuable tools for basic research and genetic engineering. By promoting high-fidelity DNA modifications, site-specific recombination systems have empowered researchers with unprecedented control over diverse biological functions, enabling countless insights into cellular structure and function. The rigid target specificities of many sites-specific recombinases, however, have limited their adoption in fields that require highly flexible recognition abilities. As a result, intense effort has been directed toward altering the properties of site-specific recombination systems by protein engineering. Here, we review key developments in the rational design and directed molecular evolution of site-specific recombinases, highlighting the numerous applications of these enzymes across diverse fields of study. © 2013 Wiley Periodicals, Inc.

  16. Structured output-feedback controller synthesis with design specifications

    NASA Astrophysics Data System (ADS)

    Hao, Yuqing; Duan, Zhisheng

    2017-03-01

    This paper considers the problem of structured output-feedback controller synthesis with finite frequency specifications. Based on the orthogonal space information of input matrix, an improved parameter-dependent Lyapunov function method is first proposed. Then, a two-stage construction method is designed, which depends on an initial centralised controller. Corresponding design conditions for three types of output-feedback controllers are presented in terms of unified representations. Moreover, heuristic algorithms are provided to explore the desirable controllers. Finally, the effectiveness of these proposed methods is illustrated via some practical examples.

  17. On the design of decoupling controllers for advanced rotorcraft in the hover case

    NASA Technical Reports Server (NTRS)

    Fan, M. K. H.; Tits, A.; Barlow, J.; Tsing, N. K.; Tischler, M.; Takahashi, M.

    1991-01-01

    A methodology for design of helicopter control systems is proposed that can account for various types of concurrent specifications: stability, decoupling between longitudinal and lateral motions, handling qualities, and physical limitations of the swashplate motions. This is achieved by synergistic use of analytical techniques (Q-parameterization of all stabilizing controllers, transfer function interpolation) and advanced numerical optimization techniques. The methodology is used to design a controller for the UH-60 helicopter in hover. Good results are achieved for decoupling and handling quality specifications.

  18. Identification of emergent off-nominal operational requirements during conceptual architecting of the more electric aircraft

    NASA Astrophysics Data System (ADS)

    Armstrong, Michael James

    Increases in power demands and changes in the design practices of overall equipment manufacturers has led to a new paradigm in vehicle systems definition. The development of unique power systems architectures is of increasing importance to overall platform feasibility and must be pursued early in the aircraft design process. Many vehicle systems architecture trades must be conducted concurrent to platform definition. With an increased complexity introduced during conceptual design, accurate predictions of unit level sizing requirements must be made. Architecture specific emergent requirements must be identified which arise due to the complex integrated effect of unit behaviors. Off-nominal operating scenarios present sizing critical requirements to the aircraft vehicle systems. These requirements are architecture specific and emergent. Standard heuristically defined failure mitigation is sufficient for sizing traditional and evolutionary architectures. However, architecture concepts which vary significantly in terms of structure and composition require that unique failure mitigation strategies be defined for accurate estimations of unit level requirements. Identifying of these off-nominal emergent operational requirements require extensions to traditional safety and reliability tools and the systematic identification of optimal performance degradation strategies. Discrete operational constraints posed by traditional Functional Hazard Assessment (FHA) are replaced by continuous relationships between function loss and operational hazard. These relationships pose the objective function for hazard minimization. Load shedding optimization is performed for all statistically significant failures by varying the allocation of functional capability throughout the vehicle systems architecture. Expressing hazards, and thereby, reliability requirements as continuous relationships with the magnitude and duration of functional failure requires augmentations to the traditional means for system safety assessment (SSA). The traditional two state and discrete system reliability assessment proves insufficient. Reliability is, therefore, handled in an analog fashion: as a function of magnitude of failure and failure duration. A series of metrics are introduced which characterize system performance in terms of analog hazard probabilities. These include analog and cumulative system and functional risk, hazard correlation, and extensions to the traditional component importance metrics. Continuous FHA, load shedding optimization, and analog SSA constitute the SONOMA process (Systematic Off-Nominal Requirements Analysis). Analog system safety metrics inform both architecture optimization (changes in unit level capability and reliability) and architecture augmentation (changes in architecture structure and composition). This process was applied for two vehicle systems concepts (conventional and 'more-electric') in terms of loss/hazard relationships with varying degrees of fidelity. Application of this process shows that the traditional assumptions regarding the structure of the function loss vs. hazard relationship apply undue design bias to functions and components during exploratory design. This bias is illustrated in terms of inaccurate estimations of the system and function level risk and unit level importance. It was also shown that off-nominal emergent requirements must be defined specific to each architecture concept. Quantitative comparisons of architecture specific off-nominal performance were obtained which provide evidence to the need for accurate definition of load shedding strategies during architecture exploratory design. Formally expressing performance degradation strategies in terms of the minimization of a continuous hazard space enhances the system architects ability to accurately predict sizing critical emergent requirements concurrent to architecture definition. Furthermore, the methods and frameworks generated here provide a structured and flexible means for eliciting these architecture specific requirements during the performance of architecture trades.

  19. A Comparative Study of the Roles and Functions of School Principals and Bilingual Program Administrators.

    ERIC Educational Resources Information Center

    Sanchez,Gilbert; Cali, Alfred J.

    This study was designed to compare time allocations to major functions actually performed and idealized by bilingual administrators and principals; to rank specific procedures used in accomplishing these functions; to determine staffing patterns, and program and organizational characteristics; and to isolate personal/professional demographics of…

  20. Thematic mapper flight model preshipment review data package. Volume 4: Appendix. Part E: Electronics module data

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Tests to verify the as-designed performance of all circuits within the thematic mapper electronics module unit are described. Specifically, the tests involved the evaluation of the scan line corrector driver, shutter drivers function, cal lamp controller function, post amplifier function, command decoder verification unit, and the temperature and actuator controllers function.

  1. ChalkBoard: Mapping Functions to Polygons

    NASA Astrophysics Data System (ADS)

    Matlage, Kevin; Gill, Andy

    ChalkBoard is a domain specific language for describing images. The ChalkBoard language is uncompromisingly functional and encourages the use of modern functional idioms. ChalkBoard uses off-the-shelf graphics cards to speed up rendering of functional descriptions. In this paper, we describe the design of the core ChalkBoard language, and the architecture of our static image generation accelerator.

  2. Hardware Trojans - Prevention, Detection, Countermeasures (A Literature Review)

    DTIC Science & Technology

    2011-07-01

    Phase and Location . . . . . . . . . . . . . . . . . . . . . . . . . 4 2.2 Hardware Trojan Actions...12 3.4 Trigger Design Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 4 Prevention 14 4.1 Prevention...The specification is then realised into specific tar- 4 UNCLASSIFIED UNCLASSIFIED DSTO–TN–1012 get technologies with consideration of functional and

  3. Transitioning from conceptual design to construction performance specification

    NASA Astrophysics Data System (ADS)

    Jeffers, Paul; Warner, Mark; Craig, Simon; Hubbard, Robert; Marshall, Heather

    2012-09-01

    On successful completion of a conceptual design review by a funding agency or customer, there is a transition phase before construction contracts can be placed. The nature of this transition phase depends on the Project's approach to construction and the particular subsystem being considered. There are generically two approaches; project retention of design authority and issuance of build to print contracts, or issuance of subsystem performance specifications with controlled interfaces. This paper relates to the latter where a proof of concept (conceptual or reference design) is translated into performance based sub-system specifications for competitive tender. This translation is not a straightforward process and there are a number of different issues to consider in the process. This paper deals with primarily the Telescope mount and Enclosure subsystems. The main subjects considered in this paper are: • Typical status of design at Conceptual Design Review compared with the desired status of Specifications and Interface Control Documents at Request for Quotation. • Options for capture and tracking of system requirements flow down from science / operating requirements and sub-system requirements, and functional requirements derived from reference design. • Requirements that may come specifically from the contracting approach. • Methods for effective use of reference design work without compromising a performance based specification. • Management of project team's expectation relating to design. • Effects on cost estimates from reference design to actual. This paper is based on experience and lessons learned through this process on both the VISTA and the ATST projects.

  4. Design and ergonomics. Methods for integrating ergonomics at hand tool design stage.

    PubMed

    Marsot, Jacques; Claudon, Laurent

    2004-01-01

    As a marked increase in the number of musculoskeletal disorders was noted in many industrialized countries and more specifically in companies that require the use of hand tools, the French National Research and Safety Institute (INRS) launched in 1999 a research project on the topic of integrating ergonomics into hand tool design, and more particularly to a design of a boning knife. After a brief recall of the difficulties of integrating ergonomics at the design stage, the present paper shows how 3 design methodological tools--Functional Analysis, Quality Function Deployment and TRIZ--have been applied to the design of a boning knife. Implementation of these tools enabled us to demonstrate the extent to which they are capable of responding to the difficulties of integrating ergonomics into product design.

  5. Design of polymer motifs for nucleic acid recognition and assembly stabilization

    NASA Astrophysics Data System (ADS)

    Zhou, Zhun

    This dissertation describes the synthesis and assembly of bio-functional polymers and the applications of these polymers to drug encapsulation, delivery, and multivalent biomimetic macromolecular recognition between synthetic polymer and nucleic acids. The main content is divided into three parts: (1) polyacidic domains as strongly stabilizing design elements for aqueous phase polyacrylate diblock assembly; (2) small molecule/polymer recognition triggered macromolecular assembly and drug encapsulation; (3) trizaine derivatized polymer as a novel class of "bifacial polymer nucleic acid" (bPoNA) and applications of bPoNA to nanoparticle loading of DNA/RNA, silencing delivery as well as control of aptamer function. Through the studies in part (1) and part (2), it was demonstrated that well-designed polymer motifs are not only able to enhance assemblies driven by non-specific hydrophobic effect, but are also able to direct assemblies based on specific recognitions. In part (3) of this dissertation, this concept was further extended by the design of polyacrylate polymers that are capable of discrete and robust hybridization with nucleic acids. This surprising finding demonstrated both fundamental and practical applications. Overall, these studies provided insights into the rational design elements for improving the bio-functions of synthetic polymers, and significantly expanded the scope of biological applications in which polymers synthesized via controlled radical polymerization may play a role.

  6. Recent advances in developing small molecules targeting RNA.

    PubMed

    Guan, Lirui; Disney, Matthew D

    2012-01-20

    RNAs are underexploited targets for small molecule drugs or chemical probes of function. This may be due, in part, to a fundamental lack of understanding of the types of small molecules that bind RNA specifically and the types of RNA motifs that specifically bind small molecules. In this review, we describe recent advances in the development and design of small molecules that bind to RNA and modulate function that aim to fill this void.

  7. Feasibility study for a numerical aerodynamic simulation facility. Volume 2: Hardware specifications/descriptions

    NASA Technical Reports Server (NTRS)

    Green, F. M.; Resnick, D. R.

    1979-01-01

    An FMP (Flow Model Processor) was designed for use in the Numerical Aerodynamic Simulation Facility (NASF). The NASF was developed to simulate fluid flow over three-dimensional bodies in wind tunnel environments and in free space. The facility is applicable to studying aerodynamic and aircraft body designs. The following general topics are discussed in this volume: (1) FMP functional computer specifications; (2) FMP instruction specification; (3) standard product system components; (4) loosely coupled network (LCN) specifications/description; and (5) three appendices: performance of trunk allocation contention elimination (trace) method, LCN channel protocol and proposed LCN unified second level protocol.

  8. SSL: A software specification language

    NASA Technical Reports Server (NTRS)

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

    1976-01-01

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

  9. Functional performance of pyrovalves

    NASA Technical Reports Server (NTRS)

    Bement, Laurence J.

    1996-01-01

    Following several flight and ground test failures of spacecraft systems using single-shot, 'normally closed' pyrotechnically actuated valves (pyrovalves), a Government/Industry cooperative program was initiated to assess the functional performance of five qualified designs. The goal of the program was to provide information on functional performance of pyrovalves to allow users the opportunity to improve procurement requirements. Specific objectives included the demonstration of performance test methods, the seating; these gases/particles entered the fluid path of measurement of 'blowby' (the passage of gases from the pyrotechnic energy source around the activating piston into the valve's fluid path), and the quantification of functional margins for each design. Experiments were conducted at NASA's Langley Research Center on several units for each of the five valve designs. The test methods used for this program measured the forces and energies required to actuate the valves, as well as the energies and the pressures (where possible) delivered by the pyrotechnic sources. Functional performance ranged widely among the designs. Blowby cannot be prevented by o-ring seals; metal-to-metal seals were effective. Functional margin was determined by dividing the energy delivered by the pyrotechnic sources in excess to that required to accomplish the function by the energy required for that function. Two of the five designs had inadequate functional margins with the pyrotechnic cartridges evaluated.

  10. Ecological Inventory Exemplars.

    ERIC Educational Resources Information Center

    Sobsey, Dick, Ed.

    The document contains 20 ecological inventories (developed at the University of Minnesota and the University of Alberta) to help severely disabled students learn functional living skills. The ecological approach is designed to uncover the functions critical for success in specific environments which the student frequently encounters. Matching the…

  11. Autonomous Integrated Receive System (AIRS) requirements definition. Volume 4: Functional specification for the prototype Automated Integrated Receive System (AIRS)

    NASA Technical Reports Server (NTRS)

    Chie, C. M.

    1984-01-01

    The functional requirements for the performance, design, and testing for the prototype Automated Integrated Receive System (AIRS) to be demonstrated for the TDRSS S-Band Single Access Return Link are presented.

  12. Space robotics in the '90s

    NASA Technical Reports Server (NTRS)

    Ruoff, Carl F.

    1989-01-01

    The use of telerobots and rovers in space missions is examined. The functioning of the telerobots and rovers and their proposed applications are described. Research developments needed to design robots for specific environments and functions are described. Examples of NASA robotics projects are presented.

  13. Design Optimization Tool for Synthetic Jet Actuators Using Lumped Element Modeling

    NASA Technical Reports Server (NTRS)

    Gallas, Quentin; Sheplak, Mark; Cattafesta, Louis N., III; Gorton, Susan A. (Technical Monitor)

    2005-01-01

    The performance specifications of any actuator are quantified in terms of an exhaustive list of parameters such as bandwidth, output control authority, etc. Flow-control applications benefit from a known actuator frequency response function that relates the input voltage to the output property of interest (e.g., maximum velocity, volumetric flow rate, momentum flux, etc.). Clearly, the required performance metrics are application specific, and methods are needed to achieve the optimal design of these devices. Design and optimization studies have been conducted for piezoelectric cantilever-type flow control actuators, but the modeling issues are simpler compared to synthetic jets. Here, lumped element modeling (LEM) is combined with equivalent circuit representations to estimate the nonlinear dynamic response of a synthetic jet as a function of device dimensions, material properties, and external flow conditions. These models provide reasonable agreement between predicted and measured frequency response functions and thus are suitable for use as design tools. In this work, we have developed a Matlab-based design optimization tool for piezoelectric synthetic jet actuators based on the lumped element models mentioned above. Significant improvements were achieved by optimizing the piezoceramic diaphragm dimensions. Synthetic-jet actuators were fabricated and benchtop tested to fully document their behavior and validate a companion optimization effort. It is hoped that the tool developed from this investigation will assist in the design and deployment of these actuators.

  14. Preliminary study for a numerical aerodynamic simulation facility. Phase 1: Extension

    NASA Technical Reports Server (NTRS)

    Lincoln, N. R.

    1978-01-01

    Functional requirements and preliminary design data were identified for use in the design of all system components and in the construction of a facility to perform aerodynamic simulation for airframe design. A skeleton structure of specifications for the flow model processor and monitor, the operating system, and the language and its compiler is presented.

  15. Onboard FPGA-based SAR processing for future spaceborne systems

    NASA Technical Reports Server (NTRS)

    Le, Charles; Chan, Samuel; Cheng, Frank; Fang, Winston; Fischman, Mark; Hensley, Scott; Johnson, Robert; Jourdan, Michael; Marina, Miguel; Parham, Bruce; hide

    2004-01-01

    We present a real-time high-performance and fault-tolerant FPGA-based hardware architecture for the processing of synthetic aperture radar (SAR) images in future spaceborne system. In particular, we will discuss the integrated design approach, from top-level algorithm specifications and system requirements, design methodology, functional verification and performance validation, down to hardware design and implementation.

  16. Synergistic Integration of Experimental and Simulation Approaches for the de Novo Design of Silk-Based Materials.

    PubMed

    Huang, Wenwen; Ebrahimi, Davoud; Dinjaski, Nina; Tarakanova, Anna; Buehler, Markus J; Wong, Joyce Y; Kaplan, David L

    2017-04-18

    Tailored biomaterials with tunable functional properties are crucial for a variety of task-specific applications ranging from healthcare to sustainable, novel bio-nanodevices. To generate polymeric materials with predictive functional outcomes, exploiting designs from nature while morphing them toward non-natural systems offers an important strategy. Silks are Nature's building blocks and are produced by arthropods for a variety of uses that are essential for their survival. Due to the genetic control of encoded protein sequence, mechanical properties, biocompatibility, and biodegradability, silk proteins have been selected as prototype models to emulate for the tunable designs of biomaterial systems. The bottom up strategy of material design opens important opportunities to create predictive functional outcomes, following the exquisite polymeric templates inspired by silks. Recombinant DNA technology provides a systematic approach to recapitulate, vary, and evaluate the core structure peptide motifs in silks and then biosynthesize silk-based polymers by design. Post-biosynthesis processing allows for another dimension of material design by controlled or assisted assembly. Multiscale modeling, from the theoretical prospective, provides strategies to explore interactions at different length scales, leading to selective material properties. Synergy among experimental and modeling approaches can provide new and more rapid insights into the most appropriate structure-function relationships to pursue while also furthering our understanding in terms of the range of silk-based systems that can be generated. This approach utilizes nature as a blueprint for initial polymer designs with useful functions (e.g., silk fibers) but also employs modeling-guided experiments to expand the initial polymer designs into new domains of functional materials that do not exist in nature. The overall path to these new functional outcomes is greatly accelerated via the integration of modeling with experiment. In this Account, we summarize recent advances in understanding and functionalization of silk-based protein systems, with a focus on the integration of simulation and experiment for biopolymer design. Spider silk was selected as an exemplary protein to address the fundamental challenges in polymer designs, including specific insights into the role of molecular weight, hydrophobic/hydrophilic partitioning, and shear stress for silk fiber formation. To expand current silk designs toward biointerfaces and stimuli responsive materials, peptide modules from other natural proteins were added to silk designs to introduce new functions, exploiting the modular nature of silk proteins and fibrous proteins in general. The integrated approaches explored suggest that protein folding, silk volume fraction, and protein amino acid sequence changes (e.g., mutations) are critical factors for functional biomaterial designs. In summary, the integrated modeling-experimental approach described in this Account suggests a more rationally directed and more rapid method for the design of polymeric materials. It is expected that this combined use of experimental and computational approaches has a broad applicability not only for silk-based systems, but also for other polymer and composite materials.

  17. Design and implementation of GaAs HBT circuits with ACME

    NASA Technical Reports Server (NTRS)

    Hutchings, Brad L.; Carter, Tony M.

    1993-01-01

    GaAs HBT circuits offer high performance (5-20 GHz) and radiation hardness (500 Mrad) that is attractive for space applications. ACME is a CAD tool specifically developed for HBT circuits. ACME implements a novel physical schematic-capture design technique where designers simultaneously view the structure and physical organization of a circuit. ACME's design interface is similar to schematic capture; however, unlike conventional schematic capture, designers can directly control the physical placement of both function and interconnect at the schematic level. In addition, ACME provides design-time parasitic extraction, complex wire models, and extensions to Multi-Chip Modules (MCM's). A GaAs HBT gate-array and semi-custom circuits have been developed with ACME; several circuits have been fabricated and found to be fully functional .

  18. SCOPIC Design and Overview

    ERIC Educational Resources Information Center

    Barth, Danielle; Evans, Nicholas

    2017-01-01

    This paper provides an overview of the design and motivation for creating the Social Cognition Parallax Interview Corpus (SCOPIC), an open-ended, accessible corpus that balances the need for language-specific annotation with typologically-calibrated markup. SCOPIC provides richly annotated data, focusing on functional categories relevant to social…

  19. Multipurpose silicon photonics signal processor core.

    PubMed

    Pérez, Daniel; Gasulla, Ivana; Crudgington, Lee; Thomson, David J; Khokhar, Ali Z; Li, Ke; Cao, Wei; Mashanovich, Goran Z; Capmany, José

    2017-09-21

    Integrated photonics changes the scaling laws of information and communication systems offering architectural choices that combine photonics with electronics to optimize performance, power, footprint, and cost. Application-specific photonic integrated circuits, where particular circuits/chips are designed to optimally perform particular functionalities, require a considerable number of design and fabrication iterations leading to long development times. A different approach inspired by electronic Field Programmable Gate Arrays is the programmable photonic processor, where a common hardware implemented by a two-dimensional photonic waveguide mesh realizes different functionalities through programming. Here, we report the demonstration of such reconfigurable waveguide mesh in silicon. We demonstrate over 20 different functionalities with a simple seven hexagonal cell structure, which can be applied to different fields including communications, chemical and biomedical sensing, signal processing, multiprocessor networks, and quantum information systems. Our work is an important step toward this paradigm.Integrated optical circuits today are typically designed for a few special functionalities and require complex design and development procedures. Here, the authors demonstrate a reconfigurable but simple silicon waveguide mesh with different functionalities.

  20. High performance VLSI telemetry data systems

    NASA Technical Reports Server (NTRS)

    Chesney, J.; Speciale, N.; Horner, W.; Sabia, S.

    1990-01-01

    NASA's deployment of major space complexes such as Space Station Freedom (SSF) and the Earth Observing System (EOS) will demand increased functionality and performance from ground based telemetry acquisition systems well above current system capabilities. Adaptation of space telemetry data transport and processing standards such as those specified by the Consultative Committee for Space Data Systems (CCSDS) standards and those required for commercial ground distribution of telemetry data, will drive these functional and performance requirements. In addition, budget limitations will force the requirement for higher modularity, flexibility, and interchangeability at lower cost in new ground telemetry data system elements. At NASA's Goddard Space Flight Center (GSFC), the design and development of generic ground telemetry data system elements, over the last five years, has resulted in significant solutions to these problems. This solution, referred to as the functional components approach includes both hardware and software components ready for end user application. The hardware functional components consist of modern data flow architectures utilizing Application Specific Integrated Circuits (ASIC's) developed specifically to support NASA's telemetry data systems needs and designed to meet a range of data rate requirements up to 300 Mbps. Real-time operating system software components support both embedded local software intelligence, and overall system control, status, processing, and interface requirements. These components, hardware and software, form the superstructure upon which project specific elements are added to complete a telemetry ground data system installation. This paper describes the functional components approach, some specific component examples, and a project example of the evolution from VLSI component, to basic board level functional component, to integrated telemetry data system.

  1. Design of multi-function sensor detection system in coal mine based on ARM

    NASA Astrophysics Data System (ADS)

    Ge, Yan-Xiang; Zhang, Quan-Zhu; Deng, Yong-Hong

    2017-06-01

    The traditional coal mine sensor in the specific measurement points, the number and type of channel will be greater than or less than the number of monitoring points, resulting in a waste of resources or cannot meet the application requirements, in order to enable the sensor to adapt to the needs of different occasions and reduce the cost, a kind of multi-functional intelligent sensor multiple sensors and ARM11 the S3C6410 processor is used to design and realize the dust, gas, temperature and humidity sensor functions together, and has storage, display, voice, pictures, data query, alarm and other new functions.

  2. Polyubiquitin-sensor proteins reveal localization and linkage-type dependence of cellular ubiquitin signaling

    PubMed Central

    Sims, Joshua J.; Scavone, Francesco; Cooper, Eric M.; Kane, Lesley A.; Youle, Richard J.; Boeke, Jef D.; Cohen, Robert E.

    2012-01-01

    Polyubiquitin (polyUb) chain topology is thought to direct modified substrates to specific fates, but this function-topology relationship is poorly understood, as are the dynamics and subcellular locations of specific polyUb signals. Experimental access to these questions has been limited because linkage-specific inhibitors and in vivo sensors have been unavailable. Here we present a general strategy to track linkage-specific polyUb signals in yeast and mammalian cells, and to probe their functions. We designed several high-affinity lysine-63-polyUb-binding proteins and demonstrate their specificity both in vitro and in cells. We apply these tools as competitive inhibitors to dissect the polyUb-linkage dependence of NF-κB activation in several cell types, inferring the essential role of lysine-63-polyUb for signaling via the IL-1β and TNF-related weak inducer of apoptosis (TWEAK) but not TNF-α receptors. We anticipate live-cell imaging, proteomic, and biochemical applications for these tools, and extension of the design strategy to other polymeric ubiquitin-like protein modifications. PMID:22306808

  3. Crew interface specification development study for in-flight maintenance and stowage functions

    NASA Technical Reports Server (NTRS)

    Carl, J. G.

    1971-01-01

    The need and potential solutions for an orderly systems engineering approach to the definition, management and documentation requirements for in-flight maintenance, assembly, servicing, and stowage process activities of the flight crews of future spacecraft were investigated. These processes were analyzed and described using a new technique (mass/function flow diagramming), developed during the study, to give visibility to crew functions and supporting requirements, including data products. This technique is usable by NASA for specification baselines and can assist the designer in identifying both upper and lower level requirements associated with these processes. These diagrams provide increased visibility into the relationships between functions and related equipments being utilized and managed and can serve as a common communicating vehicle between the designer, program management, and the operational planner. The information and data product requirements to support the above processes were identified along with optimum formats and contents of these products. The resulting data product concepts are presented to support these in-flight maintenance and stowage processes.

  4. Design of a homogeneous multifunctional supported lipid membrane on layer-by-layer coated microcarriers.

    PubMed

    Göse, Martin; Pescador, Paula; Reibetanz, Uta

    2015-03-09

    Key challenges in the development of drug delivery systems are the prevention of serum compartment interaction and the targeted delivery of the cargo. Layer-by-Layer microcarriers offer many advantages due to various options in drug assembly and multifunctional design. Surface modification with a supported lipid membrane enhances biocompatibility, drug protection ability, and specific functionality. However, the integration of functionalized lipids strongly influences the membrane formation and is often accompanied by submicrometer irregularities: The accessibility of underlying polymers to serum components may change the carrier's properties and enhances the susceptibility to opsonization. Therefore, the formation of a tightly assembled multifunctional lipid membrane has been emphasized. A phosphatidylserine/phosphatidylcholine (POPS/POPC) bilayer equipped with phosphatidylethanolamine-polyethylene glycol-biotin (PE-PEG-Biotin) was used to facilitate a biotin/streptavidin binding site for a variable attachment of an additional function, such as antibodies for specific targeting. Thus, a prefunctionalized carrier where only the outer functionality needs to be replaced without disturbing the underlying structure could be created.

  5. Soybean crop-water production functions in a humid region across years and soils determined with APEX model

    Treesearch

    Bangbang Zhang; Gary Feng; Lajpat R. Ahuja; Xiangbin Kong; Ying Ouyang; Ardeshir Adeli; Johnie N. Jenkins

    2018-01-01

    Crop production as a function of water use or water applied, called the crop water production function (CWPF), is a useful tool for irrigation planning, design and management. However, these functions are not only crop and variety specific they also vary with soil types and climatic conditions (locations). Derivation of multi-year average CWPFs through field...

  6. Modular Integrated Stackable Layers (MISL) 1.1 Design Specification. Design Guideline Document

    NASA Technical Reports Server (NTRS)

    Yim, Hester J.

    2012-01-01

    This document establishes the design guideline of the Modular Instrumentation Data Acquisition (MI-DAQ) system in utilization of several designs available in EV. The MI- DAQ provides the options to the customers depending on their system requirements i.e. a 28V interface power supply, a low power battery operated system, a low power microcontroller, a higher performance microcontroller, a USB interface, a Ethernet interface, a wireless communication, various sensor interfaces, etc. Depending on customer's requirements, the each functional board can be stacked up from a bottom level of power supply to a higher level of stack to provide user interfaces. The stack up of boards are accomplished by a predefined and standardized power bus and data bus connections which are included in this document along with other physical and electrical guidelines. This guideline also provides information for a new design options. This specification is the product of a collaboration between NASA/JSC/EV and Texas A&M University. The goal of the collaboration is to open source the specification and allow outside entities to design, build, and market modules that are compatible with the specification. NASA has designed and is using numerous modules that are compatible to this specification. A limited number of these modules will also be released as open source designs to support the collaboration. The released designs are listed in the Applicable Documents.

  7. A reliable algorithm for optimal control synthesis

    NASA Technical Reports Server (NTRS)

    Vansteenwyk, Brett; Ly, Uy-Loi

    1992-01-01

    In recent years, powerful design tools for linear time-invariant multivariable control systems have been developed based on direct parameter optimization. In this report, an algorithm for reliable optimal control synthesis using parameter optimization is presented. Specifically, a robust numerical algorithm is developed for the evaluation of the H(sup 2)-like cost functional and its gradients with respect to the controller design parameters. The method is specifically designed to handle defective degenerate systems and is based on the well-known Pade series approximation of the matrix exponential. Numerical test problems in control synthesis for simple mechanical systems and for a flexible structure with densely packed modes illustrate positively the reliability of this method when compared to a method based on diagonalization. Several types of cost functions have been considered: a cost function for robust control consisting of a linear combination of quadratic objectives for deterministic and random disturbances, and one representing an upper bound on the quadratic objective for worst case initial conditions. Finally, a framework for multivariable control synthesis has been developed combining the concept of closed-loop transfer recovery with numerical parameter optimization. The procedure enables designers to synthesize not only observer-based controllers but also controllers of arbitrary order and structure. Numerical design solutions rely heavily on the robust algorithm due to the high order of the synthesis model and the presence of near-overlapping modes. The design approach is successfully applied to the design of a high-bandwidth control system for a rotorcraft.

  8. antaRNA: ant colony-based RNA sequence design.

    PubMed

    Kleinkauf, Robert; Mann, Martin; Backofen, Rolf

    2015-10-01

    RNA sequence design is studied at least as long as the classical folding problem. Although for the latter the functional fold of an RNA molecule is to be found ,: inverse folding tries to identify RNA sequences that fold into a function-specific target structure. In combination with RNA-based biotechnology and synthetic biology ,: reliable RNA sequence design becomes a crucial step to generate novel biochemical components. In this article ,: the computational tool antaRNA is presented. It is capable of compiling RNA sequences for a given structure that comply in addition with an adjustable full range objective GC-content distribution ,: specific sequence constraints and additional fuzzy structure constraints. antaRNA applies ant colony optimization meta-heuristics and its superior performance is shown on a biological datasets. http://www.bioinf.uni-freiburg.de/Software/antaRNA CONTACT: backofen@informatik.uni-freiburg.de Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  9. Ground Operations Aerospace Language (GOAL). Volume 4: Interpretive code translator

    NASA Technical Reports Server (NTRS)

    1973-01-01

    This specification identifies and describes the principal functions and elements of the Interpretive Code Translator which has been developed for use with the GOAL Compiler. This translator enables the user to convert a compliled GOAL program to a highly general binary format which is designed to enable interpretive execution. The translator program provides user controls which are designed to enable the selection of various output types and formats. These controls provide a means for accommodating many of the implementation options which are discussed in the Interpretive Code Guideline document. The technical design approach is given. The relationship between the translator and the GOAL compiler is explained and the principal functions performed by the Translator are described. Specific constraints regarding the use of the Translator are discussed. The control options are described. These options enable the user to select outputs to be generated by the translator and to control vrious aspects of the translation processing.

  10. Eugene--a domain specific language for specifying and constraining synthetic biological parts, devices, and systems.

    PubMed

    Bilitchenko, Lesia; Liu, Adam; Cheung, Sherine; Weeding, Emma; Xia, Bing; Leguia, Mariana; Anderson, J Christopher; Densmore, Douglas

    2011-04-29

    Synthetic biological systems are currently created by an ad-hoc, iterative process of specification, design, and assembly. These systems would greatly benefit from a more formalized and rigorous specification of the desired system components as well as constraints on their composition. Therefore, the creation of robust and efficient design flows and tools is imperative. We present a human readable language (Eugene) that allows for the specification of synthetic biological designs based on biological parts, as well as provides a very expressive constraint system to drive the automatic creation of composite Parts (Devices) from a collection of individual Parts. We illustrate Eugene's capabilities in three different areas: Device specification, design space exploration, and assembly and simulation integration. These results highlight Eugene's ability to create combinatorial design spaces and prune these spaces for simulation or physical assembly. Eugene creates functional designs quickly and cost-effectively. Eugene is intended for forward engineering of DNA-based devices, and through its data types and execution semantics, reflects the desired abstraction hierarchy in synthetic biology. Eugene provides a powerful constraint system which can be used to drive the creation of new devices at runtime. It accomplishes all of this while being part of a larger tool chain which includes support for design, simulation, and physical device assembly.

  11. Flight software development for the isothermal dendritic growth experiment

    NASA Technical Reports Server (NTRS)

    Levinson, Laurie H.; Winsa, Edward A.; Glicksman, Martin E.

    1989-01-01

    The Isothermal Dendritic Growth Experiment (IDGE) is a microgravity materials science experiment scheduled to fly in the cargo bay of the shuttle on the United States Microgravity Payload (USMP) carrier. The experiment will be operated by real-time control software which will not only monitor and control onboard experiment hardware, but will also communicate, via downlink data and uplink commands, with the Payload Operations Control Center (POCC) at NASA George C. Marshall Space Flight Center (MSFC). The software development approach being used to implement this system began with software functional requirements specification. This was accomplished using the Yourdon/DeMarco methodology as supplemented by the Ward/Mellor real-time extensions. The requirements specification in combination with software prototyping was then used to generate a detailed design consisting of structure charts, module prologues, and Program Design Language (PDL) specifications. This detailed design will next be used to code the software, followed finally by testing against the functional requirements. The result will be a modular real-time control software system with traceability through every phase of the development process.

  12. Flight software development for the isothermal dendritic growth experiment

    NASA Technical Reports Server (NTRS)

    Levinson, Laurie H.; Winsa, Edward A.; Glicksman, M. E.

    1990-01-01

    The Isothermal Dendritic Growth Experiment (IDGE) is a microgravity materials science experiment scheduled to fly in the cargo bay of the shuttle on the United States Microgravity Payload (USMP) carrier. The experiment will be operated by real-time control software which will not only monitor and control onboard experiment hardware, but will also communicate, via downlink data and unlink commands, with the Payload Operations Control Center (POCC) at NASA George C. Marshall Space Flight Center (MSFC). The software development approach being used to implement this system began with software functional requirements specification. This was accomplished using the Yourdon/DeMarco methodology as supplemented by the Ward/Mellor real-time extensions. The requirements specification in combination with software prototyping was then used to generate a detailed design consisting of structure charts, module prologues, and Program Design Language (PDL) specifications. This detailed design will next be used to code the software, followed finally by testing against the functional requirements. The result will be a modular real-time control software system with traceability through every phase of the development process.

  13. Consequences of maternal morbidity on health-related functioning: a systematic scoping review

    PubMed Central

    Machiyama, Kazuyo; Hirose, Atsumi; Cresswell, Jenny A; Barreix, Maria; Chou, Doris; Kostanjsek, Nenad; Say, Lale; Filippi, Véronique

    2017-01-01

    Objectives To assess the scope of the published literature on the consequences of maternal morbidity on health-related functioning at the global level and identify key substantive findings as well as research and methodological gaps. Methods We searched for articles published between 2005 and 2014 using Medline, Embase, Popline, CINAHL Plus and three regional bibliographic databases in January 2015. Design Systematic scoping review Primary outcome Health-related functioning Results After screening 17 706 studies, 136 articles were identified for inclusion. While a substantial number of papers have documented mostly negative effects of morbidity on health-related functioning and well-being, the body of evidence is not spread evenly across conditions, domains or geographical regions. Over 60% of the studies focus on indirect conditions such as depression, diabetes and incontinence. Health-related functioning is often assessed by instruments designed for the general population including the 36-item Short Form or disease-specific tools. The functioning domains most frequently documented are physical and mental; studies that examined physical, mental, social, economic and specifically focused on marital, maternal and sexual functioning are rare. Only 16 studies were conducted in Africa. Conclusions Many assessments have not been comprehensive and have paid little attention to important functioning domains for pregnant and postpartum women. The development of a comprehensive instrument specific to maternal health would greatly advance our understanding of burden of ill health associated with maternal morbidity and help set priorities. The lack of attention to consequences on functioning associated with the main direct obstetric complications is of particular concern. Review registration CRD42015017774 PMID:28667198

  14. Design, production and first commissioning results of the electrical feedboxes of the LHC

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

    Perin, A.; Atieh, S.; Benda, V.

    2007-12-01

    A total of 44 CERN designed cryogenic electrical feedboxes are needed to power the LHC superconducting magnets. The feedboxes include more than 1000 superconducting circuits fed by high temperature superconductor and conventional current leads ranging from 120 A to 13 kA. In addition to providing the electrical current to the superconducting circuits, they also ensure specific mechanical and cryogenic functions for the LHC. The paper focuses on the main design aspects and related production operations and gives an overview of specific technologies employed. Results of the commissioning of the feedboxes of the first LHC sectors are presented.

  15. Summary of Research Adaptions of Visceral and Cerebral Resistance Arteries to Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Delp, Michael

    2003-01-01

    The proposed studies were designed address the effects of simulated microgravity on vascular smooth muscle and endothelial cell function in resistance arteries isolated from visceral tissues (spleen, mesentery and kidneys) and cerebrum. Alterations in vascular function induced by microgravity are particularly relevant to the problems of orthostatic intolerance and reduced exercise capacity experienced by astronauts upon re-entry into the earth's gravitational field. Decrements in contractile function or enhanced vasodilatory responsiveness of peripheral resistance arteries could lead to decreased peripheral resistance and orthostatic hypotension. Alternatively, augmentation of contractile function in cerebral resistance arteries could lead to increased cerebral vascular resistance and diminished perfusion of the brain. The Specific Aims and hypotheses were proposed in this grant. Following each of the Specific Aims, progress toward addressing that specific aim is presented. With the exception of Specific Aim VI (see aim for details), all aims have been experimentally addressed as proposed. The final six months of the granting period will be used for manuscript preparation; manuscripts in preparation will contain results from Specific Aims I-IV. Results from Specific Aims V and VI have been published.

  16. Exploring the impact of wheelchair design on user function in a rural South African setting.

    PubMed

    Visagie, Surona; Duffield, Svenje; Unger, Mariaan

    2015-01-01

    Wheelchairs provide mobility that can enhance function and community integration. Function in a wheelchair is influenced by wheelchair design. To explore the impact of wheelchair design on user function and the variables that guided wheelchair prescription in the study setting. A mixed-method, descriptive design using convenience sampling was implemented. Quantitative data were collected from 30 wheelchair users using the functioning every day with a Wheelchair Scale and a Wheelchair Specification Checklist. Qualitative data were collected from ten therapists who prescribed wheelchairs to these users, through interviews. The Kruskal-Wallis test was used to identify relationships, and content analysis was undertaken to identify emerging themes in qualitative data. Wheelchairs with urban designs were issued to 25 (83%) participants. Wheelchair size, fit, support and functional features created challenges concerning transport, operating the wheelchair, performing personal tasks, and indoor and outdoor mobility. Users using wheelchairs designed for use in semi-rural environments achieved significantly better scores regarding the appropriateness of the prescribed wheelchair than those using wheelchairs designed for urban use ( p = <0.01). Therapists prescribed the basic, four-wheel folding frame design most often because of a lack of funding, lack of assessment, lack of skills and user choice. Issuing urban type wheelchairs to users living in rural settings might have a negative effect on users' functional outcomes. Comprehensive assessments, further training and research, on long term cost and quality of life implications, regarding provision of a suitable wheelchair versus a cheaper less suitable option is recommended.

  17. Design review report for the SY-101 RAPID mitigation system

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

    SCHLOSSER, R.L.

    1999-05-24

    This report documents design reviews conducted of the SY-101 Respond And Pump In Days (RAPID) Mitigation System. As part of the SY-101 Surface-Level-Rise Remediation Project, the SY-101 WID Mitigation System will reduce the potential unacceptable consequences of crust growth in Tank 241-SY-101 (SY-101). Projections of the crust growth rate indicate that the waste level in the tank may reach the juncture of the primary and secondary confinement structures of the tank late in 1999. Because of this time constraint, many design activities are being conducted in parallel and design reviews were conducted for system adequacy as well as design implementationmore » throughout the process. Design implementation, as used in this design review report, is the final component selection (e.g., which circuit breaker, valve, or thermocouple) that meets the approved design requirements, system design, and design and procurement specifications. Design implementation includes the necessary analysis, testing, verification, and qualification to demonstrate compliance with the system design and design requirements. Design implementation is outside the scope of this design review. The design activities performed prior to detailed design implementation (i.e., system mission requirements, functional design requirements, technical criteria, system conceptual design, and where design and build contracts were placed, the procurement specification) have been reviewed and are within the scope of this design review report. Detailed design implementation will be controlled, reviewed, and where appropriate, approved in accordance with Tank Waste Remediation System (TWRS) engineering procedures. Review of detailed design implementation will continue until all components necessary to perform the transfer function are installed and tested.« less

  18. Composing, Analyzing and Validating Software Models

    NASA Astrophysics Data System (ADS)

    Sheldon, Frederick T.

    1998-10-01

    This research has been conducted at the Computational Sciences Division of the Information Sciences Directorate at Ames Research Center (Automated Software Engineering Grp). The principle work this summer has been to review and refine the agenda that were carried forward from last summer. Formal specifications provide good support for designing a functionally correct system, however they are weak at incorporating non-functional performance requirements (like reliability). Techniques which utilize stochastic Petri nets (SPNs) are good for evaluating the performance and reliability for a system, but they may be too abstract and cumbersome from the stand point of specifying and evaluating functional behavior. Therefore, one major objective of this research is to provide an integrated approach to assist the user in specifying both functionality (qualitative: mutual exclusion and synchronization) and performance requirements (quantitative: reliability and execution deadlines). In this way, the merits of a powerful modeling technique for performability analysis (using SPNs) can be combined with a well-defined formal specification language. In doing so, we can come closer to providing a formal approach to designing a functionally correct system that meets reliability and performance goals.

  19. Composing, Analyzing and Validating Software Models

    NASA Technical Reports Server (NTRS)

    Sheldon, Frederick T.

    1998-01-01

    This research has been conducted at the Computational Sciences Division of the Information Sciences Directorate at Ames Research Center (Automated Software Engineering Grp). The principle work this summer has been to review and refine the agenda that were carried forward from last summer. Formal specifications provide good support for designing a functionally correct system, however they are weak at incorporating non-functional performance requirements (like reliability). Techniques which utilize stochastic Petri nets (SPNs) are good for evaluating the performance and reliability for a system, but they may be too abstract and cumbersome from the stand point of specifying and evaluating functional behavior. Therefore, one major objective of this research is to provide an integrated approach to assist the user in specifying both functionality (qualitative: mutual exclusion and synchronization) and performance requirements (quantitative: reliability and execution deadlines). In this way, the merits of a powerful modeling technique for performability analysis (using SPNs) can be combined with a well-defined formal specification language. In doing so, we can come closer to providing a formal approach to designing a functionally correct system that meets reliability and performance goals.

  20. Application of Function-Failure Similarity Method to Rotorcraft Component Design

    NASA Technical Reports Server (NTRS)

    Roberts, Rory A.; Stone, Robert E.; Tumer, Irem Y.; Clancy, Daniel (Technical Monitor)

    2002-01-01

    Performance and safety are the top concerns of high-risk aerospace applications at NASA. Eliminating or reducing performance and safety problems can be achieved with a thorough understanding of potential failure modes in the designs that lead to these problems. The majority of techniques use prior knowledge and experience as well as Failure Modes and Effects as methods to determine potential failure modes of aircraft. During the design of aircraft, a general technique is needed to ensure that every potential failure mode is considered, while avoiding spending time on improbable failure modes. In this work, this is accomplished by mapping failure modes to specific components, which are described by their functionality. The failure modes are then linked to the basic functions that are carried within the components of the aircraft. Using this technique, designers can examine the basic functions, and select appropriate analyses to eliminate or design out the potential failure modes. The fundamentals of this method were previously introduced for a simple rotating machine test rig with basic functions that are common to a rotorcraft. In this paper, this technique is applied to the engine and power train of a rotorcraft, using failures and functions obtained from accident reports and engineering drawings.

  1. Prefocal station mechanical design concept study for the E-ELT

    NASA Astrophysics Data System (ADS)

    Jolley, Paul; Brunetto, Enzo; Frank, Christoph; Lewis, Steffan; Marchetti, Enrico

    2016-07-01

    The Nasmyth platforms of the E-ELT will contain one Prefocal Station (PFS) each. The main PFS functional requirements are to provide a focal plane to the three Nasmyth focal stations and the Coudé focus, optical sensing supporting telescope low order optimisation and seeing limited image quality, and optical sensing supporting characterising and phasing of M1 and other telescope subsystems. The PFS user requirements are used to derive the PFS technical requirements specification that will form the basis for design, development and production of the system. This specification process includes high-level architectural decisions and technical performance budget allocations. The mechanical design concepts reported here have been developed in order to validate key system specifications and associated technical budgets.

  2. Integrated performance and reliability specification for digital avionics systems

    NASA Technical Reports Server (NTRS)

    Brehm, Eric W.; Goettge, Robert T.

    1995-01-01

    This paper describes an automated tool for performance and reliability assessment of digital avionics systems, called the Automated Design Tool Set (ADTS). ADTS is based on an integrated approach to design assessment that unifies traditional performance and reliability views of system designs, and that addresses interdependencies between performance and reliability behavior via exchange of parameters and result between mathematical models of each type. A multi-layer tool set architecture has been developed for ADTS that separates the concerns of system specification, model generation, and model solution. Performance and reliability models are generated automatically as a function of candidate system designs, and model results are expressed within the system specification. The layered approach helps deal with the inherent complexity of the design assessment process, and preserves long-term flexibility to accommodate a wide range of models and solution techniques within the tool set structure. ADTS research and development to date has focused on development of a language for specification of system designs as a basis for performance and reliability evaluation. A model generation and solution framework has also been developed for ADTS, that will ultimately encompass an integrated set of analytic and simulated based techniques for performance, reliability, and combined design assessment.

