| 1. |
- Aniander, Gustav
(författare)
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Improved candidate screening through tailored co-culture assays and precise tuning of protein expression
- 2024
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The field of biopharmaceuticals is a rapidly growing one. In the last ten years the number of approved biopharmaceuticals has more than doubled. A major hurdle to overcome for increased availability of all the new, effective biopharmaceuticals is the cost of treatment. Much of this can be attributed to the sheer time required for their development. Owing to this, interest in improvements to the biopharmaceuticals and their development process has also rapidly increased. As costs increase the further into development a drug candidate progresses, increasing the fidelity of screening at early stages could alleviate some of the exorbitant costs of development.In paper I, we showcase a novel way of targeting the tumor microenvironment (TME) to allow for TMElocalized CD40 activation. This is of interest as CD40 agonists have shown great potential for immune activation, but with systemic activation leading to severe adverse effects. The localized activation is achieved through the construction of an affinity fusion protein termed an AffiMab through fusion of a platelet derived growth factor receptor beta (PDGFRβ) targeting affibody to the heavy chain of a CD40 agonistic monoclonal antibody (mAb). We demonstrate PDGFRβ-dependent activation in a variety of assays, showing that the approach merits further investigation.Building on the activation assays set up in paper I, we aim to generate an in vitro screening platform for immune cell engagers in paper II. Screening candidates for on-target off-tumor activation is essential, as such activation would lead to adverse effects and be a doselimiting factor. To screen for this, we construct a series of plasmids which upon transfecting cells allow for different levels of a cell-surface target protein to be expressed, a so-called target density panel. This is achieved through the use of hairpin forming elements in the 5’ untranslated region of the mRNA dubbed regulatory elements (RgEs). Through use of different RgEs, we show that a target density panel can be generated and validate it in activation assays with the AffiMab developed in paper I. The platforms’ uniform cell surface background due to all different levels of target being expressed in the same host cell line and tunability through use of different RgEs are features that make it interesting for further research.Finally in paper III, we construct and test an improved translation initiation site (TIS) sequence. Using previous studies on the impact of the nucleotides in the sequence on the efficacy of the TIS, we constructed a novel sequence, TISNOV. This sequence enhanced titer and quality for recombinant production of IgG1 and IgG4 in both stable and transient settings. Further research into other TIS sequences and their uses in regulating protein expression, as well as usage of the TISNOV to improve expression of difficult to express proteins such as bispecifics remain interesting.In conclusion this thesis focuses on different manners to improve and hasten development of new biopharmaceuticals through usage of new workflows, platforms, and genetic engineering strategies.
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| 2. |
- Heljedal, Martin
(författare)
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Factors Influencing the Choice between Road and Multimodal Transportation
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Non-sustainable transportation is a great part of the stress that human activities put on the environment. Road transportation constituted 74% of the total inland tonne-kilometres in the EU during 2009, to be compared to rail transportation at 15%. In Sweden the numbers are slightly more in favour of rail transportation, but still a small share despite the fact that the European Committee promotes sustainable modes of transport. To reduce the environmental impact from the transport sector, and be able to promote the use of sustainable transport modes, it is important to gain an understanding of why the modal balance is disposed this way. By case studies and a survey, four factors, viz costs, environmental impact, attitudes and risks, and their impact on the choice of mode of transportation for companies located in the vicinity of a rail terminal are studied.The results clearly show that the environmental impact of rail transportation is only a fraction of that of the road transportation and could possibly influence the choice of rail transportation in a positive way. However, rail transportation is less cost efficient, flexible and reliable and these aspects – despite the advantageous conditions in terms of infrastructure and geographical vicinity to a rail terminal – contribute to a negative bias towards rail transportation among companies in the study. Thus, the cost and attitudes factors counteract the choice of rail transportation. In addition, risks, as the final factor, also counteracts the choice, since it is found that respondents consider the risks of disturbances such as delays, theft and accidents to be important when considering mode of transportation and that rail transportation is viewed as lacking compared to road transportation.This thesis contributes to the existing theory about the costs-related issues and the environmental impact of rail transportation, as well as how companies with beneficial conditions to employ rail transportation consider the mode with regards to e.g. reliability and safety, and how these factors influence the modal choice among buyers of transportation services that are located close to a rail terminal. With this knowledge, policymakers are informed of which areas to concentrate taxes, subsidizations and information to. These things are in all probability necessary if a large scale modal shift is desired. The contribution of the effect a modal shift could have on the environmental impact of the transportation might make certain practitioners that compete on a market where a low environmental footprint is a strong competitive weapon to rethink their modal choice.
