Games in Education and Process Development

The aim of the thesis is to devise a framework for analyzing simulation games, in particular introductory supply chain simulation games which are used in education and process development. The framework is then applied to three case examples which are introductory supply chain simulation games used at Lappeenranta University of Technology. The theoretical part of the thesis studies simulation games in the context of education and training as well as of process management. Simulation games can be seen as learning processes which comprise of briefing, micro cycle, and debriefing which includes observation and reflection as well as conceptualization. The micro cycle, i.e. the game itself, is defined through elements and characteristics. Both briefing and debriefing ought to support the micro cycle. The whole learning process needs to support learning objectives of the simulation game. Based on the analysis of the case simulation games, suggestions on how to boost the debriefing and promote long term effects of the games are made. In addition, a framework is suggested to be used in designing simulation games and characteristics of introductory supply chain simulation games are defined. They are designed for general purposes, are simple and operated manually, are multifunctional interplays, and last about 2.5 4 hours. Participants co operate during a game run and competition arises between different runs or game sessions.

Conformational Regulation of alpha2beta1 Integrin in Ligand Binding

Integrins are heterodimeric cell adhesion receptors involved in cell-cell and cell-extracellular matrix (ECM) interactions. They transmit bidirectional signals across the cell membrane. This results in a wide range of biological events from cell differentiation to apoptosis. alpha2beta1 integrin is an abundant collagen receptor expressed on the surface of several cell types. In addition to ECM ligands, alpha2beta1 integrins are bound by echovirus 1 (EV1) which uses alpha2beta1 as a receptor to initiate its life cycle in the infected cell. The aim of this thesis project was to provide further insight into the mechanisms of alpha2beta1 integrin ligand recognition and receptor activation. Collagen fibrils are the principal tensile elements of the ECM. Yet, the interaction of alpha2beta1 integrin with the fibrillar form of collagen I has received relatively little attention. This research focused on the ability of alpha2beta1 integrin to act as a receptor for type I collagen fibrils. Also the molecular requirements of the EV1 interaction with alpha2beta1 were studied. Conventionally, ligand binding has been suggested to require integrin activation and the binding may further trigger integrin signalling. Another main objective of this study was to elucidate both the inside-out and outside-in signalling mechanisms of alpha2beta1 integrin in adherent cells. The results indicated that alpha2beta1 integrin is the principal integrin-type collagen receptor for type I collagen fibrils, and alpha2beta1 may participate in the regulation of pericellular collagen fibrillogenesis. Furthermore, alpha2beta1 integrin inside-out activation appeared to be synergistically regulated by integrin clustering and conformational activation. The triggering of alpha2beta1 integrin outside-in signalling, however, was shown to require both conformational changes and clustering. In contrast to ECM ligands, EV1 appeared to take advantage of the bent, inactive form of alpha2beta1 integrin in initiating its life cycle in the cell. This research together with other recent studies, has shed light on the molecular mechanisms of integrin activation. It is becoming evident that large ligands are able to bind to the bent form of integrin, which has been previously considered to be physiologically inactive. Consequently, our understanding of the conformational modulation of integrins upon activation is changing.

Induction Motor Drive Energy Efficiency - Simulation and Analysis

A coupled system simulator, based on analytical circuit equations and a finite element method (FEM) model of the motor has been developed and it is used to analyse a frequency-converterfed industrial squirrel-cage induction motor. Two control systems that emulate the behaviour of commercial direct-torque-controlled (DTC) and vector-controlled industrial frequency converters have been studied, implemented in the simulation software and verified by extensive laboratory tests. Numerous factors that affect the operation of a variable speed drive (VSD) and its energy efficiency have been investigated, and their significance in the simulation of the VSD results has been studied. The dependency of the frequency converter, induction motor and system losses on the switching frequency is investigated by simulations and measurements at different speeds for both the vector control and the DTC. Intensive laboratory measurements have been carried out to verify the simulation results.

