Mathematical modeling and optimal control of malaria

Malaria continues to infect millions and kill hundreds of thousands of people worldwide each year, despite over a century of research and attempts to control and eliminate this infectious disease. Challenges such as the development and spread of drug resistant malaria parasites, insecticide resistance to mosquitoes, climate change, the presence of individuals with subpatent malaria infections which normally are asymptomatic and behavioral plasticity in the mosquito hinder the prospects of malaria control and elimination. In this thesis, mathematical models of malaria transmission and control that address the role of drug resistance, immunity, iron supplementation and anemia, immigration and visitation, and the presence of asymptomatic carriers in malaria transmission are developed. A within-host mathematical model of severe Plasmodium falciparum malaria is also developed. First, a deterministic mathematical model for transmission of antimalarial drug resistance parasites with superinfection is developed and analyzed. The possibility of increase in the risk of superinfection due to iron supplementation and fortification in malaria endemic areas is discussed. The model results calls upon stakeholders to weigh the pros and cons of iron supplementation to individuals living in malaria endemic regions. Second, a deterministic model of transmission of drug resistant malaria parasites, including the inflow of infective immigrants, is presented and analyzed. The optimal control theory is applied to this model to study the impact of various malaria and vector control strategies, such as screening of immigrants, treatment of drug-sensitive infections, treatment of drug-resistant infections, and the use of insecticide-treated bed nets and indoor spraying of mosquitoes. The results of the model emphasize the importance of using a combination of all four controls tools for effective malaria intervention. Next, a two-age-class mathematical model for malaria transmission with asymptomatic carriers is developed and analyzed. In development of this model, four possible control measures are analyzed: the use of long-lasting treated mosquito nets, indoor residual spraying, screening and treatment of symptomatic, and screening and treatment of asymptomatic individuals. The numerical results show that a disease-free equilibrium can be attained if all four control measures are used. A common pitfall for most epidemiological models is the absence of real data; model-based conclusions have to be drawn based on uncertain parameter values. In this thesis, an approach to study the robustness of optimal control solutions under such parameter uncertainty is presented. Numerical analysis of the optimal control problem in the presence of parameter uncertainty demonstrate the robustness of the optimal control approach that: when a comprehensive control strategy is used the main conclusions of the optimal control remain unchanged, even if inevitable variability remains in the control profiles. The results provide a promising framework for the design of cost-effective strategies for disease control with multiple interventions, even under considerable uncertainty of model parameters. Finally, a separate work modeling the within-host Plasmodium falciparum infection in humans is presented. The developed model allows re-infection of already-infected red blood cells. The model hypothesizes that in severe malaria due to parasite quest for survival and rapid multiplication, the Plasmodium falciparum can be absorbed in the already-infected red blood cells which accelerates the rupture rate and consequently cause anemia. Analysis of the model and parameter identifiability using Markov chain Monte Carlo methods is presented.

Selective catalytic reduction of nitrogen oxides with ammonia in forced unsteady state reactors - Case based reasoning and mathematical model simulation reasoning

