Negative feedback regulation of calcineurin-dependent Prz1 transcription factor by the CaMKK-CaMK1 axis in fission yeast

Calcium signals trigger the translocation of the Prz1 transcription factor from the cytoplasm to the nucleus. The process is regulated by the calciumactivated phosphatase calcineurin, which activates Prz1 thereby maintaining active transcription during calcium signalling. When calcium signalling ceases, Prz1 is inactivated by phosphorylation and exported to the cytoplasm. In budding yeast and mammalian cells, different kinases have been reported to counter calcineurin activity and regulate nuclear export. Here, we show that the Ca2+/calmodulin-dependent kinase Cmk1 is first phosphorylated and activated by the newly identified kinase CaMKK2 homologue, Ckk2, in response to Ca2+. Then, active Cmk1 binds, phosphorylates and inactivates Prz1 transcription activity whilst at the same time cmk1 expression is enhanced by Prz1 in response to Ca2+. Furthermore, Cdc25 phosphatase is also phosphorylated by Cmk1, inducing cell cycle arrest in response to an increase in Ca2+. Moreover, cmk1 deletion shows a high tolerance to chronic exposure to Ca2+, due to the lack of cell cycle inhibition and elevated Prz1 activity. This work reveals that Cmk1 kinase activated by the newly identified Ckk2 counteracts calcineurin function by negatively regulating Prz1 activity which in turn is involved in activating cmk1 gene transcription. These results are the first insights into Cmk1 and Ckk2 function in Schizosaccharomyces pombe.

Un análisis comparativo del papel del bucle fonológico versus la agenda visoespacial en el cálculo en niños de 7-8 años = A comparative analysis of the phonological loop versus the visuo-spatial sketchpad in mental arithmetic tasks in 7-8 y.o. children

En esta investigación se ha estudiado la relación entre dos subsistemas de la memoria de trabajo (buclefonológico y agenda viso-espacial) y el rendimiento en cálculo con una muestra de 94 niños españolesde 7-8 años. Hemos administrado dos pruebas de cálculo diseñadas para este estudio y seis medidassimples de memoria de trabajo (de contenido verbal, numérico y espacial) de la «Batería de Testsde Memoria de Treball» de Pickering, Baqués y Gathercole (1999), y dos pruebas visuales complementarias.Los resultados muestran una correlación importante entre las medidas de contenido verbaly numérico y el rendimiento en cálculo. En cambio, no hemos encontrado ninguna relación con las medidasespaciales. Se concluye, por lo tanto, que en escolares españoles existe una relación importanteentre el bucle fonológico y el rendimiento en tareas de cálculo. En cambio, el rol de la agenda viso-espaciales nulo

Mutual feedback in e-portfolio assessment : an approach to the netfolio system

Peer-reviewed

Improving Evaluation and Development Capability in Verification and Validation

Validation and verification operations encounter various challenges in product development process. Requirements for increasing the development cycle pace set new requests for component development process. Verification and validation usually represent the largest activities, up to 40 50 % of R&D resources utilized. This research studies validation and verification as part of case company's component development process. The target is to define framework that can be used in improvement of the validation and verification capability evaluation and development in display module development projects. Validation and verification definition and background is studied in this research. Additionally, theories such as project management, system, organisational learning and causality is studied. Framework and key findings of this research are presented. Feedback system according of the framework is defined and implemented to the case company. This research is divided to the theory and empirical parts. Theory part is conducted in literature review. Empirical part is done in case study. Constructive methode and design research methode are used in this research A framework for capability evaluation and development was defined and developed as result of this research. Key findings of this study were that double loop learning approach with validation and verification V+ model enables defining a feedback reporting solution. Additional results, some minor changes in validation and verification process were proposed. There are a few concerns expressed on the results on validity and reliability of this study. The most important one was the selected research method and the selected model itself. The final state can be normative, the researcher may set study results before the actual study and in the initial state, the researcher may describe expectations for the study. Finally reliability of this study, and validity of this work are studied.