The Integrin Tail: A Tale of Cell Motility and Division

Integrin transmembrane receptor functions are regulated by adaptor molecules binding to their alpha and beta subunit intracellular domains, or tails, thus affecting integrin traffic and adhesion during e.g. cell motility. Interestingly, many cellular proteins function in both cell motility and cell division, thus raising the possibility that integrins might be involved in regulating the cell cycle. A thorough understanding of cell division is essential in cell biology and in human malignancies. It is well established that failures to complete cell cycle can give rise to genetically unstable cells with tumorigenic properties. Transformed cells promote the disruption of intercellular adhesions such as tight junctions, and this correlates with the onset of cell motility, invasion and unfavorable prognosis in cancer. In this study, we analyzed integrin regulation, mediated by adaptor binding to the  subunit tail, during cell motility and cell division. We revealed a novel molecular mechanism by which Rab21, through association with the integrin alpha subunits, drives integrin endosomal traffic during mitotic phases. In addition, we found indications for this finding in vivo, as RAB21 gene deletions were mapped in ovarian and prostate cancer samples. Importantly, the multinucleated phenotype of cultured ovarian cancer cells could be reverted by Rab21 overexpression. In this thesis work, we also show how the tight junction protein ZO-1 unexpectedly interacts with the 5 integrin cytoplasmic domain in the lamellipodia to promote cell motility and at the cleavage furrow to support separation of the daughter cells. The alpha5-ZO-1 complex formation was dependent on PKC which regulates ZO-1 phosphorylation and its subcellular localization. In addition, by an in situ detection method, we showed that a subset of metastatic human lung cancers expressed the alpha5beta-ZO-1 complex. Taken together, we were able to identify new molecular pathways that regulate integrin functions in an alpha tail-mediated fashion. These findings firmly suggest that genetic alterations in integrin traffic may lead to progression of tumorigenesis as a result of failed cell division. Also, the interplay of integrins and ZO-1 in forming spatially regulated adhesive structures broadens our view of crosstalk between pathways and distinct adhesive structures that can be involved in cancer cell biology.

Anchor or Accelerate – A Study on Cancer Cell Adhesion and Motility

Cell migration and adhesion to the extracellular matrix (ECM) are crucial in many biological and pathological processes such as morphogenesis, tissue repair, inflammatory responses, survival, and cancer. Cell-matrix adhesion is mediated by the integrin family of transmembrane receptors, which not only anchor cells to their surroundings, but also transmit bidirectional signalling at the cell surface and couple the ECM to the cytoskeleton. Another group of adhesion receptors are the syndecan proteoglycans, which engage the ECM and possess signalling activity in response to a variety of ligands. Cell migration is a complex process that requires spatial and temporal coordination of adhesion, cell contractility, intracellular traffic of integrins, and matrix turnover by matrix metalloproteinases (MMPs). Thus, integrins and syndecans, as well as MMPs, play essential roles in cancer cell migration and invasion. The understanding of the cooperation of syndecans and integrins was broadened in this thesis study. The results reveal that syndecan-1 functions in concert with 21 integrin in cell adhesion to collagen, whereas syndecan-4 is essential in 21 integrin-mediated matrix contraction. Finally, oncogenic K-Ras was shown to regulate 21 integrin, membrane-type 1 MMP, and syndecan-1 and -4 expression and their cooperation in cell invasion. Epithelial-mesenchymal transition (EMT) is fundamental during embryogenesis and organ development. Activation of EMT processes, including the upregulation of mesenchymal intermediate filament protein vimentin, has also been implicated in the acquisition of a malignant phenotype by epithelial cancer cells. Members of the protein kinase C (PKC) superfamily are involved in cell migration and various integrindependent cellular functions. One aim of this work was to shed light on the role of vimentin in the regulation of integrin traffic and cell motility. In addition, the mechanism by which vimentin participates in EMT was investigated. The results show that integrin recycling and motility are dependent on the PKC–mediated phosphorylation of vimentin. In addition, vimentin was found to be a positive regulator of EMT and regulate the expression of several migratory genes. Specifically, vimentin governs the expression of receptor tyrosine kinase Axl, which is implicated in tumour growth and metastasis. Taken together, the findings described in this thesis reveal novel aspects of the complex interplay between distinct cellular components: integrins, syndecans, and the vimentin cytoskeleton, which all contribute to the regulation of human cancer cell adhesion, migration, and invasion.

