927 resultados para Programmed Death Phenomena
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This master’s thesis is focused on power supply network disturbances and their effects on the frequency converter – one of the components of modern process crane electrical system. The most critical disturbance types, their causes and the effect they bring to crane electrical system was determined in this work. Variety of protective devices used for mitigation of disturbances is investigated. Device protection solutions for the frequency converter used in crane applications are presented. Analyses of the power supply requirements for frequency converter and various components of crane electrical system were carried out and as a result the crane power supply requirements list that guarantees normal crane operation was built. This list is to be included in crane projects for troubleshooting purposes in order to determine potentially dangerous network.
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Leibniz's conception of bodies seems to be a puzzling theory. Bodies are seen as aggregates of monads and as wellfounded phenomena. This has initiated controversy and unending discussions. The paper attempts to resolve the apparent inconsistencies by a new and formally spirited reconstruction of Leibniz's theory of monads and perception, on the one hand, and a (re-)formulation and precisation of his concept of preestablished harmony, on the other hand. Preestablished harmony is modelled basically as a covariation between the monadic and the ideal realm.
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The results shown in this thesis are based on selected publications of the 2000s decade. The work was carried out in several national and EC funded public research projects and in close cooperation with industrial partners. The main objective of the thesis was to study and quantify the most important phenomena of circulating fluidized bed combustors by developing and applying proper experimental and modelling methods using laboratory scale equipments. An understanding of the phenomena plays an essential role in the development of combustion and emission performance, and the availability and controls of CFB boilers. Experimental procedures to study fuel combustion behaviour under CFB conditions are presented in the thesis. Steady state and dynamic measurements under well controlled conditions were carried out to produce the data needed for the development of high efficiency, utility scale CFB technology. The importance of combustion control and furnace dynamics is emphasized when CFB boilers are scaled up with a once through steam cycle. Qualitative information on fuel combustion characteristics was obtained directly by comparing flue gas oxygen responses during the impulse change experiments with fuel feed. A one-dimensional, time dependent model was developed to analyse the measurement data Emission formation was studied combined with fuel combustion behaviour. Correlations were developed for NO, N2O, CO and char loading, as a function of temperature and oxygen concentration in the bed area. An online method to characterize char loading under CFB conditions was developed and validated with the pilot scale CFB tests. Finally, a new method to control air and fuel feeds in CFB combustion was introduced. The method is based on models and an analysis of the fluctuation of the flue gas oxygen concentration. The effect of high oxygen concentrations on fuel combustion behaviour was also studied to evaluate the potential of CFB boilers to apply oxygenfiring technology to CCS. In future studies, it will be necessary to go through the whole scale up chain from laboratory phenomena devices through pilot scale test rigs to large scale, commercial boilers in order to validate the applicability and scalability of the, results. This thesis shows the chain between the laboratory scale phenomena test rig (bench scale) and the CFB process test rig (pilot). CFB technology has been scaled up successfully from an industrial scale to a utility scale during the last decade. The work shown in the thesis, for its part, has supported the development by producing new detailed information on combustion under CFB conditions.
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Soitinnus: orkesteri.
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The nucleus is a membrane enclosed organelle containing most of the genetic information of the cell in the form of chromatin. The nucleus, which can be divided into many sub-organelles such as the nucleoli, the Cajal bodies and the nuclear lamina, is the site for several essential cellular functions such as the DNA replication and its regulation and most of the RNA synthesis and processing. The nucleus is often affected in disease: the size and the shape of the nucleus, the chromatin distribution and the size of the nucleoli have remained the basis for the grading of several cancers. The maintenance of the vertebrate body shape depends on the skeleton. Similarly, in a smaller context, the shape of the cell and the nucleus are mainly regulated by the cytoskeletal and nucleoskeletal elements. The nuclear matrix, which by definition is a detergent, DNase and salt resistant proteinaceous nuclear structure, has been suggested to form the nucleoskeleton responsible for the nuclear integrity. Nuclear mitotic apparatus protein, NuMA, a component of the nuclear matrix, is better known for its mitotic spindle organizing function. NuMA is one of the nuclear matrix proteins suggested to participate in the maintenance of the nuclear integrity during interphase but its interphase function has not been solved to date. This thesis study concentrated on the role of NuMA and the nuclear matrix as structural and functional components of the interphase nucleus. The first two studies clarified the essential role of caspase-3 in the disintegration of the nuclear structures during apoptosis. The second study also showed NuMA and chromatin to co-elute from cells in significant amounts and the apoptotic cleavage of NuMA was clarified to have an important role in the dissociation of NuMA from the chromatin. The third study concentrated on the interphase function of NuMA showing NuMA depletion to result in cell cycle arrest and the cytoplasmic relocalization of NuMA interaction partner GAS41. We suggest that the relocalization of the transcription factor GAS41 may mediate the cell cycle arrest. Thus, this study has given new aspects in the interactions of NuMA, chromatin and the nuclear matrix.