Feedback-related Brain Potential Activity Complies with Basic Assumptions of Associative Learning Theory

Feedback-related negativity (FRN) is an ERP component that distinguishes positive from negative feedback. FRN has been hypothesized to be the product of an error signal that may be used to adjust future behavior. In addition, associative learning models assume that the trial-to-trial learning of cueoutcome mappings involves the minimization of an error term. This study evaluated whether FRN is a possible electrophysiological correlate of this error term in a predictive learning task where human subjects were asked to learn different cueoutcome relationships. Specifically, we evaluated the sensitivity of the FRN to the course of learning when different stimuli interact or compete to become a predictor of certain outcomes. Importantly, some of these cues were blocked by more informative or predictive cues (i.e., the blocking effect). Interestingly, the present results show that both learning and blocking affect the amplitude of the FRN component. Furthermore, independent analyses of positive and negative feedback event-related signals showed that the learning effect was restricted to the ERP component elicited by positive feedback. The blocking test showed differences in the FRN magnitude between a predictive and a blocked cue. Overall, the present results show that ERPs that are related to feedback processing correspond to the main predictions of associative learning models. ■

Toimitusketjun mallinnuksen tarpeet ja rakenne LOCOMOTIVE projekstissa

Työn tavoitteena oli kuvata ja priorisoida toimitusketjun dynaamisen mallinnustyökalun vaatimukset, sekä muodostaa tämän pohjalta ohjelmistokehitystä tukeva oliomalli. Vaatimuksia selvitettiin teoreettisen tarkastelun, aiemmin toteutettujen kyselytutkimusten sekä viiden pilottitapauksen avulla. Toimitusketjun hallinta ei ole pelkästään materiaalivirtojen vaan myös näihin liittyvän informaation hallintaa. Holististen toimitusketjuongelmien mallintaminen edellyttää siis informaatiovirtojen ja niitä saatelevien ohjausmekanisemien mallintamista. Markkinoilla on selkeästi tilaa tukijärjestelmille, jotka mahdollistaisivat multidimensionaalisten - tuotto, aika, palvelu - toimitusketjuongelmien tarkastelun. Systeemidynamiikan teorian mukaisesti oliomallin lähtökohdaksi valittiin tärkeimpien takaisinkytkentäsilmukkojen mallinnus. Takaisinkytkentäsilmukoiden avulla kyetään mallintamaan kompleksisia systeemejä ajan suhteen. Mallinnetut toimitusketjujen takaisinkytkentäsilmukkat ovat operaatio-, ohjaus-, kysyntä- ja strategiasilmukka. Toimitusketjun ohjausmekanismien, sekä systeemidynamiikan perusteiden pohjalta mallinnustyökalun vaatimuksista muodostettiin oliomalli. Muodostettu oliomalli on Locomotiven - toimitusketjun mallinnustyökalun - perusta.

CFD Simulation of Two-phase and Three-phase Flows in Internal-loop Airlift

Airlift reactors are pneumatically agitated reactors that have been widely used in chemical, petrochemical, and bioprocess industries, such as fermentation and wastewater treatment. Computational Fluid Dynamics (CFD) has become more popular approach for design, scale-up and performance evaluation of such reactors. In the present work numerical simulations for internal-loop airlift reactors were performed using the transient Eulerian model with CFD package, ANSYS Fluent 12.1. The turbulence in the liquid phase is described using κ- ε the model. Global hydrodynamic parameters like gas holdup, gas velocity and liquid velocity have been investigated for a range of superficial gas velocities, both with 2D and 3D simulations. Moreover, the study of geometry and scale influence on the reactor have been considered. The results suggest that both, geometry and scale have significant effects on the hydrodynamic parameters, which may have substantial effects on the reactor performance. Grid refinement and time-step size effect have been discussed. Numerical calculations with gas-liquid-solid three-phase flow system have been carried out to investigate the effect of solid loading, solid particle size and solid density on the hydrodynamic characteristics of internal loop airlift reactor with different superficial gas velocities. It was observed that averaged gas holdup is significantly decreased with increasing slurry concentration. Simulations show that the riser gas holdup decreases with increase in solid particle diameter. In addition, it was found that the averaged solid holdup increases in the riser section with the increase of solid density. These produced results reveal that CFD have excellent potential to simulate two-phase and three-phase flow system.