Tutorials for MeVEA Simulation Software

The objective of the thesis was to create three tutorials for MeVEA Simulation Software to instruct the new users to the modeling methodology used in the MeVEA Simulation Software. MeVEA Simulation Software is a real-time simulation software based on multibody dynamics. The simulation software is designed to create simulation models of complete mechatronical system. The thesis begins with a more detail description of the MeVEA Simulation Software and its components. The thesis presents the three simulation models and written theory of the steps of model creation. The first tutorial introduces the basic features which are used in most simulation models. The basic features include bodies, constrains, forces, basic hydraulics and motors. The second tutorial introduces the power transmission components, tyres and user input definitions for the different components in power transmission systems. The third tutorial introduces the definitions of two different types of collisions and collision graphics used in MeVEA Simulation Software.

Methods and Models for Accelerating Dynamic Simulation of Fluid Power Circuits

The objective of this dissertation is to improve the dynamic simulation of fluid power circuits. A fluid power circuit is a typical way to implement power transmission in mobile working machines, e.g. cranes, excavators etc. Dynamic simulation is an essential tool in developing controllability and energy-efficient solutions for mobile machines. Efficient dynamic simulation is the basic requirement for the real-time simulation. In the real-time simulation of fluid power circuits there exist numerical problems due to the software and methods used for modelling and integration. A simulation model of a fluid power circuit is typically created using differential and algebraic equations. Efficient numerical methods are required since differential equations must be solved in real time. Unfortunately, simulation software packages offer only a limited selection of numerical solvers. Numerical problems cause noise to the results, which in many cases leads the simulation run to fail. Mathematically the fluid power circuit models are stiff systems of ordinary differential equations. Numerical solution of the stiff systems can be improved by two alternative approaches. The first is to develop numerical solvers suitable for solving stiff systems. The second is to decrease the model stiffness itself by introducing models and algorithms that either decrease the highest eigenvalues or neglect them by introducing steady-state solutions of the stiff parts of the models. The thesis proposes novel methods using the latter approach. The study aims to develop practical methods usable in dynamic simulation of fluid power circuits using explicit fixed-step integration algorithms. In this thesis, twomechanisms whichmake the systemstiff are studied. These are the pressure drop approaching zero in the turbulent orifice model and the volume approaching zero in the equation of pressure build-up. These are the critical areas to which alternative methods for modelling and numerical simulation are proposed. Generally, in hydraulic power transmission systems the orifice flow is clearly in the turbulent area. The flow becomes laminar as the pressure drop over the orifice approaches zero only in rare situations. These are e.g. when a valve is closed, or an actuator is driven against an end stopper, or external force makes actuator to switch its direction during operation. This means that in terms of accuracy, the description of laminar flow is not necessary. But, unfortunately, when a purely turbulent description of the orifice is used, numerical problems occur when the pressure drop comes close to zero since the first derivative of flow with respect to the pressure drop approaches infinity when the pressure drop approaches zero. Furthermore, the second derivative becomes discontinuous, which causes numerical noise and an infinitely small integration step when a variable step integrator is used. A numerically efficient model for the orifice flow is proposed using a cubic spline function to describe the flow in the laminar and transition areas. Parameters for the cubic spline function are selected such that its first derivative is equal to the first derivative of the pure turbulent orifice flow model in the boundary condition. In the dynamic simulation of fluid power circuits, a tradeoff exists between accuracy and calculation speed. This investigation is made for the two-regime flow orifice model. Especially inside of many types of valves, as well as between them, there exist very small volumes. The integration of pressures in small fluid volumes causes numerical problems in fluid power circuit simulation. Particularly in realtime simulation, these numerical problems are a great weakness. The system stiffness approaches infinity as the fluid volume approaches zero. If fixed step explicit algorithms for solving ordinary differential equations (ODE) are used, the system stability would easily be lost when integrating pressures in small volumes. To solve the problem caused by small fluid volumes, a pseudo-dynamic solver is proposed. Instead of integration of the pressure in a small volume, the pressure is solved as a steady-state pressure created in a separate cascade loop by numerical integration. The hydraulic capacitance V/Be of the parts of the circuit whose pressures are solved by the pseudo-dynamic method should be orders of magnitude smaller than that of those partswhose pressures are integrated. The key advantage of this novel method is that the numerical problems caused by the small volumes are completely avoided. Also, the method is freely applicable regardless of the integration routine applied. The superiority of both above-mentioned methods is that they are suited for use together with the semi-empirical modelling method which necessarily does not require any geometrical data of the valves and actuators to be modelled. In this modelling method, most of the needed component information can be taken from the manufacturer’s nominal graphs. This thesis introduces the methods and shows several numerical examples to demonstrate how the proposed methods improve the dynamic simulation of various hydraulic circuits.

