Understanding how genetic modifications, individual or in combination, affect organismal fitness or other phenotypes is a challenge common to several areas of biology, including human health & genetics, metabolic engineering, and evolutionary biology. The importance of a gene can be quantified by measuring the phenotypic impact of its associated genetic perturbations "here and now", e.g. the growth rate of a mutant microbe. However, each gene also maintains a historical record of its cumulative importance maintained throughout millions of years of natural selection in the form of its degree of sequence conservation along phylogenetic branches. This thesis focuses on whether and how the phenotypic and evolutionary importance of genes are related to each other. Towards this goal, I developed a new approach for characterizing the phenotypic consequences of genetic modifications in genome-scale biochemical networks using constraint-based computational models of metabolism. In particular, I investigated the impact of gene loss events on fitness in the model organism Saccharomyces cerevisiae, and found that my new metric for estimating the cost of gene deletion correlates with gene evolutionary rate. I found that previous failures to uncover this correlation using similar techniques may have been the result of an incorrect assumption about how isoenzymes deletions affect the reaction they catalyze. I next hypothesized that the improvement my metric showed in predicting the cost of isoenzyme loss could translate into an improved capacity to predict the impact of pairs of gene deletions involving isoenzymes. Studies of such pair-wise genetic perturbations are important, because the extent to which a genetic perturbation modifies any given phenotype is often dependent on the genetic background upon which it has been performed. This lack of independence within sets of perturbations is termed epistasis. My results showed that, indeed, the new metric displays an increased capacity to predict epistatic interactions between pairs of genes. In addition to shedding light on the relationship between the functional and evolutionary importance of genes, further developments of our approach may lead to better prediction of gene knockout phenotypes, with applications ranging from metabolic engineering to the search for gene targets for therapeutic applications.

Many novel materials, such as the vanadates MgV 2O5, the cuprates SrCu 2O3, conducting polymers and organic salts which involve longer-range Coulomb interactions, can be modeled by the extended Hubbard model. In this thesis, we applied the strong-coupling perturbation theory to study a generalized extended Hubbard model characterized by the inter-chain electron hopping t' and the inter-chain nearest-neighbor interaction V' as well as the on-site interaction U, the intra-chain nearest-neighbor interaction V and the intra-chain electron hopping t at strong coupling limit for quarter and half band fillings. / The early strong coupling perturbation expansion was only up to the fourth order in t/U and t/V expansion, which is good for the large values of interaction, U/t > 10. However, for real physical systems, the reasonable range of U/t should be from 4 to 10. In order to investigate the physical systems more accurately, we worked out a perturbation expansion up to the sixth order, hence obtained an effective Hamiltonian in t/U, t/V, t/V', t'/U, t'/V and t'/V' expansion for the extended Hubbard model in half and quarter band filings. The effective Hamiltonian obtained only contains the spin-spin correlation terms. For the half-filled band, we calculated the four spin-spin correlation terms and applied the first and second nearest-neighbor correlation of the linear Heisenberg model obtained by Hulthen and Takahashi and the third nearest-neighbor correlation obtained by Kazumitsu Sakai's group to calculate the ground state energy for the 1-D extended Hubbard chain with the realistic Coulomb interactions, U/t ranges from 4 to 14 and V/t ranges from 0 to 2 respectively. For the quarter-filled case, we worked out the effective Hamiltonian for the 1-D and the 2-D cases and calculated the spin-spin correlation functions by the spin-wave theory. We calculated the ground state energy with the same ranges of the on-site interaction input in the half-filled case and the V/t ranges from 1.5 to 4.0 for the 1-D, the quasi 2-D (t > t', t'/V ∼ t/V) and the isotropic 2-D (t = t', V = V') case respectively. In order to check the validity of the perturbation expansion, we proceeded numerical calculations of the ground state energy by exact diagonalization for the same values of U, V, t, V' and t' for both the half-filled and the quarter-filled cases. / Lee Wing Fai = 強耦合擴展 Hubbard模型之微擾計算 / 李榮輝. / "August 2005." / Adviser: Lin Hai Qing. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0323. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 157-160). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307. / Lee Wing Fai = Qiang ou he kuo zhan Hubbard mo xing zhi wei rao ji suan / Li Ronghui.

Pang Kam Moon. / "June 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 134-137). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese. / Pang Kam Moon.

Studying dynamical mechanisms of perturbation growth in tropical cyclones is important from a perspective of designing ensemble prediction system and adaptive observations for tropical cyclones. In this thesis, the role of perturbations in ensemble forecasting and adaptive observations for tropical cyclones is investigated, especially focusing on tropical cyclone tracks. For this purpose, ensemble initial perturbations from operational numerical weather prediction centers are first diagnosed, followed by a study in which the structure and location of singular vectors computed for tropical cyclone-like vortices in a nondivergent barotropic framework are investigated. The three most significant findings of this study are that 1) perturbations grow in the vicinity of tropical cyclones through both baroclinic and barotropic energy conversion as seen in mid-latitude dynamics, that 2) those energy conversions lead to the modification in tracks of tropical cyclones, and that 3) the structure and the location of growing perturbations are sensitive to initial temperature and wind profiles of the tropical cyclone vortex. The above results (1) and (2) determine a mechanism how the ensemble spread of tropical cyclone tracks evolves with time in ensemble prediction systems at operational numerical weather prediction centers. In addition, those results identify the reason why the ensemble spread differs from one ensemble prediction system to another. The result (3) gives an insight into understanding what sensitivity analysis guidance targeted for tropical cyclones represents and helps to optimize observation network for tropical cyclones.

Reproduction de : Thèse de doctorat : Physique : Lyon 1 : 2002. / Titre provenant de l'écran titre. 61 réf. bibliogr.

Thesis (Ph. D.)--University of Chicago, Dept. of Mathematics, December 2003. / Includes bibliographical references. Also available on the Internet.

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