Mise en oeuvre de microréseaux de lectines naturelles et recombinantes dédiés au suivi de production des glycoprotéines d’intérêt thérapeutiqueLes anticorps thérapeutiques, biomédicaments dont le marché est en pleine expansion, sont des glycoprotéines obtenues en bioproduction dans des cellules eucaryotes. Leur N-glycosylation, cruciale pour la modulation des fonctions effectrices des anticorps, confère un effet pro-inflammatoire ou anti-inflammatoire aux anticorps. Les anticorps thérapeutiques recombinants actuellement commercialisés présentent des glycosylations dites tronquées (GlcNAc terminaux) ou non humaines (α-Gal, NeuGc) rendant les anticorps immunogènes et, par conséquent, réduisant notablement leur efficacité. Les Agences de Santé exigent de réduire cet effet secondaire. La société SiaMed’Xpress a développé un savoir-faire pour obtenir une glycosylation complète, incluant la sialylation terminale des N-glycanes par ingénierie des cellules eucaryotes. Il est nécessaire de disposer d’outils d’analyse permettant de suivre la qualité de la N-glycosylation au cours de la production.La modification du milieu de culture par ajout de suppléments nutritionnels permet une modulation supplémentaire de la glycosylation. L’utilisation de suppléments nutritionnels commerciaux augmentent le taux de production mais bloquent la glycosylation au stade G0(F) (GlcNAc terminaux) alors que l’utilisation d’un supplément propre à SiaMed’Xpress permet de poursuivre jusqu’à la galactosylation et la sialylation, mettant ainsi en évidence un carrefour métabolique clé dans la glycosylation. Pour suivre les modifications de glycosylation dans différentes conditions de production, un test utilisant des lectines a été développé. Un jeu de treize lectines naturelles et recombinantes a été sélectionné par analyse bio-informatique et intégré dans un glycotest. L’utilisation de ce glycotest pour l’analyse de la glycosylation de trois anticorps produits en présence de différents suppléments nutritionnels permet d’obtenir de façon rapide, fiable et reproductible les profils de glycosylation des anticorps. Ainsi, le glycotest développé est fonctionnel et permet de caractériser la glycosylation des anticorps thérapeutiques recombinants. / Development of natural and recombinant lectin microarrays for monitoring the production of glycosylated protein drugsTherapeutic antibodies, biologic drugs whose market is growing, are glycoproteins obtained though bioproduction in eukaryotic cells. Their N-glycosylation, which is crucial for the modulation of effector functions, confers a pro-inflammatory or anti-inflammatory effect to antibodies. Currently, marketed therapeutic recombinant antibodies have truncated (terminal GlcNAc) or non human (α-Gal, NeuGc) glycosylation, inducing immunologic reaction and, consequently, reducing their effectiveness. Health agencies demand to reduce such secondary effects. SiaMed’Xpress developped a knowledge to obtained a complete glycosylation, including terminal sialylation of N-glycans by engineering eukaryotic cells for production. It is now necessary to develop analysis tools to monitor the quality of the N-glycosylation during bioproduction.Modification of culture media with feeds allows to further modulate glycosylation. The use of marketed feeds increase the production rate but block the glycosylation process in the G0(F) state (terminal GlcNAc) whereas SiaMed’Xpress feed allows for galactosylation and sialylation, highlighting a metabolic key point during the glycosylation. To follow the glycosylation modifications under different conditions of production, an assay using lectins has been developed. A panel of 13 lectins, recombinants and naturals, has been determined by bio-informatic analysis and integrated into a glycotest. The use of this glycotest to analyse glycosylation of 3 antibodies produced with different feeds allows fast, reliable and reproductible glycosylation profils of these antibodies. So, this developped glycotest is functionnal and this using permits to monitore therapeutic recombinant antibody glycosylation during bioproduction.

