876 resultados para Vihman, Marilyn May: Phonological development
Resumo:
The human adrenal cortex, involved in adaptive responses to stress, body homeostasis and secondary sexual characters, emerges from a tightly regulated development of a zone-specific secretion pattern during fetal life. Its development during fetal life is critical for the well being of pregnancy, the initiation of delivery, and even for an adequate adaptation to extra-uterine life. As early as from the sixth week of pregnancy, the fetal adrenal gland is characterized by a highly proliferative zone at the periphery, a concentric migration accompanied by cell differentiation (cortisol secretion) and apoptosis in the central androgen-secreting fetal zone. After birth, a strong reorganization occurs in the adrenal gland so that it better fulfills the newborn's needs, with aldosterone production in the external zona glomerulosa, cortisol secretion in the zona fasciculata and androgens in the central zona reticularis. In addition to the major hormonal stimuli provided by angiotensin II and adrenocorticotropin, we have tested for some years the hypotheses that such plasticity may be under the control of the extracellular matrix. A growing number of data have been harvested during the last years, in particular about extracellular matrix expression and its putative role in the development of the human adrenal cortex. Laminin, collagen and fibronectin have been shown to play important roles not only in the plasticity of the adrenal cortex, but also in cell responsiveness to hormones, thus clarifying some of the unexplained observations that used to feed controversies.
Resumo:
Matrix metalloproteinases (MMPs) are a major group of proteases known to regulate extracellular matrix (ECM) turnover and so they have been suggested to be important in the process of lung disease associated with tissue remodeling. This has led to the concept that modulation of airway remodeling including excessive proteolysis damage to the tissue may be of interest for future treatment. Within the MMP family, macrophage elastase (MMP-12) is able to degrade ECM components such as elastin and is involved in tissue remodeling processes in chronic obstructive pulmonary disease including emphysema. Pulmonary fibrosis has an aggressive course and is usually fatal within an average of 3 to 6 years after the onset of symptoms. Pulmonary fibrosis is associated with deposition of ECM components in the lung interstitium. The excessive airway remodeling as a result of an imbalance in the equilibrium of the normal processes of synthesis and degradation of ECM components could justify anti-protease treatments. Indeed, the correlation of the differences in hydroxyproline levels in the lungs of bleomycin-treated mice strongly suggests that a reduced molar pro-MMP-9/TIMP-1 ratio in bronchoalveolar lavage fluid is associated with collagen deposition, beginning as early as the inflammatory events at day 1 after bleomycin administration. Finally, these observations emphasize that effective treatment of these disorders must be started early during the natural history of the disease, prior to the development of extensive lung destruction and fibrosis.
Resumo:
Microsporogenesis and pollen development were analyzed in a tetraploid (2n = 4x = 36) accession of the forage grass Brachiaria jubata (BRA 007820) from the Embrapa Beef Cattle Brachiaria collection that showed partial male sterility. Microsporocytes and pollen grains were prepared by squashing and staining with 0.5% propionic carmine. The meiotic process was typical of polyploids, with precocious chromosome migration to the poles and laggards in both meiosis I and II, resulting in tetrads with micronuclei in some microspores. After callose dissolution, microspores were released into the anther locule and appeared to be normal. Although each microspore initiated its differentiation into a pollen grain, in 11.1% of them nucleus polarization was not observed, i.e., pollen mitosis I was symmetric and the typical hemispherical cell plate was not detected. After a central cytokinesis, two equal-sized cells showing equal chromatin condensation and the same nuclear shape and size were formed. Generative cells and vegetative cells could not be distinguished. These cells did not undergo the second pollen mitosis and after completion of pollen wall synthesis each gave rise to a sterile and uninucleate pollen grain. The frequency of abnormal pollen mitosis varied among flowers and also among inflorescences. All plants were equally affected. The absence of fertile sperm cells in a considerable amount of pollen grains in this accession of B. jubata may compromise its use in breeding and could explain, at least in part, why seed production is low when compared with the amount of flowers per raceme.
