L'objet de cette thèse est l'étude du processus métastatique par la confrontation de données in vivo chez la souris avec des modèles mathématiques. Plus précisément, des données longitudinales sur la masse métastatique totale combinées à des données IRM fournissant des informations sur le nombre et la taille des macrométastases ont été confrontées à un modèle décrivant l'évolution de la distribution en tailles des métastases par une équation aux dérivées partielles de populations structurées. La théorie sous-jacente au modèle, décrivant le processus métastatique par des métastases initiées par quelques cellules et croissant indépendamment les unes des autres, s'est révélée incapable de décrire les distributions de tailles métastatiques observées à l'IRM, suggérant la présence de phénomènes non pris en compte dans la théorie \standard" du développement métastatique. Ces résultats nous ont conduit à proposer des hypothèses expliquant les différences de distributions métastatiques entre le modèle et les données. Ces hypothèses ont été étudiées expérimentalement par nos collaborateurs biologistes mais également in silico à l'aide de modèles d'équations aux dérivées partielles décrivant la croissance de plusieurs métastases pouvant interagir spatialement. Les résultats obtenus à l'aide de notre approche de modélisation suggèrent des interactions jouant un rôle important dans la dynamique métastatique, comme l'agrégation de germes métastatiques ou l'attraction de cellules métastatiques par des foyers métastatiques déja existants. Une partie de cette thèse est également dédiée à l'analyse mathématique et numérique du nouveau modèle spatial introduit pour l'étude quantitative précédemment évoquée. Ce modèle mécanique décrit notamment l'effet de la pression sur la prolifération des cellules tumorales. Des résultats de convergence de la méthode numérique utilisée sont présentés, ainsi qu'une confrontation du modèle à des données de croissance de métastases pulmonaires. Enfin, une partie traitant des interactions métastases-microenvironnement est également présentée. Des études récentes ont en effet montré que certaines cellules progénitrices de la lignée hématopoïétique ou encore certaines cellules immunitaires pourraient jouer un r^ole important dans le développement métastatique. Au cours de cette thèse, ce phénomène appelé niche prémétastatique a été étudié dans la littérature biologique puis modélisé mathématiquement afin de mieux comprendre le rôle de cette niche dans la dynamique métastatique. / In this thesis, a quantitative study of the metastatic process in the mouse has been performed thanks to mathematical modeling. Precisely, longitudinal data of the total metastatic burden and MRI data on the macrometastatic size distribution are confronted to a mathematical model describing the metastatic process by the independent growths of metastatic foci starting from one or few cells. This \standard" theory, able to describe the dynamics of the total metastatic burden, is on the other hand unable to describe the observed metastatic size distributions. Indeed, this model predicts many small metastases, whereas the observed metastases are much larger and fewer. In order to explain these differences, we proposed two hypotheses that were not taken into account in the initial theory. In the first one, metastases that are growing in close vicinity could merge, resulting in one larger metastasis. In the second one, metastatic foci could attract arriving circulating tumor cells, resulting also in fewer foci but much larger ones. These hypotheses have been tested experimentally by our biologists collaborators, and in silico thanks to a spatial model of tumor growth. The results of this study show that the previously suggested phenomena could have a substantial impact on the number and the sizes of the metastatic foci during metastatic development. Another part of this thesis is devoted to the numerical and mathematical analysis of the previous spatial model. This model takes into account the effect of the pressure on the proliferation of tumor cells. Numerical convergence of the numerical method that has been used and data assimilation on imaging data of pulmonary metastases are presented. Finally, a last part deals with the interactions between metastasis and its supportive stroma. Recent studies shed light on the implication of hematopoietic progenitors in the formation of a permissive soil in the future metastatic site, a phenomenon so-called premetastatic niche. In this thesis, a mathematical model describing the premetastatic and metastatic dynamics is proposed to study quantitative aspects of this phenomenon.

<p>In this thesis we study a typical retailer's problem characterized by a slngle item, periodic review of inventory levels in a multi-period setting: and stochastic demands. We consider the case of full backlogging where backorders are penalized via fixed and proportional backorder costs simultaneously. This treatment of backorder costs is a nonstandard aspect of our study. The discussion begins with an introduction in Chapter 1. Next, a review of the relevant literature is provided in Chapter 2. In Chapter 3 we study the infinite horizon case which is of both theoretical and practical interest. From a theoretical point of view tile infinite horizon solution represents the limiting behavior of the finite horizon case. Solving the infinite horizon problem has also its own practical benefits since its solution is easier to compute. Our motivation to study the infinite horizon case in the first place is pragmatic. We prove that a myopic base-stock policy is optimal for the infinite horizon case, and this result provides a basis for our study. We show that the optimal myopic policy can be computed easily for the Erlang demand in Chapter 4; solve a disposal problem which arises under the myopic policy in Chapter 5, and also study in Chapters 6 and 7 the finite horizon problem for which a myopic policy is not optimal. For the finite horizon problem computation of the exact policy may require a substantial effort. From a computational point of view, there is a need for developing a method that overcomes this burden. In Chapter 6 we develop a model for such a method by restricting our attention to the class of myopic base-stock policies, and call the resulting policy the 'best myopic' policy. We discuss analytical and numerical results for the computation of the best myopic policy in Chapter 7. Finally we present a summary of our main findings in Chapter 8.</p> / Doctor of Philosophy (PhD)