Functional Study of Oncogenic Transcription Factor ERG and its Signaling in Prostate Cancer

TMPRSS2–ERG is the most frequent type of genomic rearrangement present in prostate tumors, in which the 5- prime region of the TMPRSS2 gene is fused to the ERG oncogene. TMPRSS2, containing androgen response elements (AREs), is regulated by androgens in the prostate. The truncated TMPRSS2-ERG fusion transcript is overexpressed in half of the prostate cancer patients. The formation of TMPRSS2-ERG transcript is an early event in prostate carcinogenesis and previous in vivo and in vitro studies have shown ectopic ERG expression to be associated with increased cell invasion. However, the molecular function of ERG and its role in cell signaling is poorly understood. In this study, genomic rearrangement of ERG with TMPRSS2 was studied by using comparative genomic hybridization (CGH) in prostate cancer samples. The biological processes associated with the ERG oncogene expression in prostate epithelial cells were studied, and the results were compared with findings observed in clinical prostate tumor samples. The gene expression data indicated that increased WNT signaling and loss of cell adhesion were a characteristic of TMPRSS2- ERG fusion positive prostate tumor samples. Up- regulation of WNT pathway genes were present in ERG positive prostate tumors, with frizzled receptor 4 (FZD4) presenting with the highest association with ERG overexpression, as verified by quantitative reverse transcription-PCR, immunostaining, and immunoblotting in TMPRSS2-ERG positive VCaP prostate cancer cells. Furthermore, ERG and FZD4 silencing increased cell adhesion by inducing active β1-integrin and E-cadherin expression in VCaP cells. Furthermore, we found a novel inhibitor, 4-(chloromethyl) benzoyl chloride which inhibited the WNT signaling and induced similar phenotypic effects as observed after ERG or FZD4 down regulation in VCaP cells. In conclusion, this work deepens our understanding on the complex oncogenic mechanisms of ERG in prostate cancer that may help in developing drugs against TMPRSS2-ERG positive tumors.

Episodes in carbohydrate chemistry : from β-linked mannosides to glycoconjugates

Carbohydrates are one of the most abundant classes of biomolecules on earth. In the initial stages of research on carbohydrates much effort was focused on investigation and determination of the structural aspects and complex nature of individual monosaccharides. Later on, development of protective group strategies and methods for oligosaccharide synthesis became the main topics of research. Today, the methodologies developed early on are being utilized in the production of carbohydrates for biological screening events. This multidisciplinary approach has generated the new discipline of glycobiology which focuses on research related to the appearance and biological significance of carbohydrates. In more detail, studies in glycobiology have revealed the essential roles of carbohydrates in cell-cell interactions, biological recognition events, protein folding, cell growth and tumor cell metastasis. As a result of these studies, carbohydrate derived diagnostic and therapeutic agents are likely to be of growing interest in the future. In this doctoral thesis, a journey through the fundamentals of carbohydrate synthesis is presented. The research conducted on this journey was neither limited to the study of any particular phenomena nor to the addressing of a single synthetic challenge. Instead, the focus was deliberately shifted from time to time in order to broaden the scope of the thesis, to continue the learning process and to explore new areas of carbohydrate research. Throughout the work, several previously reported synthetic protocols, especially procedures related to glycosylation reactions and protective group manipulations, were evaluated, modified and utilized or rejected. The synthetic molecules targeted within this thesis were either required for biological evaluations or utilized to study phenomena occuring in larger molecules. In addition, much effort was invested in the complete structural characterization of the synthesized compounds by a combination of NMR spectroscopic techniques and spectral simulations with the PERCH-software. This thesis provides the basics of working with carbohydrate chemistry. In more detail, synthetic strategies and experimental procedures for many different reactions and guidelines for the NMR-spectroscopic characterization of oligosaccharides and glycoconjugates are provided. Therefore, the thesis should prove valuable to researchers starting their own journeys in the ever expanding field of carbohydrate chemistry.