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| 3. |
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| 4. |
- Lund Ohlsson, Marie
(författare)
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New methods for movement technique development in cross-country skiing using mathematical models and simulation
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This Licentiate Thesis is devoted to the presentation and discussion of some new contributions in applied mathematics directed towards scientific computing in sports engineering. It considers inverse problems of biomechanical simulations with rigid body musculoskeletal systems especially in cross-country skiing. This is a contrast to the main research on cross-country skiing biomechanics, which is based mainly on experimental testing alone. The thesis consists of an introduction and five papers. The introduction motivates the context of the papers and puts them into a more general framework. Two papers (D and E) consider studies of real questions in cross-country skiing, which are modelled and simulated. The results give some interesting indications, concerning these challenging questions, which can be used as a basis for further research. However, the measurements are not accurate enough to give the final answers. Paper C is a simulation study which is more extensive than paper D and E, and is compared to electromyography measurements in the literature. Validation in biomechanical simulations is difficult and reducing mathematical errors is one way of reaching closer to more realistic results. Paper A examines well-posedness for forward dynamics with full muscle dynamics. Moreover, paper B is a technical report which describes the problem formulation and mathematical models and simulation from paper A in more detail. Our new modelling together with the simulations enable new possibilities. This is similar to simulations of applications in other engineering fields, and need in the same way be handled with care in order to achieve reliable results. The results in this thesis indicate that it can be very useful to use mathematical modelling and numerical simulations when describing cross-country skiing biomechanics. Hence, this thesis contributes to the possibility of beginning to use and develop such modelling and simulation techniques also in this context.
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| 5. |
- Nambiar, Sanjay, 1997-
(författare)
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Adaptive Automation for Customized Products
- 2024
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In today’s fast-paced industrial landscape, the drive for greater efficiency and flexibility in product development has sparked significant interest in innovative automation technologies. This thesis explores the usefulness of various automation techniques for customized products such as Knowledge-Based Engineering (KBE), Multidisciplinary Optimization (MDO) and machine learning frameworks.The research begins by establishing an automated framework for fixture design, combining design automation and MDO to streamline the design process. It then moves to optimizing gas turbines, introducing an automation framework that merges CAD templates with KBE principles.For complex and unstructured production, this thesis explores the use of Reinforcement Learning (RL) to tackle challenges in unstructured manufacturing. By utilizing lightweight physics-based engines and RL, the research advances automated assembly validation and mobile robot operations, pushing the boundaries of adaptive production automation. Furthermore, a framework is developed, which integrates smoothly with industrial robotic platforms showcases practical automation solutions and highlights the adaptability and applicability of digital twin technology in real-world situations.This thesis contributes to the field of product development by providing innovative solutions that are rooted in multidisciplinary research. It bridges the theoretical and practical aspects of automation with solutions that overcomes the obstacles to realize seamless integration between digital and physical realities in a manufacturing context.
