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No / Reconfigurable manufacturing systems (RMSs) are designed based on the current and future requirements of the market and the manufacturing system (MS). The first stage of designing an RMS at the tactical level is the evaluation of economic and manufacturing/operational feasibility. Because of risk and uncertainty in an RMS environment, this major task must be performed precisely before investment in the detailed design. The present paper highlights the importance of manufacturing capacity and functionality for the feasibility of an RMS design during reconfiguration processes. Due to uncertain demands of product families, the RMS key-design factors, i.e. capacity value, functionality degree and reconfiguration time, are characterized by the identified fuzzy sets. Consequently, an integrated structure of the analytical hierarchical process and fuzzy set theory is presented. The proposed model provides additional insights into a feasibility study of an RMS design by considering both technical and economical aspects. The fuzzy analytical hierarchical process model is examined in an industrial case study by means of Expert Choice software. Finally, the fuzzy multicriteria model is sensitively analysed within the fuzzy domains of those attributes, which are considered to be critical for the case study.

The immune defense is geared to protect against a tremendous array of invaders. The ultimate goal of the immune system is to induce effective and balanced inflammatory responses that enable the efficient elimination of possible threats while avoiding both immunodeficiency and autoimmunity. The skewness towards inflammatory responses causing excessive collateral damage could lead to diverse autoimmune conditions. These conditions could be organ-specific or result from systemic immune dysregulations called systemic autoimmunity. The multifaceted nature and the intricate clinical heterogeneity of systemic autoimmune conditions indicate a strong influence of environmental factors on their immunopathogenesis, where environmental factors could either hinder or contribute to autoimmune development. We focused our research on deciphering the complex effects of environmental factors on the immunopathogenesis of systemic immune dysregulation, taking systemic lupus erythematosus (SLE or Lupus) as a model of systemic autoimmunity. SLE is one of the most mysterious autoimmune disorders with no known cure. In SLE, breaching of tolerance to self-antigens and the subsequent persistent inflammation and collateral tissue damage in multiple organs lead to very diverse clinical manifestations. These manifestations are a result from the interplay between multiple genetic susceptibilities and diverse environmental factors. To date, management plans for SLE are based on non-selective immunosuppressants that could impose significant side effects including increased risks of infection and infection-related mortalities. In parallel, environmental factors and the quality of life could significantly impact SLE management strategies. Therefore, delineating the immunomodulatory capacities of environmental factors would likely unravel more effective management strategies for SLE patients. The current research aims to investigate the central hypothesis that dietary and hygienic components modulate the immune dysregulations of SLE in a tissue- and disease stage-specific manner. We have focused on uncovering the complex effects of Vitamin A (VA) as an essential micronutrient with very diverse immunomodulatory capacities, and quaternary ammonium compound (QAC)-based disinfectants as ubiquitously used disinfectants that have been linked to immunotoxicity, on the immunopathogenesis of SLE. Due to the strong female bias of SLE where women especially of childbearing age are more prone to lupus, we have focused our research on delineating how these diverse factors shape the immunopathogenesis of SLE in female mice only. The first project dissected the immunomodulatory effects of VA, a potent immunomodulatory dietary component. Notably, VA exerts its function through a predominant metabolite known as all-trans-retinoic acid (tRA) that, as we have previously shown, has paradoxical and tissue-specific implications on lupus inflammation. Here, we utilized a pristane-induced model of lupus to investigate the disease stage-dependent effects of tRA. Oral supplementation of tRA was given either before pristane induction of lupus from weaning (3 weeks) to 3 months of age or after pristane induction of lupus from 3 to 9 months of age. We found that tRA treatment mediated disease stage-dependent effects and differentially affected the lupus-associated kidney inflammation (lupus nephritis) when given at the initiation vs. continuation phase of lupus. Unlike tRA treatment during active disease, pre-pristane treatment with tRA aggravated