<p>We explore two novel applications of stochastic optimization inspired by real-world problems. The first application involves the optimization of appointments-based service systems. The problem here is to determine an optimal schedule of start times for jobs that have random durations, and a range of potential cost structures based on common performance metrics such as customer waiting and server idling . We show that the problem can be formulated as a two-stage stochastic linear program and develop an algorithm that utilizes the problem structure to obtain a near-optimal solution. Various aspects of the problem are considered, including the effects of job sequence, dependence on cost parameters, and job duration distributions. A range of numerical experiments is provided and some resulting insights are summarized. Some simple heuristics are proposed, based on relaxations of the problem, and evidence of their effectiveness is provided. The second application relates to inventory deployment at an integrated steel manufacturer (ISM). The models presented in this case were developed for making inventory design-choice (what to carry) and lot-size (how much to carry) decisions. They were developed by working with managers from several different functional areas at a particular ISM. They are, however, applicable to other ISMs and to other continuous-process industries with similar architectures. We discuss details of the practical implementation of the models, the structure of the problems, and algorithms and heuristics for solving them. Numerical experiments illustrate the accuracy of the heuristics, and examples based on empirical data from an ISM show the advantages of using such models in practice and suggest some managerial insights.</p> / Doctor of Philosophy (PhD)

<p>The effects of pressurization on the properties of metals has long been of interest to scientists. Bridgman found that in general, the ductility (ability of the metal to deform without fracture) increased with superimposed hydrostatic pressure. Pugh et al. confirmed similar findings.</p> <p>The effects of hydrostatistic pressure on the mechanical properties of thin anisotropic zinc, heat treated and non heat treated zinc alloy sheets subjected to biaxial tension (via the circular bulge test) is investigated in this project.</p> <p>A brief look is taken into the generalized conditions for the onset of tensile plastic instability in a thin circular diaphragm bulged under superimposed hydrostatic pressure. The material is assumed to obey Hill's theory of yielding for anisotropic materials. These predictions are verified by conducting bulge tests using back pressures up to 10,000 psi. It is concluded that within the pressure range of investigation there is no detectable changes in the properties of the materials tested.</p> <p>In the appendix section a brief look is taken into the microstructure of the materials tested.</p> / Master of Engineering (ME)

<p>The project described in this thesis was to establish the instrumentation and technique for analysing stability of machine-tools against chatter by harmonic excitation. To test out the technique, two sets of experiments were performed on centre lathes:</p> <p>1) comparison of cutting stability with tour different types of boring bars, and</p> <p>2) comparison of cutting stability of a tool oriented in seven orientations in a single plane perpendicular to the spindle axis.</p> <p>The electro-dynamic exciter was used in 1) while an electro-magnetic exciter was used in 2) Data of the excitation tests were used to compute and plot the cross-receptances which indicate the limit width of cut together with the chatter frequency and the modal shapes which identify the main masses and springs of the structure. The contribution of the individual modes to the resulting degree of stability can also be obtained. Cutting tests were conducted to provide some means of checking the reliability of the excitation test results. In this report also included are the theory of vibration, theory of chatter and specification of various parts of instrumentation.</p> / Master of Engineering (ME)

<p>The Internet provides opportunity for knowledge sharing among people with similar interests (i.e., buddies). Common methods available for people to identify buddies for knowledge sharing include emails, mailing lists, chat rooms, electronic bulletin boards, and newsgroups. However, these manual buddy finding methods are time consuming and inefficient. In this thesis, we propose an agent-based buddy finding methodology based on a combination of case-based reasoning methodology and fuzzy logic technique. We performed two experiments to assess the effectiveness of our proposed methodology. The first experiment was comprised of a stock market portfolio knowledge sharing environment in which a conventional cluster analysis was used as a benchmark to assess the technical goodness of the proposed methodology in identifying the clusters of buddies. Statistical analysis showed that there was no significant ranking difference between conventional cluster analysis and the proposed buddy-finding methodology in identifying buddies. Cluster analysis requires centralized database to form buddies (clusters) with similar properties. The unique advantage of our proposed agent-based buddy finding methodology is that it can identify similar buddies in distributed as well as centralized database environments. A second experiment, in the context of sharing musical-knowledge among human subjects, was used to find out whether selection of the buddies by the proposed methodology is as good as those done by human subjects. The findings from this latter empirical test showed that the buddies found by agents are as good as the buddies found manually by humans.</p> / Doctor of Philosophy (PhD)