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| 6. |
- Persson, Fredrik, 1971-
(författare)
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A Study of Factors Affecting the Particle Size for Water Atomised Metal Powders
- 2012
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The production of metal powders by water atomisation is a well established process, which can be used to produce a wide range of particle sizes. A careful control of the particle size distribution is necessary, to atomise powders with a high quality and at a low production cost. Therefore, it is necessary to have a substantial knowledge of the relation between operational parameters and the particle size, to be able to produce water atomised metal powders with consistent and high yields. The main purpose with this thesis was to increase the knowledge about factors which affect the mass median particle size (d50) for water atomised metal powders. The specific objectives with the study were to develop a theoretical d50 model and to investigate the relation between the particle size and the physical properties of the liquid metal. Pilot scale experiments for liquid iron showed that alloy additions of carbon and sulphur decreased the d50 value, at a maintained liquid steel temperature before atomisation. Moreover, it was indicated that the reduced particle size at increased %C and %S contents may be related to a decreased viscosity and surface tension of the liquid metal, respectively. An alternative explanation could be that raised superheats at increased carbon contents increased the total available time for atomisation, which may have contributed to a reduction of the d50 value. The theoretical d50 model developed in this work showed a very good correlation to the current experimental data. The model considers the influence of surface tension, viscosity, melt stream diameter, water pressure, water jet angle and water to metal ratio. This model was further used to analyse how the d50 value was influenced by the viscosity and the surface tension. A reduced viscosity from 4∙9 to 2∙1 mPa s decreased the d50 value with 33%. In addition, the particle size was estimated to decrease with 21% by decreasing the surface tension from 1840 to 900 mN m-1.
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| 7. |
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| 8. |
- Persson, Niclas
(författare)
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Event Based Sampling with Application to Spectral Estimation
- 2002
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis event based sampling, estimation of a single resonance frequency and the application indirect tire pressure monitoring system are studied.Event based sampling is an alternative to traditional uniform or equidistant sampling. In event based sampled systems, signals are sampled only when certain pre-defined events take place. Event based sampling occurs naturally in many contexts such as motion systems where angles and positions are measured. In this thesis special attention is paid to rotating axles where the position is measured with a rotational speed sensor. Due to production tolerances such a sensor has a nonideal performance. This causes a periodic error in the event based sampled signal which in many cases cannot be neglected. Two different methods for elimitating the sensor errors are proposed.To be able to use standard tools for analyzing the signal from the rotational speed sensor, the signal is interpolated to a uniformly sampled signal. A desirable feature of the interpolation is to incorporate a lowpass filter to avoid aliasing. We investigate and compare three different methods, all based on a non-parametric regression.A survey of different methods to estimate a single resonance frequency in the rotational speed signal is presented including aspects of estimation accuracy and computational complexity.As an application of event based sampling and spectral estimation, a Tire Pressure Monitoring System (TPMS) is designed and analyzed. The TPMS is based on event based sampled measurements from a wheel speed sensor. The tire is modeled as a spring-damper system. The idea is to monitor the resonance frequency caused by the spring-damper system. This frequency is correlated with the inflation pressure, and by monitoring the resonance frequency, it is possible to detect inflation pressure changes. The system is implemented and tested in a real vehicle with promising results.
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| 9. |
- Steins, Krisjanis, 1971-
(författare)
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Discrete-Event Simulation for Hospital Resource Planning : Possibilities and Requirements
- 2010
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The delivery of health care services has been under pressure due to limited funding and increasing demand. This has highlighted the need to increase not only the effectiveness but also the efficiency of health care delivery. Discrete-event simulation has been suggested as an analysis tool in health care management to support the planning of health care resources.The overall purpose of this thesis is to investigate the possibilities and requirements for using discrete-event simulation in analyzing and planning the use of hospital resources. This is achieved by three case studies that focus on improvements in patient flow of emergency patients that require a radiology examination, intensive care unit capacity planning and operating room allocation strategies, respectively.The first case investigates the current stage of digitization and process orientation in hospital care as a prerequisite for efficient process simulation and analysis. The study reveals an emergency-radiology patient flow process that is not very well measured and uncovers disparate information systems storing incompatible and fragmented data. These results indicate that the current degree of process orientation and the current IT infrastructure does not enable efficient use of quantitative process analysis and management tools like simulation.In the second case the possibilities to develop generic hospital unit simulation models by building and validating a generic intensive care unit (ICU) model are explored. The results show that some of the modeling approaches described in literature cannot replicate the actual behavior observed in all studied ICUs. It is important to identify patient groups for different admission priorities, to account for over-utilizations in the model logic, and to discover and properly model dependencies in the input data. The research shows that it is possible to develop a generic ICU simulation model that could realistically describe the performance of different real ICUs in terms of occupancy, coverage and transfers.The value of simulation modeling in health care management is examined in the third case through the development and use of a simulation model for optimal resource allocation and patient flow in a hospital operating department. The goal of the simulation modeling in this case was to identify bottlenecks in the patient flow and to try different alternatives for allocation of operating room capacity in order to increase the utilization of operating room resources. The final model was used to evaluate four different proposed changes to operating room time allocation.
