The automotive manufacturing facility is extremely complex and expensive system. Managing and understanding the dynamics of automotive manufacturing is a challenging endeavour. In the current era of dynamic global competition, a new concept such as Collaborative Lean Manufacturing Management (CLMM) can be implemented as an alternative for organisations to improve their Lean Manufacturing Management (LMM) processes. All members in the CLMM value chain must work together towards common objectives in order to make the LMM achievable in the collaborative environment. The novel research approach emphasises the use of Knowledge-Based (KB) approach in such activities as planning, designing, assessing and providing recommendations of CLMM implementation, through: a) developing the conceptual CLMM model; b) designing the KBCLMM System structure based on the conceptual model; and c) implementing Gauging Absences of Pre-requisites (GAP) analysis and Analytic Hierarchy Process (AHP) approach in the hybrid KBCLMM. The development of KBCLMM Model is the most detailed part in the research process and consists of five major components in two stages. Stage 1 (Planning stage) consists of Organisation Environment, Collaborative Business and Lean Manufacturing components. Stage 2 (Design stage) consists of Organisation CLMM Capability and Organisation CLMM Alignment components. Each of these components consists of sub-components and activities that represent particular issues in the CLMM development. From the conceptual model, all components were transformed into the KBCLMM System structure, which is embedded with the GAP and AHP techniques, and thus, key areas of potential improvement in the LMM are identified for each activity along with the identification of both qualitative and quantitative aspects for CLMM implementation. In order to address the real situation of CLMM operation, the research validation was conducted for an automotive manufacturer¿s Lean Manufacturing Chain in Malaysia. Published case studies were also used to test several modules for their validity and reliability. This research concludes that the developed KBCLMM System is an appropriate Decision Support System tool to provide the opportunity for academics and industrialists from the fields of industrial engineering, information technology, and operation management to plan, design and implement LMM for a collaborative environment. / Universiti Utara Malaysia and Ministry of Higher Education of Malaysia

This thesis focuses on the Swedish language, where punctuation restoration, especially as a postprocessing step for the output of Automatic Speech Recognition (ASR) applications, needs furtherresearch. I have collaborated with NewsMachine AB, a company that provides large-scale mediamonitoring services for its clients, for which it employs ASR technology to convert spoken contentinto text.This thesis follows an approach initially designed for high-resource languages such as English. Themethod is based on KB-BERT, a pre-trained Swedish neural network language model developedby the National Library of Sweden. The project uses KB-BERT with a Bidirectional Long-ShortTerm Memory (BiLSTM) layer on top for the task of punctuation restoration. The model is finetuned using the TED Talk 2020 dataset in Swedish, which is acquired from OPUS (an open-sourceparallel corpus). The punctuation marks comma, period, question mark, and colon are considered for this project. A comparative analysis is conducted between two KB-BERT models: bertbase-swedish-cased and albert-base-swedish-cased-alpha. The fine-tuned Swedish BERT-BiLSTMmodel, trained on 5 classes, achieved an overall F1-score of 81.6%, surpassing the performance ofthe ALBERT-BiLSTM model, which was also trained on 5 classes and obtained an overall F1-scoreof 66.6%. Additionally, the BERT-BiLSTM model, trained on 4 classes (excluding colon), outperformed prestoBERT, an existing model designed for the same task in Swedish, with an overallF1-score of 82.8%. In contrast, prestoBERT achieved an overall F1-score of 78.9%.As a further evaluation of the model’s performance on ASR transcribed text, noise was injectedbased on four probabilities (0.05, 0.1, 0.15, 0.2) into a copy of the test data in the form of threeword-level errors (deletion, substitution, and insertion). The performance of the BERT-BiLSTMmodel substantially decreased for all the errors as the probability of noise injected increased. Incontrast, the model still performed comparatively better when dealing with deletion errors as compared to substitution and insertion errors. Lastly, the data resources received from NewsMachineAB were used to perform a qualitative assessment of how the model performs in punctuating realtranscribed data as compared to human judgment.