The application of forced unsteady-state reactors in case of selective catalytic reduction of nitrogen oxides (NOx) with ammonia (NH3) is sustained by the fact that favorable temperature and composition distributions which cannot be achieved in any steady-state regime can be obtained by means of unsteady-state operations. In a normal way of operation the low exothermicity of the selective catalytic reduction (SCR) reaction (usually carried out in the range of 280-350°C) is not enough to maintain by itself the chemical reaction. A normal mode of operation usually requires supply of supplementary heat increasing in this way the overall process operation cost. Through forced unsteady-state operation, the main advantage that can be obtained when exothermic reactions take place is the possibility of trapping, beside the ammonia, the moving heat wave inside the catalytic bed. The unsteady state-operation enables the exploitation of the thermal storage capacity of the catalyticbed. The catalytic bed acts as a regenerative heat exchanger allowing auto-thermal behaviour when the adiabatic temperature rise is low. Finding the optimum reactor configuration, employing the most suitable operation model and identifying the reactor behavior are highly important steps in order to configure a proper device for industrial applications. The Reverse Flow Reactor (RFR) - a forced unsteady state reactor - corresponds to the above mentioned characteristics and may be employed as an efficient device for the treatment of dilute pollutant mixtures. As a main disadvantage, beside its advantages, the RFR presents the 'wash out' phenomena. This phenomenon represents emissions of unconverted reactants at every switch of the flow direction. As a consequence our attention was focused on finding an alternative reactor configuration for RFR which is not affected by the incontrollable emissions of unconverted reactants. In this respect the Reactor Network (RN) was investigated. Its configuration consists of several reactors connected in a closed sequence, simulating a moving bed by changing the reactants feeding position. In the RN the flow direction is maintained in the same way ensuring uniformcatalyst exploitation and in the same time the 'wash out' phenomena is annulated. The simulated moving bed (SMB) can operate in transient mode giving practically constant exit concentration and high conversion levels. The main advantage of the reactor network operation is emphasizedby the possibility to obtain auto-thermal behavior with nearly uniformcatalyst utilization. However, the reactor network presents only a small range of switching times which allow to reach and to maintain an ignited state. Even so a proper study of the complex behavior of the RN may give the necessary information to overcome all the difficulties that can appear in the RN operation. The unsteady-state reactors complexity arises from the fact that these reactor types are characterized by short contact times and complex interaction between heat and mass transportphenomena. Such complex interactions can give rise to a remarkable complex dynamic behavior characterized by a set of spatial-temporal patterns, chaotic changes in concentration and traveling waves of heat or chemical reactivity. The main efforts of the current research studies concern the improvement of contact modalities between reactants, the possibility of thermal wave storage inside the reactor and the improvement of the kinetic activity of the catalyst used. Paying attention to the above mentioned aspects is important when higher activity even at low feeding temperatures and low emissions of unconverted reactants are the main operation concerns. Also, the prediction of the reactor pseudo or steady-state performance (regarding the conversion, selectivity and thermal behavior) and the dynamicreactor response during exploitation are important aspects in finding the optimal control strategy for the forced unsteady state catalytic tubular reactors. The design of an adapted reactor requires knowledge about the influence of its operating conditions on the overall process performance and a precise evaluation of the operating parameters rage for which a sustained dynamic behavior is obtained. An apriori estimation of the system parameters result in diminution of the computational efforts. Usually the convergence of unsteady state reactor systems requires integration over hundreds of cycles depending on the initial guess of the parameter values. The investigation of various operation models and thermal transfer strategies give reliable means to obtain recuperative and regenerative devices which are capable to maintain an auto-thermal behavior in case of low exothermic reactions. In the present research work a gradual analysis of the SCR of NOx with ammonia process in forced unsteady-state reactors was realized. The investigation covers the presentationof the general problematic related to the effect of noxious emissions in the environment, the analysis of the suitable catalysts types for the process, the mathematical analysis approach for modeling and finding the system solutions and the experimental investigation of the device found to be more suitable for the present process. In order to gain information about the forced unsteady state reactor design, operation, important system parameters and their values, mathematical description, mathematicalmethod for solving systems of partial differential equations and other specific aspects, in a fast and easy way, and a case based reasoning (CBR) approach has been used. This approach, using the experience of past similarproblems and their adapted solutions, may provide a method for gaining informations and solutions for new problems related to the forced unsteady state reactors technology. As a consequence a CBR system was implemented and a corresponding tool was developed. Further on, grooving up the hypothesis of isothermal operation, the investigation by means of numerical simulation of the feasibility of the SCR of NOx with ammonia in the RFRand in the RN with variable feeding position was realized. The hypothesis of non-isothermal operation was taken into account because in our opinion ifa commercial catalyst is considered, is not possible to modify the chemical activity and its adsorptive capacity to improve the operation butis possible to change the operation regime. In order to identify the most suitable device for the unsteady state reduction of NOx with ammonia, considering the perspective of recuperative and regenerative devices, a comparative analysis of the above mentioned two devices performance was realized. The assumption of isothermal conditions in the beginningof the forced unsteadystate investigation allowed the simplification of the analysis enabling to focus on the impact of the conditions and mode of operation on the dynamic features caused by the trapping of one reactant in the reactor, without considering the impact of thermal effect on overall reactor performance. The non-isothermal system approach has been investigated in order to point out the important influence of the thermal effect on overall reactor performance, studying the possibility of RFR and RN utilization as recuperative and regenerative devices and the possibility of achieving a sustained auto-thermal behavior in case of lowexothermic reaction of SCR of NOx with ammonia and low temperature gasfeeding. Beside the influence of the thermal effect, the influence of the principal operating parameters, as switching time, inlet flow rate and initial catalyst temperature have been stressed. This analysis is important not only because it allows a comparison between the two devices and optimisation of the operation, but also the switching time is the main operating parameter. An appropriate choice of this parameter enables the fulfilment of the process constraints. The level of the conversions achieved, the more uniform temperature profiles, the uniformity ofcatalyst exploitation and the much simpler mode of operation imposed the RN as a much more suitable device for SCR of NOx with ammonia, in usual operation and also in the perspective of control strategy implementation. Theoretical simplified models have also been proposed in order to describe the forced unsteady state reactors performance and to estimate their internal temperature and concentration profiles. The general idea was to extend the study of catalytic reactor dynamics taking into account the perspectives that haven't been analyzed yet. The experimental investigation ofRN revealed a good agreement between the data obtained by model simulation and the ones obtained experimentally.

