Formal development and quantitative verification of dependable systems

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System-level characterization of Th2 cell development and immune cell responses to ZnO and TiO2 nanoparticles

Asthma and allergy are common diseases and their prevalence is increasing. One of the hypotheses that explains this trend is exposure to inhalable chemicals such as traffi c-related air pollution. Epidemiological research supports this theory, as a correlation between environmental chemicals and allergic respiratory diseases has been found. In addition to ambient airborne particles, one may be exposed to engineered nanosized materials that are actively produced due to their favorable physico-chemical properties compared to their bulk size counterparts. On the cellular level, improper activity of T helper (Th) cells has been connected to allergic reactions. Th cells can differentiate into functionally different effector subsets, which are identifi ed according to their characteristic cytokine profi les resulting in specifi c ability to communicate with other cells. Th2 cells activate humoral immunity and stimulate eradication of extracellular pathogens. However, persistent predominance of Th2 cells is involved in a development of number of allergic diseases. The cytokine environment at the time of antigen recognition is the major factor determining the polarization of a naïve Th cell. Th2 cell differentiation is initiated by IL4, which signals via transcription factor STAT6. Although the importance of this pathway has been evaluated in the mouse studies, the signaling components involved have been largely unknown. The aim of this thesis was to identify molecules, which are under the control of IL4 and STAT6 in Th cells. This was done by using system-level analysis of STAT6 target genes at genome, mRNA and protein level resulting in identifi cation of various genes previously not connected to Th2 cell phenotype acquisition. In the study, STAT6-mediated primary and secondary target genes were dissection from each other and a detailed transcriptional kinetics of Th2 cell polarization of naïve human CD4+ T cells was collected. Integration of these data revealed the hierarchy of molecular events that mediates the differentiation towards Th2 cell phenotype. In addition, the results highlighted the importance of exploiting proteomics tools to complement the studies on STAT6 target genes identifi ed through transcriptional profi ling. In the last subproject, the effects of the exposure with ZnO and TiO2 nanoparticles was analyzed in Jurkat T cell line and in primary human monocyte-derived macrophages and dendritic cells to evaluate their toxicity and potential to cause infl ammation. Identifi cation of ZnO-derived gene expression showed that the same nanoparticles may elicit markedly distinctive responses in different cell types, thus underscoring the need for unbiased profi ling of target genes and pathways affected. The results gave additional proof that the cellular response to nanosized ZnO is due to leached Zn2+ ions. The approach used in ZnO and TiO2 nanoparticle study demonstrated the value of assessing nanoparticle responses through a toxicogenomics approach. The increased knowledge of Th2 cell signaling will hopefully reveal new therapeutic nodes and eventually improve our possibilities to prevent and tackle allergic infl ammatory diseases.