Playing to Learn: Business Simulation Games as Leadership Learning Environments

The aim of this dissertation is to investigate if participation in business simulation gaming sessions can make different leadership styles visible and provide students with experiences beneficial for the development of leadership skills. Particularly, the focus is to describe the development of leadership styles when leading virtual teams in computer-­supported collaborative game settings and to identify the outcomes of using computer simulation games as leadership training tools. To answer to the objectives of the study, three empirical experiments were conducted to explore if participation in business simulation gaming sessions (Study I and II), which integrate face-­to-­face and virtual communication (Study III and IV), can make different leadership styles visible and provide students with experiences beneficial for the development of leadership skills. In the first experiment, a group of multicultural graduate business students (N=41) participated in gaming sessions with a computerized business simulation game (Study III). In the second experiment, a group of graduate students (N=9) participated in the training with a ‘real estate’ computer game (Study I and II). In the third experiment, a business simulation gaming session was organized for graduate students group (N=26) and the participants played the simulation game in virtual teams, which were organizationally and geographically dispersed but connected via technology (Study IV). Each team in all experiments had three to four students and students were between 22 and 25 years old. The business computer games used for the empirical experiments presented an enormous number of complex operations in which a team leader needed to make the final decisions involved in leading the team to win the game. These gaming environments were interactive;; participants interacted by solving the given tasks in the game. Thus, strategy and appropriate leadership were needed to be successful. The training was competition-­based and required implementation of leadership skills. The data of these studies consist of observations, participants’ reflective essays written after the gaming sessions, pre-­ and post-­tests questionnaires and participants’ answers to open-­ ended questions. Participants’ interactions and collaboration were observed when they played the computer games. The transcripts of notes from observations and students dialogs were coded in terms of transactional, transformational, heroic and post-­heroic leadership styles. For the data analysis of the transcribed notes from observations, content analysis and discourse analysis was implemented. The Multifactor Leadership Questionnaire (MLQ) was also utilized in the study to measure transformational and transactional leadership styles;; in addition, quantitative (one-­way repeated measures ANOVA) and qualitative data analyses have been performed. The results of this study indicate that in the business simulation gaming environment, certain leadership characteristics emerged spontaneously. Experiences about leadership varied between the teams and were dependent on the role individual students had in their team. These four studies showed that simulation gaming environment has the potential to be used in higher education to exercise the leadership styles relevant in real-­world work contexts. Further, the study indicated that given debriefing sessions, the simulation game context has much potential to benefit learning. The participants who showed interest in leadership roles were given the opportunity of developing leadership skills in practice. The study also provides evidence of unpredictable situations that participants can experience and learn from during the gaming sessions. The study illustrates the complex nature of experiences from the gaming environments and the need for the team leader and role divisions during the gaming sessions. It could be concluded that the experience of simulation game training illustrated the complexity of real life situations and provided participants with the challenges of virtual leadership experiences and the difficulties of using leadership styles in practice. As a result, the study offers playing computer simulation games in small teams as one way to exercise leadership styles in practice.

Use of preclinical and early clinical data for dose selection of a selective estrogen receptor modulator toremifene in treatment of breast cancer

In development of human medicines, it is important to predict early and accurately enough the disease and patient population to be treated as well as the effective and safe dose range of the studied medicine. This is pursued by using preclinical research models, clinical pharmacology and early clinical studies with small sample sizes. When successful, this enables effective development of medicines and reduces unnecessary exposure of healthy subjects and patients to ineffectice or harmfull doses of experimental compounds. Toremifene is a selective estrogen receptor modulator (SERM) used for treatment of breast cancer. Its development was initiated in 1980s when selection of treatment indications and doses were based on research in cell and animal models and on noncomparative clinical studies including small number of patients. Since the early development phase, the treatment indication, the patient population and the dose range were confirmed in large comparative clinical studies in patients. Based on the currently available large and long term clinical study data the aim of this study was to investigate how the early phase studies were able to predict the treatment indication, patient population and the dose range of the SERM. As a conclusion and based on the estrogen receptor mediated mechanism of action early studies were able to predict the treatment indication, target patient population and a dose range to be studied in confirmatory clinical studies. However, comparative clinical studies are needed to optimize dose selection of the SERM in treatment of breast cancer.