The purpose and aim of this study are to examine how quality control and assurance is performed and how it varies in different regions around the world and strive towards international standardization of quality assurance. The foundation to the idea of this study is a Swedish company, called Runway Safe, working with international affairs regarding a safety solution for airport runways. To complete the study, cultural differences and structural differences in organizations comes to consideration.

Prefabricated and pre-stressed reinforced concrete beams and girders are integral components of many highway structures, including those built by rapid construction techniques. Concerns exist regarding the development of cracks during curing, form removal, detensioning, transport, installation, and operation. Non-destructive, Acoustic Emission (AE) sensing techniques have the potential for detecting and locating cracking in prefabricated, pre-stressed concrete girders used as Prefabricated Bridge Elements and Systems (PBES) used in rapid construction practices as part of a Quality Assurance/Quality Control (QA/QC) program. AE sensing records transient elastic waves produced by the release of stored elastic energy resulting in plastic deformations (i.e., crack nucleation and growth) with an array of point sensors. The AE instrument system is relatively portable which can allow for it to be an option for both off-site fabrication QA/QC as well as on-site field QA/QC. This thesis presents a multi-stage research initiative on acoustic emission monitoring of prefabricated and pre-stressed reinforced concrete beams used in highway bridge construction during detensioning, craned removal from formwork and transport to bridge sites, along with supporting laboratory tests and numerical analysis. The specific objectives of this research were to: 1. Identify suitable instruments to monitor pre-stressed and/or post-tensioned concrete girders for cracking activity; 2. Design and develop a reusable instrumentation package; 3. Measure performance and condition of concrete girders during fabrication and transport; and 4. Identify test protocols and possible accept/fix/reject criteria for structural elements based on information from monitoring system. Presented are results from laboratory, full-scale girder fabrication, and transport monitoring, along with overall conclusions and recommendations for future research.

Orientador: Agnaldo Lopes da Silva Filho / Resumo: O câncer do colo uterino mantém altas taxas de incidência e mortalidade no Brasil, apesar do Programa Viva Mulher ter ampliado muito o acesso ao teste de Papanicolaou. O rastreamento desta neoplasia através do exame citológico foi responsável por redução significativa da sua ocorrência em países desenvolvidos, que monitoram a qualidade deste método em todos os passos que envolvem sua realização. Entretanto, essa realidade não é observada regularmente nos países em desenvolvimento. Partindo desta constatação, esse trabalho tem como foco as análises da visão do patologista brasileiro sobre o exame citológico e de critérios médicos necessários para melhorar a qualidade do rastreamento. Para tanto, foi realizado estudo descritivo observacional constituído por uma análise qualitativa reunindo entrevistas com patologistas, e pela aplicação de um questionário aos patologistas brasileiros, com perguntas sobre a estrutura de serviços que realizam exames citológicos no país. Os resultados evidenciaram claramente a preocupação deste profissional com seu afastamento do programa de rastreamento e com a necessidade de um controle de qualidade mais criterioso. Também foi observada uma crítica relação entre as falhas do rastreamento citológico, a atuação do patologista e a estrutura dos serviços responsáveis por este exame. Assim, o estudo identificou a imperativa necessidade de educação continuada dos profissionais responsáveis pelo exame citológico do colo uterino, além da implementação de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The uterine cervix's cancer maintains high rates of incidence and mortality in Brazil, despite of the fact that the Programa Viva Mulher have expanded the access to the Papanicolaou’s test. The screening of this neoplasm by the cytological test was responsible for a significant reduction of events in developed countries, which have well stablished quality control systems. However, this reality cannot be seen in developing countries. Therefore, this study focuses on the analysis of the Brazilian pathologist's view of the cytological test and the medical criteria needed to improve the quality of screening. For this reason, a descriptive observational study was conducted, including a qualitative analysis with interviews with pathologists and the application of a questionnaire, about the structure of services that perform cytological examinations in the country. The results clearly showed the concern of this professional with your gradative removal from the screening program, and the need for a more careful quality control. A critical relationship was also observed between the failures of cytological screening, the performance of the pathologist and the structure of the services responsible for this exam. In this way, the study identified the imperative need for continued education of the professionals responsible for cervical cytological examination, in addition to the implementation of a comprehensive and judicious external quality control. / Doutor

