Effects of retroviral vector design on expression of human adenosine deaminase in murine bone marrow transplant recipients engrafted with genetically modified cells.

To determine which features of retroviral vector design most critically affect gene expression in hematopoietic cells in vivo, we have constructed a variety of different retroviral vectors which encode the same gene product, human adenosine deaminase (EC 3.5.4.4), and possess the same vector backbone yet differ specifically in transcriptional control sequences suggested by others to be important for gene expression in vivo. Murine bone marrow cells were transduced by each of the recombinant viruses and subsequently used to reconstitute the hematopoietic system of lethally irradiated recipients. Five to seven months after transplantation, analysis of the peripheral blood of animals transplanted with cells transduced by vectors which employ viral long terminal repeats (LTRs) for gene expression indicated that in 83% (77/93) of these animals, the level of human enzyme was equal to or greater than the level of endogenous murine enzyme. Even in bone marrow transplant recipients reconstituted for over 1 year, significant levels of gene expression were observed for each of the vectors in their bone marrow, spleen, macrophages, and B and T lymphocytes. However, derivatives of the parental MFG-ADA vector which possess either a single base mutation (termed B2 mutation) or myeloproliferative sarcoma virus LTRs rather than the Moloney murine leukemia virus LTRs led to significantly improved gene expression in all lineages. These studies indicate that retroviral vectors which employ viral LTRs for the expression of inserted sequences make it possible to obtain high levels of a desired gene product in most hematopoietic cell lineages for close to the lifetime of bone marrow transplant recipients.

Construction of a Sustainable City Park in Ruddle, WV: A Model for Sustainable Park Design in Humid Climates

Three sustainable projects were studied under a sustainable park model for humid climates to determine where their costs lie in terms of installation, maintenance or both. These projects included the use of solar lighting to replace every configuration of conventional lighting, inclusion of a water garden/bog filter and Riparian Buffer System for the purposes of filtering sediments and nutrients out of runoff to prevent contaminated runoff from reaching the river that was adjacent to the park model location and construction of a LEED-inspired building to serve as the concession stand/restrooms building. The aggregate cost savings of instituting all three projects over ten years was $74,120 and the entire project paid itself off in approximately four years.

Improved commercial vehicle conspicuity and signalling systems. Task II: analyses, experiments and design recommendations. Interim report.

National Highway Traffic Safety Administration, Washington, D.C.

Roadway lighting handbook, addendum to chapter six: designing the lighting system using pavement luminance. Final report.

Federal Highway Administration, Implementation Division, Washington, D.C.

Final design and implementation plan for evaluating the effectiveness of FMVSS 108: side marker lamps and high intensity headlamps (only). Tasks #4 and #5 report.

National Highway Traffic Safety Administration, Washington, D.C.

Light and lighting.

Mode of access: Internet.

Multimodal Transportation in Northeast Seattle: An Integrated Design

Thesis (Master's)--University of Washington, 2016-06

A metacognitive contextual intervention to enhance error awareness and functional outcome following traumatic brain injury: A single-case experimental design

Very few empirically validated interventions for improving metacognitive skills (i.e., self-awareness and self-regulation) and functional outcomes have been reported. This single-case experimental study presents JM, a 36-year-old man with a very severe traumatic brain injury (TBI) who demonstrated long-term awareness deficits. Treatment at four years post-injury involved a metacognitive contextual intervention based on a conceptualization of neuro-cognitive, psychological, and socio-environmental factors contributing to his awareness deficits. The 16-week intervention targeted error awareness and self-correction in two real life settings: (a) cooking at home: and (b) volunteer work. Outcome measures included behavioral observation of error behavior and standardized awareness measures. Relative to baseline performance in the cooking setting, JM demonstrated a 44% reduction in error frequency and increased self-correction. Although no spontaneous generalization was evident in the volunteer work setting, specific training in this environment led to a 39% decrease in errors. JM later gained paid employment and received brief metacognitive training in his work environment. JM's global self-knowledge of deficits assessed by self-report was unchanged after the program. Overall, the study provides preliminary support for a metacognitive contextual approach to improve error awareness and functional Outcome in real life settings.

The design of fault tolerant software for loosely coupled distributed systems

Requirements for systems to continue to operate satisfactorily in the presence of faults has led to the development of techniques for the construction of fault tolerant software. This thesis addresses the problem of error detection and recovery in distributed systems which consist of a set of communicating sequential processes. A method is presented for the `a priori' design of conversations for this class of distributed system. Petri nets are used to represent the state and to solve state reachability problems for concurrent systems. The dynamic behaviour of the system can be characterised by a state-change table derived from the state reachability tree. Systematic conversation generation is possible by defining a closed boundary on any branch of the state-change table. By relating the state-change table to process attributes it ensures all necessary processes are included in the conversation. The method also ensures properly nested conversations. An implementation of the conversation scheme using the concurrent language occam is proposed. The structure of the conversation is defined using the special features of occam. The proposed implementation gives a structure which is independent of the application and is independent of the number of processes involved. Finally, the integrity of inter-process communications is investigated. The basic communication primitives used in message passing systems are seen to have deficiencies when applied to systems with safety implications. Using a Petri net model a boundary for a time-out mechanism is proposed which will increase the integrity of a system which involves inter-process communications.

