This thesis aims to study the theoretical complexity and empirical performance of decomposition algorithms. We focus on linear programs with a block-angular structure. Decomposition algorithms used to be the only way to solve large-scale special structured problems, in terms of memory limit and CPU time. However, with the advances in computer technology over the past few decades, many large-scale problems can now be solved simply by using some general purpose LP software, without exploiting the problems' inner structures. A question arises naturally, should we solve a structured problem with decomposition, or directly solve it as a whole? We try to understand how a problem's characteristics influence its computational performance, and compare the relative efficiency of algorithms with and without decomposition. Two comparisons are conducted in our research: first, the Dantzig-Wolfe decomposition method (DW) versus the simplex method (simplex); second, the analytic center cutting plane method (ACCPM) versus the interior point method (IPM). These comparisons fall into the two main solution approaches in linear programming: simplex-based algorithms and IPM-based algorithms. Motivated by our observations of ACCPM and DW decomposition, we devise a hybrid algorithm combining ACCPM and DW, which are the counterparts of IPM and simplex in the decomposition framework, to take the advantages of both: the quick convergence rate of IPM-based methods, as well as the accuracy of simplex-based algorithms. A large set of 316 instances is incorporated in our experiments, so that different dimensioned problems with primal or dual block-angular structures are covered to test our conclusions.

Bivariate or multivariate correlated data may be collected on a sample of unit in many applications. When the experimenters concern about the failure times of two related subjects for example paired organs or two chronic diseases, the bivariate binary data is often acquired. This type of data consists of a observation point x and indicators which represent whether the failure times happened before or after the observation point. In this work, the observed bivariate data can be written with the following form {x, £_1=I(X1≤ x), £_2=I(X2≤ x)}.The corresponding optimal design problems for parameter estimation under this type of bivariate data are discussed. For this kind of the multivariate responses with explanatory variables, their marginal distributions may be from different distributions. Copula model is a way to formulate the relationship of these responses, and the association between pairs of responses. Copula models for bivariate binary data are considered useful in practice due to its flexibility. In this dissertation for bivariate binary data, the marginal functions are assumed from exponential or Weibull distributions and two assumptions, independent or correlated, about the joint function between variables are considered. When the bivariate binary data is assumed correlated, the Clayton copula model is used as the joint cumulative distribution function. There are few works addressed the optimal design problems for bivariate binary data with copula models. The D-optimal designs aim at minimizing the volume of the confidence ellipsoid for estimating unknown parameters including the association parameter in bivariate copula models. They are used to determine the best observation points. Moreover, the Ds-optimal designs are mainly used for estimation of the important association parameter in Clayton model. The D- and Ds-optimal designs for the above copula model are found through the general equivalence theorem with numerical algorithm. Under different model assumptions, it is observed that the number of support points for D-optimal designs is at most as the number of model parameters for the numerical results. When the difference between the marginal distributions and the association are significant, the association becomes an influential factor which makes the number of supports gets larger. The performances of estimation based on optimal designs are reasonably well by simulation studies. In survival experiments, the experimenter customarily takes trials at some specific points such as the position of the 25, 50 and 75 percentile of distributions. Hence, we consider the design efficiencies when the design points for trials are at three or four particular percentiles. Although it is common in practice to take trials at several quantile positions, the allocations of the proportion of sample size also have great influence on the experimental results. To use a locally optimal design in practice, the prior information for models or parameters are needed. In case there is not enough prior knowledge about the models or parameters, it would be more flexible to use sequential experiments to obtain information in several stages. Hence with robustness consideration, a sequential procedure is proposed by combining D- and Ds-optimal designs under independent or correlated distribution in different stages of the experiment. The simulation results based on the sequential procedure are compared with those by the one step procedures. When the optimal designs obtained from an incorrect prior parameter values or distributions, those results may have poor efficiencies. The sample mean of estimators and corresponding optimal designs obtained from sequential procedure are close to the true values and the corresponding efficiencies are close to 1. Huster (1989) analyzed the corresponding modeling problems for the paired survival data and applied to the Diabetic Retinopathy Study. Huster (1989) considered the exponential and Weibull distributions as possible marginal distributions and the Clayton model as the joint function for the Diabetic Retinopathy data. This data was conducted by the National Eye Institute to assess the effectiveness of laser photocoagulation in delaying the onset of blindness in patients with diabetic retinopathy. This study can be viewed as a prior experiment and provide the experimenter some useful guidelines for collecting data in future studies. As an application with Diabetic Retinopathy Study, we develop optimal designs to collect suitable data and information for estimating the unknown model parameters. In the second part of this work, the optimal design problems for parameter estimations are considered for the type of proportional data. The nonlinear model, based on Jorgensen (1997) and named the dispersion model, provides a flexible class of non-normal distributions and is considered in this research. It can be applied in binary or count responses, as well as proportional outcomes. For continuous proportional data where responses are confined within the interval (0,1), the simplex dispersion model is considered here. D-optimal designs obtained through the corresponding equivalence theorem and the numerical results are presented. In the development of classical optimal design theory, weighted polynomial regression models with variance functions which depend on the explanatory variable have played an important role. The problem of constructing locally D-optimal designs for simplex dispersion model can be viewed as a weighted polynomial regression model with specific variance function. Due to the complex form of the weight function in the information matrix is considered as a rational function, an approximation of the weight function and the corresponding optimal designs are obtained with different parameters. These optimal designs are compared with those using the original weight function.

