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- Djerf, Emelie, 1980-
(författare)
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Studies on the effect of ErbB tyrosine kinase inhibitors on malignant melanoma growth and survival in vitro
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Malignant melanoma has one of the fastest increasing incidences among the different types of cancerin the Western world. This raise can partly be ascribed to the change in sun habits that has takenplace during the last decades, since the major external risk factor for melanoma is exposure toultraviolet radiation. Patients with early stages of melanoma can often be cured by surgery, howeverfor patients suffering from metastatic melanoma there are only a few treatment options available.Unfortunately malignant melanoma is often resistant to radio-, bio- and chemotherapy and treatmentwith the currently most frequently used agent, dacarbazine, is characterized by a very low clinicalresponse rate. Therefore, there is an urgent need for new treatment strategies which can increase theoverall survival and cause less severe side effects.The aim of this thesis was to investigate the anti-tumor effect of two different tyrosine kinaseinhibitors (TKIs), gefitinib and canertinib, on two different human malignant melanoma (RaH3 andRaH5) cell lines. We investigate the effect of these two drugs on cell proliferation and survival andstudied the effect of gefitinib and canertinib on ErbB1-4 receptor phosphorylation, as well as Akt,Erk1/2 and Stat3 activity.Our results showed that phosphorylation of ErbB1, ErbB2 and ErbB3 decreased followingtreatment with both gefitinib and canertinib and that the subsequent downstream signaling via Akt,Erk1/2 and Stat3 was inhibited after TKI treatment. However, it was noted that the gefitinibinducedinhibition of Akt, and particularly Erk1/2, was transient and only a weak inhibition of Stat3phosphorylation was seen. Gefitinib treatment of the RaH3 and RaH5 cells resulted in anaccumulation of the cells in the G1 phase of the cell cycle without any induction of apoptosis.Canertinib caused a more pronounced inhibition of Akt, Erk1/2, and Stat3 phosphorylation thangefitinib. This might be one explanation to why canertinib induced apoptosis in RaH3 and RaH5cells whereas gefitinib only caused cell cycle arrest. In conclusion, gefitinib and canertinib displaypromising anti-tumor effects on ErbB expressing malignant melanoma and might be used in futurestudies in combination with conventional chemotherapy or other targeted therapies in the treatmentof malignant melanoma.
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| 2. |
- Furunäs Åkesson, Johan
(författare)
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Interprocess communication utilising special purpose hardware
- 2001
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Real-Time Systems are computer systems with constraints on the timing of actions. To ease the development and maintenance of application software, Real-time Systems often make use of a Real-Time Operating System (RTOS). Its main task is scheduling of application processes (tasks). Other functions can be interprocess communication, interrupt handling, memory management etc.Sometimes it is hard (or even impossible) to meet the time constraints specified for a real-time system, resulting in an incorrectly functioning application. A possible remedy is to redesign the system by upgrading the processor and/or remove functionality, etc. An alternative solution could be the use of a special purpose hardware accelerated RTOS. The aim of such an accelerator is to speedup RTOS functions that impose big overhead i.e. to reduce the kernel overhead by offloading the application processor. Accordingly, the processor gets more time for executing application software, and hopefully the time constraints can be met. The main drawback is the cost of extra hardware.This thesis presents results from implementing RTOS functions in hardware, especially interprocess communication (IPC) functions. The types of systems considered are uniprocessor and shared memory multiprocessor real-time systems.IPC is used in systems with co-operating processes. The operating systems on the market support a large variation of IPC mechanisms. We will here present and evaluate three different IPC implementations. The first is an extended message queue mechanism that is used in commercial robot control applications. The second is the signal mechanism in OSE, a commercial RTOS predominantly used in telecommunication control applications, and the third is the semaphore and message queue mechanisms supported by the leading commercial RTOS VxWorks. All the implementations are based on a pre-emptive priority-based hardware real-time kernel accelerator.We show that it is not optimal, practical or desirable to implement every kernel function into hardware, regarding systems in the scope of this thesis. However, an accelerator allows new functionality to be implemented. We illustrate this by implementing a message queue mechanism that supports priority inheritance for message arrival in hardware, which is too expensive to implement in software. Also, we show that substantial speedups are possible, and that a crucial mechanism in achieving speedup is the accelerator-processor interconnect. We further note that application speedups are possible, even in cases with an IPC-mechanism slow-down. The main reasons for this is that the accelerator can off-load the processor by handling the RTOS timing mechanism (clock-ticks), reducing the RTOS code to be executed on the processor, and handling interrupts.