Resumo:
Coronary artery disease is an atherosclerotic disease, which leads to narrowing of coronary arteries, deteriorated myocardial blood flow and myocardial ischaemia. In acute myocardial infarction, a prolonged period of myocardial ischaemia leads to myocardial necrosis. Necrotic myocardium is replaced with scar tissue. Myocardial infarction results in various changes in cardiac structure and function over time that results in “adverse remodelling”. This remodelling may result in a progressive worsening of cardiac function and development of chronic heart failure. In this thesis, we developed and validated three different large animal models of coronary artery disease, myocardial ischaemia and infarction for translational studies. In the first study the coronary artery disease model had both induced diabetes and hypercholesterolemia. In the second study myocardial ischaemia and infarction were caused by a surgical method and in the third study by catheterisation. For model characterisation, we used non-invasive positron emission tomography (PET) methods for measurement of myocardial perfusion, oxidative metabolism and glucose utilisation. Additionally, cardiac function was measured by echocardiography and computed tomography. To study the metabolic changes that occur during atherosclerosis, a hypercholesterolemic and diabetic model was used with [18F] fluorodeoxyglucose ([18F]FDG) PET-imaging technology. Coronary occlusion models were used to evaluate metabolic and structural changes in the heart and the cardioprotective effects of levosimendan during post-infarction cardiac remodelling. Large animal models were used in testing of novel radiopharmaceuticals for myocardial perfusion imaging. In the coronary artery disease model, we observed atherosclerotic lesions that were associated with focally increased [18F]FDG uptake. In heart failure models, chronic myocardial infarction led to the worsening of systolic function, cardiac remodelling and decreased efficiency of cardiac pumping function. Levosimendan therapy reduced post-infarction myocardial infarct size and improved cardiac function. The novel 68Ga-labeled radiopharmaceuticals tested in this study were not successful for the determination of myocardial blood flow. In conclusion, diabetes and hypercholesterolemia lead to the development of early phase atherosclerotic lesions. Coronary artery occlusion produced considerable myocardial ischaemia and later infarction following myocardial remodelling. The experimental models evaluated in these studies will enable further studies concerning disease mechanisms, new radiopharmaceuticals and interventions in coronary artery disease and heart failure.
Resumo:
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.
Resumo:
Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH. Pregnant rats were divided into four groups (n=20 fetuses each) of four different gestational days (GD) 18.5, 19.5, 20.5, 21.5: external control (EC), exposed to olive oil (OO), exposed to 100 mg nitrofen, by gavage, without CDH (N-), and exposed to nitrofen with CDH (CDH) on GD 9.5 (term=22 days). The morphological variables studied were: body weight (BW), total lung weight (TLW), left lung weight, TLW/BW ratio, total lung volume, and left lung volume. The histometric variables studied were: left lung parenchymal area density and left lung parenchymal volume. VEGFR1 and VEGFR2 expression were determined by Western blotting. The data were analyzed using analysis of variance with the Tukey-Kramer post hoc test. CDH frequency was 37% (80/216). All the morphological and histometric variables were reduced in the N- and CDH groups compared with the controls, and reductions were more pronounced in the CDH group (P<0.05) and more evident on GD 20.5 and GD 21.5. Similar results were observed for VEGFR1 and VEGFR2 expression. We conclude that N- and CDH fetuses showed primary pulmonary hypoplasia, with a decrease in VEGFR1 and VEGFR2 expression.
Resumo:
Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.