Thinking Outside the Box: Enhancing Science Teaching by Combining (Instead of Contrasting) Laboratory and Simulation Activities

The focus of the present work was on 10- to 12-year-old elementary school students’ conceptual learning outcomes in science in two specific inquiry-learning environments, laboratory and simulation. The main aim was to examine if it would be more beneficial to combine than contrast simulation and laboratory activities in science teaching. It was argued that the status quo where laboratories and simulations are seen as alternative or competing methods in science teaching is hardly an optimal solution to promote students’ learning and understanding in various science domains. It was hypothesized that it would make more sense and be more productive to combine laboratories and simulations. Several explanations and examples were provided to back up the hypothesis. In order to test whether learning with the combination of laboratory and simulation activities can result in better conceptual understanding in science than learning with laboratory or simulation activities alone, two experiments were conducted in the domain of electricity. In these experiments students constructed and studied electrical circuits in three different learning environments: laboratory (real circuits), simulation (virtual circuits), and simulation-laboratory combination (real and virtual circuits were used simultaneously). In order to measure and compare how these environments affected students’ conceptual understanding of circuits, a subject knowledge assessment questionnaire was administered before and after the experimentation. The results of the experiments were presented in four empirical studies. Three of the studies focused on learning outcomes between the conditions and one on learning processes. Study I analyzed learning outcomes from experiment I. The aim of the study was to investigate if it would be more beneficial to combine simulation and laboratory activities than to use them separately in teaching the concepts of simple electricity. Matched-trios were created based on the pre-test results of 66 elementary school students and divided randomly into a laboratory (real circuits), simulation (virtual circuits) and simulation-laboratory combination (real and virtual circuits simultaneously) conditions. In each condition students had 90 minutes to construct and study various circuits. The results showed that studying electrical circuits in the simulation–laboratory combination environment improved students’ conceptual understanding more than studying circuits in simulation and laboratory environments alone. Although there were no statistical differences between simulation and laboratory environments, the learning effect was more pronounced in the simulation condition where the students made clear progress during the intervention, whereas in the laboratory condition students’ conceptual understanding remained at an elementary level after the intervention. Study II analyzed learning outcomes from experiment II. The aim of the study was to investigate if and how learning outcomes in simulation and simulation-laboratory combination environments are mediated by implicit (only procedural guidance) and explicit (more structure and guidance for the discovery process) instruction in the context of simple DC circuits. Matched-quartets were created based on the pre-test results of 50 elementary school students and divided randomly into a simulation implicit (SI), simulation explicit (SE), combination implicit (CI) and combination explicit (CE) conditions. The results showed that when the students were working with the simulation alone, they were able to gain significantly greater amount of subject knowledge when they received metacognitive support (explicit instruction; SE) for the discovery process than when they received only procedural guidance (implicit instruction: SI). However, this additional scaffolding was not enough to reach the level of the students in the combination environment (CI and CE). A surprising finding in Study II was that instructional support had a different effect in the combination environment than in the simulation environment. In the combination environment explicit instruction (CE) did not seem to elicit much additional gain for students’ understanding of electric circuits compared to implicit instruction (CI). Instead, explicit instruction slowed down the inquiry process substantially in the combination environment. Study III analyzed from video data learning processes of those 50 students that participated in experiment II (cf. Study II above). The focus was on three specific learning processes: cognitive conflicts, self-explanations, and analogical encodings. The aim of the study was to find out possible explanations for the success of the combination condition in Experiments I and II. The video data provided clear evidence about the benefits of studying with the real and virtual circuits simultaneously (the combination conditions). Mostly the representations complemented each other, that is, one representation helped students to interpret and understand the outcomes they received from the other representation. However, there were also instances in which analogical encoding took place, that is, situations in which the slightly discrepant results between the representations ‘forced’ students to focus on those features that could be generalised across the two representations. No statistical differences were found in the amount of experienced cognitive conflicts and self-explanations between simulation and combination conditions, though in self-explanations there was a nascent trend in favour of the combination. There was also a clear tendency suggesting that explicit guidance increased the amount of self-explanations. Overall, the amount of cognitive conflicts and self-explanations was very low. The aim of the Study IV was twofold: the main aim was to provide an aggregated overview of the learning outcomes of experiments I and II; the secondary aim was to explore the relationship between the learning environments and students’ prior domain knowledge (low and high) in the experiments. Aggregated results of experiments I & II showed that on average, 91% of the students in the combination environment scored above the average of the laboratory environment, and 76% of them scored also above the average of the simulation environment. Seventy percent of the students in the simulation environment scored above the average of the laboratory environment. The results further showed that overall students seemed to benefit from combining simulations and laboratories regardless of their level of prior knowledge, that is, students with either low or high prior knowledge who studied circuits in the combination environment outperformed their counterparts who studied in the laboratory or simulation environment alone. The effect seemed to be slightly bigger among the students with low prior knowledge. However, more detailed inspection of the results showed that there were considerable differences between the experiments regarding how students with low and high prior knowledge benefitted from the combination: in Experiment I, especially students with low prior knowledge benefitted from the combination as compared to those students that used only the simulation, whereas in Experiment II, only students with high prior knowledge seemed to benefit from the combination relative to the simulation group. Regarding the differences between simulation and laboratory groups, the benefits of using a simulation seemed to be slightly higher among students with high prior knowledge. The results of the four empirical studies support the hypothesis concerning the benefits of using simulation along with laboratory activities to promote students’ conceptual understanding of electricity. It can be concluded that when teaching students about electricity, the students can gain better understanding when they have an opportunity to use the simulation and the real circuits in parallel than if they have only the real circuits or only a computer simulation available, even when the use of the simulation is supported with the explicit instruction. The outcomes of the empirical studies can be considered as the first unambiguous evidence on the (additional) benefits of combining laboratory and simulation activities in science education as compared to learning with laboratories and simulations alone.