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| 3. |
- Gustafsson, Johan E., 1979-
(författare)
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Essays on value, preference and freedom
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Essay I develops a new framework for preference relations, that makes further preference relations beyond the trichotomy of preference, dispreference and indifference conceptually possible. The new framework models relations in terms of swaps, which are conceived of as transfers from one alternative state to another. With this new preference framework the essay presents a fitting-attitude analysis of new value relations that avoids some problems of earlier proposals. Essay II examines the small-improvement argument that is usually considered the most powerful argument against comparability, that is, the view that for any two alternatives an agent is rationally required to either prefer one of the alternatives to the other or be indifferent between them. The essay argues that while there might be reasons to believe each of the premises in the small-improvement argument, there is a conflict between these reasons. The conflict is such that we are not provided with a reason to believe the conjunction of the premises. Essay III develops a new measure of freedom of choice based on the proposal that a set offers more freedom of choice than another if, and only if, the expected degree of dissimilarity between a random alternative from the set of possible alternatives and the most similar offered alternative in the set is smaller. Furthermore, a version of this measure is developed that is able to take into account the values of the possible options.
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| 4. |
- Hansson, Johan
(författare)
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Implementation of a system for working environment management
- 2003
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis addresses the problem of developing and implementing an activity-based system for management of working environment conditions. Through explorative case studies in municipal care of the elderly the prerequisites of motivation, capacity and opportunity were examined. Systems objectives were derived from the Provisions enforced by The Swedish Working Environment Authority. The Provisions emphasize that working environment issues shall be integrated with activity-issues like economy and quality and include routines for risk analysis and action planning. An action research program was initiated including organizational interventions. A specific communication structure of meetings was designed. Simulations of workplace team meetings were accomplished including analysis and management of existing risks. The program was evaluated in the field by means of participant observation and structured interviews. The formative design of evaluation assessed the participants' motivation, capacity and opportunity to perform. The initial evaluation concerned how the participants performed risk analyses according to the action plan. Results showed that the participants operated according to the given meeting structure. Some risk factors were analyzed on numerous occasions, e.g. physical factors, while other risk factors, e.g. harassments were never considered in meeting contexts. The result implies the need of complementary work methods for risk assessment, i.e. professional employee interviews and questionnaires. The subsequent evaluation inquired into the first line managers' mental models using these methods. Results showed that the managers in general acknowledged the characteristics of the methods, i.e. strengths and sources of error. The concluding evaluation examined the working environment planning of the executive board. Results showed that the representatives in general held indistinct perceptions of the systems characteristics. A majority of the executive boards failed to communicate specific strategies for operative management. Some guiding principles for system implementation were suggested on the basis of the empirical results.
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| 6. |
- Klingspor, Måns, 1989-
(författare)
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Low-rank optimization in system identification
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, the use of low-rank approximations in connection with problems in system identification is explored. Firstly, the motivation of using low-rank approximations in system identification is presented and the framework for low-rank optimization is derived. Secondly, three papers are presented where different problems in system identification are considered within the described low-rank framework. In paper A, a novel method involving the nuclear norm forestimating a Wiener model is introduced. As shown in the paper, this method performs better than existing methods in terms of finding an accurate model. In paper B and C, a group lasso framework is used to perform input selection in the model estimation which also is connected to the low rank framework. The model structures where these novel methods of input selection is used on are ARX models and state space models, respectively. As shown in the respective papers, these strategies of performing input selection perform better than existing methods in both terms of estimation and input selection.
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