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The currently used forms of cancer therapy are associated with drug resistance and toxicity to healthy tissues. Thus, more efficient methods are needed for cancer-specific induction of growth arrest and programmed cell death, also known as apoptosis. Therapeutic forms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are investigated in clinical trials due to the capability of TRAIL to trigger apoptosis specifically in cancer cells by activation of cell surface death receptors. Many tumors, however, have acquired resistance to TRAIL-induced apoptosis and sensitizing drugs for combinatorial treatments are, therefore, in high demand. This study demonstrates that lignans, natural polyphenols enriched in seeds and cereal, have a remarkable sensitizing effect on TRAIL-induced cell death at non-toxic lignan concentrations. In TRAIL-resistant and androgen-dependent prostate cancer cells we observe that lignans repress receptor tyrosine kinase (RTK) activity and downregulate cell survival signaling via the Akt pathway, which leads to increased TRAIL sensitivity. A structure-activity relationship analysis reveals that the γ-butyrolactone ring of the dibenzylbutyrolactone lignans is essential for the rapidly reversible TRAIL-sensitizing activity of these compounds. Furthermore, the lignan nortrachelogenin (NTG) is identified as the most efficient of the 27 tested lignans and norlignans in sensitization of androgen-deprived prostate cancer cells to TRAIL-induced apoptosis. While this combinatorial anticancer approach may leave normal cells unharmed, several efficient cancer drugs are too toxic, insoluble or unstable to be used in systemic therapy. To enable use of such drugs and to protect normal cells from cytotoxic effects, cancer-targeted drug delivery vehicles of nanometer scale have recently been generated. The newly developed nanoparticle system that we tested in vitro for cancer cell targeting combines the efficient drug-loading capacity of mesoporous silica to the versatile particle surface functionalization of hyperbranched poly(ethylene imine), PEI. The mesoporous hybrid silica nanoparticles (MSNs) were functionalized with folic acid to promote targeted internalization by folate receptor overexpressing cancer cells. The presented results demonstrate that the developed carrier system can be employed in vitro for cancer selective delivery of adsorbed or covalently conjugated molecules and furthermore, for selective induction of apoptotic cell death in folate receptor expressing cancer cells. The tested carrier system displays potential for simultaneous delivery of several anticancer agents specifically to cancer cells also in vivo.
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In this study we discuss the atomic level phenomena on transition metal surfaces. Transition metals are widely used as catalysts in industry. Therefore, reactions occuring on transition metal surfaces have large industrial intrest. This study addresses problems in very small size and time scales, which is an important part in the overall understanding of these phenomena. The publications of this study can be roughly divided into two categories: The adsorption of an O2 molecule to a surface, and surface structures of preadsorbed atoms. These two categories complement each other, because in the realistic case there are always some preadsorbed atoms at the catalytically active surfaces. However, all transition metals have an active d-band, and this study is also a study of the in uence of the active d-band on other atoms. At the rst part of this study we discuss the adsorption and dissociation of an O2 molecule on a clean stepped palladium surface and a smooth palladium surface precovered with sulphur and oxygen atoms. We show how the reactivity of the surface against the oxygen molecule varies due to the geometry of the surface and preadsorbed atoms. We also show how the molecular orbitals of the oxygen molecule evolve when it approaches the di erent sites on the surface. In the second part we discuss the surface structures of transition metal surfaces. We study the structures that are intresting on account of the Rashba e ect and charge density waves. We also study the adsorption of suphur on a gold surface, and surface structures of it. In this study we use ab-initio based density functional theory methods to simulate the results. We also compare the results of our methods to the results obtained with the Low-Energy-Electron-Difraction method.