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Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Yes / Purpose– This paper develops a Knowledge-based (KB) System for Lean Six Sigma (LSS) Maintenance in environmentally Sustainable Buildings (Lean6-SBM). Design/methodology/approach– The Lean6-SBM conceptual framework has been developed using the rule base approach of KB system and joint integration with Gauge Absence Prerequisites (GAP) technique. A comprehensive literature review is given for the main pillars of the framework with a typical output of GAP analysis. Findings– Implementation of LSS in the sustainable building maintenance context requires a pre-assessment of the organisation’s capabilities. A conceptual framework with a design structure is proposed to tackle this issue with the provision of an enhancing strategic and operational decision making hierarchy. Research limitations/implications– Future research work might consider validating this framework in other type of industries. Practical implications– Maintenance activities in environmentally sustainable buildings must take prodigious standards into consideration and, therefore, a robust quality assurance measure has to be integrated. Originality/value– The significance of this research is to present a novel use of hybrid KB/GAP methodologies to develop a Lean6-SBM system. The originality and novelty of this approach will assist in identifying quality perspectives while implementing different maintenance strategies in the sustainable building context. / Ministry of Defence Engineering Services (Sultanate of Oman)

The automotive manufacturing facility is extremely complex and expensive system. Managing and understanding the dynamics of automotive manufacturing is a challenging endeavour. In the current era of dynamic global competition, a new concept such as Collaborative Lean Manufacturing Management (CLMM) can be implemented as an alternative for organisations to improve their Lean Manufacturing Management (LMM) processes. All members in the CLMM value chain must work together towards common objectives in order to make the LMM achievable in the collaborative environment. The novel research approach emphasises the use of Knowledge-Based (KB) approach in such activities as planning, designing, assessing and providing recommendations of CLMM implementation, through: a) developing the conceptual CLMM model; b) designing the KBCLMM System structure based on the conceptual model; and c) implementing Gauging Absences of Pre-requisites (GAP) analysis and Analytic Hierarchy Process (AHP) approach in the hybrid KBCLMM. The development of KBCLMM Model is the most detailed part in the research process and consists of five major components in two stages. Stage 1 (Planning stage) consists of Organisation Environment, Collaborative Business and Lean Manufacturing components. Stage 2 (Design stage) consists of Organisation CLMM Capability and Organisation CLMM Alignment components. Each of these components consists of sub-components and activities that represent particular issues in the CLMM development. From the conceptual model, all components were transformed into the KBCLMM System structure, which is embedded with the GAP and AHP techniques, and thus, key areas of potential improvement in the LMM are identified for each activity along with the identification of both qualitative and quantitative aspects for CLMM implementation. In order to address the real situation of CLMM operation, the research validation was conducted for an automotive manufacturer's Lean Manufacturing Chain in Malaysia. Published case studies were also used to test several modules for their validity and reliability. This research concludes that the developed KBCLMM System is an appropriate Decision Support System tool to provide the opportunity for academics and industrialists from the fields of industrial engineering, information technology, and operation management to plan, design and implement LMM for a collaborative environment.

La maladie de Crohn (MC) et la colite ulcéreuse (CU) sont des maladies inflammatoires chroniques du tube digestif qu’on regroupe sous le terme maladies inflammatoires de l’intestin (MII). Les mécanismes moléculaires menant au développement des MII ne sont pas entièrement connus, mais des études génétiques et fonctionnelles ont permis de mettre en évidence des interactions entre des prédispositions génétiques et des facteurs environnementaux - notamment la flore intestinale – qui contribuent au développement d’une dérégulation de la réponse immunitaire menant à l’inflammation de la muqueuse intestinale. Des études d’association pangénomiques et ciblées ont permis d’identifier plusieurs gènes de susceptibilité aux MII mais les estimations de la contribution de ces gènes à l’héritabilité suggèrent que plusieurs gènes restent à découvrir. Certains d’entre eux peuvent se trouver dans les régions identifiées par des études de liaison génétique. L’objectif de mon projet de doctorat était d’identifier un ou des facteurs de risque génétique dans la région chromosomale 19p (identifiée comme région de liaison IBD6) et de le/les caractériser au niveau fonctionnel. Nous avons d’abord entrepris une cartographie d’association de la région 19p. À la suite du génotypage successif de deux cohortes indépendantes, nous avons identifié un SNP intronique et quatre SNP codants dont un non-synonyme, rs8108738, tous localisés dans le gène microtubule associated serine threonine kinase gene-3 (MAST3) et associés aux MII. Peu d’information