10 resultados para ABNORMAL PHOSPHORYLATION

em Doria (National Library of Finland DSpace Services) - National Library of Finland, Finland


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The present study focuses on two effects of the presence of a noncondensable gas on the thermal-hydraulic behavior of thecoolant of the primary circuit of a nuclear reactor in the VVER-440 geometry inabnormal situations. First, steam condensation with the presence of air was studied in the horizontal tubes of the steam generator (SG) of the PACTEL test facility. The French thermal-hydraulic CATHARE code was used to study the heat transfer between the primary and secondary side in conditions derived from preliminary experiments performed by VTT using PACTEL. In natural circulation and single-phase vapor conditions, the injection of a volume of air, equivalent to the totalvolume of the primary side of the SG at the entrance of the hot collector, did not stop the heat transfer from the primary to the secondary side. The calculated results indicate that air is located in the second half-length (from the mid-length of the tubes to the cold collector) in all the tubes of the steam generator The hot collector remained full of steam during the transient. Secondly, the potential release of the nitrogen gas dissolved in the water of the accumulators of the emergency core coolant system of the Loviisa nuclear power plant (NPP) was investigated. The author implemented a model of the dissolution and release ofnitrogen gas in the CATHARE code; the model created by the CATHARE developers. In collaboration with VTT, an analytical experiment was performed with some components of PACTEL to determine, in particular, the value of the release time constant of the nitrogen gas in the depressurization conditions representative of the small and intermediate break transients postulated for the Loviisa NPP. Such transients, with simplified operating procedures, were calculated using the modified CATHARE code for various values of the release time constant used in the dissolution and release model. For the small breaks, nitrogen gas is trapped in thecollectors of the SGs in rather large proportions. There, the levels oscillate until the actuation of the low-pressure injection pumps (LPIS) that refill the primary circuit. In the case of the intermediate breaks, most of the nitrogen gas is expelled at the break and almost no nitrogen gas is trapped in the SGs. In comparison with the cases calculated without taking into account the release of nitrogen gas, the start of the LPIS is delayed by between 1 and 1.75 h. Applicability of the obtained results to the real safety conditions must take into accountthe real operating procedures used in the nuclear power plant.

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The main objective of the study is to form a framework that provides tools to recognise and classify items whose demand is not smooth but varies highly on size and/or frequency. The framework will then be combined with two other classification methods in order to form a three-dimensional classification model. Forecasting and inventory control of these abnormal demand items is difficult. Therefore another object of this study is to find out which statistical forecasting method is most suitable for forecasting of abnormal demand items. The accuracy of different methods is measured by comparing the forecast to the actual demand. Moreover, the study also aims at finding proper alternatives to the inventory control of abnormal demand items. The study is quantitative and the methodology is a case study. The research methods consist of theory, numerical data, current state analysis and testing of the framework in case company. The results of the study show that the framework makes it possible to recognise and classify the abnormal demand items. It is also noticed that the inventory performance of abnormal demand items differs significantly from the performance of smoothly demanded items. This makes the recognition of abnormal demand items very important.

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This study examines the short time price effect of dividend announcements during a boom and a recession. The data being used here is gathered from the years of 2000 - 2002 when it was a recession after the techno bubble burst and from the years 2005 - 2007 when investors experienced large capital gains all around the world. The data consists of dividend increases and intact observations. The aim is to find out differences in abnormal returns between a boom and a recession. Second, the study examines differences between different dividend yield brackets. Third, Finnish extra dividends, mainly being delivered to shareholders in 2004 are included to the empirical test. Generally stated, the aim is to find out do investors respect dividends more during a recession than a boom and can this be proved by using dividend yield brackets. The empirical results from U.S shows that the abnormal returns of dividend increase announcements during the recession in the beginning of this decade were larger than during the boom. Thus, investors seem to respect dividend increases more when stock prices are falling. Substantial abnormal returns of dividend increases during the time period of 2005 - 2007 could not be found. The results from the overall samples state that the abnormal returns during the recession were positively slightly higher than during the boom. No clear and strong evidence was found between different dividend yield brackets. In Finland, there were substantial abnormal returns on the announcement day of the extra dividends. Thus, indicating that investors saw the extra dividends as a good thing for shareholders' value. This paper is mostly in line with the theory that investors respect dividends more during bad times than good times.