Supersaturation-controlled crystallization

Identification of product requirements and quality, together with the management of production are key issues in chemical engineering. Quality control of crystalline products is part of the quality of many industrially manufactured products like paper, paintings, medicines and fertilizers. In most crystallization cases, quality is described with the size, polymorph, shape and purity of the crystal. The chemical composition, hydrodynamics and driving force, together with the operating temperature are in a key position when the properties of a crystalline product are controlled with the crystallization process. This study concentrates on managing the identified properties of a crystalline product with the control of a driving force. The controlling of the driving force can be based on the change of solubility or the change of concentration. Solubility can be changed with temperature, pressure and an antisolvent. The concentration of crystallizing compound, the solute can be changed with the evaporation of the solvent and with the addition of a reagent. The present study focuses on reagent addition and temperature change as methods of changing the level of the driving force. Three control structures for direct control of supersaturation are built, one for cooling crystallization and two for reactive crystallization. Closed loop feedback control structures are based on the measurement of the solute concentration with attenuated total reflection - Fourier transform infrared spectrometer. The details of the reagent feed are analyzed with experimental studies and with results of computational fluid dynamic simulations of the inert particle pulse in the premixer and inert particle injection to the mixing tank. Nucleation in conditions of controlled reactive crystallization is analyzed with Nielsen’s equation of homogeneous nucleation. The resulting control systems, based on regulation of supersaturation, can be used to produce the desired polymorph of an organic product. The polymorph composition of product crystals is controlled repeatably with the decision of a set value of supersaturation level.

Centralized Motion Control of a Linear Tooth Belt Drive: Analysis of the Performance and Limitations

A centralized robust position control for an electrical driven tooth belt drive is designed in this doctoral thesis. Both a cascaded control structure and a PID based position controller are discussed. The performance and the limitations of the system are analyzed and design principles for the mechanical structure and the control design are given. These design principles are also suitable for most of the motion control applications, where mechanical resonance frequencies and control loop delays are present. One of the major challenges in the design of a controller for machinery applications is that the values of the parameters in the system model (parameter uncertainty) or the system model it self (non-parametric uncertainty) are seldom known accurately in advance. In this thesis a systematic analysis of the parameter uncertainty of the linear tooth beltdrive model is presented and the effect of the variation of a single parameter on the performance of the total system is shown. The total variation of the model parameters is taken into account in the control design phase using a Quantitative Feedback Theory (QFT). The thesis also introduces a new method to analyze reference feedforward controllers applying the QFT. The performance of the designed controllers is verified by experimentalmeasurements. The measurements confirm the control design principles that are given in this thesis.

Promoting Programming Learning. Engagement, Automatic Assessment with Immediate Feedback in Visualizations

The skill of programming is a key asset for every computer science student. Many studies have shown that this is a hard skill to learn and the outcomes of programming courses have often been substandard. Thus, a range of methods and tools have been developed to assist students’ learning processes. One of the biggest fields in computer science education is the use of visualizations as a learning aid and many visualization based tools have been developed to aid the learning process during last few decades. Studies conducted in this thesis focus on two different visualizationbased tools TRAKLA2 and ViLLE. This thesis includes results from multiple empirical studies about what kind of effects the introduction and usage of these tools have on students’ opinions and performance, and what kind of implications there are from a teacher’s point of view. The results from studies in this thesis show that students preferred to do web-based exercises, and felt that those exercises contributed to their learning. The usage of the tool motivated students to work harder during their course, which was shown in overall course performance and drop-out statistics. We have also shown that visualization-based tools can be used to enhance the learning process, and one of the key factors is the higher and active level of engagement (see. Engagement Taxonomy by Naps et al., 2002). The automatic grading accompanied with immediate feedback helps students to overcome obstacles during the learning process, and to grasp the key element in the learning task. These kinds of tools can help us to cope with the fact that many programming courses are overcrowded with limited teaching resources. These tools allows us to tackle this problem by utilizing automatic assessment in exercises that are most suitable to be done in the web (like tracing and simulation) since its supports students’ independent learning regardless of time and place. In summary, we can use our course’s resources more efficiently to increase the quality of the learning experience of the students and the teaching experience of the teacher, and even increase performance of the students. There are also methodological results from this thesis which contribute to developing insight into the conduct of empirical evaluations of new tools or techniques. When we evaluate a new tool, especially one accompanied with visualization, we need to give a proper introduction to it and to the graphical notation used by tool. The standard procedure should also include capturing the screen with audio to confirm that the participants of the experiment are doing what they are supposed to do. By taken such measures in the study of the learning impact of visualization support for learning, we can avoid drawing false conclusion from our experiments. As computer science educators, we face two important challenges. Firstly, we need to start to deliver the message in our own institution and all over the world about the new – scientifically proven – innovations in teaching like TRAKLA2 and ViLLE. Secondly, we have the relevant experience of conducting teaching related experiment, and thus we can support our colleagues to learn essential know-how of the research based improvement of their teaching. This change can transform academic teaching into publications and by utilizing this approach we can significantly increase the adoption of the new tools and techniques, and overall increase the knowledge of best-practices. In future, we need to combine our forces and tackle these universal and common problems together by creating multi-national and multiinstitutional research projects. We need to create a community and a platform in which we can share these best practices and at the same time conduct multi-national research projects easily.