glomerulonephritis through potentiating leukocyte activation and trafficking to the kidney and augmenting renal pro-fibrotic signals. Post-pristane tRA treatment, on the other hand, exerted immunosuppressive functions of decreasing circulatory and renal deposition of autoantibodies as well as suppressing the renal expression of proinflammatory cytokines and chemokines. Interestingly, both pre- and post-pristane treatments with tRA reversed the pristane-induced leaky gut and similarly modulated the gut microbiota, suggesting a gut microbiota-independent mechanism by which tRA affects the initiation vs. continuation phase of lupus. As tRA could be protective against lupus nephritis especially during the active disease stage, and previous reports had shown hypovitaminosis A (reduced serum retinol levels) proceeding SLE, we expanded our investigation to decipher whether VA deficiency (VAD) was a contributing factor for severe SLE and to delineate how VAD affected the initiation and/or the progression of lupus nephritis in genetically-prone conditions. For that purpose, we utilized the classical murine lupus-prone model, MRL/lpr, and initiated VAD either during the gestation or after weaning to reveal potential time-dependent effects. VAD exacerbated lupus nephritis by provoking severe neutrophilic tubulointerstitial nephritis, and accelerated renal failure. This was concomitant with significantly higher mortality in all VAD mice. Mechanistically, VAD enhanced early activation of plasma cells and augmented their autoantibodies production. In addition, VAD led to an enhanced expansion of pathogenic T lymphocytes. In parallel, VAD increased renal infiltration of conventional and plasmacytoid dendritic cells. Our findings establish VAD as a driving factor for lupus nephritis progression in genetically predisposed conditions. These findings emphasize the importance of monitoring VA levels in SLE patients and urge for VA supplementations for patients at higher risk for hypovitaminosis A, especially during the maternal-neonatal interface. Additionally, this project warrants further investigations to delineate the molecular targets through which VA modulates cellular functions as well as immunopathogenesis of lupus nephritis. The information obtained from these studies may also benefit women with other autoimmune conditions and will pave the way for VA supplementations to be tested in clinical trials. The second project investigated the effects of ambient exposure to QAC-based disinfectants on the progression of murine SLE in genetically prone mice. We compared the disease progression in MRL/Lpr mice that have been exposed to QACs vs. those kept under a complete QAC-free condition. QAC-based disinfectants CP-64 or Labsan 256 were used under QAC-exposed conditions, while ethanol was used in the QAC-free environment. We found that compared to QAC-free mice, ambient exposure of lupus-prone mice to QACs led to smaller spleens with no change in circulating autoantibodies or the severity of glomerulonephritis. This suggests that QACs may have immunosuppressive effects on lupus. Using a microfluidic device, we showed that ambient exposure to QACs reduced directional migration of bone marrow-derived neutrophils toward an inflammatory chemoattractant ex vivo. Consistent with this, we found decreased infiltration of neutrophils into the spleen. While bone marrow-derived neutrophils appeared to exhibit a pro-inflammatory profile, upregulated expression of PD-L1 was observed on neutrophils that infiltrated the spleen, which in turn interacted with PD-1 on T cells and modulated their fate. Specifically, QAC exposure hindered activation of splenic T cells and increased apoptosis of effector T-cell populations. Collectively, these results suggest that ambient QAC exposure decreases lupus-associated splenomegaly likely through neutrophil-mediated toning of T-cell activation and/or apoptosis. However, our findings also indicate that even ambient exposure could alter immune cell phenotypes, functions, and their fate. Further investigations on how QACs affect immunity under steady-state conditions are warranted. Collectively, the findings of this doctoral research suggest temporal and spatial effects of diet and hygiene on systemic autoimmunity and emphasize the strong influence of environmental factors toning cellular immune responses and subsequently shaping autoimmune outcomes. Our findings could pave the way for more personalized healthcare plans for autoimmune patients that take into consideration tissue involvement, disease stages, and the patient's lifestyle. / Doctor of Philosophy / The immune system is efficiently toned to discriminate between friends and foes. It effectively protects against a wide array of pathogens while at the same time avoiding attacking self-tissues. The inability of immune defenses to achieve this optimal discrimination