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Tutkimuksen tavoitteena on tutkia epänormaalien tuottojen esiintymistä nousu- ja laskusuhdanteen aikana osingonilmoituspäivän ympärillä. Osinkoilmoitukset ovat kerätty Yhdysvaltojen markkinalta (NYSE) ajanjaksoilta 2000 - 2002, jolloin pörssit laskivat teknokuplan jälkeen ja 2005 - 2007, jolloin sijoittajat kokivat suuria kurssivoittoja. Osinkoilmoitushavainnot koostuvat yhtiöistä, jotka nostivat tai pitivät osinko per osake paikallaan. Tavoitteena on tutkia eroja epänormaaleissa tuotoissa näiden kahden ajanjakson välillä. Toiseksi, tavoitteena on tutkia miten epänormaalit tuotot poikkeavat toisistaan eri osinkotuottoluokissa. Kolmanneksi, tavoitteena on tutkia esiintyikö markkinoilla epänormaaleja tuottoja kun suomalaiset yritykset ilmoittivat ylimääräisistä osingoista, pääasiassa vuonna 2004. Yksinkertaisesti ja lyhyesti sanottuna tavoitteena on tutkia arvostavatko sijoittajat osinkoja enemmän laskukauden vai nousukauden aikana. Rahoitusteorian mukaan sijoittajien tulisi arvostaa laskukauden aikana enemmän yhtiöitä, jotka pystyvät maksamaan huonosta taloustilanteesta huolimatta hyvää osinkoa. Empiiriset testit Yhdysvalloista osoittavat, että osingon nostamisesta johtuvat epänormaalit tuotot olivat suuremmat laskusuhdanteen aikana kuin noususuhdanteen aikana. Tämä on linjassa teorian kanssa. Osingon-nostot aiheuttivat nousukauden aikana vähäisiä epänormaaleja tuottoja. Selviä eroja eri osingontuottoluokkien välillä ei pystytty havaitsemaan. Tulokset yhdistetystä aineistosta osoittavat, että sijoittajat kokivat vähäisiä positiivisia epänormaaleja tuottoja laskukauden aikana. Nousukautena tuotot olivat lähellä nollaa. Suomen markkinoilla havaittiin selvä epänormaalituotto osingonilmoituspäivänä. Tulokset ovat pääpiirteittäin linjassa teorian kanssa. Sijoittajat arvostavat osinkoja hieman enemmän lasku- kuin noususuhdanteen aikana.

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Once the seed has germinated, the plant is forced to face all the environmental changes in its habitat. In order to survive, plants have evolved a number of different acclimation systems. The primary reaction behind plant growth and development is photosynthesis. Photosynthesis captures solar energy and converts it into chemical form. Photosynthesis in turn functions under the control of environmental cues, but is also affected by the growth, development, and metabolic state of a plant. The availability of solar energy fluctuates continuously, requiring non-stop adjustment of photosynthetic efficiency in order to maintain the balance between photosynthesis and the requirements and restrictions of plant metabolism. Tight regulation is required, not only to provide sufficient energy supply but also to prevent the damage caused by excess energy. The very first reaction of photosynthesis is splitting of water into the form of oxygen, hydrogen, and electrons. This most fundamental reaction of life is run by photosystem II (PSII), and the energy required for the reaction is collected by the light harvesting complex II (LHCII). Several proteins of the PSII-LHCII complex are reversibly phosphorylated according to the energy balance between photosynthesis and metabolism. Thylakoid protein phosphorylation has been under extensive investigation for over 30 years, yet the physiological role of phosphorylation remains elusive. Recently, the kinases behind the phosphorylation of PSII-LHCII proteins (STN7 and STN8) were identified and the knockout mutants of these kinases became available, providing powerful tools to elucidate the physiological role of PSII-LHCII phosphorylation. In my work I have used the stn7 and stn8 mutants in order to clarify the role of PSII-LHCII phosphorylation in regulation and protection of the photosynthetic machinery according to environmental cues. I show that STN7- dependent PSII-LHCII protein phosphorylation is required to balance the excitation energy distribution between PSII and PSI especially under low light intensities when the excitation energy transfer from LHC to PSII and PSI is efficient. This mechanism differs from traditional light quality-induced “state 1” – “state 2” transition and ensures fluent electron transfer from PSII to PSI under low light, yet having highest physiological relevance under fluctuating light intensity. STN8-dependent phosphorylation of PSII proteins, in turn, is required for fluent turn-over of photodamaged PSII complexes and has the highest importance upon prolonged exposure of the photosynthetic apparatus to excess light.

