Every living organism is programmed to reproduce and to pass genetic information to descendants. The information has to be carefully copied and accurately transferred to the next generation.  Therefore organisms have developed the network of conserved mechanisms to survey the protection and precise transfer of the genetic information. Such mechanisms are called checkpoints and they monitor the correct execution of different cell programs. The DNA damage and the replication blocks are surveyed by the conserved Mec1-Rad53 (human ATM/ATR and Chk2, respectively) protein kinase cascade. Mec1 and Rad53 are essential for survival and when activated orchestrate the multiple cellular responses, including the activation of the ribonucleotide reductase (RNR), to the genotoxic stress. RNR is an enzyme producing all four dNTPs - the building blocks of the DNA - and is instrumental for the maintenance both proper concentration and balance of each of dNTPs. The appropriate concentration of the dNTPs should be strictly regulated since inadequate dNTP production can impede many cellular processes and lead to higher mutation rates and genome instability. Hence RNR activity is regulated at many levels, including allosteric and transcriptional regulation and the inhibition at protein level. In our research, we addressed the question of the transcriptional regulation of RNR and the consequences of dNTP malproduction in the terms of the genomic stability. In yeast S. cerevisiae, four genes encode RNR: 2 genes encode a large subunit (RNR1 and RNR3) and 2 genes encode a small subunit (RNR2 and RNR4). All 4 genes are DNA-damage inducible: transcription of RNR2, RNR3 and RNR4 is regulated via Mec1-Rad53-Dun1 pathway by targeting the transcriptional repressor Crt1 (Rfx1) for degradation; on the contrary, RNR1 gene promoter does not contain Crt1-binding sites and is not regulated through the Mec1-Rad53-Dun1 pathway. Instead, we show that intrastrand cross (X)-link recognition protein (Ixr1) is required for the proper transcription of the RNR1 gene and maintenance of the dNTP pools both during unperturbed cell cycle and after the DNA damage. Thus, we identify the novel regulator of the RNR1 transcription. Next, we show that the depletion of dNTP pools negatively affects genome stability in the hypomorphic mec1 mutants: the hyper-recombination phenotype in those mutants correlates with low dNTP levels. By introducing even lower dNTP levels the hyper-recombination increased even further and conversely all the hyper-recombination phenotypes were suppressed by artificial elevation of dNTP levels. In conclusion, we present Ixr1 as a novel regulator of the RNR activity and provide the evidence of role of dNTP concentration in the genome stability.

Human papillomavirus (HPV), a major sexually-transmitted disease, causes cervical cancer, in addition to numerous other cancers in females and males. This thesis uses mathematical modeling, theory and simulations to study the transmission dynamics of HPV, and associated dysplasia, in a community. A new deterministic model is designed and used to assess the population-level impact of Pap cytology screening on the transmission dynamics of the disease in a community. The model is rigorously analyzed for its dynamical features, vis-a-vis determining the conditions for the effective control (or elimination) and persistence of the disease. Furthermore, the effect of uncertainties in the estimates of the parameter values used in the numerical simulations of the model is accounted for via uncertainty and sensitivity analysis. Simulations of the model show that Pap screening dramatically reduces the incidence of cervical cancer in the community.

The robustness of the stability property of multivariable feedback control systems with respect to model uncertainty is studied and discussed. By introducing a topological notion of arcwise connectivity, existing and new robust stability tests are combined and unified under a common framework. The new switching-type robust stability test is easy to apply, and does not require the nominal and perturbed plants to share the same number of closed right half-plane poles, or zeros, or both. It also highlights the importance of both the sensitivity matrix and the complementary sensitivity matrix in determining the robust stability of a feedback system. More specifically, it is shown that at those frequencies where there is a possibility of an uncertain pole crossing the jw-axis, robust stability is "maximized" by minimizing the maximum singular value of the sensitivity matrix. At frequencies where there is a likelihood of uncertain zeros crossing the imaginary axis, it is then desirable to minimize the maximum singular value of the complementary sensitivity matrix. A robustness optimization problem is posed as a non-square H^∞-optimization problem. All solutions to the optimization problem are derived, and parameterized by the solutions to an "equivalent" two-parameter interpolation problem. Motivated by improvements in disturbance rejection and robust stability, additional optimization objectives are introduced to arrive at the 'best' solution.

The work in this thesis is concerned with the numerical study of some stability and scattering properties of two CP¹ models in three dimensional space-time: The non-linear 0(3) model and its modified Skyrme version. Chapter 3 focuses principally on the Skyrme model on compactified plane, the topological sphere. Such model is obtained by supplementing the ordinary 0(3) lagrangian with both a Skyrme term and a potential term which, in the present work, has a rather general form. Under the numerical simulation the skyrmions behave stably and scatter either back-to-back or at 90 to the initial direction of motion, depending on the initial velocity. In the 0(3) limit the solitons are no longer stable and scatter at 90 irrespective of the speed. In the fourth chapter the 0(3) model is studied on a flat torus. Its solitons exhibit the usual instability but can be stabilised by the sole addition of a Skyrme term to the lagrangian. Scattering at right angles is observed in all cases considered, including skyrmions colliding at speeds that would bounce them back were they evolving in compactified plane. The periodic 0(3) model has no analytic solutions of degree one, so when a field configuration that resembles a single soliton is numerically evolved, it shrinks to become infinitely thin. Interestingly, such ansatz may be regarded as a soliton of unit topological charge in the context of the periodic skyrmion model. Chapter 5 closes with a summary and suggestions for future research.

