| 1. |
- Areth Koroth, Rohith
(författare)
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Supporting production preparation during product development using production requirements
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Product development is affected by uncertainties due to changing customer requirements, changing regulations, technological developments, long lead times, high product complexities, and geopolitical issues. Automation, increased flexibility of production, and reduced lead times are drivers that allow product development to be competitive in this scenario. Design engineers should be aware of production capabilities to facilitate early producibility assessments and to avoid late changes. Production preparation is identified as an important activity in the product development process, whereby the producibility of a product is assessed. In this thesis, the current state of production preparation during product development is investigated and a method is introduced supporting production preparation using production requirements. The work was carried out using the design research methodology framework and comprised four studies based on the four steps of the framework. The research clarification and descriptive study 1 phases aimed at developing understanding and were done by means of data collection at the companies through interviews and document studies. The next two steps were prescriptive study and descriptive study 2, which aimed at developing and evaluating the support. This was done through observation, workshops, and solution development. The production preparation process is supported by Design for Manufacturing and Assembly, failure mode and effects analysis, lesson-learnt documents, and computer-aided design, and the efficiency of the process is dependent on individual skills and knowledge. Tools to support common understanding, remove ambiguity in requirements, and enable collaboration between design and production engineers are needed. The developed method allows for the identification, definition, structuring, and sharing of production requirements, aligning with varying maturities of product and production systems during product development. This helps improve the collaboration between design and production engineers for production preparation.
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| 2. |
- Arjomandi Rad, Mohammad
(författare)
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Data-driven and real-time prediction models for iterative and simulation-driven design processes
- 2022
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The development of more complex products has increased dependency on virtual/digital models and emphasized the role of simulations as a means of validation before production. This level of dependency on digital models and simulation togetherwith the customization level and continuous requirement change leads to a large number of iterations in each stage of the product development process. This research, studies such group of products that have multidisciplinary, highly iterative, and simulation-driven design processes. It is shown that these high-level technical products, which are commonly outsourced to suppliers, commonly suffer from a long development lead time. The literature points to several research tracks including design automation and data-driven design with possible support. After studying the advantages and disadvantages of each track, a data-driven approachis chosen and studied through two case studies leading to two supporting tools that are expected to improve the development lead time in associated design processes. Feature extraction in CAD as a way to facilitate metamodeling is proposed as the first solution. This support uses the concept of the medial axis to find highly correlated features that can be used in regression models. As for the second supporting tool, an automated CAD script is used to produce a library of images associated with design variants. Dynamic relaxation is used to label each variant with its finite element solution output. Finally, the library is used to train a convolutions neural network that maps screenshots of CAD as input to finite element field answers as output. Both supporting tools can be used to create real-time prediction models in the early conceptual phases of the product development process to explore design space faster and reduce lead time and cost.
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| 3. |
- Heikkinen, Tim
(författare)
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Extended product models supporting multidisciplinary design automation
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Manufacturing organizations often pursue the ability to efficiently and effectively provide custom products for its competitive advantage. Research has shown product configuration to be an effective way of achieving this goal through a modularization, product platform, and product family development approach. A core assumption behind this approach is that the module variants and their constraints are explicitly pre-defined as product knowledge. This is not always the case, however. Many companies require extensive engineering to develop each module variant but cannot afford to do so proactively to meet potential customer requirements within a predictable future. Instead, they attempt to implicitly define the module variants in terms of the process in which they can be realized. In this way, manufacturing companies develop module variants on demand efficiently and effectively when customer requirements are better defined, as justified by the increased probability of profiting from the outcome.Design automation (DA), in its broadest definition, refers to computerized engineering support that efficiently and effectively utilizes pre-planned reusable assets to progress a design process. The literature has reported several successful implementations of DA, but especially widespread higher levels of automation are yet to be seen. One DA approach involves the explicit representation of engineering process and product knowledge in the engineers preferred formats, such as computer scripts, parametric geometry models, and template spreadsheets. These design assets are developed using various computer tools, maintained within the different disciplines involved, such as design, simulation, or manufacturing, and are dependent on each other through the product model. To implement, utilize, and manage DA systems in or across multiple disciplines, it is important to understand how the disciplinary design assets depend on each other throughout the product model and how these relations should be constructed to support users without negatively affecting other aspects, such as modeling flexibility, system transparency, and software tool independence.To support the successful implementation and management of DA systems, this work focuses on understanding how digital product model constituents are, can, and, to some extent, should be extended to concretize relations toward and between design assets from different tools and disciplines. This research consists of interviews with Swedish industrial companies, technical reviews, literature reviews, and prototype developments, resulting in an increased understanding and the consequent development of a framework that highlights aspects regarding the choice and development of extension techniques.