Digitized by Kansas Correctional Industries

The aetiology and pathogenesis of primary open angle glaucoma (POAG), the second most common cause of irreversible visual loss in the United Kingdom, remains a conundrum for contemporary ophthalmology. Evidence suggests that glaucoma is a complex disorder, where multiple genes interact with each other and with factors in the environment. However, the aetiological heterogeneity of glaucoma coupled with its varied clinical presentation and course has made the study of glaucoma genes problematic. We established the Orcades Eye Study, a cross sectional family based genetic study, to explore the inheritance of primary open angle glaucoma (POAG). As POAG is a disease of late onset and low prevalence, rather than study disease per se we chose to study quantitative traits (QTs) related to POAG, in an isolated population in the northern Scottish archipelago of Orkney. A number of factors in this population, including reduced genetic heterogeneity and more homogenous environmental effects, confer certain advantages over more admixed urban populations in complex disease gene mapping. Preliminary analysis of the procured quantitative trait data (n=256) has demonstrated that the values obtained for the POAG related QTs of intraocular pressure (IOP), central corneal thickness and a number of optic disc parameters including optic cup area, disc area, retinal nerve fiber thickness, vertical cup to disc ratio and peripapillary atrophy are not dissimilar to other published White Caucasian populations. We also found that intraocular pressure shows an increase with age and is influenced by central corneal thickness but found no relationship between IOP and gender or IOP and other ocular biometric variables including optic nerve head parameters and refractive components. Neither central corneal thickness nor optic nerve head parameters had a statistically significant relationship to age, gender or other tested ocular biometric parameters. These findings are clinically important as these factors should be taken into consideration when evaluating intraocular pressure and other ocular biometric traits in the investigation of glaucoma and other ocular diseases in the population of Orkney. Data collection is ongoing, and with time, an increased sample size and a meaningful genetic analysis, the Orcades Eye Study will hopefully identify genes and regions of the genome associated with primary open angle glaucoma susceptibility in the Scottish Population Isolate of Orkney. To our knowledge, the only other population based study which has investigated as large a number of glaucoma related QTs is the Beijing Eye Study.

Three new reconstruction methods for quantitative phase imaging, including two interrelated two-dimensional methods, called multifilter phase imaging with partially coherent light and phase optical transfer function recovery, which lead to a third three-dimensional method, called tomographic deconvolution phase microscopy, were developed in response to a growing need among biomedical end users for solutions which can be integrated on standard microscope platforms. The performance of these new methods were evaluated using modelling and simulation as well as experimentation with known test cases. In addition to the development of new methods, existing methods for quantitative phase imaging were applied to characterize the effects of manufacturing, cleaving, and fusion splicing in large-mode-area erbium- and ytterbium-doped optical fibers.

Thesis (MEng)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: The assessment of dehydration is an ever elusive golden standard, even given the plethora of hydration markers that exist to date. Many literature sources acknowledge the need for a portable device that can be used as an indicative tool for hydration. This project sought to find a solution for assessing dehydration on a micro level looking for an indication of hydration by investigating the levels of water concentration in the skin and water compartments of the body using bioelectrical impedance, stratum corneum impedance and infrared spectrometry. Two studies were conducted to evaluate the efficacy of these devices: an infield study to assess the efficacy of the devices for measuring dehydration brought on by exercise in adults and an infant study where the devices where used to assess its ability to measure dehydration in infants who have succumbed to diarrhoea. The studies showed that the devices are not applicable in measuring real time hydration in exercising subjects as sweat was a perturbing factor in the measurements. The infant study provided promising results with regards to the usage of the infrared device. It is believed that these results could spur further investigation into the field of using infrared spectrometry as a dehydration marker. Dehydration still remains to be an ever elusive standard but the importance of finding a solution to quantitatively assess hydration is a field which could benefit the general population and its importance should not be underestimated. / AFRIKAANSE OPSOMMING: Die assessering van dehidrasie is steeds 'n ontwykende goue standaard selfs gegewe die oorvloed van hidrasiemerkers wat bestaan tot op datum. Baie literatuurbronne erken egter die behoefte aan 'n draagbare toestel wat as 'n hulpmiddel kan dien vir die evaluering van die vlakke van dehidrasie. Hierdie projek streef daarna om ondersoek in te stel tot die assessering van dehidrasie op 'n mikrovlak deur die waterkonsentrasies te meet in die vel en die verskeie waterkompartemente in die liggaam via die gebruik van bio-elektriese impedansie analise, stratum corneum impedansie analise en infrarooi-spektrometrie. Twee studies is gedoen om die doeltreffendheid van die toestelle te evalueer: 'n inveldstudie wat die hidrasievlakke van volwassenes meet wat ly aan dehidrasie weens oefening en 'n studie wat dehidrasie meet in neonate wat ly aan dehidrasie weens diarree. Die studies het bewyse gelewer dat die toestelle nie effektief is met betrekking tot die meet van dehidrasie in aktiewe volwassenes nie, weens die rede dat sweet 'n verstorende faktor is. Die neonate studie het belowende resultate verskaf met betrekking tot die gebruik van die infrarooi toestel. Daar word geglo dat hierdie resultate verdere ondersoek in die veld met betrekking tot infrarooi spektrometrie as 'n hidrasie merker kan motiveer. Finale bevindinge wys dat die kwantifisering van dehidrasie steeds 'n ontwykende standaard is, maar die belangrikheid van 'n moontlike oplossing sal voordelig wees vir die wêreld se volke en moet dus nie onderskat word nie.