could lead to the breakdown of tolerance to self in a wide range of autoimmune conditions. Diverse genetic susceptibilities are implicated in the development of autoimmunity. In parallel, during the recent decades, the tremendous increase in the prevalence of autoimmune conditions coincides with evolving dietary and hygiene styles in Westernized societies. This suggests a strong influence of environmental factors such as dietary and hygienic components on the way that the immune system works. Therefore, the current research investigates whether diet and hygiene modulate the immune dysregulations of lupus disease as a model for systemic autoimmunity; and if so, whether such effects are tissue- and/or disease stage-specific. We utilized different mouse models to delineate the mechanisms by which essential nutrients such as vitamin A (VA) and widely used disinfectant compounds known as quaternary ammonium disinfectants (QACs) modulate the systemic autoimmunity in lupus disease. We found that these modulators influence various aspects of the cellular immune responses including (1) leukocyte activation and subsequent expansion of pathogenic (disease contributing) lymphocytes, production of antibodies directed against self-tissue molecules (i.e., autoantibodies), and production of inflammatory mediators (i.e., cytokines and chemokines); (2) cell trafficking and their infiltration into the tissues; (3) signal transduction pathways that modulate cell fate (e.g., PD-1: PD-L1 signaling). Importantly, environmental modulation of autoimmunity during different stages of autoimmune development could significantly impact the disease outcome. VA treatment, for example, differentially modulates the progression of kidney inflammation when given during the initiation vs. progressive disease stages. Similarly, VA deficiency has the most prominent effects on worsening kidney inflammation under genetically prone conditions when the deficiency is initiated early and at the prenatal stage. In parallel, the effects of environmental factors are also tissue-specific. For example, ambient exposure to QAC-based disinfectants exerted immunosuppressive effects on lupus-associated inflammation of lymphoid tissues with no change in circulating autoantibodies or the severity of kidney inflammation. Collectively, the findings of this doctoral research delineated the cellular mechanisms through which environmental factors could shape autoimmune responses. Further studies will dig into the underlying molecular pathways. Ultimately, our research emphasizes the strong influence of exogenous factors on immunity and will pave the way for more effective healthcare management plans and benefit vulnerable populations affected by autoimmune conditions such as lupus.

Yes / To identify a subset of software issues occurring in daily Swedish healthcare practice and devise a set of local solutions to overcome the challenges. Methods: A sample of 46 incident reports was collected from one of Sweden's national incident reporting repositories, ranging from June 2019 to December 2021. The reports were first subjected to an algorithm to identify if they were health information technology-related incidents and were analysed using an existing framework, i.e., the Health Information Technology Classification System, to identify the software-related incidents. The incidents associated with software issues were then subjected to thematic analysis, in which themes were extracted and presented under the category assigned by the existing framework used. Results: Of 46 reports, 45 (with one exception) were included using the algorithm. Of 45 incidents, 31 software-related incidents were identified using the classification system. Six types of software issues were identified, including software functionality (n = 10), interface with other software systems or components (n = 10), system configuration (n = 7), interface with devices (n = 2), record migration (n = 1) and increased volume of transactions (n = 1). Each issue was further categorised into different themes; for example, software interface-related problems were grouped into ‘two patients being active in the system simultaneously’ (n = 6) and ‘transfer of patient information’ (n = 4). Conclusions: The study provided some insights into software issues and relevant consequences. A set of local solutions were devised to overcome the present challenges encountered in Swedish healthcare in their daily clinical practice. Systematic identification and characterisation of such software challenges should be a routine part of clinical practice for all major health information technology implementations. / This work has been part of being an Affiliated Researcher at the Department of Medicine and Optometry, Linnaeus University, Sweden. A publishing grant was received from Linnaeus University as a part of the University Library's research support.

