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- Abel, Frida, 1974
(författare)
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Genetic studies of neuroblastoma with emphasis on the apoptotic pathway
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: The objective of this thesis was to find genes and chromosomal regions involved in neuroblastoma (NB) tumor progression. NB is a childhood tumor of the sympathetic nervous system that generally occurs spontaneously. Biologically, NB has a complex heterogeneity from tumor progression to tumor regression, dependent on clinical stage and age at diagnosis. The main genetic markers, which are also of prognostic value in NB, are amplification of the oncogene MYCN, deletion of chromosome arm 1p and gain of chromosome arm 17q. Results: We have been shown using fluorescence in situ hybridization (FISH) on a Scandinavian tumor material, that 17q gain is present in approximately 65% of all NB stages, is significantly associated with poor prognosis and predicts survival. The gene encoding somatostatin receptor 2 (SSTR2), localized in chromosome region 17q24, was not found to be mutated in any NB, when analyzed with PCR-based single stranded conformation polymorphism/heteroduplex (SSCP/HD) and DNA sequencing. In a tentative effort of defining of the location of a general embryonal tumor suppressor gene (TSG) on 1p, we combined the smallest region of overlap (SRO) of 1p deletions in NB tumors and germ cell tumors (GCTs). We thus delimited the NB/GCT SRO to approximately 5 cM between markers D1S508 and D1S244, and fine-mapped this region by radiation hybrid mapping and construction of a bacterial artificial chromosome (BAC) contig. A homozygously deleted region in an NB cell line was found to partially overlap the proximal part of the 5 cM-SRO defined by us, which further focused our search for a TSG to a 500 kb candidate region in 1p36.22. Two attractive candidate NB TSGs, DFFA and CASP9, are both located in 1p36.2 and encode key apoptotic mediators. In fact, DFFA resides in the 500 kb TSG candidate region. Via sequence analysis of the entire tumor material, we found three different coding alterations in DFFA which all affect the highly conserved N-terminal regulatory domain of DFF45. Using RT-PCR and real-time RT-PCR (TaqMan) studies, we were able to show that both DFFA and CASP9 are preferably expressed in NB tumors with favorable outcome. It has been proposed that lack of apoptosis plays an important role in tumor progression. We therefore screened an array with cDNAs involved in the apoptotic process, to find genes differentially expressed in NB tumors with unfavorable versus favorable biology. Using real-time RT-PCR analysis, we verified the differential expression of several transcripts encoding mitochondrial apoptotic mediators. Conclusions: We have shown that 17q gain is the most frequently detected alteration in NB and that it is associated with established prognostic factors. We narrowed down the TSG candidate region on 1p and found mutations in a gene localized in the region possessing fundamental functions in apoptosis. Our results also suggest that the mitochondrial apoptotic pathway is suppressed at multiple steps in advanced stages of NB tumors, due to imbalance between anti-apoptotic and pro-apoptotic mediators.
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| 3. |
- Adolfsson, Tobias, 1970
(författare)
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Statistical Methods for Designed Experiments and Spectroscopic Data
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis consists of six papers related to saturated orthogonal designs, spectroscopic and high dimension data analysis. The first two papers deals with testing procedures for saturated orthogonal designs. Both the presented methods controls the multiple level of significance. In paper C a regression method is constructed for both multivariate and univariate situations. The correctness of the subspace of regression can be tested using the multiple testing technique constructed in paper A. Paper D gives a method for testing the chemical rank of spectroscopic data. In paper E the effectiveness of high-dimension data gathered in a random way is examined and compared to an optimality criteria. Paper F deals with partial least squares and cross validation. The paper explores, and partly explains, some of the strange behaviour of partial least squares. 2000 Mathematical subject classification: 62F03, 62F25, 62H25, 62J05, 62K15
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| 4. |
- Ahlberg, Daniel, 1982
(författare)
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Asymptotics and dynamics in first-passage and continuum percolation
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis combines the study of asymptotic properties of percolation processes with various dynamical concepts. First-passage percolation is a model for the spatial propagation of a fluid on a discrete structure; the Shape Theorem describes its almost sure convergence towards an asymptotic shape, when considered on the square (or cubic) lattice. Asking how percolation structures are affected by simple dynamics or small perturbations presents a dynamical aspect. Such questions were previously studied for discrete processes; here, sensitivity to noise is studied in continuum percolation. Paper I studies first-passage percolation on certain 1-dimensional graphs. It is found that when identifying a suitable renewal sequence, its asymptotic behaviour is much better understood compared to higher dimensional cases. Several analogues of classical 1-dimensional limit theorems are derived. Paper II is dedicated to the Shape Theorem itself. It is shown that the convergence, apart from holding almost surely and in L^1, also holds completely. In addition, inspired by dynamical percolation and dynamical versions of classical limit theorems, the almost sure convergence is proved to be dynamically stable. Finally, a third generalization of the Shape Theorem shows that the above conclusions also hold for first-passage percolation on certain cone-like subgraphs of the lattice. Paper III proves that percolation crossings in the Poisson Boolean model, also known as the Gilbert disc model, are noise sensitive. The approach taken generalizes a method introduced by Benjamini, Kalai and Schramm. A key ingredient in the argument is an extremal result on arbitrary hypergraphs, which is used to show that almost no information about the critical process is obtained when conditioning on a denser Poisson process.
