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  • Thesis


  • Authors: Kopkalli, Yasemin;  Co-Author: 2006 (There is great interest in identifying and characterizing new surfactants with predictable solubilization and reconstitution characteristics for use in membrane research. Among them, Triton X-100 and octyl glucoside (OG) are the best-studied surfactants. However, no physical data is available characterizing the interactions of two non-ionic pyrrolidinone surfactants, N-(2-ethylhexyl)-2-pyrrolidinone (C2,6P) and N-octyl-2-pyrrolidinone (C8P), with lipid bilayers. In the present study, their physical effects on dimyristoylphosphatidylcholine small unilamellar vesicles (DMPC SUVs) above the lipid phase transition temperature are described using surface tension, fluorescence spectroscopy, and isothermal titration calorimetry (ITC) methodologies. Surface tension methods show significant deviations from ideal behavior (attractive interactions) for these surfactant/lipid mixtures. In addition, fluorescence intensity studies of DPH and TMA-DPH labeled SUVs suggest that C8P interacts more favorably with both the acyl chain and head group regions of the bilayer over the corresponding branched chain C2,6P analogue. This is further supported by fluoresecence emission anisotropy measurements (EA). Both surfactants affect the membrane lipid order within the acyl chain region, and the corresponding phospholipid ‘melt’ transition temperature (Tm) values, which decrease linearly with increasing surfactant concentrations. Using the van’t Hoff model, the lipid bilayer-water partition coefficients for these surfactants have been estimated from the depression of the lipid phase transition temperature. Values for the lipid partition coefficient for C8P [(1.22±0.08)× 104] versus C2,6P [(4.09±0.78)× 103] further supports a more favorable bilayer association for C8P. ITC data reveals an endothermic association for both C8P and C2,6P together with a somewhat higher binding affinity [(6.78±0.92)×10-4M] for C8P compared with C2,6P [(8.46±0.83)×10-4 M], as predicted from fluorescence studies. We propose that C8P interacts and affects the lipid packing of bilayer membranes to a greater extent than C2,6P. Interactions of C2,6P appears to be more localized within the head group region of the bilayer. We conclude that C8P has great potential for biological applications, particularly membrane solubilization and membrane formation from micellar mixtures. In contrast, C2,6P may have potential for solubilization of extrinsic surface associated membrane proteins.)

  • Thesis


  • Authors: Bao, Yu;  Co-Author: 2006 (The mechanical behavior of saturated soil is mainly governed by the interaction between the soil skeleton and the pore fluid, and this interaction may lead to significant loss of strength known as liquefaction under seismic loadings. The main objective of this thesis is to develop and implement a cyclic constitutive model capable of modeling soil skeleton dilatancy during earthquake excitation. The constitutive model is based on the fuzzy-set plasticity theory and enhancement is made on the description of dilatancy behavior under cyclic loading. A robust Biot formulation, in which the governing equations of motion of the soil mixture are coupled with the global mass balance equations, is developed to describe the realistic behavior of saturated soil. The finite element discretization is established without neglecting the convective terms. An unconditionally stable implicit time integration scheme, Hilber-Hughes-Taylor a method is used and an iterative algorithm based on Newton-Raphson method is developed to solve the nonlinear time-discretized problem. A numerical study of sand liquefaction is performed and compared with the centrifuge experimental results to show the capabilities of the proposed formulation on pore water pressure generation and strength loss occurred in loose granular soil deposit under cyclic loading. The computed results show good agreement with the experimental data. The capability of the enhanced fuzzy-set model in simulating cyclic soil behaviors including liquefaction is validated. It is concluded that the developed Biot formulation and computational procedure are an effective means to assess liquefaction potential and liquefaction-related deformations.)

