<p>A number of active site mutants of human Alpha class glutathione transferase A1-1 (hGST A1-1) were made and characterized to determine the structural determinants for alkenal activity. The choice of mutations was based on primary structure alignments of hGST A1-1 and the Alpha class enzyme with the highest alkenal activity, hGST A4-4, from three different species and crystal structure comparisons between the human enzymes. The result was an enzyme with a 3000-fold change in substrate specificity for nonenal over 1-chloro-2,4-dinitrobenzene (CDNB).</p><p>The C-terminus of the Alpha class enzymes is an α-helix that folds over the active site upon substrate binding. The rate-determining step is product release, which is influenced by the movements of the C-terminus, thereby opening the active site. Phenylalanine 220, near the end of the C-terminus, forms an aromatic cluster with tyrosine 9 and phenylalanine 10, positioning the β-carbon of the cysteinyl moiety of glutathione. The effects of phenylalanine 220 mutations on the mobility of the C-terminus were studied by the viscosity dependence of k_cat and k_cat/K_m with glutathione and CDNB as the varied substrates. </p><p>The compatibility of slightly different subunit interfaces within the Alpha class has been studied by heterodimerization between monomers from hGST A1-1 and hGST A4-4. The heterodimer was temperature sensitive, and rehybridized into homodimers at 40 ˚C. The heterodimers did not show strictly additive activities with alkenals and CDNB. This result combined with further studies indicates that there are factors at the subunit interface influencing the catalytic properties of hGST A1-1.</p>

This thesis presents a hybrid decision aid approach for supply networks redesign and planning int the context of multi-site enterprises. This approach is iterative and integrates a mixed integer programming model and a simulation model being at different decisional levels : the mathematical model is a strategic/tactical model and the simulation model is a tactical/operational model. These two models are based on the same modelling of the supply network. First, we describe the elements constituting the decision aid approach. We present two generic mixed integer programming models, multi-product, multi-echelon and multi-period, which search to maximize the profit of the multi-site enterprise. We propose a heuristic approach to solve one of these programs. We describe the developed simulation model. It reproduces the behaviour of the whole supply chain and takes into account the management policies. then, we present the adopted integration methodology. For a problem based on industrial cases, we show that the two models have their role in the decision aid approach and that they contribute both in the search of a good quality network design.

This thesis describes the use of rational redesign to modify the properties of the enzyme Candida antarctica lipase B. Through carefully selected single-point mutations, we were able to introduce substrate-assisted catalysis and to alter the reaction specificity. Other single-point mutations afforded variants with greatly changed substrate selectivity and enantioselectivity. Mutation of the catalytic serine changed the hydrolase activity into an aldolase activity. The mutation decreased the activation energy for aldol addition by 4 kJ×mol-1, while the activation energy increased so much for hydrolysis that no hydrolysis activity could be detected. This mutant can catalyze aldol additions that no natural aldolases can catalyze. Mutation of the threonine in the oxyanion hole proved the great importance of its hydroxyl group in the transition-state stabilization. The lost transition-state stabilization was partly replaced through substrate-assisted catalysis with substrates carrying a hydroxyl group. The poor selectivity of the wild-type lipase for ethyl 2-hydroxypropanoate (E=1.6) was greatly improved in the mutant (E=22), since only one enantiomer could perform substrate-assisted catalysis. The redesign of the size of the stereospecificity pocket was very successful. Mutation of the tryptophan at the bottom of this pocket removed steric interactions with secondary alcohols that have to position a substituent larger than an ethyl in this pocket. This mutation increased the activity 5 500 times towards 5-nonanol and 130 000 times towards (S)-1-phenylethanol. The acceptance of such large substituents (butyl and phenyl) in the redesigned stereospecificity pocket increases the utility of lipases in biocatalysis. The improved activity with (S)-1-phenylethanol strongly contributed to the 8 300 000 times change in enantioselectivity towards 1-phenylethanol; example of such a large change was not found in the literature. The S-selectivity of the mutant is unique for lipases. Its enantioselectivity increases strongly with temperature reaching a useful S-selectivity (E=44) at 69 °C. Thermodynamics analysis of the enantioselectivity showed that the mutation in the stereospecificity pocket mainly changed the entropic term, while the enthalpic term was only slightly affected. This pinpoints the importance of entropy in enzyme catalysis and entropy should not be neglected in rational redesign.