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The human genome comprises roughly 20 000 protein coding genes. Proteins are the building material for cells and tissues, and proteins are functional compounds having an important role in many cellular responses, such as cell signalling. In multicellular organisms such as humans, cells need to communicate with each other in order to maintain a normal function of the tissues within the body. This complex signalling between and within cells is transferred by proteins and their post-translational modifications, one of the most important being phosphorylation. The work presented here concerns the development and use of tools for phosphorylation analysis. Mass spectrometers have become essential tools to study proteins and proteomes. In mass spectrometry oriented proteomics, proteins can be identified and their post-translational modifications can be studied. In this Ph.D. thesis the objectives were to improve the robustness of sample handling methods prior to mass spectrometry analysis for peptides and their phosphorylation status. The focus was to develop strategies that enable acquisition of more MS measurements per sample, higher quality MS spectra and simplified and rapid enrichment procedures for phosphopeptides. Furthermore, an objective was to apply these methods to characterize phosphorylation sites of phosphopeptides. In these studies a new MALDI matrix was developed which allowed more homogenous, intense and durable signals to be acquired when compared to traditional CHCA matrix. This new matrix along with other matrices was subsequently used to develop a new method that combines multiple spectra from different matrises from identical peptides. With this approach it was possible to identify more phosphopeptides than with conventional LC/ESI-MS/MS methods, and to use 5 times less sample. Also, phosphopeptide affinity MALDI target was prepared to capture and immobilise phosphopeptides from a standard peptide mixture while maintaining their spatial orientation. In addition a new protocol utilizing commercially available conductive glass slides was developed that enabled fast and sensitive phosphopeptide purification. This protocol was applied to characterize the in vivo phosphorylation of a signalling protein, NFATc1. Evidence for 12 phosphorylation sites were found, and many of those were found in multiply phosphorylated peptides

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Programmed cell death is an important physiological cellular process that maintains homeostasis and protects multicellular organisms from diseases. Apoptosis is the principal mode of cell death, which eliminates unwanted cells and an enormous effort has been made to understand the molecular mechanisms of the signaling pathway and its regulatory systems. Irregular apoptosis often has life-threatening consequences to humans, including cancer, autoimmune diseases and degenerative diseases. In cancer for example, cell death is an attractive target to eradicate uncontrollably proliferating cells that have disregard pro-apoptotic signaling. Targeted therapeutic approaches are not as effective as once expected, since now we know that the cell death pathways are not sole entities in cells, but are highly associated with various cellular processes. Proteins that regulate apoptosis can also control non-apoptotic signaling pathways. For example, c-FLIP is a protein that can either inhibit or promote caspase-8 activation, which is required to induce apoptosis. Not only has c-FLIP opposing effects on initiating apoptosis, but it also regulates various pro-survival signaling pathways in the cell. It is well known that protein expression level is a determinant of how c-FLIP can regulate different signaling pathways, but other regulatory mechanisms potentially affecting the role of c-FLIP are less well understood. This work addresses novel insights into the mechanisms of c-FLIP post-translational modifications and their functional consequences. We have identified that phosphorylation is an important inception for subcellular localization of c-FLIP, thereby dictating which apoptotic and non-apoptotic signaling pathways c-FLIP could regulate to promote cell survival. Furthermore, we have constructed mathematical models to unite independent studies to establish more systematic c-FLIP signaling pathways to understand the dynamics of extrinsically-induced apoptosis.

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Phosphorylation is amongst the most crucial and well-studied post-translational modifications. It is involved in multiple cellular processes which makes phosphorylation prediction vital for understanding protein functions. However, wet-lab techniques are labour and time intensive. Thus, computational tools are required for efficiency. This project aims to provide a novel way to predict phosphorylation sites from protein sequences by adding flexibility and Sezerman Grouping amino acid similarity measure to previous methods, as discovering new protein sequences happens at a greater rate than determining protein structures. The predictor – NOPAY - relies on Support Vector Machines (SVMs) for classification. The features include amino acid encoding, amino acid grouping, predicted secondary structure, predicted protein disorder, predicted protein flexibility, solvent accessibility, hydrophobicity and volume. As a result, we have managed to improve phosphorylation prediction accuracy for Homo sapiens by 3% and 6.1% for Mus musculus. Sensitivity at 99% specificity was also increased by 6% for Homo sapiens and for Mus musculus by 5% on independent test sets. In this study, we have managed to increase phosphorylation prediction accuracy for Homo sapiens and Mus musculus. When there is enough data, future versions of the software may also be able to predict other organisms.