  • Thesis


  • Authors: Bergseid, Jacqueline;  Co-Author: 2006 (The product of the retinoblastoma gene (pRb) is a tumor suppressor protein that regulates cellular proliferation, apoptosis and differentiation of numerous tissues in mice. It contains multiple peptide-binding pockets through which it interacts with a host of cellular and viral proteins. The LxCxE-binding pocket of pRb has been highly conserved between pRb proteins from evolutionary distant species; however, the in vivo function of this binding pocket is unknown. The crystal structure of pRB bound to LxCxE peptide was used to design a single point mutation, N757F, which specifically inactivates interactions between pRB and LxCxE-containing proteins without affecting the pRB-E2F interaction. The N750F mutation (analogous to N757F in the human RB) was introduced into the mouse Rb-1 locus by homologous recombination. The RbN750F/N750F mice do not exhibit the phenotype of embryonic lethality observed in Rb-null mice. The pRb-N750F protein does not co-immunoprecipitate with E1A, demonstrating disruption of the LxCxE-binding pocket. The Rb+/- mice develop pituitary tumors with 90% penetrance through LOH. By contrast, the pRb-N750F protein retains its pituitary tumor suppression function as evidenced by the lack of pituitary tumors in RbN750F/N750F and Rb+/N750F mice. This is consistent with the data from tissue culture experiments demonstrating that RbN750F/N750F fibroblasts do not exhibit any cell cycle defects. The lack of embryonic lethality in RbN750F/N750F mice allowed us to study the effect of this mutation on adult tissues. The RbN750F/N750F mice have elevated levels of platelets and lymphocytes in the peripheral blood. The RbN750F/N750F females are infertile due to anovulation. These findings demonstrate for the first time that the LxCxE-binding pocket of pRb plays a role in thromobopoiesis, lymphopoiesis and ovulation. The RbN750F/- mice are born at the frequency of 13% and die by the age of 8 months, indicating that, unlike Rb+ allele, the RbN750F allele is haploinsufficient. The RbN750F/-females are also infertile due to the lack of FSH and LH function in the ovaries.)

  • Thesis


  • Authors: Su, Li-Jun;  Co-Author: 2006 (Soil nailing is a technique for stabilizing soil slopes and excavations by installing a large number of closely spaced passive inclusions into the in-situ soil mass. The soil nailing technique has been increasingly used worldwide since its origination in the early 1970's because of its technical and economical advantages. In Hong Kong, soil nailing has been commonly used to stabilize new cut and sub-standard existing slopes since the late 1980's. The interface shear strength between a soil nail and the surrounding soil is a key parameter for design and stability assessment of the soil nailing system. However, in current practice in Hong Kong, this parameter is generally assumed to be the same as the shear strength of the soil and verified by field pull-out tests in the construction stage. Field verification tests are normally subjected to variations of the site conditions and the results are therefore scattered. Laboratory pull-out tests have been carried out to help overcome these problems and precisely investigate the factors influencing the nail-soil interface shear strength. However, there were still some deficiencies in these tests and can be improved. A laboratory study of the pull-out shear resistance of cement grouted soil nails was therefore conducted in compacted completely decomposed granite (CDG) fill. A pull-out box with the internal dimensions of 1.0m in length, 0.6m in width and 0.83m in height was designed and constructed to carry out the pull-out tests. An extension cylindrical chamber was provided to house an extension part of the nail and ensure that a constant 1.0m length of the test soil nail was maintained within the test box during pull-out and no cavity would be left behind the end of the test nail. A waterproof front cap was used to cover the soil nail head and prevent water leakage which made it possible to apply back pressure to saturate the testing soil in submerged tests. Comprehensive instrumentation was used and the earth pressure, suction, and pore water pressure in the soil, the deformation of the testing soil, and the pull-out force and displacement were measured. During the pull-out tests, the overburden pressure was applied before drilling to simulate the actual construction procedure of the soil nailing system. A series of pull-out tests have been conducted using two copies of the above introduced pull-out box. The test results showed that soil stresses around the hole were largely released after drilling and recovery of the stresses due to grouting of the soil nail was minimal. The development of pull-out shear resistance was mainly derived from the constrained dilatancy of the soil. Tests in soil at different degrees of saturation showed that the peak pull-out shear resistance varies with different degrees of saturation of the soil, with higher resistances at the degrees of saturation of 50% and 75%. Pressure grouting tests were carried out and showed that the average peak pull-out shear resistance of the soil nail increased almost linearly with the increase in grouting pressure. Numerical modeling was performed and agreements between the measured and simulated results were good.)

  • Thesis


  • Authors: Ohnmacht, Corey M.;  Co-Author: 2006 (This dissertation involves the detailed examination of phenytoin and its binding properties to human serum albumin (HSA). This was accomplished by implementing various affinity chromatographic techniques including zonal elution and frontal analysis along with columns containing immobilized HSA to provide estimates of equilibrium binding constants. Affinity chromatography with plate height measurements was also used with theory-derived equations to measure the rate constants for the multisite binding of phenytoin to the chromatographic column. Part one discusses the complexity of phenytoin’s multisite binding and work that has been done previously to unravel the binding properties of phenytoin. In addition an expansion of current chromatographic theory describing multisite binding and nonspecific interactions was used to measure rate constants utilizing plate height measurements. Also, frontal analysis was used to measure the overall equilibrium binding constants of this drug-protein binding system. Together these two constants measured at various temperatures were applied to thermodynamic theory to obtain a complete thermodynamic picture for phenytoin binding to HSA. Part two explores the development of a novel near infrared fluorescence and ultrafast immunoextraction/displacement assay (UFIDA) for the analysis of phenytoin’s free drug fraction. The highlights of this work included using microcolumns containing immobilized anti-phenytoin antibodies with sub-millimeter length and capability of extraction of phenytoin containing plasma in the millisecond-timescale range. The use of a phenytoin analog conjugated to a near infrared dye was used to provide the limits of detection required for such an assay. The last part of this dissertation examines a topic sometimes overlooked in protein binding studies, that is the interactions of drug metabolites with their parent compound. It was found that the metabolites of phenytoin do not share every binding site on HSA as their parent drug. However the binding of the metabolites to HSA do exhibit allosteric effects with phenytoin indicating that competition between phenytoin and its metabolites can change phenytoin’s pharmacokinetics.)