  3. Space station data system analysis/architecture study. Task 4: System definition report. Appendix

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Appendices to the systems definition study for the space station Data System are compiled. Supplemental information on external interface specification, simulation and modeling, and function design characteristics is presented along with data flow diagrams, a data dictionary, and function allocation matrices.

  4. Preliminary Candidate Advanced Avionics System (PCAAS). [reduction in single pilot workload during instrument flight rules flight

    NASA Technical Reports Server (NTRS)

    Teper, G. L.; Hon, R. H.; Smyth, R. K.

    1977-01-01

    Specifications which define the system functional requirements, the subsystem and interface needs, and other requirements such as maintainability, modularity, and reliability are summarized. A design definition of all required avionics functions and a system risk analysis are presented.

  5. Designing a freeform optic for oblique illumination

    NASA Astrophysics Data System (ADS)

    Uthoff, Ross D.; Ulanch, Rachel N.; Williams, Kaitlyn E.; Ruiz Diaz, Liliana; King, Page; Koshel, R. John

    2017-11-01

    The Functional Freeform Fitting (F4) method is utilized to design a freeform optic for oblique illumination of Mark Rothko's Green on Blue (1956). Shown are preliminary results from an iterative freeform design process; from problem definition and specification development to surface fit, ray tracing results, and optimization. This method is applicable to both point and extended sources of various geometries.

  6. A Function-Behavior-State Approach to Designing Human Machine Interface for Nuclear Power Plant Operators

    NASA Astrophysics Data System (ADS)

    Lin, Y.; Zhang, W. J.

    2005-02-01

    This paper presents an approach to human-machine interface design for control room operators of nuclear power plants. The first step in designing an interface for a particular application is to determine information content that needs to be displayed. The design methodology for this step is called the interface design framework (called framework ). Several frameworks have been proposed for applications at varying levels, including process plants. However, none is based on the design and manufacture of a plant system for which the interface is designed. This paper presents an interface design framework which originates from design theory and methodology for general technical systems. Specifically, the framework is based on a set of core concepts of a function-behavior-state model originally proposed by the artificial intelligence research community and widely applied in the design research community. Benefits of this new framework include the provision of a model-based fault diagnosis facility, and the seamless integration of the design (manufacture, maintenance) of plants and the design of human-machine interfaces. The missing linkage between design and operation of a plant was one of the causes of the Three Mile Island nuclear reactor incident. A simulated plant system is presented to explain how to apply this framework in designing an interface. The resulting human-machine interface is discussed; specifically, several fault diagnosis examples are elaborated to demonstrate how this interface could support operators' fault diagnosis in an unanticipated situation.

  7. Designing added functions in engineered cementitious composites

    NASA Astrophysics Data System (ADS)

    Yang, En-Hua

    In this dissertation, a new and systematic material design approach is developed for ECC with added functions through material microstructures linkage to composite macroscopic behavior. The thesis research embodies theoretical development by building on previous ECC micromechanical models, and experimental investigations into three specific new versions of ECC with added functions aimed at addressing societal demands of our built infrastructure. Specifically, the theoretical study includes three important ECC modeling elements: Steady-state crack propagation analyses and simulation, predictive accuracy of the fiber bridging constitutive model, and development of the rate-dependent strain-hardening criteria. The first element establishes the steady-state cracking criterion as a fundamental requirement for multiple cracking behavior in brittle matrix composites. The second element improves the accuracy of crack-width prediction in ECC. The third element establishes the micromechanics basis for impact-resistant ECC design. Three new ECCs with added functions were developed and experimentally verified in this thesis research through the enhanced theoretical framework. A green ECC incorporating a large volume of industrial waste was demonstrated to possess reduced crack width and drying shrinkage. The self-healing ECC designed with tight crack width was demonstrated to recover transport and mechanical properties after microcrack damage when exposed to wet and dry cycles. The impact-resistant ECC was demonstrated to retain tensile ductility with increased strength under moderately high strain-rate loading. These new versions of ECC with added functions are expected to contribute greatly to enhancing the sustainability, durability, and safety of civil infrastructure built with ECC. This research establishes the effectiveness of micromechanics-based design and material ingredient tailoring for ECC with added new attributes but without losing its basic tensile ductile characteristics.

  8. Vestibular Function Research (VFR) experiment. Phase B: Design definition study

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The Vestibular Functions Research (VFR) Experiment was established to investigate the neurosensory and related physiological processes believed to be associated with the space flight nausea syndrome and to develop logical means for its prediction, prevention and treatment. The VFR Project consists of ground and spaceflight experimentation using frogs as specimens. The phase B Preliminary Design Study provided for the preliminary design of the experiment hardware, preparation of performance and hardware specification and a Phase C/D development plan, establishment of STS (Space Transportation System) interfaces and mission operations, and the study of a variety of hardware, experiment and mission options. The study consist of three major tasks: (1) mission mode trade-off; (2) conceptual design; and (3) preliminary design.

  9. 40 CFR 372.3 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... means Title III. Article means a manufactured item: (1) Which is formed to a specific shape or design during manufacture; (2) which has end use functions dependent in whole or in part upon its shape or design during end use; and (3) which does not release a toxic chemical under normal conditions of...

  10. Transformation of the Schoolhouse. Annual Report for 1969.

    ERIC Educational Resources Information Center

    Coughlin, Gaila, Ed.

    This report reviews some of the more important educational innovations that have transformed the arrangement of space and design of the schoolhouse environment. Design, structural, and functional features are described for open plan schools (schools without interior walls). Consideration is given to the use of performance specifications in the…

  11. Test Review: Delis, D. (2012) "Delis Rating of Executive Function (D-REF)." Bloomington, Minnesota: Pearson

    ERIC Educational Resources Information Center

    Warnick, Brittany; Drake, Morgan; Vidrine, Stephanie

    2015-01-01

    The Delis Rating of Executive Function (D-REF) is a set of rating scales designed to assess executive functions and their constituent sub-processes in children and adolescents between the ages of 5 and 18. More specifically, the D-REF is a supplemental assessment of children and adolescents demonstrating behavioral or cognitive difficulties often…

  12. Coherent Motion Sensitivity Predicts Individual Differences in Subtraction

    ERIC Educational Resources Information Center

    Boets, Bart; De Smedt, Bert; Ghesquiere, Pol

    2011-01-01

    Recent findings suggest deficits in coherent motion sensitivity, an index of visual dorsal stream functioning, in children with poor mathematical skills or dyscalculia, a specific learning disability in mathematics. We extended these data using a longitudinal design to unravel whether visual dorsal stream functioning is able to "predict"…

  13. Programmable Numerical Function Generators: Architectures and Synthesis Method

    DTIC Science & Technology

    2005-08-01

    generates HDL (Hardware Descrip- tion Language) code from the design specification described by Scilab [14], a MATLAB-like numerical calculation soft...cad.com/Error-NFG/. [14] Scilab 3.0, INRIA-ENPC, France, http://scilabsoft.inria.fr/ [15] M. J. Schulte and J. E. Stine, “Approximating elementary functions

  14. Appearance Investment and Everyday Interpersonal Functioning: An Experience Sampling Study

    ERIC Educational Resources Information Center

    Forand, Nicholas R.; Gunthert, Kathleen C.; German, Ramaris E.; Wenze, Susan J.

    2010-01-01

    Several studies have shown that body satisfaction affects interpersonal functioning. However, few have studied the specific interpersonal correlates of another important body image dimension, appearance investment--that is, the importance a woman places on appearance. We used an experience sampling design with PDA (personal digital assistant)…

  15. Discourse Classification into Rhetorical Functions for AWE Feedback

    ERIC Educational Resources Information Center

    Cotos, Elena; Pendar, Nick

    2016-01-01

    This paper reports on the development of an analysis engine for the Research Writing Tutor (RWT), an AWE program designed to provide genre and discipline-specific feedback on the functional units of research article discourse. Unlike traditional NLP-based applications that categorize complete documents, the analyzer categorizes every sentence in…

  16. Heterogeneity in Learning Style in Asperger Syndrome and High-Functioning Autism

    ERIC Educational Resources Information Center

    Tsatsanis, Katharine D.

    2004-01-01

    Although children and adolescents with high-functioning autism and Asperger syndrome present with some similar clinical features and challenges, heterogeneity of learning style coupled with the predominance of specific "packages" of materials and methods tends to understate the need for individualization when designing an educational and/or a…

  17. Lasercom system architecture with reduced complexity

    NASA Technical Reports Server (NTRS)

    Lesh, James R. (Inventor); Chen, Chien-Chung (Inventor); Ansari, Homayoon (Inventor)

    1994-01-01

    Spatial acquisition and precision beam pointing functions are critical to spaceborne laser communication systems. In the present invention, a single high bandwidth CCD detector is used to perform both spatial acquisition and tracking functions. Compared to previous lasercom hardware design, the array tracking concept offers reduced system complexity by reducing the number of optical elements in the design. Specifically, the design requires only one detector and one beam steering mechanism. It also provides the means to optically close the point-ahead control loop. The technology required for high bandwidth array tracking was examined and shown to be consistent with current state of the art. The single detector design can lead to a significantly reduced system complexity and a lower system cost.

  18. LaserCom System Architecture With Reduced Complexity

    NASA Technical Reports Server (NTRS)

    Lesh, James R. (Inventor); Chen, Chien-Chung (Inventor); Ansari, Homa-Yoon (Inventor)

    1996-01-01

    Spatial acquisition and precision beam pointing functions are critical to spaceborne laser communication systems. In the present invention a single high bandwidth CCD detector is used to perform both spatial acquisition and tracking functions. Compared to previous lasercom hardware design, the array tracking concept offers reduced system complexity by reducing the number of optical elements in the design. Specifically, the design requires only one detector and one beam steering mechanism. It also provides means to optically close the point-ahead control loop. The technology required for high bandwidth array tracking was examined and shown to be consistent with current state of the art. The single detector design can lead to a significantly reduced system complexity and a lower system cost.

  19. Using subject-specific three-dimensional (3D) anthropometry data in digital human modelling: case study in hand motion simulation.

    PubMed

    Tsao, Liuxing; Ma, Liang

    2016-11-01

    Digital human modelling enables ergonomists and designers to consider ergonomic concerns and design alternatives in a timely and cost-efficient manner in the early stages of design. However, the reliability of the simulation could be limited due to the percentile-based approach used in constructing the digital human model. To enhance the accuracy of the size and shape of the models, we proposed a framework to generate digital human models using three-dimensional (3D) anthropometric data. The 3D scan data from specific subjects' hands were segmented based on the estimated centres of rotation. The segments were then driven in forward kinematics to perform several functional postures. The constructed hand models were then verified, thereby validating the feasibility of the framework. The proposed framework helps generate accurate subject-specific digital human models, which can be utilised to guide product design and workspace arrangement. Practitioner Summary: Subject-specific digital human models can be constructed under the proposed framework based on three-dimensional (3D) anthropometry. This approach enables more reliable digital human simulation to guide product design and workspace arrangement.

  20. "Phylogenetic and evolutionary analysis of functional divergence among Gamma glutamyl transpeptidase (GGT) subfamilies".

    PubMed

    Verma, Ved Vrat; Gupta, Rani; Goel, Manisha

    2015-09-14

    γ-glutamyltranspeptidase (GGT) is a bi-substrate enzyme conserved in all three domains of life. It catalyzes the cleavage and transfer of γ-glutamyl moiety of glutathione to either water (hydrolysis) or substrates like peptides (transpeptidation). GGTs exhibit great variability in their enzyme kinetics although the mechanism of catalysis is conserved. Recently, GGT has been shown to be a virulence factor in microbes like Helicobacter pylori and Bacillus anthracis. In mammalian cells also, GGT inhibition prior to chemotherapy has been shown to sensitize tumors to the therapy. Therefore, lately both bacterial and eukaryotic GGTs have emerged as potential drug targets, but the efforts directed towards finding suitable inhibitors have not yielded any significant results yet. We propose that delineating the residues responsible for the functional diversity associated with these proteins could help in design of species/clade specific inhibitors. In the present study, we have carried out phylogenetic analysis on a set of 47 GGT-like proteins to address the functional diversity. These proteins segregate into various subfamilies, forming separate clades on the tree. Sequence conservation and motif prediction studies show that even though most of the highly conserved residues have been characterized biochemically in previous studies, a significant number of novel putative sites and motifs are discovered that vary in a clade specific manner. Many of the putative sites predicted during the functional divergence type I and type II analysis, lie close to the known catalytic residues and line the walls of the substrate binding cavity, reinforcing their role in modulating the substrate specificity, catalytic rates and stability of this protein. The study offers interesting insights into the evolution of GGT-like proteins in pathogenic vs. non-pathogenic bacteria, archaea and eukaryotes. Our analysis delineates residues that are highly specific to each GGT subfamily. We propose that these sites not only explain the differences in stability and catalytic variability of various GGTs but can also aid in design of specific inhibitors against particular GGTs. Thus, apart from the commonly used in-silico inhibitor screening approaches, evolutionary analysis identifying the functional divergence hotspots in GGT proteins could augment the structure based drug design approaches.

  1. Architectonics: Design of Molecular Architecture for Functional Applications.

    PubMed

    Avinash, M B; Govindaraju, Thimmaiah

    2018-02-20

    The term architectonics has its roots in the architectural and philosophical (as early as 1600s) literature that refers to "the theory of structure" and "the structure of theory", respectively. The concept of architectonics has been adapted to advance the field of molecular self-assembly and termed as molecular architectonics. In essence, the methodology of organizing molecular units in the required and controlled configurations to develop advanced functional systems for materials and biological applications comprises the field of molecular architectonics. This concept of designing noncovalent systems enables to focus on different functional aspects of designer molecules for biological and nonbiological applications and also strengthens our efforts toward the mastery over the art of controlled molecular self-assemblies. Programming complex molecular interactions and assemblies for specific functions has been one of the most challenging tasks in the modern era. Meticulously ordered molecular assemblies can impart remarkable developments in several areas spanning energy, health, and environment. For example, the well-defined nano-, micro-, and macroarchitectures of functional molecules with specific molecular ordering possess potential applications in flexible electronics, photovoltaics, photonic crystals, microreactors, sensors, drug delivery, biomedicine, and superhydrophobic coatings, among others. The functional molecular architectures having unparalleled properties are widely evident in various designs of Nature. By drawing inspirations from Nature, intended molecular architectures can be designed and developed to harvest various functions, as there is an inexhaustible resource and scope. In this Account, we present exquisite designer molecules developed by our group and others with an objective to master the art of molecular recognition and self-assembly for functional applications. We demonstrate the tailor-ability of molecular self-assemblies by employing biomolecules like amino acids and nucleobases as auxiliaries. Naphthalenediimide (NDI), perylenediimide (PDI), and few other molecular systems serve as functional modules. The effects of stereochemistry and minute structural modifications in the molecular designs on the supramolecular interactions, and construction of self-assembled zero-dimensional (OD), one-dimensional (1D), and two-dimensional (2D) nano- and microarchitectures like particles, spheres, cups, bowls, fibers, belts, helical belts, supercoiled helices, sheets, fractals, and honeycomb-like arrays are discussed in extensive detail. Additionally, we present molecular systems that showcase the elegant designs of coassembly, templated assembly, hierarchical assembly, transient self-assembly, chiral denaturation, retentive helical memory, self-replication, supramolecular regulation, supramolecular speciation, supernon linearity, dynamic pathway complexity, supramolecular heterojunction, living supramolecular polymerization, and molecular machines. Finally, we describe the molecular engineering principles learnt over the years that have led to several applications, namely, organic electronics, self-cleaning, high-mechanical strength, and tissue engineering.

  2. Electrostatics of DNA-Functionalized Nanoparticles

    NASA Astrophysics Data System (ADS)

    Hoffmann, Kyle; Krishnamoorthy, Kurinji; Kewalramani, Sumit; Bedzyk, Michael; Olvera de La Cruz, Monica

    DNA-functionalized nanoparticles have applications in directed self-assembly and targeted cellular delivery of therapeutic proteins. In order to design specific systems, it is necessary to understand their self-assembly properties, of which the long-range electrostatic interactions are a critical component. We iteratively solved equations derived from classical density functional theory in order to predict the distribution of ions around DNA-functionalized Cg Catalase. We then compared estimates of the resonant intensity to those from SAXS measurements to estimate key features of DNA-functionalized proteins, such as the size of the region linking the protein and DNA and the extension of the single-stranded DNA. Using classical density functional theory and coarse-grained simulations, we are able to predict and understand these fundamental properties in order to rationally design new biomaterials.

  3. Analysis of crew functions as an aid in Space Station interior layout

    NASA Technical Reports Server (NTRS)

    Steinberg, A. L.; Tullis, Thomas S.; Bied, Barbra

    1986-01-01

    The Space Station must be designed to facilitate all of the functions that its crew will perform, both on-duty and off-duty, as efficiently and comfortably as possible. This paper examines the functions to be performed by the Space Station crew in order to make inferences about the design of an interior layout that optimizes crew productivity. Twenty-seven crew functions were defined, as well as five criteria for assessing relationships among all pairs of those functions. Hierarchical clustering and multidimensional scaling techniques were used to visually summarize the relationships. A key result was the identification of two dimensions for describing the configuration of crew functions: 'Private-Public' and 'Group-Individual'. Seven specific recommendations for Space Station interior layout were derived from the analyses.

  4. Software Dependability and Safety Evaluations ESA's Initiative

    NASA Astrophysics Data System (ADS)

    Hernek, M.

    ESA has allocated funds for an initiative to evaluate Dependability and Safety methods of Software. The objectives of this initiative are; · More extensive validation of Safety and Dependability techniques for Software · Provide valuable results to improve the quality of the Software thus promoting the application of Dependability and Safety methods and techniques. ESA space systems are being developed according to defined PA requirement specifications. These requirements may be implemented through various design concepts, e.g. redundancy, diversity etc. varying from project to project. Analysis methods (FMECA. FTA, HA, etc) are frequently used during requirements analysis and design activities to assure the correct implementation of system PA requirements. The criticality level of failures, functions and systems is determined and by doing that the critical sub-systems are identified, on which dependability and safety techniques are to be applied during development. Proper performance of the software development requires the development of a technical specification for the products at the beginning of the life cycle. Such technical specification comprises both functional and non-functional requirements. These non-functional requirements address characteristics of the product such as quality, dependability, safety and maintainability. Software in space systems is more and more used in critical functions. Also the trend towards more frequent use of COTS and reusable components pose new difficulties in terms of assuring reliable and safe systems. Because of this, its dependability and safety must be carefully analysed. ESA identified and documented techniques, methods and procedures to ensure that software dependability and safety requirements are specified and taken into account during the design and development of a software system and to verify/validate that the implemented software systems comply with these requirements [R1].

  5. Advanced information processing system: Inter-computer communication services

    NASA Technical Reports Server (NTRS)

    Burkhardt, Laura; Masotto, Tom; Sims, J. Terry; Whittredge, Roy; Alger, Linda S.

    1991-01-01

    The purpose is to document the functional requirements and detailed specifications for the Inter-Computer Communications Services (ICCS) of the Advanced Information Processing System (AIPS). An introductory section is provided to outline the overall architecture and functional requirements of the AIPS and to present an overview of the ICCS. An overview of the AIPS architecture as well as a brief description of the AIPS software is given. The guarantees of the ICCS are provided, and the ICCS is described as a seven-layered International Standards Organization (ISO) Model. The ICCS functional requirements, functional design, and detailed specifications as well as each layer of the ICCS are also described. A summary of results and suggestions for future work are presented.

  6. GeoChip 3.0 as a high-thoughput tool for analyzing microbial community composition, structure, and functional activity

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

    He, Z.; Deng, Y.; Van Nostrand, J.D.

    A new generation of functional gene arrays (FGAs; GeoChip 3.0) has been developed, with {approx}28,000 probes covering approximately 57,000 gene variants from 292 functional gene families involved in carbon, nitrogen, phosphorus and sulfur cycles, energy metabolism, antibiotic resistance, metal resistance and organic contaminant degradation. GeoChip 3.0 also has several other distinct features, such as a common oligo reference standard (CORS) for data normalization and comparison, a software package for data management and future updating and the gyrB gene for phylogenetic analysis. Computational evaluation of probe specificity indicated that all designed probes would have a high specificity to their corresponding targets.more » Experimental analysis with synthesized oligonucleotides and genomic DNAs showed that only 0.0036-0.025% false-positive rates were observed, suggesting that the designed probes are highly specific under the experimental conditions examined. In addition, GeoChip 3.0 was applied to analyze soil microbial communities in a multifactor grassland ecosystem in Minnesota, USA, which showed that the structure, composition and potential activity of soil microbial communities significantly changed with the plant species diversity. As expected, GeoChip 3.0 is a high-throughput powerful tool for studying microbial community functional structure, and linking microbial communities to ecosystem processes and functioning.« less

  7. Design of the NL-ENIGMA study: Exploring the effect of Souvenaid on cerebral glucose metabolism in early Alzheimer's disease.

    PubMed

    Scheltens, Nienke M E; Kuyper, Ingrid S; Boellaard, Ronald; Barkhof, Frederik; Teunissen, Charlotte E; Broersen, Laus M; Lansbergen, Marieke M; van der Flier, Wiesje M; van Berckel, Bart N M; Scheltens, Philip

    2016-11-01

    Alzheimer's disease is associated with early synaptic loss. Specific nutrients are known to be rate limiting for synapse formation. Studies have shown that administering specific nutrients may improve memory function, possibly by increasing synapse formation. This Dutch study explores the Effect of a specific Nutritional Intervention on cerebral Glucose Metabolism in early Alzheimer's disease (NL-ENIGMA, Dutch Trial Register NTR4718, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4718). The NL-ENIGMA study is designed to test whether the specific multinutrient combination Fortasyn Connect present in the medical food Souvenaid influences cerebral glucose metabolism as a marker for improved synapse function. This study is a double-blind, randomized controlled parallel-group single-center trial. Forty drug-naive patients with mild cognitive impairment or mild dementia with evidence of amyloid deposition are 1:1 randomized to receive either the multinutrient combination or placebo once daily. Main exploratory outcome parameters include absolute quantitative positron emission tomography with 18 F-fluorodeoxyglucose (including arterial sampling) and standard uptake value ratios normalized for the cerebellum or pons after 24 weeks. We expect the NL-ENIGMA study to provide further insight in the potential of this multinutrient combination to improve synapse function.

  8. Faster Evolution of More Multifunctional Logic Circuits

    NASA Technical Reports Server (NTRS)

    Stoica, Adrian; Zebulum, Ricardo

    2005-01-01

    A modification in a method of automated evolutionary synthesis of voltage-controlled multifunctional logic circuits makes it possible to synthesize more circuits in less time. Prior to the modification, the computations for synthesizing a four-function logic circuit by this method took about 10 hours. Using the method as modified, it is possible to synthesize a six-function circuit in less than half an hour. The concepts of automated evolutionary synthesis and voltage-controlled multifunctional logic circuits were described in a number of prior NASA Tech Briefs articles. To recapitulate: A circuit is designed to perform one of several different logic functions, depending on the value of an applied control voltage. The circuit design is synthesized following an automated evolutionary approach that is so named because it is modeled partly after the repetitive trial-and-error process of biological evolution. In this process, random populations of integer strings that encode electronic circuits play a role analogous to that of chromosomes. An evolved circuit is tested by computational simulation (prior to testing in real hardware to verify a final design). Then, in a fitness-evaluation step, responses of the circuit are compared with specifications of target responses and circuits are ranked according to how close they come to satisfying specifications. The results of the evaluation provide guidance for refining designs through further iteration.

  9. Tailored magnetoelastic sensor geometry for advanced functionality in wireless biliary stent monitoring systems

    NASA Astrophysics Data System (ADS)

    Green, Scott R.; Gianchandani, Yogesh B.

    2010-07-01

    This paper presents three types of wireless magnetoelastic resonant sensors with specific functionalities for monitoring sludge accumulation within biliary stents. The first design uses a geometry with a repeated cell shape that provides two well-separated resonant mode shapes and associated frequencies to permit spatial localization of mass loading. The second design implements a pattern with specific variation in feature densities to improve sensitivity to mass loading. The third design uses narrow ribbons joined by flexible couplers; this design adopts the advantages in flexibility and expandability of the other designs while maintaining the robust longitudinal mode shapes of a ribbon-shaped sensor. The sensors are batch patterned using photochemical machining from 25 µm thick 2605SA1 Metglas™, an amorphous Fe-Si alloy. Accumulation of biliary sludge is simulated with paraffin or gelatin, and the effects of viscous bile are simulated with a range of silicone fluids. Results from the first design show that the location of mass loads can be resolved within ~5 mm along the length of the sensor. The second design offers twice the sensitivity to mass loads (3000-36 000 ppm mg-1) of other designs. The third design provides a wide range of loading (sensitive to at least 10× the mass of the sensor) and survives compression into a 2 mm diameter tube as would be required for catheter-based delivery.

  10. Constructive Approaches for Understanding the Origin of Self-Replication and Evolution.

    PubMed

    Ichihashi, Norikazu; Yomo, Tetsuya

    2016-07-13

    The mystery of the origin of life can be divided into two parts. The first part is the origin of biomolecules: under what physicochemical conditions did biomolecules such as amino acids, nucleotides, and their polymers arise? The second part of the mystery is the origin of life-specific functions such as the replication of genetic information, the reproduction of cellular structures, metabolism, and evolution. These functions require the coordination of many different kinds of biological molecules. A direct strategy to approach the second part of the mystery is the constructive approach, in which life-specific functions are recreated in a test tube from specific biological molecules. Using this approach, we are able to employ design principles to reproduce life-specific functions, and the knowledge gained through the reproduction process provides clues as to their origins. In this mini-review, we introduce recent insights gained using this approach, and propose important future directions for advancing our understanding of the origins of life.

  11. Design Standards for Engineered Tissues

    PubMed Central

    Nawroth, Janna C.; Parker, Kevin Kit

    2013-01-01

    Traditional technologies are required to meet specific, quantitative standards of safety and performance. In tissue engineering, similar standards will have to be developed to enable routine clinical use and customized tissue fabrication. In this essay, we discuss a framework of concepts leading towards general design standards for tissue-engineering, focusing in particular on systematic design strategies, control of cell behavior, physiological scaling, fabrication modes and functional evaluation. PMID:23267860

  12. Intersubjective decision-making for computer-aided forging technology design

    NASA Astrophysics Data System (ADS)

    Kanyukov, S. I.; Konovalov, A. V.; Muizemnek, O. Yu.

    2017-12-01

    We propose a concept of intersubjective decision-making for problems of open-die forging technology design. The intersubjective decisions are chosen from a set of feasible decisions using the fundamentals of the decision-making theory in fuzzy environment according to the Bellman-Zadeh scheme. We consider the formalization of subjective goals and the choice of membership functions for the decisions depending on subjective goals. We study the arrangement of these functions into an intersubjective membership function. The function is constructed for a resulting decision, which is chosen from a set of feasible decisions. The choice of the final intersubjective decision is discussed. All the issues are exemplified by a specific technological problem. The considered concept of solving technological problems under conditions of fuzzy goals allows one to choose the most efficient decisions from a set of feasible ones. These decisions correspond to the stated goals. The concept allows one to reduce human participation in automated design. This concept can be used to develop algorithms and design programs for forging numerous types of forged parts.

  13. Eugene – A Domain Specific Language for Specifying and Constraining Synthetic Biological Parts, Devices, and Systems

    PubMed Central

    Bilitchenko, Lesia; Liu, Adam; Cheung, Sherine; Weeding, Emma; Xia, Bing; Leguia, Mariana; Anderson, J. Christopher; Densmore, Douglas

    2011-01-01

    Background Synthetic biological systems are currently created by an ad-hoc, iterative process of specification, design, and assembly. These systems would greatly benefit from a more formalized and rigorous specification of the desired system components as well as constraints on their composition. Therefore, the creation of robust and efficient design flows and tools is imperative. We present a human readable language (Eugene) that allows for the specification of synthetic biological designs based on biological parts, as well as provides a very expressive constraint system to drive the automatic creation of composite Parts (Devices) from a collection of individual Parts. Results We illustrate Eugene's capabilities in three different areas: Device specification, design space exploration, and assembly and simulation integration. These results highlight Eugene's ability to create combinatorial design spaces and prune these spaces for simulation or physical assembly. Eugene creates functional designs quickly and cost-effectively. Conclusions Eugene is intended for forward engineering of DNA-based devices, and through its data types and execution semantics, reflects the desired abstraction hierarchy in synthetic biology. Eugene provides a powerful constraint system which can be used to drive the creation of new devices at runtime. It accomplishes all of this while being part of a larger tool chain which includes support for design, simulation, and physical device assembly. PMID:21559524

  14. MAN-004 Design Standards Manual

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

    Peterson, Timothy L.

    2014-07-01

    At Sandia National Laboratories in New Mexico (SNL/NM), the design, construction, operation, and maintenance of facilities is guided by industry standards, a graded approach, and the systematic analysis of life cycle benefits received for costs incurred. The design of the physical plant must ensure that the facilities are "fit for use," and provide conditions that effectively, efficiently, and safely support current and future mission needs. In addition, SNL/NM applies sustainable design principles, using an integrated whole-building design approach, from site planning to facility design, construction, and operation to ensure building resource efficiency and the health and productivity of occupants. Themore » safety and health of the workforce and the public, any possible effects on the environment, and compliance with building codes take precedence over project issues, such as performance, cost, and schedule. These design standards generally apply to all disciplines on all SNL/NM projects. Architectural and engineering design must be both functional and cost-effective. Facility design must be tailored to fit its intended function, while emphasizing low-maintenance, energy-efficient, and energy-conscious design. Design facilities that can be maintained easily, with readily accessible equipment areas, low maintenance, and quality systems. To promote an orderly and efficient appearance, architectural features of new facilities must complement and enhance the existing architecture at the site. As an Architectural and Engineering (A/E) professional, you must advise the Project Manager when this approach is prohibitively expensive. You are encouraged to use professional judgment and ingenuity to produce a coordinated interdisciplinary design that is cost-effective, easily contractible or buildable, high-performing, aesthetically pleasing, and compliant with applicable building codes. Close coordination and development of civil, landscape, structural, architectural, fire protection, mechanical, electrical, telecommunications, and security features is expected to ensure compatibility with planned functional equipment and to facilitate constructability. If portions of the design are subcontracted to specialists, delivery of the finished design documents must not be considered complete until the subcontracted portions are also submitted for review. You must, along with support consultants, perform functional analyses and programming in developing design solutions. These solutions must reflect coordination of the competing functional, budgetary, and physical requirements for the project. During design phases, meetings between you and the SNL/NM Project Team to discuss and resolve design issues are required. These meetings are a normal part of the design process. For specific design-review requirements, see the project-specific Design Criteria. In addition to the design requirements described in this manual, instructive information is provided to explain the sustainable building practice goals for design, construction, operation, and maintenance of SNL/NM facilities. Please notify SNL/NM personnel of design best practices not included in this manual, so they can be incorporated in future updates.« less

  15. 77 FR 45282 - NRC Position on the Relationship Between General Design Criteria and Technical Specification...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-31

    ..., are described in the final safety analysis report (FSAR). The staff safety evaluation documents the acceptability of these analyses, and it is the combination of the FSAR analyses and the staff safety evaluation... analysis, maintain their capability to perform their safety functions. Technical Specification Operability...

  16. The PCP SYS IV Management System: Educational Overview.

    ERIC Educational Resources Information Center

    Siegel, Martin A.; Davis, Dennis M.

    This paper describes the structure and function of the SYS IV PLATO Curriculum Project's (PCP) computer-based management system and justifies the system design. A consideration of features most critical in the design of management systems provides the context for a discussion of specific SYS IV features, which include its ability to deliver any…

  17. Museum of Science Builds National Center for Technological Literacy (NCTL)

    ERIC Educational Resources Information Center

    Technology Teacher, 2005

    2005-01-01

    Research indicates that most Americans don't understand the technologies that surround them--the products and systems designed to fill a specific need. From water filtration to wheelchairs, from pens to PDAs, people use technology, often without fully comprehending how these tools are designed, developed, and function. In response, the Museum of…

  18. Design, development and evaluation of Stanford/Ames Extra-Vehicular Activity (EVA) prehensors

    NASA Technical Reports Server (NTRS)

    Leifer, Larry J.; Jameson, J.; Leblanc, M.; Wilson, D.; Sabelman, E.; Schwandt, D.

    1987-01-01

    A summary is given of progress to date on work proposed in 1983 and continued in 1985, including design iterations on three different types of manually powered prehensors, construction of functional mockups of each and culminating in detailed drawings and specifications for suit-compatible sealed units for testing under realistic conditions.

  19. From Science To Design: Systems Engineering For The Lsst

    NASA Astrophysics Data System (ADS)

    Claver, Chuck F.; Axelrod, T.; Fouts, K.; Kantor, J.; Nordby, M.; Sebag, J.; LSST Collaboration

    2009-01-01

    The LSST is a universal-purpose survey telescope that will address scores of scientific missions. To assist the technical teams to convergence to a specific engineering design, the LSST Science Requirements Document (SRD) selects four stressing principle scientific missions: 1) Constraining Dark Matter and Dark Energy; 2) taking an Inventory of the Solar System; 3) Exploring the Transient Optical Sky; and 4) mapping the Milky Way. From these 4 missions the SRD specifies the needed requirements for single images and the full 10 year survey that enables a wide range of science beyond the 4 principle missions. Through optical design and analysis, operations simulation, and throughput modeling the systems engineering effort in the LSST has largely focused on taking the SRD specifications and deriving system functional requirements that define the system design. A Model Based Systems Engineering approach with SysML is used to manage the flow down of requirements from science to system function to sub-system. The rigor of requirements flow and management assists the LSST in keeping the overall scope, hence budget and schedule, under control.

  20. Statistical Methods for Proteomic Biomarker Discovery based on Feature Extraction or Functional Modeling Approaches.

    PubMed

    Morris, Jeffrey S

    2012-01-01

    In recent years, developments in molecular biotechnology have led to the increased promise of detecting and validating biomarkers, or molecular markers that relate to various biological or medical outcomes. Proteomics, the direct study of proteins in biological samples, plays an important role in the biomarker discovery process. These technologies produce complex, high dimensional functional and image data that present many analytical challenges that must be addressed properly for effective comparative proteomics studies that can yield potential biomarkers. Specific challenges include experimental design, preprocessing, feature extraction, and statistical analysis accounting for the inherent multiple testing issues. This paper reviews various computational aspects of comparative proteomic studies, and summarizes contributions I along with numerous collaborators have made. First, there is an overview of comparative proteomics technologies, followed by a discussion of important experimental design and preprocessing issues that must be considered before statistical analysis can be done. Next, the two key approaches to analyzing proteomics data, feature extraction and functional modeling, are described. Feature extraction involves detection and quantification of discrete features like peaks or spots that theoretically correspond to different proteins in the sample. After an overview of the feature extraction approach, specific methods for mass spectrometry ( Cromwell ) and 2D gel electrophoresis ( Pinnacle ) are described. The functional modeling approach involves modeling the proteomic data in their entirety as functions or images. A general discussion of the approach is followed by the presentation of a specific method that can be applied, wavelet-based functional mixed models, and its extensions. All methods are illustrated by application to two example proteomic data sets, one from mass spectrometry and one from 2D gel electrophoresis. While the specific methods presented are applied to two specific proteomic technologies, MALDI-TOF and 2D gel electrophoresis, these methods and the other principles discussed in the paper apply much more broadly to other expression proteomics technologies.

  1. Cytometer on a chip

    NASA Technical Reports Server (NTRS)

    Lynes, Michael A. (Inventor); Fernandez, Salvador M. (Inventor)

    2010-01-01

    An assay technique for label-free, highly parallel, qualitative and quantitative detection of specific cell populations in a sample and for assessing cell functional status, cell-cell interactions and cellular responses to drugs, environmental toxins, bacteria, viruses and other factors that may affect cell function. The technique includes a) creating a first array of binding regions in a predetermined spatial pattern on a sensor surface capable of specifically binding the cells to be assayed; b) creating a second set of binding regions in specific spatial patterns relative to the first set designed to efficiently capture potential secreted or released products from cells captured on the first set of binding regions; c) contacting the sensor surface with the sample, and d) simultaneously monitoring the optical properties of all the binding regions of the sensor surface to determine the presence and concentration of specific cell populations in the sample and their functional status by detecting released or secreted bioproducts.

  2. The effect of basis set and exchange-correlation functional on time-dependent density functional theory calculations within the Tamm-Dancoff approximation of the x-ray emission spectroscopy of transition metal complexes.

    PubMed

    Roper, Ian P E; Besley, Nicholas A

    2016-03-21

    The simulation of X-ray emission spectra of transition metal complexes with time-dependent density functional theory (TDDFT) is investigated. X-ray emission spectra can be computed within TDDFT in conjunction with the Tamm-Dancoff approximation by using a reference determinant with a vacancy in the relevant core orbital, and these calculations can be performed using the frozen orbital approximation or with the relaxation of the orbitals of the intermediate core-ionised state included. Both standard exchange-correlation functionals and functionals specifically designed for X-ray emission spectroscopy are studied, and it is shown that the computed spectral band profiles are sensitive to the exchange-correlation functional used. The computed intensities of the spectral bands can be rationalised by considering the metal p orbital character of the valence molecular orbitals. To compute X-ray emission spectra with the correct energy scale allowing a direct comparison with experiment requires the relaxation of the core-ionised state to be included and the use of specifically designed functionals with increased amounts of Hartree-Fock exchange in conjunction with high quality basis sets. A range-corrected functional with increased Hartree-Fock exchange in the short range provides transition energies close to experiment and spectral band profiles that have a similar accuracy to those from standard functionals.

  3. System approach to distributed sensor management

    NASA Astrophysics Data System (ADS)

    Mayott, Gregory; Miller, Gordon; Harrell, John; Hepp, Jared; Self, Mid

    2010-04-01

    Since 2003, the US Army's RDECOM CERDEC Night Vision Electronic Sensor Directorate (NVESD) has been developing a distributed Sensor Management System (SMS) that utilizes a framework which demonstrates application layer, net-centric sensor management. The core principles of the design support distributed and dynamic discovery of sensing devices and processes through a multi-layered implementation. This results in a sensor management layer that acts as a System with defined interfaces for which the characteristics, parameters, and behaviors can be described. Within the framework, the definition of a protocol is required to establish the rules for how distributed sensors should operate. The protocol defines the behaviors, capabilities, and message structures needed to operate within the functional design boundaries. The protocol definition addresses the requirements for a device (sensors or processes) to dynamically join or leave a sensor network, dynamically describe device control and data capabilities, and allow dynamic addressing of publish and subscribe functionality. The message structure is a multi-tiered definition that identifies standard, extended, and payload representations that are specifically designed to accommodate the need for standard representations of common functions, while supporting the need for feature-based functions that are typically vendor specific. The dynamic qualities of the protocol enable a User GUI application the flexibility of mapping widget-level controls to each device based on reported capabilities in real-time. The SMS approach is designed to accommodate scalability and flexibility within a defined architecture. The distributed sensor management framework and its application to a tactical sensor network will be described in this paper.

  4. Rational Design of an Ultrasensitive Quorum-Sensing Switch.

    PubMed

    Zeng, Weiqian; Du, Pei; Lou, Qiuli; Wu, Lili; Zhang, Haoqian M; Lou, Chunbo; Wang, Hongli; Ouyang, Qi

    2017-08-18

    One of the purposes of synthetic biology is to develop rational methods that accelerate the design of genetic circuits, saving time and effort spent on experiments and providing reliably predictable circuit performance. We applied a reverse engineering approach to design an ultrasensitive transcriptional quorum-sensing switch. We want to explore how systems biology can guide synthetic biology in the choice of specific DNA sequences and their regulatory relations to achieve a targeted function. The workflow comprises network enumeration that achieves the target function robustly, experimental restriction of the obtained candidate networks, global parameter optimization via mathematical analysis, selection and engineering of parts based on these calculations, and finally, circuit construction based on the principles of standardization and modularization. The performance of realized quorum-sensing switches was in good qualitative agreement with the computational predictions. This study provides practical principles for the rational design of genetic circuits with targeted functions.

  5. Systems integrated human engineering on the Navy's rapid acquisition of manufactured parts/test and integration facility

    NASA Technical Reports Server (NTRS)

    Gallaway, Glen R.

    1987-01-01

    Human Engineering in many projects is at best a limited support function. In this Navy project the Human Engineering function is an integral component of the systems design and development process. Human Engineering is a member of the systems design organization. This ensures that people considerations are: (1) identified early in the project; (2) accounted for in the specifications; (3) incorporated into the design; and (4) the tested product meets the needs and expectations of the people while meeting the overall systems requirements. The project exemplifies achievements that can be made by the symbiosis between systems designers, engineers and Human Engineering. This approach increases Human Engineering's effectiveness and value to a project because it becomes an accepted, contributing team member. It is an approach to doing Human Engineering that should be considered for most projects. The functional and organizational issues giving this approach strength are described.

  6. Increasing the affinity of selective bZIP-binding peptides through surface residue redesign.

    PubMed

    Kaplan, Jenifer B; Reinke, Aaron W; Keating, Amy E

    2014-07-01

    The coiled-coil dimer is a prevalent protein interaction motif that is important for many cellular processes. The basic leucine-zipper (bZIP) transcription factors are one family of proteins for which coiled-coil mediated dimerization is essential for function, and misregulation of bZIPs can lead to disease states including cancer. This makes coiled coils attractive protein-protein interaction targets to disrupt using engineered molecules. Previous work designing peptides to compete with native coiled-coil interactions focused primarily on designing the core residues of the interface to achieve affinity and specificity. However, folding studies on the model bZIP GCN4 show that coiled-coil surface residues also contribute to binding affinity. Here we extend a prior study in which peptides were designed to bind tightly and specifically to representative members of each of 20 human bZIP families. These "anti-bZIP" peptides were designed with an emphasis on target-binding specificity, with contributions to design-target specificity and affinity engineered considering only the coiled-coil core residues. High-throughput testing using peptide arrays indicated many successes. We have now measured the binding affinities and specificities of anti-bZIPs that bind to FOS, XBP1, ATF6, and CREBZF in solution and tested whether redesigning the surface residues can increase design-target affinity. Incorporating residues that favor helix formation into the designs increased binding affinities in all cases, providing low-nanomolar binders of each target. However, changes in surface electrostatic interactions sometimes changed the binding specificity of the designed peptides. © 2014 The Protein Society.

  7. Structure based re-design of the binding specificity of anti-apoptotic Bcl-xL

    PubMed Central

    Chen, T. Scott; Palacios, Hector; Keating, Amy E.

    2012-01-01

    Many native proteins are multi-specific and interact with numerous partners, which can confound analysis of their functions. Protein design provides a potential route to generating synthetic variants of native proteins with more selective binding profiles. Re-designed proteins could be used as research tools, diagnostics or therapeutics. In this work, we used a library screening approach to re-engineer the multi-specific anti-apoptotic protein Bcl-xL to remove its interactions with many of its binding partners, making it a high affinity and selective binder of the BH3 region of pro-apoptotic protein Bad. To overcome the enormity of the potential Bcl-xL sequence space, we developed and applied a computational/experimental framework that used protein structure information to generate focused combinatorial libraries. Sequence features were identified using structure-based modeling, and an optimization algorithm based on integer programming was used to select degenerate codons that maximally covered these features. A constraint on library size was used to ensure thorough sampling. Using yeast surface display to screen a designed library of Bcl-xL variants, we successfully identified a protein with ~1,000-fold improvement in binding specificity for the BH3 region of Bad over the BH3 region of Bim. Although negative design was targeted only against the BH3 region of Bim, the best re-designed protein was globally specific against binding to 10 other peptides corresponding to native BH3 motifs. Our design framework demonstrates an efficient route to highly specific protein binders and may readily be adapted for application to other design problems. PMID:23154169

  8. Refractive laser beam shaping by means of a functional differential equation based design approach.

    PubMed

    Duerr, Fabian; Thienpont, Hugo

    2014-04-07

    Many laser applications require specific irradiance distributions to ensure optimal performance. Geometric optical design methods based on numerical calculation of two plano-aspheric lenses have been thoroughly studied in the past. In this work, we present an alternative new design approach based on functional differential equations that allows direct calculation of the rotational symmetric lens profiles described by two-point Taylor polynomials. The formalism is used to design a Gaussian to flat-top irradiance beam shaping system but also to generate a more complex dark-hollow Gaussian (donut-like) irradiance distribution with zero intensity in the on-axis region. The presented ray tracing results confirm the high accuracy of both calculated solutions and emphasize the potential of this design approach for refractive beam shaping applications.

  9. Thermally induced stresses and deformations in angle-ply composite tubes

    NASA Technical Reports Server (NTRS)

    Hyer, M. W.; Rousseau, Carl Q.

    1987-01-01

    Cure-induced uniform temperature change effects on the stresses, axial expansion, and thermally-induced twist of four specific angle-ply tube designs are discussed with a view to the tubes' use as major space structure components. The stresses and deformations in the tubes are studied as a function of the four designs, the off-axis angle, and the single-material and hybrid reinforcing-material construction used. It is found that tube design has a minor influence on the stresses, axial stiffness, and axial thermal expansion characteristics, which are more directly a function of off-axis angle and material selection; tube design is, however, the primary influence in the definition of thermally-induced twist and torsional stiffness characteristics. None of the designs is free of thermally induced twist.

  10. Formal specification and mechanical verification of SIFT - A fault-tolerant flight control system

    NASA Technical Reports Server (NTRS)

    Melliar-Smith, P. M.; Schwartz, R. L.

    1982-01-01

    The paper describes the methodology being employed to demonstrate rigorously that the SIFT (software-implemented fault-tolerant) computer meets its requirements. The methodology uses a hierarchy of design specifications, expressed in the mathematical domain of multisorted first-order predicate calculus. The most abstract of these, from which almost all details of mechanization have been removed, represents the requirements on the system for reliability and intended functionality. Successive specifications in the hierarchy add design and implementation detail until the PASCAL programs implementing the SIFT executive are reached. A formal proof that a SIFT system in a 'safe' state operates correctly despite the presence of arbitrary faults has been completed all the way from the most abstract specifications to the PASCAL program.

