The role of cathepsin K in lung development and newborn chronic lung injury.

Chronic lung diseases, specifically bronchopulmonary dysplasia (BPD), are still causing mortality and morbidity amongst newborn infants. High protease activity has been suggested to have a deleterious role in oxygen-induced lung injuries. Cathepsin K (CatK) is a potent protease found in fetal lungs, degrading collagen and elastin. We hypothesized that CatK may be an important modulator of chronic lung injury in newborn infants and neonatal mice. First we measured CatK protein levels in repeated tracheal aspirate fluid samples from 13 intubated preterm infants during the first two weeks of life. The amount of CatK at 9-13 days was low in infants developing chronic lung disease. Consequently, we studied CatK mRNA expression in oxygen-exposed wild-type (WT) rats at postnatal day (PN) 14 and found decreased pulmonary mRNA expression of CatK in whole lung samples. Thereafter we demonstrated that CatK deficiency modifies lung development by accelerating the thinning of alveolar walls in newborn mice. In hyperoxia-exposed newborn mice CatK deficiency resulted in increased number of pulmonary foam cells, macrophages and amount of reduced glutathione in lung homogenates indicating intensified pulmonary oxidative stress and worse pulmonary outcome due to CatK deficiency. Conversely, transgenic overexpression of CatK caused slight enlargement of distal airspaces with increased alveolar chord length in room air in neonatal mice. While hyperoxic exposure inhibited alveolarization and resulted in enlarged airspaces in wild-type mice, these changes were significantly milder in CatK overexpressing mice at PN7. Finally, we showed that the expression of macrophage scavenger receptor 2 (MSR2) mRNA was down-regulated in oxygen-exposed CatK-deficient mice analyzed by microarray analysis. Our results demonstrate that CatK seems to participate in normal lung development and its expression is altered during pulmonary injury. In the presence of pulmonary risk factors, like high oxygen exposure, low amount of CatK may contribute to aggravated lung injury while sustained or slightly elevated amount of CatK may even protect the newborn lungs from excessive injury. Besides collagen degrading and antifibrotic function of CatK in the lungs, it is obvious that CatK may affect macrophage activity and modify oxidative stress response. In conclusion, pulmonary proteases, specifically CatK, have distinct roles in lung homeostasis and injury development, and although suggested, broad range inhibition of proteases may not be beneficial in newborn lung injury.

Susteinable steelmaking by process integration

Environmental issues, including global warming, have been serious challenges realized worldwide, and they have become particularly important for the iron and steel manufacturers during the last decades. Many sites has been shut down in developed countries due to environmental regulation and pollution prevention while a large number of production plants have been established in developing countries which has changed the economy of this business. Sustainable development is a concept, which today affects economic growth, environmental protection, and social progress in setting up the basis for future ecosystem. A sustainable headway may attempt to preserve natural resources, recycle and reuse materials, prevent pollution, enhance yield and increase profitability. To achieve these objectives numerous alternatives should be examined in the sustainable process design. Conventional engineering work cannot address all of these substitutes effectively and efficiently to find an optimal route of processing. A systematic framework is needed as a tool to guide designers to make decisions based on overall concepts of the system, identifying the key bottlenecks and opportunities, which lead to an optimal design and operation of the systems. Since the 1980s, researchers have made big efforts to develop tools for what today is referred to as Process Integration. Advanced mathematics has been used in simulation models to evaluate various available alternatives considering physical, economic and environmental constraints. Improvements on feed material and operation, competitive energy market, environmental restrictions and the role of Nordic steelworks as energy supplier (electricity and district heat) make a great motivation behind integration among industries toward more sustainable operation, which could increase the overall energy efficiency and decrease environmental impacts. In this study, through different steps a model is developed for primary steelmaking, with the Finnish steel sector as a reference, to evaluate future operation concepts of a steelmaking site regarding sustainability. The research started by potential study on increasing energy efficiency and carbon dioxide reduction due to integration of steelworks with chemical plants for possible utilization of available off-gases in the system as chemical products. These off-gases from blast furnace, basic oxygen furnace and coke oven furnace are mainly contained of carbon monoxide, carbon dioxide, hydrogen, nitrogen and partially methane (in coke oven gas) and have proportionally low heating value but are currently used as fuel within these industries. Nonlinear optimization technique is used to assess integration with methanol plant under novel blast furnace technologies and (partially) substitution of coal with other reducing agents and fuels such as heavy oil, natural gas and biomass in the system. Technical aspect of integration and its effect on blast furnace operation regardless of capital expenditure of new operational units are studied to evaluate feasibility of the idea behind the research. Later on the concept of polygeneration system added and a superstructure generated with alternative routes for off-gases pretreatment and further utilization on a polygeneration system producing electricity, district heat and methanol. (Vacuum) pressure swing adsorption, membrane technology and chemical absorption for gas separation; partial oxidation, carbon dioxide and steam methane reforming for methane gasification; gas and liquid phase methanol synthesis are the main alternative process units considered in the superstructure. Due to high degree of integration in process synthesis, and optimization techniques, equation oriented modeling is chosen as an alternative and effective strategy to previous sequential modelling for process analysis to investigate suggested superstructure. A mixed integer nonlinear programming is developed to study behavior of the integrated system under different economic and environmental scenarios. Net present value and specific carbon dioxide emission is taken to compare economic and environmental aspects of integrated system respectively for different fuel systems, alternative blast furnace reductants, implementation of new blast furnace technologies, and carbon dioxide emission penalties. Sensitivity analysis, carbon distribution and the effect of external seasonal energy demand is investigated with different optimization techniques. This tool can provide useful information concerning techno-environmental and economic aspects for decision-making and estimate optimal operational condition of current and future primary steelmaking under alternative scenarios. The results of the work have demonstrated that it is possible in the future to develop steelmaking towards more sustainable operation.