fonctionnelle sur MAST3 était disponible. Par contre MAST2, une protéine encodée par un gène de la même famille, régule l’activité du facteur de transcription inflammatoire NF-kappaB. Nous avons confirmé l’implication de MAST3 dans l’activité de NF-kappaB via un knockdown de MAST3 et des essais gène-rapporteur. Pour poursuivre la caractérisation fonctionnelle de MAST3, nous avons choisi une approche non ciblée pour étudier les effets de la variation des niveaux d’expression de MAST3 sur la cellule. C’est-à-dire que nous avons créé un 1er modèle cellulaire de surexpression du gène MAST3 dans les cellules HEK293 et analysé l’expression pangénomique endogène. La validation de l’expression génique dans un 2e modèle cellulaire de knockdown et de type cellulaire différent (THP1), nous a permis d’identifier et de contrer les effets non-spécifiques dus aux niveaux non-physiologiques. Notre étude d’expression a mené à l’identification d’un groupe de gènes dont l’expression est régulée par MAST3. Ces gènes sont majoritairement impliqués dans des fonctions immunitaires (cytokines pro-inflammatoires, régulateurs de NF-kappaB, migration cellulaire, etc.) et une forte proportion est régulée par NF-kappaB. Nous avons évalué l’importance du groupe de gènes régulés par MAST3 dans la présentation clinique des MII à travers des études d’expression dans des biopsies intestinales de patients atteints de CU. Nous avons constaté que l’expression de ces gènes est significativement supérieure dans les régions enflammées par rapport aux régions saines de la muqueuse intestinale des patients atteints de CU. Globalement, les résultats de nos études suggèrent que le facteur de risque aux MII MAST3 agit via la voie du facteur de transcription NF-kappaB pour influencer l’expression d’un groupe de gènes impliqués dans l’inflammation intestinale typique des MII. Chaque étude génétique sur les MII a le potentiel d’orienter les recherches fonctionnelles vers de nouvelles voies biologiques causales. Le dévoilement des mécanismes moléculaires sous-jacents à ces voies permet d’augmenter les connaissances sur le développement de ces maladies vers une compréhension plus complète de la pathogenèse qui permettra d’optimiser le diagnostic et le traitement de ces maladies. / Inflammatory bowel diseases (IBD) refer to different chronic inflammatory diseases of the digestive tract mainly Crohn’s disease (CD) and ulcerative colitis (UC). Mechanisms leading to the pathogenesis of IBD are not completely understood, but genetic and functional studies have highlighted interactions between genetic predispositions and environmental factors, such as the intestinal microbiota, as contributors to the deregulation of the immune response that leads to inflammation of the intestinal mucosa. Genome-wide and targeted association studies have identified several IBD susceptibility genes. However, estimations of the contribution of these genes to heritability of the disease suggest that more are to be discovered. Some of these genes may be in previously identified IBD linkage regions. The objective of my doctoral project was first, to identify risk factors in the 19p chromosomal region (IBD6), previously identified following a genome-wide linkage study, then to characterise them functionally. We first performed a comprehensive association mapping study of the 19p region. Our two-stage genotyping strategy led to the identification of one intronic SNP and four coding SNP –including one non-synonymous SNP, rs8108738 – all located in the microtubule associated serine threonine kinase gene 3 (MAST3) and associated to IBD. Very limited functional information on MAST3 was available at that time. However MAST2 (a gene in the same family as MAST3), is involved in the regulation of inflammation master switch, transcription factor NF-B. We confirmed the involvement of MAST3 in the modulation of NF-B via a knockdown of MAST3 and gene reporter assays. In order to further characterize the function of MAST3, we chose a non-targeted approach to study the effects of the modulation of MAST3 levels on the cell. More specifically, we created a 1st cell model of MAST3 overexpression in HEK293 cells and analysed the resulting genome-wide endogenous gene expression. Validation in a 2nd cell model consisting of a knockdown of MAST3 in THP1 cells, allowed to identify non-specific gene expression due to non-physiological MAST3 levels. Our expression study led to the identification of a group of genes whose expression is modulated by MAST3. These genes are mainly involved in immune functions (pro-inflammatory cytokines, NF-B regulation, cellular migration, etc) and a majority is regulated by transcription factor NF-B. We evaluated the importance of this MAST3-regulated gene set in the clinical manifestation of IBD through an expression study on biopsies of UC patients. We found that the expression the MAST3-regulated gene set was significantly enriched in inflamed region of the intestinal mucosa of UC patients compared to healthy region. Taken together, the results of our study suggest that IBD risk factor MAST3 acts on the NF-B pathway to influence the expression of a group of genes involved in intestinal inflammation typical of IBD. Every genetic study on IBD has the potential to lead functional research towards new causal biological pathways. The unravelling of the molecular mechanisms underlying these pathways aims to improve the comprehension of the pathogenesis of IBD and hopefully will allow for optimization of diagnostic and treatment of these diseases.