Mapping financial stability

The ongoing global financial crisis has demonstrated the importance of a systemwide, or macroprudential, approach to safeguarding financial stability. An essential part of macroprudential oversight concerns the tasks of early identification and assessment of risks and vulnerabilities that eventually may lead to a systemic financial crisis. Thriving tools are crucial as they allow early policy actions to decrease or prevent further build-up of risks or to otherwise enhance the shock absorption capacity of the financial system. In the literature, three types of systemic risk can be identified: i ) build-up of widespread imbalances, ii ) exogenous aggregate shocks, and iii ) contagion. Accordingly, the systemic risks are matched by three categories of analytical methods for decision support: i ) early-warning, ii ) macro stress-testing, and iii ) contagion models. Stimulated by the prolonged global financial crisis, today's toolbox of analytical methods includes a wide range of innovative solutions to the two tasks of risk identification and risk assessment. Yet, the literature lacks a focus on the task of risk communication. This thesis discusses macroprudential oversight from the viewpoint of all three tasks: Within analytical tools for risk identification and risk assessment, the focus concerns a tight integration of means for risk communication. Data and dimension reduction methods, and their combinations, hold promise for representing multivariate data structures in easily understandable formats. The overall task of this thesis is to represent high-dimensional data concerning financial entities on lowdimensional displays. The low-dimensional representations have two subtasks: i ) to function as a display for individual data concerning entities and their time series, and ii ) to use the display as a basis to which additional information can be linked. The final nuance of the task is, however, set by the needs of the domain, data and methods. The following ve questions comprise subsequent steps addressed in the process of this thesis: 1. What are the needs for macroprudential oversight? 2. What form do macroprudential data take? 3. Which data and dimension reduction methods hold most promise for the task? 4. How should the methods be extended and enhanced for the task? 5. How should the methods and their extensions be applied to the task? Based upon the Self-Organizing Map (SOM), this thesis not only creates the Self-Organizing Financial Stability Map (SOFSM), but also lays out a general framework for mapping the state of financial stability. This thesis also introduces three extensions to the standard SOM for enhancing the visualization and extraction of information: i ) fuzzifications, ii ) transition probabilities, and iii ) network analysis. Thus, the SOFSM functions as a display for risk identification, on top of which risk assessments can be illustrated. In addition, this thesis puts forward the Self-Organizing Time Map (SOTM) to provide means for visual dynamic clustering, which in the context of macroprudential oversight concerns the identification of cross-sectional changes in risks and vulnerabilities over time. Rather than automated analysis, the aim of visual means for identifying and assessing risks is to support disciplined and structured judgmental analysis based upon policymakers' experience and domain intelligence, as well as external risk communication.

The nature of communication structures of university students in an international web-based computer-supported collaborative learning (CSCL) course

Communication, the flow of ideas and information between individuals in a social context, is the heart of educational experience. Constructivism and constructivist theories form the foundation for the collaborative learning processes of creating and sharing meaning in online educational contexts. The Learning and Collaboration in Technology-enhanced Contexts (LeCoTec) course comprised of 66 participants drawn from four European universities (Oulu, Turku, Ghent and Ramon Llull). These participants were split into 15 groups with the express aim of learning about computer-supported collaborative learning (CSCL). The Community of Inquiry model (social, cognitive and teaching presences) provided the content and tools for learning and researching the collaborative interactions in this environment. The sampled comments from the collaborative phase were collected and analyzed at chain-level and group-level, with the aim of identifying the various message types that sustained high learning outcomes. Furthermore, the Social Network Analysis helped to view the density of whole group interactions, as well as the popular and active members within the highly collaborating groups. It was observed that long chains occur in groups having high quality outcomes. These chains were also characterized by Social, Interactivity, Administrative and Content comment-types. In addition, high outcomes were realized from the high interactive cases and high-density groups. In low interactive groups, commenting patterned around the one or two central group members. In conclusion, future online environments should support high-order learning and develop greater metacognition and self-regulation. Moreover, such an environment, with a wide variety of problem solving tools, would enhance interactivity.

Histopathological, immunohistochemical, and molecular study of BHV-5 infection in the central nervous system of experimentally infected calves

Bovine meningoencephalitis caused by BHV-5, a double-stranded DNA enveloped virus that belongs to the family Herpesviridae and subfamily Alphaherpesvirinae, is an important differential diagnosis of central nervous diseases. The aim of this study was to describe the histological changes in the central nervous system of calves experimentally infected with BHV-5 and compare these changes with the PCR and IHC results. Formalin-fixed paraffin-embedded central nervous system samples from calves previously inoculated with BHV-5 were microscopically evaluated and tested using IHC and PCR. All the animals presented with nonsuppurative meningoencephalitis. From 18 evaluated areas of each calf, 32.41% and 35.19% were positive by IHC and PCR, respectively. The telencephalon presented more accentuated lesions and positive areas in the PCR than other encephalic areas and was the best sampling area for diagnostic purposes. Positive areas in the IHC and PCR were more injured than IHC and PCR negative areas. The animal with neurological signs showed more PCR- and IHC-positive areas than the other animals.

A feature-based object-oriented expert system to model and support product design

In this paper a computer program to model and support product design is presented. The product is represented through a hierarchical structure that allows the user to navigate across the product’s components, and it aims at facilitating each step of the detail design process. A graphical interface was also developed, which shows visually to the user the contents of the product structure. Features are used as building blocks for the parts that compose the product, and object-oriented methodology was used as a means to implement the product structure. Finally, an expert system was also implemented, whose knowledge base rules help the user design a product that meets design and manufacturing requirements.