A number of active site mutants of human Alpha class glutathione transferase A1-1 (hGST A1-1) were made and characterized to determine the structural determinants for alkenal activity. The choice of mutations was based on primary structure alignments of hGST A1-1 and the Alpha class enzyme with the highest alkenal activity, hGST A4-4, from three different species and crystal structure comparisons between the human enzymes. The result was an enzyme with a 3000-fold change in substrate specificity for nonenal over 1-chloro-2,4-dinitrobenzene (CDNB). The C-terminus of the Alpha class enzymes is an α-helix that folds over the active site upon substrate binding. The rate-determining step is product release, which is influenced by the movements of the C-terminus, thereby opening the active site. Phenylalanine 220, near the end of the C-terminus, forms an aromatic cluster with tyrosine 9 and phenylalanine 10, positioning the β-carbon of the cysteinyl moiety of glutathione. The effects of phenylalanine 220 mutations on the mobility of the C-terminus were studied by the viscosity dependence of kcat and kcat/Km with glutathione and CDNB as the varied substrates. The compatibility of slightly different subunit interfaces within the Alpha class has been studied by heterodimerization between monomers from hGST A1-1 and hGST A4-4. The heterodimer was temperature sensitive, and rehybridized into homodimers at 40 ˚C. The heterodimers did not show strictly additive activities with alkenals and CDNB. This result combined with further studies indicates that there are factors at the subunit interface influencing the catalytic properties of hGST A1-1.

Syfte: Syftet med detta arbete är att studera användargränssnittet på ICA-lagrets datorterminal i Västerås och ta fram ett nytt designförslag för det virtuella tangentbordet. Detta för att effektivisera det befintliga användargränssnittet och höja säkerheten för de anställda. Metod: För att nå studiens syfte har ett kvalitativt och tolkande angreppssätt använts, men med kvantitativt element. Intervjuer och mätningar har genomförts med sex respondenter respektive åtta testpersoner. Slutsats: Resultatet visade att det befintliga tangentbordet har brister. Min slutsats är att en redesign av ett virtuellt tangentbord kan minska feltryckningar och knapptryckningar, öka skrivhastigheten och påskynda navigeringen. Detta bidrar till att det blir mindre trafikstopp, irritation och stress. Detta i sin ur påverkar trafiksäkerheten på lagret till det positiva. Det gör även att utbildningstiden kan reduceras då användargränssnittet hela tiden förklarar vad man kan göra och hur.

Researchers have paid relatively little attention to the fact that most design activities are actually more like redesign. These activities are characterized by an attempt to leverage experience, knowledge, and the capital that a company has already invested into existing engineering systems. In this dissertation, it is proposed that an approach be developed to aid designers in making decisions in redesign problems when there exist systems to be leveraged and multiple new systems to be created. In addition, strategy is introduced to the problem through the consideration that new systems may not be offered all at once, as is often assumed in product family design research. In this dissertation, the aim of the designer is assumed to be a creation, through redesign, of a series of new systems with desirable and distinct performance levels. In addition, a plan is required to involve as little redesign effort throughout the life of the family of systems as possible The proposed approach is based upon the concepts of Constructal Theory and previous work to create methods for the design of mass customized families of products. The existing methods are abstracted and heavily modified through the infusion of the compromise Decision Support Problems at all stages of the decision-making process. In addition, two indices are developed to represent considerations unique to redesign as opposed to original design. These indices for redesign effort and commonality value are utilized in the overall objective formulation for the approach. Through a thorough validation process and a large number of redesign scenarios, it is shown that the overall approach proposed can lead the designer towards promising redesign plans involving leveraging of existing systems, but that the constructal-inspired approach in and of itself has certain limitations when applied to redesign.

In product manufacture and assembly it is important to lower materials usage and assembly timewhile retaining a safety margin against structural failure. In this project the ceiling attachment of theAVPOS offloading arm is redesigned based on objectives identified by Löfs Specialmaskiner. Theoriginal ceiling attachment is analysed using finite element analysis to identify any structuralweaknesses to be addressed during redesign. Based on information gained during the FEA threeconcepts are generated and rated based on their estimated assembly times, material usage, partscount and the cutting length for machining.One concept is selected for further topology optimisation and iterative FEA, where material isremoved from the selected concept design while maintaining safety objectives. The optimised designdeveloped during this project is shown to have a lower number of parts, lower usage of material andassembly time while retaining an overall FOS value of 4.In addition to redesigning the ceiling attachment, alternative bearings are also investigated whichchanges the existing ball bearings to a self-aligning sliding bearing with self-lubricating properties,lowering the machining tolerances as well as lowering the needs for service.This project contributes to lowering material usage and ease of assembly in the product AVPOS thatis manufactured by Löfs Specialmaskiner. The redesigned ceiling attachment along with thesuggested bearings will likely simplify future manufacturing as well as lower any concerns for damageto people and property as a result of structural failure.