Modeling of fireside deposit formation in two industrial furnaces

Fireside deposits can be found in many types of utility and industrial furnaces. The deposits in furnaces are problematic because they can reduce heat transfer, block gas paths and cause corrosion. To tackle these problems, it is vital to estimate the influence of deposits on heat transfer, to minimize deposit formation and to optimize deposit removal. It is beneficial to have a good understanding of the mechanisms of fireside deposit formation. Numerical modeling is a powerful tool for investigating the heat transfer in furnaces, and it can provide valuable information for understanding the mechanisms of deposit formation. In addition, a sub-model of deposit formation is generally an essential part of a comprehensive furnace model. This work investigates two specific processes of fireside deposit formation in two industrial furnaces. The first process is the slagging wall found in furnaces with molten deposits running on the wall. A slagging wall model is developed to take into account the two-layer structure of the deposits. With the slagging wall model, the thickness and the surface temperature of the molten deposit layer can be calculated. The slagging wall model is used to predict the surface temperature and the heat transfer to a specific section of a super-heater tube panel with the boundary condition obtained from a Kraft recovery furnace model. The slagging wall model is also incorporated into the computational fluid dynamics (CFD)-based Kraft recovery furnace model and applied on the lower furnace walls. The implementation of the slagging wall model includes a grid simplification scheme. The wall surface temperature calculated with the slagging wall model is used as the heat transfer boundary condition. Simulation of a Kraft recovery furnace is performed, and it is compared with two other cases and measurements. In the two other cases, a uniform wall surface temperature and a wall surface temperature calculated with a char bed burning model are used as the heat transfer boundary conditions. In this particular furnace, the wall surface temperatures from the three cases are similar and are in the correct range of the measurements. Nevertheless, the wall surface temperature profiles with the slagging wall model and the char bed burning model are different because the deposits are represented differently in the two models. In addition, the slagging wall model is proven to be computationally efficient. The second process is deposit formation due to thermophoresis of fine particles to the heat transfer surface. This process is considered in the simulation of a heat recovery boiler of the flash smelting process. In order to determine if the small dust particles stay on the wall, a criterion based on the analysis of forces acting on the particle is applied. Time-dependent simulation of deposit formation in the heat recovery boiler is carried out and the influence of deposits on heat transfer is investigated. The locations prone to deposit formation are also identified in the heat recovery boiler. Modeling of the two processes in the two industrial furnaces enhances the overall understanding of the processes. The sub-models developed in this work can be applied in other similar deposit formation processes with carefully-defined boundary conditions.