Resumo:
The monitoring and control of hydrogen sulfide (H2S) level is of great interest for a wide range of application areas including food quality control, defense and antiterrorist applications and air quality monitoring e.g. in mines. H2S is a very poisonous and flammable gas. Exposure to low concentrations of H2S can result in eye irritation, a sore throat and cough, shortness of breath, and fluid retention in the lungs. These symptoms usually disappear in a few weeks. Long-term, low-level exposure may result in fatigue, loss of appetite, headache, irritability, poor memory, and dizziness. Higher concentrations of 700 - 800 ppm tend to be fatal. H2S has a characteristic smell of rotten egg. However, because of temporary paralysis of olfactory nerves, the smelling capability at concentrations higher than 100 ppm is severely compromised. In addition, volatile H2S is one of the main products during the spoilage of poultry meat in anaerobic conditions. Currently, no commercial H2S sensor is available which can operate under anaerobic conditions and can be easily integrated in the food packaging. This thesis presents a step-wise progress in the development of printed H2S gas sensors. Efforts were made in the formulation, characterization and optimization of functional printable inks and coating pastes based on composites of a polymer and a metal salt as well as a composite of a metal salt and an organic acid. Different processing techniques including inkjet printing, flexographic printing, screen printing and spray coating were utilized in the fabrication of H2S sensors. The dispersions were characterized by measuring turbidity, surface tension, viscosity and particle size. The sensing films were characterized using X-ray photoelectron spectroscopy, X-ray diffraction, atomic force microscopy and an electrical multimeter. Thin and thick printed or coated films were developed for gas sensing applications with the aim of monitoring the H2S concentrations in real life applications. Initially, a H2S gas sensor based on a composite of polyaniline and metal salt was developed. Both aqueous and solvent-based dispersions were developed and characterized. These dispersions were then utilized in the fabrication of roll-to-roll printed H2S gas sensors. However, the humidity background, long term instability and comparatively lower detection limit made these sensors less favourable for real practical applications. To overcome these problems, copper acetate based sensors were developed for H2S gas sensing. Stable inks with excellent printability were developed by tuning the surface tension, viscosity and particle size. This enabled the formation of inkjet-printed high quality copper acetate films with excellent sensitivity towards H2S. Furthermore, these sensors showed negligible humidity effects and improved selectivity, response time, lower limit of detection and coefficient of variation. The lower limit of detection of copper acetate based sensors was further improved to sub-ppm level by incorporation of catalytic gold nano-particles and subsequent plasma treatment of the sensing film. These sensors were further integrated in an inexpensive wirelessly readable RLC-circuit (where R is resistor, L is inductor and C is capacitor). The performance of these sensors towards biogenic H2S produced during the spoilage of poultry meat in the modified atmosphere package was also demonstrated in this thesis. This serves as a proof of concept that these sensors can be utilized in real life applications.
Resumo:
The liberalisation of the wholesale electricity markets has been considered an efficient way to organise the markets. In Europe, the target is to liberalise and integrate the common European electricity markets. However, insufficient transmission capacity between the market areas hampers the integration, and therefore, new investments are required. Again, massive transmission capacity investments are not usually easy to carry through. This doctoral dissertation aims at elaborating on critical determinants required to deliver the necessary transmission capacity investments. The Nordic electricity market is used as an illustrative example. This study suggests that changes in the governance structure have affected the delivery of Nordic cross-border investments. In addition, the impacts of not fully delivered investments are studied in this doctoral dissertation. An insufficient transmission network can degrade the market uniformity and may also cause a need to split the market into smaller submarkets. This may have financial impacts on market actors when the targeted efficient sharing of resources is not met and even encourage gaming. The research methods applied in this doctoral dissertation are mainly empirical ranging from a Delphi study to case studies and numerical calculations.
Resumo:
In recent years, technological advancements in microelectronics and sensor technologies have revolutionized the field of electrical engineering. New manufacturing techniques have enabled a higher level of integration that has combined sensors and electronics into compact and inexpensive systems. Previously, the challenge in measurements was to understand the operation of the electronics and sensors, but this has now changed. Nowadays, the challenge in measurement instrumentation lies in mastering the whole system, not just the electronics. To address this issue, this doctoral dissertation studies whether it would be beneficial to consider a measurement system as a whole from the physical phenomena to the digital recording device, where each piece of the measurement system affects the system performance, rather than as a system consisting of small independent parts such as a sensor or an amplifier that could be designed separately. The objective of this doctoral dissertation is to describe in depth the development of the measurement system taking into account the challenges caused by the electrical and mechanical requirements and the measurement environment. The work is done as an empirical case study in two example applications that are both intended for scientific studies. The cases are a light sensitive biological sensor used in imaging and a gas electron multiplier detector for particle physics. The study showed that in these two cases there were a number of different parts of the measurement system that interacted with each other. Without considering these interactions, the reliability of the measurement may be compromised, which may lead to wrong conclusions about the measurement. For this reason it is beneficial to conceptualize the measurement system as a whole from the physical phenomena to the digital recording device where each piece of the measurement system affects the system performance. The results work as examples of how a measurement system can be successfully constructed to support a study of sensors and electronics.