  11. Improvement of the System of Training of Specialists by University for Coal Mining Enterprises

    NASA Astrophysics Data System (ADS)

    Mikhalchenko, Vadim; Seredkina, Irina

    2017-11-01

    In the article the ingenious technique of the Quality Function Deployment with reference to the process of training of specialists with higher education by university is considered. The method is based on the step-by-step conversion of customer requirements into specific organizational, meaningful and functional transformations of the technological process of the university. A fully deployed quality function includes four stages of tracking customer requirements while creating a product: product planning and design, process design, production design. The Quality Function Deployment can be considered as one of the methods for optimizing the technological processes of training of specialists with higher education in the current economic conditions. Implemented at the initial stages of the life cycle of the technological process, it ensures not only the high quality of the "product" of graduate school, but also the fullest possible satisfaction of consumer's requests and expectations.

  12. Form and Function of Educational Technology in Developmental Curricula in a Community College

    ERIC Educational Resources Information Center

    Hess, Patrice M.

    2012-01-01

    This qualitative action research study examines the form (where and how) and function (specific use) of Educational Technology in developmental curricula at a community college. The study uses theoretical frameworks of Educational Technology and Instructional Systems Design to review and analyze curricular materials (print and electronic) and…

  13. Design Principles of Regulatory Networks: Searching for the Molecular Algorithms of the Cell

    PubMed Central

    Lim, Wendell A.; Lee, Connie M.; Tang, Chao

    2013-01-01

    A challenge in biology is to understand how complex molecular networks in the cell execute sophisticated regulatory functions. Here we explore the idea that there are common and general principles that link network structures to biological functions, principles that constrain the design solutions that evolution can converge upon for accomplishing a given cellular task. We describe approaches for classifying networks based on abstract architectures and functions, rather than on the specific molecular components of the networks. For any common regulatory task, can we define the space of all possible molecular solutions? Such inverse approaches might ultimately allow the assembly of a design table of core molecular algorithms that could serve as a guide for building synthetic networks and modulating disease networks. PMID:23352241

  14. Ada Software Design Methods Formulation.

    DTIC Science & Technology

    1982-10-01

    aside for one-to-one, non -judgemental discussions between SofTech and the design teams. SofTech’s role in the meetings was to address any Ada-specific...assurance 1.0 prepare version audits 1.0 monitoring contracts 1.0 library control 1.0 other development 1.0 correspondence 1.0 conduct support design ...quality assurance 2.0 Control Board update training manuals 2.0 participation 2.5 being trained 2.0 formulation of policy 2.5 functional system design

  15. Work boot design affects the way workers walk: A systematic review of the literature.

    PubMed

    Dobson, Jessica A; Riddiford-Harland, Diane L; Bell, Alison F; Steele, Julie R

    2017-05-01

    Safety boots are compulsory in many occupations to protect the feet of workers from undesirable external stimuli, particularly in harsh work environments. The unique environmental conditions and varying tasks performed in different occupations necessitate a variety of boot designs to match each worker's occupational safety and functional requirements. Unfortunately, safety boots are often designed more for occupational safety at the expense of functionality and comfort. In fact, there is a paucity of published research investigating the influence that specific variations in work boot design have on fundamental tasks common to many occupations, such as walking. This literature review aimed to collate and examine what is currently known about the influence of boot design on walking in order to identify gaps in the literature and develop evidence-based recommendations upon which to design future research studies investigating work boot design. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Choice of design and outcomes in trials among children with moderate acute malnutrition.

    PubMed

    Friis, Henrik; Michaelsen, Kim F; Wells, Jonathan C

    2015-03-01

    There is a need for trials on the effects of food aid products for children with moderate acute malnutrition, to identify how best to restore body tissues and function. The choice of control intervention is a major challenge, with both ethical and scientific implications. While randomized trials are needed, special designs, such as cluster-randomized, stepped-wedged or factorial designs may offer advantages. Anthropometry is widely used as the primary outcome in such trials, but anthropometric traits do not refer directly to specific organs, tissues, or functions. Thus, it is difficult to understand what components of health might be impacted by public health programs, or the underlying mechanisms whereby improved nutritional status might benefit short- and long-term health. Measurement of body composition, specific growth markers and functional outcomes may provide greater insight into the nature and implications of growth failure and recovery. There are now several methodologies suitable for application in infants and young children, e.g., measuring body composition with deuterium dilution, physical activity with accelerometers and linear growth with knemometers. To evaluate the generalizability of the findings from nutrition trials, it is important to collect data on baseline nutritional status.

  17. Automatic Molecular Design using Evolutionary Techniques

    NASA Technical Reports Server (NTRS)

    Globus, Al; Lawton, John; Wipke, Todd; Saini, Subhash (Technical Monitor)

    1998-01-01

    Molecular nanotechnology is the precise, three-dimensional control of materials and devices at the atomic scale. An important part of nanotechnology is the design of molecules for specific purposes. This paper describes early results using genetic software techniques to automatically design molecules under the control of a fitness function. The fitness function must be capable of determining which of two arbitrary molecules is better for a specific task. The software begins by generating a population of random molecules. The population is then evolved towards greater fitness by randomly combining parts of the better individuals to create new molecules. These new molecules then replace some of the worst molecules in the population. The unique aspect of our approach is that we apply genetic crossover to molecules represented by graphs, i.e., sets of atoms and the bonds that connect them. We present evidence suggesting that crossover alone, operating on graphs, can evolve any possible molecule given an appropriate fitness function and a population containing both rings and chains. Prior work evolved strings or trees that were subsequently processed to generate molecular graphs. In principle, genetic graph software should be able to evolve other graph representable systems such as circuits, transportation networks, metabolic pathways, computer networks, etc.

  18. Discovering rules for protein-ligand specificity using support vector inductive logic programming.

    PubMed

    Kelley, Lawrence A; Shrimpton, Paul J; Muggleton, Stephen H; Sternberg, Michael J E

    2009-09-01

    Structural genomics initiatives are rapidly generating vast numbers of protein structures. Comparative modelling is also capable of producing accurate structural models for many protein sequences. However, for many of the known structures, functions are not yet determined, and in many modelling tasks, an accurate structural model does not necessarily tell us about function. Thus, there is a pressing need for high-throughput methods for determining function from structure. The spatial arrangement of key amino acids in a folded protein, on the surface or buried in clefts, is often the determinants of its biological function. A central aim of molecular biology is to understand the relationship between such substructures or surfaces and biological function, leading both to function prediction and to function design. We present a new general method for discovering the features of binding pockets that confer specificity for particular ligands. Using a recently developed machine-learning technique which couples the rule-discovery approach of inductive logic programming with the statistical learning power of support vector machines, we are able to discriminate, with high precision (90%) and recall (86%) between pockets that bind FAD and those that bind NAD on a large benchmark set given only the geometry and composition of the backbone of the binding pocket without the use of docking. In addition, we learn rules governing this specificity which can feed into protein functional design protocols. An analysis of the rules found suggests that key features of the binding pocket may be tied to conformational freedom in the ligand. The representation is sufficiently general to be applicable to any discriminatory binding problem. All programs and data sets are freely available to non-commercial users at http://www.sbg.bio.ic.ac.uk/svilp_ligand/.

  19. Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents

    DOEpatents

    Katti, Kattesh V.; Gali, Hariprasad; Volkert, Wynn A.

    2004-08-24

    This invention describes a novel strategy to produce phosphine-functionalized biomolecules (e.g. peptides or proteins) for potential use in the design and development of site-specific radiopharmaceuticals for diagnosis or therapy of specific cancers. Hydrophilic alkyl phosphines, in general, tend to be oxidatively unstable. Therefore, incorporation of such phosphine functionalities on peptide (and other biomolecule) backbones, without oxidizing the P.sup.III centers, is difficult. In this context this discovery reports on a new technology by which phosphines, in the form of bifunctional chelating agents, can be directly incorporated on biomolecular backbones using manual synthetic or solid phase peptide synthesis methodologies. The superior ligating abilities of phosphine ligands, with various diagnostically (e.g. TC-99m) or therapeutically (e.g. Re186/188, Rh-105, Au-199) useful radiometals, coupled with the findings that the resulting complexes demonstrate high in vivo stability makes this approach useful in the development of radiolabeled biomolecules for applications in the design of tumor-specific radiopharmaceuticals.

  20. Parametric study of two planar high power flexible solar array concepts

    NASA Technical Reports Server (NTRS)

    Garba, J. A.; Kudija, D. A.; Zeldin, B.; Costogue, E. N.

    1978-01-01

    The design parameters examined were: frequency, aspect ratio, packaging constraints, and array blanket flatness. Specific power-to-mass ratios for both solar arrays as a function of array frequency and array width were developed and plotted. Summaries of the baseline design data, developed equations, the computer program operation, plots of the parameters, and the process for using the information as a design manual are presented.

  1. Biometric Data Safeguarding Technologies Analysis and Best Practices

    DTIC Science & Technology

    2011-12-01

    fuzzy vault” scheme proposed by Juels and Sudan. The scheme was designed to encrypt data such that it could be unlocked by similar but inexact matches... designed transform functions. Multifactor Key Generation Multifactor key generation combines a biometric with one or more other inputs, such as a...cooperative, off-angle iris images.  Since the commercialized system is designed for images acquired from a specific, paired acquisition system

  2. 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.

  3. Earth Observatory Satellite system definition study. Report no. 3: Design/cost tradeoff studies. Appendix C: EOS program requirements document

    NASA Technical Reports Server (NTRS)

    1974-01-01

    An analysis of the requirements for the Earth Observatory Satellite (EOS) system specifications is presented. The analysis consists of requirements obtained from existing documentation and those derived from functional analysis. The requirements follow the hierarchy of program, mission, system, and subsystem. The code for designating specific requirements is explained. Among the subjects considered are the following: (1) the traffic model, (2) space shuttle related performance, (3) booster related performance, (4) the data collection system, (5) spacecraft structural tests, and (6) the ground support requirements.

  4. Invited commentary: on population subgroups, mathematics, and interventions.

    PubMed

    Jacobs, David R; Meyer, Katie A

    2011-02-15

    New sex-specific equations, each with race/ethnic-specific intercept, for predicted lung function illustrate a methodological point, that complex differences between groups may not imply interactions with other predictors, such as age and height. The new equations find that race/ethnic identity does not interact with either age or height in the prediction equations, although there are race/ethnic-specific offsets. Further study is warranted of the effect of possible small race/ethnic interactions on disease classification. Additional study of repeated measures of lung function is warranted, given that the new equations were developed in cross-sectional designs. Predicting lung function is more than a methodological exercise. Predicted values are important in disease diagnosis and monitoring. It is suggested that measurement and tracking of lung function throughout young adulthood could be used to provide an early warning of potential long-term lung function losses to encourage improvement of risky behaviors including smoking and failure to maintain normal body weight in the general population.

  5. Design Approach and Implementation of Application Specific Instruction Set Processor for SHA-3 BLAKE Algorithm

    NASA Astrophysics Data System (ADS)

    Zhang, Yuli; Han, Jun; Weng, Xinqian; He, Zhongzhu; Zeng, Xiaoyang

    This paper presents an Application Specific Instruction-set Processor (ASIP) for the SHA-3 BLAKE algorithm family by instruction set extensions (ISE) from an RISC (reduced instruction set computer) processor. With a design space exploration for this ASIP to increase the performance and reduce the area cost, we accomplish an efficient hardware and software implementation of BLAKE algorithm. The special instructions and their well-matched hardware function unit improve the calculation of the key section of the algorithm, namely G-functions. Also, relaxing the time constraint of the special function unit can decrease its hardware cost, while keeping the high data throughput of the processor. Evaluation results reveal the ASIP achieves 335Mbps and 176Mbps for BLAKE-256 and BLAKE-512. The extra area cost is only 8.06k equivalent gates. The proposed ASIP outperforms several software approaches on various platforms in cycle per byte. In fact, both high throughput and low hardware cost achieved by this programmable processor are comparable to that of ASIC implementations.

  6. Polymer adsorption-driven self-assembly of nanostructures.

    PubMed

    Chakraborty, A K; Golumbfskie, A J

    2001-01-01

    Driven by prospective applications, there is much interest in developing materials that can perform specific functions in response to external conditions. One way to design such materials is to create systems which, in response to external inputs, can self-assemble to form structures that are functionally useful. This review focuses on the principles that can be employed to design macromolecules that when presented with an appropriate two-dimensional surface, will self-assemble to form nanostructures that may be functionally useful. We discuss three specific examples: (a) biomimetic recognition between polymers and patterned surfaces. (b) control and manipulation of nanomechanical motion generated by biopolymer adsorption and binding, and (c) creation of patterned nanostructuctures by exposing molten diblock copolymers to patterned surfaces. The discussion serves to illustrate how polymer sequence can be manipulated to affect self-assembly characteristics near adsorbing surfaces. The focus of this review is on theoretical and computational work aimed toward elucidating the principles underlying the phenomena pertinent to the three topics noted above. However, synergistic experiments are also described in the appropriate context.

  7. Pattern Genes Suggest Functional Connectivity of Organs

    NASA Astrophysics Data System (ADS)

    Qin, Yangmei; Pan, Jianbo; Cai, Meichun; Yao, Lixia; Ji, Zhiliang

    2016-05-01

    Human organ, as the basic structural and functional unit in human body, is made of a large community of different cell types that organically bound together. Each organ usually exerts highly specified physiological function; while several related organs work smartly together to perform complicated body functions. In this study, we present a computational effort to understand the roles of genes in building functional connection between organs. More specifically, we mined multiple transcriptome datasets sampled from 36 human organs and tissues, and quantitatively identified 3,149 genes whose expressions showed consensus modularly patterns: specific to one organ/tissue, selectively expressed in several functionally related tissues and ubiquitously expressed. These pattern genes imply intrinsic connections between organs. According to the expression abundance of the 766 selective genes, we consistently cluster the 36 human organs/tissues into seven functional groups: adipose & gland, brain, muscle, immune, metabolism, mucoid and nerve conduction. The organs and tissues in each group either work together to form organ systems or coordinate to perform particular body functions. The particular roles of specific genes and selective genes suggest that they could not only be used to mechanistically explore organ functions, but also be designed for selective biomarkers and therapeutic targets.

  8. Specific or nonspecific? Evaluation of band, baseline, and cognitive specificity of sensorimotor rhythm- and gamma-based neurofeedback.

    PubMed

    Kober, Silvia Erika; Witte, Matthias; Neuper, Christa; Wood, Guilherme

    2017-10-01

    Neurofeedback (NF) is often criticized because of the lack of empirical evidence of its specificity. Our present study thus focused on the specificity of NF on three levels: band specificity, cognitive specificity, and baseline specificity. Ten healthy middle-aged individuals performed ten sessions of SMR (sensorimotor rhythm, 12-15Hz) NF training. A second group (N=10) received feedback of a narrow gamma band (40-43Hz). Effects of NF on EEG resting measurements (tonic EEG) and cognitive functions (memory, intelligence) were evaluated using a pre-post design. Both training groups were able to linearly increase the target training frequencies (either SMR or gamma), indicating the trainability of these EEG frequencies. Both NF training protocols led to nonspecific changes in other frequency bands during NF training. While SMR NF only led to concomitant changes in slower frequencies, gamma training affected nearly the whole power spectrum. SMR NF specifically improved memory functions. Gamma training showed only marginal effects on cognitive functions. SMR power assessed during resting measurements significantly increased after SMR NF training compared to a pre-assessment, indicating specific effects of SMR NF on baseline/tonic EEG. The gamma group did not show any pre-post changes in their EEG resting activity. In conclusion, SMR NF specifically affects cognitive functions (cognitive specificity) and tonic EEG (baseline specificity), while increasing SMR during NF training nonspecifically affects slower EEG frequencies as well (band non-specificity). Gamma NF was associated with nonspecific effects on the EEG power spectrum during training, which did not lead to considerable changes in cognitive functions or baseline EEG activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Computational redesign of a protein-protein interface for high affinity and binding specificity using modular architecture and naturally occurring template fragments.

    PubMed

    Potapov, V; Reichmann, D; Abramovich, R; Filchtinski, D; Zohar, N; Ben Halevy, D; Edelman, M; Sobolev, V; Schreiber, G

    2008-12-05

    A new method is presented for the redesign of protein-protein interfaces, resulting in specificity of the designed pair while maintaining high affinity. The design is based on modular interface architecture and was carried out on the interaction between TEM1 beta-lactamase and its inhibitor protein, beta-lactamase inhibitor protein. The interface between these two proteins is composed of several mostly independent modules. We previously showed that it is possible to delete a complete module without affecting the overall structure of the interface. Here, we replace a complete module with structure fragments taken from nonrelated proteins. Nature-optimized fragments were chosen from 10(7) starting templates found in the Protein Data Bank. A procedure was then developed to identify sets of interacting template residues with a backbone arrangement mimicking the original module. This generated a final list of 361 putative replacement modules that were ranked using a novel scoring function based on grouped atom-atom contact surface areas. The top-ranked designed complex exhibited an affinity of at least the wild-type level and a mode of binding that was remarkably specific despite the absence of negative design in the procedure. In retrospect, the combined application of three factors led to the success of the design approach: utilizing the modular construction of the interface, capitalizing on native rather than artificial templates, and ranking with an accurate atom-atom contact surface scoring function.

  10. SU-E-T-760: Tolerance Design for Site-Specific Range in Proton Patient QA Process Using the Six Sigma Model

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

    Lah, J; Shin, D; Kim, G

    Purpose: To show how tolerance design and tolerancing approaches can be used to predict and improve the site-specific range in patient QA process in implementing the Six Sigma. Methods: In this study, patient QA plans were selected according to 6 site-treatment groups: head &neck (94 cases), spine (76 cases), lung (89 cases), liver (53 cases), pancreas (55 cases), and prostate (121 cases), treated between 2007 and 2013. We evaluated a model of the Six Sigma that determines allowable deviations in design parameters and process variables in patient-specific QA, where possible, tolerance may be loosened, then customized if it necessary tomore » meet the functional requirements. A Six Sigma problem-solving methodology is known as DMAIC phases, which are used stand for: Define a problem or improvement opportunity, Measure process performance, Analyze the process to determine the root causes of poor performance, Improve the process by fixing root causes, Control the improved process to hold the gains. Results: The process capability for patient-specific range QA is 0.65 with only ±1 mm of tolerance criteria. Our results suggested the tolerance level of ±2–3 mm for prostate and liver cases and ±5 mm for lung cases. We found that customized tolerance between calculated and measured range reduce that patient QA plan failure and almost all sites had failure rates less than 1%. The average QA time also improved from 2 hr to less than 1 hr for all including planning and converting process, depth-dose measurement and evaluation. Conclusion: The objective of tolerance design is to achieve optimization beyond that obtained through QA process improvement and statistical analysis function detailing to implement a Six Sigma capable design.« less

  11. MicroShell Minimalist Shell for Xilinx Microprocessors

    NASA Technical Reports Server (NTRS)

    Werne, Thomas A.

    2011-01-01

    MicroShell is a lightweight shell environment for engineers and software developers working with embedded microprocessors in Xilinx FPGAs. (MicroShell has also been successfully ported to run on ARM Cortex-M1 microprocessors in Actel ProASIC3 FPGAs, but without project-integration support.) Micro Shell decreases the time spent performing initial tests of field-programmable gate array (FPGA) designs, simplifies running customizable one-time-only experiments, and provides a familiar-feeling command-line interface. The program comes with a collection of useful functions and enables the designer to add an unlimited number of custom commands, which are callable from the command-line. The commands are parameterizable (using the C-based command-line parameter idiom), so the designer can use one function to exercise hardware with different values. Also, since many hardware peripherals instantiated in FPGAs have reasonably simple register-mapped I/O interfaces, the engineer can edit and view hardware parameter settings at any time without stopping the processor. MicroShell comes with a set of support scripts that interface seamlessly with Xilinx's EDK tool. Adding an instance of MicroShell to a project is as simple as marking a check box in a library configuration dialog box and specifying a software project directory. The support scripts then examine the hardware design, build design-specific functions, conditionally include processor-specific functions, and complete the compilation process. For code-size constrained designs, most of the stock functionality can be excluded from the compiled library. When all of the configurable options are removed from the binary, MicroShell has an unoptimized memory footprint of about 4.8 kB and a size-optimized footprint of about 2.3 kB. Since MicroShell allows unfettered access to all processor-accessible memory locations, it is possible to perform live patching on a running system. This can be useful, for instance, if a bug is discovered in a routine but the system cannot be rebooted: Shell allows a skilled operator to directly edit the binary executable in memory. With some forethought, MicroShell code can be located in a different memory location from custom code, permitting the custom functionality to be overwritten at any time without stopping the controlling shell.

  12. Spiral Gradient Coil Design for Use in Cylindrical MRI Systems.

    PubMed

    Wang, Yaohui; Xin, Xuegang; Liu, Feng; Crozier, Stuart

    2018-04-01

    In magnetic resonance imaging, the stream function based method is commonly used in the design of gradient coils. However, this method can be prone to errors associated with the discretization of continuous current density and wire connections. In this paper, we propose a novel gradient coil design scheme that works directly in the wire space, avoiding the system errors that may appear in the stream function approaches. Specifically, the gradient coil pattern is described with dedicated spiral functions adjusted to allow the coil to produce the required field gradients in the imaging area, minimal stray field, and other engineering terms. The performance of a designed spiral gradient coil was compared with its stream-function counterpart. The numerical evaluation shows that when compared with the conventional solution, the inductance and resistance was reduced by 20.9 and 10.5%, respectively. The overall coil performance (evaluated by the figure of merit (FoM)) was improved up to 26.5% for the x -gradient coil design; for the z-gradient coil design, the inductance and resistance were reduced by 15.1 and 6.7% respectively, and the FoM was increased by 17.7%. In addition, by directly controlling the wire distributions, the spiral gradient coil design was much sparser than conventional coils.

  13. Equilibrium Structures and Absorption Spectra for SixOy Molecular Clusters using Density Functional Theory

    DTIC Science & Technology

    2017-05-05

    dependent density functional theory (TD-DFT). The size of the clusters considered is relatively large compared to those considered in previous studies...are characterized by many different geometries, which potentially can be optimized with respect to specific materials design criteria, i.e., molecular...SixOy molecular clusters using density functional theory (DFT). The size of the clusters considered, however, is relatively large compared to those

  14. Cofactor specificity switch in Shikimate dehydrogenase by rational design and consensus engineering.

    PubMed

    García-Guevara, Fernando; Bravo, Iris; Martínez-Anaya, Claudia; Segovia, Lorenzo

    2017-08-01

    Consensus engineering has been used to design more stable variants using the most frequent amino acid at each site of a multiple sequence alignment; sometimes consensus engineering modifies function, but efforts have mainly been focused on studying stability. Here we constructed a consensus Rossmann domain for the Shikimate dehydrogenase enzyme; separately we decided to switch the cofactor specificity through rational design in the Escherichia coli Shikimate dehydrogenase enzyme and then analyzed the effect of consensus mutations on top of our design. We found that consensus mutations closest to the 2' adenine moiety increased the activity in our design. Consensus engineering has been shown to result in more stable proteins and our findings suggest it could also be used as a complementary tool for increasing or modifying enzyme activity during design. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Screening and Diagnostic Procedure for Identification of Adult Learning Problems. 309 Demonstration Project.

    ERIC Educational Resources Information Center

    International Labour Office, Islamabad (Pakistan). Asian and Pacific Skill Development Programme.

    This screening and diagnostic procedure is intended to identify Level 1 adults with specific learning problems. The adults not meeting criteria on the assessments for visual and auditory functions should be referred to proper medical services for full evaluations. A prescriptive teaching program should be specifically designed to meet needs of…

  16. Antibiotic loaded nanocapsules functionalized with aptamer gates for targeted destruction of pathogens.

    PubMed

    Kavruk, M; Celikbicak, O; Ozalp, V C; Borsa, B A; Hernandez, F J; Bayramoglu, G; Salih, B; Arica, M Y

    2015-05-18

    In this study, we designed aptamer-gated nanocapsules for the specific targeting of cargo to bacteria with controlled release of antibiotics based on aptamer-receptor interactions. Aptamer-gates caused a specific decrease in minimum inhibitory concentration (MIC) values of vancomycin for Staphylococcus aureus when mesoporous silica nanoparticles (MSNs) were used for bacteria-targeted delivery.

  17. Working Memory Deficits in Children with Specific Learning Disorders

    ERIC Educational Resources Information Center

    Schuchardt, Kirsten; Maehler, Claudia; Hasselhorn, Marcus

    2008-01-01

    This article examines working memory functioning in children with specific developmental disorders of scholastic skills as defined by ICD-10. Ninety-seven second to fourth graders with a minimum IQ of 80 are compared using a 2 x 2 factorial (dyscalculia vs. no dyscalculia; dyslexia vs. no dyslexia) design. An extensive test battery assesses the…

  18. Cognitive Mechanisms, Specificity and Neural Underpinnings of Visuospatial Peaks in Autism

    ERIC Educational Resources Information Center

    Caron, M.-J.; Mottron, L.; Berthiaume, C.; Dawson, M.

    2006-01-01

    In order to explain the cognitive and cerebral mechanisms responsible for the visuospatial peak in autism, and to document its specificity to this condition, a group of eight high-functioning individuals with autism and a visuospatial peak (HFA-P) performed a modified block-design task (BDT; subtest from Wechsler scales) at various levels of…

  19. Development of a parameter optimization technique for the design of automatic control systems

    NASA Technical Reports Server (NTRS)

    Whitaker, P. H.

    1977-01-01

    Parameter optimization techniques for the design of linear automatic control systems that are applicable to both continuous and digital systems are described. The model performance index is used as the optimization criterion because of the physical insight that can be attached to it. The design emphasis is to start with the simplest system configuration that experience indicates would be practical. Design parameters are specified, and a digital computer program is used to select that set of parameter values which minimizes the performance index. The resulting design is examined, and complexity, through the use of more complex information processing or more feedback paths, is added only if performance fails to meet operational specifications. System performance specifications are assumed to be such that the desired step function time response of the system can be inferred.

  20. 78 FR 19713 - Possible Role of Independent Third Parties in Industry-Sponsored Tobacco Product Research...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-02

    ... tobacco product research could be subject to third-party governance? For example, could it be applied to... governance? For example, should both the design and conduct of research studies be subject to third-party... more key functions, including the design and conduct of research, the oversight of specific studies...

  1. New York State Educational Information System (NYSEIS) Systems Design. Volume I, Phase II. Final Report.

    ERIC Educational Resources Information Center

    Price Waterhouse and Co., New York, NY.

    This volume on Phase II of the New York State Educational Information System (NYSEIS) describes the Gross Systems Analysis and Design, which includes the general flow diagram and processing chart for each of the student, personnel, and financial subsystems. Volume II, Functional Specifications, includes input/output requirements and file…

  2. 77 FR 20026 - Draft Guidance for Industry: Modified Risk Tobacco Product Applications; Availability; Agency...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-03

    ... appropriate scientific and medical experts, on the design and conduct of studies required for the assessment... functions, including the design and conduct of research, the oversight of specific studies, and the... any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency considers your comment on this draft...

  3. Gender Differences in Figural Matrices: The Moderating Role of Item Design Features

    ERIC Educational Resources Information Center

    Arendasy, Martin E.; Sommer, Markus

    2012-01-01

    There is a heated debate on whether observed gender differences in some figural matrices in adults can be attributed to gender differences in inductive reasoning/G[subscript f] or differential item functioning and/or test bias. Based on previous studies we hypothesized that three specific item design features moderate the effect size of the gender…

  4. Enhanced sensitivity of CpG island search and primer design based on predicted CpG island position.

    PubMed

    Park, Hyun-Chul; Ahn, Eu-Ree; Jung, Ju Yeon; Park, Ji-Hye; Lee, Jee Won; Lim, Si-Keun; Kim, Won

    2018-05-01

    DNA methylation has important biological roles, such as gene expression regulation, as well as practical applications in forensics, such as in body fluid identification and age estimation. DNA methylation often occurs in the CpG site, and methylation within the CpG islands affects various cellular functions and is related to tissue-specific identification. Several programs have been developed to identify CpG islands; however, the size, location, and number of predicted CpG islands are not identical due to different search algorithms. In addition, they only provide structural information for predicted CpG islands without experimental information, such as primer design. We developed an analysis pipeline package, CpGPNP, to integrate CpG island prediction and primer design. CpGPNP predicts CpG islands more accurately and sensitively than other programs, and designs primers easily based on the predicted CpG island locations. The primer design function included standard, bisulfite, and methylation-specific PCR to identify the methylation of particular CpG sites. In this study, we performed CpG island prediction on all chromosomes and compared CpG island search performance of CpGPNP with other CpG island prediction programs. In addition, we compared the position of primers designed for a specific region within the predicted CpG island using other bisulfite PCR primer programs. The primers designed by CpGPNP were used to experimentally verify the amplification of the target region of markers for body fluid identification and age estimation. CpGPNP is freely available at http://forensicdna.kr/cpgpnp/. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Final design review summary report for the TN-WHC cask and transportation system

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

    Kee, A.T.

    1997-01-17

    This document represents comments generated from a review of Transnuclear`s Final Design Package distributed on December 10, 1996 and a review of the Final Design Analysis Report meeting held on December 17 & 18, 1996. The Final design describes desicn features and presents final analyses @j performed to fabricate and operate the system while meeting the Cask/Transportation Functions and Requirements, WHC-SD-SNF-FRD-011, Rev. 0 and specification WHC-S-0396, Rev. 1.

  6. European Workshop Industrical Computer Science Systems approach to design for safety

    NASA Technical Reports Server (NTRS)

    Zalewski, Janusz

    1992-01-01

    This paper presents guidelines on designing systems for safety, developed by the Technical Committee 7 on Reliability and Safety of the European Workshop on Industrial Computer Systems. The focus is on complementing the traditional development process by adding the following four steps: (1) overall safety analysis; (2) analysis of the functional specifications; (3) designing for safety; (4) validation of design. Quantitative assessment of safety is possible by means of a modular questionnaire covering various aspects of the major stages of system development.

  7. Apollo experience report: Guidance and control systems - Digital autopilot design development

    NASA Technical Reports Server (NTRS)

    Peters, W. H.; Cox, K. J.

    1973-01-01

    The development of the Apollo digital autopilots (the primary attitude control systems that were used for all phases of the lunar landing mission) is summarized. This report includes design requirements, design constraints, and design philosophy. The development-process functions and the essential information flow paths are identified. Specific problem areas that existed during the development are included. A discussion is also presented on the benefits inherent in mechanizing attitude-controller logic and dynamic compensation in a digital computer.

  8. Contamination control engineering design guidelines for the aerospace community

    NASA Technical Reports Server (NTRS)

    Tribble, A. C. (Principal Investigator); Boyadjian, B.; Davis, J.; Haffner, J.; McCullough, E.

    1996-01-01

    Thermal control surfaces, solar arrays, and optical devices may be adversely affected by a small quantity of molecular and/or particulate contamination. What is rarely discussed is how one: (1) quantifies the level of contamination that must be maintained in order for the system to function properly, and (2) enforces contamination control to ensure compliance with requirements. This document is designed to address these specific issues and is intended to serve as a handbook on contamination control for the reader, illustrating process and methodology while providing direction to more detailed references when needed. The effects of molecular contamination on reflecting and transmitting surfaces are examined and quantified in accordance with MIL STD 1246C. The generation, transportation, and deposition of molecular contamination is reviewed and specific examples are worked to illustrate the process a design engineer can use to estimate end of life cleanliness levels required by solar arrays, thermal control surfaces, and optical surfaces. A similar process is used to describe the effect of particulate contamination as related to percent area coverage (PAC) and bi-directional reflectance distribution function (BRDF). Relationships between PAC and surface cleanliness, which include the effects of submicron sized particles, are developed and BRDF is related to specific sensor design parameters such as Point Source Transmittance (PST). The pros and cons of various methods of preventing, monitoring, and cleaning surfaces are examined and discussed.

  9. Research on the optimization of quota design in real estate

    NASA Astrophysics Data System (ADS)

    Sun, Chunling; Ma, Susu; Zhong, Weichao

    2017-11-01

    Quota design is one of the effective methods of cost control in real estate development project and widely used in the current real estate development project to control the engineering construction cost, but quota design have many deficiencies in design process. For this purpose, this paper put forward a method to achieve investment control of real estate development project, which combine quota design and value engineering(VE) at the stage of design. Specifically, it’s an optimizing for the structure of quota design. At first, determine the design limits by investment estimate value, then using VE to carry on initial allocation of design limits and gain the functional target cost, finally, consider the whole life cycle cost (LCC) and operational problem in practical application to finish complex correction for the functional target cost. The improved process can control the project cost more effectively. It not only can control investment in a certain range, but also make the project realize maximum value within investment.

  10. Ice pack heat sink subsystem - phase 1, volume 2

    NASA Technical Reports Server (NTRS)

    Roebelen, G. J., Jr.

    1973-01-01

    The design, development, and test of a functional laboratory model ice pack heat sink subsystem are discussed. Operating instructions to include mechanical and electrical schematics, maintenance instructions, and equipment specifications are presented.

  11. Conceptual design studies of control and instrumentation systems for ignition experiments

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

    Nicholson, P.J.; Dewolf, J.B.; Heinemann, P.C.

    1978-03-01

    Studies at the Charles Stark Draper Laboratory in the past year were a continuation of prior studies of control and instrumentation systems for current and next generation Tokomaks. Specifically, the FY 77 effort has focused on the following two main efforts: (1) control requirements--(a) defining and evolving control requirements/concepts for a prototype experimental power reactor(s), and (b) defining control requirements for diverters and mirror machines, specifically the MX; and (2) defining requirements and scoping design for a functional control simulator. Later in the year, a small additional task was added: (3) providing analysis and design support to INESCO for itsmore » low cost fusion power system, FPC/DMT.« less

  12. Layered approach to workstation design for medical image viewing

    NASA Astrophysics Data System (ADS)

    Haynor, David R.; Zick, Gregory L.; Heritage, Marcus B.; Kim, Yongmin

    1992-07-01

    Software engineering principles suggest that complex software systems are best constructed from independent, self-contained modules, thereby maximizing the portability, maintainability and modifiability of the produced code. This principal is important in the design of medical imaging workstations, where further developments in technology (CPU, memory, interface devices, displays, network connections) are required for clinically acceptable workstations, and it is desirable to provide different hardware platforms with the ''same look and feel'' for the user. In addition, the set of desired functions is relatively well understood, but the optimal user interface for delivering these functions on a clinically acceptable workstation is still different depending on department, specialty, or individual preference. At the University of Washington, we are developing a viewing station based on the IBM RISC/6000 computer and on new technologies that are just becoming commercially available. These include advanced voice recognition systems and an ultra-high-speed network. We are developing a set of specifications and a conceptual design for the workstation, and will be producing a prototype. This paper presents our current concepts concerning the architecture and software system design of the future prototype. Our conceptual design specifies requirements for a Database Application Programming Interface (DBAPI) and for a User API (UAPI). The DBAPI consists of a set of subroutine calls that define the admissible transactions between the workstation and an image archive. The UAPI describes the requests a user interface program can make of the workstation. It incorporates basic display and image processing functions, yet is specifically designed to allow extensions to the basic set at the application level. We will discuss the fundamental elements of the two API''s and illustrate their application to workstation design.

  13. Engineering and commercialization of human-device interfaces, from bone to brain.

    PubMed

    Knothe Tate, Melissa L; Detamore, Michael; Capadona, Jeffrey R; Woolley, Andrew; Knothe, Ulf

    2016-07-01

    Cutting edge developments in engineering of tissues, implants and devices allow for guidance and control of specific physiological structure-function relationships. Yet the engineering of functionally appropriate human-device interfaces represents an intractable challenge in the field. This leading opinion review outlines a set of current approaches as well as hurdles to design of interfaces that modulate transfer of information, i.a. forces, electrical potentials, chemical gradients and haptotactic paths, between endogenous and engineered body parts or tissues. The compendium is designed to bridge across currently separated disciplines by highlighting specific commonalities between seemingly disparate systems, e.g. musculoskeletal and nervous systems. We focus on specific examples from our own laboratories, demonstrating that the seemingly disparate musculoskeletal and nervous systems share common paradigms which can be harnessed to inspire innovative interface design solutions. Functional barrier interfaces that control molecular and biophysical traffic between tissue compartments of joints are addressed in an example of the knee. Furthermore, we describe the engineering of gradients for interfaces between endogenous and engineered tissues as well as between electrodes that physically and electrochemically couple the nervous and musculoskeletal systems. Finally, to promote translation of newly developed technologies into products, protocols, and treatments that benefit the patients who need them most, regulatory and technical challenges and opportunities are addressed on hand from an example of an implant cum delivery device that can be used to heal soft and hard tissues, from brain to bone. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  14. Functional Specifications for Computer Aided Training Systems Development and Management (CATSDM) Support Functions. Final Report.

    ERIC Educational Resources Information Center

    Hughes, John; And Others

    This report provides a description of a Computer Aided Training System Development and Management (CATSDM) environment based on state-of-the-art hardware and software technology, and including recommendations for off the shelf systems to be utilized as a starting point in addressing the particular systematic training and instruction design and…

  15. Role-Playing and Problem-Based Learning: The Use of Cross-Functional Student Teams in Business Application Development

    ERIC Educational Resources Information Center

    Pike, Jacqueline C.; Spangler, William; Williams, Valerie; Kollar, Robert

    2017-01-01

    To create a learning experience which replicates the process by which consultants, systems developers and business end users collaborate to design and implement a business application, a cross-functional student team project was developed and is described. The overall learning experience was distinguished by specific components and characteristics…

  16. Adult Roles & Functions. Objective Based Evaluation System.

    ERIC Educational Resources Information Center

    West Virginia State Vocational Curriculum Lab., Cedar Lakes.

    This book of objective-based test items is designed to be used with the Adult Roles and Functions curriculum for a non-laboratory home economic course for grades eleven and twelve. It contains item banks for each cognitive objective in the curriculum. In addition, there is a form for the table of specifications to be developed for each unit. This…

  17. Unidirectional transmission using array of zero-refractive-index metamaterials

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

    Fu, Yangyang; Xu, Lin; Hong Hang, Zhi

    2014-05-12

    In this Letter, we find that high efficient unidirectional transmission occurs for an array of prisms made of zero-refractive-index metamaterials. As a specific demonstration, we further design the device using Dirac-cone-like photonic crystals. The device can function for a broadband of spectrum. Numerical simulations are performed to verify the one-way wave functionality.

  18. Computer-aided system design

    NASA Technical Reports Server (NTRS)

    Walker, Carrie K.

    1991-01-01

    A technique has been developed for combining features of a systems architecture design and assessment tool and a software development tool. This technique reduces simulation development time and expands simulation detail. The Architecture Design and Assessment System (ADAS), developed at the Research Triangle Institute, is a set of computer-assisted engineering tools for the design and analysis of computer systems. The ADAS system is based on directed graph concepts and supports the synthesis and analysis of software algorithms mapped to candidate hardware implementations. Greater simulation detail is provided by the ADAS functional simulator. With the functional simulator, programs written in either Ada or C can be used to provide a detailed description of graph nodes. A Computer-Aided Software Engineering tool developed at the Charles Stark Draper Laboratory (CSDL CASE) automatically generates Ada or C code from engineering block diagram specifications designed with an interactive graphical interface. A technique to use the tools together has been developed, which further automates the design process.

  19. Common modular avionics - Partitioning and design philosophy

    NASA Astrophysics Data System (ADS)

    Scott, D. M.; Mulvaney, S. P.

    The design objectives and definition criteria for common modular hardware that will perform digital processing functions in multiple avionic subsystems are examined. In particular, attention is given to weapon system-level objectives, such as increased supportability, reduced life cycle costs, and increased upgradability. These objectives dictate the following overall modular design goals: reduce test equipment requirements; have a large number of subsystem applications; design for architectural growth; and standardize for technology transparent implementations. Finally, specific partitioning criteria are derived on the basis of the weapon system-level objectives and overall design goals.

  20. Planetary mission requirements, technology and design considerations for a solar electric propulsion stage

    NASA Technical Reports Server (NTRS)

    Cork, M. J.; Hastrup, R. C.; Menard, W. A.; Olson, R. N.

    1979-01-01

    High energy planetary missions such as comet rendezvous, Saturn orbiter and asteroid rendezvous require development of a Solar Electric Propulsion Stage (SEPS) for augmentation of the Shuttle-IUS. Performance and functional requirements placed on the SEPS are presented. These requirements will be used in evolution of the SEPS design, which must be highly interactive with both the spacecraft and the mission design. Previous design studies have identified critical SEPS technology areas and some specific design solutions which are also presented in the paper.

  1. Functional mixed effects spectral analysis

    PubMed Central

    KRAFTY, ROBERT T.; HALL, MARTICA; GUO, WENSHENG

    2011-01-01

    SUMMARY In many experiments, time series data can be collected from multiple units and multiple time series segments can be collected from the same unit. This article introduces a mixed effects Cramér spectral representation which can be used to model the effects of design covariates on the second-order power spectrum while accounting for potential correlations among the time series segments collected from the same unit. The transfer function is composed of a deterministic component to account for the population-average effects and a random component to account for the unit-specific deviations. The resulting log-spectrum has a functional mixed effects representation where both the fixed effects and random effects are functions in the frequency domain. It is shown that, when the replicate-specific spectra are smooth, the log-periodograms converge to a functional mixed effects model. A data-driven iterative estimation procedure is offered for the periodic smoothing spline estimation of the fixed effects, penalized estimation of the functional covariance of the random effects, and unit-specific random effects prediction via the best linear unbiased predictor. PMID:26855437

  2. Synthesis, hybridization characteristics, and fluorescence properties of oligonucleotides modified with nucleobase-functionalized locked nucleic acid adenosine and cytidine monomers.

    PubMed

    Kaura, Mamta; Kumar, Pawan; Hrdlicka, Patrick J

    2014-07-03

    Conformationally restricted nucleotides such as locked nucleic acid (LNA) are very popular as affinity-, specificity-, and stability-enhancing modifications in oligonucleotide chemistry to produce probes for nucleic acid targeting applications in molecular biology, biotechnology, and medicinal chemistry. Considerable efforts have been devoted in recent years to optimize the biophysical properties of LNA through additional modification of the sugar skeleton. We recently introduced C5-functionalization of LNA uridines as an alternative and synthetically more straightforward approach to improve the biophysical properties of LNA. In the present work, we set out to test the generality of this concept by studying the characteristics of oligonucleotides modified with four different C5-functionalized LNA cytidine and C8-functionalized LNA adenosine monomers. The results strongly suggest that C5-functionalization of LNA pyrimidines is indeed a viable approach for improving the binding affinity, target specificity, and/or enzymatic stability of LNA-modified ONs, whereas C8-functionalization of LNA adenosines is detrimental to binding affinity and specificity. These insights will impact the future design of conformationally restricted nucleotides for nucleic acid targeting applications.

  3. Proposal for the design of a zero gravity tool storage device

    NASA Technical Reports Server (NTRS)

    Stuckwisch, Sue; Carrion, Carlos A.; Phillips, Lee; Laughlin, Julia; Francois, Jason

    1994-01-01

    Astronauts frequently use a variety of hand tools during space missions, especially on repair missions. A toolbox is needed to allow storage and retrieval of tools with minimal difficulties. The toolbox must contain tools during launch, landing, and on-orbit operations. The toolbox will be used in the Shuttle Bay and therefore must withstand the hazardous space environment. The three main functions of the toolbox in space are: to protect the tools from the space environment and from damaging one another, to allow for quick, one-handed access to the tools; and to minimize the heat transfer between the astronaut's hand and the tools. This proposal explores the primary design issues associated with the design of the toolbox. Included are the customer and design specifications, global and refined function structures, possible solution principles, concept variants, and finally design recommendations.

  4. Design intent optimization at the beyond 7nm node: the intersection of DTCO and EUVL stochastic mitigation techniques

    NASA Astrophysics Data System (ADS)

    Crouse, Michael; Liebmann, Lars; Plachecki, Vince; Salama, Mohamed; Chen, Yulu; Saulnier, Nicole; Dunn, Derren; Matthew, Itty; Hsu, Stephen; Gronlund, Keith; Goodwin, Francis

    2017-03-01

    The initial readiness of EUV patterning was demonstrated in 2016 with IBM Alliance's 7nm device technology. The focus has now shifted to driving the 'effective' k1 factor and enabling the second generation of EUV patterning. Thus, Design Technology Co-optimization (DTCO) has become a critical part of technology enablement as scaling has become more challenging and the industry pushes the limits of EUV lithography. The working partnership between the design teams and the process development teams typically involves an iterative approach to evaluate the manufacturability of proposed designs, subsequent modifications to those designs and finally a design manual for the technology. While this approach has served the industry well for many generations, the challenges at the Beyond 7nm node require a more efficient approach. In this work, we describe the use of "Design Intent" lithographic layout optimization where we remove the iterative component of DTCO and replace it with an optimization that achieves both a "patterning friendly" design and minimizes the well-known EUV stochastic effects. Solved together, this "design intent" approach can more quickly achieve superior lithographic results while still meeting the original device's functional specifications. Specifically, in this work we will demonstrate "design intent" optimization for critical BEOL layers using design tolerance bands to guide the source mask co-optimization. The design tolerance bands can be either supplied as part of the original design or derived from some basic rules. Additionally, the EUV stochastic behavior is mitigated by enhancing the image log slope (ILS) for specific key features as part of the overall optimization. We will show the benefit of the "design intent approach" on both bidirectional and unidirectional 28nm min pitch standard logic layouts and compare the more typical iterative SMO approach. Thus demonstrating the benefit of allowing the design to float within the specified range. Lastly, we discuss how the evolution of this approach could lead to layout optimization based entirely on some minimal set of functional requirements and process constraints.