Scrub typhus is a potentially fatal infection that threatens one billion persons in the Asia-Pacific region and is caused by the obligate intracellular bacterium, Orientia tsutsugamushi. How this organism facilitates its intracellular survival and pathogenesis is poorly understood. Intracellular bacterial pathogens utilize the Type 1 (T1SS) or Type 4 secretion system (T4SS) to translocate ankyrin repeat-containing proteins (Anks) into the host cell to modulate host cell processes. The O. tsutsugamushi genome encodes one of the largest known bacterial Ank libraries as well as Type 1 and Type 4 secretion systems (T1SS and T4SS), which are expressed during infection. In silico analyses of the Anks’ C-termini revealed that they possess characteristics of T1SS secretion signals. Escherichia coli expressing a functional T1SS was able to secrete chimeric hemolysin proteins bearing the C-termini of 19 of 20 O. tsutsugamushi Anks. In addition to infecting endothelial cells, O. tsutsugamushi infects professional phagocytes. To better understand why these innate immune cells are unable to eliminate O. tsutsugamushi, we addressed the activity of host NF-κB proinflammatory transcription factor. Screening of O. tsutsugamushi infected cells at an MOI of 1 revealed inhibition of NF-κB nuclear accumulation as early as 8 hours in HeLa and bone-marrow derived macrophage cells. When stimulating infected cells with TNF-α, IκBα degradation still occurs, however NF-κB dependent gene transcription remains downregulated. Immunofluorescence microscopic analysis of TNF-α treated cells ectopically expressing all O. tsutsugamushi Anks revealed that two nuclear trafficking Anks, Ank1 and Ank6, result in a significant decrease in NF-κB nuclear accumulation. Additionally, these Anks also significantly inhibited NF-κB dependent gene transcription. Co-immunoprecipitation experiments revealed that both Anks interact with importin-β1, exportin-1, and the p65 NF-κB subunit. Treating cells with importazole significantly reduces the nuclear accumulation of Ank1 and Ank6. Finally, treating infected cells or cells ectopically expressing Ank1 or Ank6 with leptomycin B resulted in restoration of NF-κB nuclear accumulation. With these data, we propose that O. tsutsugamushi secretes Ank1 and Ank6 to initially interact with importin-β1, which permits their nuclear entry where they then interact with NF-κB and subsequently exportin-1 to prevent NF-κB nuclear accumulation.

The product development process for the automotive industry is normally complicated, lengthy, expensive, and risky. Hence, a study on a new concept for Low Volume Automotive Manufacturing (LVAM), used for niche car models manufacturing, is proposed to overcome this issue. The development of a hybrid Knowledge Based (KB) System, which is a blend of KB System, Gauging Absences of Pre-requisites (GAP), and Analytic Hierarchy Process (AHP) is proposed for LVAM research. The hybrid KB/GAP/AHP System identifies all potential elements of LVAM issues throughout the development of this system. The KB System used in the LVAM analyses the gap between the existing and the benchmark organisations for an effective implementation. The novelty and differences in the current research approach emphasises the use of Knowledge Based (KB) System in the planning and designing stages by suggesting recommendations of LVAM implementation, through: a) developing the conceptual LVAM model; b) designing the KBLVAM System structure based on the conceptual LVAM model; and c) embedding Gauging Absences of Pre-requisites (GAP) analysis and Analytic Hierarchy Process (AHP) approach in the hybrid KBLVAM System. The KBLVAM Model explores five major perspectives in two stages. Planning Stage (Stage 1) consists of Manufacturer Environment Perspective (Level 0), LVAM Manufacturer Business Perspective (Level 1), and LVAM Manufacturer Resource Perspective (Level 2). Design Stage (Stage 2) consists of LVAM Manufacturer Capability - Car Body Part Manufacturing Perspective (Level 3), LVAM Manufacturer Capability - Competitive Priorities Perspective (Level 4), and LVAM Manufacturer Capability - Lean Process Optimisation Perspective (Level 5). Each of these perspectives consists of modules and sub-modules that represent specific subjects in the LVAM development. Based on the conceptual LVAM model, all perspectives were transformed into the KBLVAM System structure, which is embedded with the GAP and AHP techniques, hence, key areas of potential improvement are recommended for each activity for LVAM implementation. In order to be able to address the real situation of LVAM environment, the research verification was conducted for two automotive manufacturers in Malaysia. Some published case studies were also used to check several modules for their validity and reliability. This research concludes that the developed KBLVAM System provides valuable decision making information and knowledge to assist LVAM practitioners to plan, design and implement LVAM in terms of business organisation, manufacturing aspects and practices.