The impact of globalisation and advanced information technology on service and knowledgebased industries in South Africa contributes to these workplaces becoming increasingly virtual. Virtual teams can be seen as a mechanism that organisations could use to increase their orientation for change through enhancing and integrating key organisational resources such as people, space and information technology to deliver greater business value. The findings of several studies suggest that the implementation of virtual teams is associated with benefits such as cost and time saving, increased employee productivity and employee empowerment. There are however salient barriers to effective virtual teamwork that organisations need to address before engaging in the transformational process towards virtual teamwork. The literature review identified ineffective leadership practices, factors relating to virtual team development, inadequate use of information technology and a paucity of social and organisational cultural integration, as the most salient features that impede effective virtual teamwork. The objective of this research was to develop a basic theoretical framework for the implementation of virtual teams. Since virtual teams emanate from a relatively new area of research an inductive methodology, based on a literature review, was used to achieve the research objective. Several theoretical models on virtual teams and their effectiveness thereon were explored to conceptualise the dynamic nature of virtual teams and the requirements for implementing them in the workplace. The results of the study indicated that an emergent approach to change be followed and that the following factors be addressed to determine an organisation's readiness for the implementation of virtual teams, namely: the degree of interdependence between tasks, structural requirements, technological requirements, process redesign and the selection of appropriate people. A methodology for work transformation towards virtual teamwork was suggested based on an integration of these factors. / Thesis (M.Sc. (Industrial Psychology))--North-West University, Potchefstroom Campus, 2004.

The impact of globalisation and advanced information technology on service and knowledgebased industries in South Africa contributes to these workplaces becoming increasingly virtual. Virtual teams can be seen as a mechanism that organisations could use to increase their orientation for change through enhancing and integrating key organisational resources such as people, space and information technology to deliver greater business value. The findings of several studies suggest that the implementation of virtual teams is associated with benefits such as cost and time saving, increased employee productivity and employee empowerment. There are however salient barriers to effective virtual teamwork that organisations need to address before engaging in the transformational process towards virtual teamwork. The literature review identified ineffective leadership practices, factors relating to virtual team development, inadequate use of information technology and a paucity of social and organisational cultural integration, as the most salient features that impede effective virtual teamwork. The objective of this research was to develop a basic theoretical framework for the implementation of virtual teams. Since virtual teams emanate from a relatively new area of research an inductive methodology, based on a literature review, was used to achieve the research objective. Several theoretical models on virtual teams and their effectiveness thereon were explored to conceptualise the dynamic nature of virtual teams and the requirements for implementing them in the workplace. The results of the study indicated that an emergent approach to change be followed and that the following factors be addressed to determine an organisation's readiness for the implementation of virtual teams, namely: the degree of interdependence between tasks, structural requirements, technological requirements, process redesign and the selection of appropriate people. A methodology for work transformation towards virtual teamwork was suggested based on an integration of these factors. / Thesis (M.Sc. (Industrial Psychology))--North-West University, Potchefstroom Campus, 2004.

Design denotes the transformation of an identified need to its physical embodiment in a traditionally iterative approach of trial and error. Conceptual design plays a prominent role but an almost infinite number of possible solutions at the outset of design necessitates fast evaluations. The traditional practice of empirical databases loses adequacy for novel concepts and an ever increasing system complexity and resource scarsity mandate new approaches to adequately capture system characteristics. Contemporary concerns in atmospheric science and homeland security created an operational need for unconventional configurations. Unmanned long endurance flight at high altitudes offers a unique showcase for the exploration of new design spaces and the incidental deficit of conceptual modeling and simulation capabilities. The present research effort evolves around the development of an efficient and accurate optimization algorithm for high aspect ratio wings subject to natural frequency constraints. Foundational corner stones are beam dimensional reduction and modal perturbation redesign. Local and global analyses inherent to the former suggest corresponding levels of local and global optimization. The present approach departs from this suggestion. It introduces local level surrogate models to capacitate a methodology that consists of multi level analyses feeding into a single level optimization. The innovative heart of the new algorithm originates in small perturbation theory. A sequence of small perturbation solutions allows the optimizer to make incremental movements within the design space. It enables a directed search that is free of costly gradients. System matrices are decomposed based on a Timoshenko stiffness effect separation. The formulation of respective linear changes falls back on surrogate models that approximate cross sectional properties. Corresponding functional responses are readily available. Their direct use by the small perturbation based optimizer ensures constitutive laws and eliminates a previously necessary optimization at the local level. The great economy of the developed algorithm makes it suitable for the conceptual phase of aircraft design.