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| 4. |
- Honarpardaz, Mohammadali, 1986-
(författare)
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Finger Design Automation for Industrial Robots : A Generic and Agile Approach
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- ROBOT fingers play a crucial role in the success and performance of workcells, as fingers are the only interfaces that connect the robot to the physical working environment. Fingers are responsible for grasping and manipulating workpieces without dropping or damaging them. Designing industrial robot fingers to accomplish assigned tasks is therefore tremendously complex and requires high skills in robotics and designing at the same time.Today, there is a trend toward products with short lifecycles and, as a result, many robot industries have focused on enhancing the competitiveness of robotic automation in the agile market. SARAFun and Factory-in-a-day are two large European Commission projects which are formed to enable a non-expert user to integrate a robot system for an assembly task in one single day. Currently, fingers of industrial grippers (e.g. parallel- jaw) are designed manually, a process that requires several exhaustive and time- consuming trial and error iterations even for highly skilled specialists. The average iteration time is about three to four working days and the total time for designing fingers can amount to around two weeks depending on the complexity requirements.The present iterative procedure of manual finger design is unable to fulfil the demands of ‘‘burst’’ production (i.e. ramp up to full volume in a very short time, run production for 3–12 months, and then change to produce a new product). Finger design automation has therefore been increasingly attracting the attention of the robot industry. However, very few researchers have studied finger design automation and unfortunately no one has validated the proposed approaches with a generic experimental method.This research therefore proposes the generic optimized finger design (GOFD) framework in order to automate the design process of robotic fingers. The framework is optimized to reduce the design process time while maintaining high reliability and performance of the fingers. The functionality and general applicability of the framework is examined in various case studies and applications with a diverse range of workpieces. In order to be able to benchmark the functionality of robotic fingers, an experimental method is also developed to measure the stability and performance of the fingers in industrial practice. The proposed experimental method is employed to evaluate the functionality of the GOFD fingers and compare it with that of other fingers. Results are comprehensively analysed and the strengths and weaknesses of each method are highlighted. This thesis thus presents a design automation processes that automates the design procedure for robotic fingers, together with an experimental method to compare the performance of different finger designs. The introduced GOFD method can help robot industries comply with the trending agile market. Moreover, scholars who are inexpert in robotics may benefit from utilizing GOFD in their research to generate functional fingers.
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| 5. |
- Lager, Malin, 1975-
(författare)
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Molecular and serological tools for clinical diagnostics of Lyme borreliosis - can the laboratory analysis be improved?
