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- Jönsson, Göran B
(författare)
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Genetic characterization of malignant melanoma and breast cancer
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Malignant melanoma and breast cancer are common malignant diseases characterized by considerable heterogeneity with respect to genetics, histopathology, biology and clinical course. In breast cancer, two major susceptibility genes have been identified, BRCA1 and BRCA2, which account for a significant proportion of high-risk breast cancer families. Breast tumors arising in BRCA1 or BRCA2 mutation carriers typically have distinct histopathological and molecular features, suggesting that tumor genotype and phenotype can be used to trace genetic origin also in non-BRCA1/2 familial cases. In melanoma, one major susceptibility gene, CDKN2A, is responsible for approximately 25% of multi-case melanoma families. Kindreds with cases of both ocular and cutaneous malignant melanoma are predominantly CDKN2A negative, implying that additional melanoma susceptibility genes exist. Tumors from both malignant melanoma patients and breast cancer patients harbor numerous genomic alterations, which pinpoint genes of importance for tumor development, and may be used as tools for improved diagnostics and prediction of clinical course. The advent of the microarray technology for comparative genomic hybridization (CGH) has increased the resolution dramatically for analysis of DNA copy number changes. The current thesis is focused on analysis of DNA copy number changes in tumors and genetic linkage analysis of breast cancer and malignant melanoma. A novel melanoma susceptibility locus was mapped to chromosome 9q21.32 by genome wide linkage analysis of two unique Danish pedigrees with multiple cases of ocular and cutaneous malignant melanoma (PAPER I). To investigate chromosomal aberration patterns in cancer cells we constructed a high-resolution BAC microarray platform with tiling and contiguous coverage of the human genome and used CGH analysis of breast cancer cell lines to reveal novel amplifications and homozygous deletions (PAPER IV). Using tiling array CGH, we further characterized the genomic profiles of 40 melanoma cell lines, again revealing novel aberrations and patterns/combinations of chromosomal changes, suggesting specific genomic programs in melanoma development (PAPER II). In PAPER III we investigated whether DNA copy number analysis can be used for classification of inherited breast cancer. Array CGH analysis was shown to discriminate BRCA1, BRCA2 associated and sporadic breast cancers. This implicates that an underlying genetic predisposition may give rise to specific chromosomal aberration patterns during tumor progression. Taken together, our results have provided novel insights into the genetic and genomic mechanisms of malignant melanoma and breast cancer development.
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| 2. |
- Jönsson, Jörgen, 1969-
(författare)
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Phase transformation and surface chemistry of secondary iron minerals formed from acid mine drainage
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The mining of sulphidic ore to extract metals such as zinc and copper produces huge quantities of waste material. The weathering and oxidation of the waste produces what is commonly known as Acid Mine Drainage (AMD), a dilute sulphuric acid rich in Fe(II) and heavy metals. This thesis serves to summarise five papers reporting how the precipitation of Fe(III) phases can attenuate the contamination of heavy metals by adsorption processes.Schwertmannite (Fe8O8(OH)6SO4) is a common Fe(III) mineral precipitating in AMD environments at pH 3-4. The stability and surface chemistry of this mineral was investigated. It was shown that the stability depended strongly on pH and temperature, an increase in either promoted transformation to goethite (α-FeOOH). Two pH dependent surface species of SO42- were detected with infrared (ATR-FTIR) spectroscopy.The adsorption of Cu(II), Pb(II) and Zn(II) to schwertmannite occurred at lower pH than to goethite, whereas Cd(II) adsorption occurred in a similar pH range on both schwertmannite and goethite. Extended x-ray absorption fine structure (EXAFS) spectroscopy suggests two surface species for Cu(II) and Cd(II) at the schwertmannite surface. Cu(II) adsorbs monodentately and Cd(II) bridging bidentately to adsorbed SO42-. Both metal ions also adsorb in a bridging bidentate mode to the surface hydroxyl groups. At pH 7.5 up to 2.7 μmol Cd(II) m-2 could be adsorbed to schwertmannite, indicating a large adsorption capacity for this mineral.The acid-base properties of two NOM samples were characterised and could be well described as diprotic acids below pH 6. The adsorption of NOM to schwertmannite and goethite was very similar and adsorption occured in a very wide pH range.High concentrations of NOM increased the adsorption of Cu(II) to goethite at low pH whereas a slight decrease was noted at low concentrations of NOM. No effect was detected in the schwertmannite system.The formation of Fe(III) phases from precipitation of AMD was shown to be very pH dependent. At pH 5.5 a mixture of minerals, including schwertmannite, formed whereas at pH 7 only lepidocrocite (γ-FeOOH) formed. The concentration of Zn(II) in AMD could by adsorption/coprecipitation be reduced to environmentally acceptable levels.
