Molecular patterns behind immunological and metabolic alterations in lysinuric protein intolerance

Lysinuric protein intolerance (LPI) is a recessively inherited disorder characterised by reduced plasma and increased urinary levels of cationic amino acids (CAAs), protein malnutrition, growth failure and hyperlipidemia. Some patients develop severe immunological, renal and pulmonary complications. All Finnish patients share the same LPIFin mutation in the SLC7A7 gene that encodes CAA transporter y+LAT1. The aim of this study was to examine molecular factors contributing to the various symptoms, systemic metabolic and lipid profiles, and innate immune responses in LPI. The transcriptomes, metabolomes and lipidomes were analysed in whole-blood cells and plasma using RNA microarrays and gas or liquid chromatography-mass spectrometry techniques, respectively. Toll-like receptor (TLR) signalling in monocyte-derived macrophages exposed to pathogens was scrutinised using qRT-PCR and the Luminex technology. Altered levels of transcripts participating in amino acid transport, immune responses, apoptosis and pathways of hepatic and renal metabolism were identified in the LPI whole-blood cells. The patients had increased non-essential amino acid, triacylglycerol and fatty acid levels, and decreased plasma levels of phosphatidylcholines and practically all essential amino acids. In addition, elevated plasma levels of eight metabolites, long-chain triacylglycerols, two chemoattractant chemokines and nitric oxide correlated with the reduced glomerular function in the patients with kidney disease. Accordingly, it can be hypothesised that the patients have increased autophagy, inflammation, oxidative stress and apoptosis, leading to hepatic steatosis, uremic toxicity and altered intestinal microbe metabolism. Furthermore, the LPI macrophages showed disruption in the TLR2/1, TLR4 and TLR9 pathways, suggesting innate immune dysfunctions with an excessive response to bacterial infections but a deficient viral DNA response.

Static waves in corporate space : characterizing oscillating trading patterns in New York stock exchange

Various researches in the field of econophysics has shown that fluid flow have analogous phenomena in financial market behavior, the typical parallelism being delivered between energy in fluids and information on markets. However, the geometry of the manifold on which market dynamics act out their dynamics (corporate space) is not yet known. In this thesis, utilizing a Seven year time series of prices of stocks used to compute S&P500 index on the New York Stock Exchange, we have created local chart to the corporate space with the goal of finding standing waves and other soliton like patterns in the behavior of stock price deviations from the S&P500 index. By first calculating the correlation matrix of normalized stock price deviations from the S&P500 index, we have performed a local singular value decomposition over a set of four different time windows as guides to the nature of patterns that may emerge. I turns out that in almost all cases, each singular vector is essentially determined by relatively small set of companies with big positive or negative weights on that singular vector. Over particular time windows, sometimes these weights are strongly correlated with at least one industrial sector and certain sectors are more prone to fast dynamics whereas others have longer standing waves.

University students’ regulation of learning and text processing – examples from medical and teacher education

The general aim of the thesis was to study university students’ learning from the perspective of regulation of learning and text processing. The data were collected from the two academic disciplines of medical and teacher education, which share the features of highly scheduled study, a multidisciplinary character, a complex relationship between theory and practice and a professional nature. Contemporary information society poses new challenges for learning, as it is not possible to learn all the information needed in a profession during a study programme. Therefore, it is increasingly important to learn how to think and learn independently, how to recognise gaps in and update one’s knowledge and how to deal with the huge amount of constantly changing information. In other words, it is critical to regulate one’s learning and to process text effectively. The thesis comprises five sub-studies that employed cross-sectional, longitudinal and experimental designs and multiple methods, from surveys to eye tracking. Study I examined the connections between students’ study orientations and the ways they regulate their learning. In total, 410 second-, fourth- and sixth-year medical students from two Finnish medical schools participated in the study by completing a questionnaire measuring both general study orientations and regulation strategies. The students were generally deeply oriented towards their studies. However, they regulated their studying externally. Several interesting and theoretically reasonable connections between the variables were found. For instance, self-regulation was positively correlated with deep orientation and achievement orientation and was negatively correlated with non-commitment. However, external regulation was likewise positively correlated with deep orientation and achievement orientation but also with surface orientation and systematic orientation. It is argued that external regulation might function as an effective coping strategy in the cognitively loaded medical curriculum. Study II focused on medical students’ regulation of learning and their conceptions of the learning environment in an innovative medical course where traditional lectures were combined wth problem-based learning (PBL) group work. First-year medical and dental students (N = 153) completed a questionnaire assessing their regulation strategies of learning and views about the PBL group work. The results indicated that external regulation and self-regulation of the learning content were the most typical regulation strategies among the participants. In line with previous studies, self-regulation wasconnected with study success. Strictly organised PBL sessions were not considered as useful as lectures, although the students’ views of the teacher/tutor and the group were mainly positive. Therefore, developers of teaching methods are challenged to think of new solutions that facilitate reflection of one’s learning and that improve the development of self-regulation. In Study III, a person-centred approach to studying regulation strategies was employed, in contrast to the traditional variable-centred approach used in Study I and Study II. The aim of Study III was to identify different regulation strategy profiles among medical students (N = 162) across time and to examine to what extent these profiles predict study success in preclinical studies. Four regulation strategy profiles were identified, and connections with study success were found. Students with the lowest self-regulation and with an increasing lack of regulation performed worse than the other groups. As the person-centred approach enables us to individualise students with diverse regulation patterns, it could be used in supporting student learning and in facilitating the early diagnosis of learning difficulties. In Study IV, 91 student teachers participated in a pre-test/post-test design where they answered open-ended questions about a complex science concept both before and after reading either a traditional, expository science text or a refutational text that prompted the reader to change his/her beliefs according to scientific beliefs about the phenomenon. The student teachers completed a questionnaire concerning their regulation and processing strategies. The results showed that the students’ understanding improved after text reading intervention and that refutational text promoted understanding better than the traditional text. Additionally, regulation and processing strategies were found to be connected with understanding the science phenomenon. A weak trend showed that weaker learners would benefit more from the refutational text. It seems that learners with effective learning strategies are able to pick out the relevant content regardless of the text type, whereas weaker learners might benefit from refutational parts that contrast the most typical misconceptions with scientific views. The purpose of Study V was to use eye tracking to determine how third-year medical studets (n = 39) and internal medicine residents (n = 13) read and solve patient case texts. The results revealed differences between medical students and residents in processing patient case texts; compared to the students, the residents were more accurate in their diagnoses and processed the texts significantly faster and with a lower number of fixations. Different reading patterns were also found. The observed differences between medical students and residents in processing patient case texts could be used in medical education to model expert reasoning and to teach how a good medical text should be constructed. The main findings of the thesis indicate that even among very selected student populations, such as high-achieving medical students or student teachers, there seems to be a lot of variation in regulation strategies of learning and text processing. As these learning strategies are related to successful studying, students enter educational programmes with rather different chances of managing and achieving success. Further, the ways of engaging in learning seldom centre on a single strategy or approach; rather, students seem to combine several strategies to a certain degree. Sometimes, it can be a matter of perspective of which way of learning can be considered best; therefore, the reality of studying in higher education is often more complicated than the simplistic view of self-regulation as a good quality and external regulation as a harmful quality. The beginning of university studies may be stressful for many, as the gap between high school and university studies is huge and those strategies that were adequate during high school might not work as well in higher education. Therefore, it is important to map students’ learning strategies and to encourage them to engage in using high-quality learning strategies from the beginning. Instead of separate courses on learning skills, the integration of these skills into course contents should be considered. Furthermore, learning complex scientific phenomena could be facilitated by paying attention to high-quality learning materials and texts and other support from the learning environment also in the university. Eye tracking seems to have great potential in evaluating performance and growing diagnostic expertise in text processing, although more research using texts as stimulus is needed. Both medical and teacher education programmes and the professions themselves are challenging in terms of their multidisciplinary nature and increasing amounts of information and therefore require good lifelong learning skills during the study period and later in work life.