Novel word learning ability in chronic post-stroke aphasia : variability and modality effects

Novel word learning has been rarely studied in people with aphasia (PWA), although it can provide a relatively pure measure of their learning potential, and thereby contribute to the development of effective aphasia treatment methods. The main aim of the present thesis was to explore the capacity of PWA for associative learning of word–referent pairings and cognitive-linguistic factors related to it. More specifically, the thesis examined learning and long-term maintenance of the learned pairings, the role of lexical-semantic abilities in learning as well as acquisition of phonological versus semantic information in associative novel word learning. Furthermore, the effect of modality on associative novel word learning and the neural underpinnings of successful learning were explored. The learning experiments utilized the Ancient Farming Equipment (AFE) paradigm that employs drawings of unfamiliar referents and their unfamiliar names. Case studies of Finnishand English-speaking people with chronic aphasia (n = 6) were conducted in the investigation. The learning results of PWA were compared to those of healthy control participants, and active production of the novel words and their semantic definitions was used as learning outcome measures. PWA learned novel word–novel referent pairings, but the variation between individuals was very wide, from more modest outcomes (Studies I–II) up to levels on a par with healthy individuals (Studies III–IV). In incidental learning of semantic definitions, none of the PWA reached the performance level of the healthy control participants. Some PWA maintained part of the learning outcomes up to months post-training, and one individual showed full maintenance of the novel words at six months post-training (Study IV). Intact lexical-semantic processing skills promoted learning in PWA (Studies I–II) but poor phonological short-term memory capacities did not rule out novel word learning. In two PWA with successful learning and long-term maintenance of novel word–novel referent pairings, learning relied on orthographic input while auditory input led to significantly inferior learning outcomes (Studies III–IV). In one of these individuals, this previously undetected modalityspecific learning ability was successfully translated into training with familiar but inaccessible everyday words (Study IV). Functional magnetic resonance imaging revealed that this individual had a disconnected dorsal speech processing pathway in the left hemisphere, but a right-hemispheric neural network mediated successful novel word learning via reading. Finally, the results of Study III suggested that the cognitive-linguistic profile may not always predict the optimal learning channel for an individual with aphasia. Small-scale learning probes seem therefore useful in revealing functional learning channels in post-stroke aphasia.

Modelling Energy Consumption of a Switch using Fuzzy-Rule Classifier

The energy consumption of IT equipments is becoming an issue of increasing importance. In particular, network equipments such as routers and switches are major contributors to the energy consumption of internet. Therefore it is important to understand how the relationship between input parameters such as bandwidth, number of active ports, traffic-load, hibernation-mode and their impact on energy consumption of a switch. In this paper, the energy consumption of a switch is analyzed in extensive experiments. A fuzzy rule-based model of energy consumption of a switch is proposed based on the result of experiments. The model can be used to predict the energy saving when deploying new switches by controlling the parameters to achieve desired energy consumption and subsequent performance. Furthermore, the model can also be used for further researches on energy saving techniques such as energy-efficient routing protocol, dynamic link shutdown, etc.

Determining vehicle drivetrain dynamics using system identification

Target of this book is to propose an approach for modelling drivetrain dynamics in order to design further a vibration control system of a hybrid bus. In this thesis two approaches are examined and compared. First model is obtained by theoretical means: drivetrain is represented as a system of rotating masses, which motion is described with differential equations. Second model is obtained using system identification method: mathematical description of the dynamic behavior of a system is formed based on measured input (torque) and output (speed) data. Then two models are compared and an optimal approach is suggested.