DTC-OHJATUN TAHTIKONEKÄYTÖN PYÖRIMISNOPEUSSÄÄDÖN ANALYYSI INTEGROIDUN SIMULOINTIMALLIN AVULLA

Työssä rakennettiin integroitu simulointimalli sähkökäytölle, jonka mekaniikka koostuu joustava-akselisesta kaksimassa systeemistä. Lisäksi tarkasteltiin kyseiselle sähkökäytölle ominaisia piirteitä ja niiden aiheuttamia ongelmia eri sovelluksissa, sekä tutkittiin teollisuudessa yleisesti esiintyvän pyörimisnopeussäädön, PI-säädön, parametrien vaikutusta kyseisen mekaniikan omaaviin sähkökäyttöihin. Taajuusmuuttajalle kehiteltiin yksinkertaistettu simulointimalli, jolla pystytään pienentämään merkittävästi simuloinnin laskenta-aikaa. Vääntövärähtelyiden kompensointiin tutkittiin optimaalista tilasäätöä, jossa Kalman suotimella estimoidaan systeemin tilojen lisäksi myös kuormamomentti ja jossa nopeussäätö suunnitellaan lineaarisella neliöllisellä menetelmällä (Linear Quadratic).

Managing Subsidiary Integration During Corporate Expansion in Russia

Kansallisten rajojen yli laajentuvat yritykset kohtaavat kasvavia paineita yhtenäistää eri yksiköiden toimintatapoja, prosesseja ja järjestelmiä. Hyvin toteutettuna organisaation sisäinen integrointi voi johtaa tytäryritysten tuottavuuden parantumiseen ja strategisiin mittakaavaetuihin, kun taas huonosti toteutettuna integrointi voi johtaa lisääntyviin konflikteihin ja emoyhtiön kontrollin katoamiseen. Integroinnin kannalta Venäjälle perustettavat tytäryritykset asettavat suuria haasteita. Kasvava ja kehittyvä kansantalous on jatkuvassa muutoksessa kohti edistyneempiä ja tuottavampia toimintamalleja, mutta toisaalta yritystoiminnantaustalla vaikuttaa edelleenkin Neuvostoajan perinnöt, jotka muokkaavat yritysten johtamisrakenteita ja prosesseja. Nämä taustavaikuttajat vaikeuttavat kansainvälisen yrityksen yhtenäistämistä, mutta toisaalta tarjoavat suuria mahdollisuuksia yrityksille, jotka oppivat elämään Venäjän markkinoiden ehdoilla. Tämä tutkimus käyttää apunaan konstruktiivista tutkimustyötä ratkoakseenYIT:n Venäjälle perustettavien yritysten integrointiin liittyviä ongelmia ja mahdollisuuksia. Työn lopputuloksena syntyy oppimiseen pohjautuva integraatiostrategia ja tätä strategiaa tukeva integroinnin johtamisjärjestelmä.

Kaksiakselisen välijäähdytyksellä, välipoltolla ja rekuperaattorilla varustetun mikrokaasuturbiinin osakuormahyötysuhteen säilyvyyden optimointi

Työssä pyrittiin etsimään differentiaalievoluutioalgoritmilla kaksiakseliselle, välijäähdytyksellä, välipoltolla ja rekuperaattorilla varustetulle mikrokaasuturbiinille sellaiset kompressorien painesuhteet ja rekuperaattorin rekuperaatioaste, että saavutettaisiin mandollisimman hyvä osakuormahyötysuhteen säilyvyys. Osakuormatehon säätömenetelmäksi oli valittu pyörimisnopeussäädön ja turbiinien sisääntulolämpötilan alentamisen yhdistelmä, jossa generaattorilla varustetun akselin pyörimisnopeus sekä molempien turbiinien sisääntulolämpötilat olivat toisistaan riippumatta vapaasti säädettävissä. Työssä löydettiin optimaalinen säätömenetelmien yhdistelmä, jolla saavutetaan parempi osakuormahyötysuhteen säilyvyys, kuin millään käytetyistä menetelmistä yksinään. Lisäksi havaittiin, ettei optimaalinen säätömenetelmä merkittävästi riipu koneikolle valituista suunnittelupisteen parametreista. Osakuormahyötysuhteen säilyvyyden kannalta optimaalinen koneikko ei merkittävästi poikennut suunnittelupisteen hyötysuhteen kannalta optimaalisesta.

