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Genome-Wide Compensatory Changes Accompany Drug-Selected Mutations In The Plasmodium Falciparum Crt Gene, Hongying Jiang, Jigar J. Patel, Ming Yi, Jianbing Mu, Jinhui Ding, Robert Stephens, Roland A. Cooper, Michael T. Ferdig, Xin-Zhuan Su Jan 2008

Genome-Wide Compensatory Changes Accompany Drug-Selected Mutations In The Plasmodium Falciparum Crt Gene, Hongying Jiang, Jigar J. Patel, Ming Yi, Jianbing Mu, Jinhui Ding, Robert Stephens, Roland A. Cooper, Michael T. Ferdig, Xin-Zhuan Su

Biological Sciences Faculty Publications

Mutations in PfCRT (Plasmodium falciparum chloroquine-resistant transporter), particularly the substitution at amino acid position 76, confer chloroquine (CQ) resistance in P. falciparum. Point mutations in the homolog of the mammalian multidrug resistance gene (pfmdr1) can also modulate the levels of CQ response. Moreover, parasites with the same pfcrt and pfmdr1 alleles exhibit a wide range of drug sensitivity, suggesting that additional genes contribute to levels of CQ resistance (CQR). Reemergence of CQ sensitive parasites after cessation of CQ use indicates that changes in PfCRT are deleterious to the parasite. Some CQR parasites, however, persist in the …


Improved Constrained Global Optimization For Estimating Molecular Structure From Atomic Distances, Terri Marie Grant Jan 2008

Improved Constrained Global Optimization For Estimating Molecular Structure From Atomic Distances, Terri Marie Grant

Mathematics & Statistics Theses & Dissertations

Determination of molecular structure is commonly posed as a nonlinear optimization problem. The objective functions rely on a vast amount of structural data. As a result, the objective functions are most often nonconvex, nonsmooth, and possess many local minima. Furthermore, introduction of additional structural data into the objective function creates barriers in finding the global minimum, causes additional computational issues associated with evaluating the function, and makes physical constraint enforcement intractable. To combat the computational problems associated with standard nonlinear optimization formulations, Williams et al. (2001) proposed an atom-based optimization, referred to as GNOMAD, which complements a simple interatomic distance …


Biological Networks: Modeling And Structural Analysis, Emad Y. Ramadan Jan 2008

Biological Networks: Modeling And Structural Analysis, Emad Y. Ramadan

Computer Science Theses & Dissertations

Biological networks are receiving increased attention due to their importance in understanding life at the cellular level. There exist many different kinds of biological networks, and different models have been proposed for them. In this dissertation we focus on suitable network models for representing experimental data on protein interaction networks and protein complex networks (protein complexes are groups of proteins that associate to accomplish some function in the cell), and to design algorithms for exploring such networks. Our goal is to enable biologists to identify the general principles that govern the organization of protein-protein interaction networks and protein complex networks. …