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lyme borreliosis (LB) is caused by spirochetes within the Borrelia burgdorferi sensu lato complex and is the most common tick-transmitted disease in the northern hemisphere. The transmission of the spirochetes to humans in Europe is done by the Ixodes ricinus ticks, which can also transmit the relapsing fever species Borrelia miyamotoi. LB may cause clinical manifestations in the skin, in the central nervous system, in joints, and in the heart. Diagnosis of LB is mainly based on the patient´s medical history, self-described symptoms, and clinical signs in combination with the detection of Borrelia-specific antibodies (serological methods). In some cases/issues, detection of Borrelia-specific deoxyribonucleic acid (molecular methods) may be used as a complement to serology. All diagnosed LB infections are treated with antibiotics to prevent disease progression, and most patients fully recover without further sequelae. The overall aims of this thesis were to evaluate molecular and serological tools for laboratory diagnosis of LB, with a special focus on Lyme neuroborreliosis (LNB), and to identify potential improvements.The results presented in this thesis showed that the immunoglobulin (Ig) G assays, currently in use in northern Europe for detection of antibodies in serum, had high diagnostic sensitivity (88 %) together with comparable results both between and within assays. For the IgM assays, the diagnostic sensitivity was lower (59 %) with more heterogeneous results. Small variations in diagnostic performance for IgM and IgG were mainly presented for samples within the borderline zone. These results support the theory that separate testing of IgM antibodies in serum has low diagnostic value. However, simultaneous detection in serum and cerebrospinal fluid (CSF) for both IgM and IgG antibodies was essential for the diagnosis of LNB, at least for certain assays.So far (to our knowledge), no systematic evaluation and optimisation of the pre-analytical handling of CSF samples before molecular testing has been performed. By use of the precipitate concentrated by moderate centrifugation, extraction of total nucleic acid followed by reversetranscription to complementary deoxyribonucleic acid, in combination with the absence of polymerase chain reaction (PCR) inhibitors, detection of Borrelia garinii, Borrelia afzelii, Borrelia burgdorferi sensu stricto, and B. miyamotoi was possible. These four species are all known to be pathogenic to humans. The results revealed a high analytical sensitivity and specificity for the optimised pre-analytical conditions. The thesis also presents results showing that the real-time PCR protocols currently used in Scandinavia have high analytical sensitivity, specificity, and concordance. This indicates that the low diagnostic sensitivity for detection of Borrelia in CSF was not a result of poorly designed and evaluated PCR protocols, but was possibly due to the low number of spirochetes in the samples. However, to further evaluate the diagnostic performance for detection of Borrelia in CSF by PCR, clinical samples need to be evaluated based on our new recommendations for the pre-analytical handling of CSF samples.In conclusion, this thesis presents results revealing that both molecular and serological tools for detection of Borrelia have, in general high sensitivity and specificity with results comparable between different protocols and different laboratories. It also presents recommendations for pre-analytical handling of CSF samples before PCR-analysis, and shows the benefits in diagnostic performance by simultaneous detection of IgM and IgG antibodies in serum and CSF for accurate diagnosis of LNB. Even though the techniques mentioned above have high analytical performance, the ability to discriminate an active infection from a previous one is limited and further studies need to be carried out. These studies need to focus on finding diagnostic tools that can help physicians to determine ongoing infection to ensure adequate treatment. It is also desirable to improve the standardisation of the diagnostic tools and to find methods that can discriminate between different Borrelia species.