  5. Launch Vehicle Design Process Description and Training Formulation

    NASA Technical Reports Server (NTRS)

    Atherton, James; Morris, Charles; Settle, Gray; Teal, Marion; Schuerer, Paul; Blair, James; Ryan, Robert; Schutzenhofer, Luke

    1999-01-01

    A primary NASA priority is to reduce the cost and improve the effectiveness of launching payloads into space. As a consequence, significant improvements are being sought in the effectiveness, cost, and schedule of the launch vehicle design process. In order to provide a basis for understanding and improving the current design process, a model has been developed for this complex, interactive process, as reported in the references. This model requires further expansion in some specific design functions. Also, a training course for less-experienced engineers is needed to provide understanding of the process, to provide guidance for its effective implementation, and to provide a basis for major improvements in launch vehicle design process technology. The objective of this activity is to expand the description of the design process to include all pertinent design functions, and to develop a detailed outline of a training course on the design process for launch vehicles for use in educating engineers whose experience with the process has been minimal. Building on a previously-developed partial design process description, parallel sections have been written for the Avionics Design Function, the Materials Design Function, and the Manufacturing Design Function. Upon inclusion of these results, the total process description will be released as a NASA TP. The design function sections herein include descriptions of the design function responsibilities, interfaces, interactive processes, decisions (gates), and tasks. Associated figures include design function planes, gates, and tasks, along with other pertinent graphics. Also included is an expanded discussion of how the design process is divided, or compartmentalized, into manageable parts to achieve efficient and effective design. A detailed outline for an intensive two-day course on the launch vehicle design process has been developed herein, and is available for further expansion. The course is in an interactive lecture/workshop format to engage the participants in active learning. The course addresses the breadth and depth of the process, requirements, phases, participants, multidisciplinary aspects, tasks, critical elements,as well as providing guidance from previous lessons learned. The participants are led to develop their own understanding of the current process and how it can be improved. Included are course objectives and a session-by-session outline of course content. Also included is an initial identification of visual aid requirements.

  6. Specific, Measureable, Attainable, Relevant, and Timely (SMART) Documents: Utilized in Assessing Socioeconomic Impacts of Cascading Infrastructure Disruptions

    DTIC Science & Technology

    2017-02-01

    their respective owners. The findings of this report are not to be construed as an official Department of the Army position unless so designated by...Even with properly designed infrastructures that sat- isfy people’s needs in normal-functioning scenarios, infrastructure performance is often...Army-relevant contexts can be explored. This model will be designed to provide possible policy insights into how best to protect crucial

  7. External validity of randomized controlled trials in older adults, a systematic review.

    PubMed

    van Deudekom, Floor J; Postmus, Iris; van der Ham, Danielle J; Pothof, Alexander B; Broekhuizen, Karen; Blauw, Gerard J; Mooijaart, Simon P

    2017-01-01

    To critically assess the external validity of randomized controlled trials (RCTs) it is important to know what older adults have been enrolled in the trials. The aim of this systematic review is to study what proportion of trials specifically designed for older patients report on somatic status, physical and mental functioning, social environment and frailty in the patient characteristics. PubMed was searched for articles published in 2012 and only RCTs were included. Articles were further excluded if not conducted with humans or only secondary analyses were reported. A random sample of 10% was drawn. The current review analyzed this random sample and further selected trials when the reported mean age was ≥ 60 years. We extracted geriatric assessments from the population descriptives or the in- and exclusion criteria. In total 1396 trials were analyzed and 300 trials included. The median of the reported mean age was 66 (IQR 63-70) and the median percentage of men in the trials was 60 (IQR 45-72). In 34% of the RCTs specifically designed for older patients somatic status, physical and mental functioning, social environment or frailty were reported in the population descriptives or the in- and exclusion criteria. Physical and mental functioning was reported most frequently (22% and 14%). When selecting RCTs on a mean age of 70 or 80 years the report of geriatric assessments in the patient characteristics was 46% and 85% respectively but represent only 5% and 1% of the trials. Somatic status, physical and mental functioning, social environment and frailty are underreported even in RCTs specifically designed for older patients published in 2012. Therefore, it is unclear for clinicians to which older patients the results can be applied. We recommend systematic to transparently report these relevant characteristics of older participants included in RCTs.

  8. Automated design synthesis of robotic/human workcells for improved manufacturing system design in hazardous environments

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

    Williams, Joshua M.

    Manufacturing tasks that are deemed too hazardous for workers require the use of automation, robotics, and/or other remote handling tools. The associated hazards may be radiological or nonradiological, and based on the characteristics of the environment and processing, a design may necessitate robotic labor, human labor, or both. There are also other factors such as cost, ergonomics, maintenance, and efficiency that also effect task allocation and other design choices. Handling the tradeoffs of these factors can be complex, and lack of experience can be an issue when trying to determine if and what feasible automation/robotics options exist. To address thismore » problem, we utilize common engineering design approaches adapted more for manufacturing system design in hazardous environments. We limit our scope to the conceptual and embodiment design stages, specifically a computational algorithm for concept generation and early design evaluation. In regard to concept generation, we first develop the functional model or function structure for the process, using the common 'verb-noun' format for describing function. A common language or functional basis for manufacturing was developed and utilized to formalize function descriptions and guide rules for function decomposition. Potential components for embodiment are also grouped in terms of this functional language and are stored in a database. The properties of each component are given as quantitative and qualitative criteria. Operators are also rated for task-relevant criteria which are used to address task compatibility. Through the gathering of process requirements/constraints, construction of the component database, and development of the manufacturing basis and rule set, design knowledge is stored and available for computer use. Thus, once the higher level process functions are defined, the computer can automate the synthesis of new design concepts through alternating steps of embodiment and function structure updates/decomposition. In the process, criteria guide function allocation of components/operators and help ensure compatibility and feasibility. Through multiple function assignment options and varied function structures, multiple design concepts are created. All of the generated designs are then evaluated based on a number of relevant evaluation criteria: cost, dose, ergonomics, hazards, efficiency, etc. These criteria are computed using physical properties/parameters of each system based on the qualities an engineer would use to make evaluations. Nuclear processes such as oxide conversion and electrorefining are utilized to aid algorithm development and provide test cases for the completed program. Through our approach, we capture design knowledge related to manufacturing and other operations in hazardous environments to enable a computational program to automatically generate and evaluate system design concepts.« less

  9. Numerical aerodynamic simulation facility. Preliminary study extension

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The production of an optimized design of key elements of the candidate facility was the primary objective of this report. This was accomplished by effort in the following tasks: (1) to further develop, optimize and describe the function description of the custom hardware; (2) to delineate trade off areas between performance, reliability, availability, serviceability, and programmability; (3) to develop metrics and models for validation of the candidate systems performance; (4) to conduct a functional simulation of the system design; (5) to perform a reliability analysis of the system design; and (6) to develop the software specifications to include a user level high level programming language, a correspondence between the programming language and instruction set and outline the operation system requirements.

  10. Special Issue: "Functional Dendrimers".

    PubMed

    Tomalia, Donald A

    2016-08-09

    This special issue entitled "Functional Dendrimers" focuses on the manipulation of at least six "critical nanoscale design parameters" (CNDPs) of dendrimers including: size, shape, surface chemistry, flexibility/rigidity, architecture and elemental composition. These CNDPs collectively define properties of all "functional dendrimers". This special issue contains many interesting examples describing the manipulation of certain dendrimer CNDPs to create new emerging properties and, in some cases, predictive nanoperiodic property patterns (i.e., dendritic effects). The systematic engineering of CNDPs provides a valuable strategy for optimizing functional dendrimer properties for use in specific applications.

  11. Computational multiscale modeling in protein--ligand docking.

    PubMed

    Taufer, Michela; Armen, Roger; Chen, Jianhan; Teller, Patricia; Brooks, Charles

    2009-01-01

    In biological systems, the binding of small molecule ligands to proteins is a crucial process for almost every aspect of biochemistry and molecular biology. Enzymes are proteins that function by catalyzing specific biochemical reactions that convert reactants into products. Complex organisms are typically composed of cells in which thousands of enzymes participate in complex and interconnected biochemical pathways. Some enzymes serve as sequential steps in specific pathways (such as energy metabolism), while others function to regulate entire pathways and cellular functions [1]. Small molecule ligands can be designed to bind to a specific enzyme and inhibit the biochemical reaction. Inhibiting the activity of key enzymes may result in the entire biochemical pathways being turned on or off [2], [3]. Many small molecule drugs marketed today function in this generic way as enzyme inhibitors. If research identifies a specific enzyme as being crucial to the progress of disease, then this enzyme may be targeted with an inhibitor, which may slow down or reverse the progress of disease. In this way, enzymes are targeted from specific pathogens (e.g., virus, bacteria, fungi) for infectious diseases [4], [5], and human enzymes are targeted for noninfectious diseases such as cardiovascular disease, cancer, diabetes, and neurodegenerative diseases [6].

  12. Designing patient-specific 3D printed craniofacial implants using a novel topology optimization method.

    PubMed

    Sutradhar, Alok; Park, Jaejong; Carrau, Diana; Nguyen, Tam H; Miller, Michael J; Paulino, Glaucio H

    2016-07-01

    Large craniofacial defects require efficient bone replacements which should not only provide good aesthetics but also possess stable structural function. The proposed work uses a novel multiresolution topology optimization method to achieve the task. Using a compliance minimization objective, patient-specific bone replacement shapes can be designed for different clinical cases that ensure revival of efficient load transfer mechanisms in the mid-face. In this work, four clinical cases are introduced and their respective patient-specific designs are obtained using the proposed method. The optimized designs are then virtually inserted into the defect to visually inspect the viability of the design . Further, once the design is verified by the reconstructive surgeon, prototypes are fabricated using a 3D printer for validation. The robustness of the designs are mechanically tested by subjecting them to a physiological loading condition which mimics the masticatory activity. The full-field strain result through 3D image correlation and the finite element analysis implies that the solution can survive the maximum mastication of 120 lb. Also, the designs have the potential to restore the buttress system and provide the structural integrity. Using the topology optimization framework in designing the bone replacement shapes would deliver surgeons new alternatives for rather complicated mid-face reconstruction.

  13. The Choice between MapMan and Gene Ontology for Automated Gene Function Prediction in Plant Science

    PubMed Central

    Klie, Sebastian; Nikoloski, Zoran

    2012-01-01

    Since the introduction of the Gene Ontology (GO), the analysis of high-throughput data has become tightly coupled with the use of ontologies to establish associations between knowledge and data in an automated fashion. Ontologies provide a systematic description of knowledge by a controlled vocabulary of defined structure in which ontological concepts are connected by pre-defined relationships. In plant science, MapMan and GO offer two alternatives for ontology-driven analyses. Unlike GO, initially developed to characterize microbial systems, MapMan was specifically designed to cover plant-specific pathways and processes. While the dependencies between concepts in MapMan are modeled as a tree, in GO these are captured in a directed acyclic graph. Therefore, the difference in ontologies may cause discrepancies in data reduction, visualization, and hypothesis generation. Here provide the first systematic comparative analysis of GO and MapMan for the case of the model plant species Arabidopsis thaliana (Arabidopsis) with respect to their structural properties and difference in distributions of information content. In addition, we investigate the effect of the two ontologies on the specificity and sensitivity of automated gene function prediction via the coupling of co-expression networks and the guilt-by-association principle. Automated gene function prediction is particularly needed for the model plant Arabidopsis in which only half of genes have been functionally annotated based on sequence similarity to known genes. The results highlight the need for structured representation of species-specific biological knowledge, and warrants caution in the design principles employed in future ontologies. PMID:22754563

  14. Advanced information processing system

    NASA Technical Reports Server (NTRS)

    Lala, J. H.

    1984-01-01

    Design and performance details of the advanced information processing system (AIPS) for fault and damage tolerant data processing on aircraft and spacecraft are presented. AIPS comprises several computers distributed throughout the vehicle and linked by a damage tolerant data bus. Most I/O functions are available to all the computers, which run in a TDMA mode. Each computer performs separate specific tasks in normal operation and assumes other tasks in degraded modes. Redundant software assures that all fault monitoring, logging and reporting are automated, together with control functions. Redundant duplex links and damage-spread limitation provide the fault tolerance. Details of an advanced design of a laboratory-scale proof-of-concept system are described, including functional operations.

  15. A Review of Function Allocation and En Route Separation Assurance

    NASA Technical Reports Server (NTRS)

    Lewis, Timothy A.; Aweiss, Arwa S.; Guerreiro, Nelson M.; Daiker, Ronald J.

    2016-01-01

    Today's air traffic control system has reached a limit to the number of aircraft that can be safely managed at the same time. This air traffic capacity bottleneck is a critical problem along the path to modernization for air transportation. The design of the next separation assurance system to address this problem is a cornerstone of air traffic management research today. This report reviews recent work by NASA and others in the areas of function allocation and en route separation assurance. This includes: separation assurance algorithms and technology prototypes; concepts of operations and designs for advanced separation assurance systems; and specific investigations into air-ground and human-automation function allocation.

  16. Development of bubble memory recorder onboard Japan Earth Resources Satellite-1

    NASA Astrophysics Data System (ADS)

    Araki, Tsunehiko; Ishida, Chu; Ochiai, Kiyoshi; Nozue, Tatsuhiro; Tachibana, Kyozo; Yoshida, Kazutoshi

    The Bubble Memory Recorder (BMR) developed for use on the Earth Resources Satellite is described in terms of its design, capabilities, and functions. The specifications of the BMR are given listing memory capacity, functions, and interface types for data, command, and telemetry functions. The BMR has an emergency signal interface to provide contingency recording, and a satellite-separation signal interface can be turned on automatically by signal input. Data are stored in a novolatile memory device so that the memory is retained during power outages. The BMR is characterized by a capability for random access, nonvolatility, and a solid-state design that is useful for space operations since it does not disturb spacecraft attitude.

  17. 78 FR 39493 - Patient Protection and Affordable Care Act; Exchange Functions: Eligibility for Exemptions...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ...This final rule implements certain functions of the Affordable Insurance Exchanges (``Exchanges''). These specific statutory functions include determining eligibility for and granting certificates of exemption from the individual shared responsibility payment described in section 5000A of the Internal Revenue Code. Additionally, this final rule implements the responsibilities of the Secretary of Health and Human Services, in coordination with the Secretary of the Treasury, to designate other health benefits coverage as minimum essential coverage by providing that certain coverage be designated as minimum essential coverage. It also outlines substantive and procedural requirements that other types of individual coverage must fulfill in order to be certified as minimum essential coverage.

  18. Multiplexed mRNA Sensing and Combinatorial-Targeted Drug Delivery Using DNA-Gold Nanoparticle Dimers.

    PubMed

    Kyriazi, Maria-Eleni; Giust, Davide; El-Sagheer, Afaf H; Lackie, Peter M; Muskens, Otto L; Brown, Tom; Kanaras, Antonios G

    2018-04-24

    The design of nanoparticulate systems which can perform multiple synergistic functions in cells with high specificity and selectivity is of great importance in applications. Here we combine recent advances in DNA-gold nanoparticle self-assembly and sensing to develop gold nanoparticle dimers that are able to perform multiplexed synergistic functions within a cellular environment. These dimers can sense two mRNA targets and simultaneously or independently deliver one or two DNA-intercalating anticancer drugs (doxorubicin and mitoxantrone) in live cells. Our study focuses on the design of sophisticated nanoparticle assemblies with multiple and synergistic functions that have the potential to advance sensing and drug delivery in cells.

  19. Optical processing for future computer networks

    NASA Technical Reports Server (NTRS)

    Husain, A.; Haugen, P. R.; Hutcheson, L. D.; Warrior, J.; Murray, N.; Beatty, M.

    1986-01-01

    In the development of future data management systems, such as the NASA Space Station, a major problem represents the design and implementation of a high performance communication network which is self-correcting and repairing, flexible, and evolvable. To obtain the goal of designing such a network, it will be essential to incorporate distributed adaptive network control techniques. The present paper provides an outline of the functional and communication network requirements for the Space Station data management system. Attention is given to the mathematical representation of the operations being carried out to provide the required functionality at each layer of communication protocol on the model. The possible implementation of specific communication functions in optics is also considered.

  20. TRL - A FORMAL TEST REPRESENTATION LANGUAGE AND TOOL FOR FUNCTIONAL TEST DESIGNS

    NASA Technical Reports Server (NTRS)

    Hops, J. M.

    1994-01-01

    A Formal Test Representation Language and Tool for Functional Test Designs (TRL) is an automatic tool and a formal language that is used to implement the Category-Partition Method and produce the specification of test cases in the testing phase of software development. The Category-Partition Method is particularly useful in defining the inputs, outputs and purpose of the test design phase and combines the benefits of choosing normal cases with error exposing properties. Traceability can be maintained quite easily by creating a test design for each objective in the test plan. The effort to transform the test cases into procedures is simplified by using an automatic tool to create the cases based on the test design. The method allows the rapid elimination of undesired test cases from consideration, and easy review of test designs by peer groups. The first step in the category-partition method is functional decomposition, in which the specification and/or requirements are decomposed into functional units that can be tested independently. A secondary purpose of this step is to identify the parameters that affect the behavior of the system for each functional unit. The second step, category analysis, carries the work done in the previous step further by determining the properties or sub-properties of the parameters that would make the system behave in different ways. The designer should analyze the requirements to determine the features or categories of each parameter and how the system may behave if the category were to vary its value. If the parameter undergoing refinement is a data-item, then categories of this data-item may be any of its attributes, such as type, size, value, units, frequency of change, or source. After all the categories for the parameters of the functional unit have been determined, the next step is to partition each category's range space into mutually exclusive values that the category can assume. In choosing partition values, all possible kinds of values should be included, especially the ones that will maximize error detection. The purpose of the final step, partition constraint analysis, is to refine the test design specification so that only the technically effective and economically feasible test cases are implied. TRL is written in C-language to be machine independent. It has been successfully implemented on an IBM PC compatible running MS DOS, a Sun4 series computer running SunOS, an HP 9000/700 series workstation running HP-UX, a DECstation running DEC RISC ULTRIX, and a DEC VAX series computer running VMS. TRL requires 1Mb of disk space and a minimum of 84K of RAM. The documentation is available in electronic form in Word Perfect format. The standard distribution media for TRL is a 5.25 inch 360K MS-DOS format diskette. Alternate distribution media and formats are available upon request. TRL was developed in 1993 and is a copyrighted work with all copyright vested in NASA.

  1. Energy design for protein-protein interactions

    PubMed Central

    Ravikant, D. V. S.; Elber, Ron

    2011-01-01

    Proteins bind to other proteins efficiently and specifically to carry on many cell functions such as signaling, activation, transport, enzymatic reactions, and more. To determine the geometry and strength of binding of a protein pair, an energy function is required. An algorithm to design an optimal energy function, based on empirical data of protein complexes, is proposed and applied. Emphasis is made on negative design in which incorrect geometries are presented to the algorithm that learns to avoid them. For the docking problem the search for plausible geometries can be performed exhaustively. The possible geometries of the complex are generated on a grid with the help of a fast Fourier transform algorithm. A novel formulation of negative design makes it possible to investigate iteratively hundreds of millions of negative examples while monotonically improving the quality of the potential. Experimental structures for 640 protein complexes are used to generate positive and negative examples for learning parameters. The algorithm designed in this work finds the correct binding structure as the lowest energy minimum in 318 cases of the 640 examples. Further benchmarks on independent sets confirm the significant capacity of the scoring function to recognize correct modes of interactions. PMID:21842951

  2. Property-driven functional verification technique for high-speed vision system-on-chip processor

    NASA Astrophysics Data System (ADS)

    Nshunguyimfura, Victor; Yang, Jie; Liu, Liyuan; Wu, Nanjian

    2017-04-01

    The implementation of functional verification in a fast, reliable, and effective manner is a challenging task in a vision chip verification process. The main reason for this challenge is the stepwise nature of existing functional verification techniques. This vision chip verification complexity is also related to the fact that in most vision chip design cycles, extensive efforts are focused on how to optimize chip metrics such as performance, power, and area. Design functional verification is not explicitly considered at an earlier stage at which the most sound decisions are made. In this paper, we propose a semi-automatic property-driven verification technique. The implementation of all verification components is based on design properties. We introduce a low-dimension property space between the specification space and the implementation space. The aim of this technique is to speed up the verification process for high-performance parallel processing vision chips. Our experimentation results show that the proposed technique can effectively improve the verification effort up to 20% for the complex vision chip design while reducing the simulation and debugging overheads.

  3. Design of affordable and ruggedized biomedical devices using virtual instrumentation.

    PubMed

    Mathern, Ryan Michael; Schopman, Sarah; Kalchthaler, Kyle; Mehta, Khanjan; Butler, Peter

    2013-05-01

    Abstract This paper presents the designs of four low-cost and ruggedized biomedical devices, including a blood pressure monitor, thermometer, weighing scale and spirometer, designed for the East African context. The design constraints included a mass-production price point of $10, accuracy and precision comparable to commercial devices and ruggedness to function effectively in the harsh environment of East Africa. The blood pressure device, thermometer and weighing scale were field-tested in Kenya and each recorded data within 6% error of the measurements from commercial devices and withstood the adverse climate and rough handling. The spirometer functioned according to specifications, but a re-design is needed to improve operability and usability by patients. This article demonstrates the feasibility of designing and commercializing virtual instrumentation-based biomedical devices in resource-constrained environments through context-driven design. The next steps for the devices include designing them such that they can be more easily manufactured, use standardized materials, are easily calibrated in the field and have more user-friendly software programs that can be updated remotely.

  4. The use of multidimensional scaling for facilities layout - An application to the design of the Space Station

    NASA Technical Reports Server (NTRS)

    Tullis, Thomas S.; Bied Sperling, Barbra; Steinberg, A. L.

    1986-01-01

    Before an optimum layout of the facilities for the proposed Space Station can be designed, it is necessary to understand the functions that will be performed by the Space Station crew and the relationships among those functions. Five criteria for assessing functional relationships were identified. For each of these criteria, a matrix representing the degree of association of all pairs of functions was developed. The key to making inferences about the layout of the Space Station from these matrices was the use of multidimensional scaling (MDS). Applying MDS to these matrices resulted in spatial configurations of the crew functions in which smaller distances in the MDS configuration reflected closer associations. An MDS analysis of a composite matrix formed by combining the five individual matrices resulted in two dimensions that describe the configuration: a 'private-public' dimension and a 'group-individual' dimension. Seven specific recommendations for Space Station layout were derived from analyses of the MDS configurations. Although these techniques have been applied to the design of the Space Station, they can be applied to the design of any facility where people live or work.

  5. A sequence-based hybrid predictor for identifying conformationally ambivalent regions in proteins.

    PubMed

    Liu, Yu-Cheng; Yang, Meng-Han; Lin, Win-Li; Huang, Chien-Kang; Oyang, Yen-Jen

    2009-12-03

    Proteins are dynamic macromolecules which may undergo conformational transitions upon changes in environment. As it has been observed in laboratories that protein flexibility is correlated to essential biological functions, scientists have been designing various types of predictors for identifying structurally flexible regions in proteins. In this respect, there are two major categories of predictors. One category of predictors attempts to identify conformationally flexible regions through analysis of protein tertiary structures. Another category of predictors works completely based on analysis of the polypeptide sequences. As the availability of protein tertiary structures is generally limited, the design of predictors that work completely based on sequence information is crucial for advances of molecular biology research. In this article, we propose a novel approach to design a sequence-based predictor for identifying conformationally ambivalent regions in proteins. The novelty in the design stems from incorporating two classifiers based on two distinctive supervised learning algorithms that provide complementary prediction powers. Experimental results show that the overall performance delivered by the hybrid predictor proposed in this article is superior to the performance delivered by the existing predictors. Furthermore, the case study presented in this article demonstrates that the proposed hybrid predictor is capable of providing the biologists with valuable clues about the functional sites in a protein chain. The proposed hybrid predictor provides the users with two optional modes, namely, the high-sensitivity mode and the high-specificity mode. The experimental results with an independent testing data set show that the proposed hybrid predictor is capable of delivering sensitivity of 0.710 and specificity of 0.608 under the high-sensitivity mode, while delivering sensitivity of 0.451 and specificity of 0.787 under the high-specificity mode. Though experimental results show that the hybrid approach designed to exploit the complementary prediction powers of distinctive supervised learning algorithms works more effectively than conventional approaches, there exists a large room for further improvement with respect to the achieved performance. In this respect, it is of interest to investigate the effects of exploiting additional physiochemical properties that are related to conformational ambivalence. Furthermore, it is of interest to investigate the effects of incorporating lately-developed machine learning approaches, e.g. the random forest design and the multi-stage design. As conformational transition plays a key role in carrying out several essential types of biological functions, the design of more advanced predictors for identifying conformationally ambivalent regions in proteins deserves our continuous attention.

  6. Functional characterization of three MicroRNAs of the Asian Tiger Mosquito, Aedes albopictus

    PubMed Central

    2013-01-01

    Background Temporal and stage specific expression of microRNAs (miRNAs) in embryos, larvae, pupae and adults of Aedes albopictus showed differential expression levels across the four developmental stages, indicating their potential regulatory roles in mosquito development. The functional characterization of these miRNAs was not known. Accordingly our study evaluated the functional characterization of three miRNAs, which are temporally up-regulated in the various developmental stages of Ae. albopictus mosquitoes. Methods miRNA mimics, inhibitors and negative controls were designed and their knock-in and knock-down efficiency were analyzed by qRT-PCR after transfecting the mosquito cell lines C6/36, and also by injecting in their specific developmental stages. The functional role of each individual miRNA was analyzed with various parameters of development such as, hatching rate and hatching time in embryos, eclosion rate in larvae, longevity and fecundity in the adult mosquitoes. Results The knock-in with the specifically designed miRNA mimics showed increased levels of expression of miRNA compared with their normal controls. We confirmed these findings using qRT-PCR, both by in vitro expression in C6/36 mosquito cell lines after transfection as well as in in vivo expression in developmental stages of mosquitoes by microinjection. The knock-down of expression with the corresponding inhibitors showed a considerable decrease in the expression levels of these miRNAs and obvious functional effects in Ae. albopictus development, detected by a decrease in the hatching rate of embryos and eclosion rate in larvae and a marked reduction in longevity and fecundity in adults. Conclusion This study carried out by knock-in and knock-down of specifically and temporally expressed miRNAs in Ae. albopictus by microinjection is a novel study to delineate the importance of the miRNA expression in regulating mosquito development. The knock-down and loss of function of endogenously expressed miRNAs by the miRNA inhibitors in specific developmental stages had considerable effects on development, but enhancement of their gain of function was not observed on knock-in of these specific miRNAs. Hence, our study indicates that an optimal level of endogenous expression of miRNA is indispensable for the normal development and maintenance of the vectorial population density and pathogen transmissibility of this mosquito vector. PMID:23924583

  7. Reliability, construct validity, and responsiveness of the neck disability index, patient-specific functional scale, and numeric pain rating scale in patients with cervical radiculopathy.

    PubMed

    Young, Ian A; Cleland, Joshua A; Michener, Lori A; Brown, Chris

    2010-10-01

    To examine the psychometric properties of the Neck Disability Index, Patient-Specific Functional Scale, and the Numeric Pain Rating Scale in a cohort of patients with cervical radiculopathy. A single-group repeated-measures design. Patients (n = 165) presenting to physical therapy with cervical radiculopathy completed the Neck Disability Index, Patient-Specific Functional Scale, and Numeric Pain Rating Scale at the baseline examination and at a follow-up. At the time of follow-up, all patients also completed the Global Rating of Change, which was used to dichotomize patients as improved or stable. Baseline and follow-up scores were used to determine the test-retest reliability, construct validity, and minimal levels of detectable and clinically important change for the Neck Disability Index, Patient-Specific Functional Scale, and Numeric Pain Rating Scale. Both the Neck Disability Index and Numeric Pain Rating Scale exhibited fair test-retest reliability, whereas the Patient-Specific Functional Scale exhibited poor reliability in patients with cervical radiculopathy. All three outcome measures showed adequate responsiveness in this patient population. The minimal detectable change was 13.4 for the Neck Disability Index, 3.3 for the Patient-Specific Functional Scale, and 4.1 for the Numeric Pain Rating Scale. The threshold for the minimal clinically important difference was 8.5 for the Neck Disability Index and 2.2 for both the Patient-Specific Functional Scale and Numeric Pain Rating Scale. In light of the varied distribution of symptoms in patients with cervical radiculopathy, future studies should investigate the psychometric properties of other neck-related disability measures in this patient population.

  8. Performance of Comorbidity, Risk Adjustment, and Functional Status Measures in Expenditure Prediction for Patients With Diabetes

    PubMed Central

    Maciejewski, Matthew L.; Liu, Chuan-Fen; Fihn, Stephan D.

    2009-01-01

    OBJECTIVE—To compare the ability of generic comorbidity and risk adjustment measures, a diabetes-specific measure, and a self-reported functional status measure to explain variation in health care expenditures for individuals with diabetes. RESEARCH DESIGN AND METHODS—This study included a retrospective cohort of 3,092 diabetic veterans participating in a multisite trial. Two comorbidity measures, four risk adjusters, a functional status measure, a diabetes complication count, and baseline expenditures were constructed from administrative and survey data. Outpatient, inpatient, and total expenditure models were estimated using ordinary least squares regression. Adjusted R2 statistics and predictive ratios were compared across measures to assess overall explanatory power and explanatory power of low- and high-cost subgroups. RESULTS—Administrative data–based risk adjusters performed better than the comorbidity, functional status, and diabetes-specific measures in all expenditure models. The diagnostic cost groups (DCGs) measure had the greatest predictive power overall and for the low- and high-cost subgroups, while the diabetes-specific measure had the lowest predictive power. A model with DCGs and the diabetes-specific measure modestly improved predictive power. CONCLUSIONS—Existing generic measures can be useful for diabetes-specific research and policy applications, but more predictive diabetes-specific measures are needed. PMID:18945927

  9. Dual immobilization and magnetic manipulation of magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Yang, S. Y.; Jian, Z. F.; Horng, H. E.; Hong, Chin-Yih; Yang, H. C.; Wu, C. C.; Lee, Y. H.

    By suitably bio-functionalizing the surfaces, magnetic nanoparticles are able to bind specific biomolecules, and may serve as vectors for delivering bio-entities to target tissues. In this work, the synthesis of bio-functionalized magnetic nanoparticles with two kinds of bio-probes is developed. Here, the stem cell is selected as a to-be-delivered bio-entity and infarcted myocardium is the target issue. Thus, cluster designation-34 (CD-34) on stem cell and creatine kinase-MB (CK-MB) (or troponin I) on infarcted myocardium are the specific biomolecules to be bound with bio-functionalized magnetic nanoparticles. In addition to demonstrating the co-coating of two kinds of bio-probes on a magnetic nanoparticle, the feasibility of manipulation on bio-functionalized magnetic nanoparticles by external magnetic fields is investigated.

  10. Functional Cellular Mimics for the Spatiotemporal Control of Multiple Enzymatic Cascade Reactions.

    PubMed

    Liu, Xiaoling; Formanek, Petr; Voit, Brigitte; Appelhans, Dietmar

    2017-12-18

    Next-generation therapeutic approaches are expected to rely on the engineering of biomimetic cellular systems that can mimic specific cellular functions. Herein, we demonstrate a highly effective route for constructing structural and functional eukaryotic cell mimics by loading pH-sensitive polymersomes as membrane-associated and free-floating organelle mimics inside the multifunctional cell membrane. Metabolism mimicry has been validated by performing successive enzymatic cascade reactions spatially separated at specific sites of cell mimics in the presence and absence of extracellular organelle mimics. These enzymatic reactions take place in a highly controllable, reproducible, efficient, and successive manner. Our biomimetic approach to material design for establishing functional principles brings considerable enrichment to the fields of biomedicine, biocatalysis, biotechnology, and systems biology. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Robust Design of Biological Circuits: Evolutionary Systems Biology Approach

    PubMed Central

    Chen, Bor-Sen; Hsu, Chih-Yuan; Liou, Jing-Jia

    2011-01-01

    Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter fluctuations and environmental molecular noise from the cellular context in the host cell. Based on evolutionary systems biology algorithm, the design parameters of target gene circuits can evolve to specific values in order to robustly track a desired biologic function in spite of intrinsic and environmental noise. The fitness function is selected to be inversely proportional to the tracking error so that the evolutionary biological circuit can achieve the optimal tracking mimicking the evolutionary process of a gene circuit. Finally, several design examples are given in silico with the Monte Carlo simulation to illustrate the design procedure and to confirm the robust performance of the proposed design method. The result shows that the designed gene circuits can robustly track desired behaviors with minimal errors even with nontrivial intrinsic and external noise. PMID:22187523

  12. Robust design of biological circuits: evolutionary systems biology approach.

    PubMed

    Chen, Bor-Sen; Hsu, Chih-Yuan; Liou, Jing-Jia

    2011-01-01

    Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter fluctuations and environmental molecular noise from the cellular context in the host cell. Based on evolutionary systems biology algorithm, the design parameters of target gene circuits can evolve to specific values in order to robustly track a desired biologic function in spite of intrinsic and environmental noise. The fitness function is selected to be inversely proportional to the tracking error so that the evolutionary biological circuit can achieve the optimal tracking mimicking the evolutionary process of a gene circuit. Finally, several design examples are given in silico with the Monte Carlo simulation to illustrate the design procedure and to confirm the robust performance of the proposed design method. The result shows that the designed gene circuits can robustly track desired behaviors with minimal errors even with nontrivial intrinsic and external noise.

  13. Non-linear Mechanics of Three-dimensional Architected Materials; Design of Soft and Functional Systems and Structures

    NASA Astrophysics Data System (ADS)

    Babaee, Sahab

    In the search for materials with new properties, there have been significant advances in recent years aimed at the construction of architected materials whose behavior is governed by structure, rather than composition. Through careful design of the material's architecture, new mechanical properties have been demonstrated, including negative Poisson's ratio, high stiffness to weight ratio and mechanical cloaking. However, most of the proposed architected materials (also known as mechanical metamaterials) have a unique structure that cannot be recon figured after fabrication, making them suitable only for a specific task. This thesis focuses on the design of architected materials that take advantage of the applied large deformation to enhance their functionality. Mechanical instabilities, which have been traditionally viewed as a failure mode with research focusing on how to avoid them, are exploited to achieve novel and tunable functionalities. In particular I demonstrate the design of mechanical metamaterials with tunable negative Poisson ratio, adaptive phononic band gaps, acoustic switches, and reconfigurable origami-inspired waveguides. Remarkably, due to large deformation capability and full reversibility of soft materials, the responses of the proposed designs are reversible, repeatable, and scale independent. The results presented here pave the way for the design of a new class of soft, active, adaptive, programmable and tunable structures and systems with unprecedented performance and improved functionalities.

  14. The development of anti-heat stress clothing for construction workers in hot and humid weather.

    PubMed

    Chan, Albert P C; Guo, Y P; Wong, Francis K W; Li, Y; Sun, S; Han, X

    2016-04-01

    The purpose of this study was to develop anti-heat stress clothing for construction workers in hot and humid weather. Following DeJonge's functional clothing design process, the design situation was explored, including clothing fabric heat/moisture transporting properties and UV protection and the aspects of clothing ergonomic design (mobility, convenience, and safety). The problem structure was derived from the results of the surveys in three local construction sites, which agreed well with the task requirements and observations. Specifications were consequently described and 30 commercially available fabrics were identified and tested. Fabric testing data and design considerations were inputted in S-smart system to predict the thermal functional performance of the clothing. A new uniform prototype was developed and evaluated. The results of all measurements suggest that the new uniform which incorporated fabrics with superior heat/moisture transporting properties and loose-fitting design could reduce the workers' heat stress and improve their comfort and work performance. Practitioner Summary: The construction workers' uniform currently used in Hong Kong during summer was unsatisfactory. Following DeJonge's functional clothing design process, an anti-heat stress uniform was developed by testing 30 fabrics and predicting clothing thermal functional performance using S-smart system. The new uniform could reduce the workers' heat stress and improve their comfort and work performance.

  15. Elastic properties of protein functionalized nanoporous polymer films

    DOE PAGES

    Charles T. Black; Wang, Haoyu; Akcora, Pinar

    2015-12-16

    Retaining the conformational structure and bioactivity of immobilized proteins is important for biosensor designs and drug delivery systems. Confined environments often lead to changes in conformation and functions of proteins. In this study, lysozyme is chemically tethered into nanopores of polystyrene thin films, and submicron pores in poly(methyl methacrylate) films are functionalized with streptavidin. Nanoindentation experiments show that stiffness of streptavidin increases with decreasing submicron pore sizes. Lysozymes in polystyrene nanopores are found to behave stiffer than the submicron pore sizes and still retain their specific bioactivity relative to the proteins on flat surfaces. Lastly, our results show that proteinmore » functionalized ordered nanoporous polystyrene/poly(methyl methacrylate) films present heterogeneous elasticity and can be used to study interactions between free proteins and designed surfaces.« less

  16. Modeling biology with HDL languages: a first step toward a genetic design automation tool inspired from microelectronics.

    PubMed

    Gendrault, Yves; Madec, Morgan; Lallement, Christophe; Haiech, Jacques

    2014-04-01

    Nowadays, synthetic biology is a hot research topic. Each day, progresses are made to improve the complexity of artificial biological functions in order to tend to complex biodevices and biosystems. Up to now, these systems are handmade by bioengineers, which require strong technical skills and leads to nonreusable development. Besides, scientific fields that share the same design approach, such as microelectronics, have already overcome several issues and designers succeed in building extremely complex systems with many evolved functions. On the other hand, in systems engineering and more specifically in microelectronics, the development of the domain has been promoted by both the improvement of technological processes and electronic design automation tools. The work presented in this paper paves the way for the adaptation of microelectronics design tools to synthetic biology. Considering the similarities and differences between the synthetic biology and microelectronics, the milestones of this adaptation are described. The first one concerns the modeling of biological mechanisms. To do so, a new formalism is proposed, based on an extension of the generalized Kirchhoff laws to biology. This way, a description of all biological mechanisms can be made with languages widely used in microelectronics. Our approach is therefore successfully validated on specific examples drawn from the literature.

  17. From design to manufacturing of asymmetric teeth gears using computer application

    NASA Astrophysics Data System (ADS)

    Suciu, F.; Dascalescu, A.; Ungureanu, M.

    2017-05-01

    The asymmetric cylindrical gears, with involutes teeth profiles having different base circle diameters, are nonstandard gears, used with the aim to obtain better function parameters for the active profile. We will expect that the manufacturing of these gears became possible only after the design and realization of some specific tools. The paper present how the computer aided design and applications developed in MATLAB, for obtain the geometrical parameters, in the same time for calculation some functional parameters like stress and displacements, transmission error, efficiency of the gears and the 2D models, generated with AUTOLISP applications, are used for computer aided manufacturing of asymmetric gears with standard tools. So the specific tools considered one of the disadvantages of these gears are not necessary and implicitly the expected supplementary costs are reduced. The calculus algorithm established for the asymmetric gear design application use the „direct design“ of the spur gears. This method offers the possibility of determining first the parameters of the gears, followed by the determination of the asymmetric gear rack’s parameters, based on those of the gears. Using original design method and computer applications have been determined the geometrical parameters, the 2D and 3D models of the asymmetric gears and on the base of these models have been manufacturing on CNC machine tool asymmetric gears.

  18. Design of Solid-Gas Interfaces for Enhanced Thermal Transfer

    DTIC Science & Technology

    2015-09-28

    modifications. Specifically, for metal surfaces modified with organic self - assembled monolayers (SAMs), both TAC and MAC are close to its theoretical...we designed solid surfaces functionalized with organic self - assembled monolayers (SAMs) and demonstrated associated significant improvement of the...at solid-gas interfaces by self - assembled monolayers ” Applied Physics Letters 102, 061907 (2013). 2. Zhi Liang, William Evans, and Pawel Keblinski

  19. Performance prediction evaluation of ceramic materials in point-focusing solar receivers

    NASA Technical Reports Server (NTRS)

    Ewing, J.; Zwissler, J.

    1979-01-01

    A performance prediction was adapted to evaluate the use of ceramic materials in solar receivers for point focusing distributed applications. System requirements were determined including the receiver operating environment and system operating parameters for various engine types. Preliminary receiver designs were evolved from these system requirements. Specific receiver designs were then evaluated to determine material functional requirements.

  20. 77 FR 20835 - National Customs Automation Program (NCAP) Test Concerning Automated Commercial Environment (ACE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ... designed to replace a specific legacy ACS function. Each release will begin with a test and will end with... Pre-Approval Please be advised that this first phase of the DIS test is limited to the above CBP and... all interested parties to comment on the design, implementation and conduct of the test at any time...

  1. Switchable Shape Memory Alloys (SMA) Thermal Materials Project

    NASA Technical Reports Server (NTRS)

    Falker, John; Zeitlin, Nancy; Williams, Martha; Fesmire, James

    2014-01-01

    Develop 2-way switchable thermal systems for use in systems that function in cold to hot temperature ranges using different alloy designs for SMA system concepts. In this project, KSC will specifically address designs of two proof of concept SMA systems with transition temperatures in the 65-95 C range and investigate cycle fatigue and "memory loss" due to thermal cycling.

  2. Kinds of Designing and Their Functions in Analyzing

    ERIC Educational Resources Information Center

    Christenson, Mike

    2017-01-01

    In this paper, I mine the scholarly work of longtime MIT professor Donald Schön for a set of tactics which, having originated in his studies of the architectural design studio, are shown to be relevant to the architectural analysis of existing buildings. In this way, a specific and hitherto untapped potential of Schön's work is developed, but more…

  3. CONDUIT: A New Multidisciplinary Integration Environment for Flight Control Development

    NASA Technical Reports Server (NTRS)

    Tischler, Mark B.; Colbourne, Jason D.; Morel, Mark R.; Biezad, Daniel J.; Levine, William S.; Moldoveanu, Veronica

    1997-01-01

    A state-of-the-art computational facility for aircraft flight control design, evaluation, and integration called CONDUIT (Control Designer's Unified Interface) has been developed. This paper describes the CONDUIT tool and case study applications to complex rotary- and fixed-wing fly-by-wire flight control problems. Control system analysis and design optimization methods are presented, including definition of design specifications and system models within CONDUIT, and the multi-objective function optimization (CONSOL-OPTCAD) used to tune the selected design parameters. Design examples are based on flight test programs for which extensive data are available for validation. CONDUIT is used to analyze baseline control laws against pertinent military handling qualities and control system specifications. In both case studies, CONDUIT successfully exploits trade-offs between forward loop and feedback dynamics to significantly improve the expected handling, qualities and minimize the required actuator authority. The CONDUIT system provides a new environment for integrated control system analysis and design, and has potential for significantly reducing the time and cost of control system flight test optimization.

  4. Use of the Collaborative Optimization Architecture for Launch Vehicle Design

    NASA Technical Reports Server (NTRS)

    Braun, R. D.; Moore, A. A.; Kroo, I. M.

    1996-01-01

    Collaborative optimization is a new design architecture specifically created for large-scale distributed-analysis applications. In this approach, problem is decomposed into a user-defined number of subspace optimization problems that are driven towards interdisciplinary compatibility and the appropriate solution by a system-level coordination process. This decentralized design strategy allows domain-specific issues to be accommodated by disciplinary analysts, while requiring interdisciplinary decisions to be reached by consensus. The present investigation focuses on application of the collaborative optimization architecture to the multidisciplinary design of a single-stage-to-orbit launch vehicle. Vehicle design, trajectory, and cost issues are directly modeled. Posed to suit the collaborative architecture, the design problem is characterized by 5 design variables and 16 constraints. Numerous collaborative solutions are obtained. Comparison of these solutions demonstrates the influence which an priori ascent-abort criterion has on development cost. Similarly, objective-function selection is discussed, demonstrating the difference between minimum weight and minimum cost concepts. The operational advantages of the collaborative optimization

  5. Development of real-time software environments for NASA's modern telemetry systems

    NASA Technical Reports Server (NTRS)

    Horner, Ward; Sabia, Steve

    1989-01-01

    An effort has been made to maintain maximum performance and flexibility for NASA-Goddard's VLSI telemetry system elements through the development of two real-time systems: (1) the Base System Environment, which supports generic system integration and furnishes the basic porting of various manufacturers' cards, and (2) the Modular Environment for Data Systems, which supports application-specific developments and furnishes designers with a set of tested generic library functions that can be employed to speed up the development of such application-specific real-time codes. The performance goals and design rationale for these two systems are discussed.

  6. CHAMPION: Intelligent Hierarchical Reasoning Agents for Enhanced Decision Support

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

    Hohimer, Ryan E.; Greitzer, Frank L.; Noonan, Christine F.

    2011-11-15

    We describe the design and development of an advanced reasoning framework employing semantic technologies, organized within a hierarchy of computational reasoning agents that interpret domain specific information. Designed based on an inspirational metaphor of the pattern recognition functions performed by the human neocortex, the CHAMPION reasoning framework represents a new computational modeling approach that derives invariant knowledge representations through memory-prediction belief propagation processes that are driven by formal ontological language specification and semantic technologies. The CHAMPION framework shows promise for enhancing complex decision making in diverse problem domains including cyber security, nonproliferation and energy consumption analysis.

  7. SIPSim: A Modeling Toolkit to Predict Accuracy and Aid Design of DNA-SIP Experiments.

    PubMed

    Youngblut, Nicholas D; Barnett, Samuel E; Buckley, Daniel H

    2018-01-01

    DNA Stable isotope probing (DNA-SIP) is a powerful method that links identity to function within microbial communities. The combination of DNA-SIP with multiplexed high throughput DNA sequencing enables simultaneous mapping of in situ assimilation dynamics for thousands of microbial taxonomic units. Hence, high throughput sequencing enabled SIP has enormous potential to reveal patterns of carbon and nitrogen exchange within microbial food webs. There are several different methods for analyzing DNA-SIP data and despite the power of SIP experiments, it remains difficult to comprehensively evaluate method accuracy across a wide range of experimental parameters. We have developed a toolset (SIPSim) that simulates DNA-SIP data, and we use this toolset to systematically evaluate different methods for analyzing DNA-SIP data. Specifically, we employ SIPSim to evaluate the effects that key experimental parameters (e.g., level of isotopic enrichment, number of labeled taxa, relative abundance of labeled taxa, community richness, community evenness, and beta-diversity) have on the specificity, sensitivity, and balanced accuracy (defined as the product of specificity and sensitivity) of DNA-SIP analyses. Furthermore, SIPSim can predict analytical accuracy and power as a function of experimental design and community characteristics, and thus should be of great use in the design and interpretation of DNA-SIP experiments.

  8. SIPSim: A Modeling Toolkit to Predict Accuracy and Aid Design of DNA-SIP Experiments

    PubMed Central

    Youngblut, Nicholas D.; Barnett, Samuel E.; Buckley, Daniel H.