  • Thesis


  • Authors: Araujo, Kenneth Michael;  Co-Author: 2006 (The use of design patterns in software development has become more attractive given the rise in popularity of development tools utilizing a model driven architecture (MDA) philosophy. If a given piece of software is designed from a collection of standard design patterns, we should be able to test that software based on the designer's intent as captured by those patterns. In testing object oriented software, we must be aware that the state of an object at any time depends on the sequence of messages received by the object up to that point in time. As these messages are passed by method calls, the number of methods calls and the order in which they occur must be given consideration. A metric based on method coverage is suitable in this context. This dissertation examines the utility of design patterns in the practice of software testing. We employ a metric of method coverage to gauge the efficiency obtained by the inclusion of design patterns in two traditional test procedures, statistical design of experiments and reliability block diagrams. In the process, a new type of software system diagram, the Pattern Block Diagram, is developed.)

  • Thesis


  • Authors: Herzig, Florian;  Co-Author: 2006 (We formulate a conjecture generalising the weight in Serre's Conjecture to n-dimensional representations p : Gal(U/Q) -* GLn(IF,) that are tamely ramified at p. A weight in this context is an irreducible representation of GLn(1Fp) over Pp. The conjecture describes the predicted set of weights in terms of the reduction modulo p of a Deligne-Lusztig repre¬sentation of GLn(Fp) which only depends on the restriction of p to the inertia subgroup at p. When n = 3 a weight conjecture had already been made by Ash, Doud, Pollack and Sinnott. The advantage of our conjecture is that it is more conceptual. It moreover predicts more weights for many representations p. We give computational examples which strongly suggest the existence of these extra weights. When n = 4 we obtain some theoretical evidence by considering automorphic inductions of Hecke characters over non Galois quartic CM fields. Finally we show that the recent conjecture of Buzzard, Diamond and Jarvis on the weights associated to p : Gal(K/K) -* GL2(IFp), where K is a totally real number field unramified at p, is related in an analogous way to the reduction modulo p of Deligne-Lusztig representations if p is tamely ramified at p. This improves on a result of Diamond.)

  • Thesis


  • Authors: Douglas, Michael Jay;  Co-Author: 2006 (Effective software cost estimation is one of the most challenging and important activities in software development. The software industry does not estimate projects well. Poor estimation leads to poor project planning with resulting schedule overruns, inadequate staffing, low system quality, and many aborted projects. Research on software estimation is needed to build more accurate models of the key aspects of software development. The goals of research in this dissertation are to investigate and improve the modeling of team size and project structures in current software estimation methods. Mathematical models for estimating the impacts of project team size and three variations of project structure are developed. These models accept the outputs of the COCOMO II software estimation tool, allow variation in both team size and project structure, and produce more detailed project estimates. This new extended model of COCOMO II is implemented in a decision support tool for software estimators called PSEstimate. Following the design science research paradigm, the artifact is evaluated with an experiment with experienced software project managers. Three treatment groups: a manual (no tool) group, a COCOMO II group, and a PSEstimate group, completed two multipart software cost estimation tasks. The accuracy and consistency of the cost and schedule estimates, the participants’ confidence in their estimates, and their satisfaction with and perceived usefulness of the cost estimation tool are measured. The experimental results support most of the hypotheses of the dissertation. For most tasks, individuals aided by computer-based decision support tools produce more accurate project effort estimates and are more confident in their estimates than manual estimators. There are no significant differences between the three groups on schedule estimation. A possible explanation is that experienced estimators in the manual group compensate for the inaccuracy of their effort estimates by adding time to their schedule estimates. The research contributions are new mathematical models for software estimation based on project team size and structure; a decision support tool (PSEstimate) that incorporates these models; and the experimental results that demonstrate improvements in software estimation by experienced project managers when the new models and tool are applied in practice.)