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| 6. |
- Panda, Swarupa, 1985-
(författare)
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The role and mechanism of ubiquitin system in innate immune regulation
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pattern-recognition receptors (PRRs) include the cell surface or endosomal membrane localized Toll-like receptors (TLRs) and the cytoplasmic PRRs such as RIG-I-like receptors (RLRs), NOD-like receptors (NLRs) and cytoplasmic DNA receptors (CDRs). Triggering of PRRs culminates in the transcriptional induction of pro-inflammatory cytokines and type I interferons (IFNs) that coordinate protection against pathogens but require tight control to avert inflammatory diseases. The mechanisms underlying this strict regulation are unclear.Ubiquitiation is a reversible post-translational modification that controls nearly all cellular processes including the immune system. We identified, H2A deubiquitinase myb-like SWIM and MPN domains 1 (MYSM1) a previously described as a key component of epigenetic signaling machinery as a key negative regulator of the innate immune system that guards against an overzealous self-destructive immune response. In response to microbial stimuli, MYSM1 accumulated in the cytoplasm where it interacted with and inactivated TRAF3 and TRAF6 complexes to terminate TLR, RLR and CDR pathways for pro-inflammatory and type I interferone responses. Consequently, MYSM1 deficiency in mice resulted in hyper-inflammation and enhanced viral clearance but also susceptibility to septic shock.NOD2, belonging to the intracellular NLR family. A focal point of NOD2 signalling is RIP2, which upon polyubiquitination nucleates the NOD2:RIP2 complex, enabling signaling events leading to inflammation, yet the precise nature and the regulation of the polyubiquitins coordinating this process remains unclear. We show that NOD2 signaling involves conjugation of RIP2 with K63, K48 and M1 polyubiquitin chains as well as with non-canonical K27 chains. Furthermore, we identify MYSM1 as the proximal deubiquitinase that attenuates NOD2- RIP2 complex assembly by selectively removing the K63, M1 and K27 chains. Consequently, MYSM1 deficient mice have unrestrained NOD2-mediated peritonitis and liver injury. Henceforth, this study provide a complete description of the polyubiquitin modifications in the NOD2:RIP2 signalling and reveal MYSM1 as a central negative regulator that prevents excessive inflammation.In order to overcome the host barrier to infection, some pathogens elude the immune defense by hijacking the ubiquitin system. Francisella tularensis is one of the most infectious bacteria. It employs several mechanisms to evade detection by the innate immune system, but how remains obscure. Here, we showed that Francisella triggers but concomitantly inhibits the TLRs, RLRs and CDRs pathway by inhibiting K63-linked polyubiquitination and assembly of TRAF6 and TRAF3 complexes that control the transcriptional responses of PRRs.In summary, my work identify MYSM1 as a key negative regulator of the innate immune system. Although, mainly located in the nucleus MYSM1 rapidly amass in the cytoplasm, where it interacts with and inactivates the key PRR signalling complexes. Afterward, MYSM1 undergoes proteaosomal degradation to avert sustained immune suppression. Thus, MYSM1 is part of a highly versatile negative feedback regulatory mechanism, which in response to biological danger is swiftly activated in “on-and-off” manner to restore immune homeostasis. Furthermore, Francisella targets the ubiquitin system to inhibt multiple PRRs hence allowing this bacterium to invade and proliferate in the host without evoking a self-limiting innate immune response.
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| 7. |
- Poorkiany, Morteza, 1980-
(författare)
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Managing design rationale in the development of product families and related design automation systems
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- As the markets’ needs change rapidly, developing a variety of products that meet customers’ diverse needs is a competitive factor for many manufacturing companies. Development of highly customized products requires following an engineer-to-order business process to allow the products to be modified or adapted to new customers’ specifications, which brings more value to the customer and profit to the company.The design of a new product variant involves a large amount of repetitive and time-consuming tasks but also information handling activities that are sometimes beyond human capabilities. Such work that does not rely so much on creativity can be carried out more efficiently by applying design automation systems. Design automation stands out as an effective means of cutting costs and lead time for a range of well-defined design activities and is mainly considered as a computer-based tool that processes and manipulates the design information.Variant design usually concern generating a new variant of a basic design, that has been developed and proved previously, according to new customer’s demands. To efficiently generate a new variant, a deep understanding of the intention and fundamentals of the design is essential and can be achieved through access to design rationale—the explanation of the reasons and justifications behind the design.The maintenance of product families and their corresponding design automation systems is essential to retaining their usefulness over time and adapting them to new circumstances. Examples of new circumstances can include the introduction of new variants of existing products, changes in design rules to meet new standards or legislations, or changes in technology. To maintain a design automation system, updating the design knowledge (e.g. design rules) is required. The use of design rationale will normally become a necessity for allowing a better understanding of the knowledge. Consequently, there is a need for principles and methods that enable the capture and structure of the design rationale and sharing them with the users.This study presents methods and tools for modeling design knowledge and managing design rationale in order to support the utilization and maintenance of design automation systems. Managing design rationale concerns enabling the capturing, structuring, and sharing of design rationale. The results have been evaluated through design automation systems in two case companies.