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| 5. |
- Ahlström, Bodil, 1968
(författare)
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Structure, phase behavior, and dynamics of colloidal systems characterized by strong, short- and moderate-ranged attractions: a computational study
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Attractions between colloidal particles are often so strong that non-equilibrium behavior results. However, dissolved non-adsorbing polymer can be added to give a weak attraction between particles so that equilibrium phase transitions appear at moderate polymer concentrations. At higher polymer concentrations and small polymer-colloid size ratios non-equilibrium effects like gelation occur, for which a complete understanding is lacking. Monte Carlo and Monte Carlo-like computer simulations have been used to investigate the role of many-body effects and the structures that colloidal particles adopt under influence of a polymer-induced depletion attraction. The phase diagram proves difficult to determine for these systems by direct application of the Gibbs ensemble Monte Carlo method, especially for small polymer-colloid size ratios that correspond to short-range attractions. However, a sequential equilibration scheme is shown be able to give equilibrated fluid-fluid coexistence data where usual application of the method fails. The dynamics of colloidal particles along this fluid-fluid coexistence curve is studied by a Brownian dynamics algorithm, corrected for the use of a large time step. The dynamics slows down as the particle and polymer concentrations are increased, but the systems appear to reach equilibrium for the cases studied. This is in contrast to what is found by applying mode coupling theory; it predicts glass-like transitions already at modest polymer concentrations for short-range attractive systems, which is an issue that is investigated to some extent. In addition, a number of approximate theories have been developed and tested against the results from the computer simulations.
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| 6. |
- Aires, Nibia, 1959
(författare)
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Techniques to Calculate Exact Inclusion Probabilities for Conditional Poisson Sampling and Pareto .pi.ps Sampling Designs
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis consists of five papers and treats two finite population sampling methods, viz. the Conditional Poisson and the Pareto .pi.ps sampling schemes. Both methods belong to a class of sampling schemes with unequal inclusion probabilities, commonly used in approximate probability to size sampling schemes. Paper A addresses the problem of determining first and second order inclusion probabilities for both methods, which is a vital element in deriving linear estimators. Tools which consist of dynamic programming algorithms, are created to calculate these exact inclusion probabilities. They make it possible to compute the inclusion probabilities in reasonable execution time for small and moderate samples. Algorithms to adjust the parameters so that arbitrary desirable exact inclusion probabilities are achieved are also given. The results in this paper opened the possibility to use the exact Horvitz-Thompson and Yates-Grundy-Sen variance estimators for quite large samples for Conditional Poisson and for moderate samples in the Pareto case. In Paper B, using those algorithms, a computer system was developed to compare and contrast the Conditional Poisson and Pareto .pi.ps sampling designs in terms of estimators of population totals, biases and variances. The computer programme produced an empirical comparison of both methods to check the convergence to the asymptotical inclusions. It also enabled adjustment of the parameters to obtain exact variances and make comparisons in these terms. The results from these studies show that the Pareto scheme approaches asymptotical inclusions faster than the Conditional Poisson, and that both methods are very similar in terms of second order inclusions for the adjusted procedures for moderate samples. The second order inclusion algorithms for the Conditional Poisson Sampling design are generalised in Paper C to a recursive fast procedure to derive higher order inclusion probabilities of arbitrary order. Paper D proves the existence and partial uniqueness of a set of scale parameters when exact inclusion probabilities are required for any order sampling of fixed distribution shape, a class of schemes of which Pareto .pi.ps sampling is a special case. Lastly, Paper E reports on a thorough study of approximation accuracy for Pareto inclusion probabilities, aiming at practical use recommendations, for using asymptotically motivated approximations. Numerical results in this study are presented in Appendix 1 and 2.