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| 10. |
- Thunberg, Micael
(författare)
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Towards a Framework for Process Mapping and Performance Measurement in Construction Supply Chains
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose with this study is to develop a framework for process mapping and performance measurement in construction supply chains. This is done as current literature suggest that many of the problems that cause the cost- and time overruns in construction can be mitigated by implementing supply chain management (SCM) principles. For example, temporary organisations, fragmentation, etc. can affect the time and cost as work and information among members easily are delayed and even distorted. It is also recognised by many authors that planning the construction work and logistics often are tainted with synchronisation and coordination problems between supply chain members. It is deemed necessary with a framework for mapping logistic activities and measuring supply chain performance. Up until now, there exists no framework for mapping the whole construction supply chain and measuring its performance, that encompasses the whole chain from raw material to the finished building.As stated above, the purpose with this thesis is to develop such a framework. In order to do so an existing framework is used as a basis, the Supply Chain Operations Reference (SCOR) model. The SCOR model consists of five process groups (Plan, Source, Make, Deliver, and Return) hierarchically structured in three levels and some 500 predefined performance metrics. This framework is proven fruitful in other industries but it is also proven by other authors in the field suitable as a basis for a construction adapted version. Other frameworks do exist, but none of these are as comprehensive as the SCOR model. Resent research also suggests that the SCOR model is possible to adjust to unique industry settings. It is identified in this study that the SCOR model has to be adapted to the characteristics of the construction industry. Therefore, the framework presented in this thesis is developed via adaption of the SCOR model to the characteristics of the construction industry. In doing so, a total of four research objectives corresponding to the process groups in the SCOR model are considered for adapting the SCOR model. The Return process, however, is not included in this thesis.Objective 1. Adapt the SCOR model’s Deliver process to the characteristics of the construction industry.Objective 2. Adapt the SCOR model’s Source processes to the characteristics of the construction industry.Objective 3. Adapt the SCOR model’s Make processes to the characteristics of the construction industry.Objective 4. Adapt the SCOR model’s Plan processes to the characteristics of the construction industry.The main method utilised in the study is case study research. The results are derived from a total of three case studies. The SCOR model is applied to the cases as it is. Through observing how suitable the framework is for the industry the four aforementioned objectives are addressed. Except from direct observations (with time measurements), other data gathering methods utilised are questionnaires and interviews.The adapted version of the SCOR model is entitled the Builder’s SCOR model (BSCOR). Findings from the studies indicate that necessary changes to the SCOR model concerns how the material flow in the processes are separated. The SCOR model suggests separating materials based on type of end product (e.g. Make-to-Stock – MTS, Make-to-Order – MTO, or Engineer-to-Order – ETO character). In the BSCOR model, the flow of materials are separated based on who orders them (the main contractor or any of the subcontractors), rather than type of material. The BSCOR model also suggests how the planning process should be organised in order to overcome coordination issues. Finally, one measurement included in the BSCOR model is to keep track of whether an incoming delivery of construction materials is notified in time. An order is not perfectly delivered if it is not notified in time.One managerial contribution with the study is a framework for mapping supply chain activities and measuring supply chain performance. The framework also offers the ability to measure how the supply chain of a company performs compared to other companies’ supply chains. The study contributes to the academia as it fills the gap of a lack in frameworks suitable for mapping and measuring construction logistics. It also contributes in reporting on the current logistics status in the construction industry.
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