An Inspection System to Identify Fatigue Damage on Steel-Bridge Structures

Crack formation and growth in steel bridge structural elements may be due to loading oscillations. The welded elements are liable to internal discontinuities along welded joints and sensible to stress variations. The evaluation of the remaining life of a bridge is needed to make cost-effective decisions regarding inspection, repair, rehabilitation, and replacement. A steel beam model has been proposed to simulate crack openings due to cyclic loads. Two possible alternatives have been considered to model crack propagation, which the initial phase is based on the linear fracture mechanics. Then, the model is extended to take into account the elastoplastic fracture mechanic concepts. The natural frequency changes are directly related to moment of inertia variation and consequently to a reduction in the flexural stiffness of a steel beam. Thus, it is possible to adopt a nondestructive technique during steel bridge inspection to quantify the structure eigenvalue variation that will be used to localize the grown fracture. A damage detection algorithm is developed for the proposed model and the numerical results are compared with the solutions achieved by using another well know computer code.

Eucalyptus growth in silvopastoral system under different crown dia meters

The aim of this study was to evaluate the effect of different crown diameters on the early growth of eucalyptus intercropped with Brachiaria decumbens in a silvopastoral system. The experiment was conducted in a B. decumbens established pasture, where hybrid eucalyptus urograndis (clone GG100) was planted, spaced 8 x 3 m. A randomized block design was used, with six replicates. Treatments consisted of five crown diameters (0.0, 1.0, 1.5, 2.0, and 3.0 m) surrounding the eucalyptus plants. Five weeding hoes were performed throughout the experiment, according to the different crown diameters, aiming to maintain the eucalyptus plants free from B. decumbens interference. At 90, 180, 270, and 360 DAP, the height and the diameter of the eucalyptus plants were evaluated, and at 360 DAP, surface biomass and leaf area were evaluated. At 90 DAP, it was verified that the non-weeded plants had lower growth, compared to those submitted to crowns. Crown diameters of 2.51 and 2.64 m allowed greater growth in height and diameter at ground level of eucalyptus plants, respectively, in all periods evaluated. Biomass production and leaf area per plant at 360 DAP were also influenced by the different crown diameters. It was concluded that crown diameter around 2 meters provided favorable conditions for early growth of eucalyptus and less involvement in the area occupied by forage.

SYLI - an external workflow system for DSpace

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Nurses’ Acceptance of an Internet-Based Support System in The Care of Adolescents with Depression

The overall goal of the study was to describe nurses’ acceptance of an Internet-based support system in the care of adolescents with depression. The data were collected in four phases during the period 2006 – 2010 from nurses working in adolescent psychiatric outpatient clinics and from professionals working with adolescents in basic public services. In the first phase, the nurses’ anticipated perceptions of the usefulness of the Internet-based support system before its implementation was explored. In the second phase, the nurses’ perceived ease of computer and Internet use and attitudes toward it were explored. In the third phase, the features of the support system and its implementation process were described. In the fourth phase, the nurses’ experiences of behavioural intention and actual system use of the Internet-based support were described in psychiatric out-patient care after one year use. The Technology Acceptance Model (TAM) was used to structure the various research phases. Several benefits were identified from the nurses’ perspective in using the Internet-based support system in the care of adolescents with depression. The nurses’ technology skills were good and their attitudes towards computer use were positive. The support system was developed in various phases to meet the adolescents’ needs. Before the implementation of the information technology (IT)-based support system, it is important to pay attention to the nurses’ IT-training, technology support, resources, and safety as well as ethical issues related to the support system. After one year of using the system, the nurses perceived the Internet-based support system to be useful in the care of adolescents with depression. The adolescents’ independent work with the support system at home and the program’s systematic character were experienced as conducive from the point of view of the treatment. However, the Internet-based support system was integrated only partly into the nurseadolescent interaction even though the nurses’ perceptions of it were positive. The use of the IT-based system as part of the adolescents’ depression care was seen positively and its benefits were recognized. This serves as a good basis for future IT-based techniques. Successful implementations of IT-based support systems need a systematic implementation plan and commitment from the part of the organization and its managers. Supporting and evaluating the implementation of an IT-based system should pay attention to changing the nurses’ work styles. Health care organizations should be offered more flexible opportunities to utilize IT-based systems in direct patient care in the future.