Feedback como estratégia de aprendizado no ensino médico

Fornecer feedback aos alunos é um importante aspecto da aprendizagem e um papel essencial dos docentes. No contexto da educação médica clínica, feedback se refere às informações que descrevem o desempenho dos alunos em determinada situação ou atividade. A habilidade de dar e receber feedback melhora os resultados da aprendizagem, uma vez que fornece a base para a aprendizagem autodirecionada e para a reflexão crítica, auxilia os alunos a corrigirem seus erros, reforça comportamentos desejáveis e mostra como o aluno pode melhorar. Apesar da evidente falta de feedback durante o curso médico, os alunos desejam e valorizam essa ferramenta construtiva, considerando-a um aspecto importante do ensino de qualidade. O feedback eficaz deve ser: assertivo, respeitoso, descritivo, oportuno e específico. Docentes e alunos deveriam ser preparados para dar e receber feedback. Coordenadores e diretores deveriam reconhecer o papel do feedback como uma importante estratégia de ensino- aprendizagem na graduação.

Feedback de usuários como subsídio para avaliação do estudante de medicina

A avaliação é fundamental para o processo ensino-aprendizagem. Diferentes métodos de avaliação e diversos atores envolvidos na avaliação podem fornecer elementos distintos, que, somados, fornecem melhor compreensão sobre a efetividade do processo educacional em suas variadas dimensões. A avaliação de habilidades e atitudes de estudantes tem recebido grande atenção recentemente. O envolvimento de pacientes no processo pode ser contributivo, pois sua perspectiva acrescenta informações ímpares. O presente estudo avaliou a aquisição de competências e habilidades de estudantes de Medicina no internato de Obstetrícia, sob o ponto de vista de gestantes. As pacientes responderam a um questionário segundo escala de Likert, com itens de avaliação divididos em habilidades de comunicação, exame físico e profissionalismo. Os resultados mostraram boa avaliação dos estudantes em geral, o que atribuímos ao sentimento de gratidão das pacientes. Algumas questões com maiores frequências de respostas negativas, porém, apontam aspectos que merecem maior atenção da escola médica pelo impacto que podem trazer à prática profissional. A perspectiva de pacientes na avaliação do estudante de Medicina poderá balizar estratégias de feedback para qualificar a formação médica.

Studies on Neuromuscular Blocking Agents and Their Antagonists During Anaesthesia