Thesis (Ph.D.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Virology, Medical Microbiology and Immunology. Title from pdf file main screen (viewed on January 10, 2010). Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 106-125).

In this thesis modelling and solution methods for portfolio optimisation are presented. The investigations reported in this thesis extend the Markowitz mean-variance model to the domain of quadratic mixed integer programming (QMIP) models which are 'NP-hard' discrete optimisation problems. In addition to the modelling extensions a number of challenging aspects of solution algorithms are considered. The relative performances of sparse simplex (SSX) as well as the interior point method (IPM) are studied in detail. In particular, the roles of 'warmstart' and dual simplex are highlighted as applied to the construction of the efficient frontier which requires processing a family of problems; that is, the portfolio planning model stated in a parametric form. The method of solving QMIP models using the branch and bound algorithm is first developed; this is followed up by heuristics which improve the performance of the (discrete) solution algorithm. Some properties of the efficient frontier with discrete constraints are considered and a method of computing the discrete efficient frontier (DEF) efficiently is proposed. The computational investigation considers the efficiency and effectiveness in respect of the scale up properties of the proposed algorithm. The extensions of the real world models and the proposed solution algorithms make contribution as new knowledge.

Thesis (Ph. D.)--University of Texas Health Science Center at Houston, School of Public Health, 2007. / "December 2007." Source: Dissertation Abstracts International, Volume: 68-11, Section: B, page: 7222. Adviser: Zuber D. Mulla. Includes bibliographical references (leaves 157-169).

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 46-53).

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T19:30:32Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) JESSICA BRANDAO REOLON.pdf: 405938 bytes, checksum: 02d1f792d3137ced3fc728e0e11dcb3e (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T19:34:00Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) JESSICA BRANDAO REOLON.pdf: 405938 bytes, checksum: 02d1f792d3137ced3fc728e0e11dcb3e (MD5) / Made available in DSpace on 2016-09-22T19:34:01Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) JESSICA BRANDAO REOLON.pdf: 405938 bytes, checksum: 02d1f792d3137ced3fc728e0e11dcb3e (MD5) Previous issue date: 2016 / O herpesvírus simples (HSV) é um importante problema de saúde pública em vários países provocando ulceração genital. Dentre o arsenal terapêutico para o tratamento da infecção por HSV destaca-se o aciclovir (ACV). No entanto, este apresenta limitações no seu uso como um tempo de meia-vida curto e uma baixa solubilidade aquosa. A curcumina (CUR) é um composto natural que vem demonstrando diversas atividades terapêuticas, dentre estas a atividade antiviral, porém o seu uso por via oral também é comprometido pela baixa solubilidade em água. A encapsulação em micropartículas poliméricas (MPs) é uma abordagem farmacotécnica que podem superar as dificuldades do uso terapêutico destes dois compostos. Em vista disto, o presente trabalho visou desenvolver e caracterizar MPs pelo método de aspersão compostas por HPMC e Eudragit® RS100 como materiais poliméricos, além de manitol como adjuvante de secagem. Os resultados demonstraram que o método de preparo por aspersão (spray drying) apresentou um rendimento em torno de 50% para todas as formulações desenvolvidas, mostrando um fluxo tecnológico mais vantajoso para as partículas sem manitol. O doseamento demonstrou teores de 82 a 99% e de 81 a 94%, para ACV e CUR, respectivamente. A análise granulométrica mostrou micropartículas de tamanho micrométrico entre 8,7 e 15,3 μm. A análise morfológica evidenciou o formato esférico e confirmou o resultado das análises de tamanho. A espectroscopia na região do infravermelho mostrou uma sobreposição dos espectros obtidos pelos componentes isolados indicando boa compatibilidade entre os materiais. O perfil de liberação in vitro permitiu observar que as MPs foram capazes de controlar a liberação e melhorar a solubilidade dos compostos, destacando-se, neste quesito, as MPs compostas por HPMC. A avaliação preliminar da atividade antiviral in vitro demonstrou que a associação de ACV e CUR possui um efeito sinérgico frente ao vírus BoVH-1, sendo que as MPs foram capazes de potencializar este efeito. Neste contexto, as MPs mostraram-se sistemas promissores para a veiculação de ACV e CUR por via oral, com elevado potencial para constituir um tratamento alternativo para o herpes viral. / The herpes simplex virus (HSV), also known as human herpes virus, infects humans causing mainly genital and labial ulcerations. Among the drugs available for the treatment of HSV infection the acyclovir (ACV) is an effective antiviral drug. However this drug presents limitations in its use due to the short half-life and low water solubility. Curcumin (CUR) has demonstrated several therapeutic activities, including antiviral activity, but the oral administration of this natural compound is also compromised by low solubility. The polymeric microparticles (MP) are a pharmacotechnical approach that modifies the pharmacokinetics of the compounds and offers a possibility to overcome the difficulties of the therapeutic use. In view of this, this study aimed to develop MPs by spray drying method composed of HPMC and Eudragit® RS100 as polymeric materials, and mannitol as drying material. The results showed a yield around 50% for all developed formulations and a better technological flow rate for the particles without mannitol. The assay showed levels 82-99 and 81% to 94%, to ACV and CUR, respectively. The particle size analysis showed microparticles micrometric size between 8.7 and 15.3 micrometers. Morphological analysis showed the spherical shape and confirmed the results of size analysis. Spectroscopy in the infrared showed an overlap of the spectra obtained by the individual components indicating good compatibility between the materials. The in vitro release profile observed that the PMs were able to control the release and improved the solubility of the compounds, especially when composed of HPMC. Besides, an in vitro preliminary assessment of antiviral activity demonstrated that the combination of ACV and CUR presented a synergistic effect against BoVH-1 virus, and the MPs were able to enhance this effect. The MPs showed to be promising systems for the oral administration of ACV and CUR and could be an improved alternative treatment for viral herpes.

A fototerapia com lasers em baixa intensidade de lesões de herpes simples tem sido demonstrada clinicamente ora prevenindo a formação de vesículas, ora cicatrizando rapidamente as lesões e até aumentando o espaço de tempo entre o aparecimento dessas manifestações recorrentes. No entanto, os mecanismos básicos de ação dos lasers nessas situações são desconhecidos. Dessa forma, o objetivo do trabalho foi realizar ensaios in vitro utilizando células epiteliais em cultivo e culturas do vírus HSV-1 para estudar a interferência do laser em baixa intensidade na infecção do HSV-1. Material e Métodos: Culturas de vírus HSV-1 e de células epiteliais de macaco (linhagem Vero) infectadas ou não infectadas, crescidas em déficit nutricional (2 % de soro fetal bovino - sfb) foram utilizadas. As irradiações foram realizadas com um laser de GaAlAs (660 e 780 nm, área focal de 3,6 mm2). Uma, duas e três irradiações com intervalos de 6 h foram realizadas. Os grupos experimentais foram: Controle: não-irradiadas; 660 nm/ 3 J/cm2 (28 s); 660 nm/ 5 J/cm2 (38 s); 780 nm/ 3 J/cm2 (19 s) e, 780 nm/ 5 J/cm2 (25 s). Os efeitos citopáticos do HSV-1 e a viabilidade celular de culturas irradiadas e controles foram analisadas em 4 condições: 1) irradiação das células epiteliais não infectadas; 2) células epiteliais irradiadas antes da infecção; 3) irradiação dos vírus antes da infecção; 4) irradiação das células previamente infectadas pelo HSV-1. A viabilidade celular foi obtida pelo teste da redução do MTT e os efeitos citopáticos por observação em microscopia de luz. Resultados: A viabilidade celular de culturas irradiadas crescidas em déficit nutricional, independentemente do número de irradiações, foi sempre significantemente menor que aquela de culturas não-irradiadas e crescidas nas condições ideais de concentração de sfb (10 %). A viabilidade celular de culturas não infectadas foi similar em todos os grupos. O número de irradiações influenciou o crescimento celular positiva e proporcionalmente ao número de irradiações, exceto para o grupo 660 nm/ 3 J/cm2. Nenhuma diferença nos efeitos citopáticos foi observada entre os grupos, independentemente do número de irradiações nas 3 condições do estudo. A viabilidade celular de todos os grupos não mudou nem pela irradiação das células nem do vírus antes da inoculação nas células. A viabilidade de células infectadas antes da irradiação foi significantemente maior que o controle quando 2 irradiações foram realizadas. Conclusão: Nas condições deste estudo a radiação laser em baixa intensidade é capaz de aumentar o crescimento de células Vero crescidas em déficit, no entanto, não o suficiente para atingir o crescimento característico dessas células crescidas nas suas condições ideais. O número de irradiações influencia o crescimento das células de forma positiva e proporcional ao número de irradiações, exceto para o parâmetro 660 nm/ 3 J/cm2. A radiação laser não altera nem a susceptibilidade das células à infecção, nem a virulência do HSV-1. No entanto, ela prolonga a viabilidade das células infectadas pelo HSV-1. Efeitos positivos da fototerapia que tem sido relatados clinicamente parecem ser devido a efeitos no hospedeiro não relacionados com a replicação viral nas células infectadas. / Purpose: The clinical effects attributed to phototherapy relative to Herpes simplex lesions have included prevention of lesion formation, speeding the healing of lesions, and decreasing the frequency of recurrent lesions. The mechanisms underlying these findings have not been established yet. The aim of this in vitro study was to analyze the effect of phototherapy on epithelial cells, on HSV-1, and on infected epithelial cells in culture. Material and Methods: Cultures of HSV-1 and infected or non-infected monkey epithelial cells (Vero cell line) grown in deficient media (2 % fetal bovine serum-fbs) were used. The laser irradiation was delivered using a GaAlAs laser (660 and 780 nm, focal spot of 3.6 mm2). One, two and three irradiations with 6 hourintervals were done. The experimental groups were: Control: non-irradiated; 660 nm/3 J/cm2 (28 sec); 660 nm/5 J/cm2 (38 sec); 780 nm/3 J/cm2 (19 sec), and 780 nm/5 J/cm2 (25 sec). The HSV-1 cytopatic effects and the cell viability of irradiated cultures and controls were analyzed in four different conditions: 1) irradiation of noninfected epithelial cells; 2) epithelial cells irradiated prior infection; 3) virus irradiated prior infection; and 4) irradiation of HSV-1 infected cells. The cell viability was assessed by the reduction of the MTT test and the cytopatic effects by the light microscopy observation. Results: The cell viability of irradiated cultures grown in nutritional deficit, independently of the irradiation numbers, was always significantly smaller than that of non-irradiated cultures grown at the ideal serum concentration condition (10 %). The cell viability of non-infected cells was similar amongst the groups. The number of irradiations influenced the cell growth positively and proportionally to the number of irradiations, except for the 660 nm/3J/cm2 group. Any variation in cytopatic effects was observed amongst the experimental groups, independently of the irradiation numbers at the 3 conditions analyzed. The cell viability of all experimental groups were not altered either by irradiation of the cells or of the virus prior infection. The viability of infected cells prior irradiation was significantly higher than that of non-irradiated cultures when 2 irradiations were done. Conclusion: The experimental conditions for this study demonstrate that the phototherapy is capable of enhancing the growth of Vero cells grown under nutritional deficit conditions, however, not enough to reach the characteristic cell growth of cells grown at the ideal serum concentration condition. The number of irradiations influences the cell growth positive and proportionally, except when the parameter 660 nm and 3 J/cm2 was used. The laser radiation does not change either the susceptibility of the Vero cell to the HSV-1 infection or the HSV-1 virulence; however, prolongs the cell viability of HSV-1 infected cells. Positive benefits of phototherapy that have been reported clinically would appear to be due to host effects unrelated to viral replication in infected cells.

Syftet med denna valideringsstudie är att värdera lämpligheten att överföra den manuella analysen av aktuell infektion av Varicella Zoster Virus (aVZV IgM) och Herpes Simplex Virus (aHSV IgM) med SIEMENS Enzygnost® till en av de automatiserade analysinstrumenten EUROIMMUN Analyzer I (ELISA) eller DiaSorin LIAISON® XL. Arbetet utfördes på Klinisk Mikrobiologi i Lund. Konsekutiva serumprover för VZV IgM (n=108) och för HSV IgM (n=116) från det vardagliga flödet analyserades, tillsammans med 10 PCR- eller serokonversion-konfirmerade positiva serumprover av primär infektion VZV och HSV samt 10 positiva för reaktiverad infektion av VZV och HSV. Utöver det användes 10 serumprover konfirmerade positiva för Cytomegalovirus (CMV) respektive 10 för Epstein-Barr Virus (EBV) för att testa korsreaktionen metoderna emellan. Resultatet från VZV-valideringen i Analyzer I samt LIAISON® XL gav en överensstämmelse på 93% respektive 94% av de konsekutiva proverna, 71% respektive 86% av de primärinfekterade proverna och 75% respektive 58% av de reaktiverade proverna, samt en korsreaktivitet (positiva och gränsvärden) på totalt 33% respektive 20% av proverna. Resultatet från HSV-valideringen i Analyzer I samt LIAISON® XL gav en överensstämmelse på 84% respektive 87% av de konsekutiva proverna, 82% respektive 18% av de primärinfekterade proverna och 40% respektive 10% av de reaktiverade proverna, samt en korsreaktivitet (positiva och gränsvärden) på totalt 67% respektive 47% av proverna. Enligt rekommendation efter utförandet av denna studie så bör analysen av HSV IgM uteslutas från båda automatiserade metoder medan VZV IgM bör kontrolleras något ytterligare i Analyzer I, med förhoppning om att denna metod kan vara känsligare. / The approach of this validation study is to evaluate the adequacy for transferring the manual analysis method of ongoing infection of Varicella Zoster Virus (aVZV IgM) and Herpes Simplex Virus (aHSV IgM) with SIEMENS Enzygnost® to one of the automated instruments EUROIMMUN Analyzer I (ELISA) or DiaSorin LIAISON® XL. The study was carried out at Clinical Microbiology in Lund. Consecutive serum samples for VZV IgM (n=108) and HSV IgM (n=116) from the daily local flow of tests were analyzed, along with 10 positive for primary infection of VZV and HSV, confirmed by PCR or seroconversion, and 10 with reactivated infection of VZV and HSV. Beyond those, 10 serum samples confirmed positive for Cytomegalovirus (CMV) respectively 10 for Epstein-Barr Virus (EBV) to test the cross-reaction between the three methods. The results from the validation of VZV in Analyzer I and LIAISON® XL gave an agreement of 93% and 94% respectively in the consecutive tests, 71% and 86% respectively in the primary infected tests and 75% and 58% respectively in the reactivated tests, and also a cross-reactivity (both positive and in between-values) at a total of 33% respectively 20% of the tests. The results from the validation of HSV in Analyzer I and LIAISON® XL gave an agreement of 84% and 87% respectively in the consecutive tests, 82% and 18% respectively in the primary infected tests and 40% and 10% respectively in the reactivated tests, and also a cross-reactivity (both positive and in between-values) at a total of 67% respectively 47% of the tests. According recommendations after the performance of this study, the analysis of HSV IgM should be excluded from both of the automated methods while VZV IgM should be controlled further in Analyzer I, with hopes that this new method could be more sensitive.