The research aims at modeling and analyzing the interactions among functional process variables (FPVs) for process control in semiconductor manufacturing. Interaction is a universal phenomenon and different interaction patterns among system components might characterize the system conditions. To monitor and control the system, process variables are normally collected for observation which could vary with time and present in a functional form. These FPVs interact with each other and contain rich information regarding the process conditions. As an example in one of the semiconductor manufacturing processes, changes of interactions among FPVs like temperature and coefficient of friction (COF) might characterize different process conditions. This dissertation systematically developed a methodology to study interaction among FPVs through statistical and physical modeling. Three main topics are discussed in this dissertation: (1) Interaction patterns of FPVs under varying process conditions are studied both through experiments and statistical approaches. A method based on functional canonical correlation analysis (FCCA) is employed to extract the interaction patterns between FPVs and experiments of wafer polishing processes are conducted to verify the patterns of FPVs under varying process conditions. (2) Interaction among FPVs is further studied based on physics for process condition diagnosis. A mathematical model based on nonlinear dynamics is developed to study the strength of interaction and their directionalities, and advanced statistical control charts followed by this nonlinear dynamics model are established for process monitoring. (3) Complex interaction structures among multiple FPVs are analyzed based on nonlinear dynamics for a better understanding of process mechanism. An approach with extended nonlinear dynamics model is proposed to characterize process conditions, and combined engineering knowledge, complex interaction structure patterns are concluded accordingly for interpretation of process mechanism. The main contribution of this dissertation is to propose a novel methodology based on nonlinear dynamics, which could investigate interactions between components of systems and provide physical understanding of process mechanism for process monitoring and diagnosis. Through studies on interaction among FPVs in semiconductor manufacturing, this research provides guidance for improvement of manufacturing processes. Not limited to manufacturing, the developed methodology can be applied to other areas such as healthcare delivery.

During the past decade, nurses in the clinical setting have began making a paradigm shift from Quality Assurance to Total Quality Management, or as it is commonly referred to within health care facililties, Continuous Quality Improvement.In contrast, scant attention has been paid to quality management practices in nursing in the higher education sector. This study provides an applied example of where it investigates quality management practices in the context of organisational culture and human resource management with the aim of developing a quality culture model for a school of nursing in higher education.The research study that was conducted produced several major findings from the views of nurse academics who participated in it. Several issues associated with nurse academics' opinions of quality management practices utilised in schools of nursing have been unravelled.The fundamental issue is that procedures and policies formulated for nurses in the hospital setting do not serve the needs of nursing education.The most crucial factor to be considered in policy developments and future research is that it needs to be contextualised in the culture of nursing in higher education.It has become imperative that a transparent quality culture reflects contemporary nursing in Australia and the proposed model in this thesis provides nurses with an opportunity to shape a quality system for the nursing profession. / Doctor of Philosophy (PhD)

The aim of this thesis is to assist industry leaders in Australia understand the nature of employee empowerment by identifying the characteristics of employee empowerment, the leadership strategies required to guide employee behaviour changes and the interaction between the two concepts. This thesis argues that in the 1990's the role of leadership needs to change in order to address the threat of increasing competition. The role of leadership needs to focus on employee development and enhancing their ability to adapt to change, be innovative, creative and committed to achieving the goals of the organisation. Effective leadership is therefore reflected in the behaviour of employees. A characteristic identified as employee empowerment. The research for this study had two components. First was the development of the model to investigate the relationship between leadership strategies and employee empowerment behaviour in a workplace setting. The second research component of the study was testing the model. Testing required the development of a multi-component workplace survey instrument. A range of validation methodologies supported the survey instrument. The case study site was a government organisation. Results provided answers to each of the research questions. Among other findings, it was found that factors other than leadership could also moderate empowerment behaviours. The results of the study, if replicated, have important significance to Australian industry. Serious questions are raised concerning the direction of previous leadership research. Furthermore a new focus is provided to explain why TQM fails in organisations. Another key point highlighted in the study was the importance of using practical models that can be tested in the workplace. / Doctor of Philosophy (PhD)