Resumo:
Resilience is the property of a system to remain trustworthy despite changes. Changes of a different nature, whether due to failures of system components or varying operational conditions, significantly increase the complexity of system development. Therefore, advanced development technologies are required to build robust and flexible system architectures capable of adapting to such changes. Moreover, powerful quantitative techniques are needed to assess the impact of these changes on various system characteristics. Architectural flexibility is achieved by embedding into the system design the mechanisms for identifying changes and reacting on them. Hence a resilient system should have both advanced monitoring and error detection capabilities to recognise changes as well as sophisticated reconfiguration mechanisms to adapt to them. The aim of such reconfiguration is to ensure that the system stays operational, i.e., remains capable of achieving its goals. Design, verification and assessment of the system reconfiguration mechanisms is a challenging and error prone engineering task. In this thesis, we propose and validate a formal framework for development and assessment of resilient systems. Such a framework provides us with the means to specify and verify complex component interactions, model their cooperative behaviour in achieving system goals, and analyse the chosen reconfiguration strategies. Due to the variety of properties to be analysed, such a framework should have an integrated nature. To ensure the system functional correctness, it should rely on formal modelling and verification, while, to assess the impact of changes on such properties as performance and reliability, it should be combined with quantitative analysis. To ensure scalability of the proposed framework, we choose Event-B as the basis for reasoning about functional correctness. Event-B is a statebased formal approach that promotes the correct-by-construction development paradigm and formal verification by theorem proving. Event-B has a mature industrial-strength tool support { the Rodin platform. Proof-based verification as well as the reliance on abstraction and decomposition adopted in Event-B provides the designers with a powerful support for the development of complex systems. Moreover, the top-down system development by refinement allows the developers to explicitly express and verify critical system-level properties. Besides ensuring functional correctness, to achieve resilience we also need to analyse a number of non-functional characteristics, such as reliability and performance. Therefore, in this thesis we also demonstrate how formal development in Event-B can be combined with quantitative analysis. Namely, we experiment with integration of such techniques as probabilistic model checking in PRISM and discrete-event simulation in SimPy with formal development in Event-B. Such an integration allows us to assess how changes and di erent recon guration strategies a ect the overall system resilience. The approach proposed in this thesis is validated by a number of case studies from such areas as robotics, space, healthcare and cloud domain.
Resumo:
The number of security violations is increasing and a security breach could have irreversible impacts to business. There are several ways to improve organization security, but some of them may be difficult to comprehend. This thesis demystifies threat modeling as part of secure system development. Threat modeling enables developers to reveal previously undetected security issues from computer systems. It offers a structured approach for organizations to find and address threats against vulnerabilities. When implemented correctly threat modeling will reduce the amount of defects and malicious attempts against the target environment. In this thesis Microsoft Security Development Lifecycle (SDL) is introduced as an effective methodology for reducing defects in the target system. SDL is traditionally meant to be used in software development, principles can be however partially adapted to IT-infrastructure development. Microsoft threat modeling methodology is an important part of SDL and it is utilized in this thesis to find threats from the Acme Corporation’s factory environment. Acme Corporation is used as a pseudonym for a company providing high-technology consumer electronics. Target for threat modeling is the IT-infrastructure of factory’s manufacturing execution system. Microsoft threat modeling methodology utilizes STRIDE –mnemonic and data flow diagrams to find threats. Threat modeling in this thesis returned results that were important for the organization. Acme Corporation now has more comprehensive understanding concerning IT-infrastructure of the manufacturing execution system. On top of vulnerability related results threat modeling provided coherent views of the target system. Subject matter experts from different areas can now agree upon functions and dependencies of the target system. Threat modeling was recognized as a useful activity for improving security.