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| 8. |
- Thajudeen, Shamnath
(författare)
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A product platform approach to support the design phase of industrialised house building : A framework conceptualisation when using mixed production strategies
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ability to offer unique solutions that meet customer demands has been considered a competitive advantage in the industrialised house building (IHB) industry. However, IHB companies are struggling due to varying customer needs and the simultaneous need to fulfil legal regulations, market demands, and production constraints. This has forced companies to develop unique solutions for every housing project to satisfy individual requirements, which automatically drives them to follow an engineer-to-order (ETO)-based strategy. The high involvement of customers in the design process results in the need for considerable engineering activities to validate and adjust to the customer demands, thereby providing individualised solutions. Moreover, designers adopt different production strategies based on the degree of pre-engineering. Product platform approaches have been acknowledged as one of the prominent means to improve both internal and external efficiencies. However, the use of traditional platform-based strategies does not suffice for the design of ETO-based components in an IHB system. A systematic approach is required to align the product platform and different production strategies so that customer requirements can be easily managed. Thus, this research aims to outline the means to support the design phase of IHB by applying a product platform approach when using a mixed production strategy.A Swedish multi-storey house building company that uses a glulam-based post and beam building system was used as the main case in this research. Empirical data were collected mainly from interviews, observations, workshops, and document analysis. This research proposes a framework for the systematic development and use of the product platform by following an inductive approach. Further, a parametric design platform method is proposed to achieve a platform-based development for ETO-based components by identifying, formalising, and reusing the design assets. The findings reveal how the transition of production strategies can be managed with supporting tools and methods. Moreover, this thesis emphasizes the importance of adopting the design for manufacturing and assembly (DfMA) in IHB. In addition, the research contributes to the existing knowledge on product platforms in IHB by providing the context of mixed production strategies and best practices to improve the IHB design process.
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| 9. |
- Tjernberg, Ivar, 1973-
(författare)
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Laboratory Diagnosis of Lyme Borreliosis : Anti-Borrelia Antibodies and the Chemokine CXCL13
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lyme borreliosis (LB), the most common tick-borne disease in Europe and North America, is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. The spirochetes can invade several different organs, thereby causing many different symptoms and signs. Diagnosis of LB relies on patient history, physical examination, and detection of anti-Borrelia antibodies. However, anti-Borrelia antibodies are not always detectable, and they commonly persist even after LB is successfully treated or spontaneously healed.The aim of my work was to study diagnostic aspects on clinical cases of LB and control subjects in an area endemic to LB, with a focus on newly developed anti-Borrelia antibody tests. A total of 617 patients with symptoms and/or signs consistent with LB, as well as 255 control subjects, were studied. The diagnostic panel included the following new LB tests: Immunetics Quick ELISA C6 Borrelia assay kit (C6), invariable region 6 peptide antibody assays (IR6), Liaison Borrelia CLIA (Li) and the chemokine CXCL13. Results were compared with the older Virotech Borrelia burgdorferi ELISA (VT) and with a Western blot method, the Virotech Borrelia Ecoline IgG/IgM Line Immunoblot (WB EL), when appropriate.In general, no significant differences were noted between the C6, VT and Li tests regarding serosensitivity in various LB manifestations. However, the seropositivity rate was lower for the C6 test compared with the VT and Li tests 2–3 and 6 months after diagnosis of erythema migrans (EM), indicating normalization of antibody levels. In addition, EM patients reporting a previous LB episode