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| 3. |
- Liu, Yu, 1990-
(författare)
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Thermodynamics and Kinetics in Metallurgical Processes - with a Special Focus on Bubble Dynamics
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gas stirring is commonly used in the steelmaking processes to reinforce chemical reactions, kinetic transfer, and inclusion removal, etc. This dissertation concentrates on multiphase flows with gas bubbling to study fluid dynamics and thermodynamics in metallurgical processes. A study of bubble behavior has been carried out using a multiscale approach as follows: Prototype scale (macro) → Plume scale → Single bubble scale → Reaction scale (micro).Initially, previous works on physical modeling and mathematical modeling in relation to the gas bubbling in the ladle have been reviewed. From that, several aspects that can be improved were found:For physical modeling, such as mixing and homogenization in ladles, the general empirical rules have not been analyzed sufficiently;The mathematical models focusing on inclusion behaviors at the steel-slag interface need to be improved;The phenomena governing the transfer of elements, vacuum degassing, and the combination of fluid dynamics and thermodynamics, such as in desulfurization, need to be investigated further.The kinetics transfer with regards to temperature and element homogenization is one of the most extensive research fields in steel metallurgy. For the analysis on prototype scale, the optimal plug configuration has been studied for a 50t ladle. For stirring using bottom-blowing, a separation angle between dual plugs of 160 degree is mostly recommended, and the optimal dual-plug radial position is around 0.65R. Moreover, the influence of the tracer’s natural convection on its homogenization pattern cannot be neglected, especially for ‘soft bubbling’ conditions using low gas flow rates.Subsequently, in studies of the statistical behavior of gas bubbling in the plume, mathematical modeling using an Euler-Euler approach and an Euler-Lagrange approach have been compared. With respect to the bubble coalescence and breakup, the Euler-Lagrange approach is more accurate in predicting the flow pattern for gas injection using a porous plug. With regards to the effect of plug design on the statistical behavior of gas bubbling, gas injection using a slot plug promotes kinetic reactions close to the open eye due to the concentrated plume structure, and gas bubbling using a porous plug promotes a good inclusion removal because of the increased amount of bubbles.Focusing on single bubble behavior, under the same flow rate, as the top gauge pressure is reduced, the bubble diameter increases and the bubble generation frequency decreases. During the bubble ascent, a large bubble gradually reaches stable conditions by means of shedding several small bubbles. In a steel-argon system, under a flow rate in the range of 5.0(mL‧min-1)STP to 2000(mL‧min-1)STP, the bubble diameter is in the range of 6.0mm to 20.0mm. Under laminar conditions, the maximum bubble width is 65mm when the surrounding pressure is 0.2bar, and the steady bubble width is around 58mm under a pressure of 2.0bar.Finally, a coupling method, named Multi-zone Reaction Model, has been developed to predict the conditions in the EAF refining process. Using a combined injection of O2 and argon, and the same injected mass of O2, the decarburization rate increases due to an efficient kinetic mass transfer of carbon in the molten steel. Furthermore, using CO2 to replace argon, as the ratio of the CO2 content in the injection increases, the maximum hot spot temperature, the increment rate of average temperature, and the decarburization rate decrease dramatically.The research step from multiphase fluid dynamics to its coupling with high temperature thermodynamics is a large advancement in this study. Moreover, the research process using open source software to replace the commercial software is also an important technical route. This can help the transparent development of future modules for reacting flow in metallurgical processes.
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