Neuromuscular blocking agents (NMBAs) are widely used in clinical anaesthesia and emergency medicine. Main objectives are to facilitate endotracheal intubation and to allow surgery by reducing muscle tone and eliminating sudden movements, which may otherwise lead to trauma and complications. The most commonly used NMBAs are non-depolarizing agents with a medium duration of action, such as rocuronium and cisatracurium. They bind to the acetylcholine receptors in the neuromuscular junction, thus inhibiting the depolarization of the postsynaptic (muscular) membrane, which is a prerequisite for muscle contraction to take place. Previously, it has been assumed that nitrous oxide (N2O), which is commonly used in combination with volatile or intravenous anaesthetics during general anaesthesia, has no effect on NMBAs. Several studies have since claimed that N2O in fact does increase the effect of NMBAs when using bolus administration of the relaxant. The effect of N2O on the infusion requirements of two NMBAs (rocuronium and cisatracurium) with completely different molecular structure and pharmacological properties was assessed. A closed-loop feedback controlled infusion of NMBA with duration of at least 90 minutes at a 90% level of neuromuscular block was used. All patients received total intravenous anaesthesia (TIVA) with propofol and remifentanil. In both studies the study group (n=35) received N2O/Oxygen and the control group (n=35) Air/Oxygen. There were no significant differences in the mean steady state infusion requirements of NMBA (rocuronium in Study I; cisatracurium in Study II) between the groups in either study. In Study III the duration of the unsafe period of recovery after reversal of rocuronium-induced neuromuscular block by using neostigmine or sugammadex as a reversal agent was analyzed. The unsafe period of recovery was defined as the time elapsed from the moment of no clinical (visual) fade in the train-of-four (TOF) sequence until an objectively measured TOF-ratio of 0.90 was achieved. The duration of these periods were 10.3 ± 5.5 and 0.3 ± 0.3 min after neostigmine and sugammadex, respectively (P < 0.001). Study IV investigated the possible effect of reversal of a rocuronium NMB by sugammadex on depth of anaesthesia as indicated by the bispectral index and entropy levels in thirty patients. Sugammadex did not affect the level of anaesthesia as determined by EEG-derived indices of anaesthetic depth such as the bispectral index and entropy.

Development of Cost Estimation with Feedback Information in EPCM Business

Target company of this study is a large machinery company, which is, inter alia, engaged in energy and pulp engineering, procurement and construction management (EPCM) supply business. The main objective of this study was to develop cost estimation of the target company by providing more accurate, reliable and up-to-date information through enterprise resource planning (ERP) system. Another objective was to find cost-effective methods to collect total cost of ownership information to support more informed supplier selection decision making. This study is primarily action-oriented, but also constructive, and it can be divided in two sections: theoretical literature review and empirical study on the abovementioned part of the target company’s business. Development of information collection is, in addition to literature review, based on nearly 30 qualitative interviews of employees at various organizational units, functions and levels at the target company. At the core of development was to make initial data more accurate, reliable and available, a necessary prerequisite for informed use of the information. Certain development suggestions and paths were presented in order to regain confidence in ERP system as information source by reorganizing work breakdown structure and by complementing mere cost information with quantitative, technical and scope information. Several methods to use the information ever more effectively were also discussed. While implementation of the development suggestions outreached the scope of this study, it was forwarded in test environment and interest groups.

AMB system for high-speed motors using automatic commissioning

The general trend towards increasing e ciency and energy density drives the industry to high-speed technologies. Active Magnetic Bearings (AMBs) are one of the technologies that allow contactless support of a rotating body. Theoretically, there are no limitations on the rotational speed. The absence of friction, low maintenance cost, micrometer precision, and programmable sti ness have made AMBs a viable choice for highdemanding applications. Along with the advances in power electronics, such as signi cantly improved reliability and cost, AMB systems have gained a wide adoption in the industry. The AMB system is a complex, open-loop unstable system with multiple inputs and outputs. For normal operation, such a system requires a feedback control. To meet the high demands for performance and robustness, model-based control techniques should be applied. These techniques require an accurate plant model description and uncertainty estimations. The advanced control methods require more e ort at the commissioning stage. In this work, a methodology is developed for an automatic commissioning of a subcritical, rigid gas blower machine. The commissioning process includes open-loop tuning of separate parts such as sensors and actuators. The next step is to apply a system identi cation procedure to obtain a model for the controller synthesis. Finally, a robust model-based controller is synthesized and experimentally evaluated in the full operating range of the system. The commissioning procedure is developed by applying only the system components available and a priori knowledge without any additional hardware. Thus, the work provides an intelligent system with a self-diagnostics feature and an automatic commissioning.