had a C6 seropositivity rate similar to that of patients without a previous LB episode, and seroprevalence in healthy blood donors was lower in the C6 test than the VT and Li tests. Taken together, these results support the recommendation of the serum C6 test as a Borrelia serological test due to its ability to reflect ongoing or recent infection.Although the majority of EM patients at presentation showed concordant serological responses to IR6 peptides representing the three main Borrelia species and the C6 peptide, there were also clinical EM cases that were C6-negative and could be detected mainly by a seroresponse to a B. burgdorferi sensu stricto-derived IR6 peptide. Thus, an antibody test combining antigens could be of value in the serodiagnosis of LB in Europe.The serosensitivity of the C6 test in cases of Lyme neuroborreliosis (LNB) was shown to be associated with symptom duration. A serosensitivity rate of 93% was found in LNB patients ³ 12 years of age with a symptom duration of more than 30 days. Therefore, a negative C6 test in serum in such a patient argues against an LNB diagnosis.The presence of chemokine CXCL13 in cerebrospinal fluid was confirmed to be a reliable marker of LNB. CXCL13 differentiated LNB from other conditions and also indicated a high probability of LNB in children with short symptom duration where anti-Borrelia antibodies were still lacking in the cerebrospinal fluid.A two-tiered approach (C6 test in combination with WB EL) showed no significant improvement in specificity over the C6 test alone. However, WB EL may be useful in diagnosing suspected cases of acrodermatitis chronicum atrophicans and Lyme arthritis, usually displaying multiple IgG bands.In conclusion, although the serodiagnosis of LB remains to be settled, this thesis provides some practical tools regarding the use and interpretation of Borrelia serology including proposed diagnostic routines.
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| 10. |
- Wallménius, Katarina, 1983-
(författare)
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Studies of Spotted Fever Rickettsia - Distribution, Detection, Diagnosis and Clinical Context : With a Focus on Vectors and Patients in Sweden
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The spotted fever rickettsia, Rickettsia helvetica, is an endemic tick-borne bacteria in Sweden. It causes infections in humans, manifested as aneruptive fever, headache, arthralgia and myalgia, and sometimes an inoculation eschar or a rash. There have also been two known cases of human infections with R. felis in Sweden.The present thesis starts by investigating dispersal of ticks and Rickettsia spp. by migrating birds flying from Africa to Europe. Almost 15,000 birds were searched and 734 ticks collected, mainly of the species Hyalomma marginatum complex. Almost half (48%) of the ticks were infected with Rickettsia spp., 96% of which was R. aeschlimannii, the remaining R. africae and undefined species.The next study focused on questing ticks over a large area in Sweden and determining the prevalence of Rickettsia spp., Anaplasma spp. and Coxiella burnetii. Rickettsia spp. was found in 9.5-9.6% of the ticks and A. phagocytophilum in 0.7%; no C. burnetii was found.The last three papers in the thesis focused on the clinical presentation of rickettsiosis, the symptoms associated with the infection in general and particularly in patients with neurological complications. A tick-exposed population in Sweden was investigated to gain a better understanding of symptoms due to rickettsioses, also in relation to co-infections with other tick-borne bacteria. Based on symptoms, it was not possible to distinguish what pathogen caused the infections. Most patients had erythema migrans, some had serological reactions to Rickettsia spp., Borrelia spp. or co-infections by Rickettsia spp., Borrelia spp. and/or Anaplasma spp. In the fourth and fifth papers, we found associations between antibodies against Rickettsia spp. and sudden deafness (in 10-24% of patients) and facial nerve paralysis (in 8.3-25% of patients). In three patients R. felis was detected in the cerebrospinal fluids. Briefly, the thesis helps to clarify our knowledge about tick dispersal, shows a narrower prevalence estimate of Rickettsia spp. in Swedish ticks, and illuminates symptoms of rickettsioses and co-infections with other tick-borne infections. It also shows that presence of erythema migrans may be explained by more than Lyme disease and indicates a possible association between rickettsiosis and sudden deafness and facial nerve paralysis.
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