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| 8. |
- Alm, Jonas, 1984
(författare)
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Insurance: solvency and valuation
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns mathematical and statistical concepts useful to assess an insurer's risk of insolvency. We study company internal claims payment data and publicly available market data with the aim of estimating (the right tail of) the insurer's aggregate loss distribution. To this end, we also develop a framework for market-consistent valuation of insurance liabilities. Moreover, we discuss Solvency II, the risk-based regulatory regime in the European Union, in some detail. In Paper I, we construct a multidimensional simulation model that could be used to get a better understanding of the stochastic nature of insurance claims payments, and to calculate solvency capital requirements. The assumptions made in the paper are based on an analysis of motor insurance data from the Swedish insurance company Folksam. In Paper II, we investigate risks related to the common industry practice of engaging in interest-rate swaps to increase the duration of assets. Our main focus is on foreign-currency swaps, but the same risks are present in domestic-currency swaps if there is a spread between the swap-zero-rate curve and the zero-rate curve used for discounting insurance liabilities. In Paper III, we study data from the yearly reports the four major Swedish non-life insurers have sent to the Swedish Financial Supervisory Authority (FSA). Our aim is to find the marginal distributions of, and dependence between, losses in the five largest lines of business. In Paper IV, we study the valuation of stochastic cash flows that exhibit dependence on interest rates. We focus on insurance liability cash flows linked to an index, such as a consumer price index or wage index, where changes in the index value can be partially understood in terms of changes in the term structure of interest rates. %We focus primarily on the case when a deep and liquid market for index-linked bonds is absent, or when the market price data are unreliable. Papers I and III are based on data that are difficult to get hold of for people in academia. The FSA reports are publicly available, but actuarial experience is needed to find and interpret them. These two papers contribute to a better understanding of the stochastic nature of insurance claims by providing data-driven models, and analyzing their usefulness and limitations. Paper II contributes by highlighting what may happen when an idea that is theoretically sound (reducing interest-rate risk with swaps) is applied in practice. Paper IV contributes by explicitly showing how the dependence between interest rates and inflation can be modeled, and hence reducing the insurance liability valuation problem to estimation of pure insurance risk.
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| 9. |
- Almanasreh, Hasan, 1981
(författare)
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The Dirac Equation: Numerical and Asymptotic Analysis
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis consists of three parts, although each part belongs to a specific subject area in mathematics, they are considered as subfields of the perturbation theory. The main objective of the presented work is the study of the Dirac operator; the first part concerns the treatment of the spurious eigenvalues in the computation of the discrete spectrum. The second part considers G-convergence theory for positive definite parts of a family of Dirac operators and general positive definite self-adjoint operators. The third part discusses the convergence of wave operators for some families of Dirac operators and for general self-adjoint operators. In the first and main part, a stable numerical scheme, using finite element and Galerkin-based $hp$-cloud methods, is developed to remove the spurious eigenvalues from the computational solution of the Dirac eigenvalue problem. The scheme is based on applying a Petrov-Galerkin formulation to introduce artificial diffusivity to stabilize the solution. The added diffusion terms are controlled by a stability parameter which is derived for the particular problem. The derivation of the stability parameter is the main part of the scheme, it is obtained for specific basis functions in the finite element method and then generalized for any set of admissible basis functions in the $hp$-cloud method. In the second part, G-convergence theory is applied to positive definite parts of the Dirac operator perturbed by $h$-dependent abstract potentials, where $h$ is a parameter allowed to grow to infinity. After shifting the perturbed Dirac operator so that the point spectrum is positive definite, the spectral measure is used to obtain projected positive definite parts of the operator, in particular the part that is restricted to the point spectrum. Using the general definition of G-convergence, G-limits, as $h$ approaches infinity, are proved for these projected parts under suitable conditions on the perturbations. Moreover, G-convergence theory is also discussed for some positive definite self-adjoint $h$-dependent operators. The purpose of applying G-convergence is to study the asymptotic behavior of the corresponding eigenvalue problems. In this regard, the eigenvalue problems for the considered operators are shown to converge, as $h$ approaches infinity, to the eigenvalue problems of their associated G-limits. In the third part, scattering theory is studied for the Dirac operator and general self-adjoint operators with classes of $h$-dependent perturbations. For the Dirac operator with different power-like decay $h$-dependent potentials, the wave operators exist and are complete. In our study, strong convergence, as $h$ approaches infinity, of these wave operators is proved and their strong limits are characterized for specific potentials. For general self-adjoint operators, the stationary approach of scattering theory is employed to study the existence and convergence of the stationary and time-dependent $h$-dependent wave operators.
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| 10. |
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