Durante as últimas décadas, pesquisas em biologia do tumor com a utilização de novas técnicas de biologia molecular produziram informações em profusão, motivando e dando condições para que fossem criados novos modelos matemáticos dedicados à análise de vários aspectos de crescimento e proliferação da população celular. Alguns desses modelos têm sido dedicados à descrição e análise do regime estacionário do processo de desenvolvimento de uma população celular sob condições químicas que se consideram favorecer a aceleração ou desaceleração do crescimento da população de células tumorais. Todavia, a dinâmica temporal do crescimento de uma população de células tumorais ainda não foi analisada nesses trabalhos. Uma das dificuldades é o estabelecimento da interação entre células de múltiplos tipos que sirvam como descrição para essa dinâmica. Nosso trabalho vem preencher essa lacuna e a presente dissertação tem como objetivo a apresentação do modelo, desenvolvido por nós, de simulação da dinâmica do crescimento e proliferação celular do melanoma (câncer de baixa incidência, mas de letalidade extremamente alta) e também dos resultados obtidos através das simulações deste modelo computacional / During the last decades, tumor biology research with the use of new techniques in molecular biology resulted in a profusion of information that have given conditions and motivated the development of new mathematical models dedicated to analyzing various aspects of growth and proliferation of the cell population. Some of these models have been devoted to the description and analysis of the steady state of the development process of a cell population under chemical conditions that, in theory, promote the acceleration or deceleration of the growth of tumor cell population. However, these studies have not yet analyzed the temporal dynamics of growth of a tumor cell population. One of the difficulties is the establishment of the interaction between cells of multiple types that serve as the description for this dynamic. Our work fills this gap and this dissertation aims to present the model, developed by us, to simulate the growth dynamics and cellular proliferation of melanoma (cancer of low incidence but of extremely high lethality) and the results obtained through the simulations of this computational model

Durante as últimas décadas, pesquisas em biologia do tumor com a utilização de novas técnicas de biologia molecular produziram informações em profusão, motivando e dando condições para que fossem criados novos modelos matemáticos dedicados à análise de vários aspectos de crescimento e proliferação da população celular. Alguns desses modelos têm sido dedicados à descrição e análise do regime estacionário do processo de desenvolvimento de uma população celular sob condições químicas que se consideram favorecer a aceleração ou desaceleração do crescimento da população de células tumorais. Todavia, a dinâmica temporal do crescimento de uma população de células tumorais ainda não foi analisada nesses trabalhos. Uma das dificuldades é o estabelecimento da interação entre células de múltiplos tipos que sirvam como descrição para essa dinâmica. Nosso trabalho vem preencher essa lacuna e a presente dissertação tem como objetivo a apresentação do modelo, desenvolvido por nós, de simulação da dinâmica do crescimento e proliferação celular do melanoma (câncer de baixa incidência, mas de letalidade extremamente alta) e também dos resultados obtidos através das simulações deste modelo computacional / During the last decades, tumor biology research with the use of new techniques in molecular biology resulted in a profusion of information that have given conditions and motivated the development of new mathematical models dedicated to analyzing various aspects of growth and proliferation of the cell population. Some of these models have been devoted to the description and analysis of the steady state of the development process of a cell population under chemical conditions that, in theory, promote the acceleration or deceleration of the growth of tumor cell population. However, these studies have not yet analyzed the temporal dynamics of growth of a tumor cell population. One of the difficulties is the establishment of the interaction between cells of multiple types that serve as the description for this dynamic. Our work fills this gap and this dissertation aims to present the model, developed by us, to simulate the growth dynamics and cellular proliferation of melanoma (cancer of low incidence but of extremely high lethality) and the results obtained through the simulations of this computational model

Modeling of nonlinear systems based on special Hammerstein forms has been considered. In Hammerstein system modeling a static nonlinearity is connected to a dynamic linearity in cascade form. Fundamental contributions of this work are: 1) Introduction of Bezier curve nonlinearity representations / 2) Introduction of B-Spline curve nonlinearity representations instead of polynomials in cascade modeling. As a result, local control in nonlinear system modeling is achieved. Thus, unexpected variations of the output can be modeled more closely. As an important demonstration case, a model is developed and named as Middle East Technical University Neural Networks and Cascade Model (METU-NN-C). Application examples are chosen by considering the Near-Earth space processes, which are important for navigation, telecommunication and many other technical applications. It is demonstrated that the models developed based on the contributions of this work are especially more accurate under disturbed conditions, which are quantified by considering Space Weather parameters. Examples include forecasting of Total Electron Content (TEC), and mapping / estimation of joint angle of simple forced pendulum / estimation of joint angles of spring loaded inverted double pendulum with forced table / identification of Van der Pol oscillator / and identification of speakers. The operation performance results of the International Reference Ionosphere (IRI-2001), METU Neural Networks (METU-NN) and METU-NN-C models are compared qualitatively and quantitatively. As a numerical example, in forecasting the TEC by using the METU-NN-C having Bezier curves in nonlinearity representation, the average absolute error is 1.11 TECu. The new cascade models are shown to be promising for system designers and operators.

<p>It is essential that breast cancer be detected at its earliest stages for better prognosis. Advanced imaging techniques and systems are constantly under development and study to improve the screening and detection of breast cancer. Like every technological advancement in medical care, these techniques and systems need to be tested and verified before their clinical translation. What are currently considered the gold standard for justification of clinical translation are randomized clinical trials. Clinical trials are time-consuming, costly, and expose the population to extra irradiation in the case of x-ray imaging. Given the recent advances in computation and modeling, virtual clinical trials can be carefully designed and carried out to inform, orient, or potentially replace clinical trials given adequate validation and credibility. This dissertation elaborates on the design, implementation, and performance analysis of virtual clinical trials, which is made possible through the employment and advancement of sophisticated tools and models.</p> / Dissertation

Protection of both the wind plant and the interconnecting transmission system during short-circuit faults is imperative for maintaining system structural integrity and reliability. The circuit breakers and protective relays used to protect the power system during such events are designed based upon calculations of the current that will flow in the circuit during the fault. Sequence-network models of various power-system components, such as synchronous generators, transformers, transmission lines, etc., are often used to perform these calculations. However, there are no such models widely accepted for certain types of wind-turbine generators used in modern wind plants. The problem with developing sequence-network models of wind plants is that several different wind-turbine generator designs exist; yet, each exhibit very different short-circuit behavior. Therefore, a “one size fits all” approach is not appropriate for modeling wind plants, as has been the case for conventional power plants based on synchronous-generator technology. Further, many of the newer wind-turbine designs contain proprietary controls that affect the short-circuit behavior, and wind-turbine manufacturers are often not willing to disclose these controls. Thus, protection engineers do not have a standard or other well-established model for calculating short-circuit currents in power systems with wind plants. Therefore, the research described in this dissertation involves the development of such models for calculating short-circuit currents from wind-turbine generators. The focus of this dissertation is on the four existing wind-turbine generator designs (identified as Types 1 – 4). Only AC-transmission-interconnected wind-turbine generators are considered in this dissertation. The primary objective of this research is the development of sequence-network models, which are frequency-domain analysis tools, for each wind-turbine generator design. The time-domain behavior of each wind-turbine generator is thoroughly analyzed through transient simulations, experimental tests on scaled wind-turbine generator test beds, and solutions to the system dynamic equations. These time-domain analyses are used to support the development of the sequence-network models.

Biomass-based reducing agents have a potential to substitute fossil reducing agents in the steel industry. However, the industrial use of biomass-based reducing agents is currently in an early stage of development and has not yet been considered as a means to reduce fossil CO2 emissions, even though the use of fossil-based reducing agents for the iron and steel making cause the highest share of CO2 emissions. This master thesis presents a techno-economic analysis of a 10 MW biochar production plant integrated with sponge iron production in Höganäs. In this study, a steady-state process model was developed, where state-of-the-art research and development in biochar production for increased biochar yield was applied and adapted, using the principle of bio-oil recycle. The developed process model was used to evaluate the biochar production plant, in terms of conversion efficiency, production costs and CO2 emissions, for different process configurations. The results show that bio-oil recycle with 20 wt.% bio-oil increases the energy yield of biochar with 14%. However, it was found that bio-oil recycle increases the required heat input of pyrolysis which led to reduced plant efficiency with 4%-units and increased biochar production costs of 500-1000 SEK/ton biochar. It was found that system integration with Höganäs can reduce the production cost of biochar from over 5000 SEK/ton to under 2000 SEK/ton, where the most significant integration aspect was flue gas integration. The sensitivity analysis showed that the cost of biomass feedstock and total capital investment were the most sensitive input parameters. It was found that system integration with Höganäs was essential to achieve production costs of biochar below the price of fossil reducing agents. It was also found that co-produced bio-oil becomes a main product, essential for the economic performance of the biochar plant, even though the intended main product was the biochar.

A modelagem farmacocinética permite prever a concentração de medicamentos em diferentes tecidos do organismo humano. O desenvolvimento de modelos matemáticos é importante para verificar a adequação de certos procedimentos realizados na administração de medicamentos. O objetivo deste trabalho é o desenvolvimento de um modelo farmacocinético capaz de prever a concentração plasmática de drogas no organismo para diversas formas de infusão. Foram utilizados dois tipos de abordagem. Inicialmente, na abordagem monocompartimental, considerou-se que a droga adentra ao organismo diretamente no compartimento sanguíneo, que representa todo o corpo humano. Já na abordagem bicompartimental foram considerados os seguintes compartimentos: um representando o meio pelo qual a droga é infundida no organismo (podendo ser via gastrointestinal, transdermal ou pulmonar) e outro representando o plasma sanguíneo. Em ambos os casos, foi considerada a hipótese de concentração homogênea da droga nos compartimentos em questão. O modelo foi estruturado na forma de diagramas de blocos e a solução foi feita com a utilização da Transformada de Laplace. Foi feita a validação dos modelos e verificou-se que os resultado gerados foram muito próximos dos resultados presentes na literatura. A utilização do modelo monocompartimental permitiu comparar os resultados da administração da mesma quantidade de droga por infusão constante e por infusão periódica. A análise dos resultados gerados pelo modelo mostrou que as concentrações atingidas pelos dois métodos não são as mesmas. O modelo bicompartimental permitiu simular administrações orais e transdermais, e inalação. Foi possível prever a concentração sanguínea após a interrupção da terapia com anti-concepcionais e anti-depressivos e foi verificado o tempo necessário para que esta concentração seja atingida novamente. Foram propostos métodos para que esta concentração fosse atingida em um menor período de tempo. Outra aplicação foi na comparação entre o tratamento com comprimidos inteiros e tomados pela metade em um intervalo menor de tempo. Verificou-se que a concentração atingida é diferente mesmo que a massa ingerida seja a mesma. O modelo também foi utilizado para calcular a concentração de nicotina após o consumo de cigarros e verificou-se que, o indivíduo que fuma a cada três horas não consegue eliminar totalmente a nicotina de seu organismo. Além disso, foi possível simular a sobredosagem de um anti-inflamatório e verificar o tempo em que a concentração fica acima do nível terapêutico. Foi proposto um método para obtenção do parâmetro farmacocinético relacionado à absorção, que pode ser obtido facilmente a partir de dados presentes nas bulas dos medicamentos. Este método é muito mais simples e preciso do que e proposto na literatura, que utiliza análise gráfica e dados clínicos que não são obtidos com tanta facilidade. / The pharmacokinetic modeling can predict the concentration of drug in different tissues of the human body. The development of mathematical models is an important tool to verify the appropriateness of certain procedures performed in medication administration. The objective of this work is to develop a pharmacokinetic model able to predict the plasma concentration of drug in the body after various forms of infusion. Two approaches were used. Initially, in the one-compartment approach it was considered that the drug enters the body directly into the blood compartment, which represents the entire human body. In the two-compartment approach it was considered the following compartments: one representing the means by which the drug is infused into the body (either via the gastrointestinal tract, lung, or transdermal) and one representing the blood plasma. In both cases, it was considered homogeneous concentration of the drug in the compartments. The model was built by using block diagrams and the solution was obtained using the Laplace Transform. The model was validated by comparing its results to literature data, with very good agreement. The model allowed comparing the one-compartment constant infusion of drug in the body with the periodic infusion. The analysis of the results generated by the model showed that the concentrations achieved by these methods are not the same. The two-compartment model allowed simulating oral and transdermal administration, and inhalation. It was possible to predict blood concentration after interruption of therapy with anti-depressants and anti-conceptional drugs. The model was able to verify the time it takes to reach the former level. Methods have been proposed to achieve the same concentration in a shorter period of time. Another application was the comparison of the treatment with whole tablets and taken by half in a smaller interval of time. It was found that the concentration achieved is different even though the same mass is ingested in both cases. The model was also used to calculate the concentration of nicotine after cigarette smoking and it was found that the individual who smokes every three hours, nicotine is not entirely eliminated from body. Furthermore, it was possible to simulate overdose of an anti-inflammatory and the period of time when the concentration is above the therapeutic level. It has been proposed a method to obtain pharmacokinetic parameter related to absorption, which can be easily obtained based on data present in the drug bull. This method is much simpler and more accurate than the method proposed in the, which uses graphical analysis and clinical data that are not so easy to be obtained.

Companies that operate with critical infrastructure face a growing threat from cyber-attacks while at the same time the development in the business is rapidly moving towards a higher level of digitalization. A common type of system in critical infrastructure is supervisory control and data acquisition systems, these systems have properties that can affect their security and will therefore serve as the basis for this thesis work. To stay protected despite systems changes, companies need to make risk assessments in order to analyze how changes will affect the overall system. One thing that is important to focus on is dependencies within the system, this means that not only interaction among computers and networks are concerned but instead a more holistic view of the system need to be considered. This thesis aims to aid the process of a future risk assessment by providing a methodology to be used as a preparatory step before a risk assessment by describing the current situation of the system. This is done by evaluating two system modeling approaches, and also by proposing a number of perspectives that each provides different kind of information about the system’s dependencies. These perspectives are then evaluated by creating system models and dependency graphs, and discussing the outcomes with experts in a utility company to find out their applicability. According to the experts, the proposed perspectives have promising properties that can be useful in future risk assessments as well as in other scenarios. Moreover, the evaluated modeling approaches got positive comments during evaluation and are considered to serve their purpose.

Water shortage, water contamination, and the emerging challenges in sustainable water resources management (e.g., the likely impacts of climate change and population growth) necessitate adopting a reverse logistics approach, which is the process of moving wastewater from its typical final destination back to the water supply chain for reuse purposes. This practice not only reduces the negative impacts of wastewater on the environment, but also provides an alternative to withdrawal from natural water resources, forming a closed-loop water supply chain. However, the design of such a supply chain requires an appropriate sustainability assessment, which simultaneously accounts for economic, environmental, and social dimensions. The overall aim of this work was therefore to contribute to the literature by evaluating the impacts of water reclamation and reuse according to the triple-bottom-line sustainability indicators (i.e., economic, environmental, and social) and to develop frameworks and mathematical models to help decision-makers, stakeholders, and officials with the design of sustainable water reclamation and reuse systems. The applicability of the developed frameworks and models was examined using real case studies and hypothetical scenario analyses. This enactment also revealed the tradeoffs and thresholds associated with the design of sustainable water reclamation and reuse systems. To conquer the mentioned goal, the research was conducted in three major sections. The first part of the research was outlined to design possible scenarios for water reuse based on water reuse guidelines and evaluate the different types of end-use based on the three major dimensions of sustainability (i.e., economic, environmental and social aspects), simultaneously. The different reuse types considered include unrestricted urban reuse, agricultural reuse, indirect potable reuse (IPR), direct potable reuse (DPR), distributed unrestricted urban reuse, as well as some degree of decentralization of treatment plants for distributed unrestricted urban reuse. The tradeoff investigation and decision-making framework were demonstrated in a case study and a regret-based model was adopted as the support tool for multi-criteria decision-making. This study revealed that although increasing the degree of treatment for water reuse required implementation of advanced treatment options and it increased the implementation, operation, and maintenance (O&M) costs of the design, it increased the value of resource recovery significantly, such that it can offset the capital and O&M costs associated with the treatment and distribution for DPR. Improving the reclaimed water quality also reduced the environmental footprint (eutrophication) to almost 50% for DPR compared to the other reuse scenarios. This study revealed that the distance between the water reclamation facility and the end use plays a significant role in economic and environmental (carbon footprint) indicators. In the second part of this research, a multi-objective optimization model was developed to minimize the costs and environmental footprint (greenhouse gas emissions), and maximize social benefits (value of resource recovery) of the water reclamation systems by locating the treatment facility, allocating treatment capacity, selecting treatment technology, and allocating customers (final reclaimed water users). The expansion of the water reclamation system in Hillsborough County, Florida was evaluated to illustrate the use of the model. The impacts of population density and topography (elevation variation) of the water service area on the model outputs were also investigated. Although the centralization of treatment facilities takes advantage of the economies of scale, the results revealed that simultaneous consideration of economic and environmental indicators favored decentralization of treatment facilities in the study area. This was mainly due to the significant decrease in water transfer requirements, especially in less populous areas. Moreover, the results revealed that contribution of population density to the optimal degree of decentralization of treatment facilities was significant. In the last part of this work, hypothetical scenarios for a water service area were generated to evaluate the impacts of external variables on the design of water reclamation and reuse systems. Although the conducted sensitivity analyses in the previous sections revealed the tradeoffs and thresholds associated with the design of water reclamation systems, the concept of a hypothetical study helped with the elimination of case-specific factors and local conditions that could possibly influenced the outcomes. These factors, which were specific to the case studies (e.g., the location of candidate sites for implementation of water reclamation facilities and special population distribution patters) made barriers to the conclusions and hurdled the interpretation of findings. Two major factors, which were found to be significant among the factors influencing the design of water systems (i.e., elevation variation and population density), were selected for the evaluation. Accordingly, three different topographies (i.e., flat region, medium elevation variation, and hilly) and three types of population density (i.e., low, medium, and high) were considered for the design of hypothetical cases and the previous model developed in the second section was modified and used to evaluate the impacts. The results revealed that although decentralization of water reclamation facilities decreases the costs and environmental impacts associated with water transfer phase (i.e., wastewater collection and reclaimed water distribution), there were tradeoffs between the impacts of decentralization of treatment plants and the benefits from economies of scale for treatment. The results showed that when the population density is high and there is moderate to high elevation variations in the water service area, decentralization of treatment facilities is the beneficiary option. However, if the population density is low, economies of scale for treatment becomes more influential and lower degrees of decentralization of treatment facilities is preferred.

Aus der Einführung "Kreative Ideen sind die Grundlage für Unternehmen, um eigene Produkte an sich verändernde Marktbedingungen anzupassen, neue Möglichkeiten zu nutzen und auf dem Markt zu bestehen (Shalley et al. 2004). Organisationen versuchen deshalb, kreativitätsfördernde Arbeitsbedingungen zu schaffen, indem die Unternehmenskultur und Arbeitsumgebungen entsprechend gestaltet oder spezielle Werkzeuge zur Verfügung gestellt werden. Ein im Produktentwicklungsprozess häufig eingesetztes Werkzeug ist das parametrisch assoziative CAD-System (Computer-Aided Design). Die effiziente Bedienung einer umfangreichen WIMP (Window, Icon, Menu, Pointing)- basierten Software muss durch umfangreiche Schulungen erlernt und regelmäßig angewendet werden, um die Modellierfähigkeiten zu erhalten. Die zur Bedienung erforderliche kognitive Leistung führt häufig zur Beeinträchtigung der Kreativität eines Konstruktionsingenieurs (Chandrasegaran et al. 2013), v. a. bei wenig geübten Nutzergruppen. Am Übergang zwischen Konzeptphase und der frühen Entwurfsphase (Arbeitsabschnitt 5 der VDI 2221) wird deshalb vorwiegend mit Skizzen und noch nicht im parametrischen CAD-System gearbeitet (VDI 2223 2004). Für die Erstellung der Vorentwürfe wäre es im Sinne des „Frontloading“ jedoch wünschenswert, früh erste rechnergestützte Methoden zur Gestaltung einsetzen zu können. Durch den Einsatz von virtueller Realität (VR) eröffnet sich die Möglichkeit zur Entwicklung intuitiver Interaktionsmethoden, die eventuell neue Modellierstrategien ermöglichen. Diese erlauben dem Produktentwickler, natürlich mit den virtuellen Modellen umzugehen. Durch die im Vergleich zum parametrisch assoziativen CAD-System intuitive Bedienung würde die Kreativität bei der groben Gestaltung der Vorentwürfe weniger eingeschränkt. ..."