Unidirectional fiber-reinforced composite as an oral implant abutment material: Experimental studies of E-glass fiber/BisGMA-TEGDMA polymer in vitro

Fiber-reinforced composites (FRCs) are a new group of non-metallic biomaterials showing a growing popularity in many dental and medical applications. As an oral implant material, FRC is biocompatible in bone tissue environment. Soft tissue integration to FRC polymer material is unclear. This series of in vitro studies aimed at evaluating unidirectional E-glass FRC polymer in terms of mechanical, chemical, and biological properties in an attempt to develop a new non-metallic oral implant abutment alternative. Two different types of substrates were investigated: (a) Plain polymer (BisGMA 50%–TEGDMA 50%) and (b) Unidirectional FRC. The mechanical behavior of high fiber-density FRCs was assessed using a three-point bending test. Surface characterization was performed using scanning electron and spinning disk confocal microscopes. The surface wettability/energy was determined using sessile drop method. The blood response, including blood-clotting ability and platelet morphology was evaluated. Human gingival fibroblast cell responses - adhesion kinetics, adhesion strength, and proliferation activity - were studied in cell culture environment using routine test conditions. A novel tissue culture method was developed and used to evaluate porcine gingival tissue graft attachment and growth on the experimental composite implants. The analysis of the mechanical properties showed that there is a direct proportionality in the relationship between E-glass fiber volume fraction and toughness, modulus of elasticity, and load bearing capacity; however, flexural strength did not show significant improvement when high fiber-density FRC is used. FRCs showed moderate hydrophilic properties owing to the presence of exposed glass fibers on the polymer surface. Blood-clotting time was shorter on FRC substrates than on plain polymer. The FRC substrates also showed higher platelet activation state than plain polymer substrates. Fibroblast cell adhesion strength and proliferation rate were highly pronounced on FRCs. A tissue culture study revealed that gingival epithelium and connective tissue established an immediate close contact with both plain polymer and FRC implants. However, FRC seemed to guide epithelial migration outwards from the tissue/implant interface. Due to the anisotropic and hydrophilic nature of FRC, it can be concluded that this material enhances biological events related with soft tissue integration on oral implant surface.

Alpha- and gamma-melanocyte stimulating hormones in obesity. A study of the key central areas of metabolic regulation

The melanocortin system is an important regulator of feeding, energy metabolism,and cardiovascular function and it consists of the pro-opiomelanocortin (POMC) derived melanocyte stimulating hormones (α-, β- and γ-MSH) and their endogenous melanocortin receptors, MC1R to MC5R. In the hypothalamus, α-MSH reduces food intake, and increases energy expenditure and sympathetic tone by binding to MC4R. Mutations affecting the MC4R gene lead to obesity in mammals. On the other hand, the metabolic effects of MC3R stimulation using agonists such as the endogenously expressed γ-MSH have been less extensively explored. The main objective of this study was to investigate the long-term effects of increased melanocortin tone in key areas of metabolic regulation in the central nervous system (CNS) in order to investigate the sitespecific roles of both α-MSH and γ-MSH. The aim was to stereotaxically induce local overexpression of single melanocortin peptides using lentiviral vectors expressing α-MSH (LVi-α-MSH-EGFP) and γ-MSH (LVi-γ-MSH-EGFP). The lentiviral vectors were shown to produce a long-term overexpression and biologically active peptides in cell-based assays. The LVi-α-MSHEGFP was targeted to the arcuate nucleus in the hypothalamus of diet induced obese mice where it reduced weight gain and adiposity independently of food intake. When the nucleus tractus solitarus in the brainstem was targeted, the LVi-α-MSH-EGFP treatment was shown to cause a small decrease in adiposity, which did not impact weight development. However, the α-MSH treatment increased heart rate, which was attenuated by adrenergic receptor blockade indicative of increased sympathetic activity. The LVi-γ-MSH-EGFP was targeted to the hypothalamus where it decreased fat mass in mice eating the standard diet, but the effect was abated if animals consumed a high-fat Western type diet. When the diet induced obese mice were subjected again to the standard diet, the LVi-γ-MSH-EGFP treated animals displayed increased weight loss and reduced adiposity. These results indicate that the long-term central anti-obesity effects of α-MSH are independent of food intake. In addition, overexpression of α-MSH in the brain stem efficiently blocked the development of adiposity, but increased sympathetic tone. The evidence presented in this thesis also indicates that selective MC3R agonists such as γ-MSH could be potential therapeutics in combination with low fat diets.