Design and evaluation of web interface signs to improve web usability : a semiotic framework

Technological innovations, the development of the internet, and globalization have increased the number and complexity of web applications. As a result, keeping web user interfaces understandable and usable (in terms of ease-of-use, effectiveness, and satisfaction) is a challenge. As part of this, designing userintuitive interface signs (i.e., the small elements of web user interface, e.g., navigational link, command buttons, icons, small images, thumbnails, etc.) is an issue for designers. Interface signs are key elements of web user interfaces because ‘interface signs’ act as a communication artefact to convey web content and system functionality, and because users interact with systems by means of interface signs. In the light of the above, applying semiotic (i.e., the study of signs) concepts on web interface signs will contribute to discover new and important perspectives on web user interface design and evaluation. The thesis mainly focuses on web interface signs and uses the theory of semiotic as a background theory. The underlying aim of this thesis is to provide valuable insights to design and evaluate web user interfaces from a semiotic perspective in order to improve overall web usability. The fundamental research question is formulated as What do practitioners and researchers need to be aware of from a semiotic perspective when designing or evaluating web user interfaces to improve web usability? From a methodological perspective, the thesis follows a design science research (DSR) approach. A systematic literature review and six empirical studies are carried out in this thesis. The empirical studies are carried out with a total of 74 participants in Finland. The steps of a design science research process are followed while the studies were designed and conducted; that includes (a) problem identification and motivation, (b) definition of objectives of a solution, (c) design and development, (d) demonstration, (e) evaluation, and (f) communication. The data is collected using observations in a usability testing lab, by analytical (expert) inspection, with questionnaires, and in structured and semi-structured interviews. User behaviour analysis, qualitative analysis and statistics are used to analyze the study data. The results are summarized as follows and have lead to the following contributions. Firstly, the results present the current status of semiotic research in UI design and evaluation and highlight the importance of considering semiotic concepts in UI design and evaluation. Secondly, the thesis explores interface sign ontologies (i.e., sets of concepts and skills that a user should know to interpret the meaning of interface signs) by providing a set of ontologies used to interpret the meaning of interface signs, and by providing a set of features related to ontology mapping in interpreting the meaning of interface signs. Thirdly, the thesis explores the value of integrating semiotic concepts in usability testing. Fourthly, the thesis proposes a semiotic framework (Semiotic Interface sign Design and Evaluation – SIDE) for interface sign design and evaluation in order to make them intuitive for end users and to improve web usability. The SIDE framework includes a set of determinants and attributes of user-intuitive interface signs, and a set of semiotic heuristics to design and evaluate interface signs. Finally, the thesis assesses (a) the quality of the SIDE framework in terms of performance metrics (e.g., thoroughness, validity, effectiveness, reliability, etc.) and (b) the contributions of the SIDE framework from the evaluators’ perspective.

Low-cost automatic activity data recording system

We describe a low-cost, high quality device capable of monitoring indirect activity by detecting touch-release events on a conducting surface, i.e., the animal's cage cover. In addition to the detecting sensor itself, the system includes an IBM PC interface for prompt data storage. The hardware/software design, while serving for other purposes, is used to record the circadian activity rhythm pattern of rats with time in an automated computerized fashion using minimal cost computer equipment (IBM PC XT). Once the sensor detects a touch-release action of the rat in the upper portion of the cage, the interface sends a command to the PC which records the time (hours-minutes-seconds) when the activity occurred. As a result, the computer builds up several files (one per detector/sensor) containing a time list of all recorded events. Data can be visualized in terms of actograms, indicating the number of detections per hour, and analyzed by mathematical tools such as Fast Fourier Transform (FFT) or cosinor. In order to demonstrate method validation, an experiment was conducted on 8 Wistar rats under 12/12-h light/dark cycle conditions (lights on at 7:00 a.m.). Results show a biological validation of the method since it detected the presence of circadian activity rhythm patterns in the behavior of the rats

