4 resultados para Birth-death Process

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


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Muokatun matriisi-geometrian tekniikan kehitys yleimmäksi jonoksi on esitelty tässä työssä. Jonotus systeemi koostuu useista jonoista joilla on rajatut kapasiteetit. Tässä työssä on myös tutkittu PH-tyypin jakautumista kun ne jaetaan. Rakenne joka vastaa lopullista Markovin ketjua jossa on itsenäisiä matriiseja joilla on QBD rakenne. Myös eräitä rajallisia olotiloja on käsitelty tässä työssä. Sen esitteleminen matriisi-geometrisessä muodossa, muokkaamalla matriisi-geometristä ratkaisua on tämän opinnäytetyön tulos.

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Tässä päättötyössä annetaan kuvaus kehitetystä sovelluksesta Quasi Birth Death processien ratkaisuun. Tämä ohjelma on tähän mennessä ainutlaatuinen ja sen avulla voi ratkaista sarjan tehtäviä ja sitä tarvitaan kommunikaatio systeemien analyysiin. Mainittuun sovellukseen on annettu kuvaus ja määritelmä. Lyhyt kuvaus toisesta sovelluksesta Quasi Birth Death prosessien tehtävien ratkaisuun on myös annettu

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Cell division (mitosis) is a fundamental process in the life cycle of a cell. Equal distribution of chromosomes between the daughter cells is essential for the viability and well-being of an organism: loss of fidelity of cell division is a contributing factor in human cancer and also gives rise to miscarriages and genetic birth defects. For maintaining the proper chromosome number, a cell must carefully monitor cell division in order to detect and correct mistakes before they are translated into chromosomal imbalance. For this purpose an evolutionarily conserved mechanism termed the spindle assembly checkpoint (SAC) has evolved. The SAC comprises a complex network of proteins that relay and amplify mitosis-regulating signals created by assemblages called kinetochores (KTs). Importantly, minor defects in SAC signaling can cause loss or gain of individual chromosomes (aneuploidy) which promotes tumorigenesis while complete failure of SAC results in cell death. The latter event has raised interest in discovery of low molecular weight (LMW) compounds targeting the SAC that could be developed into new anti-cancer therapeutics. In this study, we performed a cell-based, phenotypic high-throughput screen (HTS) to identify novel LMW compounds that inhibit SAC function and result in loss of cancer cell viability. Altogether, we screened 65 000 compounds and identified eight that forced the cells prematurely out of mitosis. The flavonoids fisetin and eupatorin, as well as the synthetic compounds termed SACi2 and SACi4, were characterized in more detail utilizing versatile cell-based and biochemical assays. To identify the molecular targets of these SAC-suppressing compounds, we investigated the conditions in which SAC activity became abrogated. Eupatorin, SACi2 and SACi4 preferentially abolished the tensionsensitive arm of the SAC, whereas fisetin lowered also the SAC activity evoked by lack of attachments between microtubules (MTs) and KTs. Consistent with the abrogation of SAC in response to low tension, our data indicate that all four compounds inhibited the activity of Aurora B kinase. This essential mitotic protein is required for correction of erratic MT-KT attachments, normal SAC signaling and execution of cytokinesis. Furthermore, eupatorin, SACi2 and SACi4 also inhibited Aurora A kinase that controls the centrosome maturation and separation and formation of the mitotic spindle apparatus. In line with the established profound mitotic roles of Aurora kinases, these small compounds perturbed SAC function, caused spindle abnormalities, such as multi- and monopolarity and fragmentation of centrosomes, and resulted in polyploidy due to defects in cytokinesis. Moreover, the compounds dramatically reduced viability of cancer cells. Taken together, using a cell-based HTS we were able to identify new LMW compounds targeting the SAC. We demonstrated for the first time a novel function for flavonoids as cellular inhibitors of Aurora kinases. Collectively, our data support the concept that loss of mitotic fidelity due to a non-functional SAC can reduce the viability of cancer cells, a phenomenon that may possess therapeutic value and fuel development of new anti-cancer drugs.

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The present investigation looks into the attitudes toward death in Paul’s authentic letters, and puts them in relation to modern theories of psychological coping. Drawing on psychologically-oriented hermeneutic theory, and theories about psychological coping in particular, I argue that each case of psychological coping must be understood in its historical situation as strategies emanating from a specific person’s subjective appraisal (cf. Pargament, Lazarus and Folkman). Paul’s letters frequently refer to persecution and violent death. To aid in psychological coping is often integral to the purpose of the letters, which makes the perspective of psychological coping akin to their genre. In the course of a tentatively assumed chronological order of 1 Thessalonians, Galatians, 1 Corinthians, 2 Corinthians, Romans, Philippians, and Philemon, Paul moves from the perception of Jesus dying for the faithful to the understanding of dying with Jesus. His coping strategies concerning death are gradually transformed from conservative and deferring coping styles, to a more self-directing coping style, to collaborative and transformative coping styles, and finally to a new sense of deferring coping style in prison. The last case of deferring coping carries the traits of generosity and flexibility even in the face of death, which is in contrast to his previous letters. Through his correspondence, we see Paul’s attitude toward death transformed from denial to reaction, to processing, to acceptance (cf. Lindemann, Kübler-Ross, Bowlby, Parkes, among others). His strategies also shift in accordance with these understandings. Denial is accompanied by diversion, threat by aggression, processing by rumination, and acceptance by joy. The study shows the hermeneutic benefits of reading Paul’s letters as the rhetorically framed expressions of a person in a particular historical situation. The letters open small windows through which we can glimpse the coping process of a person of antiquity. In adopting the method of psychological exegesis, the study shows that the variety of attitudes toward death in Paul’s letters makes sense from the perspective of psychological coping. The psychological aspect of these letters is an underexamined richness that can extend into areas of contemporary individual and group identity, and from there to public policy and ethics.