| 1. |
- Fransén, Karin, 1973-
(författare)
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Molecular genetic aspects of colorectal cancer development
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer (CRC) is one of the most common cancer diseases in the world after lung and female breast cancer and approximately 945 000 new cases are diagnosed every year. CRC is caused by genetic alterations in the DNA, which results in cell cycle acceleration, escape from apoptosis, senescence, angiogenesis, invasion and metastasis. In this thesis, we have investigated molecular genetic alterations for the development of CRC and focused on the MAPK pathway, HIF-1 α and NOS2 genes.Alterations in the MAPK pathway have been found in several different cancer forms, including CRe. In the present study, we found somatic mutations in the MAPK pathway in 50% of the CRCs; 40% of the tumors carried mutations in the KRAS gene and 10% carried BRAF mutations. No genetic alterations were found in the ARAF or RAF-1 genes. B&4F gene mutations were present only in exon 15 and were associated with micro satellite instability. Three mutation types were identified; V599E, D593G and K600N, whereof the latter has not previously been described.The hypoxia inducible factor (HIF)-la protein is involved in the oxygen sensing mechanism and several tumor types show HIF-la overexpression due to hypoxia. At normoxia, HIF-la is degraded by interaction with the von Hippel-Lindau (VHL) tumor suppressor protein followed by an ubiquitin-proteasome dependent degradation mechanism, which prevents HIF-l a from nuclear translocation and transcription of downstream target genes. Fifteen percent of CRC patients and normal healthy population was found to carry the P582S polymorphism in the HIF-1 α gene, which previously has been associated to higher transactivating capacity. In the present study, the polymorphism was associated to ulcerative tumor development. In addition, loss of heterozygosity of the wild type P582 allele in heterozygotes may contribute to the development of ulcerative CRCs. However, the overall mechanism for ulcerative tumor development is still unclear.Nitric oxide (NO) is involved in several physiological processes, such as apoptosis, neurotransmission, angiogenesis and immune defence and is produced by three nitric oxide synthases; NOSl-3. In the present study, NOS2 upregulation was identified in CRCs compared to normal intestinal mucosa. Moreover, the contribution of NOS2 in CRC development was investigated in APCMin/+ and APCMin/+ NOS2-/- mice. The APCMin/+ NOS-/- mice developed a higher polyp frequency compared to APCMin/+ mice, indicating a protective role for the presence of NOS2 in intestinal cancer development. The elevated polyp formation in the APCMin/+ NOS-/- mice was independent of the expression of Notch-l and p21. We also investigated whether polymorphisms in the NOS2 promoter affected the onset of CRC, but no differences in allele or genotype frequencies were observed in normal healthy population compared to CRC patients.
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| 2. |
- Jansson, Mattias, 1973-
(författare)
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Molecular Genetic Studies of Genes Predisposing for Glaucoma
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glaucoma is one of the leading causes of visual impairment in the world. In glaucoma, the patient’s peripheral vision is lost due to progressive and irreversible deterioration of the retinal ganglion cells and atrophy of the optic nerve. The effect on the visual field is gradual and painless, and the progression so slow, that the patient may not notice until a substantial part of the visual field is lost. If left untreated, glaucoma can lead to blindness.In this thesis, genes associated to glaucoma have been analysed in Swedish patients with primary open angle and exfoliative glaucoma. The genes studied were MYOC, oculomedin, GSTM1 and OPTN.The coding sequence of MYOC was analysed and mutations were found in 1% of the primary open angle glaucoma patients. Additionally, a predisposing variant was found in 1% of the patients as well as in 0.5% of the controls. No disease-associated variation was found in the exfoliative glaucoma cases. Mutations were also found in two families affected by glaucoma. The coding sequence of oculomedin was analysed, but none of the variants found were classified as disease causing in either patient group. GSTM1 was analysed for its presence in the patients. No association could be found for either hetero- or homozygous deletions. The coding sequence and haplotype distribution of OPTN was analysed. None of the variants found were classified as disease causing and none of the haplotypes were associated to the disease in either patient group.There are just a few per cent of the Swedish primary open angle glaucoma patients with genetic variation associated to disease, in the genes analysed in this study. No association to exfoliative glaucoma was found. This indicates heterogeneity in the genetics of glaucoma when different subtypes and different populations are compared. Likely, there are genes still to be identified.
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| 3. |
- Thellman, Sam
(författare)
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Social Robots as Intentional Agents
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Social robots are robots that are intended for social interaction with people. Because of the societal benefits that they are expected to bring, social robots are likely to become more common. Notably, social robots may be able to perform tasks that require social skills, such as communicating efficiently, coordinating actions, managing relationships, and building trust and rapport. However, robotic systems currently lack most of the technological preconditions for interacting socially. This means that until the necessary technology is developed, humans will have to do most of the work coordinating social interactions with robots. However, social robots are a phenomenon that might also challenge the human ability to interact socially. In particular, the actions of social robots may be less predictable to the ordinary people who will interact with them than the comparable actions of humans. In anticipating the actions of other people, we commonly employ folk-psychological assumptions about what others are likely to believe, want, and intend to do, given the situation that they are in. Folk psychology allows us to make instantaneous, unconscious judgments about the likely actions of others around us, and therefore, to interact socially. However, the application of folk psychology will be challenged in the context of social interaction with robots because of significant differences between humans and robots.This thesis addresses the scope and limits of people's ability to interact socially with robots by treating them as intentional agents, i.e., agents whose behavior is most appropriately predicted by attributing it to underlying intentional states, such as beliefs and desires. The thesis provides an analysis of the problem(s) of attributing behavior-congruent intentional states to robots, with a particular focus on the perceptual belief problem, i.e., the problem of understanding what robots know (and do not know) about objects and events in the environment based on their perception. The thesis presents evidence that people's understanding of robots as intentional agents is important to their ability to interact socially with them but that it may also be significantly limited by (1) the extendability of the rich folk-psychological understanding that people have gained from sociocultural experiences with humans and other social animals to interactions with robots, and (2) the integrability of new experiences with robots into a usable and reasonable accurate folk psychological understanding of them. Studying the formation and application of folk psychology in interactions with robots should therefore be a central undertaking in social robotics research.
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