Resumo:
Mitt övergripande forskningsintresse är grammatikdidaktik, medan det explicita syftet med denna licentiatavhandling är att erhålla ny kunskap om grammatikdidaktik så som den synliggörs i nutida läromedel för grundskolans första årskurser. Den empiriska undersökningen är gjord i tre nutida läromedelspaket avsedda för undervisning i skolämnet modersmål och litteratur i årskurs ett och två, läromedlen som undersöks är de finlandssvenska serierna Läseboken och Litteraturboken samt den sverigesvenska serien Kom och läs! Bland resultaten kan nämnas att det finns ett brett spektrum av nivåer av extern grammatik i alla de undersökta läromedelspaketen. Den fonologiska och syntaktiska medvetenheten, vilka bägge är viktiga för läs- och skrivutvecklingen i de diskuterade årskurserna, satsas på i alla tre läromedelspaket. Det jag dock också märkt i läromedlen som kan påverka läs- och skrivutvecklingen är att andelen belägg för grafonomi är större i årskurs två än i årskurs ett. Härigenom får eleverna på detta sätt småningom växa in i en skriftkultur. Det finns betydligt fler muntliga uppgifter i lärarhandledningarna till serierna Litteraturboken och Kom och läs! än i Läseboken. Det exakta ”hur” står inte alltid utskrivet i lärarhandledningarna, men de flesta gånger verkar tanken vara att det rör sig om diskussioner eller andra muntliga genrer. I många fall känns de muntliga uppgifterna mer funktionella än skriftliga uppgifter som inte verkar vara helt genomtänkta. Att mitt material innehåller fler funktionella uppgifter i lärarhandledningar och fler formalistiska eller delvis funktionella uppgifter i arbetsböcker överensstämmer med att lärarhandledningar kan vara en bättre väg för att öka elevernas kunskapssökande och minska förmedlingspedagogiken.
Resumo:
Trade between South America and China has been an important source of the high growth shown by those economies in the 2000s. During the globalization of the 1990s, trade between the region and China had not developed so much. A rather sharp growth in China's presence in world trade since the beginning of the 2000s changed the world trade trends for MERCOSUR countries, or, at least, for many of them. The impact of the increasing trade of agrifood has been very relevant, and different per country. Strategy is another important issue, referring to bilateral relations with China. This country should be seen as a partner in the global trade, and not as a new foreign investor for the region, but this may be different in the context of different national strategies of South American countries.
Resumo:
The Finnish legislation requires for a safe and secure learning environment. However, the comprehensive, risk based safety and security management (SSM) and the management commitment in the implementation and development of the SSM are not mentioned in the legislation. Multiple institutions, operators and researchers have studied and developed safety and security in educational institutions over the past decade. Typically the approach has been fragmented and without bringing up the importance of the comprehensive SSM. The development needs of the safety and security operations in universities have been studied. However, in universities of applied sciences (UASs) and in elementary schools (ESs), the performance level, strengths and weaknesses of the comprehensive SSM have not been studied. The objective of this study was to develop the comprehensive, risk based SSM of educational institutions by developing the new Asteri consultative auditing process and study its effects on auditees. Furthermore, the performance level in the comprehensive SSM in UASs and ESs were studied using Asteri and the TUTOR model developed by the Keski-Uusimaa Department for Rescue Services. In addition, strengths, development needs and differences were identified. In total, 76 educational institutions were audited between the years 2011 and 2014. The study is based on logical empiricism, and an observational applied research design was used. Auditing, observation and an electronic survey were used for data collection. Statistical analysis was used to analyze the collected information. In addition, thematic analysis was used to analyze the development areas of the organizations mentioned by the respondents in the survey. As one of the main contributions, this research presents the new Asteri consultative auditing process. Organizations with low performance levels on the audited subject benefit the most from the Asteri consultative auditing process. Asteri may be usable in many different types of audits, not only in SSM audits. As a new result, this study provides new knowledge on attitudes related to auditing. According to the research findings, auditing may generate negative attitudes and the auditor should take them into account when planning and preparing for audits. Negative attitudes can be compensated by producing added value, objectivity and positivity for the audit and, thus, improve the positive effects of auditing on knowledge and skills. Moreover, as the results of this study shows, auditing safety and security issues do not increase feelings of insecurity, but rather increase feelings of safety and security when using the new Asteri consultative auditing process with the TUTOR model. The results showed that the SSM in the audited UASs was statistically significantly more advanced than that in the audited ESs. However, there is still room for improvement in the ESs and the UASs as the approach to the SSM was fragmented. It can be assumed that the majority of Finnish UASs and ESs do not likely meet the basic level of the comprehensive, risk based the SSM.