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- Wetterbom, Anna, 1977-
(author)
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Genome and Transcriptome Comparisons between Human and Chimpanzee
- 2010
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Doctoral thesis (other academic/artistic)abstract
- The chimpanzee is humankind’s closest living relative and the two species diverged ~6 million years ago. Comparative studies of the human and chimpanzee genomes and transcriptomes are of great interest to understand the molecular mechanisms of speciation and the development of species-specific traits. The aim of this thesis is to characterize differences between the two species with regard to their genome sequences and the resulting transcript profiles. The first two papers focus on indel divergence and in particular, indels causing premature termination codons (PTCs) in 8% of the chimpanzee genes. The density of PTC genes is correlated with both the distance to the telomere and the indel divergence. Many PTC genes have several associated transcripts and since not all are affected by the PTC we propose that PTCs may affect the pattern of expressed isoforms. In the third paper, we investigate the transcriptome divergence in cerebellum, heart and liver, using high-density exon arrays. The results show that gene expression differs more between tissues than between species. Approximately 15% of the genes are differentially expressed between species, and half of the genes show different splicing patterns. We identify 28 cassette exons which are only included in one of the species, often in a tissue-specific manner. In the fourth paper, we use massive parallel sequencing to study the chimpanzee transcriptome in frontal cortex and liver. We estimate gene expression and search for novel transcribed regions (TRs). The majority of TRs are located close to genes and possibly extend the annotations. A subset of TRs are not found in the human genome. The brain transcriptome differs substantially from that of the liver and we identify a subset of genes enriched with TRs in frontal cortex. In conclusion, this thesis provides evidence of extensive genomic and transcriptomic variability between human and chimpanzee. The findings provide a basis for further studies of the underlying differences affecting phenotypic divergence between human and chimpanzee.
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| 2. |
- Medvedeva, Anna, 1981-
(author)
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Performance of advanced tool steels for cutting tool bodies
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Performance of indexable insert cutting tools is not only about the performance of cutting inserts. It is also about the cutting tool body, which has to provide a secure and accurate insert positioning as well as its quick and easy handling under severe working conditions. The common damage mechanisms of cutting tool bodies are fatigue and plastic deformation. Cutting tools undergo high dynamic stresses going in and out cutting engagement; as a result, an adequate level of fatigue strength is the essential steel property. Working temperatures of tool bodies in the insert pocket can reach up to 600°C, why the tool steel requires high softening resistance to avoid plastic deformation. Machinability is also essential, as machining of the steel represents a large fraction of the production cost of a cutting tool. The overall aim of the study is to improve the tool body performance by use of an advanced steel grade with an optimized combination of all the demanding properties. Due to the high-temperature conditions, the thesis concerns mostly hot-work tool steels increasing also the general knowledge of their microstructure, mechanical properties and machinability. Knowing the positive effect of sulphur on machinability of steels, the first step was to indentify a certain limit of the sulphur addition, which would not reduce the fatigue strength of the tool body below an acceptable level. In tool bodies, where the demand on surface roughness was low and a geometrical stress concentrator was present, the addition of sulphur could be up to 0.09 wt%. Fatigue performance of the cutting tools to a large extent depended on the steel resistance to stress relaxation under high dynamic loading and elevated temperatures. The stress relaxation behaviour, material substructure and dislocation characteristics in low-alloyed and hot-work tool steels were studied using X-ray diffraction under thermal and mechanical loading. Different tool steels exhibited different stress relaxation resistance depending on their microstructure, temper resistance and working temperature. Hot-work tool steels showed to be more preferable to low-alloyed tool steels because of their ability to inhibit the rearrangement and annihilation of induced dislocations. High-temperature softening resistance of the hot-work tool steels was investigated during high-temperature hold-times and isothermal fatigue and discussed with respect to their microstructure. Carbide morphology and precipitation were determined using scanning and transmission electron microscopy. Machinability of a prehardened hot-work tool steel of varying nickel content from 1 to 5 wt% was investigated in end milling and drilling operations. Machining the higher nickel containing steels resulted in longer tool life and generated lower cutting forces and tool/workpiece interface temperature. The difference in machinability of the steels was discussed in terms of their microstructure and mechanical properties.
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