Expression of Fos protein in the rat central nervous system in response to noxious stimulation: effects of chronic inflammation of the superior cervical ganglion

The aim of this study was to investigate the possible interactions between the nociceptive system, the sympathetic system and the inflammatory process. Thus, the superior cervical ganglion of rats was submitted to chronic inflammation and Fos expression was used as a marker for neuronal activity throughout central neurons following painful peripheral stimulation. The painful stimulus consisted of subcutaneously injected formalin applied to the supra-ocular region. Fos-positive neurons were identified by conventional immunohistochemical techniques, and analyzed from the obex through the cervical levels of the spinal cord. In the caudal sub-nucleus of the spinal trigeminal nuclear complex, the number of Fos-positive neurons was much higher in rats with inflammation of the superior cervical ganglion than in control rats, either sham-operated or with saline applied to the ganglion. There was a highly significant difference in the density of Fos-positive neurons between the inflamed and control groups. No significant difference was found between control groups. These results suggest that the inflammation of the superior cervical ganglion generated an increased responsiveness to painful stimuli, which may have been due to a diminished sympathetic influence upon the sensory peripheral innervation.

VVER-440 Thermal Hydraulics as a Computer Code Validation Challenge

This thesis concentrates on the validation of a generic thermal hydraulic computer code TRACE under the challenges of the VVER-440 reactor type. The code capability to model the VVER-440 geometry and thermal hydraulic phenomena specific to this reactor design has been examined and demonstrated acceptable. The main challenge in VVER-440 thermal hydraulics appeared in the modelling of the horizontal steam generator. The major challenge here is not in the code physics or numerics but in the formulation of a representative nodalization structure. Another VVER-440 specialty, the hot leg loop seals, challenges the system codes functionally in general, but proved readily representable. Computer code models have to be validated against experiments to achieve confidence in code models. When new computer code is to be used for nuclear power plant safety analysis, it must first be validated against a large variety of different experiments. The validation process has to cover both the code itself and the code input. Uncertainties of different nature are identified in the different phases of the validation procedure and can even be quantified. This thesis presents a novel approach to the input model validation and uncertainty evaluation in the different stages of the computer code validation procedure. This thesis also demonstrates that in the safety analysis, there are inevitably significant uncertainties that are not statistically quantifiable; they need to be and can be addressed by other, less simplistic means, ultimately relying on the competence of the analysts and the capability of the community to support the experimental verification of analytical assumptions. This method completes essentially the commonly used uncertainty assessment methods, which are usually conducted using only statistical methods.

Measurement of epidermal thickness in a patient with psoriasis by computer-supported image analysis

The aim of the present study was to measure full epidermal thickness, stratum corneum thickness, rete length, dermal papilla widening and suprapapillary epidermal thickness in psoriasis patients using a light microscope and computer-supported image analysis. The data obtained were analyzed in terms of patient age, type of psoriasis, total body surface area involvement, scalp and nail involvement, duration of psoriasis, and family history of the disease. The study was conducted on 64 patients and 57 controls whose skin biopsies were examined by light microscopy. The acquired microscopic images were transferred to a computer and measurements were made using image analysis. The skin biopsies, taken from different body areas, were examined for different parameters such as epidermal, corneal and suprapapillary epidermal thickness. The most prominent increase in thickness was detected in the palmar region. Corneal thickness was more pronounced in patients with scalp involvement than in patients without scalp involvement (t = -2.651, P = 0.008). The most prominent increase in rete length was observed in the knees (median: 491 µm, t = 10.117, P = 0.000). The difference in rete length between patients with a positive and a negative family history was significant (t = -3.334, P = 0.03), being 27% greater in psoriasis patients without a family history. The differences in dermal papilla distances among patients were very small. We conclude that microscope-supported thickness measurements provide objective results.