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Regulation of cell growth, death, and polarization by ERBB4 ErbB4 is a member of the epidermal growth factor receptor (EGFR, ErbB) family. The other members are EGFR, ErbB2 and ErbB3. ErbB receptors are important regulators for example in cardiovascular, neural and breast development but control key cellular functions also in many adult tissues. Abnormal ErbB signaling has been shown to be involved in various illnesses such as cancers and heart diseases. Among the ErbBs, ErbB4 has been shown to have unique signaling characteristics. ErbB4 exists in four alternatively spliced isoforms that are expressed in a tissue-specific manner. Two of the isoforms can be cleaved by membrane proteases, resulting in release of soluble intracellular domains (ICD). Once released into the cytosol, the ICD is capable of translocating into the nucleus and participating in regulation of transcription. The functional differences and the tissue-specific expression patterns suggest isoformspecific roles for ErbB4 isoforms. However, the abilities of ErbB4 isoforms to differently regulate cellular functions were discovered only recently and are not well understood. This study aimed to determine the expression patterns of ErbB4 in normal and diseased tissue, and to define whether the cleavable and non-cleavable isoforms could regulate different target genes and therefore, cellular functions. In this study, a comprehensive ErbB4 expression pattern in several normal tissues, various cancers and non-neoplastic diseases was determined. In addition, the data demonstrated that the cleavable and non-cleavable ErbB4 isoforms could regulate different cellular functions and target genes. Finally, this study defined the cellular responses regulated by ErbB4 during kidney development.
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The condensation rate has to be high in the safety pressure suppression pool systems of Boiling Water Reactors (BWR) in order to fulfill their safety function. The phenomena due to such a high direct contact condensation (DCC) rate turn out to be very challenging to be analysed either with experiments or numerical simulations. In this thesis, the suppression pool experiments carried out in the POOLEX facility of Lappeenranta University of Technology were simulated. Two different condensation modes were modelled by using the 2-phase CFD codes NEPTUNE CFD and TransAT. The DCC models applied were the typical ones to be used for separated flows in channels, and their applicability to the rapidly condensing flow in the condensation pool context had not been tested earlier. A low Reynolds number case was the first to be simulated. The POOLEX experiment STB-31 was operated near the conditions between the ’quasi-steady oscillatory interface condensation’ mode and the ’condensation within the blowdown pipe’ mode. The condensation models of Lakehal et al. and Coste & Lavi´eville predicted the condensation rate quite accurately, while the other tested ones overestimated it. It was possible to get the direct phase change solution to settle near to the measured values, but a very high resolution of calculation grid was needed. Secondly, a high Reynolds number case corresponding to the ’chugging’ mode was simulated. The POOLEX experiment STB-28 was chosen, because various standard and highspeed video samples of bubbles were recorded during it. In order to extract numerical information from the video material, a pattern recognition procedure was programmed. The bubble size distributions and the frequencies of chugging were calculated with this procedure. With the statistical data of the bubble sizes and temporal data of the bubble/jet appearance, it was possible to compare the condensation rates between the experiment and the CFD simulations. In the chugging simulations, a spherically curvilinear calculation grid at the blowdown pipe exit improved the convergence and decreased the required cell count. The compressible flow solver with complete steam-tables was beneficial for the numerical success of the simulations. The Hughes-Duffey model and, to some extent, the Coste & Lavi´eville model produced realistic chugging behavior. The initial level of the steam/water interface was an important factor to determine the initiation of the chugging. If the interface was initialized with a water level high enough inside the blowdown pipe, the vigorous penetration of a water plug into the pool created a turbulent wake which invoked the chugging that was self-sustaining. A 3D simulation with a suitable DCC model produced qualitatively very realistic shapes of the chugging bubbles and jets. The comparative FFT analysis of the bubble size data and the pool bottom pressure data gave useful information to distinguish the eigenmodes of chugging, bubbling, and pool structure oscillations.
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There are few studies that approach the epidemiology of deaths in racehorses in a broad manner. The majority focus on a specific affection or procedure. Brazil does not have a program instituted for the monitoring of deaths of horses. By means of a descriptive study in association with a multivariate analysis method, an epidemiologic profile was determined for deaths related to musculoskeletal (MS), gastrointestinal (GI), respiratory (RES) systems, neurologic origin (NEU) and sudden death (SD) for the years of 2002 to 2008, at the Octavio Dupont Veterinary Hospital-Rio de Janeiro (ODVH). Males comprised the majority of deaths and that deaths were related to, decreasing order, MS>GI>SD>NEU>RES, with respect to general mortality rate per large group of determined causes (TSPMr). The majority of deaths registered included horses aged four to five years (ID4-ID5). We observed the following correspondence relations: (3-year period = SM - ID>5 - SD; ID>5 - GI; ID4-5 - MS; SF - ID<4 - RES/ NEU); (4-year period = SM - ID>5 - GI; SF - ID<4 - NEU; ID4-5 - MS; GI - ID>5). The present study points out the importance and necessity of epidemiologic studies of lesions in horses, based on diagnosis for the recognition of predisposing factors and prevention.
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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.