Diel patterns and tissue-specificity of environmental responses in fish

Humans are profoundly changing aquatic environments through climate change and the release of nutrients and chemicals. To understand the effects of these changes on natural populations, knowledge on individuals’ environmental responses is needed. At the molecular level, the environmental responses are partly mediated by chances in messenger RNA and protein levels. In this thesis I study messenger RNA and protein responses to an assortment of environmental stressors in fish. As daily (diel) rhythms are known to be ubiquitous in different tissues, I particularly focus on diel patterns in the responses. The studied species are the three-spined stickleback (Gasterosteus aculeatus L.) and the Arctic char (Salvelinus alpinus L.), both of which have circumpolar distribution in the Northern hemisphere. In the first two studies, three-spined sticklebacks were exposed to both the non-steroidal anti-inflammatory drug diclofenac and low-oxygen conditions (hypoxia), and their responses measured at separate time points in the liver and gills. The results show how the seemingly unrelated environmental stressors, hypoxia and anti-inflammatory drugs, can have harmful combined effects that differ from the effects of each stressor alone. Moreover, both stressors disturbed natural diel patterns in gene expression. In the third study, I studied the responses of three-spined sticklebacks to two test chemicals: one used in hormonal medicine (17α-ethinyl-oestradiol) and one used as a plasticizer and solvent chemical (di-n-butyl phthalate). The results suggest that the phthalate can affect genes related to spermatogenesis in fish testes, while estrogen-mimicking compounds can lead to numerous disturbances in the endocrine system. In the final study, the temperature-dependence of diel rhythms in messenger RNA levels were evaluated in the liver tissue of the Arctic char, a cold-adapted salmonid. The results show that cold acclimation repressed diel rhythms in gene expression compared to warm-acclimated fish, in which the expression of hundreds of genes was rhythmic, suggesting the circadian clock of the Arctic fish species can be sensitive to temperature. Overall, the results of the thesis indicate that fishes’ responses to abiotic factors interact with their diel rhythms, and more studies on the consequences of these interactions are needed to comprehensively understand human impacts on ecosystems.

User Experience Patterns for/of Innovation by Design: A Survey on Design Practices in the Software Development and Innovation Lifecycle

The User Experience (UX) designers are undoubtedly aware of how many UX design methods currently exist and that sometimes it becomes a problem to choose an appropriate one. What are all of methods that designers have in their “arsenal”? When can they use them? This thesis presents the research on the design methods in the contemporary context of User Experience (UX) and Innovations by using a survey approach. The study is limited to cover the domain of consumer mobile services development and provider companies around the world. The study follows 2 clear objectives: (1) to understand what design methods are currently used in that context and to what extent they are used (2) to identify at what stage according to the UX design thinking process for creating innovations they are placed. The study contributes to the research in the field of UX design and Innovations and extends the knowledge in that field together with communities’ (UXPA, SIGCHI, SIGSOFT) members’ cooperation. The research is vital due to lack of information on design practices and their application in the chosen context.