Adaptive Markov chain Monte Carlo and Bayesian filtering for state space models

This thesis is concerned with the state and parameter estimation in state space models. The estimation of states and parameters is an important task when mathematical modeling is applied to many different application areas such as the global positioning systems, target tracking, navigation, brain imaging, spread of infectious diseases, biological processes, telecommunications, audio signal processing, stochastic optimal control, machine learning, and physical systems. In Bayesian settings, the estimation of states or parameters amounts to computation of the posterior probability density function. Except for a very restricted number of models, it is impossible to compute this density function in a closed form. Hence, we need approximation methods. A state estimation problem involves estimating the states (latent variables) that are not directly observed in the output of the system. In this thesis, we use the Kalman filter, extended Kalman filter, Gauss–Hermite filters, and particle filters to estimate the states based on available measurements. Among these filters, particle filters are numerical methods for approximating the filtering distributions of non-linear non-Gaussian state space models via Monte Carlo. The performance of a particle filter heavily depends on the chosen importance distribution. For instance, inappropriate choice of the importance distribution can lead to the failure of convergence of the particle filter algorithm. In this thesis, we analyze the theoretical Lᵖ particle filter convergence with general importance distributions, where p ≥2 is an integer. A parameter estimation problem is considered with inferring the model parameters from measurements. For high-dimensional complex models, estimation of parameters can be done by Markov chain Monte Carlo (MCMC) methods. In its operation, the MCMC method requires the unnormalized posterior distribution of the parameters and a proposal distribution. In this thesis, we show how the posterior density function of the parameters of a state space model can be computed by filtering based methods, where the states are integrated out. This type of computation is then applied to estimate parameters of stochastic differential equations. Furthermore, we compute the partial derivatives of the log-posterior density function and use the hybrid Monte Carlo and scaled conjugate gradient methods to infer the parameters of stochastic differential equations. The computational efficiency of MCMC methods is highly depend on the chosen proposal distribution. A commonly used proposal distribution is Gaussian. In this kind of proposal, the covariance matrix must be well tuned. To tune it, adaptive MCMC methods can be used. In this thesis, we propose a new way of updating the covariance matrix using the variational Bayesian adaptive Kalman filter algorithm.

Superjumborullien rullauksen hallinta

UPM-Kymmene Oyj:n Jämsänkosken PK6:n ongelmana ovat olleet ajoittaiset pohjakatkot suurilla rullilla. Diplomityön tavoitteena oli parantaa superjumborullien rullauksen hallintaa Jagenbergin rakentamalla VariTop keskiörullaimella. Kirjallisuusosassa selvitettiin rullanmuodostumista ja erilaisia rullausteorioita. Samalla käytiin läpi paperin rullautuvuuteen vaikuttavia tekijöitä, rullausperäisten vikojen muodostumisen syitä sekä pehmeän rullaussylinterin etuja verrattuna kovaan sylinteriin. Kokeellisessa osassa suoritettiin koeajoja tuotannon pituusleikkurilla. Näistä kokeista saatujen tulosten perusteella leikkurin ajoreseptit päivitettiin vastaamaanoptimaalisinta rullarakennetta. Pehmeän rullaussylinterin etuja verrattuna kovaan rullaussylinteriin selvitettiin koeajoissa Voithin koeleikkurilla Saksan Krefeldissä. Tuloksista selvisi, että samalla ajoreseptillä rullattaessa pehmeä sylinteri antoi valmiille rullalle suuremman kovuuden. Myös paperissa olevien profiilivirheiden vaikutukset lievenivät käytettäessä pehmeää rullaussylinteriä. Istukoiden luistamisesta johtuvaa hylsyjen sisäpinnan jauhautumista on ilmennyt suurilla jumborullilla. Tämä johtuu todennäköisimmin kasvaneesta rasituksesta hylsyn sisäpinnalla, mikä on seurausta rullien kasvusta. Ratkaisuina tälle ongelmalle on mahdollinen istukan pidentäminen sekä välyksen pienentäminen istukan ja hylsyn välissä. Myös hylsyjen toimintaa testattiin rullauksessa jahuomattiin niiden täyttävän toimittajien antamat laatuarvot. Lepo- ja liikekitkalla tiedetään olevan suuri merkitys rullausperäisten vikojenmuodostumiseen. Eri lajeista lähetettiin paperinäytteitä UPM-Kymmene Oyj:n Lappeenrannan tutkimuskeskukseen kitkojen määrittämiseksi. Tulosten perusteella havaittiin luettelolajilla lepo- ja liikekitkassa merkittävä ero. Standardi SC lajilla ero oli selvästi pienempi kuin luettelolajilla. Tämä saattaa olla yksi syy luettelolajeilla ilmeneviin pohjaongelmiin.

Analysis of Active Magnet Bearing Control Software

Problems of the designing active magnet bearingcontrol are developed. The estimation controller are designed and applied to a rigid rotor. The mathematical model of the active magnet bearing controller is developed. This mathematical model is realized on a DSP. The results of this realization are analyzed. The conclusions about the digital signal processing are made.