    2018-01-01

    DNA Stable isotope probing (DNA-SIP) is a powerful method that links identity to function within microbial communities. The combination of DNA-SIP with multiplexed high throughput DNA sequencing enables simultaneous mapping of in situ assimilation dynamics for thousands of microbial taxonomic units. Hence, high throughput sequencing enabled SIP has enormous potential to reveal patterns of carbon and nitrogen exchange within microbial food webs. There are several different methods for analyzing DNA-SIP data and despite the power of SIP experiments, it remains difficult to comprehensively evaluate method accuracy across a wide range of experimental parameters. We have developed a toolset (SIPSim) that simulates DNA-SIP data, and we use this toolset to systematically evaluate different methods for analyzing DNA-SIP data. Specifically, we employ SIPSim to evaluate the effects that key experimental parameters (e.g., level of isotopic enrichment, number of labeled taxa, relative abundance of labeled taxa, community richness, community evenness, and beta-diversity) have on the specificity, sensitivity, and balanced accuracy (defined as the product of specificity and sensitivity) of DNA-SIP analyses. Furthermore, SIPSim can predict analytical accuracy and power as a function of experimental design and community characteristics, and thus should be of great use in the design and interpretation of DNA-SIP experiments. PMID:29643843

  9. Scalable, Lightweight, Integrated and Quick-to-Assemble (SLIQ) Hyperdrives for Functional Circuit Dissection.

    PubMed

    Liang, Li; Oline, Stefan N; Kirk, Justin C; Schmitt, Lukas Ian; Komorowski, Robert W; Remondes, Miguel; Halassa, Michael M

    2017-01-01

    Independently adjustable multielectrode arrays are routinely used to interrogate neuronal circuit function, enabling chronic in vivo monitoring of neuronal ensembles in freely behaving animals at a single-cell, single spike resolution. Despite the importance of this approach, its widespread use is limited by highly specialized design and fabrication methods. To address this, we have developed a Scalable, Lightweight, Integrated and Quick-to-assemble multielectrode array platform. This platform additionally integrates optical fibers with independently adjustable electrodes to allow simultaneous single unit recordings and circuit-specific optogenetic targeting and/or manipulation. In current designs, the fully assembled platforms are scalable from 2 to 32 microdrives, and yet range 1-3 g, light enough for small animals. Here, we describe the design process starting from intent in computer-aided design, parameter testing through finite element analysis and experimental means, and implementation of various applications across mice and rats. Combined, our methods may expand the utility of multielectrode recordings and their continued integration with other tools enabling functional dissection of intact neural circuits.

  10. A design for an intelligent monitor and controller for space station electrical power using parallel distributed problem solving

    NASA Technical Reports Server (NTRS)

    Morris, Robert A.

    1990-01-01

    The emphasis is on defining a set of communicating processes for intelligent spacecraft secondary power distribution and control. The computer hardware and software implementation platform for this work is that of the ADEPTS project at the Johnson Space Center (JSC). The electrical power system design which was used as the basis for this research is that of Space Station Freedom, although the functionality of the processes defined here generalize to any permanent manned space power control application. First, the Space Station Electrical Power Subsystem (EPS) hardware to be monitored is described, followed by a set of scenarios describing typical monitor and control activity. Then, the parallel distributed problem solving approach to knowledge engineering is introduced. There follows a two-step presentation of the intelligent software design for secondary power control. The first step decomposes the problem of monitoring and control into three primary functions. Each of the primary functions is described in detail. Suggestions for refinements and embelishments in design specifications are given.

  11. Build-a-Brain Project: Students Design and Model the Brain of an Imaginary Animal

    ERIC Educational Resources Information Center

    Demetrikopoulos, Melissa K.; Pecore, John; Rose, Jordan D.; Fobbs, Archibald J., Jr.; Johnson, John I.; Carruth, Laura L.

    2006-01-01

    The brain is a truly fascinating structure! It controls the body and allows everyone to think, learn, speak, move, feel, remember, and experience emotions. Although the brain is a single organ, it is very complex and has several regions, each having a specific function. These functionally diverse regions work together to allow for coordination of…

  12. Promoting Secondary Teachers' Diagnostic Competence with Respect to Functions: Development of a Scalable Unit in Continuous Professional Development

    ERIC Educational Resources Information Center

    Busch, Julia; Barzel, Bärbel; Leuders, Timo

    2015-01-01

    Diagnosing student achievement in a formative way is a crucial skill for planning and carrying out effective mathematics lessons. This study takes a subject-specific view and aims at investigating diagnostic competence in the field of mathematical functions at secondary level and how to improve it. Following three evidence-based design principles,…

  13. Integrating self-determined needs into the relationship among product design, willingness-to-pay a premium, and word-of-mouth: a cross-cultural gender-specific study.

    PubMed

    Gilal, Faheem Gul; Zhang, Jian; Gilal, Naeem Gul; Gilal, Rukhsana Gul

    2018-01-01

    The present study integrates self-determined needs satisfaction into a relationship between product design (eg, aesthetic, functional, and symbolic design) and consumer behavior (eg, willingness-to-pay [WTP] a premium and negative word-of-mouth [WOM]) and to explore whether gender can differentiate the effects of aesthetic, functional, and symbolic product designs on self-determined needs satisfaction. To this end, participants from Pakistan and China were recruited, and the hypotheses for this study were tested using structural equation modeling and SPSS-PROCESS. The effects of three product designs on self-determined needs satisfaction were significantly positive across samples. The results further show that self-determined needs satisfaction had the strongest positive effect on WTP a premium and the strongest negative effect on vindictive WOM for Pakistanis. Self-determined needs frustration had the strongest negative effect on the WTP a premium for Chinese participants and an equivalent magnitude effect on vindictive WOM for Pakistani and Chinese participants. The cross-cultural gender-specific findings revealed that Pakistani men are more aesthetic and hedonic than women in Pakistan. Surprisingly, Chinese women resemble Pakistani men in the sense that they prefer aesthetically pleasing products. Chinese men resemble Pakistani women in terms of little interest in symbolic products, whereas Chinese women and Pakistani men respond similarly regarding their decisions to choose symbolic products. To the best of the authors' knowledge, the present study is one of the initial attempts to integrate self-determined needs into the relationship between product design and consumer WTP a premium and WOM, and further explore cross-cultural gender-specific differences across Pakistan and China. The findings of the present study may help international marketers in terms of segmenting, targeting, and positioning their markets.

  14. ChemTrove: enabling a generic ELN to support chemistry through the use of transferable plug-ins and online data sources.

    PubMed

    Day, Aileen E; Coles, Simon J; Bird, Colin L; Frey, Jeremy G; Whitby, Richard J; Tkachenko, Valery E; Williams, Antony J

    2015-03-23

    In designing an Electronic Lab Notebook (ELN), there is a balance to be struck between keeping it as general and multidisciplinary as possible for simplicity of use and maintenance and introducing more domain-specific functionality to increase its appeal to target research areas. Here, we describe the results of a collaboration between the Royal Society of Chemistry (RSC) and the University of Southampton, guided by the aims of the Dial-a-Molecule Grand Challenge, intended to achieve the best of both worlds and augment a discipline-agnostic ELN, LabTrove, with chemistry-specific functionality and using data provided by the ChemSpider platform. This has been done using plug-in technology to ensure maximum transferability with minimal effort of the chemistry functionality to other ELNs and equally other subject-specific functionality to LabTrove. The resulting product, ChemTrove, has undergone a usability trial by selected academics, and the resulting feedback will guide the future development of the underlying ELN technology.

  15. Sequences Associated with Centromere Competency in the Human Genome

    PubMed Central

    Hayden, Karen E.; Strome, Erin D.; Merrett, Stephanie L.; Lee, Hye-Ran; Rudd, M. Katharine

    2013-01-01

    Centromeres, the sites of spindle attachment during mitosis and meiosis, are located in specific positions in the human genome, normally coincident with diverse subsets of alpha satellite DNA. While there is strong evidence supporting the association of some subfamilies of alpha satellite with centromere function, the basis for establishing whether a given alpha satellite sequence is or is not designated a functional centromere is unknown, and attempts to understand the role of particular sequence features in establishing centromere identity have been limited by the near identity and repetitive nature of satellite sequences. Utilizing a broadly applicable experimental approach to test sequence competency for centromere specification, we have carried out a genomic and epigenetic functional analysis of endogenous human centromere sequences available in the current human genome assembly. The data support a model in which functionally competent sequences confer an opportunity for centromere specification, integrating genomic and epigenetic signals and promoting the concept of context-dependent centromere inheritance. PMID:23230266

  16. Preliminary design package for solar heating and hot water system

    NASA Technical Reports Server (NTRS)

    1977-01-01

    The preliminary design review on the development of two prototype solar heating and hot water systems is presented. The information contained in this report includes system certification, system functional description, system configuration, system specification, system performance and other documents pertaining to the progress and the design of the system. This system, which is intended for use in the normal single-family residence, consists of the following subsystems: collector, storage, control, transport, and Government-furnished Site Data Acquisition.

  17. P/CAF Function in Transcriptional Activation by Steroid Hormone Receptors and Mammary Cell Proliferation

    DTIC Science & Technology

    1999-07-01

    author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation...material. Where material from documents designated for limited distribution is quoted, permission has been obtained to use the material. Citations of...mammary tissue in the PCAF knock out mice, was actually completed last year. We are beginning the design and cloning of the breast-specific knock out

  18. [Application of digital design and three-dimensional printing technique on individualized medical treatment].

    PubMed

    Qin, Mian; Liu, Yaxiong; He, Jiankang; Wang, Ling; Lian, Qin; Li, Dichen; Jin, Zhongmin; He, Sanhu; Li, Gang; Liu, Yanpu; Wang, Zhen

    2014-03-01

    To summarize the latest research development of the application of digital design and three-dimensional (3-D) printing technique on individualized medical treatment. Recent research data and clinical literature about the application of digital design and 3-D printing technique on individualized medical treatment in Xi'an Jiaotong University and its cooperation unit were summarized, reviewed, and analyzed. Digital design and 3-D printing technique can design and manufacture individualized implant based on the patient's specific disease conditions. And the implant can satisfy the needs of specific shape and function of the patient, reducing dependence on the level of experience required for the doctor. So 3-D printing technique get more and more recognition of the surgeon on the individualized repair of human tissue. Xi'an Jiaotong University is the first unit to develop the commercial 3-D printer and conduct depth research on the design and manufacture of individualized medical implant. And complete technological processes and quality standards of product have been developed. The individualized medical implant manufactured by 3-D printing technique can not only achieve personalized match but also meet the functional requirements and aesthetic requirements of patients. In addition, the individualized medical implant has the advantages of accurate positioning, stable connection, and high strength. So 3-D printing technique has broad prospects in the manufacture and application of individualized implant.

  19. A new computerized cognitive and social cognition training specifically designed for patients with schizophrenia/schizoaffective disorder in early stages of illness: A pilot study.

    PubMed

    Fernandez-Gonzalo, Sol; Turon, Marc; Jodar, Merce; Pousa, Esther; Hernandez Rambla, Carla; García, Rebeca; Palao, Diego

    2015-08-30

    People with schizophrenia/schizoaffective disorders at early stages of the illness present cognitive and social cognition deficits that have a great impact in functional outcomes. Cognitive Remediation Therapy (CRT) has demonstrated consistent effect in cognitive performance, symptoms and psychosocial functioning. However, any CRT intervention or social cognition training have been specifically designed for patients in the early stages of psychosis. The aim of this pilot study is to assess the efficacy of a new computerized cognitive and social cognition program for patients with schizophrenia/schizoaffective disorder with recent diagnosis. A comprehensive assessment of clinical, social and non-social cognitive and functional measures was carried out in 53 randomized participants before and after the 4-months treatment. Significant results were observed in Spatial Span Forwards, Immediate Logical Memory and Pictures of Facial Affect (POFA) total score. None of these results were explained by medication, premorbid social functioning or psychopathological symptoms. No impact of the intervention was observed in other cognitive and social cognition outcome neither in clinical and functional outcomes. This new computerized intervention may result effective ameliorating visual attention, logical memory and emotional processing in patients in the early stages of schizophrenia/schizoaffective disorder. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Systems engineering principles for the design of biomedical signal processing systems.

    PubMed

    Faust, Oliver; Acharya U, Rajendra; Sputh, Bernhard H C; Min, Lim Choo

    2011-06-01

    Systems engineering aims to produce reliable systems which function according to specification. In this paper we follow a systems engineering approach to design a biomedical signal processing system. We discuss requirements capturing, specification definition, implementation and testing of a classification system. These steps are executed as formal as possible. The requirements, which motivate the system design, are based on diabetes research. The main requirement for the classification system is to be a reliable component of a machine which controls diabetes. Reliability is very important, because uncontrolled diabetes may lead to hyperglycaemia (raised blood sugar) and over a period of time may cause serious damage to many of the body systems, especially the nerves and blood vessels. In a second step, these requirements are refined into a formal CSP‖ B model. The formal model expresses the system functionality in a clear and semantically strong way. Subsequently, the proven system model was translated into an implementation. This implementation was tested with use cases and failure cases. Formal modeling and automated model checking gave us deep insight in the system functionality. This insight enabled us to create a reliable and trustworthy implementation. With extensive tests we established trust in the reliability of the implementation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  1. A Framework for Robust Multivariable Optimization of Integrated Circuits in Space Applications

    NASA Technical Reports Server (NTRS)

    DuMonthier, Jeffrey; Suarez, George

    2013-01-01

    Application Specific Integrated Circuit (ASIC) design for space applications involves multiple challenges of maximizing performance, minimizing power and ensuring reliable operation in extreme environments. This is a complex multidimensional optimization problem which must be solved early in the development cycle of a system due to the time required for testing and qualification severely limiting opportunities to modify and iterate. Manual design techniques which generally involve simulation at one or a small number of corners with a very limited set of simultaneously variable parameters in order to make the problem tractable are inefficient and not guaranteed to achieve the best possible results within the performance envelope defined by the process and environmental requirements. What is required is a means to automate design parameter variation, allow the designer to specify operational constraints and performance goals, and to analyze the results in a way which facilitates identifying the tradeoffs defining the performance envelope over the full set of process and environmental corner cases. The system developed by the Mixed Signal ASIC Group (MSAG) at the Goddard Space Flight Center is implemented as framework of software modules, templates and function libraries. It integrates CAD tools and a mathematical computing environment, and can be customized for new circuit designs with only a modest amount of effort as most common tasks are already encapsulated. Customization is required for simulation test benches to determine performance metrics and for cost function computation. Templates provide a starting point for both while toolbox functions minimize the code required. Once a test bench has been coded to optimize a particular circuit, it is also used to verify the final design. The combination of test bench and cost function can then serve as a template for similar circuits or be re-used to migrate the design to different processes by re-running it with the new process specific device models. The system has been used in the design of time to digital converters for laser ranging and time-of-flight mass spectrometry to optimize analog, mixed signal and digital circuits such as charge sensitive amplifiers, comparators, delay elements, radiation tolerant dual interlocked (DICE) flip-flops and two of three voter gates.

  2. Prevention of errors and user alienation in healthcare IT integration programmes.

    PubMed

    Benson, Tim

    2007-01-01

    The design, development and implementation stages of integrated computer projects require close collaboration between users and developers, but this is particularly difficult where there are multiple specialties, organisations and system suppliers. Users become alienated if they are not consulted, but consultation is meaningless if they cannot understand the specifications showing exactly what is proposed. We need stringent specifications that users and developers can review and check before most of the work is done. Avoidable errors lead to delays and cost over-runs. The number of errors is a function of the likelihood of misunderstanding any part of the specification, the number of individuals involved and the number of choices or options. One way to reduce these problems is to provide a conceptual design specification, comprising detailed Unified Modelling Language (UML) class and activity diagrams, data definitions and terminology, in addition to conventional technology-specific specifications. A conceptual design specification needs to be straightforward to understand and use, transparent and unambiguous. People find structured diagrams, such as maps, charts and blueprints, easier to use than reports or tables. Other desirable properties include being technology-independent, comprehensive, stringent, coherent, consistent, composed from reusable elements and computer-readable (XML). When users and developers share the same agreed conceptual design specification, this can be one of the master documents of a formal contract between the stakeholders. No extra meaning should be added during the later stages of the project life cycle.

  3. Validation of Shared and Specific Independent Component Analysis (SSICA) for Between-Group Comparisons in fMRI

    PubMed Central

    Maneshi, Mona; Vahdat, Shahabeddin; Gotman, Jean; Grova, Christophe

    2016-01-01

    Independent component analysis (ICA) has been widely used to study functional magnetic resonance imaging (fMRI) connectivity. However, the application of ICA in multi-group designs is not straightforward. We have recently developed a new method named “shared and specific independent component analysis” (SSICA) to perform between-group comparisons in the ICA framework. SSICA is sensitive to extract those components which represent a significant difference in functional connectivity between groups or conditions, i.e., components that could be considered “specific” for a group or condition. Here, we investigated the performance of SSICA on realistic simulations, and task fMRI data and compared the results with one of the state-of-the-art group ICA approaches to infer between-group differences. We examined SSICA robustness with respect to the number of allowable extracted specific components and between-group orthogonality assumptions. Furthermore, we proposed a modified formulation of the back-reconstruction method to generate group-level t-statistics maps based on SSICA results. We also evaluated the consistency and specificity of the extracted specific components by SSICA. The results on realistic simulated and real fMRI data showed that SSICA outperforms the regular group ICA approach in terms of reconstruction and classification performance. We demonstrated that SSICA is a powerful data-driven approach to detect patterns of differences in functional connectivity across groups/conditions, particularly in model-free designs such as resting-state fMRI. Our findings in task fMRI show that SSICA confirms results of the general linear model (GLM) analysis and when combined with clustering analysis, it complements GLM findings by providing additional information regarding the reliability and specificity of networks. PMID:27729843

  4. Turboelectric Aircraft Drive Key Performance Parameters and Functional Requirements

    NASA Technical Reports Server (NTRS)

    Jansen, Ralph H.; Brown, Gerald V.; Felder, James L.; Duffy, Kirsten P.

    2016-01-01

    The purpose of this paper is to propose specific power and efficiency as the key performance parameters for a turboelectric aircraft power system and investigate their impact on the overall aircraft. Key functional requirements are identified that impact the power system design. Breguet range equations for a base aircraft and a turboelectric aircraft are found. The benefits and costs that may result from the turboelectric system are enumerated. A break-even analysis is conducted to find the minimum allowable electric drive specific power and efficiency that can preserve the range, initial weight, operating empty weight, and payload weight of the base aircraft.

  5. Turboelectric Aircraft Drive Key Performance Parameters and Functional Requirements

    NASA Technical Reports Server (NTRS)

    Jansen, Ralph; Brown, Gerald V.; Felder, James L.; Duffy, Kirsten P.

    2015-01-01

    The purpose of this presentation is to propose specific power and efficiency as the key performance parameters for a turboelectric aircraft power system and investigate their impact on the overall aircraft. Key functional requirements are identified that impact the power system design. Breguet range equations for a base aircraft and a turboelectric aircraft are found. The benefits and costs that may result from the turboelectric system are enumerated. A break-even analysis is conducted to find the minimum allowable electric drive specific power and efficiency that can preserve the range, initial weight, operating empty weight, and payload weight of the base aircraft.

  6. Turboelectric Aircraft Drive Key Performance Parameters and Functional Requirements

    NASA Technical Reports Server (NTRS)

    Jansen, Ralph H.; Brown, Gerald V.; Felder, James L.; Duffy, Kirsten P.

    2015-01-01

    The purpose of this paper is to propose specific power and efficiency as the key performance parameters for a turboelectric aircraft power system and investigate their impact on the overall aircraft. Key functional requirements are identified that impact the power system design. Breguet range equations for a base aircraft and a turboelectric aircraft are found. The benefits and costs that may result from the turboelectric system are enumerated. A break-even analysis is conducted to find the minimum allowable electric drive specific power and efficiency that can preserve the range, initial weight, operating empty weight, and payload weight of the base aircraft.

  7. Analysis of tasks for dynamic man/machine load balancing in advanced helicopters

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

    Jorgensen, C.C.

    1987-10-01

    This report considers task allocation requirements imposed by advanced helicopter designs incorporating mixes of human pilots and intelligent machines. Specifically, it develops an analogy between load balancing using distributed non-homogeneous multiprocessors and human team functions. A taxonomy is presented which can be used to identify task combinations likely to cause overload for dynamic scheduling and process allocation mechanisms. Designer criteria are given for function decomposition, separation of control from data, and communication handling for dynamic tasks. Possible effects of n-p complete scheduling problems are noted and a class of combinatorial optimization methods are examined.

  8. A direct approach to the design of linear multivariable systems

    NASA Technical Reports Server (NTRS)

    Agrawal, B. L.

    1974-01-01

    Design of multivariable systems is considered and design procedures are formulated in the light of the most recent work on model matching. The word model matching is used exclusively to mean matching the input-output behavior of two systems. The term is used in the frequency domain to indicate the comparison of two transfer matrices containing transfer functions as elements. Design methods where non-interaction is not used as a criteria were studied. Two design methods are considered. The first method of design is based solely upon the specification of generalized error coefficients for each individual transfer function of the overall system transfer matrix. The second design method is called the pole fixing method because all the system poles are fixed at preassigned positions. The zeros of terms either above or below the diagonal are partially fixed via steady state error coefficients. The advantages and disadvantages of each method are discussed and an example is worked to demonstrate their uses. The special cases of triangular decoupling and minimum constraints are discussed.

  9. The Importance of Information Requirements in Designing Acquisition to Information Systems

    NASA Technical Reports Server (NTRS)

    Davis, Bruce A.; Hill, Chuck; Maughan, Paul M.

    1998-01-01

    The partnership model used by NASA's Commercial Remote Sensing Program has been successful in better defining remote sensing functional requirements and translation to technical specifications to address environmental needs of the 21st century.

  10. Asteroid Crewed Segment Mission Lean Development

    NASA Technical Reports Server (NTRS)

    Gard, Joe; McDonald, Mark; Jermstad, Wayne

    2014-01-01

    The next generation of human spaceflight missions presents numerous challenges to designers that must be addressed to produce a feasible concept. The specific challenges of designing an exploration mission utilizing the Space Launch System and the Orion spacecraft to carry astronauts beyond earth orbit to explore an asteroid stored in a distant retrograde orbit around the moon will be addressed. Mission designers must carefully balance competing constraints including cost, schedule, risk, and numerous spacecraft performance metrics including launch mass, nominal landed mass, abort landed mass, mission duration, consumable limits and many others. The Asteroid Redirect Crewed Mission will be described along with results from the concurrent mission design trades that led to its formulation. While the trades presented are specific to this mission, the integrated process is applicable to any potential future mission. The following trades were critical in the mission formulation and will be described in detail: 1) crew size, 2) mission duration, 3) trajectory design, 4) docking vs grapple, 5) extravehicular activity tasks, 6) launch mass and integrated vehicle performance, 7) contingency performance, 8) crew consumables including food, clothing, oxygen, nitrogen and water, and 9) mission risk. The additional Orion functionality required to perform the Asteroid Redirect Crewed Mission and how it is incorporated while minimizing cost, schedule and mass impacts will be identified. Existing investments in the NASA technology portfolio were leveraged to provide the added functionality that will be beneficial to future exploration missions. Mission kits are utilized to augment Orion with the necessary functionality without introducing costly new requirements to the mature Orion spacecraft design effort. The Asteroid Redirect Crewed Mission provides an exciting early mission for the Orion and SLS while providing a stepping stone to even more ambitious missions in the future.

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

    Janjusic, Tommy; Kartsaklis, Christos

    Memory scalability is an enduring problem and bottleneck that plagues many parallel codes. Parallel codes designed for High Performance Systems are typically designed over the span of several, and in some instances 10+, years. As a result, optimization practices which were appropriate for earlier systems may no longer be valid and thus require careful optimization consideration. Specifically, parallel codes whose memory footprint is a function of their scalability must be carefully considered for future exa-scale systems. In this paper we present a methodology and tool to study the memory scalability of parallel codes. Using our methodology we evaluate an applicationmore » s memory footprint as a function of scalability, which we coined memory efficiency, and describe our results. In particular, using our in-house tools we can pinpoint the specific application components which contribute to the application s overall memory foot-print (application data- structures, libraries, etc.).« less

  12. Graphical method to design multilayer phase retarders.

    PubMed

    Apfel, J H

    1981-03-15

    When multilayer reflectors are used at nonnormal incidence, the two planes of polarization generally have different phase shifts. This difference, known as phase retardance, depends on the multilayer design, the incidence angle, and the wavelength. Heretofore, the design of reflectors with specific phase retardance has been carried out by computer optimization except for the case of a single layer on a metal substrate. A graph of phase retardance D vs the average phase shift A as a function of layer thickness provides a means for visualization that is useful in reflector designs. A D-A graph predicts the phase properties of a reflector as a function of the index and thickness of an added layer. Graphs of phase retardance vs average phase for two different materials can be superposed to predict the composite performance of a multilayer reflector. This graphical technique is employed to design and analyze reflectors with specified phase retardance.

  13. Design of transparent conductors and periodic two-dimensional electron gases without doping

    NASA Astrophysics Data System (ADS)

    Zhang, Xiuwen; Zhang, Lijun; Zunger, Alex; Perkins, John; Materials by Design Team; John D. Perkins Collaboration

    The functionality of transparency plus conductivity plays an important role in renewable energy and information technologies, including applications such as solar cells, touch-screen sensors, and flat panel display. However, materials with such seemingly contraindicated properties are difficult to come by. The traditional strategy for designing bulk transparent conductors (TCs) starts from a wide-gap insulator and finds ways to make it conductive by extensive doping. We propose a different strategy for TC design--starting with a metallic conductor and designing transparency by control of intrinsic interband transitions and intraband plasmonic frequency. We identified specific design principles for prototypical intrinsic TC classes and searched computationally for materials that satisfy them. The electron gases in the 3D intrinsic TCs demonstrate intriguing properties, such as periodic 2D electron gas regions with very high carrier density. We will discuss a more extended search of these functionalities, in parallel with stability and growability calculations

  14. Compact representation of continuous energy surfaces for more efficient protein design

    PubMed Central

    Hallen, Mark A.; Gainza, Pablo; Donald, Bruce R.

    2015-01-01

    In macromolecular design, conformational energies are sensitive to small changes in atom coordinates, so modeling the small, continuous motions of atoms around low-energy wells confers a substantial advantage in structural accuracy; however, modeling these motions comes at the cost of a very large number of energy function calls, which form the bottleneck in the design calculation. In this work, we remove this bottleneck by consolidating all conformational energy evaluations into the precomputation of a local polynomial expansion of the energy about the “ideal” conformation for each low-energy, “rotameric” state of each residue pair. This expansion is called Energy as Polynomials in Internal Coordinates (EPIC), where the internal coordinates can be sidechain dihedrals, backrub angles, and/or any other continuous degrees of freedom of a macromolecule, and any energy function can be used without adding any asymptotic complexity to the design. We demonstrate that EPIC efficiently represents the energy surface for both molecular-mechanics and quantum-mechanical energy functions, and apply it specifically to protein design to model both sidechain and backbone degrees of freedom. PMID:26089744

  15. Approximate analytical relationships for linear optimal aeroelastic flight control laws

    NASA Astrophysics Data System (ADS)

    Kassem, Ayman Hamdy

    1998-09-01

    This dissertation introduces new methods to uncover functional relationships between design parameters of a contemporary control design technique and the resulting closed-loop properties. Three new methods are developed for generating such relationships through analytical expressions: the Direct Eigen-Based Technique, the Order of Magnitude Technique, and the Cost Function Imbedding Technique. Efforts concentrated on the linear-quadratic state-feedback control-design technique applied to an aeroelastic flight control task. For this specific application, simple and accurate analytical expressions for the closed-loop eigenvalues and zeros in terms of basic parameters such as stability and control derivatives, structural vibration damping and natural frequency, and cost function weights are generated. These expressions explicitly indicate how the weights augment the short period and aeroelastic modes, as well as the closed-loop zeros, and by what physical mechanism. The analytical expressions are used to address topics such as damping, nonminimum phase behavior, stability, and performance with robustness considerations, and design modifications. This type of knowledge is invaluable to the flight control designer and would be more difficult to formulate when obtained from numerical-based sensitivity analysis.

  16. Numerical simulation study on the optimization design of the crown shape of PDC drill bit.

    PubMed

    Ju, Pei; Wang, Zhenquan; Zhai, Yinghu; Su, Dongyu; Zhang, Yunchi; Cao, Zhaohui

    The design of bit crown is an important part of polycrystalline diamond compact (PDC) bit design, although predecessors have done a lot of researches on the design principles of PDC bit crown, the study of the law about rock-breaking energy consumption according to different bit crown shape is not very systematic, and the mathematical model of design is over-simplified. In order to analyze the relation between rock-breaking energy consumption and bit crown shape quantificationally, the paper puts forward an idea to take "per revolution-specific rock-breaking work" as objective function, and analyzes the relationship between rock properties, inner cone angle, outer cone arc radius, and per revolution-specific rock-breaking work by means of explicit dynamic finite element method. Results show that the change law between per revolution-specific rock-breaking work and the radius of gyration is similar for rocks with different properties, it is beneficial to decrease rock-breaking energy consumption by decreasing inner cone angle or outer cone arc radius. Of course, we should also consider hydraulic structure and processing technology in the optimization design of PDC bit crown.

  17. Design of Neural Networks for Fast Convergence and Accuracy

    NASA Technical Reports Server (NTRS)

    Maghami, Peiman G.; Sparks, Dean W., Jr.

    1998-01-01

    A novel procedure for the design and training of artificial neural networks, used for rapid and efficient controls and dynamics design and analysis for flexible space systems, has been developed. Artificial neural networks are employed to provide a means of evaluating the impact of design changes rapidly. Specifically, two-layer feedforward neural networks are designed to approximate the functional relationship between the component spacecraft design changes and measures of its performance. A training algorithm, based on statistical sampling theory, is presented, which guarantees that the trained networks provide a designer-specified degree of accuracy in mapping the functional relationship. Within each iteration of this statistical-based algorithm, a sequential design algorithm is used for the design and training of the feedforward network to provide rapid convergence to the network goals. Here, at each sequence a new network is trained to minimize the error of previous network. The design algorithm attempts to avoid the local minima phenomenon that hampers the traditional network training. A numerical example is performed on a spacecraft application in order to demonstrate the feasibility of the proposed approach.

  18. Traumatic fifth finger amputation due to pontoon boat railing design.

    PubMed

    Sullivan, John C; Buckner, Billy; Pigott, David C

    2012-12-01

    Boating is a common recreational activity that may subject its participants to specific patterns of injury. We describe two unrelated cases of fifth-finger amputation associated with a specific pontoon boat guardrail design. The individuals in these cases sustained an avulsion-type amputation injury to the fifth finger when their fingers became entrapped in a narrowed portion of the boat railing before jumping into the water. Given the widespread use of this type of recreational boat, this apparent design flaw may place additional individuals at risk of significant hand injury with cosmetic and functional loss. Methods to reduce the public health impact of this type of injury are also discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Rational approaches for engineering novel functionalities in carbon-carbon bond forming enzymes

    PubMed Central

    Baker, Perrin; Seah, Stephen Y. K.

    2012-01-01

    Enzymes that catalyze carbon-carbon bond formation can be exploited as biocatalyst for synthetic organic chemistry. However, natural enzymes frequently do not possess the required properties or specificities to catalyze industrially useful transformations. This mini-review describes recent work using knowledge-guided site-specific mutagenesis of key active site residues to alter substrate specificity, stereospecificity and reaction specificity of these enzymes. In addition, examples of de novo designed enzymes that catalyze C-C bond reactions not found in nature will be discussed. PMID:24688644

  20. Pore surface engineering in covalent organic frameworks.

    PubMed

    Nagai, Atsushi; Guo, Zhaoqi; Feng, Xiao; Jin, Shangbin; Chen, Xiong; Ding, Xuesong; Jiang, Donglin

    2011-11-15

    Covalent organic frameworks (COFs) are a class of important porous materials that allow atomically precise integration of building blocks to achieve pre-designable pore size and geometry; however, pore surface engineering in COFs remains challenging. Here we introduce pore surface engineering to COF chemistry, which allows the controlled functionalization of COF pore walls with organic groups. This functionalization is made possible by the use of azide-appended building blocks for the synthesis of COFs with walls to which a designable content of azide units is anchored. The azide units can then undergo a quantitative click reaction with alkynes to produce pore surfaces with desired groups and preferred densities. The diversity of click reactions performed shows that the protocol is compatible with the development of various specific surfaces in COFs. Therefore, this methodology constitutes a step in the pore surface engineering of COFs to realize pre-designed compositions, components and functions.

  1. Human factor implications of the Eurocopter AS332L-1 Super Puma cockpit

    NASA Technical Reports Server (NTRS)

    Padfield, R. Randall

    1993-01-01

    The purpose of this paper is to identify and describe some of the human factor problems which can occur in the cockpit of a modern civilian helicopter. After examining specific hardware and software problems in the cockpit design of the Eurocopter (Aerospatiale) AS332L-1 Super Puma, the author proposes several principles that can be used to avoid similar human factors problems in the design of future cockpits. These principles relate to the use and function of warning lights, the design of autopilots in two-pilot aircraft, and the labeling of switches and warning lights, specifically with respect to abbreviations and translations from languages other than English. In the final section of the paper, the author describes current trends in society which he suggests should be taken into consideration when designing future aircraft cockpits.

  2. Design of a clinical notification system.

    PubMed

    Wagner, M M; Tsui, F C; Pike, J; Pike, L

    1999-01-01

    We describe the requirements and design of an enterprise-wide notification system. From published descriptions of notification schemes, our own experience, and use cases provided by diverse users in our institution, we developed a set of functional requirements. The resulting design supports multiple communication channels, third party mappings (algorithms) from message to recipient and/or channel of delivery, and escalation algorithms. A requirement for multiple message formats is addressed by a document specification. We implemented this system in Java as a CORBA object. This paper describes the design and current implementation of our notification system.

  3. Evaluation of an exercise concept focusing on eccentric strength training of the rotator cuff for patients with subacromial impingement syndrome.

    PubMed

    Bernhardsson, Susanne; Klintberg, Ingrid Hultenheim; Wendt, Gunilla Kjellby

    2011-01-01

    To evaluate the effect on pain intensity and function of an exercise concept focusing on specific eccentric strength training of the rotator cuff in patients with subacromial impingement syndrome. Single-subject research design with baseline and treatment phases (AB design). Home-based training programme supervised and supported by visits to physiotherapy clinic. Ten patients, mean (SD) age 54 (8.6) years, symptom duration 12 (9.1) months. Daily eccentric strengthening exercises of the rotator cuff during 12 weeks. Pain intensity, assessed with a visual analogue scale, and function, using the Patient-Specific Functional Scale. Shoulder function evaluated with the Constant score, and shoulder-related quality of life evaluated with the Western Ontario Rotator Cuff Index. Pain intensity decreased significantly in eight of the ten subjects. Function improved significantly in all ten subjects. Constant score increased in nine subjects and Western Ontario Rotator Cuff Index increased in seven subjects. Mean Constant score for the whole group increased significantly from 44 to 69 points (P = 0.008). Mean Western Ontario Rotator Cuff Index increased from 51 to 71% (P = 0.021). A 12-week eccentric strengthening programme targeting the rotator cuff and incorporating scapular control and correct movement pattern can be effective in decreasing pain and increasing function in patients with subacromial impingement syndrome. A randomized controlled trial is necessary to provide stronger evidence of the method.

  4. Formal specification and verification of Ada software

    NASA Technical Reports Server (NTRS)

    Hird, Geoffrey R.

    1991-01-01

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

  5. Parametric fMRI of paced motor responses uncovers novel whole-brain imaging biomarkers in spinocerebellar ataxia type 3.

    PubMed

    Duarte, João Valente; Faustino, Ricardo; Lobo, Mercês; Cunha, Gil; Nunes, César; Ferreira, Carlos; Januário, Cristina; Castelo-Branco, Miguel

    2016-10-01

    Machado-Joseph Disease, inherited type 3 spinocerebellar ataxia (SCA3), is the most common form worldwide. Neuroimaging and neuropathology have consistently demonstrated cerebellar alterations. Here we aimed to discover whole-brain functional biomarkers, based on parametric performance-level-dependent signals. We assessed 13 patients with early SCA3 and 14 healthy participants. We used a combined parametric behavioral/functional neuroimaging design to investigate disease fingerprints, as a function of performance levels, coupled with structural MRI and voxel-based morphometry. Functional magnetic resonance imaging (fMRI) was designed to parametrically analyze behavior and neural responses to audio-paced bilateral thumb movements at temporal frequencies of 1, 3, and 5 Hz. Our performance-level-based design probing neuronal correlates of motor coordination enabled the discovery that neural activation and behavior show critical loss of parametric modulation specifically in SCA3, associated with frequency-dependent cortico/subcortical activation/deactivation patterns. Cerebellar/cortical rate-dependent dissociation patterns could clearly differentiate between groups irrespective of grey matter loss. Our findings suggest functional reorganization of the motor network and indicate a possible role of fMRI as a tool to monitor disease progression in SCA3. Accordingly, fMRI patterns proved to be potential biomarkers in early SCA3, as tested by receiver operating characteristic analysis of both behavior and neural activation at different frequencies. Discrimination analysis based on BOLD signal in response to the applied parametric finger-tapping task significantly often reached >80% sensitivity and specificity in single regions-of-interest.Functional fingerprints based on cerebellar and cortical BOLD performance dependent signal modulation can thus be combined as diagnostic and/or therapeutic targets in hereditary ataxia. Hum Brain Mapp 37:3656-3668, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Engineering of the function of diamond-like carbon binding peptides through structural design.

    PubMed

    Gabryelczyk, Bartosz; Szilvay, Géza R; Singh, Vivek K; Mikkilä, Joona; Kostiainen, Mauri A; Koskinen, Jari; Linder, Markus B

    2015-02-09

    The use of phage display to select material-specific peptides provides a general route towards modification and functionalization of surfaces and interfaces. However, a rational structural engineering of the peptides for optimal affinity is typically not feasible because of insufficient structure-function understanding. Here, we investigate the influence of multivalency of diamond-like carbon (DLC) binding peptides on binding characteristics. We show that facile linking of peptides together using different lengths of spacers and multivalency leads to a tuning of affinity and kinetics. Notably, increased length of spacers in divalent systems led to significantly increased affinities. Making multimers influenced also kinetic aspects of surface competition. Additionally, the multivalent peptides were applied as surface functionalization components for a colloidal form of DLC. The work suggests the use of a set of linking systems to screen parameters for functional optimization of selected material-specific peptides.

  7. Engineering integrated digital circuits with allosteric ribozymes for scaling up molecular computation and diagnostics.

    PubMed

    Penchovsky, Robert

    2012-10-19

    Here we describe molecular implementations of integrated digital circuits, including a three-input AND logic gate, a two-input multiplexer, and 1-to-2 decoder using allosteric ribozymes. Furthermore, we demonstrate a multiplexer-decoder circuit. The ribozymes are designed to seek-and-destroy specific RNAs with a certain length by a fully computerized procedure. The algorithm can accurately predict one base substitution that alters the ribozyme's logic function. The ability to sense the length of RNA molecules enables single ribozymes to be used as platforms for multiple interactions. These ribozymes can work as integrated circuits with the functionality of up to five logic gates. The ribozyme design is universal since the allosteric and substrate domains can be altered to sense different RNAs. In addition, the ribozymes can specifically cleave RNA molecules with triplet-repeat expansions observed in genetic disorders such as oculopharyngeal muscular dystrophy. Therefore, the designer ribozymes can be employed for scaling up computing and diagnostic networks in the fields of molecular computing and diagnostics and RNA synthetic biology.

  8. Decision Support System Requirements Definition for Human Extravehicular Activity Based on Cognitive Work Analysis

    PubMed Central

    Miller, Matthew James; McGuire, Kerry M.; Feigh, Karen M.

    2016-01-01

    The design and adoption of decision support systems within complex work domains is a challenge for cognitive systems engineering (CSE) practitioners, particularly at the onset of project development. This article presents an example of applying CSE techniques to derive design requirements compatible with traditional systems engineering to guide decision support system development. Specifically, it demonstrates the requirements derivation process based on cognitive work analysis for a subset of human spaceflight operations known as extravehicular activity. The results are presented in two phases. First, a work domain analysis revealed a comprehensive set of work functions and constraints that exist in the extravehicular activity work domain. Second, a control task analysis was performed on a subset of the work functions identified by the work domain analysis to articulate the translation of subject matter states of knowledge to high-level decision support system requirements. This work emphasizes an incremental requirements specification process as a critical component of CSE analyses to better situate CSE perspectives within the early phases of traditional systems engineering design. PMID:28491008

  9. Design of Tunable Oscillatory Dynamics in a Synthetic NF-κB Signaling Circuit.

    PubMed

    Zhang, Zhi-Bo; Wang, Qiu-Yue; Ke, Yu-Xi; Liu, Shi-Yu; Ju, Jian-Qi; Lim, Wendell A; Tang, Chao; Wei, Ping

    2017-11-22

    Although oscillatory circuits are prevalent in transcriptional regulation, it is unclear how a circuit's structure and the specific parameters that describe its components determine the shape of its oscillations. Here, we engineer a minimal, inducible human nuclear factor κB (NF-κB)-based system that is composed of NF-κB (RelA) and degradable inhibitor of NF-κB (IκBα), into the yeast, Saccharomyces cerevisiae. We define an oscillation's waveform quantitatively as a function of signal amplitude, rest time, rise time, and decay time; by systematically tuning RelA concentration, the strength of negative feedback, and the degradation rate of IκBα, we demonstrate that peak shape and frequency of oscillations can be controlled in vivo and predicted mathematically. In addition, we show that nested negative feedback loops can be employed to specifically tune the frequency of oscillations while leaving their peak shape unchanged. In total, this work establishes design principles that enable function-guided design of oscillatory signaling controllers in diverse synthetic biology applications. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Decision Support System Requirements Definition for Human Extravehicular Activity Based on Cognitive Work Analysis.

    PubMed

    Miller, Matthew James; McGuire, Kerry M; Feigh, Karen M

    2017-06-01

    The design and adoption of decision support systems within complex work domains is a challenge for cognitive systems engineering (CSE) practitioners, particularly at the onset of project development. This article presents an example of applying CSE techniques to derive design requirements compatible with traditional systems engineering to guide decision support system development. Specifically, it demonstrates the requirements derivation process based on cognitive work analysis for a subset of human spaceflight operations known as extravehicular activity . The results are presented in two phases. First, a work domain analysis revealed a comprehensive set of work functions and constraints that exist in the extravehicular activity work domain. Second, a control task analysis was performed on a subset of the work functions identified by the work domain analysis to articulate the translation of subject matter states of knowledge to high-level decision support system requirements. This work emphasizes an incremental requirements specification process as a critical component of CSE analyses to better situate CSE perspectives within the early phases of traditional systems engineering design.

  11. Influence of different emulsifiers on characteristics of eggless cake containing soy milk: Modeling of physical and sensory properties by mixture experimental design.

    PubMed

    Rahmati, Nazanin Fatemeh; Mazaheri Tehrani, Mostafa

    2014-09-01

    Emulsifiers of different structures and functionalities are important ingredients usually used in baking cakes with satisfactory properties. In this study, three emulsifiers including distilled glycerol mono stearate (DGMS), lecithin and sorbitan mono stearate (SMS) were used to bake seven eggless cakes containing soy milk and optimization was performed by using mixture experimental design to produce an eggless cake sample with optimized properties. Physical properties of cake batters (viscosity, specific gravity and stability), cake quality parameters (moisture loss, density, specific volume, volume index, contour, symmetry, color and texture) and sensory attributes of eggless cakes were analyzed to investigate functional potential of the emulsifiers and results were compared with those of control cake containing egg. Almost in all cases emulsifiers, compared to the control cake, changed properties of eggless cakes significantly. Regarding models of different response variables (except for some properties) and their high R(2) (99.51-100), it could be concluded that models obtained by mixture design were significantly fitted for the studied responses.

  12. Specific language impairment and executive functioning: parent and teacher ratings of behavior.

    PubMed

    Wittke, Kacie; Spaulding, Tammie J; Schechtman, Calli J

    2013-05-01

    The current study used the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P; Gioia, Espy, & Isquith, 2003), a rating scale designed to investigate executive behaviors in everyday activities, to examine the executive functioning of preschool children with specific language impairment (SLI) relative to their typically developing (TD) peers. Nineteen preschool children with SLI were age- and gender-matched to 19 TD peers. Both parents and teachers of the participants completed the BRIEF-P. The executive functioning of children with SLI were rated significantly worse than those of controls by both parents and teachers. Adults' perceptions of the children's executive functioning significantly correlated with the children's language abilities. Parent and teacher perceptions of executive functioning in children with SLI align with prior findings of executive deficits that have been documented on neuropsychological assessments and experimental tasks. Furthermore, the results provide additional supporting evidence of the relationship between language abilities and executive functioning in early child development.

  13. [Assessment of Functioning when Conducting Occupational Capacity Evaluations--What is "Evidence-Based"?].

    PubMed

    Canela, Carlos; Schleifer, Roman; Dube, Anish; Hengartner, Michael P; Ebner, Gerhard; Seifritz, Erich; Liebrenz, Michael

    2016-03-01

    Occupational capacity evaluations have previously been subject to criticism for lacking in quality and consistency. To the authors' knowledge, there is no clear consensus on the best way to formally assess functioning within capacity evaluations. In this review we investigated different instruments that are used to assess functioning in occupational capacity evaluations. Systematic review of the literature. Though several instruments that assess functional capacity were found in our search, a specific validated instrument assessing occupational capacity as part of a larger psychiatric evaluation was not found. The limitations of the existing instruments on assessing functional capacity are discussed. Medical experts relying on instruments to conduct functional capacity evaluations should be cognizant of their limitations. The findings call for the development and use of an instrument specifically designed to assess the functional and occupational capacity of psychiatric patients, which is also likely to improve the quality of these reports. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Accounting for substitution and spatial heterogeneity in a labelled choice experiment.

    PubMed

    Lizin, S; Brouwer, R; Liekens, I; Broeckx, S

    2016-10-01

    Many environmental valuation studies using stated preferences techniques are single-site studies that ignore essential spatial aspects, including possible substitution effects. In this paper substitution effects are captured explicitly in the design of a labelled choice experiment and the inclusion of different distance variables in the choice model specification. We test the effect of spatial heterogeneity on welfare estimates and transfer errors for minor and major river restoration works, and the transferability of river specific utility functions, accounting for key variables such as site visitation, spatial clustering and income. River specific utility functions appear to be transferable, resulting in low transfer errors. However, ignoring spatial heterogeneity increases transfer errors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. A highly functional synthetic phage display library containing over 40 billion human antibody clones.

    PubMed

    Weber, Marcel; Bujak, Emil; Putelli, Alessia; Villa, Alessandra; Matasci, Mattia; Gualandi, Laura; Hemmerle, Teresa; Wulhfard, Sarah; Neri, Dario

    2014-01-01

    Several synthetic antibody phage display libraries have been created and used for the isolation of human monoclonal antibodies. The performance of antibody libraries, which is usually measured in terms of their ability to yield high-affinity binding specificities against target proteins of interest, depends both on technical aspects (such as library size and quality of cloning) and on design features (which influence the percentage of functional clones in the library and their ability to be used for practical applications). Here, we describe the design, construction and characterization of a combinatorial phage display library, comprising over 40 billion human antibody clones in single-chain fragment variable (scFv) format. The library was designed with the aim to obtain highly stable antibody clones, which can be affinity-purified on protein A supports, even when used in scFv format. The library was found to be highly functional, as >90% of randomly selected clones expressed the corresponding antibody. When selected against more than 15 antigens from various sources, the library always yielded specific and potent binders, at a higher frequency compared to previous antibody libraries. To demonstrate library performance in practical biomedical research projects, we isolated the human antibody G5, which reacts both against human and murine forms of the alternatively spliced BCD segment of tenascin-C, an extracellular matrix component frequently over-expressed in cancer and in chronic inflammation. The new library represents a useful source of binding specificities, both for academic research and for the development of antibody-based therapeutics.

  16. A Highly Functional Synthetic Phage Display Library Containing over 40 Billion Human Antibody Clones

    PubMed Central

    Weber, Marcel; Bujak, Emil; Putelli, Alessia; Villa, Alessandra; Matasci, Mattia; Gualandi, Laura; Hemmerle, Teresa; Wulhfard, Sarah; Neri, Dario

    2014-01-01

    Several synthetic antibody phage display libraries have been created and used for the isolation of human monoclonal antibodies. The performance of antibody libraries, which is usually measured in terms of their ability to yield high-affinity binding specificities against target proteins of interest, depends both on technical aspects (such as library size and quality of cloning) and on design features (which influence the percentage of functional clones in the library and their ability to be used for practical applications). Here, we describe the design, construction and characterization of a combinatorial phage display library, comprising over 40 billion human antibody clones in single-chain fragment variable (scFv) format. The library was designed with the aim to obtain highly stable antibody clones, which can be affinity-purified on protein A supports, even when used in scFv format. The library was found to be highly functional, as >90% of randomly selected clones expressed the corresponding antibody. When selected against more than 15 antigens from various sources, the library always yielded specific and potent binders, at a higher frequency compared to previous antibody libraries. To demonstrate library performance in practical biomedical research projects, we isolated the human antibody G5, which reacts both against human and murine forms of the alternatively spliced BCD segment of tenascin-C, an extracellular matrix component frequently over-expressed in cancer and in chronic inflammation. The new library represents a useful source of binding specificities, both for academic research and for the development of antibody-based therapeutics. PMID:24950200

  17. A Randomized Controlled Trial of an Activity Specific Exercise Program for Individuals With Alzheimer Disease in Long-term Care Settings

    PubMed Central

    Roach, Kathryn E.; Tappen, Ruth M.; Kirk-Sanchez, Neva; Williams, Christine L.; Loewenstein, David

    2011-01-01

    Objective To determine whether an activity specific exercise program could improve ability to perform basic mobility activities in long-term care residents with Alzheimer disease (AD). Design Randomized, controlled, single-blinded clinical trial. Setting Residents of 7 long-term care facilities. Participants Eighty-two long-term care residents with mild to severe AD. Intervention An activity specific exercise program was compared to a walking program and to an attention control. Measurements Ability to perform bed mobility and transfers were assessed using the subscales of the Acute Care Index of Function; functional mobility was measured using the 6-Minute Walk test. Results Subjects receiving the activity specific exercise program improved in ability to perform transfers, whereas subjects in the other 2 groups declined. PMID:21937893

  18. Compiler writing system detail design specification. Volume 2: Component specification

    NASA Technical Reports Server (NTRS)

    Arthur, W. J.

    1974-01-01

    The logic modules and data structures composing the Meta-translator module are desribed. This module is responsible for the actual generation of the executable language compiler as a function of the input Meta-language. Machine definitions are also processed and are placed as encoded data on the compiler library data file. The transformation of intermediate language in target language object text is described.

  19. Behavioral phenotyping of mice in pharmacological and toxicological research.

    PubMed

    Karl, Tim; Pabst, Reinhard; von Hörsten, Stephan

    2003-07-01

    The evaluation of behavioral effects is an important component for the in vivo screening of drugs or potentially toxic compounds in mice. Ideally, such screening should be composed of monitoring general health, sensory functions, and motor abilities, right before specific behavioral domains are tested. A rational strategy in the design and procedure of testing as well as an effective composition of different well-established and reproducible behavioral tests can minimize the risk of false positive and false negative results in drug screening. In the present review we describe such basic considerations in planning experiments, selecting strains of mice, and propose groups of behavioral tasks suitable for a reliable detection of differences in specific behavioral domains in mice. Screening of general health and neurophysiologic functions (reflexes, sensory abilities) and motor function (pole test, wire hang test, beam walking, rotarod, accelerod, and footprint) as well as specific hypothesis-guided testing in the behavioral domains of learning and memory (water maze, radial maze, conditioned fear, and avoidance tasks), emotionality (open field, hole board, elevated plus maze, and object exploration), nociception (tail flick, hot plate), psychiatric-like conditions (porsolt swim test, acoustic startle response, and prepulse inhibition), and aggression (isolation-induced aggression, spontaneous aggression, and territorial aggression) are described in further detail. This review is designed to describe a general approach, which increases reliability of behavioral screening. Furthermore, it provides an overview on a selection of specific procedures suitable for but not limited to behavioral screening in pharmacology and toxicology.

  20. Contribution of transposable elements and distal enhancers to evolution of human-specific features of interphase chromatin architecture in embryonic stem cells.

    PubMed

    Glinsky, Gennadi V

    2018-03-01

    Transposable elements have made major evolutionary impacts on creation of primate-specific and human-specific genomic regulatory loci and species-specific genomic regulatory networks (GRNs). Molecular and genetic definitions of human-specific changes to GRNs contributing to development of unique to human phenotypes remain a highly significant challenge. Genome-wide proximity placement analysis of diverse families of human-specific genomic regulatory loci (HSGRL) identified topologically associating domains (TADs) that are significantly enriched for HSGRL and designated rapidly evolving in human TADs. Here, the analysis of HSGRL, hESC-enriched enhancers, super-enhancers (SEs), and specific sub-TAD structures termed super-enhancer domains (SEDs) has been performed. In the hESC genome, 331 of 504 (66%) of SED-harboring TADs contain HSGRL and 68% of SEDs co-localize with HSGRL, suggesting that emergence of HSGRL may have rewired SED-associated GRNs within specific TADs by inserting novel and/or erasing existing non-coding regulatory sequences. Consequently, markedly distinct features of the principal regulatory structures of interphase chromatin evolved in the hESC genome compared to mouse: the SED quantity is 3-fold higher and the median SED size is significantly larger. Concomitantly, the overall TAD quantity is increased by 42% while the median TAD size is significantly decreased (p = 9.11E-37) in the hESC genome. Present analyses illustrate a putative global role for transposable elements and HSGRL in shaping the human-specific features of the interphase chromatin organization and functions, which are facilitated by accelerated creation of novel transcription factor binding sites and new enhancers driven by targeted placement of HSGRL at defined genomic coordinates. A trend toward the convergence of TAD and SED architectures of interphase chromatin in the hESC genome may reflect changes of 3D-folding patterns of linear chromatin fibers designed to enhance both regulatory complexity and functional precision of GRNs by creating predominantly a single gene (or a set of functionally linked genes) per regulatory domain structures. Collectively, present analyses reveal critical evolutionary contributions of transposable elements and distal enhancers to creation of thousands primate- and human-specific elements of a chromatin folding code, which defines the 3D context of interphase chromatin both restricting and facilitating biological functions of GRNs.

  1. Aptamers as tools for target prioritization and lead identification.

    PubMed

    Burgstaller, Petra; Girod, Anne; Blind, Michael

    2002-12-15

    The increasing number of potential drug target candidates has driven the development of novel technologies designed to identify functionally important targets and enhance the subsequent lead discovery process. Highly specific synthetic nucleic acid ligands--also known as aptamers--offer a new exciting route in the drug discovery process by linking target validation directly with HTS. Recently, aptamers have proven to be valuable tools for modulating the function of endogenous cellular proteins in their natural environment. A set of technologies has been developed to use these sophisticated ligands for the validation of potential drug targets in disease models. Moreover, aptamers that are specific antagonists of protein function can act as substitute interaction partners in HTS assays to facilitate the identification of small-molecule lead compounds.

  2. Dystrophin Immunity in Duchenne’s Muscular Dystrophy

    PubMed Central

    Mendell, Jerry R.; Campbell, Katherine; Rodino-Klapac, Louise; Sahenk, Zarife; Shilling, Chris; Lewis, Sarah; Bowles, Dawn; Gray, Steven; Li, Chengwen; Galloway, Gloria; Malik, Vinod; Coley, Brian; Clark, K. Reed; Li, Juan; Xiao, Xiao; Samulski, Jade; McPhee, Scott W.; Samulski, R. Jude; Walker, Christopher M.

    2010-01-01

    SUMMARY We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne’s muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from the deleted endogenous gene after spontaneous in-frame splicing, contained epitopes targeted by the autoreactive T cells. The potential for T-cell immunity to self and nonself dystrophin epitopes should be considered in designing and monitoring experimental therapies for this disease. (Funded by the Muscular Dystrophy Association and others; ClinicalTrials.gov number, NCT00428935.) PMID:20925545

  3. Test-specific control conditions for functional analyses.

    PubMed

    Fahmie, Tara A; Iwata, Brian A; Querim, Angie C; Harper, Jill M

    2013-01-01

    Most functional analyses of problem behavior include a common condition (play or noncontingent reinforcement) as a control for both positive and negative reinforcement. However, test-specific conditions that control for each potential source of reinforcement may be beneficial occasionally. We compared responding during alone, ignore, play, and differential reinforcement of other behavior (DRO) control conditions for individuals whose problem behavior was maintained by positive or negative reinforcement. Results showed that all of the conditions were effective controls for problem behavior maintained by positive reinforcement; however, the DRO condition was consistently ineffective as a control for problem behavior maintained by negative reinforcement. Implications for the design of functional analyses and future research are discussed. © Society for the Experimental Analysis of Behavior.

  4. Athletic Lockers for Schools and Colleges; Their Design--Selection--and Purchase with Functional Tips and Suggestions for the Modern Athletic Locker Room.

    ERIC Educational Resources Information Center

    Dickey, Donald D.

    Information is provided relative to the design, selection, and purchase of locker equipment for athletic and physical education use. Some suggestions offered are for both specific applications, and some are general to any locker dressing room. Among the topics discussed are construction and joining of lockers, ventilation and drying,…

  5. Random Measurement Error Does Not Bias the Treatment Effect Estimate in the Regression-Discontinuity Design. II. When an Interaction Effect Is Present.

    ERIC Educational Resources Information Center

    Trochim, William M. K.; And Others

    1991-01-01

    The regression-discontinuity design involving a treatment interaction effect (TIE), pretest-posttest functional form specification, and choice of point-of-estimation of the TIE are examined. Formulas for controlling the magnitude of TIE in simulations can be used for simulating the randomized experimental case where estimation is not at the…

  6. Using Desktop Publishing To Create Newsletters, Handouts, and Web Pages: A How-To-Do-It Manual. How-To-Do-It Manuals for Librarians. Number 74.

    ERIC Educational Resources Information Center

    Maxymuk, John

    This guide provides desktop publishing basics and instructions for specific library applications, enabling any librarian to function as the writer, editor, designer, proofreader, and printer of a variety of different publications. The guide is designed to help librarians create publications that are attractive, effective, useful, and easily read.…

  7. Formal functional test designs with a test representation language

    NASA Technical Reports Server (NTRS)

    Hops, J. M.

    1993-01-01

    The application of the category-partition method to the test design phase of hardware, software, or system test development is discussed. The method provides a formal framework for reducing the total number of possible test cases to a minimum logical subset for effective testing. An automatic tool and a formal language were developed to implement the method and produce the specification of test cases.

  8. OGO-1 and OGO-3 MIT plasma experiments S4903

    NASA Technical Reports Server (NTRS)

    1968-01-01

    Plasma proton and plasma electron prototype and flight models were designed, fabricated, and tested. Ground support equipment for the models was also prepared. The flight models were launched aboard the first and third Orbiting Geophysical Observatories on 4 Sept. 1964 and 6 June 1966. These experiments have generally functioned in accordance with the design specifications and useful data are still being received.

  9. Spreading activation in nonverbal memory networks.

    PubMed

    Foster, Paul S; Wakefield, Candias; Pryjmak, Scott; Roosa, Katelyn M; Branch, Kaylei K; Drago, Valeria; Harrison, David W; Ruff, Ronald

    2017-09-01

    Theories of spreading activation primarily involve semantic memory networks. However, the existence of separate verbal and visuospatial memory networks suggests that spreading activation may also occur in visuospatial memory networks. The purpose of the present investigation was to explore this possibility. Specifically, this study sought to create and describe the design frequency corpus and to determine whether this measure of visuospatial spreading activation was related to right hemisphere functioning and spreading activation in verbal memory networks. We used word frequencies taken from the Controlled Oral Word Association Test and design frequencies taken from the Ruff Figural Fluency Test as measures of verbal and visuospatial spreading activation, respectively. Average word and design frequencies were then correlated with measures of left and right cerebral functioning. The results indicated that a significant relationship exists between performance on a test of right posterior functioning (Block Design) and design frequency. A significant negative relationship also exists between spreading activation in semantic memory networks and design frequency. Based on our findings, the hypotheses were supported. Further research will need to be conducted to examine whether spreading activation exists in visuospatial memory networks as well as the parameters that might modulate this spreading activation, such as the influence of neurotransmitters.

  10. Universal Verification Methodology Based Register Test Automation Flow.

    PubMed

    Woo, Jae Hun; Cho, Yong Kwan; Park, Sun Kyu

    2016-05-01

    In today's SoC design, the number of registers has been increased along with complexity of hardware blocks. Register validation is a time-consuming and error-pron task. Therefore, we need an efficient way to perform verification with less effort in shorter time. In this work, we suggest register test automation flow based UVM (Universal Verification Methodology). UVM provides a standard methodology, called a register model, to facilitate stimulus generation and functional checking of registers. However, it is not easy for designers to create register models for their functional blocks or integrate models in test-bench environment because it requires knowledge of SystemVerilog and UVM libraries. For the creation of register models, many commercial tools support a register model generation from register specification described in IP-XACT, but it is time-consuming to describe register specification in IP-XACT format. For easy creation of register model, we propose spreadsheet-based register template which is translated to IP-XACT description, from which register models can be easily generated using commercial tools. On the other hand, we also automate all the steps involved integrating test-bench and generating test-cases, so that designers may use register model without detailed knowledge of UVM or SystemVerilog. This automation flow involves generating and connecting test-bench components (e.g., driver, checker, bus adaptor, etc.) and writing test sequence for each type of register test-case. With the proposed flow, designers can save considerable amount of time to verify functionality of registers.

  11. A tool for design of primers for microRNA-specific quantitative RT-qPCR.

    PubMed

    Busk, Peter K

    2014-01-28

    MicroRNAs are small but biologically important RNA molecules. Although different methods can be used for quantification of microRNAs, quantitative PCR is regarded as the reference that is used to validate other methods. Several commercial qPCR assays are available but they often come at a high price and the sequences of the primers are not disclosed. An alternative to commercial assays is to manually design primers but this work is tedious and, hence, not practical for the design of primers for a larger number of targets. I have developed the software miRprimer for automatic design of primers for the method miR-specific RT-qPCR, which is one of the best performing microRNA qPCR methods available. The algorithm is based on an implementation of the previously published rules for manual design of miR-specific primers with the additional feature of evaluating the propensity of formation of secondary structures and primer dimers. Testing of the primers showed that 76 out of 79 primers (96%) worked for quantification of microRNAs by miR-specific RT-qPCR of mammalian RNA samples. This success rate corresponds to the success rate of manual primer design. Furthermore, primers designed by this method have been distributed to several labs and used successfully in published studies. The software miRprimer is an automatic and easy method for design of functional primers for miR-specific RT-qPCR. The application is available as stand-alone software that will work on the MS Windows platform and in a developer version written in the Ruby programming language.

  12. High-level user interfaces for transfer function design with semantics.

    PubMed

    Salama, Christof Rezk; Keller, Maik; Kohlmann, Peter

    2006-01-01

    Many sophisticated techniques for the visualization of volumetric data such as medical data have been published. While existing techniques are mature from a technical point of view, managing the complexity of visual parameters is still difficult for non-expert users. To this end, this paper presents new ideas to facilitate the specification of optical properties for direct volume rendering. We introduce an additional level of abstraction for parametric models of transfer functions. The proposed framework allows visualization experts to design high-level transfer function models which can intuitively be used by non-expert users. The results are user interfaces which provide semantic information for specialized visualization problems. The proposed method is based on principal component analysis as well as on concepts borrowed from computer animation.

  13. Decoupling local mechanics from large-scale structure in modular metamaterials.

    PubMed

    Yang, Nan; Silverberg, Jesse L

    2017-04-04

    A defining feature of mechanical metamaterials is that their properties are determined by the organization of internal structure instead of the raw fabrication materials. This shift of attention to engineering internal degrees of freedom has coaxed relatively simple materials into exhibiting a wide range of remarkable mechanical properties. For practical applications to be realized, however, this nascent understanding of metamaterial design must be translated into a capacity for engineering large-scale structures with prescribed mechanical functionality. Thus, the challenge is to systematically map desired functionality of large-scale structures backward into a design scheme while using finite parameter domains. Such "inverse design" is often complicated by the deep coupling between large-scale structure and local mechanical function, which limits the available design space. Here, we introduce a design strategy for constructing 1D, 2D, and 3D mechanical metamaterials inspired by modular origami and kirigami. Our approach is to assemble a number of modules into a voxelized large-scale structure, where the module's design has a greater number of mechanical design parameters than the number of constraints imposed by bulk assembly. This inequality allows each voxel in the bulk structure to be uniquely assigned mechanical properties independent from its ability to connect and deform with its neighbors. In studying specific examples of large-scale metamaterial structures we show that a decoupling of global structure from local mechanical function allows for a variety of mechanically and topologically complex designs.

  14. Positive technology: using interactive technologies to promote positive functioning.

    PubMed

    Riva, Giuseppe; Baños, Rosa M; Botella, Cristina; Wiederhold, Brenda K; Gaggioli, Andrea

    2012-02-01

    It is generally assumed that technology assists individuals in improving the quality of their lives. However, the impact of new technologies and media on well-being and positive functioning is still somewhat controversial. In this paper, we contend that the quality of experience should become the guiding principle in the design and development of new technologies, as well as a primary metric for the evaluation of their applications. The emerging discipline of Positive Psychology provides a useful framework to address this challenge. Positive Psychology is the scientific study of optimal human functioning and flourishing. Instead of drawing on a "disease model" of human behavior, it focuses on factors that enable individuals and communities to thrive and build the best in life. In this paper, we propose the "Positive Technology" approach--the scientific and applied approach to the use of technology for improving the quality of our personal experience through its structuring, augmentation, and/or replacement--as a way of framing a suitable object of study in the field of cyberpsychology and human-computer interaction. Specifically, we suggest that it is possible to use technology to influence three specific features of our experience--affective quality, engagement/actualization, and connectedness--that serve to promote adaptive behaviors and positive functioning. In this framework, positive technologies are classified according to their effects on a specific feature of personal experience. Moreover, for each level, we have identified critical variables that can be manipulated to guide the design and development of positive technologies.

  15. Molecular Studies on MIC1/PDF in Human Prostate Cancer

    DTIC Science & Technology

    2005-09-01

    expression of secreted MIC-1 protein (Aim 2). Moreover, the functions of MIC-1 have been studied in vitro by using specific antibody directed against MIC-1... antibody M2 (Sigma). The FLAG tag was inserted at the 3’-translated region of the MIC-l/PDF cDNA. A double stranded, synthetic oligonucleotide was designed...B) Lower panel showed the coomassie blue of specific antibody directed against stained gel as a loading control. MIC-1 protein. More specifically

  16. Universal Design as a Booster for Housing Quality and Architectural Practice.

    PubMed

    Denizou, Karine

    2016-01-01

    Norwegian central government has for the last decade increasingly focused on universal design. Fundamental changes in the Norwegian building code and corresponding regulations in 2010 give an apparently clear framework for the implementation of accessibility and universal design. However, it seems that neither increased awareness of accessibility requirements and universal design, nor compliance with the building code guarantees improvement of housing quality and usability. The Norwegian regulations have gone further in the direction of performance requirements than most other countries. This applies to all types of requirements, including requirements for usability, functionality and accessibility. Hardly any specifications are to be found in the regulations. Ideally, this lack of specifications should give designers the opportunity to develop innovative answers and hence to respond to different contexts and needs. Still, many architects and builders ask for clear specifications, in order to simplify and speed up design processes and make control of solutions easier. Many architects understand guidelines as minimum requirements, and are thus reproducing the identical solutions without considering the context and the needs of the users. They see accessibility as another regulatory pressure and requirements as restrictions rather than positive incentives. However, there are examples of designers who have internalised the regulatory framework and thus are able to create and integrate inclusive design in their daily work. Based on recent research conducted by SINTEF Building and Infrastructure and financed by the Norwegian State Housing Bank, this paper presents examples of practice where dwellings have been developed within a framework of universal design. Focus of the research has been on the approach of the design team and their understanding and use of the regulatory framework in order to create better homes in dialogue with the building authorities. Main objectives are to: - Contribute to better understanding of universal design as a tool and a method to improve housing quality and usability - Investigate the conditions for developing dwellings with innovative and functional solutions in compliance with the building code - Discuss challenges in interpreting the requirements and in taking the needs of various resident groups into account.

  17. Next Generation Ship-Borne ASW-System: An Exemplary Exertion of Methodologies and Tools Applied According to the German Military Acquisition Guidelines

    DTIC Science & Technology

    2013-06-01

    as well as the evaluation of product parameters, operational test and functional limits. The product will be handed over to the designated ...which results in a system design that can be tested , produced, and fielded to satisfy the need. The concept development phase enables us to determine...specifications that can be tested or verified. The requirements presented earlier are the minimum necessary to allow the design process to find

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

    Bachan, John

    Chisel is a new open-source hardware construction language developed at UC Berkeley that supports advanced hardware design using highly parameterized generators and layered domain-specific hardware languages. Chisel is embedded in the Scala programming language, which raises the level of hardware design abstraction by providing concepts including object orientation, functional programming, parameterized types, and type inference. From the same source, Chisel can generate a high-speed C++-based cycle-accurate software simulator, or low-level Verilog designed to pass on to standard ASIC or FPGA tools for synthesis and place and route.

  19. HuMiChip: Development of a Functional Gene Array for the Study of Human Microbiomes

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

    Tu, Q.; Deng, Ye; Lin, Lu

    Microbiomes play very important roles in terms of nutrition, health and disease by interacting with their hosts. Based on sequence data currently available in public domains, we have developed a functional gene array to monitor both organismal and functional gene profiles of normal microbiota in human and mouse hosts, and such an array is called human and mouse microbiota array, HMM-Chip. First, seed sequences were identified from KEGG databases, and used to construct a seed database (seedDB) containing 136 gene families in 19 metabolic pathways closely related to human and mouse microbiomes. Second, a mother database (motherDB) was constructed withmore » 81 genomes of bacterial strains with 54 from gut and 27 from oral environments, and 16 metagenomes, and used for selection of genes and probe design. Gene prediction was performed by Glimmer3 for bacterial genomes, and by the Metagene program for metagenomes. In total, 228,240 and 801,599 genes were identified for bacterial genomes and metagenomes, respectively. Then the motherDB was searched against the seedDB using the HMMer program, and gene sequences in the motherDB that were highly homologous with seed sequences in the seedDB were used for probe design by the CommOligo software. Different degrees of specific probes, including gene-specific, inclusive and exclusive group-specific probes were selected. All candidate probes were checked against the motherDB and NCBI databases for specificity. Finally, 7,763 probes covering 91.2percent (12,601 out of 13,814) HMMer confirmed sequences from 75 bacterial genomes and 16 metagenomes were selected. This developed HMM-Chip is able to detect the diversity and abundance of functional genes, the gene expression of microbial communities, and potentially, the interactions of microorganisms and their hosts.« less

  20. Construction of Nanowire Heterojunctions: Photonic Function-Oriented Nanoarchitectonics.

    PubMed

    Li, Yong Jun; Yan, Yongli; Zhao, Yong Sheng; Yao, Jiannian

    2016-02-10

    Nanophotonics has received broad research interest because it may provide an alternative opportunity to overcome the fundamental limitations of electronic circuits. So far, diverse photonic functions, such as light generation, modulation, and detection, have been realized based on various nano-materials. The exact structural features of these material systems, including geometric characteristics, surface morphology, and material composition, play a key role in determining the photonic functions. Therefore, rational designs and constructions of materials on both morphological and componential levels, namely nanoarchitectonics, are indispensable for any photonic device with specific functionalities. Recently, a series of nanowire heterojunctions (NWHJs), which are usually made from two or more kinds of material compositions, were constructed for novel photonic applications based on various interactions between different materials at the junctions, for instance, energy transfer, exciton-plasmon coupling, or photon-plasmon coupling. A summary of these works is necessary to get a more comprehensive understanding of the relationship between photonic functions and architectonics of NWHJs, which will be instructive for designing novel photonic devices towards integrated circuits. Here, photonic function oriented nanoarchitectonics based on recent breakthroughs in nanophotonic devices are discussed, with emphasis on the design mechanisms, fabrication strategies, and excellent performances. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. New classes of piezoelectrics, ferroelectrics, and antiferroelectrics by first-principles high-throughput materials design

    NASA Astrophysics Data System (ADS)

    Bennett, Joseph

    2013-03-01

    Functional materials, such as piezoelectrics, ferroelectrics, and antiferroelectrics, exhibit large changes with applied fields and stresses. This behavior enables their incorporation into a wide variety of devices in technological fields such as energy conversion/storage and information processing/storage. Discovery of functional materials with improved performance or even new types of responses is thus not only a scientific challenge, but can have major impacts on society. In this talk I will review our efforts to uncover new families of functional materials using a combined crystallographic database/high-throughput first-principles approach. I will describe our work on the design and discovery of thousands of new functional materials, specifically the LiAlSi family as piezoelectrics, the LiGaGe family as ferroelectrics, and the MgSrSi family as antiferroelectrics.

  2. Sandia National Laboratories Facilities Management and Operations Center Design Standards Manual

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

    Peterson, Timothy L.

    2014-09-01

    At Sandia National Laboratories in New Mexico (SNL/NM), the design, construction, operation, and maintenance of facilities is guided by industry standards, a graded approach, and the systematic analysis of life cycle benefits received for costs incurred. The design of the physical plant must ensure that the facilities are "fit for use," and provide conditions that effectively, efficiently, and safely support current and future mission needs. In addition, SNL/NM applies sustainable design principles, using an integrated whole-building design approach, from site planning to facility design, construction, and operation to ensure building resource efficiency and the health and productivity of occupants. Themore » safety and health of the workforce and the public, any possible effects on the environment, and compliance with building codes take precedence over project issues, such as performance, cost, and schedule. These design standards generally apply to all disciplines on all SNL/NM projects. Architectural and engineering design must be both functional and cost-effective. Facility design must be tailored to fit its intended function, while emphasizing low-maintenance, energy-efficient, and energy-conscious design. Design facilities that can be maintained easily, with readily accessible equipment areas, low maintenance, and quality systems. To promote an orderly and efficient appearance, architectural features of new facilities must complement and enhance the existing architecture at the site. As an Architectural and Engineering (A/E) professional, you must advise the Project Manager when this approach is prohibitively expensive. You are encouraged to use professional judgment and ingenuity to produce a coordinated interdisciplinary design that is cost-effective, easily contractible or buildable, high-performing, aesthetically pleasing, and compliant with applicable building codes. Close coordination and development of civil, landscape, structural, architectural, fire protection, mechanical, electrical, telecommunications, and security features is expected to ensure compatibility with planned functional equipment and to facilitate constructability. If portions of the design are subcontracted to specialists, delivery of the finished design documents must not be considered complete until the subcontracted portions are also submitted for review. You must, along with support consultants, perform functional analyses and programming in developing design solutions. These solutions must reflect coordination of the competing functional, budgetary, and physical requirements for the project. During design phases, meetings between you and the SNL/NM Project Team to discuss and resolve design issues are required. These meetings are a normal part of the design process. For specific design-review requirements, see the project-specific Design Criteria. In addition to the design requirements described in this manual, instructive information is provided to explain the sustainable building practice goals for design, construction, operation, and maintenance of SNL/NM facilities. Please notify SNL/NM personnel of design best practices not included in this manual, so they can be incorporated in future updates. You must convey all documents describing work to the SNL/NM Project Manager in both hard copy and in an electronic format compatible with the SNL/NM-prescribed CADD and other software packages, and in accordance with a SNL/NM approved standard format. Print all hard copy versions of submitted documents (excluding drawings and renderings) double-sided when practical.« less

  3. Biomaterial design for specific cellular interactions: Role of surface functionalization and geometric features

    NASA Astrophysics Data System (ADS)

    Kolhar, Poornima

    The areas of drug delivery and tissue engineering have experienced extraordinary growth in recent years with the application of engineering principles and their potential to support and improve the field of medicine. The tremendous progress in nanotechnology and biotechnology has lead to this explosion of research and development in biomedical applications. Biomaterials can now be engineered at a nanoscale and their specific interactions with the biological tissues can be modulated. Various design parameters are being established and researched for design of drug-delivery carriers and scaffolds to be implanted into humans. Nanoparticles made from versatile biomaterial can deliver both small-molecule drugs and various classes of bio-macromolecules, such as proteins and oligonucleotides. Similarly in the field of tissue engineering, current approaches emphasize nanoscale control of cell behavior by mimicking the natural extracellular matrix (ECM) unlike, traditional scaffolds. Drug delivery and tissue engineering are closely connected fields and both of these applications require materials with exceptional physical, chemical, biological, and biomechanical properties to provide superior therapy. In the current study the surface functionalization and the geometric features of the biomaterials has been explored. In particular, a synthetic surface for culture of human embryonic stem cells has been developed, demonstrating the importance of surface functionalization in maintaining the pluripotency of hESCs. In the second study, the geometric features of the drug delivery carriers are investigated and the polymeric nanoneedles mediated cellular permeabilization and direct cytoplasmic delivery is reported. In the third study, the combined effect of surface functionalization and geometric modification of carriers for vascular targeting is enunciated. These studies illustrate how the biomaterials can be designed to achieve various cellular behaviors and control the interactions with cells in vivo .

  4. Space-based multifunctional end effector systems functional requirements and proposed designs

    NASA Technical Reports Server (NTRS)

    Mishkin, A. H.; Jau, B. M.

    1988-01-01

    The end effector is an essential element of teleoperator and telerobot systems to be employed in space in the next decade. The report defines functional requirements for end effector systems to perform operations that are currently only feasible through Extra-Vehicular Activity (EVA). Specific tasks and functions that the end effectors must be capable of performing are delineated. Required capabilities for forces and torques, clearances, compliance, and sensing are described, using current EVA requirements as guidelines where feasible. The implications of these functional requirements on the elements of potential end effector systems are discussed. The systems issues that must be considered in the design of space-based manipulator systems are identified; including impacts on subsystems tightly coupled to the end effector, i.e., control station, information processing, manipulator arm, tool and equipment stowage. Possible end effector designs are divided into three categories: single degree-of-freedom end effectors, multiple degree of freedom end effectors, and anthropomorphic hands. Specific design alternatives are suggested and analyzed within the individual categories. Two evaluations are performed: the first considers how well the individual end effectors could substitute for EVA; the second compares how manipulator systems composed of the top performers from the first evaluation would improve the space shuttle Remote Manipulator System (RMS) capabilities. The analysis concludes that the anthropomorphic hand is best-suited for EVA tasks. A left- and right-handed anthropomorphic manipulator arm configuration is suggested as appropriate to be affixed to the RMS, but could also be used as part of the Smart Front End for the Orbital Maneuvering Vehicle (OMV). The technical feasibility of the anthropomorphic hand and its control are demonstrated. An evolutionary development approach is proposed and approximate scheduling provided for implementing the suggested manipulator systems in time for space stations operations in the early 1990s.

  5. Electro-Optic Computing Architectures: Volume II. Components and System Design and Analysis

    DTIC Science & Technology

    1998-02-01

    The objective of the Electro - Optic Computing Architecture (EOCA) program was to develop multi-function electro - optic interfaces and optical...interconnect units to enhance the performance of parallel processor systems and form the building blocks for future electro - optic computing architectures...Specifically, three multi-function interface modules were targeted for development - an Electro - Optic Interface (EOI), an Optical Interconnection Unit

  6. Network dysfunction predicts speech production after left hemisphere stroke.

    PubMed

    Geranmayeh, Fatemeh; Leech, Robert; Wise, Richard J S

    2016-03-09

    To investigate the role of multiple distributed brain networks, including the default mode, fronto-temporo-parietal, and cingulo-opercular networks, which mediate domain-general and task-specific processes during speech production after aphasic stroke. We conducted an observational functional MRI study to investigate the effects of a previous left hemisphere stroke on functional connectivity within and between distributed networks as patients described pictures. Study design included various baseline tasks, and we compared results to those of age-matched healthy participants performing the same tasks. We used independent component and psychophysiological interaction analyses. Although activity within individual networks was not predictive of speech production, relative activity between networks was a predictor of both within-scanner and out-of-scanner language performance, over and above that predicted from lesion volume, age, sex, and years of education. Specifically, robust functional imaging predictors were the differential activity between the default mode network and both the left and right fronto-temporo-parietal networks, respectively activated and deactivated during speech. We also observed altered between-network functional connectivity of these networks in patients during speech production. Speech production is dependent on complex interactions among widely distributed brain networks, indicating that residual speech production after stroke depends on more than the restoration of local domain-specific functions. Our understanding of the recovery of function following focal lesions is not adequately captured by consideration of ipsilesional or contralesional brain regions taking over lost domain-specific functions, but is perhaps best considered as the interaction between what remains of domain-specific networks and domain-general systems that regulate behavior. © 2016 American Academy of Neurology.

  7. Network dysfunction predicts speech production after left hemisphere stroke

    PubMed Central

    Leech, Robert; Wise, Richard J.S.

    2016-01-01

    Objective: To investigate the role of multiple distributed brain networks, including the default mode, fronto-temporo-parietal, and cingulo-opercular networks, which mediate domain-general and task-specific processes during speech production after aphasic stroke. Methods: We conducted an observational functional MRI study to investigate the effects of a previous left hemisphere stroke on functional connectivity within and between distributed networks as patients described pictures. Study design included various baseline tasks, and we compared results to those of age-matched healthy participants performing the same tasks. We used independent component and psychophysiological interaction analyses. Results: Although activity within individual networks was not predictive of speech production, relative activity between networks was a predictor of both within-scanner and out-of-scanner language performance, over and above that predicted from lesion volume, age, sex, and years of education. Specifically, robust functional imaging predictors were the differential activity between the default mode network and both the left and right fronto-temporo-parietal networks, respectively activated and deactivated during speech. We also observed altered between-network functional connectivity of these networks in patients during speech production. Conclusions: Speech production is dependent on complex interactions among widely distributed brain networks, indicating that residual speech production after stroke depends on more than the restoration of local domain-specific functions. Our understanding of the recovery of function following focal lesions is not adequately captured by consideration of ipsilesional or contralesional brain regions taking over lost domain-specific functions, but is perhaps best considered as the interaction between what remains of domain-specific networks and domain-general systems that regulate behavior. PMID:26962070

  8. Classifying the molecular functions of Rab GTPases in membrane trafficking using deep convolutional neural networks.

    PubMed

    Le, Nguyen-Quoc-Khanh; Ho, Quang-Thai; Ou, Yu-Yen

    2018-06-13

    Deep learning has been increasingly used to solve a number of problems with state-of-the-art performance in a wide variety of fields. In biology, deep learning can be applied to reduce feature extraction time and achieve high levels of performance. In our present work, we apply deep learning via two-dimensional convolutional neural networks and position-specific scoring matrices to classify Rab protein molecules, which are main regulators in membrane trafficking for transferring proteins and other macromolecules throughout the cell. The functional loss of specific Rab molecular functions has been implicated in a variety of human diseases, e.g., choroideremia, intellectual disabilities, cancer. Therefore, creating a precise model for classifying Rabs is crucial in helping biologists understand the molecular functions of Rabs and design drug targets according to such specific human disease information. We constructed a robust deep neural network for classifying Rabs that achieved an accuracy of 99%, 99.5%, 96.3%, and 97.6% for each of four specific molecular functions. Our approach demonstrates superior performance to traditional artificial neural networks. Therefore, from our proposed study, we provide both an effective tool for classifying Rab proteins and a basis for further research that can improve the performance of biological modeling using deep neural networks. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Pilates-based therapeutic exercise: effect on subjects with nonspecific chronic low back pain and functional disability: a randomized controlled trial.

    PubMed

    Rydeard, Rochenda; Leger, Andrew; Smith, Drew

    2006-07-01

    A randomized controlled trial, prestest-posttest design, with a 3-, 6-, and 12-month follow-up. To investigate the efficacy of a therapeutic exercise approach in a population with chronic low back pain (LBP). Therapeutic approaches developed from the Pilates method are becoming increasingly popular; however, there have been no reports on their efficacy. Thirty-nine physically active subjects between 20 and 55 years old with chronic LBP were randomly assigned to 1 of 2 groups. The specific-exercise-training group participated in a 4-week program consisting of training on specialized (Pilates) exercise equipment, while the control group received the usual care, defined as consultation with a physician and other specialists and healthcare professionals, as necessary. Treatment sessions were designed to train the activation of specific muscles thought to stabilize the lumbar-pelvic region. Functional disability outcomes were measured with The Roland Morris Disability Questionnaire (RMQ/RMDQ-HK) and average pain intensity using a 101-point numerical rating scale. There was a significantly lower level of functional disability (P = .023) and average pain intensity (P = .002) in the specific-exercise-training group than in the control group following the treatment intervention period. The posttest adjusted mean in functional disability level in the specific-exercise-training group was 2.0 (95% CI, 1.3 to 2.7) RMQ/RMDQ-HK points compared to a posttest adjusted mean in the control group of 3.2 (95% CI, 2.5 to 4.0) RMQ/RMDQ-HK points. The posttest adjusted mean in pain intensity in the specific-exercise-training group was 18.3 (95% CI, 11.8 to 24.8), as compared to 33.9 (95% CI, 26.9 to 41.0) in the control group. Improved disability scores in the specific-exercise-training group were maintained for up to 12 months following treatment intervention. The individuals in the specific-exercise-training group reported a significant decrease in LBP and disability, which was maintained over a 12-month follow-up period. Treatment with a modified Pilates-based approach was more efficacious than usual care in a population with chronic, unresolved LBP.

  10. RNAblueprint: flexible multiple target nucleic acid sequence design.

    PubMed

    Hammer, Stefan; Tschiatschek, Birgit; Flamm, Christoph; Hofacker, Ivo L; Findeiß, Sven

    2017-09-15

    Realizing the value of synthetic biology in biotechnology and medicine requires the design of molecules with specialized functions. Due to its close structure to function relationship, and the availability of good structure prediction methods and energy models, RNA is perfectly suited to be synthetically engineered with predefined properties. However, currently available RNA design tools cannot be easily adapted to accommodate new design specifications. Furthermore, complicated sampling and optimization methods are often developed to suit a specific RNA design goal, adding to their inflexibility. We developed a C ++  library implementing a graph coloring approach to stochastically sample sequences compatible with structural and sequence constraints from the typically very large solution space. The approach allows to specify and explore the solution space in a well defined way. Our library also guarantees uniform sampling, which makes optimization runs performant by not only avoiding re-evaluation of already found solutions, but also by raising the probability of finding better solutions for long optimization runs. We show that our software can be combined with any other software package to allow diverse RNA design applications. Scripting interfaces allow the easy adaption of existing code to accommodate new scenarios, making the whole design process very flexible. We implemented example design approaches written in Python to demonstrate these advantages. RNAblueprint , Python implementations and benchmark datasets are available at github: https://github.com/ViennaRNA . s.hammer@univie.ac.at, ivo@tbi.univie.ac.at or sven@tbi.univie.ac.at. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

  11. Tailoring vibration mode shapes using topology optimization and functionally graded material concepts

    NASA Astrophysics Data System (ADS)

    Montealegre Rubio, Wilfredo; Paulino, Glaucio H.; Nelli Silva, Emilio Carlos

    2011-02-01

    Tailoring specified vibration modes is a requirement for designing piezoelectric devices aimed at dynamic-type applications. A technique for designing the shape of specified vibration modes is the topology optimization method (TOM) which finds an optimum material distribution inside a design domain to obtain a structure that vibrates according to specified eigenfrequencies and eigenmodes. Nevertheless, when the TOM is applied to dynamic problems, the well-known grayscale or intermediate material problem arises which can invalidate the post-processing of the optimal result. Thus, a more natural way for solving dynamic problems using TOM is to allow intermediate material values. This idea leads to the functionally graded material (FGM) concept. In fact, FGMs are materials whose properties and microstructure continuously change along a specific direction. Therefore, in this paper, an approach is presented for tailoring user-defined vibration modes, by applying the TOM and FGM concepts to design functionally graded piezoelectric transducers (FGPT) and non-piezoelectric structures (functionally graded structures—FGS) in order to achieve maximum and/or minimum vibration amplitudes at certain points of the structure, by simultaneously finding the topology and material gradation function. The optimization problem is solved by using sequential linear programming. Two-dimensional results are presented to illustrate the method.

  12. Versatile Gene-Specific Sequence Tags for Arabidopsis Functional Genomics: Transcript Profiling and Reverse Genetics Applications

    PubMed Central

    Hilson, Pierre; Allemeersch, Joke; Altmann, Thomas; Aubourg, Sébastien; Avon, Alexandra; Beynon, Jim; Bhalerao, Rishikesh P.; Bitton, Frédérique; Caboche, Michel; Cannoot, Bernard; Chardakov, Vasil; Cognet-Holliger, Cécile; Colot, Vincent; Crowe, Mark; Darimont, Caroline; Durinck, Steffen; Eickhoff, Holger; de Longevialle, Andéol Falcon; Farmer, Edward E.; Grant, Murray; Kuiper, Martin T.R.; Lehrach, Hans; Léon, Céline; Leyva, Antonio; Lundeberg, Joakim; Lurin, Claire; Moreau, Yves; Nietfeld, Wilfried; Paz-Ares, Javier; Reymond, Philippe; Rouzé, Pierre; Sandberg, Goran; Segura, Maria Dolores; Serizet, Carine; Tabrett, Alexandra; Taconnat, Ludivine; Thareau, Vincent; Van Hummelen, Paul; Vercruysse, Steven; Vuylsteke, Marnik; Weingartner, Magdalena; Weisbeek, Peter J.; Wirta, Valtteri; Wittink, Floyd R.A.; Zabeau, Marc; Small, Ian

    2004-01-01

    Microarray transcript profiling and RNA interference are two new technologies crucial for large-scale gene function studies in multicellular eukaryotes. Both rely on sequence-specific hybridization between complementary nucleic acid strands, inciting us to create a collection of gene-specific sequence tags (GSTs) representing at least 21,500 Arabidopsis genes and which are compatible with both approaches. The GSTs were carefully selected to ensure that each of them shared no significant similarity with any other region in the Arabidopsis genome. They were synthesized by PCR amplification from genomic DNA. Spotted microarrays fabricated from the GSTs show good dynamic range, specificity, and sensitivity in transcript profiling experiments. The GSTs have also been transferred to bacterial plasmid vectors via recombinational cloning protocols. These cloned GSTs constitute the ideal starting point for a variety of functional approaches, including reverse genetics. We have subcloned GSTs on a large scale into vectors designed for gene silencing in plant cells. We show that in planta expression of GST hairpin RNA results in the expected phenotypes in silenced Arabidopsis lines. These versatile GST resources provide novel and powerful tools for functional genomics. PMID:15489341

  13. Modern Technologies for Creating Synthetic Antibodies for Clinical application

    PubMed Central

    Lebedenko, E. N.

    2009-01-01

    The modular structure and versatility of antibodies enables one to modify natural immunoglobulins in different ways for various clinical applications. Rational design and molecular engineering make it possible to directionally modify the molecular size, affinity, specificity, and immunogenicity and effector functions of an antibody, as well as to combine them with other functional agents. This review focuses on up-to-date methods of antibody engineering for diagnosing and treating various diseases, particularly on new technologies meant to refine the effector functions of therapeutic antibodies. PMID:22649585

  14. Applying Quality Function Deployment Model in Burn Unit Service Improvement.

    PubMed

    Keshtkaran, Ali; Hashemi, Neda; Kharazmi, Erfan; Abbasi, Mehdi

    2016-01-01

    Quality function deployment (QFD) is one of the most effective quality design tools. This study applies QFD technique to improve the quality of the burn unit services in Ghotbedin Hospital in Shiraz, Iran. First, the patients' expectations of burn unit services and their priorities were determined through Delphi method. Thereafter, burn unit service specifications were determined through Delphi method. Further, the relationships between the patients' expectations and service specifications and also the relationships between service specifications were determined through an expert group's opinion. Last, the final importance scores of service specifications were calculated through simple additive weighting method. The findings show that burn unit patients have 40 expectations in six different areas. These expectations are in 16 priority levels. Burn units also have 45 service specifications in six different areas. There are four-level relationships between the patients' expectations and service specifications and four-level relationships between service specifications. The most important burn unit service specifications have been identified in this study. The QFD model developed in the study can be a general guideline for QFD planners and executives.

  15. Designed protein reveals structural determinants of extreme kinetic stability

    PubMed Central

    Broom, Aron; Ma, S. Martha; Xia, Ke; Rafalia, Hitesh; Trainor, Kyle; Colón, Wilfredo; Gosavi, Shachi; Meiering, Elizabeth M.

    2015-01-01

    The design of stable, functional proteins is difficult. Improved design requires a deeper knowledge of the molecular basis for design outcomes and properties. We previously used a bioinformatics and energy function method to design a symmetric superfold protein composed of repeating structural elements with multivalent carbohydrate-binding function, called ThreeFoil. This and similar methods have produced a notably high yield of stable proteins. Using a battery of experimental and computational analyses we show that despite its small size and lack of disulfide bonds, ThreeFoil has remarkably high kinetic stability and its folding is specifically chaperoned by carbohydrate binding. It is also extremely stable against thermal and chemical denaturation and proteolytic degradation. We demonstrate that the kinetic stability can be predicted and modeled using absolute contact order (ACO) and long-range order (LRO), as well as coarse-grained simulations; the stability arises from a topology that includes many long-range contacts which create a large and highly cooperative energy barrier for unfolding and folding. Extensive data from proteomic screens and other experiments reveal that a high ACO/LRO is a general feature of proteins with strong resistances to denaturation and degradation. These results provide tractable approaches for predicting resistance and designing proteins with sufficient topological complexity and long-range interactions to accommodate destabilizing functional features as well as withstand chemical and proteolytic challenge. PMID:26554002

  16. SU-E-T-785: Using Systems Engineering to Design HDR Skin Treatment Operation for Small Lesions to Enhance Patient Safety

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

    Saw, C; Baikadi, M; Peters, C

    2015-06-15

    Purpose: Using systems engineering to design HDR skin treatment operation for small lesions using shielded applicators to enhance patient safety. Methods: Systems engineering is an interdisciplinary field that offers formal methodologies to study, design, implement, and manage complex engineering systems as a whole over their life-cycles. The methodologies deal with human work-processes, coordination of different team, optimization, and risk management. The V-model of systems engineering emphasize two streams, the specification and the testing streams. The specification stream consists of user requirements, functional requirements, and design specifications while the testing on installation, operational, and performance specifications. In implementing system engineering tomore » this project, the user and functional requirements are (a) HDR unit parameters be downloaded from the treatment planning system, (b) dwell times and positions be generated by treatment planning system, (c) source decay be computer calculated, (d) a double-check system of treatment parameters to comply with the NRC regulation. These requirements are intended to reduce human intervention to improve patient safety. Results: A formal investigation indicated that the user requirements can be satisfied. The treatment operation consists of using the treatment planning system to generate a pseudo plan that is adjusted for different shielded applicators to compute the dwell times. The dwell positions, channel numbers, and the dwell times are verified by the medical physicist and downloaded into the HDR unit. The decayed source strength is transferred to a spreadsheet that computes the dwell times based on the type of applicators and prescribed dose used. Prior to treatment, the source strength, dwell times, dwell positions, and channel numbers are double-checked by the radiation oncologist. No dosimetric parameters are manually calculated. Conclusion: Systems engineering provides methodologies to effectively design the HDR treatment operation that minimize human intervention and improve patient safety.« less

  17. An investigation of the validity of six measures of physical function in people awaiting joint replacement surgery of the hip or knee.

    PubMed

    Gill, Stephen D; de Morton, Natalie A; Mc Burney, Helen

    2012-10-01

    To assess and compare the validity of six physical function measures in people awaiting hip or knee joint replacement. Eighty-two people awaiting hip or knee replacement were assessed using six physical function measures including the WOMAC Function scale, SF-36 Physical Function scale, SF-36 Physical Component Summary scale, Patient Specific Functional Scale, 30-second chair stand test, and 50-foot timed walk. Validity was assessed using a head-to-head comparison design. Convergent validity was demonstrated with significant correlations between most measures (Spearman's rho 0.22 to 0.71). The Patient Specific Functional Scale had the lowest correlations with other measures of physical function. Discriminant validity was demonstrated with low correlations between mental health and physical function scores (Spearman's rho -0.12 to 0.33). Only the WOMAC Function scale, 30-second chair stand test, and 50-foot timed walk demonstrated known groups validity when scores for participants who walked with a gait aid were compared with those who did not. Standardized response means and Guyatt's responsiveness indexes indicated that the SF-36 was the least responsive measure. For those awaiting joint replacement surgery of the hip or knee, the current investigation found that the WOMAC Function scale, 30-second chair stand test, and 50-foot timed walk demonstrated the most evidence of validity. The Patient Specific Functional Scale might complement other measures by capturing a different aspect of physical function.

  18. Rationale for windshield glass system specification requirements for shuttle orbiter

    NASA Technical Reports Server (NTRS)

    Hayashida, K.; King, G. L.; Tesinsiky, J.; Wittenburg, D. R.

    1972-01-01

    A preliminary procurement specification for the space shuttle orbiter windshield pane, and some of the design considerations and rationale leading to its development are presented. The windshield designer is given the necessary methods and procedures for assuring glass pane structural integrity by proof test. These methods and procedures are fully developed for annealed and thermally tempered aluminosilicate, borosilicate, and soda lime glass and for annealed fused silica. Application of the method to chemically tempered glass is considered. Other considerations are vision requirements, protection against bird impact, hail, frost, rain, and meteoroids. The functional requirements of the windshield system during landing, ferrying, boost, space flight, and entry are included.

  19. Design optimization of axial flow hydraulic turbine runner: Part II - multi-objective constrained optimization method

    NASA Astrophysics Data System (ADS)

    Peng, Guoyi; Cao, Shuliang; Ishizuka, Masaru; Hayama, Shinji

    2002-06-01

    This paper is concerned with the design optimization of axial flow hydraulic turbine runner blade geometry. In order to obtain a better design plan with good performance, a new comprehensive performance optimization procedure has been presented by combining a multi-variable multi-objective constrained optimization model with a Q3D inverse computation and a performance prediction procedure. With careful analysis of the inverse design of axial hydraulic turbine runner, the total hydraulic loss and the cavitation coefficient are taken as optimization objectives and a comprehensive objective function is defined using the weight factors. Parameters of a newly proposed blade bound circulation distribution function and parameters describing positions of blade leading and training edges in the meridional flow passage are taken as optimization variables.The optimization procedure has been applied to the design optimization of a Kaplan runner with specific speed of 440 kW. Numerical results show that the performance of designed runner is successfully improved through optimization computation. The optimization model is found to be validated and it has the feature of good convergence. With the multi-objective optimization model, it is possible to control the performance of designed runner by adjusting the value of weight factors defining the comprehensive objective function. Copyright

  20. Brazilian remote sensing receiving, recording and processing ground systems in the 1980's

    NASA Technical Reports Server (NTRS)

    Parada, N. D. J. (Principal Investigator)

    1984-01-01

    A ground station was built in Brazil to receive, record, and process TM data from LANDSAT satellites. The receiving/recording subsystem and the processing subsystem are discussed. Functional design specifications for the facility are addressed.

  1. Reusable rocket engine intelligent control system framework design, phase 2

    NASA Technical Reports Server (NTRS)

    Nemeth, ED; Anderson, Ron; Ols, Joe; Olsasky, Mark

    1991-01-01

    Elements of an advanced functional framework for reusable rocket engine propulsion system control are presented for the Space Shuttle Main Engine (SSME) demonstration case. Functional elements of the baseline functional framework are defined in detail. The SSME failure modes are evaluated and specific failure modes identified for inclusion in the advanced functional framework diagnostic system. Active control of the SSME start transient is investigated, leading to the identification of a promising approach to mitigating start transient excursions. Key elements of the functional framework are simulated and demonstration cases are provided. Finally, the advanced function framework for control of reusable rocket engines is presented.

  2. 3D Printed Surgical Instruments: The Design and Fabrication Process.

    PubMed

    George, Mitchell; Aroom, Kevin R; Hawes, Harvey G; Gill, Brijesh S; Love, Joseph

    2017-01-01

    3D printing is an additive manufacturing process allowing the creation of solid objects directly from a digital file. We believe recent advances in additive manufacturing may be applicable to surgical instrument design. This study investigates the feasibility, design and fabrication process of usable 3D printed surgical instruments. The computer-aided design package SolidWorks (Dassault Systemes SolidWorks Corp., Waltham MA) was used to design a surgical set including hemostats, needle driver, scalpel handle, retractors and forceps. These designs were then printed on a selective laser sintering (SLS) Sinterstation HiQ (3D Systems, Rock Hill SC) using DuraForm EX plastic. The final printed products were evaluated by practicing general surgeons for ergonomic functionality and performance, this included simulated surgery and inguinal hernia repairs on human cadavers. Improvements were identified and addressed by adjusting design and build metrics. Repeated manufacturing processes and redesigns led to the creation of multiple functional and fully reproducible surgical sets utilizing the user feedback of surgeons. Iterative cycles including design, production and testing took an average of 3 days. Each surgical set was built using the SLS Sinterstation HiQ with an average build time of 6 h per set. Functional 3D printed surgical instruments are feasible. Advantages compared to traditional manufacturing methods include no increase in cost for increased complexity, accelerated design to production times and surgeon specific modifications.

  3. GETPrime: a gene- or transcript-specific primer database for quantitative real-time PCR.

    PubMed

    Gubelmann, Carine; Gattiker, Alexandre; Massouras, Andreas; Hens, Korneel; David, Fabrice; Decouttere, Frederik; Rougemont, Jacques; Deplancke, Bart

    2011-01-01

    The vast majority of genes in humans and other organisms undergo alternative splicing, yet the biological function of splice variants is still very poorly understood in large part because of the lack of simple tools that can map the expression profiles and patterns of these variants with high sensitivity. High-throughput quantitative real-time polymerase chain reaction (qPCR) is an ideal technique to accurately quantify nucleic acid sequences including splice variants. However, currently available primer design programs do not distinguish between splice variants and also differ substantially in overall quality, functionality or throughput mode. Here, we present GETPrime, a primer database supported by a novel platform that uniquely combines and automates several features critical for optimal qPCR primer design. These include the consideration of all gene splice variants to enable either gene-specific (covering the majority of splice variants) or transcript-specific (covering one splice variant) expression profiling, primer specificity validation, automated best primer pair selection according to strict criteria and graphical visualization of the latter primer pairs within their genomic context. GETPrime primers have been extensively validated experimentally, demonstrating high transcript specificity in complex samples. Thus, the free-access, user-friendly GETPrime database allows fast primer retrieval and visualization for genes or groups of genes of most common model organisms, and is available at http://updepla1srv1.epfl.ch/getprime/. Database URL: http://deplanckelab.epfl.ch.

  4. GETPrime: a gene- or transcript-specific primer database for quantitative real-time PCR

    PubMed Central

    Gubelmann, Carine; Gattiker, Alexandre; Massouras, Andreas; Hens, Korneel; David, Fabrice; Decouttere, Frederik; Rougemont, Jacques; Deplancke, Bart

    2011-01-01

    The vast majority of genes in humans and other organisms undergo alternative splicing, yet the biological function of splice variants is still very poorly understood in large part because of the lack of simple tools that can map the expression profiles and patterns of these variants with high sensitivity. High-throughput quantitative real-time polymerase chain reaction (qPCR) is an ideal technique to accurately quantify nucleic acid sequences including splice variants. However, currently available primer design programs do not distinguish between splice variants and also differ substantially in overall quality, functionality or throughput mode. Here, we present GETPrime, a primer database supported by a novel platform that uniquely combines and automates several features critical for optimal qPCR primer design. These include the consideration of all gene splice variants to enable either gene-specific (covering the majority of splice variants) or transcript-specific (covering one splice variant) expression profiling, primer specificity validation, automated best primer pair selection according to strict criteria and graphical visualization of the latter primer pairs within their genomic context. GETPrime primers have been extensively validated experimentally, demonstrating high transcript specificity in complex samples. Thus, the free-access, user-friendly GETPrime database allows fast primer retrieval and visualization for genes or groups of genes of most common model organisms, and is available at http://updepla1srv1.epfl.ch/getprime/. Database URL: http://deplanckelab.epfl.ch. PMID:21917859

  5. Development and fabrication of patient-specific knee implant using additive manufacturing techniques

    NASA Astrophysics Data System (ADS)

    Zammit, Robert; Rochman, Arif

    2017-10-01

    Total knee replacement is the most effective treatment to relief pain and restore normal function in a diseased knee joint. The aim of this research was to develop a patient-specific knee implant which can be fabricated using additive manufacturing techniques and has reduced wear rates using a highly wear resistant materials. The proposed design was chosen based on implant requirements, such as reduction in wear rates as well as strong fixation. The patient-specific knee implant improves on conventional knee implants by modifying the articulating surfaces and bone-implant interfaces. Moreover, tribological tests of different polymeric wear couples were carried out to determine the optimal materials to use for the articulating surfaces. Finite element analysis was utilized to evaluate the stresses sustained by the proposed design. Finally, the patient-specific knee implant was successfully built using additive manufacturing techniques.

  6. Cosmic-ray interaction data for designing biological experiments in space

    NASA Astrophysics Data System (ADS)

    Straume, T.; Slaba, T. C.; Bhattacharya, S.; Braby, L. A.

    2017-05-01

    There is growing interest in flying biological experiments beyond low-Earth orbit (LEO) to measure biological responses potentially relevant to those expected during a human mission to Mars. Such experiments could be payloads onboard precursor missions, including unmanned private-public partnerships, as well as small low-cost spacecraft (satellites) designed specifically for biosentinel-type missions. It is the purpose of this paper to provide physical cosmic-ray interaction data and related information useful to biologists who may be planning such experiments. It is not the objective here to actually design such experiments or provide radiobiological response functions, which would be specific for each experiment and biological endpoint. Nuclide-specific flux and dose rates were calculated using OLTARIS and these results were used to determine particle traversal rates and doses in hypothetical biological targets. Comparisons are provided between GCR in interplanetary space and inside the ISS. Calculated probabilistic estimates of dose from solar particle events are also presented. Although the focus here is on biological experiments, the information provided may be useful for designing other payloads as well if the space radiation environment is a factor to be considered.

  7. Computational design of protein antigens that interact with the CDR H3 loop of HIV broadly neutralizing antibody 2F5

    PubMed Central

    Azoitei, M.L.; Ban, Y.A.; Kalyuzhny, O.; Guenaga, J.; Schroeter, A.; Porter, J.; Wyatt, R.; Schief, W.R.

    2015-01-01

    Rational design of proteins with novel binding specificities and increased affinity is one of the major goals of computational protein design. Epitope-scaffolds are a new class of antigens engineered by transplanting viral epitopes of pre-defined structure to protein scaffolds, or by building protein scaffolds around such epitopes. Epitope-scaffolds are of interest as vaccine components to attempt to elicit neutralizing antibodies targeting the specified epitope. In this study we developed a new computational protocol, MultiGraft Interface, that transplants epitopes but also designs additional scaffold features outside the epitope to enhance antibody-binding specificity and potentially influence the specificity of elicited antibodies. We employed MultiGraft Interface to engineer novel epitope-scaffolds that display the known epitope of HIV-1 neutralizing antibody 2F5 and that also interact with the functionally important CDR H3 antibody loop. MultiGraft Interface generated an epitope-scaffold that bound 2F5 with sub-nanomolar affinity (KD = 400 pM) and that interacted with the antibody CDR H3 loop through computationally designed contacts. Substantial structural modifications were necessary to engineer this antigen, with the 2F5 epitope replacing a helix in the native scaffold and with 15% of the native scaffold sequence being modified in the design stage. This epitope-scaffold represents a successful example of rational protein backbone engineering and protein-protein interface design and could prove useful in the field of HIV vaccine design. MultiGraft Interface can be generally applied to engineer novel binding partners with altered specificity and optimized affinity. PMID:25043744

  8. Rotor-state feedback in the design of flight control laws for a hovering helicopter

    NASA Technical Reports Server (NTRS)

    Takahashi, Marc D.

    1994-01-01

    The use of rigid-body and rotor-state feedback gains in the design of helicopter flight control laws was investigated analytically on a blade element, articulated rotor, helicopter model. The study was conducted while designing a control law to meet an existing military rotorcraft handling qualities design specification (ADS-33C) in low-speed flight. A systematic approach to meet this specification was developed along with an assessment of the function of these gains in the feedback loops. Using the results of this assessment, the pitch and roll crossover behavior was easily modified by adjusting the body attitude and rotor-flap feedback gains. Critical to understanding the feedback gains is that the roll and pitch rate dynamics each have second-order behavior, not the classic first-order behavior, which arises from a quasi-static rotor, six degree-of-freedom model.

  9. Conceptual design and structural analysis for an 8.4-m telescope

    NASA Astrophysics Data System (ADS)

    Mendoza, Manuel; Farah, Alejandro; Ruiz Schneider, Elfego

    2004-09-01

    This paper describes the conceptual design of the optics support structures of a telescope with a primary mirror of 8.4 m, the same size as a Large Binocular Telescope (LBT) primary mirror. The design goal is to achieve a structure for supporting the primary and secondary mirrors and keeping them joined as rigid as possible. With this purpose an optimization with several models was done. This iterative design process includes: specifications development, concepts generation and evaluation. Process included Finite Element Analysis (FEA) as well as other analytical calculations. Quality Function Deployment (QFD) matrix was used to obtain telescope tube and spider specifications. Eight spiders and eleven tubes geometric concepts were proposed. They were compared in decision matrixes using performance indicators and parameters. Tubes and spiders went under an iterative optimization process. The best tubes and spiders concepts were assembled together. All assemblies were compared and ranked according to their performance.

  10. Principles of nanoparticle design for overcoming biological barriers to drug delivery

    PubMed Central

    Blanco, Elvin; Shen, Haifa; Ferrari, Mauro

    2016-01-01

    Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery. PMID:26348965

  11. Waveform generation in the EETS

    NASA Astrophysics Data System (ADS)

    Wilshire, J. P.

    1985-05-01

    Design decisions and analysis for the waveform generation portion of an electrical equipment test set are discussed. This test set is unlike conventional ATE in that it is portable and designed to operate in forward area sites for the USMC. It is also unique in that it provides for functional testing for 32 electronic units from the AV-88 Harrier II aircraft. Specific requirements for the waveform generator are discussed, including a wide frequency range, high resolution and accuracy, and low total harmonic distortion. Several approaches to meet these requirements are considered and a specific concept is presented in detail, which consists of a digitally produced waveform that feeds a deglitched analog conversion circuit. Rigorous mathematical analysis is presented to prove that this concept meets the requirements. Finally, design alternatives and enhancements are considered.

  12. Enhanced protective role in materials with gradient structural orientations: Lessons from Nature.

    PubMed

    Liu, Zengqian; Zhu, Yankun; Jiao, Da; Weng, Zhaoyong; Zhang, Zhefeng; Ritchie, Robert O

    2016-10-15

    Living organisms are adept at resisting contact deformation and damage by assembling protective surfaces with spatially varied mechanical properties, i.e., by creating functionally graded materials. Such gradients, together with multiple length-scale hierarchical structures, represent the two prime characteristics of many biological materials to be translated into engineering design. Here, we examine one design motif from a variety of biological tissues and materials where site-specific mechanical properties are generated for enhanced protection by adopting gradients in structural orientation over multiple length-scales, without manipulation of composition or microstructural dimension. Quantitative correlations are established between the structural orientations and local mechanical properties, such as stiffness, strength and fracture resistance; based on such gradients, the underlying mechanisms for the enhanced protective role of these materials are clarified. Theoretical analysis is presented and corroborated through numerical simulations of the indentation behavior of composites with distinct orientations. The design strategy of such bioinspired gradients is outlined in terms of the geometry of constituents. This study may offer a feasible approach towards generating functionally graded mechanical properties in synthetic materials for improved contact damage resistance. Living organisms are adept at resisting contact damage by assembling protective surfaces with spatially varied mechanical properties, i.e., by creating functionally-graded materials. Such gradients, together with multiple length-scale hierarchical structures, represent the prime characteristics of many biological materials. Here, we examine one design motif from a variety of biological tissues where site-specific mechanical properties are generated for enhanced protection by adopting gradients in structural orientation at multiple length-scales, without changes in composition or microstructural dimension. The design strategy of such bioinspired gradients is outlined in terms of the geometry of constituents. This study may offer a feasible approach towards generating functionally-graded mechanical properties in synthetic materials for improved damage resistance. Published by Elsevier Ltd.

  13. Just-in-time Design and Additive Manufacture of Patient-specific Medical Implants

    NASA Astrophysics Data System (ADS)

    Shidid, Darpan; Leary, Martin; Choong, Peter; Brandt, Milan

    Recent advances in medical imaging and manufacturing science have enabled the design and production of complex, patient-specific orthopaedic implants. Additive Manufacture (AM) generates three-dimensional structures layer by layer, and is not subject to the constraints associated with traditional manufacturing methods. AM provides significant opportunities for the design of novel geometries and complex lattice structures with enhanced functional performance. However, the design and manufacture of patient-specific AM implant structures requires unique expertise in handling various optimization platforms. Furthermore, the design process for complex structures is computationally intensive. The primary aim of this research is to enable the just-in-time customisation of AM prosthesis; whereby AM implant design and manufacture be completed within the time constraints of a single surgical procedure, while minimising prosthesis mass and optimising the lattice structure to match the stiffness of the surrounding bone tissue. In this research, a design approach using raw CT scan data is applied to the AM manufacture of femoral prosthesis. Using the proposed just-in-time concept, the mass of the prosthesis was rapidly designed and manufactured while satisfying the associated structural requirements. Compressive testing of lattice structures manufactured using proposed method shows that the load carrying capacity of the resected composite bone can be recovered by up to 85% and the compressive stiffness of the AM prosthesis is statistically indistinguishable from the stiffness of the initial bone.

  14. A patient self-assessment tool for cardiac rehabilitation.

    PubMed

    Phelan, C; Finnell, M D; Mottla, K A

    1989-01-01

    A patient self-assessment tool was designed, tested, and implemented to promote cardiac-specific data collection, based on Gordon's Functional Health Patterns, to maximize patient/family involvement in determining a plan of care, and to streamline primary nurses' documentation requirements. Retrospective and concurrent chart reviews provided data for quality assurance monitoring. The results of the monitoring demonstrated that the self-assessment tool markedly improved the patient-specific data base.

  15. Geonames Processing System Functional Design Specification. Volume 5. Performance Specifications.

    DTIC Science & Technology

    1985-03-01

    Chinese, Japanese , and Thai are the important ideographies to consider for electronic names processing. Chinese and Japanese character sets are...was no written Japanese language. Chinese characters are called Kanji by the Japanese . There are approximately 55(X) Chinese characters of common...Kanji was taken from A.V. Hershey, "Calligraphy for Computers," U.S. Naval Weapons Laboratory, Dahlgren, VA, August 1967. AD (-2398. C-1 Japanese

  16. Usability flaws of medication-related alerting functions: A systematic qualitative review.

    PubMed

    Marcilly, Romaric; Ammenwerth, Elske; Vasseur, Francis; Roehrer, Erin; Beuscart-Zéphir, Marie-Catherine

    2015-06-01

    Medication-related alerting functions may include usability flaws that limit their optimal use. A first step on the way to preventing usability flaws is to understand the characteristics of these usability flaws. This systematic qualitative review aims to analyze the type of usability flaws found in medication-related alerting functions. Papers were searched via PubMed, Scopus and Ergonomics Abstracts databases, along with references lists. Paper selection, data extraction and data analysis was performed by two to three Human Factors experts. Meaningful semantic units representing instances of usability flaws were the main data extracted. They were analyzed through qualitative methods: categorization following general usability heuristics and through an inductive process for the flaws specific to medication-related alerting functions. From the 6380 papers initially identified, 26 met all eligibility criteria. The analysis of the papers identified a total of 168 instances of usability flaws that could be classified into 13 categories of usability flaws representing either violations of general usability principles (i.e. they could be found in any system, e.g. guidance and workload issues) or infractions specific to medication-related alerting functions. The latter refer to issues of low signal-to-noise ratio, incomplete content of alerts, transparency, presentation mode and timing, missing alert features, tasks and control distribution. The list of 168 instances of usability flaws of medication-related alerting functions provides a source of knowledge for checking the usability of medication-related alerting functions during their design and evaluation process and ultimately constructs evidence-based usability design principles for these functions. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Image-Based Patient-Specific Ventricle Models with Fluid-Structure Interaction for Cardiac Function Assessment and Surgical Design Optimization

    PubMed Central

    Tang, Dalin; Yang, Chun; Geva, Tal; del Nido, Pedro J.

    2010-01-01

    Recent advances in medical imaging technology and computational modeling techniques are making it possible that patient-specific computational ventricle models be constructed and used to test surgical hypotheses and replace empirical and often risky clinical experimentation to examine the efficiency and suitability of various reconstructive procedures in diseased hearts. In this paper, we provide a brief review on recent development in ventricle modeling and its potential application in surgical planning and management of tetralogy of Fallot (ToF) patients. Aspects of data acquisition, model selection and construction, tissue material properties, ventricle layer structure and tissue fiber orientations, pressure condition, model validation and virtual surgery procedures (changing patient-specific ventricle data and perform computer simulation) were reviewed. Results from a case study using patient-specific cardiac magnetic resonance (CMR) imaging and right/left ventricle and patch (RV/LV/Patch) combination model with fluid-structure interactions (FSI) were reported. The models were used to evaluate and optimize human pulmonary valve replacement/insertion (PVR) surgical procedure and patch design and test a surgical hypothesis that PVR with small patch and aggressive scar tissue trimming in PVR surgery may lead to improved recovery of RV function and reduced stress/strain conditions in the patch area. PMID:21344066

  18. Geometrical specifications accuracy influence on the quality of electromechanical devices

    NASA Astrophysics Data System (ADS)

    Glukhov, V. I.; Lakeenko, M. N.; Dolzhikov, S. N.

    2017-06-01

    To improve the quality of electromechanical products is possible due to the geometrical specifications optimization of values and tolerances. Electromechanical products longevity designates the rolling-contact bearings of the armature shaft. Longevity of the rolling-contact bearings is less than designed one, since assembly and fitting alter gaps, sizes and geometric tolerances for the working parts of the basic rolling bearing details. Geometrical models of the rolling-contact bearing details for the armature shaft and the end shield are developed on the basis of an electric locomotive traction motor in the present work. The basic elements of the details conjugating with the adjacent details and materializing the generalized and auxiliary coordinate systems are determined. Function, informativeness and the number of geometrical specifications for the elements location are specified. The recommendations on amending the design documentation due to geometrical models to improve the accuracy and the quality of the products are developed: the replacement of the common axis of the shaft’s technological datums by the common axis of the basic design datums; coaxiality tolerances for these design datums with respect to their common axis; the modifiers for these auxiliary datums and these datums location tolerances according to the principles of datums uniformity, inversion and the shortest dimension chains. The investigation demonstrated that the problem of enhancing the durability, longevity, and efficiency coefficient for electromechanical products can be solved with the systematic normalizations of geometrical specifications accuracy on the basis of the coordinate systems introduced in the standards on geometrical product specifications (GPS).

  19. Acute Achilles Tendon Rupture: Clinical Evaluation, Conservative Management, and Early Active Rehabilitation.

    PubMed

    Kauwe, Merrell

    2017-04-01

    The Achilles tendon (AT) is the strongest, largest, and most commonly ruptured tendon in the human body. Physical examination provides high sensitivity and specificity. Imaging studies are not recommended unless there are equivocal findings in the physical examination. Recent studies have shown that the risk of re-rupture is negated with implementation of functional rehabilitation protocols. Heterogeneity in study design makes conclusions on the specifics of functional rehabilitation protocols difficult; however, it is clear that early weight bearing and early controlled mobilization lead to better patient outcome and satisfaction in both surgically and conservatively treated populations. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Selective targeting of melanoma by PEG-masked protein-based multifunctional nanoparticles

    PubMed Central

    Vannucci, Luca; Falvo, Elisabetta; Fornara, Manuela; Di Micco, Patrizio; Benada, Oldrich; Krizan, Jiri; Svoboda, Jan; Hulikova-Capkova, Katarina; Morea, Veronica; Boffi, Alberto; Ceci, Pierpaolo

    2012-01-01

    Background Nanoparticle-based systems are promising for the development of imaging and therapeutic agents. The main advantage of nanoparticles over traditional systems lies in the possibility of loading multiple functionalities onto a single molecule, which are useful for therapeutic and/or diagnostic purposes. These functionalities include targeting moieties which are able to recognize receptors overexpressed by specific cells and tissues. However, targeted delivery of nanoparticles requires an accurate system design. We present here a rationally designed, genetically engineered, and chemically modified protein-based nanoplatform for cell/tissue-specific targeting. Methods Our nanoparticle constructs were based on the heavy chain of the human protein ferritin (HFt), a highly symmetrical assembly of 24 subunits enclosing a hollow cavity. HFt-based nanoparticles were produced using both genetic engineering and chemical functionalization methods to impart several functionalities, ie, the α-melanocyte-stimulating hormone peptide as a melanoma-targeting moiety, stabilizing and HFt-masking polyethylene glycol molecules, rhodamine fluorophores, and magnetic resonance imaging agents. The constructs produced were extensively characterized by a number of physicochemical techniques, and assayed for selective melanoma-targeting in vitro and in vivo. Results Our HFt-based nanoparticle constructs functionalized with the α-melanocyte-stimulating hormone peptide moiety and polyethylene glycol molecules were specifically taken up by melanoma cells but not by other cancer cell types in vitro. Moreover, experiments in melanoma-bearing mice indicate that these constructs have an excellent tumor-targeting profile and a long circulation time in vivo. Conclusion By masking human HFt with polyethylene glycol and targeting it with an α-melanocyte-stimulating hormone peptide, we developed an HFt-based melanoma-targeting nanoplatform for application in melanoma diagnosis and treatment. These results could be of general interest, because the same strategy can be exploited to develop ad hoc nanoplatforms for specific delivery towards any cell/tissue type for which a suitable targeting moiety is available. PMID:22619508

  1. The Designed Environment and How it Affects Brain Morphology and Mental Health.

    PubMed

    Golembiewski, Jan A

    2016-01-01

    The environment is inextricably related to mental health. Recent research replicates findings of a significant, linear correlation between a childhood exposure to the urban environment and psychosis. Related studies also correlate the urban environment and aberrant brain morphologies. These findings challenge common beliefs that the mind and brain remain neutral in the face of worldly experience. There is a signature within these neurological findings that suggests that specific features of design cause and trigger mental illness. The objective in this article is to work backward from the molecular dynamics to identify features of the designed environment that may either trigger mental illness or protect against it. This review analyzes the discrete functions putatively assigned to the affected brain areas and a neurotransmitter called dopamine, which is the primary target of most antipsychotic medications. The intention is to establish what the correlations mean in functional terms, and more specifically, how this relates to the phenomenology of urban experience. In doing so, environmental mental illness risk factors are identified. Having established these relationships, the review makes practical recommendations for those in public health who wish to use the environment itself as a tool to improve the mental health of a community through design. © The Author(s) 2015.

  2. Decoupling local mechanics from large-scale structure in modular metamaterials

    NASA Astrophysics Data System (ADS)

    Yang, Nan; Silverberg, Jesse L.

    2017-04-01

    A defining feature of mechanical metamaterials is that their properties are determined by the organization of internal structure instead of the raw fabrication materials. This shift of attention to engineering internal degrees of freedom has coaxed relatively simple materials into exhibiting a wide range of remarkable mechanical properties. For practical applications to be realized, however, this nascent understanding of metamaterial design must be translated into a capacity for engineering large-scale structures with prescribed mechanical functionality. Thus, the challenge is to systematically map desired functionality of large-scale structures backward into a design scheme while using finite parameter domains. Such “inverse design” is often complicated by the deep coupling between large-scale structure and local mechanical function, which limits the available design space. Here, we introduce a design strategy for constructing 1D, 2D, and 3D mechanical metamaterials inspired by modular origami and kirigami. Our approach is to assemble a number of modules into a voxelized large-scale structure, where the module’s design has a greater number of mechanical design parameters than the number of constraints imposed by bulk assembly. This inequality allows each voxel in the bulk structure to be uniquely assigned mechanical properties independent from its ability to connect and deform with its neighbors. In studying specific examples of large-scale metamaterial structures we show that a decoupling of global structure from local mechanical function allows for a variety of mechanically and topologically complex designs.

  3. Ligand-targeted theranostic nanomedicines against cancer

    DOE PAGES

    Yao, Virginia J.; D'Angelo, Sara; Butler, Kimberly S.; ...

    2016-01-06

    Nanomedicines have significant potential for cancer treatment. Although the majority of nanomedicines currently tested in clinical trials utilize simple, biocompatible liposome-based nanocarriers, their widespread use is limited by non-specificity and low target site concentration and thus, do not provide a substantial clinical advantage over conventional, systemic chemotherapy. In the past 20 years, we have identified specific receptors expressed on the surfaces of tumor endothelial and perivascular cells, tumor cells, the extracellular matrix and stromal cells using combinatorial peptide libraries displayed on bacteriophage. These studies corroborate the notion that unique receptor proteins such as IL-11Rα, GRP78, EphA5, among others, are differentiallymore » overexpressed in tumors and present opportunities to deliver tumor-specific therapeutic drugs. By using peptides that bind to tumor-specific cell-surface receptors, therapeutic agents such as apoptotic peptides, suicide genes, imaging dyes or chemotherapeutics can be precisely and systemically delivered to reduce tumor growth in vivo, without harming healthy cells. Given the clinical applicability of peptide-based therapeutics, targeted delivery of nanocarriers loaded with therapeutic cargos seems plausible. We propose a modular design of a functionalized protocell in which a tumor-targeting moiety, such as a peptide or recombinant human antibody single chain variable fragment (scFv), is conjugated to a lipid bilayer surrounding a silica-based nanocarrier core containing a protected therapeutic cargo. The functionalized protocell can be tailored to a specific cancer subtype and treatment regimen by exchanging the tumor-targeting moiety and/or therapeutic cargo or used in combination to create unique, theranostic agents. In this review, we summarize the identification of tumor-specific receptors through combinatorial phage display technology and the use of antibody display selection to identify recombinant human scFvs against these tumor-specific receptors. We compare the characteristics of different types of simple and complex nanocarriers, and discuss potential types of therapeutic cargos and conjugation strategies. As a result, the modular design of functionalized protocells may improve the efficacy and safety of nanomedicines for future cancer therapy.« less

  4. Ligand-targeted theranostic nanomedicines against cancer

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

    Yao, Virginia J.; D'Angelo, Sara; Butler, Kimberly S.

    Nanomedicines have significant potential for cancer treatment. Although the majority of nanomedicines currently tested in clinical trials utilize simple, biocompatible liposome-based nanocarriers, their widespread use is limited by non-specificity and low target site concentration and thus, do not provide a substantial clinical advantage over conventional, systemic chemotherapy. In the past 20 years, we have identified specific receptors expressed on the surfaces of tumor endothelial and perivascular cells, tumor cells, the extracellular matrix and stromal cells using combinatorial peptide libraries displayed on bacteriophage. These studies corroborate the notion that unique receptor proteins such as IL-11Rα, GRP78, EphA5, among others, are differentiallymore » overexpressed in tumors and present opportunities to deliver tumor-specific therapeutic drugs. By using peptides that bind to tumor-specific cell-surface receptors, therapeutic agents such as apoptotic peptides, suicide genes, imaging dyes or chemotherapeutics can be precisely and systemically delivered to reduce tumor growth in vivo, without harming healthy cells. Given the clinical applicability of peptide-based therapeutics, targeted delivery of nanocarriers loaded with therapeutic cargos seems plausible. We propose a modular design of a functionalized protocell in which a tumor-targeting moiety, such as a peptide or recombinant human antibody single chain variable fragment (scFv), is conjugated to a lipid bilayer surrounding a silica-based nanocarrier core containing a protected therapeutic cargo. The functionalized protocell can be tailored to a specific cancer subtype and treatment regimen by exchanging the tumor-targeting moiety and/or therapeutic cargo or used in combination to create unique, theranostic agents. In this review, we summarize the identification of tumor-specific receptors through combinatorial phage display technology and the use of antibody display selection to identify recombinant human scFvs against these tumor-specific receptors. We compare the characteristics of different types of simple and complex nanocarriers, and discuss potential types of therapeutic cargos and conjugation strategies. As a result, the modular design of functionalized protocells may improve the efficacy and safety of nanomedicines for future cancer therapy.« less

  5. Computation-Guided Backbone Grafting of a Discontinuous Motif onto a Protein Scaffold

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

    Azoitei, Mihai L.; Correia, Bruno E.; Ban, Yih-En Andrew

    2012-02-07

    The manipulation of protein backbone structure to control interaction and function is a challenge for protein engineering. We integrated computational design with experimental selection for grafting the backbone and side chains of a two-segment HIV gp120 epitope, targeted by the cross-neutralizing antibody b12, onto an unrelated scaffold protein. The final scaffolds bound b12 with high specificity and with affinity similar to that of gp120, and crystallographic analysis of a scaffold bound to b12 revealed high structural mimicry of the gp120-b12 complex structure. The method can be generalized to design other functional proteins through backbone grafting.

  6. Synthetic biology through biomolecular design and engineering.

    PubMed

    Channon, Kevin; Bromley, Elizabeth H C; Woolfson, Derek N

    2008-08-01

    Synthetic biology is a rapidly growing field that has emerged in a global, multidisciplinary effort among biologists, chemists, engineers, physicists, and mathematicians. Broadly, the field has two complementary goals: To improve understanding of biological systems through mimicry and to produce bio-orthogonal systems with new functions. Here we review the area specifically with reference to the concept of synthetic biology space, that is, a hierarchy of components for, and approaches to generating new synthetic and functional systems to test, advance, and apply our understanding of biological systems. In keeping with this issue of Current Opinion in Structural Biology, we focus largely on the design and engineering of biomolecule-based components and systems.

  7. SODR Memory Control Buffer Control ASIC

    NASA Technical Reports Server (NTRS)

    Hodson, Robert F.

    1994-01-01

    The Spacecraft Optical Disk Recorder (SODR) is a state of the art mass storage system for future NASA missions requiring high transmission rates and a large capacity storage system. This report covers the design and development of an SODR memory buffer control applications specific integrated circuit (ASIC). The memory buffer control ASIC has two primary functions: (1) buffering data to prevent loss of data during disk access times, (2) converting data formats from a high performance parallel interface format to a small computer systems interface format. Ten 144 p in, 50 MHz CMOS ASIC's were designed, fabricated and tested to implement the memory buffer control function.

  8. An improved design method for EPC middleware

    NASA Astrophysics Data System (ADS)

    Lou, Guohuan; Xu, Ran; Yang, Chunming

    2014-04-01

    For currently existed problems and difficulties during the small and medium enterprises use EPC (Electronic Product Code) ALE (Application Level Events) specification to achieved middleware, based on the analysis of principle of EPC Middleware, an improved design method for EPC middleware is presented. This method combines the powerful function of MySQL database, uses database to connect reader-writer with upper application system, instead of development of ALE application program interface to achieve a middleware with general function. This structure is simple and easy to implement and maintain. Under this structure, different types of reader-writers added can be configured conveniently and the expandability of the system is improved.

  9. Ion transport across the biological membrane by computational protein design

    NASA Astrophysics Data System (ADS)

    Grigoryan, Gevorg

    The cellular membrane is impermeable to most of the chemicals the cell needs to take in or discard to survive. Therefore, transporters-a class of transmembrane proteins tasked with shuttling cargo chemicals in and out of the cell-are essential to all cellular life. From existing crystal structures, we know transporters to be complex machines, exquisitely tuned for specificity and controllability. But how could membrane-bound life have evolved if it needed such complex machines to exist first? To shed light onto this question, we considered the task of designing a transporter de novo. As our guiding principle, we took the ``alternating-access model''-a conceptual mechanism stating that transporters work by rocking between two conformations, each exposing the cargo-binding site to either the intra- or the extra-cellular environment. A computational design framework was developed to encode an anti-parallel four-helix bundle that rocked between two alternative states to orchestrate the movement of Zn(II) ions across the membrane. The ensemble nature of both states was accounted for using a free energy-based approach, and sequences were chosen based on predicted formation of the targeted topology in the membrane and bi-stability. A single sequence was prepared experimentally and shown to function as a Zn(II) transporter in lipid vesicles. Further, transport was specific to Zn(II) ions and several control peptides supported the underlying design principles. This included a mutant designed to retain all properties but with reduced rocking, which showed greatly depressed transport ability. These results suggest that early transporters could have evolved in the context of simple topologies, to be later tuned by evolution for improved properties and controllability. Our study also serves as an important advance in computational protein design, showing the feasibility of designing functional membrane proteins and of tuning conformational landscapes for desired function. Alfred P. Sloan Foundation Research Fellowship.

  10. Model-based Utility Functions

    NASA Astrophysics Data System (ADS)

    Hibbard, Bill

    2012-05-01

    Orseau and Ring, as well as Dewey, have recently described problems, including self-delusion, with the behavior of agents using various definitions of utility functions. An agent's utility function is defined in terms of the agent's history of interactions with its environment. This paper argues, via two examples, that the behavior problems can be avoided by formulating the utility function in two steps: 1) inferring a model of the environment from interactions, and 2) computing utility as a function of the environment model. Basing a utility function on a model that the agent must learn implies that the utility function must initially be expressed in terms of specifications to be matched to structures in the learned model. These specifications constitute prior assumptions about the environment so this approach will not work with arbitrary environments. But the approach should work for agents designed by humans to act in the physical world. The paper also addresses the issue of self-modifying agents and shows that if provided with the possibility to modify their utility functions agents will not choose to do so, under some usual assumptions.

  11. Cushing's syndrome mutant PKA L205R exhibits altered substrate specificity

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

    Lubner, Joshua M.; Dodge-Kafka, Kimberly L.; Carlson, Cathrine R.

    The PKA L205R hotspot mutation has been implicated in Cushing's syndrome through hyperactive gain-of-function PKA signaling; however, its influence on substrate specificity has not been investigated. Here, we employ the Proteomic Peptide Library (ProPeL) approach to create high-resolution models for PKA WT and PKA L205R substrate specificity. We reveal that the L205R mutation reduces canonical hydrophobic preference at the substrate P + 1 position, and increases acidic preference in downstream positions. Using these models, we designed peptide substrates that exhibit altered selectivity for specific PKA variants, and demonstrate the feasibility of selective PKA L205R loss-of-function signaling. Through these results, wemore » suggest that substrate rewiring may contribute to Cushing's syndrome disease etiology, and introduce a powerful new paradigm for investigating mutation-induced kinase substrate rewiring in human disease.« less

  12. Cushing's syndrome mutant PKA L205R exhibits altered substrate specificity

    DOE PAGES

    Lubner, Joshua M.; Dodge-Kafka, Kimberly L.; Carlson, Cathrine R.; ...

    2017-02-01

    The PKA L205R hotspot mutation has been implicated in Cushing's syndrome through hyperactive gain-of-function PKA signaling; however, its influence on substrate specificity has not been investigated. Here, we employ the Proteomic Peptide Library (ProPeL) approach to create high-resolution models for PKA WT and PKA L205R substrate specificity. We reveal that the L205R mutation reduces canonical hydrophobic preference at the substrate P + 1 position, and increases acidic preference in downstream positions. Using these models, we designed peptide substrates that exhibit altered selectivity for specific PKA variants, and demonstrate the feasibility of selective PKA L205R loss-of-function signaling. Through these results, wemore » suggest that substrate rewiring may contribute to Cushing's syndrome disease etiology, and introduce a powerful new paradigm for investigating mutation-induced kinase substrate rewiring in human disease.« less

  13. Space Station Freedom biomedical monitoring and countermeasures: Biomedical facility hardware catalog

    NASA Technical Reports Server (NTRS)

    1990-01-01

    This hardware catalog covers that hardware proposed under the Biomedical Monitoring and Countermeasures Development Program supported by the Johnson Space Center. The hardware items are listed separately by item, and are in alphabetical order. Each hardware item specification consists of four pages. The first page describes background information with an illustration, definition and a history/design status. The second page identifies the general specifications, performance, rack interface requirements, problems, issues, concerns, physical description, and functional description. The level of hardware design reliability is also identified under the maintainability and reliability category. The third page specifies the mechanical design guidelines and assumptions. Described are the material types and weights, modules, and construction methods. Also described is an estimation of percentage of construction which utilizes a particular method, and the percentage of required new mechanical design is documented. The fourth page analyzes the electronics, the scope of design effort, and the software requirements. Electronics are described by percentages of component types and new design. The design effort, as well as, the software requirements are identified and categorized.

  14. Optimization of infobutton design and Implementation: A systematic review.

    PubMed

    Teixeira, Miguel; Cook, David A; Heale, Bret S E; Del Fiol, Guilherme

    2017-10-01

    Infobuttons are clinical decision tools embedded in the electronic health record that attempt to link clinical data with context sensitive knowledge resources. We systematically reviewed technical approaches that contribute to improved infobutton design, implementation and functionality. We searched databases including MEDLINE, EMBASE, and the Cochrane Library database from inception to March 1, 2016 for studies describing the use of infobuttons. We selected full review comparative studies, usability studies, and qualitative studies examining infobutton design and implementation. We abstracted usability measures such as user satisfaction, impact, and efficiency, as well as prediction accuracy of infobutton content retrieval algorithms and infobutton adoption/interoperability. We found 82 original research studies on infobuttons. Twelve studies met criteria for detailed abstraction. These studies investigated infobutton interoperability (1 study); tools to help tailor infobutton functionality (1 study); interventions to improve user experience (7 studies); and interventions to improve content retrieval by improving prediction of relevant knowledge resources and information needs (3 studies). In-depth interviews with implementers showed the Health Level Seven (HL7) Infobutton standard to be simple and easy to implement. A usability study demonstrated the feasibility of a tool to help medical librarians tailor infobutton functionality. User experience studies showed that access to resources with which users are familiar increased user satisfaction ratings; and that links to specific subsections of drug monographs increased information seeking efficiency. However, none of the user experience improvements led to increased usage uptake. Recommender systems based on machine learning algorithms outperformed hand-crafted rules in the prediction of relevant resources and clinicians' information needs in a laboratory setting, but no studies were found using these techniques in clinical settings. Improved content indexing in one study led to improved content retrieval across three health care organizations. Best practice technical approaches to ensure optimal infobutton functionality, design and implementation remain understudied. The HL7 Infobutton standard has supported wide adoption of infobutton functionality among clinical information systems and knowledge resources. Limited evidence supports infobutton enhancements such as links to specific subtopics, configuration of optimal resources for specific tasks and users, and improved indexing and content coverage. Further research is needed to investigate user experience improvements to increase infobutton use and effectiveness. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. System engineering toolbox for design-oriented engineers

    NASA Technical Reports Server (NTRS)

    Goldberg, B. E.; Everhart, K.; Stevens, R.; Babbitt, N., III; Clemens, P.; Stout, L.