Packet switched wireless networks have become increasingly popular due to improvements in transmission speed, ease of deployment and mobility. Wireless technologies such as the IEEE 802.11 Wireless Local Area Networks provide transmission speeds capable of supporting multimedia applications. However, wireless channels suffer from short term effects such as interference and fading, and long term effects such as signal strength changes that are caused by user mobility. In multi-rate networks, stations can adapt to the channel variations by adjusting their physical transmission rates. This introduces resource management problems as resource usage depends on the application's bit rate as well as the physical transmission rate used. Multimedia applications demand consistent Quality of Service (QoS) performance from the network. This does not fit well with the dynamic nature of wireless networks. In this thesis, we propose a link layer resource manager to maintain application QoS requirements in multi-rate wireless networks. It consists of two components - Resource reservation and Medium Access Control (MAC) parameters selection. The resource reservation algorithm determines the current and future amount of channel resources required by a multimedia application and performs the function of admission control. This prevents any new traffic or physical transmission rate changes from degrading the QoS of the admitted traffic. The design of the MAC parameters selection algorithm is based on the IEEE 802.11e Enhanced Distributed Channel Access (EDCA) scheme. The algorithm enables the provision of QoS to individual multimedia applications with the prioritised service of EDCA. Analytical and simulation studies were performed to demonstrate the efficiency and effectiveness of the algorithms. The results highlighted the ability of the algorithms to mitigate the QoS provision problem in multi-rate wireless networks introduced by channel variations.

The current work used discrete event simulation techniques to model the economics of quality within an actual automotive stamping plant. Automotive stamping is a complex, capital intensive process requiring part-specific tooling and specialised machinery. Quality control and quality improvement is difficult in the stamping environment due to the general lack of process understanding and the large number to interacting variables. These factors have prevented the widespread use of statistical process control. In this work, a model of the quality control techniques used at the Ford Geelong Stamping plant is developed and indirectly validated against results from production. To date, most discrete event models are of systems where the quality control process is clearly defined by the rules of statistical process control. However, the quality control technique used within the stamping plant is for the operator to perform a 100% visual inspection while unloading the finished panels. In the developed model, control is enacted after a cumulative count of defective items is observed, thereby approximating the operator who allows a number of defective panels to accumulate before resetting the line. Analysis of this model found that the cost sensitivity to inspection error is dependent upon the level of control and that the level of control determines line utilisation. Additional analysis of this model demonstrated that additional inspection processes would lead to more stable cost structures but these structures many not necessarily be lower cost. The model was subsequently applied to investigate the economics of quality improvement. The quality problem of panel blemishes, induced by slivers (small metal fragments), was chosen as a case stuffy. Errors of 20-30% were observed during direct validation of the cost model and it was concluded that the use of discrete event simulation models for applications requiring high accuracy would not be possible unless the production system was of low complexity. However, the model could be used to evaluate the sensitivity of input factors and investigating the effects of a number of potential improvement opportunities. Therefore, the research concluded that it is possible to use discrete event simulation to determine the quality economics of an actual stamping plant. However, limitations imposed by inability of the model to consider a number of external factors, such as continuous improvement, operator working conditions or wear and the lack of reliable quality data, result in low cost accuracy. Despite this, it still can be demonstrated that discrete event simulation has significant benefits over the alternate modelling methods.

Typescript (photocopy) By using a regression equation relating the difference between dye binding and Kjeldahl values with the total protein concentration of the milk, the accuracy of estimates of casein in milk from individual cows was improved.