Computer aided design and manufacture for three dimensional milling

Advances in both computer technology and the necessary mathematical models capable of capturing the geometry of arbitarily shaped objects has led to the development in this thesis of a surface generation package called 'IBSCURF' aimed at providing a more economically viable solution to free-form surface manufacture. A suit of computer programs written in FORTRAN 77 has been developed to provide computer aids for every aspect of work in designing and machining free-form surfaces. A vector-valued parametric method was used for shape description and a lofting technique employed for the construction of the surface. The development of the package 'IBSCURF' consists of two phases. The first deals with CAD. The design process commences in defining the cross-sections which are represented by uniform B-spline curves as approximations to give polygons. The order of the curve and the position and number of the polygon vertices can be used as parameters for the modification to achieve the required curves. When the definitions of the sectional curves is complete, the surface is interpolated over them by cubic cardinal splines. To use the CAD function of the package to design a mould for a plastic handle, a mathematical model was developed. To facilitate the integration of design and machining using the mathematical representation of the surface, the second phase of the package is concerned with CAM which enables the generation of tool offset positions for ball-nosed cutters and a general post-processor has been developed which automatically generates NC tape programs for any CNC milling machine. The two phases of these programs have been successfully implemented, as a CAD/CAM package for free-form surfaces on the VAX 11/750 super-minicomputer with graphics facilities for displaying drawings interactively on the terminal screen. The development of this package has been beneficial in all aspects of design and machining of free form surfaces.

Computer aided design and analysis of cold formed sections

The work reported in this thesis is concerned with the improvement and expansion of the assistance given to the designer by the computer in the design of cold formed sections. The main contributions have been in four areas, which have consequently led to the fifth, the development of a methodology to optimise designs. This methodology can be considered an `Expert Design System' for cold formed sections. A different method of determining section properties of profiles was introduced, using the properties of line and circular elements. Graphics were introduced to show the outline of the profile on screen. The analysis of beam loading has been expanded to beam loading conditions where the number of supports, point loads, and uniform distributive loads can be specified by the designer. The profile can then be checked for suitability for the specified type of loading. Artificial Intelligence concepts have been introduced to give the designer decision support from the computer, in combination with the computer aided design facilities. The more complex decision support was adopted through the use of production rules. All the support was based on the British standards. A method has been introduced, by which the appropriate use of stiffeners can be determined and consequently designed by the designer. Finally, the methodology by which the designer is given assistance from the computer, without constraining the designer, was developed. This methodology gives advice to the designer on possible methods of improving the design, but allows the designer to reject that option, and analyse the profile accordingly. The methodology enables optimisation to be achieved by the designer, designing variety of profiles for a particular loading, and determining which one is best suited.

Design and construction for traditional house building

This study is concerned with quality and productivity aspects of traditional house building. The research focuses on these issues by concentrating on the services and finishing stages of the building process. These are work stages which have not been fully investigated in previous productivity related studies. The primary objective of the research is to promote an integrated design and construction led approach to traditional house building based on an original concept of 'development cycles'. This process involves the following: site monitoring; the analysis of work operations; implementing design and construction changes founded on unique information collected during site monitoring; and subsequent re-monitoring to measure and assess Ihe effect of change. A volume house building firm has been involved in this applied research and has allowed access to its sites for production monitoring purposes. The firm also assisted in design detailing for a small group of 'experimental' production houses where various design and construction changes were implemented. Results from the collaborative research have shown certain quality and productivity improvements to be possible using this approach, albeit on a limited scale at this early experimental stage. The improvements have been possible because an improved activity sampling technique, developed for, and employed by the study, has been able to describe why many quality and productivity related problems occur during site building work. Experience derived from the research has shown the following attributes to be important: positive attitudes towards innovation; effective communication; careful planning and organisation; and good coordination and control at site level. These are all essential aspects of quality led management and determine to a large extent the overall success of this approach. Future work recommendations must include a more widespread use of innovative practices so that further design and construction modifications can be made. By doing this, productivity can be improved, cost savings made and better quality afforded.

Market-driven strategies and the design of flexible production systems: evidence from the electronics industry

Links the concept of market-driven business strategies with the design of production systems. It draws upon the case of a firm which, during the last decade, changed its strategy from being “technology led” to “market driven”. The research, based on interdisciplinary fieldwork involving long-term participant observation, investigated the factors which contribute to the successful design and implementation of flexible production systems in electronics assembly. These investigations were conducted in collaboration with a major computer manufacturer, with other electronics firms being studied for comparison. The research identified a number of strategies and actions seen as crucial to the development of efficient flexible production systems, namely: effective integration of subsystems, development of appropriate controls and performance measures, compatibility between production system design and organization structure, and the development of a climate conducive to organizational change. Overall, the analysis suggests that in the electronics industry there exists an extremely high degree of environmental complexity and turbulence. This serves to shape the strategic, technical and social structures that are developed to match this complexity, examples of which are niche marketing, flexible manufacturing and employee harmonization.

A design and implementation methodology for high variety electronics assembly systems

Small indigenous manufacturers of electronic equipment are coming under increasingly severe pressure to adopt a strong defensive position against large multinational and Far Eastern companies. A common response to this threat has been for these firms to adopt a 'market driven' business strategy based on quality and customer service, rather than a 'technology led' strategy which uses technical specification and price to compete. To successfully implement this type of strategy there is a need for production systems to be redesigned to suit the new demands of marketing. Increased range and fast response require economy of scope rather t ban economy or scale while the organisation's culture must promote quality and process consciousness. This paper describes the 'Modular Assembly Cascade' concept which addresses these needs by applying the principles of flexible manufacturing (FMS) and just in time (,JlT) to electronics assembly. A methodology for executing the concept is also outlined. This is called DRAMA (Design Houtirw !'or· Adopting Modular Assembly).

Design and implementation of production systems for high variety electronics assembly

Information technology companies are having to broaden their overall strategic view in deference to the premise that it is better to be market-driven than technology-led. Cost and technical performance are no longer the only considerations, as quality and service now demand equal recognition. The production of a high volume single item has given way to that of low volume multiple items, which in turn requires some modification of production systems and brings flexible manufacturing, Just-in-Time production and total quality control into sharper focus for the achievement of corporate objectives.