Дисертації: "M-cycle"

1

LeaÌƒo, Maria JoaÌƒo de Lemos Pinto Estrela. "Modulation of G2/M cell cycle checkpoints by Epstein-Barr virus." Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414473.

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2

Blakemore, Louise Margaret. "Curcumin-induced G2/M cell cycle arrest in colorectal cancer cells." Thesis, University of Leicester, 2011. http://hdl.handle.net/2381/9809.

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Curcumin, a diet-derived chemopreventive and chemotherapeutic agent has been shown to induce G2/M cell cycle arrest, and previous studies suggested that microtubule depolymerisation may be linked to M-phase arrest. However, mechanisms involved have not been elucidated and often non-physiological concentrations of curcumin were used. The goal of this study was to characterise in more detail curcumin-induced cell cycle arrest using a panel of human colorectal cancer cell (CRC) lines, HT-29, SW480, HCT116 p53+/+, HCT116 p53-/- and HCT116 p21-/-. Using physiologically relevant concentrations of curcumin (5-10μM), achievable in the gut tissue following oral ingestion, cell cycle analysis showed that treatment for 12 hours results in significant G2/M arrest in all five cell lines. Curcumin treatment significantly increased the number of cells in M phase in 4 out of the 5 lines tested for this duration, and those with microsatellite instability (HCT116) were found to have a higher mitotic index than those with chromosomal instability. Pre-treatment with caffeine abrogated mitotic arrest in these cell lines, indicating the involvement of the ATM/ATR kinases. Activating phosphorylation of the Chk1 kinase was increased and total protein levels of CDC25C reduced, further implicating the DNA damage pathway in the induction of arrest. Higher levels of HSP70 were also found, indicating proteotoxic stress such as proteasomal inhibition. Image analysis revealed impaired mitotic progression, and significantly higher levels of mitotic spindle abnormalities following curcumin treatment. Aurora B mislocalisation and significantly lower levels of centrosomal separation were found in the HCT116 p53+/+ line. Furthermore, the high levels of pH2A.X staining seen in curcumin-treated mitotic but not interphase cells suggest that aberrant mitosis may result in DNA damage. This proteotoxic and genotoxic stress incurred following curcumin treatment may contribute to the upregulation of NKG2D ligands on the cell surface, leading to CRC lysis and enhancement of the anti-cancer immune response.

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3

Quinn, Jennifer E. "BRCA1 mediated G2/M cell cycle arrest in response to taxol." Thesis, Queen's University Belfast, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326034.

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4

Winks, Joanna Shaw. "Agonist-induced inhibition of the m-current : involvement of the phosphoinositide cycle." Thesis, University College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405561.

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5

Hirabayashi, Shigeki. "APOBEC3B is preferentially expressed at the G2/M phase of cell cycle." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/264663.

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京都大学
新制・課程博士
博士(医学)
甲第23382号
医博第4751号
新制||医||1052(附属図書館)
京都大学大学院医学研究科医学専攻
(主査)教授伊藤貴浩, 教授滝田順子, 教授江藤浩之
学位規則第4条第1項該当
Doctor of Medical Science
Kyoto University
DFAM

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6

El, Dika Mohammed. "Régulation de la phase M du cycle cellulaire par CDK1, PP2A et CDC6." Thesis, Rennes 1, 2013. http://www.theses.fr/2013REN1S068.

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L'objectif de cette thèse est de mieux comprendre la régulation de la phase M du cycle cellulaire. Nos expériences ont été effectuées dans des extraits acellulaires d’embryons de Xenopus laevis. Tout d'abord, nous montrons que le moment de l'entrée en phase M est précisément déterminé par un équilibre entre l'activité de la protéine kinase CDK1 et l’activité d’une protéine phosphatase sensible à l'acide okadaïque, PP2A. Nous montrons également le rôle de la protéine CDC6 dans la régulation de l'entrée dans la première phase M embryonnaire. En effet, CDC6 inhibe CDK1 et à travers cette action régule la dynamique de cette kinase lors de l'entrée et de la progression en phase M. Ces résultats mettent en évidence un nouveau contrôle qui précise le moment du clivage embryonnaire. Ce contrôle joue un rôle clé dans la coordination entre les mécanismes de régulation du cycle cellulaire et le programme de développement de l'embryon
The aim of this thesis is to understand better the regulation of the M-phase of the cell cycle. Experiments were done in cell-free extracts of Xenopus laevis one-cell embryos. Firstly, we show that the timing of the M-phase entry is precisely determined by a balance between the activity of CDK1 kinase and okadaic acid sensitive phosphatase, mainly PP2A. Secondly, we show the role of CDC6 protein in regulation of the entry into the first embryonic M-phase. CDC6 inhibits CDK1 and through this action regulates the dynamic of this kinase upon M-phase entry and during M-phase progression. This mechanism discovered during my PhD allows controlling precisely the timing of embryonic cleavage. This control plays a key role in coordinating the cell cycle regulating machinery and the development program of the embryo

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7

Lorca, Thierry. "Mécanisme de sortie de la phase M du cycle cellulaire : inactivation de la kinase cdc2." Montpellier 1, 1993. http://www.theses.fr/1993MON1T004.

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8

Costa, Marylia Gabriella Silva [UNESP]. "Resistência de nogueira-macadâmia (Macadamia integrifolia Maiden e Betche) aos nematoides-das-galhas." Universidade Estadual Paulista (UNESP), 2018. http://hdl.handle.net/11449/154207.

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A nogueira-macadâmia pertence à família Proteaceae e é originária da Austrália. Sua noz é considerada a mais saborosa entre as nozes comercializadas. No Brasil, nos últimos anos, há uma expansão da macadamicultura e de seu plantio em cafezais. Além da sua consorciação com o cafeeiro, a macadâmia é uma opção de plantio em consórcio com outras culturas de ciclo curto e alternativa para o plantio em novas áreas. Embora haja um aumento da área plantada de macadâmia, as informações sobre danos causados por nematoides nessa cultura são escassas. Principalmente, aos nematoides-das-galhas, onde com frequência, as populações desses patógenos são altas em áreas cultivadas com café. No Brasil, a produção de mudas de macadâmia se dá quase que exclusivamente pelo método de enxertia, tendo como principal porta-enxerto a variedade 10-14 (Aloha). Portanto, o objetivo do trabalho foi avaliar a resistência da variedade 10-14 (Aloha) e das cultivares HAES344, HAES-660, HAES 816, IAC 4-12B, IAC 9-20 e IAC 4-20 a Meloidogyne incognita raça 2, M. paranaensis, M. exigua, M. enterolobii e M. javanica, além de estudar o ciclo de vida dos nematoides-das-galhas na variedade 10-14 (Aloha) por ser a mais utilizada como porta-enxerto na produção de mudas. O substrato de cada parcela foi infestado com aproximadamente 5.000 ovos e eventuais juvenis dos nematoides estudados, separadamente, provenientes de populações puras, processadas segundo o método proposto por Hussey e Barker. Tomateiros ‘Rutgers’ foram utilizados como padrão de viabilidade do inóculo de M. incognita raça 2, de M. enterolobii e de M. javanica, plantas de café ‘Mundo Novo’ foram utilizadas para atestar a viabilidade de M. paranaensis e M. exigua. O delineamento experimental utilizado foi inteiramente ao acaso, com cinco repetições. As avaliações foram feitas aos 120 dias após a inoculação. Os índices de galhas (IG) e índices de massas de ovos (IMO) foram obtidos de acordo com a escala de notas proposta por Taylor e Sasser. Para a obtenção do fator de reprodução (FR=PF/PI), os sistemas radiculares foram processados separadamente de acordo com o método de Coolen e D’Herde. Os experimentos para a avaliação do ciclo de vida das espécies de Meloidogyne foram montados em câmaras incubadoras (BOD) sob temperatura e fotoperíodo controlados. As plântulas de macadâmia, após a germinação, foram transplantadas para copos de 210 mL com substrato autoclavado. Para a obtenção do juvenil de segundo estágio (J2), os nematoides foram processados separadamente de acordo com a técnica proposta por Hussey e Barker, em seguida, as suspensões de cada espécie do nematoide foram colocadas em aparatos de Baermanns modificados para recipiente raso. Cinco dias após o transplante, cada plântula foi inoculada com 300 (J2) de M. incognita, M. paranaensis, M. exígua, M. enterolobii ou M. javanica. As avaliações foram aos 5, 15, 25 e 35 dias após a inoculação (DAI). Os sistemas radiculares das plantas foram lavados e coloridos com fucsina ácida para a classificação dos estádios de desenvolvimento do nematoide. Os resultados mostraram que todas as cultivares e a variedade 10-14 (Aloha) de macadâmia foram resistentes aos nematoides estudados, demostrando a resistência. Os nematoides não completaram o ciclo de vida na variedade 10-14 (Aloha), podendo ser utilizada como porta-enxerto na produção de mudas.
The macadamia nut belongs to the Proteaceae family, is originally from Australia, and is considered one of the most flavorful nuts in the market. In Brazil, macadamia nuts have been increasingly planted alongside coffee. In addition to its consortium with this crop, macadamia can also be planted alongside other short cycle cultures, and is also an alternative to planting in new areas. Although an increase in planted macadamia areas has been observed, information on nematode damage to this crop is scarce, mainly regarding root-knot nematodes, which are frequently observed in high populations in coffee crop areas. In Brazil, the production of macadamia seedlings occurs almost exclusively by the grafting method, with the 10-14 (Aloha) variety as the rootstock. In this context, the aim of this research was to evaluate the resistance of macadamia variety 10-14 (Aloha) and macadamia cultivars, HAES-344, HAES-660, HAES 816, IAC 4-12B, IAC 9-20 and IAC 4-20 to Meloidogyne incognita race 2, M. paranaensis, M. exigua, M. enterolobii and M. javanica, and to study the life cycle of root-knot nematodes in the variety 10-14 (Aloha), as it is the most frequent rootstock for seedling production. The substrate of each plot was infested with approximately 5,000 nematode eggs, separately, from pure populations processed according to the Hussey and Barker method. 'Rutgers' tomatoes were used as the viability standard for the M. incognita race 2, M. enterolobii and M. javanica inocula. 'Mundo Novo' coffee plants were used to confirm M. paranaensis and M. exigua viability. The experimental design was completely randomized, with five replications and the evaluations were carried out at 120 days after inoculation. The Gall index (GI) and egg mass index (EMI) were obtained according to the scale proposed by Taylor and Sasser. To calculate the reproduction factor (RF = PF/PI), the root systems were processed separately according to the Coolen and D'Herde method. The experiments carried out for the Meloidogyne species life cycle evaluation were mounted in incubators (BOD) under controlled temperature and photoperiod. After germination, Macadamia seedlings were transplanted into 210 mL bowls with autoclaved substrate. To obtain the juvenile second stage (J2), the nematodes were processed separately according to the technique proposed by Hussey and Barker. Suspensions of each nematode species were placed in a Baermanns apparatus, modified to a shallow container. Five days after transplantation, each seedling was inoculated with 300 (J2) M. incognita, M. paranaensis, M. exigua, M. enterolobii or M. javanica. Evaluations were carried out at 5, 15, 25 and 35 days post-inoculation (DPI). The plant root systems were washed and stained with acid fuchsin for nematode development stage classification. The results indicate that all macadamia cultivars and variety 10-14 (Aloha) were resistant to the studied nematodes, demonstrating resistance. The nematodes did not complete their life cycle on the 10-14 (Aloha) variety, indicating that it may be used as the rootstock for seedlings.

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9

Montanez-Wiscovich, Marjorie E. "Discerning the Role of LMO4 as a Global Modulator of G2/M Cell Cycle Progression and Centrosome Cycle in Breast Cancer Cells." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1259899890.

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10

Cervigni, Romina Ines. "Analysis of the molecular mechanisms of the Golgi-based G2/M cell cycle checkpoint." Thesis, Open University, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.580685.

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This thesis is focused on the role of Golgi fragmentation in the regulation of the G2/M transition of the cell cycle, and it is based on previous findings that Golgi fragmentation is required to enter into mitosis. The Golgi complex is composed of many cisternal stacks that are interconnected by tubules, to form a continuous 'ribbon-like' structure. During mitosis, the Golgi ribbon undergoes extensive fragmentation through a multi stage process that promotes its correct partitioning and inheritance by the daughter cells. The first part of my work is focused on the understanding of the mechanisms which block cells in G2 when Golgi fragmentation is inhibited. I show that the Golgi-dependent G2 arrest is mediated by a failure of centrosome maturation, an event that is essential to achieve activation of the CdkllCyclinB (Cdkl/CycB) complex, the master regulator of mitosis. Indeed, the failure of Golgi fragmentation inhibits the recruitment to and activation at the centrosome of the kinase Aurora-A. This kinase is essential for the activation of Cdkl/CycB at the centrosome. This part of the thesis contributes to the definition of a previously unidentified point of dialogue between the Golgi apparatus and the centrosome in the regulation of G2/M transition. The second part of the thesis describes the development of three novel experimental approaches to induce the block of Golgi fragmentation. They integrate a previously developed assay that is based on the microinjection of blockers of Golgi fragmentation, a reliable but demanding approach. The assays that I have developed are based on the ability of the GRASP65 protein to regulate Golgi fragmentation. As well as being essential for inducing the Golgi checkpoint in a wide cell population, they are also useful for the unravelling of the mechanism through which GRASP65 acts in the Golgi checkpoint.

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11

Labbe, Jean-Claude. "Identification de MPF : un facteur universel contrôlant l'entrée en phase M du cycle cellulaire." Montpellier 2, 1990. http://www.theses.fr/1990MON20269.

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Chez les eucaryotes, l'entree en phase m du cycle cellulaire est controlee par un facteur (mpf: m-phase promoting factor) dont l'activite oscille au cours du cycle cellulaire. Ce facteur ne presente pas de specificite zoologique. Nous l'avons purifie a partir d'ovocytes d'etoile de mer et identifie a une serine-threonine kinase consistant en un complexe de deux sous-unites, une sous-unite catalytique (p34#c#d#c#2) et une sous-unite regulatrice (cycline b), homologue respectivement aux produits des genes cdc2#+ et cdc13#+ de la levure schizosaccharomyces pombe

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12

Hamanowicz, Aleksandra [Verfasser], and Simon D. M. [Akademischer Betreuer] White. "The 3D view on cosmic baryon cycle / Aleksandra Hamanowicz ; Betreuer: Simon D. M. White." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1218466111/34.

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13

Trevino, Cantu Hector. "Life-Cycle Cost Analysis for Offshore Wind Farms:Reliability and Maintenance.O&M Cost Drivers Analysis." Thesis, Högskolan på Gotland, Institutionen för kultur, energi och miljö, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-217018.

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Operations and maintenance (O&M) activities represent a significant share of the expenses during the lifetime of offshore wind farms. When compared to onshore wind farms, O&M costs are increased for the offshore case, as specialized vessels, weather windows and rough conditions mean more failures, downtime (decreasing availability), spare parts, and man-hours.This study comprises an analysis of the available O&M data from a selected offshore wind farm. The results and conclusions from this investigation could then be used to evaluate possible reliability improvements and compare options for the maintenance strategies, as well as to ponder the convenience of warranty periods and O&M agreements between wind farm operators and wind turbine manufacturers or O&M service providers.The life-cycle cost (LCC) concept is utilized in the analysis of the wind farm survey for this thesis. LCC analysis could be the starting point to make decisions regarding specific wind turbine models, as selecting the turbines with the lowest initial cost may not be necessarily the scenario which also costs the least amount of money when taking into consideration the whole life cycle. It may also be a great tool to forecast future operational incomes and expenses of offshore wind farms.

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14

Martín, Rodríguez Elena 1989. "Control of G2/M cell cycle transition by a complex of the splicing factors SPF45/SR140/CHERP." Doctoral thesis, Universitat Pompeu Fabra, 2018. http://hdl.handle.net/10803/572042.

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A splicing network analysis that captured functional similarities among spliceosomal components, revealed a prominent core module containing splicing factors SPF45, SR140 and CHERP. We report that these factors form a complex, as they stabilize each other’s protein levels, coimmunoprecipitate and co-sediment in glycerol gradients. Depletion of SPF45, SR140 or CHERP in HeLa cells impairs progression through the G2/M phase of the cell cycle and this is correlated with decreased cell proliferation and increased apoptosis. Transcriptome-wide analyses revealed extensive overlap between alternative splicing events regulated by SPF45, SR140 or CHERP and that common targets are enriched in G2/M transition genes. A relevant alternative splicing change was identified in FOXM1, a key transcriptional regulator of G2/M transition. Depletion of SPF45, SR140 or CHERP promotes total or partial inclusion of FOXM1 exon 9, which disrupts the transactivation domain and results in a non-functional FOXM1 isoform. We propose that alternative splicing regulation of FOXM1 contributes to the cell cycle G2/M phase arrest observed upon SPF45, SR140 or CHERP knock down and discuss possible physiological scenarios for this regulation.
Un análisis de red de factores de splicing capturó similaridades funcionales entre componentes del spliceosoma y reveló un prominente módulo central que contiene a los factores de splicing SPF45, SR140 y CHERP. Hemos demostrado que estos factores forman un complejo, ya que estabilizan mutuamente sus niveles de proteínas, coinmunoprecipitan y co-sedimentan en gradientes de glicerol. La depleción de SPF45, SR140 o CHERP en células HeLa impide la progresión a través de la fase G2/M del ciclo celular y ello se correlaciona con una disminución de la proliferación celular y un aumento de la apoptosis. Análisis globales del transcriptoma han revelado un sustancial solapamiento entre los eventos de splicing alternativo regulados por SPF45, SR140 o CHERP y que las dianas comunes están enriquecidas en genes implicados en la transición G2/M. Se ha identificado un cambio de splicing alternativo relevante en FOXM1, un regulador transcripcional clave en la transición G2/M. La depleción de SPF45, SR140 o CHERP promueve la inclusión total o parcial del exon 9 de FOXM1, lo que interrumpe el dominio de transactivación y da lugar a una isoforma no funcional de FOXM1. Proponemos que la regulación del splicing alternativo de FOXM1 contribuye al arresto en la fase G2/M del ciclo celular observado cuando se deplecionan SPF45, SR140 o CHERP y discutimos posibles escenarios fisiológicos para esta regulación.

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15

Taheri, Hadi [Verfasser], and M. [Akademischer Betreuer] Gabi. "Numerical Investigation of Stratified Thermal Storage Tank Applied in Adsorption Heat Pump Cycle / Hadi Taheri. Betreuer: M. Gabi." Karlsruhe : KIT-Bibliothek, 2014. http://d-nb.info/1051848180/34.

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16

Joshi, Chirag [Verfasser], and M. [Akademischer Betreuer] Gabi. "Experimental Investigations of Adsorption Chiller Cycle Using Stratified Thermal Storage for Heat Recovery / Chirag Joshi. Betreuer: M. Gabi." Karlsruhe : KIT-Bibliothek, 2016. http://d-nb.info/1103574078/34.

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17

PUERTOLLANO, AZUCENA A. "Contributions a l'etude du cycle thermodynamique a mousse pour l'exploitation de l'energie thermique des mers (e. T. M. )." Paris 7, 1987. http://www.theses.fr/1987PA077283.

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Apres avoir defini une methode d'evaluation des cycles d'energie thermique des mers (e. T. M. ), le cycle a mousse est etudie en considerant la mousse comme un systeme diphasique obeissant aux lois des ecoulements diphasiques. Une modelisation du cycle est proposee et l'application energetique du cycle a mousse est discutee

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18

MORDRET, GUY. "Regulation des map kinases pendant la la phase m du cycle cellulaire dans les ovocytes d'etoile de mer." Rennes 1, 1993. http://www.theses.fr/1993REN10115.

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Les map kinases sont des serine/threonine kinases regulees par phosphorylation sur deux sites adjacents tyrosine et threonine en reponse a des stimuli varies. Elles sont activees apres stimulation des cellules quiescentes en g#o par des agents mitogeniques, ou pendant la transition g2/m du cycle cellulaire. Les proteines kinases responsables de leur activation sont appelees map kinase kinase (mapkks). Plusieurs mapkks ont deja ete clonees chez le xenope et chez les mammiferes. Dans les ovocytes d'etoiles de mer bloques en prophase de la premiere division meiotique, la seule map kinase caracterisee est p44#m#p#k. Par differentes approches (chromatographie, immunologique, biologie moleculaire), il est possible de montrer qu'il existe d'autres map kinases, d'ou probablement plusieurs mapkks. En utilisant une proteine recombinante humaine p44#e#r#k#1 que nous avons caracterisee, nous avons ete capables de purifier un activateur a partir des ovocytes d'etoile de mer. Cet activateur n'est pas une proteine kinase et semble n'activer que l'activite autophosphotransferase de p44#e#r#k#1. L'identite d'un tel activateur est encore inconnue. Des controles ont ete effectues en parallele avec une mapkk purifiee partiellement a partir de plaquettes sanguines de mouton

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19

Cude, Kelly J. "Activation of a novel ERK5-NF-kappaB pathway is required for G2/M progression in the cell cycle /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/5003.

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20

Palmquist, Samuel, and Vincent Sandberg. "The art of surfing the waves of mergers and acquisitions : An empirical study on the macroeconomic determinants of mergers and acquisitions in Sweden." Thesis, Örebro universitet, Handelshögskolan vid Örebro Universitet, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-25832.

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This thesis examines the linkages between macroeconomic variables and the number of domestic Mergers & Acquisitions (M&A) in Sweden during 1998-2011 (in terms of changes). This study treats stationary times series data, from which multiple regression models are assembled. These models include gross domestic product, OMX Stockholm price index, lending rate, money supply, debt rate, consumer confidence, the unemployment rate and capacity utilization as explanatory variables. Aggregate number of M&As is set to the dependent variable. The outcome was that gross domestic product, money supply, unemployment rate and stock prices can help explain fluctuations in M&A activity during different time frames. However, the majority of the explanation for fluctuations in M&A activity lies within factors beyond ourestimation model. Through a Granger-causality test, we establish if the significant variables can help to predict M&A activity and vice versa. During different time periods gross domestic product and unemployment helps in predicting M&A activity. M&A activity also improves the prediction of gross domestic product in some time periods.

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21

Le, Breton Magali. "Caractérisation et identification d'ARNms différentiellement recrutés dans les polysomes en fonction de l'activité du complexe CDK1/cycline B." Paris 6, 2004. http://hal.upmc.fr/tel-01117534.

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22

Carabédian, Alice. "Le devenir-autre de l'utopie : représentations d'un imaginaire politique conflictuel dans le Cycle de la Culture d'Iain M. Banks." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC322.

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Il est difficile de ne pas concevoir l’utopie du côté de la rupture : division spatiale originelle, tension temporelle, désaccord critique. Pourtant les théories et attaques des anti-utopistes voient dans l’utopie un monde illusoire voire inutile, clos, signant la fin des temps et potentiellement dangereux pour l’humanité. Et si l’utopie n’était pas le programme de la société meilleure à réaliser, mais bien au contraire une pratique transgressive, une apparition de discontinuité dans notre « ici et maintenant », un excès qui vient doubler le réel plutôt qu’un possible à réaliser dans le futur ?Iain M. Banks est un auteur de science-fiction contemporain original et audacieux, qui, conscient des dangers inhérents à l’utopie, a su jouer avec ces limites pour proposer une société utopique totalement inédite : cette utopie s’appelle la Culture. Comment réinvestir singulièrement l’utopie ? Comment la science-fiction – et plus précisément le genre du space-opéra – permet-elle de mettre en scène des problématiques politiques dignes d’un intérêt philosophique ?Iain M. Banks imagine une utopie tout entière tournée vers la rencontre, la proximité, la nouveauté. Subvertissant les traditions utopique et science-fictionnelle, le Cycle de la Culture est traversé par l’altérité et le conflit. Ces deux caractéristiques sont les fils directeurs de cette thèse qui vise à reconceptualiser l’utopie dans une perspective philosophique, politique et littéraire, en travaillant les représentations du discours utopique au sein du laboratoire science fictionnel.Ce discours prend ici trois formes : dystopie, hétérotopie, (e)utopie. Ensemble, elles dessinent une « culture utopique radicale »
It is difficult not to conceive utopia as a rupture: through original spatial division, temporal tension, critical discordance. Yet, theories and attacks from anti-utopians consider utopia as an illusory world, even useless, enclosed, marking the end of times and potentially dangerous for humanity. What if utopia was not the programme of a better society to realize,but instead a transgressive practice, an apparition of discontinuity in our « now and here », an excess which overtakes reality rather than a possible that has yet to be realized in the future? Iain M. Banks is a contemporary, original and audacious science-fiction author, who,aware of the inherent dangers of utopia, has known how to challenge these limits in order to provide a completely unique utopian society: this utopia is called the Culture. How to critically reinvest utopia? How can science fiction – and more precisely the genre of space-opera – depict political issues, worthy of philosophical enquiry? Iain M. Banks imagines a space for utopia, entirely oriented towards encounter,proximity, and novelty. Subverting science-fictional and utopian traditions, notions of alterity and conflict span the Culture Cycle. These two characteristics are the guiding principles of this dissertation, which aims at reconceptualizing utopia through a philosophical, political and literary perspective, by way of analysing the representations of utopian discourses within the science-fictional laboratory. These discourses take three shapes: dystopia, heterotopia, (e)utopia. Together, they outline a “radical utopian culture”

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Mailhat, Charlotte. "Etudes des modifications post-traductionnelles de la phosphatase Cdc25C lors de la régulation de la transition G2/M du cycle cellulaire." Toulouse 3, 2007. http://www.theses.fr/2007TOU30310.

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La phosphatase Cdc25C est un acteur critique de la progression du cycle cellulaire par son rôle jouée dans le contrôle de l'activation du complexe CDK1-Cycline B lors de l'entrée en mitose et de la mise en place des mécanismes de surveillance. Son activité est régulée par de nombreuses kinases impliquées dans les cascades de signalisation cellulaire résultant dans la phosphorylation de nombreux résidus. Au cours de cette étude, nous avons purifié Cdc25C à partir de cellules humaines et réalisé une approche protéomique globale dans le but d'identifier de nouvelles modifications régulatrices. Nous présentons dans ce manuscrit la mise au point des conditions de purification de la phosphatase et les différentes modifications post-traductionnelles que nous avons identifiées par spectrométrie de masse, en particulier deux phosphorylations sur les résidus S168 et S263 et une méthylation sur le résidu R35. Pour terminer nous avons réalisé une analyse fonctionnelle des phosphorylations sur les S168 et S263. Nous avons montré par imagerie cellulaire que la mutation de la S263 en alanine conduisait à l'accumulation nucléaire de Cdc25C. Nous proposons ainsi que la phosphorylation de la S263 soit impliquée dans un mécanisme de régulation qui module l'import nucléaire de Cdc25C
CDC25C phosphatase is a key actor in cell cycle progression that controls the activation of CDK1-cyclin B at mitosis and during the G2/M DNA damage. Its activity is known to be highly regulated by a number of signalling pathway-activated kinases resulting in its phosphorylation on multiple residues. In this study, we have purified CDC25C from cells and have used a proteomic approach to identify new regulatory phosphorylations. Here, we report the identification by mass spectrometry of two phosphorylations on serine 168 and 263, and one méthylation on arginine 35. To conclude we have realized a functional analysis of S168 and S263 phosphorylations. We demonstrate by cell imaging that mutation of S263 to alanine leads to a nuclear accumulation of CDC25C. We propose that phosphorylation at S263 is part of the regulatory mechanism that modulates nuclear import of CDC25C, thus preventing cytoplasm to nucleus shuttling

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Lo, On-Hei Solomon [Verfasser], Jens M. [Akademischer Betreuer] Schmidt, Matthias [Gutachter] Kriesell, and Tomáš [Gutachter] Madaras. "Subtrees search, cycle spectra and edge-connectivity structures / On-Hei Solomon Lo ; Gutachter: Matthias Kriesell, Tomáš Madaras ; Betreuer: Jens M. Schmidt." Ilmenau : TU Ilmenau, 2019. http://d-nb.info/1196968438/34.

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Putnam, Charles Wellington. "Integration of G2/M checkpoint, spindle assembly checkpoint,and Ran cycle regulators in the Saccharomyces cerevisiae DNA damage mitotic arrest response." Diss., The University of Arizona, 2004. http://hdl.handle.net/10150/280738.

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It is axiomatic that genomic stability is dependent upon regulatory pathways, termed checkpoints, which sense perturbations of cell cycle execution including damage to chromosomal DNA. In Saccharomyces cerevisiae, the principal DNA damage checkpoint is at G2/M. Heretofore, this and other checkpoints, such as the spindle assembly checkpoint, which is also operative at the metaphase/anaphase transition, have been viewed as essentially linear pathways, responding to a specific type of damage, signaling via sui generis proteins, and targeting a limited number of effectors for arrest. In a 1999 report, our laboratory reported bifurcation of the pathway downstream from Mec1 activation; this established the genetic basis of a previously unexplained phenotype: partial arrest defects of rad53 and pds1 strains. Moreover, the bifurcated pathway model established the framework for subsequent studies which determined the molecular targets of each. Here, I present evidence that the DNA damage and spindle checkpoint pathways are part of a network which is capable of bilaterally responding to damage. After DNA damage the Mec1-centric pathway is initially preeminent; the spindle pathway is redundant. After prolonged damage, however, the spindle checkpoint components become required for arrest. In studies of overexpression of the Mec1 homologue Tel1, I delineated the pathway responsible for the resultant constitutive delay; strikingly, the spindle components Mad1 and Mad2 are activated, not from the kinetochore, but from the nuclear periphery. This off-kinetochore pool of Mad proteins, anchored by the myosin-like proteins, Mlp1 and Mlp2, is likewise activated by the DNA damage response. Tel1 physically interacts with Xrs2 of the Mre11·Rad50·Xrs2 complex; evidence that Xrs2 participates in these same responses is also presented. Finally, the sensitivity of xrs2 to a microtubule poison, benomyl, suggests that M R·X may also participate in sensing spindle disruption. From a screen for novel checkpoint genes, I isolated Gtr1 (and later, Gtr2), which are negative regulators of the Ran cycle. Here, I provide evidence that deletion of either produces an identical partial arrest defect, which is independent of the Mec1-centric pathway. Because Gtr2 physically interacts with Esp1, I surmise that Gtr1/Gtr2 may enforce cytosolic localization of Pds1/Esp1 after DNA damage.

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Moyal, Élizabeth. "Implication des protéines controlant le point de transition G2/M du cycle cellulaire et des protéines prénylées dans les mécanismes de radiorésistance." Toulouse 3, 1997. http://www.theses.fr/1997TOU30066.

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La radioresistance tumorale a ete associee a un arret prolonge en phase g2 des cellules soumises aux rayonnements ionisants et a une inhibition de l'activite du complexe associant la serine threonine kinase p34cdc2 et la cycline b, complexe controlant le point de passage g2/m. Nous avons tout d'abord etudie l'expression et la localisation de p34cdc2 et de la cycline b dans des carcinomes des voies aerodigestives superieures ayant ou non recidive dans les champs d'irradiation. Nous montrons que, dans les tumeurs ayant recidives dans les champs d'irradiation, p34cdc2 presente une localisation preferentiellement cytoplasmique, dans la recidive mais aussi dans la tumeur primitive. Ce resultat suggere une inactivation intrinseque de p34cdc2 dans les tumeurs radioresistantes. Nous avons ensuite cherche a construire un modele cellulaire d'etude des mecanismes de radioresistance. Il a ete demontre que des facteurs de croissance fibroblastique (fgf) exercaient un effet radioprotecteur in vitro, par inhibition de l'apoptose radioinduite pour le fgfb ou par un arret prolonge en phase g2 pour le fgf4. L'arnm du fgfb etant traduit en 4 isoformes proteiques, nous avons transfecte des cellules hela par les adnc du fgfb mutes codant pour chacune de ces isoformes. Seule la lignee exprimant uniquement la forme 24kda (hela 3a) presente une radioresistance accrue par rapport aux cellules controles associee a un arret prolonge en phase g2 apres irradiation et a une hyperphosphorylation de p34cdc2. Le traitement par un inhibiteur specifique de farnesyltransferase, fti 277, radiosensibilise uniquement les cellules hela3a. Cette radiosensibilisation est associee a une diminution de l'arret en g2 des cellules hela 3a apres irradiation. Ce resultat demontre l'implication de proteine(s) prenylee(s) dans les mecanismes de radioresistance cellulaire. La mise en evidence de ces proteines devrait permettre a moyen terme d'envisager l'utilisation de nouveaux agents radiosensibilisateurs.

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Oulhen, Nathalie. "Analyse fonctionnelle de la traduction dépendante de la coiffe m⁷GTP en réponse à la fécondation et au cours du cycle cellulaire de l'embryon d'oursin." Rennes 1, 2008. http://hal.upmc.fr/tel-01111009v1.

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Chez l’oursin, la fécondation induit une augmentation de synthèse protéique indispensable à l’entrée et à la poursuite du cycle cellulaire de l’embryon. L’une des étapes limitantes pour la traduction est l’initiation. La protéine eIF4E (eukaryotic Initiation Factor 4E) se lie à la coiffe m7GTP des ARNm et régule la synthèse protéique en fonction de ses partenaires 4E-BP et eIF4G. La fécondation dissocie eIF4E de son répresseur 4E-BP (eIF4E-Binding Protein). Nos résultats montrent que dans les ovules, eIF4G (eukaryotic Initiation Factor 4G) se présente sous plusieurs isoformes qui sont modifiées de façons post-traductionnelles en réponse à la fécondation. Ces isoformes s’associent à eIF4E après fécondation. La dissociation eIF4E/4E-BP et l’association eIF4E/eIF4G sont nécessaires à la première division cellulaire. La dissociation eIF4E/4E-BP est classiquement décrite comme dépendante de l’hyperphosphorylation de 4E-BP ; nous montrons que chez l’oursin, 4 sites de phosphorylation sont conservés sur 4E-BP. Les protéines de fusion de 4E-BP, sauvage ou mimant une hyperphosphorylation, s’associent à eIF4E in vitro et inhibent la traduction dépendante de la coiffe dans des extraits acellulaires d’oursin. Ces résultats suggèrent que la phosphorylation de 4E-BP induite après fécondation n’est pas suffisante pour libérer eIF4E et met en avant l’importance de la dégradation de 4E-BP dans le contrôle de la synthèse protéique chez l’oursin. Nous montrons que les facteurs 4E-BP, eIF4G, eIF4E, eIF2 (eukaryotic Initiation Factor 2) et eEF2 (eukaryotic Elongation Factor 2) sont modifiés en réponse à la fécondation mais aussi après activation artificielle des ovules d’oursin par le calcium ionophore et le NH4Cl. Ces modifications induites après activation artificielle permettent de synthétiser la cycline B mais sont insuffisantes pour activer le complexe CDK1/cycline B et entraîner la division cellulaire. Enfin, nous montrons que le complexe 4E-BP/eIF4E est aussi régulé au cours de la maturation méiotique de l’étoile de mer. Dans ces conditions physiologiques, la synthèse de la cycline B implique des régulations différentes de celles observées après fécondation chez l’oursin
Sea urchin eggs fertilization induces a protein synthesis increase required for cell cycle entry and progression in embryo. Translation initiation represents a rate limiting step. EIF4E (eukaryotic Initiation Factor 4E) is a cap binding protein that regulates protein synthesis according to its partners 4E-BP (eIF4E Binding Protein) and eIF4G (eukaryotic Initiation Factor 4G). Fertilization provokes eIF4E/4E-BP dissociation. Our results indicate that several isoforms of eIF4G are present in unfertilized eggs and post-translationally modified after fertilization. These isoforms associate with eIF4E after fertilization. EIF4E/4E-BP dissociation and eIF4E/eIF4G association are required for the first mitotic division. EIF4E/4E-BP dissociation is classically described as dependent on 4E-BP hyperphosphorylation; we show that in sea urchin, 4 phosphorylation sites are conserved on 4E-BP. Sea urchin 4E-BP fusion proteins, wild type and mutant mimicking hyperphosphorylation, associate with eIF4E in vitro and inhibit cap dependent translation in cell free extracts. These results suggest that 4E-BP phosphorylation induced after fertilization is not sufficient to release eIF4E and highlight the role of 4E-BP degradation in protein synthesis regulation in sea urchin. We show that 4E-BP, eIF4G, eIF4E, eIF2 (eukaryotic Initiation Factor 2) and eEF2 (eukaryotic Elongation Factor 2) are modified after sea urchin eggs fertilization but also after artificial activation by calcium ionophore or NH4Cl. These modifications mediated by artificial activation induce cyclin B synthesis but are not sufficient to activate CDK1/cyclin B and cell division. Finally, we show that 4E-BP/eIF4E complex is also regulated during the meiotic maturation in starfish oocytes. In these physiological conditions, cyclin B synthesis involves regulations different from the ones observed after sea urchin eggs fertilization

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Gaffré, Melina. "De la progestérone à l'activation du MPF dans l'ovocyte de Xénope : quels rôles pour H-Ras et la kinase Myt1 ?" Paris 6, 2007. https://tel.archives-ouvertes.fr/tel-00180525.

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L’objectif était d’améliorer la compréhension des mécanismes présidant à l’activation du MPF (M-Phase promoting Factor). Le modèle d’étude a été les divisions méiotiques de l’ovocyte de Xénope. Ils sont naturellement bloqués en prophase de méiose I. En réponse à la progestérone, ils reprennent la méiose et se re-bloquent en métaphase II en attente de la fécondation. Ce processus, appelé maturation méiotique, est sous le contrôle du complexe Cdc2-Cycline B, facteur universel de division des cellules eucaryotes. Nous avons étudié la régulation de Myt1, une kinase qui catalyse les phosphorylations inhibitrice sur la protéine Cdc2 et est donc responsable du maintien du MPF sous une forme inactive pendant la phase G2. L’activation du MPF repose sur la conversion du stock de pré-MPF inactif en stock de MPF actif, suite à la déphosphorylation activatrice de Cdc2 par la phosphatase Cdc25, et à l’inhibition de Myt1. Nous avons montré que l’activité de Cdc2 était nécessaire à l’inhibition de Myt1 et que deux kinases, p90Rsk et Plx1, sont recrutées l’une ou l’autre pour contribuer à cette inhibition. Puis, nous avons étudié l’implication de la protéine H-Ras lors de la reprise de la méiose. Nous avons montré que l’injection de H-Ras induit la reprise de la méiose par le recrutement d’une PI3 kinase particulière. Cette voie, bien que présente et activable dans l’ovocyte, n’est pas recrutée in vivo par la progestérone en conditions normales. L’ovocyte est donc équipé de plusieurs voies de signalisation fonctionnellement redondantes, qui peuvent être recrutées dans des conditions pathologiques pour assurer la reprise de la méiose quand les effecteurs normaux ne sont pas disponibles.

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Jones, Mark. "The relationship between RAF-1 protein level, radiosensitivity, and post-irradiation G2+M cell cycle accumulation in the context of P53 mutational status." Thesis, University of Liverpool, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526795.

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DE, ALMEIDA RESTOY ANNABELLE. "La proteine phosphatase cdc14 de s. Cerevisiae : une sequestration nucleolaire pour le regulateur en chef de la transition m/g1 du cycle cellulaire." Lyon, École normale supérieure (sciences), 2000. http://www.theses.fr/2000ENSL0152.

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Chez les eucaryotes, l'activation des cdks mitotiques provoque l'entree en mitose, alors que leur inactivation conduit a la sortie de mitose. Chez la levure s. Cerevisiae, deux mecanismes redondants induisent l'inactivation de la seule cdk essentielle, la kinase cdk1. D'un cote le systeme de proteolyse specifique dependant de l'apc intervient pour degrader les cyclines mitotiques, qui sont des sous-unites activatrices des cdks ; de l'autre la kinase sic1 se lie a cdk1 et inhibe son activite. La phosphatase cdc 14 est impliquee dans ces deux processus. Elle stabilise en effet sic 1 en dephosphorylant cette proteine ainsi que son facteur de transcription swi5, et active l'apc en dephosphorylant cdh 1. Comment cdc 14 est-elle regulee? nous avons montre que cette phosphatase etait sequestree dans le nucleole pendant la plus grande partie du cycle, puis relarguee en fin de mitose au moment ou elle doit agir sur ses cibles. Dans le nucleole, cdc 14 appartient a un complexe nomme rent qui intervient notamment sur l'organisation de ce compartiment. Lors d'un criblage, nous avons isole un element de ce complexe, la proteine net1, par ailleurs identifiee comme un substrat et un inhibiteur potentiel de cdc14, responsable de son ancrage dans le nucleole. En amont de cdc14, il existe une voie de transduction du signal nommee men impliquant notamment la gtpase tem1, et les kinases dbf2 et cdc15. Nous avons observe que cdc15 n'etait pas regulee par son abondance et son activite kinase, mais par sa localisation. Recemment il a ete montre que la regulation de cette kinase impliquait sa localisation au niveau des spbs, et sa dephosphorylation par cdc14. Les resultats obtenus avec tem1 nous ont revele que cette proteine pouvait etre phosphorylee. La kinase dbf2, appartenant au complexe de transcription ccr4, peut etre impliquee dans la regulation de cette proteine. Nos resultats ont confirme le role central joue par cdc14 en fin de mitose, le fonctionnement du men restant a elucider.

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Girard, Franck. "Régulation du cycle cellulaire des cellules somatiques mammifères : rôle de de la cycline A en phase S : importance de la compartimentation dans l'activation du MPF à la transition G2/M." Montpellier 1, 1993. http://www.theses.fr/1993MON1T027.

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Sontheimer, Jana [Verfasser], M. Teresa [Akademischer Betreuer] Pisabarro, Francis [Akademischer Betreuer] Stewart, and Frank [Akademischer Betreuer] Buchholz. "Functional characterization of proteins involved in cell cycle by structure-based computational methods / Jana Sontheimer. Gutachter: Francis Stewart ; Frank Buchholz. Betreuer: M. Teresa Pisabarro." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://d-nb.info/1068443146/34.

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Kuttler, Fabien. "Equilibre profilération / apoptose dans les lymphomes B du centre germinatif : modification fonctionnelle de c-Myc et promotion de la transition G2/M du cycle cellulaire." Besançon, 2003. http://www.theses.fr/2003BESAA006.

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Le cancer peut être défini comme une expansion pathologique d'un tissu conduisant à la morbidité. La dérégulation de la balance entre prolifération cellulaire et apoptose s'avère être un élément clé de ce processus. Nous avons choisi d'étudier les caractéristiques de cette balance à travers différents lymphomes B du centre germinatif, dont les altérations chromosomiques et géniques au niveau d'oncogènes cellulaires sont bien caractérisées. Nous avons tout d'abord réalisé une étude globale de l'expression de gènes impliqués dans la régulation du cycle cellulaire et de l'apoptose par la technique de protection à la ribonucléase. Nous avons ainsi montré, dans les lymphomes diffus à grandes cellules B, une altération de l'expression de ces gènes. Ces modifications permettent de distinguer deux types de lymphomes diffus à grandes cellules B associés à des survies cliniques différentes. Nous avons pu, en particulier, mettre en évidence une relation préférentielle entre l'expression de deux gènes, cycline B1 et survivin, suggérant une promotion spécifique de la transition G2/M du cycle cellulaire, associée à une inhibition de l'apoptose, dans cette maladie. Nous nous sommes ensuite restreints au gène c-myc, fréquemment altéré dans de nombreux cancers et impliqué à la fois dans la régulation de la prolifération cellulaire et dans l'induction d'apoptose. Nous nous sommes intéressés à une mutation ponctuelle de celui-ci, fréquemment retrouvée dans les cas de lymphomes de Burkitt, et localisée au niveau du codon 138 de la boîte II de la protéine. Nous avons montré que les protéines mutées possèdent des capacités fonctionnelles altérées. L'activité de transformation cellulaire est diminuée par rapport à la protéine c-Myc sauvage, mais s'accompagne également d'une sensibilisation plus faible à l'apoptose. Nous suggérons donc que ces mutations sont sélectionnées lors du processus de développement tumoral par un déséquilibre de la balance prolifération / apoptose en faveur d'une réduction des capacités pro-apoptotiques de c-Myc, conférant ainsi un avantage de survie aux cellules. Par ailleurs, nous avons caractérisé cette modulation de l'apoptose induite par c-Myc mutée au niveau moléculaire et confirmé notamment l'activation des caspases et l'effet inhibiteur de la protéine Bcl-2. Il reste à expliquer le comportement apoptotique des mutants via des modifications d'évènements mitochondriaux induites par c-Myc. Finalement, nous avons montré des altérations du contrôle de la transition G2/M par la protéine c-Myc mutée. Après irradiation, les cellules exprimant les mutants présentent un arrêt en G2/M moins stable que celles exprimant c-Myc sauvage, et présentent parallèlement une accumulation d'anomalies génétiques. Ceci suggère un lien entre la mutation ponctuelle de la boîte II retrouvée dans certains cas de lymphome de Burkitt et la promotion de l'instabilité génomique caractéristique de nombreux cancers. En conclusion, la mutation ponctuelle de c-Myc que nous avons étudiée se traduit par des modifications fonctionnelles de la protéine, 1) sur la régulation du cycle cellulaire, notamment au niveau de la transition G2/M, 2) sur la transformation cellulaire et 3) sur l'apoptose. Cette mutation ponctuelle de c-Myc dans le lymphome de Burkitt, et l'expression conjointe de cycline B1 et survivin dans le lymphome diffus à grandes cellules B conduisent par conséquent à des déséquilibres types entre prolifération cellulaire et apoptose lors du développement d'un cancer.

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Duranteau, Marie. "Rôle de la kinase BUBR1 dans le contrôle de la division mitotique et dans la prévention de l’aneuploïdie." Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCC260.

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La protéine BubR1 est une protéine clé du mécanisme de surveillance de la transition métaphase-anaphase, lors de la mitose, appelé Spindle Assembly Checkpoint (SAC). Le SAC est essentiel chez les eucaryotes car il permet d'assurer une transmission fidèle de l'information génétique entre les deux cellules filles. Un premier aspect de ma thèse a consisté à étudier la fonction « mitotic timer » de BubR1 chez Drosophila melanogaster, qui régule la durée de la division mitotique. Mes résultats montrent qu'un nouveau motif de BubR1, localisé dans son domaine N-terminal, joue un rôle dans le recrutement de Fzy/Cdc20 au kinétochore et en conséquence dans l'activation du SAC. De plus, il apparaît que cette fonction de BubR1 est corrélée à la quantité de Fzy/Cdc20 recrutée au kinétochore. Dans un second temps, mes travaux de thèse se sont concentrés sur l'identification de nouveaux partenaires de BubR1 durant la mitose. A l'aide de la spectrométrie de masse, nous avons pu identifier la protéine Gnfl, comme étant un partenaire de BubRl. De plus, l'analyse du phénotype mitotique in vivo associé à la perte d'expression endogène du gène Gnfl (par expression de l'ARNi Gnfl) chez D. Melanogaster a permis de mettre en évidence un possible rôle de Gnfl dans la croissance ou l'assemblage des microtubules. En parallèle de l'identification de nouveaux partenaires de BubR1, nous nous sommes intéressés à l'activité kinase controversée de celle-ci. Les essais kinase in vitro ont permis de mettre en évidence une activité kinase de BubR1 et des substrats potentiels : Eip63 et Pontin. De la même façon que pour Gnfl, des analyses phénotypiques in vivo ont été réalisées et semblent montrer des défauts du fuseau mitotique. L'ensemble de mes travaux ont permis de mieux comprendre la fonction « mitotic timer » de BubR1 ainsi que sa fonction SAC, au cours de la mitose, via son interaction avec de nouveaux partenaires
The protein is a key-component of the mitotic surveillance mechanism called the Spindle Assembly Checkpoint which occurs during metaphase-anaphase transition. The SAC is essential in eukaryotes because it ensures the equal transmission of the genetic content between the two future daughter cells. In one aspect of my thesis work, I looked in more detail at the "mitotic timer" function of BubR1, responsible for regulating the basal timing of mitotic division, in Drosophila melanogaster. My results showed that a new Linear motif, localized in the N-terminal domain of BubR1, is involved in the recruitment of Fzy/Cdc20 to kinetochore and consequently in the SAC activation. Moreover, my data provide evidence that the mitotic function of BubR1 is correlated with the level of recruitment of Fzy/Cdc20 to the kinetochore in Drosophila. In the second part, I looked for new partners of BubRI during mitosis. Using Mass Spectrometry, we were able to identify the protein Gnfl as a new BubR1 partner. Moreover, the in vivo analysis of the mitotic phenotype associated with the endogenous loss of Gnfl expression (by Gnfl RNAi expression) has provided new evidence for a role of Gnfl in the spindle microtubules dynamics. Finally, I got interested in the kinase catalytic activity of BubRI which has been so far controversial. I showed by in vitro kinase assays that Drosophila BubRI kinase is indeed catalytically active and that it phosphorylates in vitro two novel substrates, Eip63E and Pontin. Using the same approach as for Gnfl, in vivo phenotypic analysis were carried out in ARNi expressing neuroblasts and preliminary data show defects in the mitotic spindle assembly. Altogether, my data has provided novel insights to better understand the "mitotic timer" function of BubR1 as well as its SAC function during mitosis via the identification of novel BubRI partners and substrates

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Dann, Jeremiah J. "Immunological characterization and histone kinase activity of cyclin B1 and Cdk1 at G1 and G2/M phase of the cell division cycle in one-cell mouse embryos." Virtual Press, 2004. http://liblink.bsu.edu/uhtbin/catkey/1306852.

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Cyclin B1 is a cell cycle protein typically associated with the regulation of cellular division (mitosis). Previous studies in this laboratory involving preimplantation mouse embryos found that cyclin B1, or a cyclin B 1-related protein, were present at both G1 and G2/M phase of the cell cycle. Not only was cyclin Bi detected during G1 phase in this study, it was found to be present in higher concentrations at G1 phase through the first three cell cycles. These findings were unexpected, because most of the literature suggests that cyclin B1 is normally degraded during G1 phase. Using immunoprecipitation and immunoblot techniques, a more detailed study of cyclin B1 expression was inititated. Using two different primary antibodies direct against cyclin B1, a 48.97 kDa protein band, which is believed to be cyclin B1, was detected at both G1 and G2/M phases in 1-cell mouse embryos. Using another antibody directed against Cdk1, the kinase that forms a complex with cyclin B1 in order to direct the G2/M transition, a 37 kDa protein band was also detected at both G1 and G2/M phases in 1-cell mouse embryos. In order to determine whether cyclin B1 was present as a complex with Cdk1, immunoblotting with the anti-Cdk1 antibody. Again, a 37kDa protein band was detected at both G1 and G2/M phases. Finally, in order to determine whether the cyclin B1/Cdk1 complex exists in its active form, histone kinase assays were performed using anti-cyclin B1 immunoprecipitates. Kinase activity was detected in immunoprecipitates collected from G2/M phase 1-cell embryos, but no kinase activity was detected from immunoprecipitates collected from G1 phase 1-cell embryos. These data indicate that cyclin B1 and Cdk1 are present and exist as a complex in both G1 and G2/M phases of 1-cell mouse embryos, although the complex only appears to be active at the G2/M phase.
Department of Biology

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36

Strågefors, Emma, and Maja Schölin. "När ska man vara djärv för att genomföra ett förvärv? : En eventstudie om företagsförvärv och dess påverkan på aktiekursen på kort sikt." Thesis, Södertörns högskola, Företagsekonomi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-43702.

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Purpose The main purpose of this study is to test in which part of the economic cycle that generates the best results on corporate acquisitions for the acquirer in the short-term. The study examines the Swedish market and has the aim to study both domestic and foreign acquisitions made by Swedish acquirers. The study also has a purpose of examining if there is a difference in results with domestic acquisitions and foreign acquisitions. Theory The theoretical perspective will include previous research, concepts and theories. The theoretical framework includes Efficient market hypothesis, The random walk theory and the Non-random walk theory. Method This study undertakes a quantitative approach with a deductive reasoning. The event study includes a 10 day event window (t-4, t+5). It is an event study that examines 100 acquisitions listed on the Nasdaq OMX Stockholm during the time period 2008- 2018. Results Data has been collected from the databases Zephyr, Orbis and Nasdaq OMX Nordic. In the empirical foundation AAR and CAR is presented. The results show that it is better to make acquisitions during a upturn in the short-term perspective. The results also show a very slim difference between domestic and foreign acquisitions.
Syfte Syftet med denna studie är att undersöka i vilket konjunkturläge företagsförvärv genererar högst abnormal avkastning på det förvärvande företagets aktie på kort sikt. Studien mäter förvärv på den svenska marknaden och avser att analysera om förvärv utförda mellan svenska företag kontra svenska förvärv på utländska företag påverkar den abnormala avkastningen på. Teori Studien utgår från två stycken teorier och innefattar en referensram med utvalda tidigare forskningar inom området. Teorierna som ingår i studien är Effektiva marknadshypotesen och The Random walk som även inkluderar non-random walk. Metod Denna studie har en kvantitativ forskningsdesign med deduktiv ansats som bygger på ett metodval i form av eventstudie. Eventstudien består av ett eventfönster på 10 dagar (t-4 till t+5)och undersöker reaktionen på marknaden vid 100 stycken förvärv där det förvärvande företaget är börsnoterat på OMX Stockholm nasdaq. Resultat Datan är insamlad via databaserna Zephyr, Orbis och Nasdaq OMX Nordic. I empirinpresenteras AAR och CAR där resultaten visar på att det är bättre att genomföra förvärv i högkonjunktur i ett kortsiktigt perspektiv. Resultaten för inhemska kontra utländska marknadenvisar på väldigt små skillnader.

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37

Altenhofer, Christian [Verfasser], Michael W. [Akademischer Betreuer] [Gutachter] Pfaffl, and Wilhelm M. [Gutachter] Windisch. "Influence of feeding supplementation and lactation cycle on milk cholesterol, fatty acid profile and milk fat globule size / Christian Altenhofer. Betreuer: Michael W. Pfaffl. Gutachter: Michael W. Pfaffl ; Wilhelm M. Windisch." München : Universitätsbibliothek der TU München, 2016. http://d-nb.info/1103135376/34.

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Wolf, Christian M. Verfasser], Klaus [Akademischer Betreuer] [Gutachter] Richter, Stefanie [Gutachter] [Hellweg, and Gabriele [Gutachter] Weber-Blaschke. "Life Cycle Assessment of Wood Energy Services on a Regional Scale : Methodological Development and Case Study Application / Christian M. Wolf ; Gutachter: Stefanie Hellweg, Gabriele Weber-Blaschke, Klaus Richter ; Betreuer: Klaus Richter." München : Universitätsbibliothek der TU München, 2017. http://d-nb.info/113878785X/34.

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39

Stracke, Christian M. [Verfasser], Heimo H. [Akademischer Betreuer] Adelsberger, and Tobias [Akademischer Betreuer] Kollmann. "Integrierte Qualitäts- und Kompetenzentwicklung : Das Life-Cycle-Modell IDEAL für Innovationen im E-Learning durch Qualitätsmanagement und Kompetenzaufbau, Standards und Open Learning / Christian M. Stracke. Gutachter: Tobias Kollmann. Betreuer: Heimo H. Adelsberger." Duisburg, 2014. http://d-nb.info/1057837210/34.

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Berg, Sophia von [Verfasser], Wolfgang [Akademischer Betreuer] Pfau, and Thomas M. [Akademischer Betreuer] Cerbe. "The business model cycle : a dynamic and user-centric perspective on business model design and change with a case study from the mobility sector / Sophia von Berg ; Wolfgang Pfau, Thomas M. Cerbe." Clausthal-Zellerfeld : Technische Universität Clausthal, 2021. http://d-nb.info/1231239042/34.

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Stracke, Christian M. [Verfasser], Heimo H. Akademischer Betreuer] Adelsberger, and Tobias [Akademischer Betreuer] [Kollmann. "Integrierte Qualitäts- und Kompetenzentwicklung : Das Life-Cycle-Modell IDEAL für Innovationen im E-Learning durch Qualitätsmanagement und Kompetenzaufbau, Standards und Open Learning / Christian M. Stracke. Gutachter: Tobias Kollmann. Betreuer: Heimo H. Adelsberger." Duisburg, 2014. http://nbn-resolving.de/urn:nbn:de:hbz:464-20140822-070801-1.

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42

Horník, Vít. "Základní mechanismy únavového a kombinovaného poškození únava-creep niklových superslitin MAR-M 247 a IN 713LC." Doctoral thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2021. http://www.nusl.cz/ntk/nusl-433626.

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The thesis is focused on clarifying fatigue damage mechanisms and fatigue-creep damage mechanisms of MAR-M 247 and IN 713LC polycrystalline Ni-based superalloys. This thesis begins with basic information about nickel-based superalloys and their microstructure, followed by a description of fatigue and creep mechanisms and their mutual interaction. The next part contains experimentally obtained results describing the behavior of MAR-M 247 and IN 713LC superalloys under various sets of conditions. Three testing temperatures - 800, 900 and 950 °C were used for the measurement of fatigue properties under symmetrical loading cycle, because in the temperature range 800 – 950 °C, the mechanism of fatigue crack propagation of both superalloys should change from the originally crystallographic at "lower" temperatures (800 °C) to non-crystallographic at "higher" temperatures (950 °C). In addition the effect of processing technology on fatigue properties was studied on the superalloy IN 713LC. High-frequency cyclic loading (about 120 Hz) with high mean stress at elevated temperatures was applied to induce fatigue-creep interaction. The combined fatigue-creep loading was performed on the IN 713LC superalloy at 800 °C and on the MAR-M 247 superalloy at 900 °C.

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Schwamberger, Valentin [Verfasser], and M. [Akademischer Betreuer] Gabi. "Thermodynamische und numerische Untersuchung eines neuartigen Sorptionszyklus zur Anwendung in Adsorptionswärmepumpen und -kältemaschinen = