Master of Science / In this thesis, a recently developed physiologically-based model of the sleep-wake switch is analyzed and applied to a variety of clinically-relevant protocols. In contrast to phenomenological models, which have dominated sleep modeling in the past, the present work demonstrates the advantages of the physiologically-based approach. Dynamical and linear stability analyses of the Phillips-Robinson sleep model allow us to create a general framework for determining its response to arbitrary external stimuli. The effects of near-stable wake and sleep ghosts on the model’s dynamics are found to have implications for arousal during sleep, sleep deprivation, and sleep inertia. Impulsive sensory stimuli during sleep are modeled modeled according to their known physiological mechanism. The predicted arousal threshold variation matches experimental data from the literature. In simulating a sleep fragmentation protocol, the model simultaneously reproduces the body temperature and arousal threshold variation measured in another existing clinical study. In the second part of the thesis, we simulate sleep deprivation by introducing a wake-effort drive that is required to maintain wakefulness during normal sleeping periods. We interpret this drive both physiologically and psychologically, and demonstrate quantitative agreement between the model’s output and experimental subjective fatigue-related data. As well as subjective fatigue, the model is simultaneously able to reproduce adrenaline excretion and body temperature variations. In the final part of the thesis, the model is extended to include the orexinergic neurons of the lateral hypothalamic area. Due to the dynamics of the orexin group, the extended model exhibits sleep inertia, and an inhibitory circadian projection to the orexin group produces a postlunch dip in performance – both of which are well-known behavioral features. Including both homeostatic and circadian inputs to the orexin group, the model produces a waking arousal variation that quantitatively matches published clinical data.

Master of Science / In this thesis, a recently developed physiologically-based model of the sleep-wake switch is analyzed and applied to a variety of clinically-relevant protocols. In contrast to phenomenological models, which have dominated sleep modeling in the past, the present work demonstrates the advantages of the physiologically-based approach. Dynamical and linear stability analyses of the Phillips-Robinson sleep model allow us to create a general framework for determining its response to arbitrary external stimuli. The effects of near-stable wake and sleep ghosts on the model’s dynamics are found to have implications for arousal during sleep, sleep deprivation, and sleep inertia. Impulsive sensory stimuli during sleep are modeled modeled according to their known physiological mechanism. The predicted arousal threshold variation matches experimental data from the literature. In simulating a sleep fragmentation protocol, the model simultaneously reproduces the body temperature and arousal threshold variation measured in another existing clinical study. In the second part of the thesis, we simulate sleep deprivation by introducing a wake-effort drive that is required to maintain wakefulness during normal sleeping periods. We interpret this drive both physiologically and psychologically, and demonstrate quantitative agreement between the model’s output and experimental subjective fatigue-related data. As well as subjective fatigue, the model is simultaneously able to reproduce adrenaline excretion and body temperature variations. In the final part of the thesis, the model is extended to include the orexinergic neurons of the lateral hypothalamic area. Due to the dynamics of the orexin group, the extended model exhibits sleep inertia, and an inhibitory circadian projection to the orexin group produces a postlunch dip in performance – both of which are well-known behavioral features. Including both homeostatic and circadian inputs to the orexin group, the model produces a waking arousal variation that quantitatively matches published clinical data.

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Remanufacturing is an important product recovery option that benefits our sustainable development. Cores, i.e. the used products/parts, are essential resources for remanufacturing. Without cores, there will not be any remanufactured products. Challenges in the core acquisition process are mainly caused by the uncertainties of: return volume, timing and core quality. Core Acquisition Management actively attempts to reduce these uncertainties and achieve a better balance of demand and return for the remanufacturers. The aim of this dissertation is to extend the knowledge of Core Acquisition Management in remanufacturing, by investigating the current status of research and industrial practice, and developing quantitative models that assist the decision making in the core acquisition process. In the dissertation, a literature review is firstly conducted to provide an overview about the current research in Core Acquisition Management. Possible further research interests, for example, more studies based on non-hybrid remanufacturing systems and imperfect substitution assumption are suggested. Through an industrial survey carried out in a fast developing remanufacturing market - China, environmental responsibility and ethical  concerns, customer orientation and strategic advantage are identified as the most important motives for the remanufacturers, while customer recognition is their most serious barrier at present. Suggestions for further improving the Chinese remanufacturing industry from the policy-makers’ perspective are provided. After the above investigation, mathematical models are then developed to assist the acquisition decisions in two aspects: to deal with the uncertainties of return volume and timing, and to deal with the uncertainties of core quality. Acquisition decision about volume and timing is firstly studied from a product life cycle perspective, where the demands for remanufactured products and the core availability change over time. According to industrial observations, the remanufacturing cost decreases with respect to its core inventory. Using optimal control theory, core acquisition and remanufacturing decisions are derived to maximize the remanufacturer's profit. It is found that besides a simple bang-bang type control policy (either collecting as much as possible, or nothing), a special form of synchronizing policy (adjusting the core collection rate with demand rate) also exists. Furthermore, the acquisition decision depends greatly on the valuation of cores, and Real Option Valuation approaches are later used to capture the value of flexibility provided by owning cores when different aspects of remanufacturing environment are random. More specifically, the value of disposing a core earlier is investigated when the price of remanufactured product is uncertain, and the impact of the correlation between stochastic demand and return is also studied. To deal with the uncertainties of core quality, refund policies with different numbers of quality classes are studied. Under the assumption of uniformly distributed quality, analytical solutions for these refund policies are derived. Numerical examples indicate that the customers’ valuation of cores is an important factor influencing the return rates and the remanufacturer’s profit. Refund policies with a small number of quality classes could already bring major advantages. Credit refund policies (without deposits) are included for comparisons. In addition, within a game theory framework, the trade-off of two types of errors of the quality inspection in a deposit-refund policy is studied. The salvage values of different cores show great influences on the remanufacturer’s policy choices. The value of information transparency about the inspection errors are studied under different conditions. Interestingly, the customer may actually return more low quality cores when the inspection accuracy is improved.

[pt] O objetivo deste trabalho é responder a seguinte pergunta: Quais são os fatores que influenciam o desempenho das firmas? Para isso, foi desenvolvido um modelo integrativo utilizando o conhecimento produzido pelas escolas consagradas posicionamento e resource-based. Esse modelo prega que o desempenho é influenciado pelos recursos da firma, pela estratégia que ela adota e pela estrutura da indústria onde ela está inserida. Por sua vez, esses três fatores são influenciados pelo ambiente que cerca a firma. Esse modelo, então, foi testado pelo método de modelagem de equações estruturais Maximum likelihood estimation (MLE) com dados simulados. Juntamente com o modelo proposto, foram testados dois modelos consagrados na literatura. Um baseado nas teorias da escola posicionamento (adaptado de Hill & Deeds, 1996), e o outro baseado nas teorias da escola resource-based (adaptado de Schroeder et al., 2002). O teste do modelo proposto mostrou que o desempenho realmente é afetado pelos três fatores citados acima, porém os indicadores de fit mostraram que o modelo não representa bem os dados utilizados para testá-lo. Em contrapartida, os dois modelos consagrados na literatura tiveram indicadores de fit bem melhores, o que mostra que eles representam melhor os dados simulados usados para fazer o teste com a técnica estatística utilizada. / [en] This study will address the proposed research question: Which factors influence the performance of the firms? To answer that question, an integrative model was developed based on the knowledge produced by the consecrated positioning school and resource-based view. This model says that the firm resources, the strategy adopted by the firm and the industry structure are the factors that influence the performance. In addition, the tree factors cited above are influenced by the environment. This model was, then, tested by the structural equation modeling method Maximum likelihood estimation (MLE) with simulated data. Altogether with the proposed model, two consecrated by literature models were tested. The first one is based on positioning school theories (adopted from Hill & Deeds, 1996) and the second one is based on resource-based view theories (adopted from Schroeder et al., 2002). The poposed model test demonstrated that, although performance is really affected by the tree factors cited above, the fit indicators showed that the model doesn´t represent very well the data used to test it. On the other hand, the two consecrated by literature models had much better fit indicators. It shows that they represent much better the simulated data used to test them with the statistical method used.

The quantification of choice has been a major area of research for behavioural scientists for several decades. This is, in part, due to the discovery of the matching law (Herrnstein, 1961) which stipulates that relative response rates on concurrently available alternatives “match” the available relative reinforcement rates. This theoretical construct has been developed to describe response allocation in more complex situations, such as concurrent chains, and successfully describes both human and non-human behaviour. Typically, this phenomenon becomes evident when behaviour settles at an asymptote after several sessions of training where contingencies are held constant, and is often called “steady-state” behaviour. However, a fundamental question still remains: what causes matching – that is, what are the underlying momentary process(es) that produce matching? Researchers have suggested that what is necessary to answer this question is to take a molecular approach to the analysis of choice behaviour, thereby assessing choice in transition (Grace, 2002a). Recently, a new model of choice acquisition has been developed that appears to offer promise. It combines two separate mechanisms; a “winner-takes-all” categorical discrimination, and a linear-operator acquisition process (Grace & McLean, 2006). The initial results suggest this model could provide an alternative explanation for what underlies matching – that two separate processes are cooccurring in the acquisition of choice behaviour – allowing response allocation to be either linear or non-linear. This thesis extends the Grace and McLean model to include the situation of response strength ‘carrying-over’ from session to session to describe the process of acquisition gradually accumulating with experience. Moreover, additional assumptions have been added to describe temporal phenomena 2 and presumed discounting of previous experience on current choice behaviour. A steady-state version of the extended model was derived and, when fitted to published data sets, describes choice behaviour equally well when compared to existing models of steady-state choice. As a consequence of these additions, the Extended Decision Model (EDM) predicts a unique response allocation pattern – choice behaviour follows a bitonic function when initial-link durations were increased and the terminallink delays were held constant. The results from experiments presented in this thesis support this prediction, whilst steady-state analyses found the EDM was parameter invariant – differences between parameters from two schedule types across several archival data sets were non-significant, while existing steady-state models had significant differences. These findings provide further support for the claim that the EDM and the Decision Model (DM) mechanisms provide unique and accurate descriptions of the molecular processes governing choice behaviour. Moreover, the implication from these results is that the underlying assumption of the EDM and DM – that choice is determined by the propensity to respond rather than conditioned reinforcement – appears to have further foundation. This challenges the assumptions of existing models of choice behaviour and presents the possibility that probabilistic approaches are perhaps more appropriate for describing response allocations than discrete estimates of relative value when contingencies change.

The quantification of choice has been a major area of research for behavioural scientists for several decades. This is, in part, due to the discovery of the matching law (Herrnstein, 1961) which stipulates that relative response rates on concurrently available alternatives “match” the available relative reinforcement rates. This theoretical construct has been developed to describe response allocation in more complex situations, such as concurrent chains, and successfully describes both human and non-human behaviour. Typically, this phenomenon becomes evident when behaviour settles at an asymptote after several sessions of training where contingencies are held constant, and is often called “steady-state” behaviour. However, a fundamental question still remains: what causes matching – that is, what are the underlying momentary process(es) that produce matching? Researchers have suggested that what is necessary to answer this question is to take a molecular approach to the analysis of choice behaviour, thereby assessing choice in transition (Grace, 2002a). Recently, a new model of choice acquisition has been developed that appears to offer promise. It combines two separate mechanisms; a “winner-takes-all” categorical discrimination, and a linear-operator acquisition process (Grace & McLean, 2006). The initial results suggest this model could provide an alternative explanation for what underlies matching – that two separate processes are cooccurring in the acquisition of choice behaviour – allowing response allocation to be either linear or non-linear. This thesis extends the Grace and McLean model to include the situation of response strength ‘carrying-over’ from session to session to describe the process of acquisition gradually accumulating with experience. Moreover, additional assumptions have been added to describe temporal phenomena 2 and presumed discounting of previous experience on current choice behaviour. A steady-state version of the extended model was derived and, when fitted to published data sets, describes choice behaviour equally well when compared to existing models of steady-state choice. As a consequence of these additions, the Extended Decision Model (EDM) predicts a unique response allocation pattern – choice behaviour follows a bitonic function when initial-link durations were increased and the terminallink delays were held constant. The results from experiments presented in this thesis support this prediction, whilst steady-state analyses found the EDM was parameter invariant – differences between parameters from two schedule types across several archival data sets were non-significant, while existing steady-state models had significant differences. These findings provide further support for the claim that the EDM and the Decision Model (DM) mechanisms provide unique and accurate descriptions of the molecular processes governing choice behaviour. Moreover, the implication from these results is that the underlying assumption of the EDM and DM – that choice is determined by the propensity to respond rather than conditioned reinforcement – appears to have further foundation. This challenges the assumptions of existing models of choice behaviour and presents the possibility that probabilistic approaches are perhaps more appropriate for describing response allocations than discrete estimates of relative value when contingencies change.

Made available in DSpace on 2014-06-11T19:31:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-12-18Bitstream added on 2014-06-13T19:20:51Z : No. of bitstreams: 1 gabriel_jef_dr_botfca.pdf: 1111786 bytes, checksum: 023e779f2eb92ebb3f9736d54080e275 (MD5) / Diversos estudos realizados com sistemas orgânicos têm mostrado a viabilidade e sustentabilidade ecológica, social e econômica desses agroecossistemas, principalmente pela sua alta capacidade de resiliência, confiabilidade, auto-suficiência e produtividade, ao contrário dos sistemas agroquímicos (convencionais) de produção. Alguns estudos concluíram que o modelo agroquímico existe pouca interação entre os fluxos de energia interna, basicamente a lavoura recebe todos os insumos para a produção não havendo aumento na “qualidade energética” interna ao sistema. No entanto, o modelo orgânico de produção apresenta maior interação entre os diferentes recursos existentes no sistema. A maior utilização de insumos externos na produção agroquímica obriga, em contra partida, maiores gastos de capital pelos produtores relativos à contratação de financiamentos para compra dos materiais, o que acaba por criar um ciclo de dependência dos produtores por financiamentos externos e aumentando consideravelmente os custos finais de produção. As atuais crises econômica e ecológica, expõem a insustentabilidade do padrão produtivo da agricultura desenvolvida de forma industrializada, evidenciando à dependência dos países do primeiro mundo na importação de commodities agrícolas produzidas no terceiro mundo, dentre elas, o café. Agravando-se o problema no Brasil que também existe uma demanda reprimida no mercado interno.Diante destes fatos desenvolveu-se uma pesquisa para identificar os problemas na região da Alta Paulista, Oeste do Estado de São Paulo, com relação aos sistemas de produção de café. Atualmente, os problemas fundamentais, de acordo com a pesquisa realizada, dos agricultores nesta região, residem: (i) na escolha de um sistema de produção corretamente viável... / Several studies of organic systems have shown the feasibility and ecological, social and economic sustainability such agroecosystems, mainly because of its high resilience, reliability, self-sufficiency and productivity, in contrary to chemicals (conventional) production. Some studies have concluded that the agrochemical model there is little interaction between the flow of internal energy, basically the crop receives all the inputs for production with no increase in energy quality inside the system. However, the organic model of production has increased interaction between the different resources in the system. The increased use of external inputs in the agrochemical production forces, although, higher capital spending by producers concerning the employment of funding for purchase of materials, which ultimately create a cycle of dependence on external financing by producers and increasing costs considerably final production. The current economic and ecological crises expose the unsustainable pattern of production of agriculture developed in an industrial manner, showing the dependence of the leading industrial countries on imports of agricultural commodities produced in the third world, among them coffee. Compounding the problem in Brazil that there is also a pent-up demand in the domestic market.Given these facts, developed a survey to identify problems in the region of High Paulista, west of the State of São Paulo, in relation to production systems of coffee. Currently, the fundamental problems, according to the survey, farmers in this region reside: (i) the choice of a production system correctly viable (environmentally, socially and economically) agrochemical or organic and (ii) the method of investment appraisal safer because resources are scarce and the risks enormous. The objectives of this study are... (Complete abstract click electronic access below)

Orientador: Elias José Simon / Banca: Odivaldo José Seraphim / Banca: Sergio Campos / Banca: Pascol Perdão Junior / Banca: Jurandir Savi / Resumo: Diversos estudos realizados com sistemas orgânicos têm mostrado a viabilidade e sustentabilidade ecológica, social e econômica desses agroecossistemas, principalmente pela sua alta capacidade de resiliência, confiabilidade, auto-suficiência e produtividade, ao contrário dos sistemas agroquímicos (convencionais) de produção. Alguns estudos concluíram que o modelo agroquímico existe pouca interação entre os fluxos de energia interna, basicamente a lavoura recebe todos os insumos para a produção não havendo aumento na "qualidade energética" interna ao sistema. No entanto, o modelo orgânico de produção apresenta maior interação entre os diferentes recursos existentes no sistema. A maior utilização de insumos externos na produção agroquímica obriga, em contra partida, maiores gastos de capital pelos produtores relativos à contratação de financiamentos para compra dos materiais, o que acaba por criar um ciclo de dependência dos produtores por financiamentos externos e aumentando consideravelmente os custos finais de produção. As atuais crises econômica e ecológica, expõem a insustentabilidade do padrão produtivo da agricultura desenvolvida de forma industrializada, evidenciando à dependência dos países do primeiro mundo na importação de commodities agrícolas produzidas no terceiro mundo, dentre elas, o café. Agravando-se o problema no Brasil que também existe uma demanda reprimida no mercado interno.Diante destes fatos desenvolveu-se uma pesquisa para identificar os problemas na região da Alta Paulista, Oeste do Estado de São Paulo, com relação aos sistemas de produção de café. Atualmente, os problemas fundamentais, de acordo com a pesquisa realizada, dos agricultores nesta região, residem: (i) na escolha de um sistema de produção corretamente viável... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract : Several studies of organic systems have shown the feasibility and ecological, social and economic sustainability such agroecosystems, mainly because of its high resilience, reliability, self-sufficiency and productivity, in contrary to chemicals (conventional) production. Some studies have concluded that the agrochemical model there is little interaction between the flow of internal energy, basically the crop receives all the inputs for production with no increase in "energy quality" inside the system. However, the organic model of production has increased interaction between the different resources in the system. The increased use of external inputs in the agrochemical production forces, although, higher capital spending by producers concerning the employment of funding for purchase of materials, which ultimately create a cycle of dependence on external financing by producers and increasing costs considerably final production. The current economic and ecological crises expose the unsustainable pattern of production of agriculture developed in an industrial manner, showing the dependence of the leading industrial countries on imports of agricultural commodities produced in the third world, among them coffee. Compounding the problem in Brazil that there is also a pent-up demand in the domestic market.Given these facts, developed a survey to identify problems in the region of High Paulista, west of the State of São Paulo, in relation to production systems of coffee. Currently, the fundamental problems, according to the survey, farmers in this region reside: (i) the choice of a production system correctly viable (environmentally, socially and economically) agrochemical or organic and (ii) the method of investment appraisal safer because resources are scarce and the risks enormous. The objectives of this study are... (Complete abstract click electronic access below) / Doutor

Les bactéries ajustent constamment leur composition moléculaire pour répondre à deschangements environnementaux. Nous nous intéressons aux systèmes de régulation métabolique et génique permettant une telle adaptation, notamment dans le contexte de la diauxie chez Escherichia coli lors de la transition de croissance sur une source de carbone riche, le glucose, à une source plus pauvre, l’acétate. Afin de modéliser de tels réseaux métaboliques, nous utilisons un formalisme cinétique approché appelé linlog et abordons les problèmes ren- contrés lors de l’estimation de paramètres. Ainsi, nous proposons une méthode d’estimationde paramètres à partir de jeux de données incomplets basée sur l’algorithme EM (“Expec- tation Maximization”) et l’appliquons au modèle linlog du métabolisme central du carbone. Nous proposons également une méthode d’analyse d’identifiabilité et de réduction de modèles non identifiables que nous appliquons ensuite sur des jeux de données simulés ou obtenus expérimentalement. Par ailleurs, nous mesurons des profils temporels d’expression de gènes impliqués dans le contrôle de la diauxie et mettons en évidence, à l’aide de modèles cinétiques développés dans ces travaux, l’importance de la contribution de l’état physiologique de la cellule dans la régulation génique. En se confrontant aux défis méthodologiques rencontrés lors du développement de modèles de réseaux métabolique et génique, cette thèse contribue aux efforts futurs portant sur l’intégration de ces deux types de réseaux dans des modèles quantitatifs. / Bacteria manage to constantly adapt their molecular composition to respond to environmentalchanges. We focus on systems of both metabolic and gene regulation that enablesuch type of adaptation, notably in the context of diauxic growth of Escherichia coli, when itshifts from glucose to acetate as a carbon source. To model a metabolic network, we use anapproximate kinetic formalism called linlog and address methodological issues encounteredwhen performing parameter estimation. We propose a maximum-likelihood method basedon Expectation Maximization for parameter estimation from incomplete datasets. We then apply it to the linlog model of central carbon metabolism. We also propose a method foridentifiability analysis and reduction of nonidentifiable models that we then apply to bothsimulated and experimental datasets. Moreover, we monitored gene expression patterns for agene network involved in the control of diauxie and highlight, by means of kinetic models developedin this study, the role of the global physiological state of the cell in regulation of geneexpression. By addressing methodological challenges encountered with models of metabolicand gene networks, this thesis contributes to future efforts integrating both types of networksinto quantitative models