published_or_final_version / abstract / toc / Transport Policy and Planning / Master / Master of Arts in Transport Policy and Planning

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No description available.

Software product lines (SPLs) manage product variants in a systematical way and allow stakeholders to derive variants by selecting features. Finding a desirable variant is hard, due to the huge configuration space and usually conflicting objectives (e.g., lower cost and higher performance). This scenario can be reduced to a multi-objective optimization prob- lem in SPLs. We address the problem using an exact and an approximate algorithm and compare their accuracy, time consumption, scalability and parameter setting requirements on five case studies with increasing complexity. Our empirical results show that (1) it is feasible to use exact techniques for small SPL multi-objective optimization problems, and (2) approximate methods can be used for large problems but require substantial effort to find the best parameter settings for acceptable approximation. Finally, we discuss the tradeoff between accuracy and time consumption when using exact and approximate techniques for SPL multi-objective optimization and guide stakeholders to choose one or the other in practice.

MTHFD is a folate-dependent trifunctional protein comprised of three activities: N$ sp5$,N$ sp{10}$-methylenetetrahydrofolate dehydrogenase, N$ sp5$,N$ sp{10}$-methenyltetrahydrofolate cyclohydrolase and N$ sp{10}$-formyltetrahydrofolate synthetase. The enzymes catalyse the sequential interconversion of tetrahydrofolate derivatives required for purine, methionine and thymidylate synthesis. A Chinese hamster ovary cell line, reported to have reduced cyclohydrolase activity, was studied to characterize the nature of its mutation. / Enzymatic assays showed reduced activities of all three enzymes. Immunoblotting and immunoprecipitation of radiolabelled cell extracts indicated that the gene product was greatly reduced or absent in the mutant. Southern analysis showed no differences between normal and mutant cells, indicating that the defect was not due to a major gene rearrangement. RNA analysis, by Northern blotting and by RNA amplification using the polymerase chain reaction, showed that a mRNA for MTHFD of normal size was present in mutant cells. These results suggest that the mutation is post-transcriptional and that it disrupts the synthesis of MTHFD.

Clonal cell lines were isolated from mammary gland tissue epithelial cell cultures of lactating cows. Early passage clonal bovine mammary epithelial cells (clone LMH17) gave rise to several established cell lines (MAC-T lines) after being cotransfected with plasmids containing the temperature sensitive mutant SV40 large T antigen gene (pBAPSV40TtsA58) and the bacterial phosphotransferase gene (pSV2-neo). Unlike other cell types which were transformed after being transfected with SV40, MAC-T cells maintained many characteristics of non-transformed cells: MAC-T cells were serum and anchorage dependent, showed contact inhibition, and were not tumorigenic in immunodeficient mice. However, Southern transfer analysis revealed an integrated SV40 gene and cells showed no senescence after 50 passages. These cells are morphologically indistinguishable from parental LMH17 cells and retain the typical morphology of mammary epithelial cells. Positive cytokeratin immunostaining and the absence of vimentin staining indicated that these cells were epithelial in origin. / MAC-T cells grew rapidly on plastic substratum with a doubling time of approximately 17 hours and became differentiated when grown on floating collagen gels in the presence of prolactin. The differentiated phenotype was characterized to include (1) the ability to form secretory domes with a lumen from a pavement of columnar cells; (2) increased casein mRNA abundance; (3) increased alpha S and beta casein secretion; (4) increased number and size of casein secretory vesicles; and (5) increased lactose synthesis and secretion.

With the increasing market demand for wideband multifunctional electronic systems, real-time broadband measurement systems with few picoseconds switching rates are essential. Furthermore, stable millimeter wave sources are required to drive these wideband electronic systems. Nonlinear transmission lines (NLTLs) are high impedance transmission lines periodically loaded with reverse biased diode serving as varactors. Extremely high bandwidths are achievable because of the possibility to fabricate these structures monolithically, which is why pulses with ultra short transitions can be generated using NLTLs. Also, efficient wideband frequency conversion is made possible by NLTL technology. / In this thesis, a comprehensive study of NLTLs and their applications is presented. Sharpening of the edges of electrical pulses, voltage dependent true time delay, and harmonic generation in NLTLs are investigated through analytical studies as well as circuit simulations and experimental measurements. Designing the best possible mixers, frequency doublers, and edge sharpeners and optimizing them are not the objects of this thesis. The main objective is to study an alternative design approach by using NLTLs. To this end, analytical solution for the magnitude of the third harmonic along a nonlinear transmission line is derived for the first time. Also, for the first time the lowpass nature of the NLTL is combined with the solutions for the magnitudes of harmonics in order to improve the validity range of the predicted harmonics. An NLTL harmonic generator is fabricated and measurement results are reported. / Inspired by the distributed nature of nonlinear transmission lines, a novel filtering method is introduced for the suppression of the unwanted signals in different NLTL applications. The filtering method is applied to a nonlinear transmission line frequency multiplier in order to filter the third harmonic. The distributed filtering is also used to suppress the image signal in an NLTL mixer. The proposed filtering method is general and can be applied to other periodic structure as well (such as distributed amplifiers and distributed mixers). For implementing the filtering, compact complementary split ring resonators are proposed and designed for an NLTL frequency doubler.

In this thesis, the problem of overvoltage calculation on multiconductor transmission lines due to nonuniform external electromagnetic field excitations, such as lightning, is investigated by introducing a field-voltage macromodel. The main purpose of this thesis is to find a fast and efficient algorithm to model the effect of the radiated electromagnetic fields on transmission lines. This is done by replacing distributed voltage and current sources along the transmission line which are as a result of external electromagnetic field radiation, by voltage and current sources at the terminals of the transmission line. For this purpose, the knowledge of electromagnetic field at every point on the transmission line is required. A transfer function based pole-residue tracing technique will be introduced in this thesis. By using the proposed algorithm, a closed form solution for the lumped sources at the terminals of transmission line in the frequency domain is obtainable. This approach will enable us to bridge the software working in frequency domain with those working in the time domain. The effect of different parameters on calculated overvoltage such as finite conductivity of the ground and lightning return stroke channel (RSC) specifications are studied. The theoretical background and extent of validity of the proposed algorithm are reviewed in this thesis.

While extirpative surgery is curative for localized clear cell renal cell carcinoma (ccRCC), many patients develop recurrences or present with metastatic disease. Several aspects of ccRCC biology have been investigated, but these have been done in cell lines, which are known to poorly represent the tumour. Since cell lines are amenable to a wide array of experimental testing, the studies presented here demonstrate a novel method to generate ccRCC cell lines from primary tumours, which increases the rate of primary tumour cell line generation four fold. Additionally, ccRCC cells do not grow in serum-free media, which has been shown to be beneficial in other cancers. Therefore, we interrogated the effect of exogenous growth factors to optimize our serum-free media growth conditions, among which TGFb1 appeared to elicit the largest mitogenic effect. Once optimized, these findings will provide a valuable tool for understanding ccRCC tumour cell biology and identifying therapeutic targets.