    1994-01-01

    This system engineering toolbox is designed to provide tools and methodologies to the design-oriented systems engineer. A tool is defined as a set of procedures to accomplish a specific function. A methodology is defined as a collection of tools, rules, and postulates to accomplish a purpose. For each concept addressed in the toolbox, the following information is provided: (1) description, (2) application, (3) procedures, (4) examples, if practical, (5) advantages, (6) limitations, and (7) bibliography and/or references. The scope of the document includes concept development tools, system safety and reliability tools, design-related analytical tools, graphical data interpretation tools, a brief description of common statistical tools and methodologies, so-called total quality management tools, and trend analysis tools. Both relationship to project phase and primary functional usage of the tools are also delineated. The toolbox also includes a case study for illustrative purposes. Fifty-five tools are delineated in the text.

  16. Properties of a center/surround retinex. Part 2: Surround design

    NASA Technical Reports Server (NTRS)

    Jobson, Daniel J.; Woodell, Glenn A.

    1995-01-01

    The last version of Edwin Land's retinex model for human vision's lightness and color constancy has been implemented. Previous research has established the mathematical foundations of Land's retinex but has not examined specific design issues and their effects on the properties of the retinex operation. We have sought to define a practical implementation of the retinex without particular concern for its validity as a model for human lightness and color perception. Here we describe issues involved in designing the surround function. We find that there is a trade-off between rendition and dynamic range compression that is governed by the surround space constant. Various functional forms for the retinex surround are evaluated and a Gaussian form is found to perform better than the inverse square suggested by Land. Preliminary testing led to the design of a Gaussian surround with a space constant of 80 pixels as a reasonable compromise between dynamic range compression and rendition.

  17. Protein design to understand peptide ligand recognition by tetratricopeptide repeat proteins.

    PubMed

    Cortajarena, Aitziber L; Kajander, Tommi; Pan, Weilan; Cocco, Melanie J; Regan, Lynne

    2004-04-01

    Protein design aims to understand the fundamentals of protein structure by creating novel proteins with pre-specified folds. An equally important goal is to understand protein function by creating novel proteins with pre-specified activities. Here we describe the design and characterization of a tetratricopeptide (TPR) protein, which binds to the C-terminal peptide of the eukaryotic chaperone Hsp90. The design emphasizes the importance of both direct, short-range protein-peptide interactions and of long-range electrostatic optimization. We demonstrate that the designed protein binds specifically to the desired peptide and discriminates between it and the similar C-terminal peptide of Hsp70.

  18. Annotations for the Collaboration of the Health Professionals

    PubMed Central

    Bringay, Sandra; Barry, Catherine; Charlet, Jean

    2006-01-01

    In the French DocPatient project, we work on documentary functionalities to improve the use of the electronic medical record. We suggest that integration of specific uses for paper medical documents in the design of the electronic medical record will improve its utility, use and acceptance. We propose in this paper to add a functionality of annotations in the electronic medical record to reinforce collaboration, coordination and awareness. PMID:17238309

  19. Team Training for Dynamic Cross-Functional Teams in Aviation: Behavioral, Cognitive, and Performance Outcomes.

    PubMed

    Littlepage, Glenn E; Hein, Michael B; Moffett, Richard G; Craig, Paul A; Georgiou, Andrea M

    2016-12-01

    This study evaluates the effectiveness of a training program designed to improve cross-functional coordination in airline operations. Teamwork across professional specializations is essential for safe and efficient airline operations, but aviation education primarily emphasizes positional knowledge and skill. Although crew resource management training is commonly used to provide some degree of teamwork training, it is generally focused on specific specializations, and little training is provided in coordination across specializations. The current study describes and evaluates a multifaceted training program designed to enhance teamwork and team performance of cross-functional teams within a simulated airline flight operations center. The training included a variety of components: orientation training, position-specific declarative knowledge training, position-specific procedural knowledge training, a series of high-fidelity team simulations, and a series of after-action reviews. Following training, participants demonstrated more effective teamwork, development of transactive memory, and more effective team performance. Multifaceted team training that incorporates positional training and team interaction in complex realistic situations and followed by after-action reviews can facilitate teamwork and team performance. Team training programs, such as the one described here, have potential to improve the training of aviation professionals. These techniques can be applied to other contexts where multidisciplinary teams and multiteam systems work to perform highly interdependent activities. © 2016, Human Factors and Ergonomics Society.

  20. DNA Photo Lithography with Cinnamate-based Photo-Bio-Nano-Glue

    NASA Astrophysics Data System (ADS)

    Feng, Lang; Li, Minfeng; Romulus, Joy; Sha, Ruojie; Royer, John; Wu, Kun-Ta; Xu, Qin; Seeman, Nadrian; Weck, Marcus; Chaikin, Paul

    2013-03-01

    We present a technique to make patterned functional surfaces, using a cinnamate photo cross-linker and photolithography. We have designed and modified a complementary set of single DNA strands to incorporate a pair of opposing cinnamate molecules. On exposure to 360nm UV, the cinnamate makes a highly specific covalent bond permanently linking only the complementary strands containing the cinnamates. We have studied this specific and efficient crosslinking with cinnamate-containing DNA in solution and on particles. UV addressability allows us to pattern surfaces functionally. The entire surface is coated with a DNA sequence A incorporating cinnamate. DNA strands A'B with one end containing a complementary cinnamated sequence A' attached to another sequence B, are then hybridized to the surface. UV photolithography is used to bind the A'B strand in a specific pattern. The system is heated and the unbound DNA is washed away. The pattern is then observed by thermo-reversibly hybridizing either fluorescently dyed B' strands complementary to B, or colloids coated with B' strands. Our techniques can be used to reversibly and/or permanently bind, via DNA linkers, an assortment of molecules, proteins and nanostructures. Potential applications range from advanced self-assembly, such as templated self-replication schemes recently reported, to designed physical and chemical patterns, to high-resolution multi-functional DNA surfaces for genetic detection or DNA computing.

  1. Rapid Design of Knowledge-Based Scoring Potentials for Enrichment of Near-Native Geometries in Protein-Protein Docking.

    PubMed

    Sasse, Alexander; de Vries, Sjoerd J; Schindler, Christina E M; de Beauchêne, Isaure Chauvot; Zacharias, Martin

    2017-01-01

    Protein-protein docking protocols aim to predict the structures of protein-protein complexes based on the structure of individual partners. Docking protocols usually include several steps of sampling, clustering, refinement and re-scoring. The scoring step is one of the bottlenecks in the performance of many state-of-the-art protocols. The performance of scoring functions depends on the quality of the generated structures and its coupling to the sampling algorithm. A tool kit, GRADSCOPT (GRid Accelerated Directly SCoring OPTimizing), was designed to allow rapid development and optimization of different knowledge-based scoring potentials for specific objectives in protein-protein docking. Different atomistic and coarse-grained potentials can be created by a grid-accelerated directly scoring dependent Monte-Carlo annealing or by a linear regression optimization. We demonstrate that the scoring functions generated by our approach are similar to or even outperform state-of-the-art scoring functions for predicting near-native solutions. Of additional importance, we find that potentials specifically trained to identify the native bound complex perform rather poorly on identifying acceptable or medium quality (near-native) solutions. In contrast, atomistic long-range contact potentials can increase the average fraction of near-native poses by up to a factor 2.5 in the best scored 1% decoys (compared to existing scoring), emphasizing the need of specific docking potentials for different steps in the docking protocol.

  2. The role of nutritional support in the physical and functional recovery of critically ill patients: a narrative review.

    PubMed

    Bear, Danielle E; Wandrag, Liesl; Merriweather, Judith L; Connolly, Bronwen; Hart, Nicholas; Grocott, Michael P W

    2017-08-26

    The lack of benefit from randomised controlled trials has resulted in significant controversy regarding the role of nutrition during critical illness in terms of long-term recovery and outcome. Although methodological caveats with a failure to adequately appreciate biological mechanisms may explain these disappointing results, it must be acknowledged that nutritional support during early critical illness, when considered alone, may have limited long-term functional impact.This narrative review focuses specifically on recent clinical trials and evaluates the impact of nutrition during critical illness on long-term physical and functional recovery.Specific focus on the trial design and methodological limitations has been considered in detail. Limitations include delivery of caloric and protein targets, patient heterogeneity, short duration of intervention, inappropriate clinical outcomes and a disregard for baseline nutritional status and nutritional intake in the post-ICU period.With survivorship at the forefront of critical care research, it is imperative that nutrition studies carefully consider biological mechanisms and trial design because these factors can strongly influence outcomes, in particular long-term physical and functional outcome. Failure to do so may lead to inconclusive clinical trials and consequent rejection of the potentially beneficial effects of nutrition interventions during critical illness.

  3. Bioinspired synthesis and self-assembly of hybrid organic–inorganic nanomaterials

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

    Zhang, Honghu

    Nature is replete with complex organic–inorganic hierarchical materials of diverse yet specific functions. These materials are intricately designed under physiological conditions through biomineralization and biological self-assembly processes. Tremendous efforts have been devoted to investigating mechanisms of such biomineralization and biological self-assembly processes as well as gaining inspiration to develop biomimetic methods for synthesis and self-assembly of functional nanomaterials. In this work, we focus on the bioinspired synthesis and self-assembly of functional inorganic nanomaterials templated by specialized macromolecules including proteins, DNA and polymers. The in vitro biomineralization process of the magnetite biomineralizing protein Mms6 has been investigated using small-angle X-ray scattering.more » Templated by Mms6, complex magnetic nanomaterials can be synthesized on surfaces and in the bulk. DNA and synthetic polymers have been exploited to construct macroscopic two- and three-dimensional (2D and 3D) superlattices of gold nanocrystals. Employing X-ray scattering and spectroscopy techniques, the self-assembled structures and the self-assembly mechanisms have been studied, and theoretical models have been developed. Our results show that specialized macromolecules including proteins, DNA and polymers act as effective templates for synthesis and self-assembly of nanomaterials. These bottom-up approaches provide promising routes to fabricate hybrid organic–inorganic nanomaterials with rationally designed hierarchical structures, targeting specific functions.« less

  4. [Steroid hormones and pancreas: a new paradigm].

    PubMed

    Morales-Miranda, Angélica; Robles-Díaz, Guillermo; Díaz-Sánchez, Vicente

    2007-01-01

    The relation between steroid hormones and pancreatic function has been poorly discussed and not very well understood. In general, there is a lack of recognition among the scientific community about the importance of steroids in pancreatic function (current paradigm). In the present article we present basic, as well as clinic and epidemiologic data that demonstrate steroid synthesis and steroid biotransformation by pancreatic tissue, how exocrine and endocrine functions are modulated by steroids, the gender specific frequency and behavior of some tumors and the use of synthetic steroids and steroid action antagonists as therapeutic agents. With the available information it is possible to establish that: 1. Pancreatic tissue synthesize and transform steroid hormones. 2. Pancreatic tissue respond to steroid hormones and express steroid specific receptor molecules. 3. Some endocrine functions such as insulin synthesis and release are modulated by steroids. 4. Tumor growth is modulated by steroids and anti-steroid drugs. This set of data creates a new paradigm for the holistic study of pancreas and opens new research fields. The application of this new paradigm might result in an increase in the knowledge of pancreatic physiology, in the design of new and better diagnostic methods and eventually in the design of more effective medical treatments for the pancreatic cancers.

  5. Design and testing of RFID sensor tag fabricated using inkjet-printing and electrodeposition

    NASA Astrophysics Data System (ADS)

    Chien Dang, Mau; Son Nguyen, Dat; Dung Dang, Thi My; Tedjini, Smail; Fribourg-Blanc, Eric

    2014-06-01

    The passive RFID tag with an added sensing function is of interest to many applications. In particular, applications where RFID tagging is already considered to be the next step, such as food items, are a specific target. This paper demonstrates a flexible RFID tag sensor fabricated using a low cost technique with an added zero-cost sensing function. It is more specifically applied to the sensing of degradable food, in particular beef meat in our demonstrated example. To reach this, the antenna is designed in such a way to be sensitive to the variation of the dielectric permittivity of the meat over time. The design of the sensing tag as well as its fabrication process are described. The fabrication involves inkjet printing of a silver nanoparticle based ink on a commercial low cost PET film to create a seed layer. It is followed by a copper electrodeposition step on top of the silver pattern to complete the tag to obtain the desired thickness and conductivity of the tag antenna. The results of the electrical tests showed that with the inkjet printing-electrodeposition combination it is possible to produce flexible electrically conductive patterns for practical RFID applications. The tag was then tested in close-to-real-world conditions and it is demonstrated that it can provide a sensing function to detect the consumption limit of the packaged beef.

  6. A new adaptive videogame for training attention and executive functions: design principles and initial validation.

    PubMed

    Montani, Veronica; De Filippo De Grazia, Michele; Zorzi, Marco

    2014-01-01

    A growing body of evidence suggests that action videogames could enhance a variety of cognitive skills and more specifically attention skills. The aim of this study was to develop a novel adaptive videogame to support the rehabilitation of the most common consequences of traumatic brain injury (TBI), that is the impairment of attention and executive functions. TBI patients can be affected by psychomotor slowness and by difficulties in dealing with distraction, maintain a cognitive set for a long time, processing different simultaneously presented stimuli, and planning purposeful behavior. Accordingly, we designed a videogame that was specifically conceived to activate those functions. Playing involves visuospatial planning and selective attention, active maintenance of the cognitive set representing the goal, and error monitoring. Moreover, different game trials require to alternate between two tasks (i.e., task switching) or to perform the two tasks simultaneously (i.e., divided attention/dual-tasking). The videogame is controlled by a multidimensional adaptive algorithm that calibrates task difficulty on-line based on a model of user performance that is updated on a trial-by-trial basis. We report simulations of user performance designed to test the adaptive game as well as a validation study with healthy participants engaged in a training protocol. The results confirmed the involvement of the cognitive abilities that the game is supposed to enhance and suggested that training improved attentional control during play.

  7. A new adaptive videogame for training attention and executive functions: design principles and initial validation

    PubMed Central

    Montani, Veronica; De Filippo De Grazia, Michele; Zorzi, Marco

    2014-01-01

    A growing body of evidence suggests that action videogames could enhance a variety of cognitive skills and more specifically attention skills. The aim of this study was to develop a novel adaptive videogame to support the rehabilitation of the most common consequences of traumatic brain injury (TBI), that is the impairment of attention and executive functions. TBI patients can be affected by psychomotor slowness and by difficulties in dealing with distraction, maintain a cognitive set for a long time, processing different simultaneously presented stimuli, and planning purposeful behavior. Accordingly, we designed a videogame that was specifically conceived to activate those functions. Playing involves visuospatial planning and selective attention, active maintenance of the cognitive set representing the goal, and error monitoring. Moreover, different game trials require to alternate between two tasks (i.e., task switching) or to perform the two tasks simultaneously (i.e., divided attention/dual-tasking). The videogame is controlled by a multidimensional adaptive algorithm that calibrates task difficulty on-line based on a model of user performance that is updated on a trial-by-trial basis. We report simulations of user performance designed to test the adaptive game as well as a validation study with healthy participants engaged in a training protocol. The results confirmed the involvement of the cognitive abilities that the game is supposed to enhance and suggested that training improved attentional control during play. PMID:24860529

  8. Genome health nutrigenomics and nutrigenetics--diagnosis and nutritional treatment of genome damage on an individual basis.

    PubMed

    Fenech, Michael

    2008-04-01

    The term nutrigenomics refers to the effect of diet on gene expression. The term nutrigenetics refers to the impact of inherited traits on the response to a specific dietary pattern, functional food or supplement on a specific health outcome. The specific fields of genome health nutrigenomics and genome health nutrigenetics are emerging as important new research areas because it is becoming increasingly evident that (a) risk for developmental and degenerative disease increases with DNA damage which in turn is dependent on nutritional status and (b) optimal concentration of micronutrients for prevention of genome damage is also dependent on genetic polymorphisms that alter function of genes involved directly or indirectly in uptake and metabolism of micronutrients required for DNA repair and DNA replication. Development of dietary patterns, functional foods and supplements that are designed to improve genome health maintenance in humans with specific genetic backgrounds may provide an important contribution to a new optimum health strategy based on the diagnosis and individualised nutritional treatment of genome instability i.e. Genome Health Clinics.

  9. 22 CFR 121.1 - General. The United States Munitions List.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Firearms or other weapons (e.g. insurgency-counterinsurgency, close assault weapons systems) having a... IV. * (d) Kinetic energy weapon systems specifically designed or modified for destruction or... physical test models. (i) Autoloading systems for electronic programming of projectile function for the...

  10. 22 CFR 209.3 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Relations AGENCY FOR INTERNATIONAL DEVELOPMENT NON-DISCRIMINATION IN FEDERALLY-ASSISTED PROGRAMS OF THE... person specifically designated by him to perform any function provided for under this part. (c) The term..., or by a primary recipient as a condition to eligibility for Federal financial assistance, and the...

  11. 22 CFR 209.3 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Relations AGENCY FOR INTERNATIONAL DEVELOPMENT NON-DISCRIMINATION IN FEDERALLY-ASSISTED PROGRAMS OF THE... person specifically designated by him to perform any function provided for under this part. (c) The term..., or by a primary recipient as a condition to eligibility for Federal financial assistance, and the...

  12. 22 CFR 209.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Relations AGENCY FOR INTERNATIONAL DEVELOPMENT NON-DISCRIMINATION IN FEDERALLY-ASSISTED PROGRAMS OF THE... person specifically designated by him to perform any function provided for under this part. (c) The term..., or by a primary recipient as a condition to eligibility for Federal financial assistance, and the...

  13. 22 CFR 209.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Relations AGENCY FOR INTERNATIONAL DEVELOPMENT NON-DISCRIMINATION IN FEDERALLY-ASSISTED PROGRAMS OF THE... person specifically designated by him to perform any function provided for under this part. (c) The term..., or by a primary recipient as a condition to eligibility for Federal financial assistance, and the...

  14. 22 CFR 209.3 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Relations AGENCY FOR INTERNATIONAL DEVELOPMENT NON-DISCRIMINATION IN FEDERALLY-ASSISTED PROGRAMS OF THE... person specifically designated by him to perform any function provided for under this part. (c) The term..., or by a primary recipient as a condition to eligibility for Federal financial assistance, and the...

  15. 40 CFR 85.1902 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... POLLUTION FROM MOBILE SOURCES Emission Defect Reporting Requirements § 85.1902 Definitions. For the purposes...) which affects any parameter or specification enumerated in appendix VIII of this part; or (2) A defect..., components, systems, software or elements of design which must function properly to ensure continued...

  16. 40 CFR 85.1902 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... POLLUTION FROM MOBILE SOURCES Emission Defect Reporting Requirements § 85.1902 Definitions. For the purposes...) which affects any parameter or specification enumerated in appendix VIII of this part; or (2) A defect..., components, systems, software or elements of design which must function properly to assure continued...

  17. 40 CFR 85.1902 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... POLLUTION FROM MOBILE SOURCES Emission Defect Reporting Requirements § 85.1902 Definitions. For the purposes...) which affects any parameter or specification enumerated in appendix VIII of this part; or (2) A defect..., components, systems, software or elements of design which must function properly to ensure continued...

  18. 40 CFR 85.1902 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... POLLUTION FROM MOBILE SOURCES Emission Defect Reporting Requirements § 85.1902 Definitions. For the purposes...) which affects any parameter or specification enumerated in appendix VIII of this part; or (2) A defect..., components, systems, software or elements of design which must function properly to ensure continued...

  19. Advanced information processing system: Input/output system services

    NASA Technical Reports Server (NTRS)

    Masotto, Tom; Alger, Linda

    1989-01-01

    The functional requirements and detailed specifications for the Input/Output (I/O) Systems Services of the Advanced Information Processing System (AIPS) are discussed. The introductory section is provided to outline the overall architecture and functional requirements of the AIPS system. Section 1.1 gives a brief overview of the AIPS architecture as well as a detailed description of the AIPS fault tolerant network architecture, while section 1.2 provides an introduction to the AIPS systems software. Sections 2 and 3 describe the functional requirements and design and detailed specifications of the I/O User Interface and Communications Management modules of the I/O System Services, respectively. Section 4 illustrates the use of the I/O System Services, while Section 5 concludes with a summary of results and suggestions for future work in this area.

  20. Chance of Vulnerability Reduction in Application-Specific NoC through Distance Aware Mapping Algorithm

    NASA Astrophysics Data System (ADS)

    Janidarmian, Majid; Fekr, Atena Roshan; Bokharaei, Vahhab Samadi

    2011-08-01

    Mapping algorithm which means which core should be linked to which router is one of the key issues in the design flow of network-on-chip. To achieve an application-specific NoC design procedure that minimizes the communication cost and improves the fault tolerant property, first a heuristic mapping algorithm that produces a set of different mappings in a reasonable time is presented. This algorithm allows the designers to identify the set of most promising solutions in a large design space, which has low communication costs while yielding optimum communication costs in some cases. Another evaluated parameter, vulnerability index, is then considered as a principle of estimating the fault-tolerance property in all produced mappings. Finally, in order to yield a mapping which considers trade-offs between these two parameters, a linear function is defined and introduced. It is also observed that more flexibility to prioritize solutions within the design space is possible by adjusting a set of if-then rules in fuzzy logic.

  1. Advanced photovoltaic solar array - Design and performance

    NASA Technical Reports Server (NTRS)

    Kurland, Richard; Stella, Paul

    1992-01-01

    This paper reports on the development of an ultralightweight flexible blanket, flatpack, foldout solar array design that can provide 3- to 4-fold improvement on specific power performance of current rigid panel arrays and a factor of two improvement over a first-generation flexible blanket array developed as a forerunner to the Space Station Freedom array. To date a prototype wing has been built with a projected specific power performance of about 138 W/kg at beginning-of-life (BOL) and 93 W/kg end-of-life (EOL) at 12 kW (BOL) for a 10-year geosynchronous (GEO) mission. The prototype wing hardware has been subjected to a series of system-level tests to demonstrate design feasibility. The design of the array is summarized. The major trade studies that led to the selection of the baseline design are discussed. Key system-level and component-level testing are described. Array-level performance projections are presented as a function of existing and advanced solar array component technology for various mission applications.

  2. The Influence of Free Space Environment in the Mission Life Cycle: Material Selection

    NASA Technical Reports Server (NTRS)

    Edwards, David L.; Burns, Howard D.; de Groh, Kim K.

    2014-01-01

    The natural space environment has a great influence on the ability of space systems to perform according to mission design specification. Understanding the natural space environment and its influence on space system performance is critical to the concept formulation, design, development, and operation of space systems. Compatibility with the natural space environment is a primary factor in determining the functional lifetime of the space system. Space systems being designed and developed today are growing in complexity. In many instances, the increased complexity also increases its sensitivity to space environmental effects. Sensitivities to the natural space environment can be tempered through appropriate design measures, material selection, ground processing, mitigation strategies, and/or the acceptance of known risks. The design engineer must understand the effects of the natural space environment on the space system and its components. This paper will discuss the influence of the natural space environment in the mission life cycle with a specific focus on the role of material selection.

  3. Effects of an Advanced Reactor’s Design, Use of Automation, and Mission on Human Operators

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

    Jeffrey C. Joe; Johanna H. Oxstrand

    The roles, functions, and tasks of the human operator in existing light water nuclear power plants (NPPs) are based on sound nuclear and human factors engineering (HFE) principles, are well defined by the plant’s conduct of operations, and have been validated by years of operating experience. However, advanced NPPs whose engineering designs differ from existing light-water reactors (LWRs) will impose changes on the roles, functions, and tasks of the human operators. The plans to increase the use of automation, reduce staffing levels, and add to the mission of these advanced NPPs will also affect the operator’s roles, functions, and tasks.more » We assert that these factors, which do not appear to have received a lot of attention by the design engineers of advanced NPPs relative to the attention given to conceptual design of these reactors, can have significant risk implications for the operators and overall plant safety if not mitigated appropriately. This paper presents a high-level analysis of a specific advanced NPP and how its engineered design, its plan to use greater levels of automation, and its expanded mission have risk significant implications on operator performance and overall plant safety.« less

  4. A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions

    PubMed Central

    Khalil, Ahmad S.; Lu, Timothy K.; Bashor, Caleb J.; Ramirez, Cherie L.; Pyenson, Nora C.; Joung, J. Keith; Collins, James J.

    2013-01-01

    SUMMARY Eukaryotic transcription factors (TFs) perform complex and combinatorial functions within transcriptional networks. Here, we present a synthetic framework for systematically constructing eukaryotic transcription functions using artificial zinc fingers, modular DNA-binding domains found within many eukaryotic TFs. Utilizing this platform, we construct a library of orthogonal synthetic transcription factors (sTFs) and use these to wire synthetic transcriptional circuits in yeast. We engineer complex functions, such as tunable output strength and transcriptional cooperativity, by rationally adjusting a decomposed set of key component properties, e.g., DNA specificity, affinity, promoter design, protein-protein interactions. We show that subtle perturbations to these properties can transform an individual sTF between distinct roles (activator, cooperative factor, inhibitory factor) within a transcriptional complex, thus drastically altering the signal processing behavior of multi-input systems. This platform provides new genetic components for synthetic biology and enables bottom-up approaches to understanding the design principles of eukaryotic transcriptional complexes and networks. PMID:22863014

  5. Designing food structures for nutrition and health benefits.

    PubMed

    Norton, Jennifer E; Wallis, Gareth A; Spyropoulos, Fotis; Lillford, Peter J; Norton, Ian T

    2014-01-01

    In addition to providing specific sensory properties (e.g., flavor or textures), there is a need to produce foods that also provide functionality within the gastrointestinal (GI) tract, over and above simple nutrition. As such, there is a need to understand the physical and chemical processes occurring in the mouth, stomach, small intestine, and large intestine, in addition to the food structure-physiology interactions. In vivo techniques and in vitro models have allowed us to study and simulate these processes, which aids us in the design of food microstructures that can provide functionality within the human body. Furthermore, it is important to be aware of the health or nutritional needs of different groups of consumers when designing food structures, to provide targeted functionality. Examples of three groups of consumers (elderly, obese, and athletes) are given to demonstrate their differing nutritional requirements and the formulation engineering approaches that can be utilized to improve the health of these individuals. Eating is a pleasurable process, but foods of the future will be required to provide much more in terms of functionality for health and nutrition.

  6. An innovative approach to compensator design

    NASA Technical Reports Server (NTRS)

    Mitchell, J. R.; Mcdaniel, W. L., Jr.

    1973-01-01

    The design is considered of a computer-aided-compensator for a control system from a frequency domain point of view. The design technique developed is based on describing the open loop frequency response by n discrete frequency points which result in n functions of the compensator coefficients. Several of these functions are chosen so that the system specifications are properly portrayed; then mathematical programming is used to improve all of these functions which have values below minimum standards. To do this, several definitions in regard to measuring the performance of a system in the frequency domain are given, e.g., relative stability, relative attenuation, proper phasing, etc. Next, theorems which govern the number of compensator coefficients necessary to make improvements in a certain number of functions are proved. After this a mathematical programming tool for aiding in the solution of the problem is developed. This tool is called the constraint improvement algorithm. Then for applying the constraint improvement algorithm generalized, gradients for the constraints are derived. Finally, the necessary theory is incorporated in a Computer program called CIP (compensator Improvement Program). The practical usefulness of CIP is demonstrated by two large system examples.

  7. Spatial design and strength of spatial signal: Effects on covariance estimation

    USGS Publications Warehouse

    Irvine, Kathryn M.; Gitelman, Alix I.; Hoeting, Jennifer A.

    2007-01-01

    In a spatial regression context, scientists are often interested in a physical interpretation of components of the parametric covariance function. For example, spatial covariance parameter estimates in ecological settings have been interpreted to describe spatial heterogeneity or “patchiness” in a landscape that cannot be explained by measured covariates. In this article, we investigate the influence of the strength of spatial dependence on maximum likelihood (ML) and restricted maximum likelihood (REML) estimates of covariance parameters in an exponential-with-nugget model, and we also examine these influences under different sampling designs—specifically, lattice designs and more realistic random and cluster designs—at differing intensities of sampling (n=144 and 361). We find that neither ML nor REML estimates perform well when the range parameter and/or the nugget-to-sill ratio is large—ML tends to underestimate the autocorrelation function and REML produces highly variable estimates of the autocorrelation function. The best estimates of both the covariance parameters and the autocorrelation function come under the cluster sampling design and large sample sizes. As a motivating example, we consider a spatial model for stream sulfate concentration.

  8. Special Features of Using Secondary Materials in the Interior Design of Public Dining Establishments

    NASA Astrophysics Data System (ADS)

    Kuznetsova, Irina; Hapchuk, Olena; Lukinov, Vitaly

    2017-10-01

    This article analyses the latest publications studying the use and practical application of secondary resources as raw materials in design. This analysis is based on the list of secondary resources and their applications in interior decoration. In particular, the interiors of public catering enterprises were analysed. Restaurants with different functional purposes that were classified into several categories with specific peculiarities of interior design were identified. This article presents and describes different types of public catering enterprises based on those categories. The interior design of a public catering enterprise is regarded as a considerably complex system. Different types of secondary materials were reviewed to identify the most frequently used materials for interior space design. This article describes the main peculiarities of the use of secondary materials and presents examples of their practical application. The function of secondary materials in the interior design of public catering enterprises were detected and reviewed. On the basis of the analysis, several directions for the practical application of our results in the field of public catering enterprise design were suggested.

  9. Vulnerability-Based Critical Neurons, Synapses, and Pathways in the Caenorhabditis elegans Connectome

    PubMed Central

    Kim, Seongkyun; Kim, Hyoungkyu; Kralik, Jerald D.; Jeong, Jaeseung

    2016-01-01

    Determining the fundamental architectural design of complex nervous systems will lead to significant medical and technological advances. Yet it remains unclear how nervous systems evolved highly efficient networks with near optimal sharing of pathways that yet produce multiple distinct behaviors to reach the organism’s goals. To determine this, the nematode roundworm Caenorhabditis elegans is an attractive model system. Progress has been made in delineating the behavioral circuits of the C. elegans, however, many details are unclear, including the specific functions of every neuron and synapse, as well as the extent the behavioral circuits are separate and parallel versus integrative and serial. Network analysis provides a normative approach to help specify the network design. We investigated the vulnerability of the Caenorhabditis elegans connectome by performing computational experiments that (a) “attacked” 279 individual neurons and 2,990 weighted synaptic connections (composed of 6,393 chemical synapses and 890 electrical junctions) and (b) quantified the effects of each removal on global network properties that influence information processing. The analysis identified 12 critical neurons and 29 critical synapses for establishing fundamental network properties. These critical constituents were found to be control elements—i.e., those with the most influence over multiple underlying pathways. Additionally, the critical synapses formed into circuit-level pathways. These emergent pathways provide evidence for (a) the importance of backward locomotion, avoidance behavior, and social feeding behavior to the organism; (b) the potential roles of specific neurons whose functions have been unclear; and (c) both parallel and serial design elements in the connectome—i.e., specific evidence for a mixed architectural design. PMID:27540747

  10. Shape-specific nanostructured protein mimics from de novo designed chimeric peptides.

    PubMed

    Jiang, Linhai; Yang, Su; Lund, Reidar; Dong, He

    2018-01-30

    Natural proteins self-assemble into highly-ordered nanoscaled architectures to perform specific functions. The intricate functions of proteins have provided great impetus for researchers to develop strategies for designing and engineering synthetic nanostructures as protein mimics. Compared to the success in engineering fibrous protein mimetics, the design of discrete globular protein-like nanostructures has been challenging mainly due to the lack of precise control over geometric packing and intermolecular interactions among synthetic building blocks. In this contribution, we report an effective strategy to construct shape-specific nanostructures based on the self-assembly of chimeric peptides consisting of a coiled coil dimer and a collagen triple helix folding motif. Under salt-free conditions, we showed spontaneous self-assembly of the chimeric peptides into monodisperse, trigonal bipyramidal-like nanoparticles with precise control over the stoichiometry of two folding motifs and the geometrical arrangements relative to one another. Three coiled coil dimers are interdigitated on the equatorial plane while the two collagen triple helices are located in the axial position, perpendicular to the coiled coil plane. A detailed molecular model was proposed and further validated by small angle X-ray scattering experiments and molecular dynamics (MD) simulation. The results from this study indicated that the molecular folding of each motif within the chimeric peptides and their geometric packing played important roles in the formation of discrete protein-like nanoparticles. The peptide design and self-assembly mechanism may open up new routes for the construction of highly organized, discrete self-assembling protein-like nanostructures with greater levels of control over assembly accuracy.

  11. Atrium building study

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

    Not Available

    1990-01-01

    The CIGNA design team was faced with creating a new 500,000 square foot office building on a pastoral 610 acre corporate campus in Bloomfield, Connecticut, just outside of Hartford. Challenges abounded during the design process, from the selection of a specific building site on the sprawling campus to the evolution of a building form incorporating an atrium, to the selection of building systems and materials, to the design to the office interiors and atrium landscape. This document summarizes the original design problem, focusing on design criteria and performance standards that led to the decision to design an atrium building asmore » well as decision concerning its function, its form, its building systems and materials, and its passive energy strategies.« less

  12. Design for Additive Bio-Manufacturing: From Patient-Specific Medical Devices to Rationally Designed Meta-Biomaterials.

    PubMed

    Zadpoor, Amir A

    2017-07-25

    Recent advances in additive manufacturing (AM) techniques in terms of accuracy, reliability, the range of processable materials, and commercial availability have made them promising candidates for production of functional parts including those used in the biomedical industry. The complexity-for-free feature offered by AM means that very complex designs become feasible to manufacture, while batch-size-indifference enables fabrication of fully patient-specific medical devices. Design for AM (DfAM) approaches aim to fully utilize those features for development of medical devices with substantially enhanced performance and biomaterials with unprecedented combinations of favorable properties that originate from complex geometrical designs at the micro-scale. This paper reviews the most important approaches in DfAM particularly those applicable to additive bio-manufacturing including image-based design pipelines, parametric and non-parametric designs, metamaterials, rational and computationally enabled design, topology optimization, and bio-inspired design. Areas with limited research have been identified and suggestions have been made for future research. The paper concludes with a brief discussion on the practical aspects of DfAM and the potential of combining AM with subtractive and formative manufacturing processes in so-called hybrid manufacturing processes.

  13. Design for Additive Bio-Manufacturing: From Patient-Specific Medical Devices to Rationally Designed Meta-Biomaterials

    PubMed Central

    Zadpoor, Amir A.

    2017-01-01

    Recent advances in additive manufacturing (AM) techniques in terms of accuracy, reliability, the range of processable materials, and commercial availability have made them promising candidates for production of functional parts including those used in the biomedical industry. The complexity-for-free feature offered by AM means that very complex designs become feasible to manufacture, while batch-size-indifference enables fabrication of fully patient-specific medical devices. Design for AM (DfAM) approaches aim to fully utilize those features for development of medical devices with substantially enhanced performance and biomaterials with unprecedented combinations of favorable properties that originate from complex geometrical designs at the micro-scale. This paper reviews the most important approaches in DfAM particularly those applicable to additive bio-manufacturing including image-based design pipelines, parametric and non-parametric designs, metamaterials, rational and computationally enabled design, topology optimization, and bio-inspired design. Areas with limited research have been identified and suggestions have been made for future research. The paper concludes with a brief discussion on the practical aspects of DfAM and the potential of combining AM with subtractive and formative manufacturing processes in so-called hybrid manufacturing processes. PMID:28757572

  14. NetList(+): A simple interface language for chip design

    NASA Astrophysics Data System (ADS)

    Wuu, Tzyh-Yung

    1991-04-01

    NetList (+) is a design specification language developed at MOSIS for rapid turn-around cell-based ASIC prototyping. By using NetList (+), a uniform representation is achieved for the specification, simulation, and physical description of a design. The goal is to establish an interfacing methodology between design specification and independent computer aided design tools. Designers need only to specify a system by writing a corresponding netlist. This netlist is used for both functional simulation and timing simulation. The same netlist is also used to derive the low level physical tools to generate layout. Another goal of using NetList (+) is to generate parts of a design by running it through different kinds of placement and routing (P and R) tools. For example some parts of a design will be generated by standard cell P and R tools. Other parts may be generated by a layout tiler; i.e., datapath compiler, RAM/ROM generator, or PLA generator. Finally all different parts of a design can be integrated by general block P and R tools as a single chip. The NetList (+) language can actually act as an interface among tools. Section 2 shows a flowchart to illustrate the NetList (+) system and its relation with other related design tools. Section 3 shows how to write a NetList (+) description from the block diagram of a circuit. In section 4 discusses how to prepare a cell library or several cell libraries for a design system. Section 5 gives a few designs by NetList (+) and shows their simulation and layout results.

  15. Definition of Specific Functions and Procedural Skills Required by Cuban Specialists in Intensive Care and Emergency Medicine.

    PubMed

    Véliz, Pedro L; Berra, Esperanza M; Jorna, Ana R

    2015-07-01

    INTRODUCTION Medical specialties' core curricula should take into account functions to be carried out, positions to be filled and populations to be served. The functions in the professional profile for specialty training of Cuban intensive care and emergency medicine specialists do not include all the activities that they actually perform in professional practice. OBJECTIVE Define the specific functions and procedural skills required of Cuban specialists in intensive care and emergency medicine. METHODS The study was conducted from April 2011 to September 2013. A three-stage methodological strategy was designed using qualitative techniques. By purposive maximum variation sampling, 82 professionals were selected. Documentary analysis and key informant criteria were used in the first stage. Two expert groups were formed in the second stage: one used various group techniques (focus group, oral and written brainstorming) and the second used a three-round Delphi method. In the final stage, a third group of experts was questioned in semistructured in-depth interviews, and a two-round Delphi method was employed to assess priorities. RESULTS Ultimately, 78 specific functions were defined: 47 (60.3%) patient care, 16 (20.5%) managerial, 6 (7.7%) teaching, and 9 (11.5%) research. Thirty-one procedural skills were identified. The specific functions and procedural skills defined relate to the profession's requirements in clinical care of the critically ill, management of patient services, teaching and research at the specialist's different occupational levels. CONCLUSIONS The specific functions and procedural skills required of intensive care and emergency medicine specialists were precisely identified by a scientific method. This product is key to improving the quality of teaching, research, administration and patient care in this specialty in Cuba. The specific functions and procedural skills identified are theoretical, practical, methodological and social contributions to inform future curricular reform and to help intensive care specialists enhance their performance in comprehensive patient care. KEYWORDS Intensive care, urgent care, emergency medicine, continuing medical education, curriculum, diagnostic techniques and procedures, medical residency, Cuba.

  16. Polymorphic Electronic Circuits

    NASA Technical Reports Server (NTRS)

    Stoica, Adrian

    2004-01-01

    Polymorphic electronics is a nascent technological discipline that involves, among other things, designing the same circuit to perform different analog and/or digital functions under different conditions. For example, a circuit can be designed to function as an OR gate or an AND gate, depending on the temperature (see figure). Polymorphic electronics can also be considered a subset of polytronics, which is a broader technological discipline in which optical and possibly other information- processing systems could also be designed to perform multiple functions. Polytronics is an outgrowth of evolvable hardware (EHW). The basic concepts and some specific implementations of EHW were described in a number of previous NASA Tech Briefs articles. To recapitulate: The essence of EHW is to design, construct, and test a sequence of populations of circuits that function as incrementally better solutions of a given design problem through the selective, repetitive connection and/or disconnection of capacitors, transistors, amplifiers, inverters, and/or other circuit building blocks. The evolution is guided by a search-and-optimization algorithm (in particular, a genetic algorithm) that operates in the space of possible circuits to find a circuit that exhibits an acceptably close approximation of the desired functionality. The evolved circuits can be tested by computational simulation (in which case the evolution is said to be extrinsic), tested in real hardware (in which case the evolution is said to be intrinsic), or tested in random sequences of computational simulation and real hardware (in which case the evolution is said to be mixtrinsic).

  17. Design of Heteronuclear Metalloenzymes

    PubMed Central

    Bhagi-Damodaran, Ambika; Hosseinzadeh, Parisa; Mirts, Evan; Reed, Julian; Petrik, Igor D.; Lu, Yi

    2016-01-01

    Heteronuclear metalloenzymes catalyze some of the most fundamentally interesting and practically useful reactions in nature. However, the presence of two or more metal ions in close proximity in these enzymes makes them more difficult to prepare and study than homonuclear metalloenzymes. To meet these challenges, heteronuclear metal centers have been designed into small and stable proteins with rigid scaffolds to understand how these heteronuclear centers are constructed and the mechanism of their function. This chapter describes methods for designing heterobinuclear metal centers in a protein scaffold by giving specific examples of a few heme-nonheme bimetallic centers engineered in myoglobin and cytochrome c peroxidase. We provide step-by-step procedure on how to choose the protein scaffold, design a heterobinuclear metal center in the protein computationally, incorporate metal centers in the protein and characterize the resulting metalloprotein, both structurally and functionally. Finally, we discuss how an initial design can be further improved by rationally tuning its secondary coordination sphere, electron/proton transfer rates, and the substrate affinity. PMID:27586347

  18. Design of a functional cyclic HSV1-TK reporter and its application to PET imaging of apoptosis

    PubMed Central

    Wang, Zhe; Wang, Fu; Hida, Naoki; Kiesewetter, Dale O; Tian, Jie; Niu, Gang; Chen, Xiaoyuan

    2017-01-01

    Positron emission tomography (PET) is a sensitive and noninvasive imaging method that is widely used to explore molecular events in living subjects. PET can precisely and quantitatively evaluate cellular apoptosis, which has a crucial role in various physiological and pathological processes. In this protocol, we describe the design and use of an engineered cyclic herpes simplex virus 1–thymidine kinase (HSV1-TK) PET reporter whose kinase activity is specifically switched on by apoptosis. The expression of cyclic TK (cTK) in healthy cells leads to inactive product, whereas the activation of apoptosis through the caspase-3 pathway cleaves cTK, thus restoring its activity and enabling PET imaging. In addition to detailing the design and construction of the cTK plasmid in this protocol, we include assays for evaluating the function and specificity of the cTK reporter in apoptotic cells, such as assays for measuring the cell uptake of PET tracer in apoptotic cells, correlating doxorubicin (Dox)-induced cell apoptosis to cTK function recovery, and in vivo PET imaging of cancer cell apoptosis, and we also include corresponding data acquisition methods. The time to build the entire cTK reporter is ~2–3 weeks. The selection of a stable cancer cell line takes ~4–6 weeks. The time to implement assays regarding cTK function in apoptotic cells and the in vivo imaging varies depending on the experiment. The cyclization strategy described in this protocol can also be adapted to create other reporter systems for broad biomedical applications. PMID:25927390

  19. A compact, in vivo screen of all 6-mers reveals drivers of tissue-specific expression and guides synthetic regulatory element design.

    PubMed

    Smith, Robin P; Riesenfeld, Samantha J; Holloway, Alisha K; Li, Qiang; Murphy, Karl K; Feliciano, Natalie M; Orecchia, Lorenzo; Oksenberg, Nir; Pollard, Katherine S; Ahituv, Nadav

    2013-07-18

    Large-scale annotation efforts have improved our ability to coarsely predict regulatory elements throughout vertebrate genomes. However, it is unclear how complex spatiotemporal patterns of gene expression driven by these elements emerge from the activity of short, transcription factor binding sequences. We describe a comprehensive promoter extension assay in which the regulatory potential of all 6 base-pair (bp) sequences was tested in the context of a minimal promoter. To enable this large-scale screen, we developed algorithms that use a reverse-complement aware decomposition of the de Bruijn graph to design a library of DNA oligomers incorporating every 6-bp sequence exactly once. Our library multiplexes all 4,096 unique 6-mers into 184 double-stranded 15-bp oligomers, which is sufficiently compact for in vivo testing. We injected each multiplexed construct into zebrafish embryos and scored GFP expression in 15 tissues at two developmental time points. Twenty-seven constructs produced consistent expression patterns, with the majority doing so in only one tissue. Functional sequences are enriched near biologically relevant genes, match motifs for developmental transcription factors, and are required for enhancer activity. By concatenating tissue-specific functional sequences, we generated completely synthetic enhancers for the notochord, epidermis, spinal cord, forebrain and otic lateral line, and show that short regulatory sequences do not always function modularly. This work introduces a unique in vivo catalog of short, functional regulatory sequences and demonstrates several important principles of regulatory element organization. Furthermore, we provide resources for designing compact, reverse-complement aware k-mer libraries.

  20. Quantification of the transferability of a designed protein specificity switch reveals extensive epistasis in molecular recognition

    DOE PAGES

    Melero, Cristina; Ollikainen, Noah; Harwood, Ian; ...

    2014-10-13

    Re-engineering protein–protein recognition is an important route to dissecting and controlling complex interaction networks. Experimental approaches have used the strategy of “second-site suppressors,” where a functional interaction is inferred between two proteins if a mutation in one protein can be compensated by a mutation in the second. Mimicking this strategy, computational design has been applied successfully to change protein recognition specificity by predicting such sets of compensatory mutations in protein–protein interfaces. To extend this approach, it would be advantageous to be able to “transplant” existing engineered and experimentally validated specificity changes to other homologous protein–protein complexes. Here, we test thismore » strategy by designing a pair of mutations that modulates peptide recognition specificity in the Syntrophin PDZ domain, confirming the designed interaction biochemically and structurally, and then transplanting the mutations into the context of five related PDZ domain–peptide complexes. We find a wide range of energetic effects of identical mutations in structurally similar positions, revealing a dramatic context dependence (epistasis) of designed mutations in homologous protein–protein interactions. To better understand the structural basis of this context dependence, we apply a structure-based computational model that recapitulates these energetic effects and we use this model to make and validate forward predictions. The context dependence of these mutations is captured by computational predictions, our results both highlight the considerable difficulties in designing protein–protein interactions and provide challenging benchmark cases for the development of improved protein modeling and design methods that accurately account for the context.« less

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