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- Andersson, Patiyan, 1978-
(författare)
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Molecular Genetic Studies on Prostate and Penile Cancer
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is comprised of two parts. In the first part we study the influence of four frequently disputed genes on the susceptibility for developing prostate cancer, and in the second part we attempt to establish a basic understanding of the molecular genetic events in penile cancer.In a prostate cancer cohort we have investigated the relation of prostate cancer risk and single nucleotide polymorphisms (SNPs) in four different genes coding for the androgen receptor (AR), the vitamin D receptor (VDR), insulin (INS) and insulin receptor substrate 1 (IRS1). Despite strong biological indications of an involvement of these genes in prostate carcinogenesis, the results from different studies are contradictory and inconclusive.The action of the AR varies between individuals in part owing to a repetitive CAG sequence (polyglutamine) in the first exon of the AR gene. The results presented in this thesis show that in our cohort of prostate cancer patients the average number of repeats is 20.1, which is significantly (p<0.001) fewer repeats compared to healthy control individuals, where the average is 22.5 repeats. We find a 4.94 fold (p=0.00003) increased risk of developing prostate cancer associated with having short repeat lengths (≤19 repeats), compared with long repeats (≥23 repeats). In paper I we also study the TaqI polymorphism in the VDR gene, and find that it does not modify the risk of prostate cancer.In the INS gene we study the +1127 PstI polymorphism and find no overall effect on the risk of prostate cancer. However, we do find that the CC genotype is associated with low grade disease defined as having a Gleason score ≤6 (OR=1.46; p=0.018). In the IRS1 gene we study the G972R polymorphism and observe that the R allele is significantly associated with a 2.44 fold increased prostate cancer risk (p=0.010).The knowledge of molecular genetic events in penile cancer is very scarce and to date very few genes have been identified to be involved in penile carcinogenesis. We chose therefore to analyse the penile cancer samples using genome-wide high-density SNP arrays. We find major regions of frequent copy number gain in chromosome arms 3q, 5p and 8q, and slightly less frequent in 1p, 16q and 20q. The chromosomal regions of most frequent copy number losses are 3p, 4q, 11p and 13q. We suggest four candidate genes residing in these areas, the PIK3CA gene (3q26.32), the hTERT gene (5p15.33), the MYC gene (8q24.21) and the FHIT gene (3p14.2).The mutational status of the PIK3CA and PTEN genes in the PI3K/AKT pathway and the HRAS, KRAS, NRAS and BRAF genes in the RAS/MAPK pathway was assessed in the penile cancer samples. We find the PIK3CA, HRAS and KRAS genes to be mutated in 29%, 7% and 3% of the cases, respectively. All mutations are mutually exclusive. In total the PI3K/AKT and RAS/MAPK pathways were found to be activated through mutation or amplification in 64% of the cases, indicating the significance of these pathways in the aetiology of penile cancer.
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| 2. |
- Höglund, Linda, 1974-
(författare)
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Growth and characterisation of InGaAs-based quantum dots-in-a-well infrared photodetectors
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents results from the development of quantum dot (QD) based infrared photodetectors (IPs). The studies include epitaxial growth of QDs, investigations of the structural, optical and electronic properties of QD-based material as well as characterisation of the resulting components.Metal-organic vapour phase epitaxy is used for growth of self-assembled indium arsenide (InAs) QDs on gallium arsenide (GaAs) substrates. Through characterisation by atomic force microscopy, the correlation between size distribution and density of quantum dots and different growth parameters, such as temperature, InAs deposition time and V/III-ratio (ratio between group V and group III species) is achieved. The V/III-ratio is identified as the most important parameter in finding the right growth conditions for QDs. A route towards optimisation of the dot size distribution through successive variations of the growth parameters is presented.The QD layers are inserted in In0.15Ga0.85As/GaAs quantum wells (QWs), forming so-called dots-in-a-well (DWELL) structures. These structures are used to fabricate IPs, primarily for detection in the long wavelength infrared region (LWIR, 8-14 μm).The electron energy level schemes of the DWELL structures are revealed by a combination of different experimental techniques. From Fourier transform photoluminescence (FTPL) and FTPL excitation (FTPLE) measurements the energy level schemes of the DWELL structures are deduced. Additional information on the energy level schemes is obtained from tunneling capacitance measurements and the polarization dependence studies of the interband transitions. From tunneling capacitance measurements, the QD electron energy level separation is confirmed to be 40-50 meV and from the polarization dependence measurements, the heavy hole character of the upper hole states are revealed.Further characterisation of the IPs, by interband and intersubband photocurrent measurements as well as dark current measurements, is performed. By comparing the deduced energy level scheme of the DWELL structure and the results of the intersubband photocurrent measurements, the origin of the photocurrent is determined. The main intersubband transition contributing to the photocurrent is identified as the QD ground state to a QW excited state transition. Optical pumping is employed to gain information on the origin of an additional photocurrent peak observed only at temperatures below 60 K. By pumping resonantly with transitions associated with certain quantum dot energy levels, this photocurrent peak is identified as an intersubband transition emanating from the quantum dot excited state. Furthermore, the detector response is increased by a factor of 10, when using simultaneous optical pumping into the quantum dots states, due to the increasing electron population created by the pumping. In this way, the potentially achievable responsivity of the detector is predicted to be 250 mA/W.Significant variations of photocurrent and dark currents are observed, when bias and temperature are used as variable parameters. The strong bias and temperature dependence of the photocurrent is attributed to the escape route from the final state in the QW, which is limited by tunneling through the triangular barrier. Also the significant bias and temperature dependence of the dark current could be explained in terms of the strong variation of the escape probability from different energy states in the DWELL structure, as revealed by interband photocurrent measurements. These results are important for the future optimisation of the DWELL IP.Tuning of the detection wavelength within the LWIR region is achieved by means of a varying bias across the DWELL structure. By positioning the InAs quantum dot layer asymmetrically in a 8 nm wide In0.15Ga0.85As/GaAs quantum well, a step-wise shift in the detection wavelength from 8.4 to 10.3 μm could be achieved by varying the magnitude and polarity of the applied bias. These tuning properties could be essential for applications such as odulators and dual-colour infrared detection.
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