The ANSI/AISC 360-10 Appendix-6 provisions provide limited guidance on the bracing requirements for beam-columns. In cases involving point (nodal) or shear panel (relative) lateral bracing only, these provisions simply sum the corresponding strength and stiffness requirements for column and beam bracing. Based on prior research evidence, it is expected that this approach is accurate to conservative when the requirements can be logically added. However, in many practical beam-column bracing situations, the requirements cannot be logically added. This is because of the importance of the brace and transverse load position through the cross-section depth, as well as the fact that both torsional and lateral restraint can be important attributes of the general bracing problem. These attributes of the bracing problem can cause the current beam-column bracing requirement predictions to be unconservative. In addition, limited guidance is available in the broader literature at the current time regarding the appropriate consideration of combined lateral and torsional bracing of I-section beams and beam-columns. Nevertheless, this situation is quite common, particularly for beam-columns, since it is rare that separate and independent lateral bracing systems would be provided for both flanges. More complete guidance is needed for the proper consideration of combined bracing of I-section beams and beam-columns in structural design. This research focuses on a reasonably comprehensive evaluation of the bracing strength and stiffness requirements for doubly-symmetric I-section beams and beam-columns using refined Finite Element Analysis (FEA) test simulation. The research builds on recent simulation studies of the basic bracing behavior of beams subjected to uniform bending. Various cases of beam members subjected to moment gradient are considered first. This is followed by a wide range of studies of beam-column members subjected to constant axial load and uniform bending as well as axial load combined with moment gradient loading. A range of unbraced lengths are considered resulting in different levels of plasticity at the member strength limit states. In addition, various bracing configurations are addressed including point (nodal) lateral, shear panel (relative) lateral, point torsional, combined point lateral and point torsional, and combined shear panel lateral and point torsional bracing.

No description available.

This study is concerned with flow and stability of thin liquid films flowing over the surface of a disc rotating about a vertical axis. The work consists of a theoretical and experimental investigation into the flow of the steady-state film, and the waves which occur on it. The theoretical model is investigated in its steady-state form (no waves present) using both asymptotic and numerical techniques. The unsteady problem is also examined, using asymptotic methods, for the inception and propagation of waves of small amplitude with respect to the mean film thickness. The experimental investigation employs a light absorption technique to obtain accurate film thickness measurements across individual three dimensional wave profiles. The results are used to test the validity of the small amplitude assumption of the theoretical model, which is found to be restrictive, and to give both qualitative and quantitative data about the large amplitude waves that are often observed.

A single tube flow heat exchanger was designed and built to thermally stress Jet A-1 with air-saturated and deoxygenated levels of dissolved oxygen over a range of fuel temperatures, pressures, and flow rates. Liquid samples of thermally degraded Jet A-1 were analyzed using various physical and optical methods to determine which methods were sensitive enough to measure compositional changes in thermally degraded liquid fuel and to correlate these changes to the measured amount of deposits produced. Temperature programmed oxidation (TPO) was shown to be successful in measuring deposit quantity and structure, while UV-visible absorption and UV-visible fluorescence were sensitive enough to quickly measure the relative population growth of large aromatic compounds that lead to deposit formation in thermally stressed Jet A-1.

A single tube flow heat exchanger was designed and built to thermally stress Jet A-1 with air-saturated and deoxygenated levels of dissolved oxygen over a range of fuel temperatures, pressures, and flow rates. Liquid samples of thermally degraded Jet A-1 were analyzed using various physical and optical methods to determine which methods were sensitive enough to measure compositional changes in thermally degraded liquid fuel and to correlate these changes to the measured amount of deposits produced. Temperature programmed oxidation (TPO) was shown to be successful in measuring deposit quantity and structure, while UV-visible absorption and UV-visible fluorescence were sensitive enough to quickly measure the relative population growth of large aromatic compounds that lead to deposit formation in thermally stressed Jet A-1.

The design of embankments usually involves a stability analysis by one or more of the various slip surface methods. A common feature of these methods is the assumption that a state of limiting plastic equilibrium exists over the surface of failure. The shape of the potential failure surface is, however, determined empirically. In recent years various refinements have been introduced in the most generally used method (the Swedish slip-circle); but these refinements have been superficial and the underlying assumptions of the method continue to be accepted, to a greater or lesser degree. (For complete introduction open document)