The goal of the project is to develop a news widget for the company Atega In-sight. This news widget will be integrated into their Priceagent application and improve the ability of customers to set prices for their products. Daily meetings with the company as well as communication via chat and other spontaneous meetings. The project includes adjustments to previous sketches to meet current requirements as well as planning the functionality of the widget in the design tool Figma. The project's code will primarily be written in Visual Studio Code. The back-end is developed with NodeJS and the Serverless Framework as the basis for the API, while MongoDB is used as the database manager. Testing of the back-end takes place using the Postman API platform. On the front-end side, reusable components are created with React, mainly written in TypeScript. Ready-made components from Ant Design and styling are done with Styled-Components. The front-end structure follows the Atomic Design Pattern. The result of the project has given the company a functional widget where users can add, remove, edit and view their news feeds. Users can also switch between different tabs and paginate the news articles. Testing of the widget has mainly been performed with various browser add-ons, including VisBug to see if the size of the various components matches the sketches and responsiveness. Wave for testing availability and Lighthouse for performance. However, there is room for more superficial development, such as a better implementation of the NewsAPI in the back-end and small adjustments to improve the user experience, as the widget can sometimes be perceived as slow. / Målet med projektet är att utveckla en nyhetswidget åt företaget Atega Insight. Denna nyhetswidget ska integreras i deras Priceagent -applikation och förbättra kundernas förmåga att satta priser på sina produkter. Dagliga möten med företaget samt kommunikation via chatt och andra spontana möten. Projektet innefattar justeringar av tidigare skisser för att möta aktuella krav samt planering av widgetens funktionalitet i designverktyget Figma. Projektets kod kommer främst att skrivas i Visual Studio Code. Back-end utvecklas med NodeJS och Serverless Framework som grund för API: et, medan MongoDB används som databashanterare. Testning av back-end sker med hjälp av API-plattformen Postman. På front-end-sidan skapas återanvändbara komponenter med React, huvudsakligen skrivet i TypeScript. Färdiga komponenter från Ant Design och styling sker med Styled Components. Front-end-strukturen följer designmönstret Atomic Design Pattern. Resultatet av projektet har gett företaget en funktionell widget där man kan lagga till, ta bort, redigera och se sina nyhetsflöden. Användarna kan ocksa byta mellan olika flikar och paginera nyhetsartiklarna. Testning av widgeten har främst utförts med olika webbläsartillägg, bland annat VisBug för att se om storleken på de olika komponenterna stämmer överens med skisserna och responsivitet. Wave för att testa tillgängligheten och Lighthöuse för prestanda. Det finns dock utrymme för ytterligare utveckling, såsom en bättre implementering av NewsAPI i back-end öch sma justeringar för att förbättra användarupplevelsen, då widgeten ibland kan upplevas som långsam.

Objetivo: Establecer la asociación entre el nivel de funcionalidad y la fuerza miembros inferiores en adultos mayores en comunidad. Materiales y métodos: Se realizó un estudio de transversal analítico en una comunidad de adulto mayor en Lima Perú. La población está conformada por adultos mayores de 60 años. Las variables de resultado fue la funcionalidad y las de exposición fueron la fuerza funcional en miembros inferiores y como confusoras el equilibrio y la masa magra apendicular para ello se aplicaron 6 pruebas. La primera evalúa la funcionalidad en general del adulto mayor mediante el SF-36, el cual abarca 8 dimensiones como funcionamiento físico, rol físico, dolor corporal, salud general, vitalidad, funcionamiento social, rol emocional y salud mental, el segundo evalúa la funcionalidad de miembros inferiores del adulto mayor. El tercero es el test de cinco veces pararse de sedente, que evalúa la fuerza muscular funcional de miembros inferiores. Para la medición de las variables confusoras utilizamos: El test de alcance máximo que mide la flexibilidad de miembros inferiores. Ponte de pie y anda que mide el equilibrio dinámico, coordinación y velocidad. Finalmente, se midió la masa muscular de miembros inferiores con la fórmula de Masa magra apendicular esquelética (MMAE). La recolección de datos se realizó con 2 personas y la muestra fue estratificada en edad y sexo. Se evaluó a cada participante en un ambiente específico para las evaluaciones en la misma comunidad de adulto mayor. Resultados: Se encontró asociación estadísticamente significativa entre la funcionalidad de miembros inferiores y la fuerza funcional de miembros inferiores (β =-0.642, p=0.003). Asimismo, otras variables que estuvieron asociadas a la funcionalidad de miembros inferiores son flexibilidad (p=0.006) y caídas (p=0.001). Conclusión: En el presente estudio fue realizado en Lima Perú; en el distrito de Molina Centro Integral del adulto mayor (CIAM) se encontró que existe asociación entre el nivel de funcionalidad de miembros inferiores con la fuerza funcional de miembros inferiores en adultos mayores. Asimismo, las variables caídas y flexibilidad también estuvieron relacionadas con el nivel de funcionalidad. / Objective: establish the association between the level of functionality and the lower member force in community older adults. Materials and methods: An analytical cross-sectional study was conducted in an older adult community in Lima Peru. The population is made up of adults over 60 years. The outcome variables were the functionality and the exposure variables were the functional force in the lower limbs and as balance the balance and the appendicular lean mass for this purpose, 6 tests were applied. The first assesses the functionality of the elderly in general through the SF-36, which covers 8 dimensions such as physical functioning, physical role, body pain, general health, vitality, social functioning, emotional role and mental health, the second evaluates functionality of lower limbs of the elderly. The third is the five-times sit to stand test, which evaluates the functional muscle strength of the lower limbs. For the measurement of confusing variables, we use: The maximum range test that measures the flexibility of lower limbs. Stand up and walk that measures dynamic balance, coordination and speed. Finally, the lower limb muscle mass was measured with the skeletal appendicular lean mass (MMAE) formula. Data collection was performed with 2 people and the sample was stratified in age and sex. Each participant was evaluated in a specific environment for assessments in the same senior community. Results: A statistically significant association was found between lower limb functionality and lower limb functional strength (β = -0.642, p = 0.003). Likewise, other variables that were associated with lower limb functionality are flexibility (p = 0.006) and falls (p = 0.001). Conclusions: In the present study, it was made in Lima Peru; In the district of Molina Centro Integral for the Elderly (CIAM) it was found that there is an association between the level of functionality of the lower limbs and the functional strength of the lower limbs in older adults. Likewise, the variables falls, and flexibility were also related to the level of functionality. / Tesis

This dissertation seeks to capture Muhammad's emergence as Prophet. It starts from the premise that he located himself as a Prophet within a fraternity of prophethood. More specifically he has seen his work as a continuation of the Biblical prophetic tradition. However he has stressed his election as correcting what has been altered in this Biblical tradition. Muhammad: A prophet of God argues that he has as prophet the same defining elements as Biblical prophets; as result we must not criticise him unnecessarily, that is, for the sake of fitting him into our categories. Muhammad must be seen terms of his experiences. In addition we must capture his contribution to humanity. / Religious Studies & Arabic / M.A. (Religious Studies)

This thesis proposes a new methodology to extend the software performance engineering process. Common performance measurement and tuning principles mainly target to improve the software function itself. Hereby, the application source code is studied and improved independently of the overall system performance behavior. Moreover, the optimization of the software function has to be done without an estimation of the expected optimization gain. This often leads to an under- or overoptimization, and hence, does not utilize the system sufficiently. The proposed performance improvement methodology and framework, called dynamic performance stubs, improves the before mentioned insufficiencies by evaluating the overall system performance improvement. This is achieved by simulating the performance behavior of the original software functionality depending on an adjustable optimization level prior to the real optimization. So, it enables the software performance analyst to determine the systems’ overall performance behavior considering possible outcomes of different improvement approaches. Moreover, by using the dynamic performance stubs methodology, a cost-benefit analysis of different optimizations regarding the performance behavior can be done. The approach of the dynamic performance stubs is to replace the software bottleneck by a stub. This stub combines the simulation of the software functionality with the possibility to adjust the performance behavior depending on one or more different performance aspects of the replaced software function. A general methodology for using dynamic performance stubs as well as several methodologies for simulating different performance aspects is discussed. Finally, several case studies to show the application and usability of the dynamic performance stubs approach are presented.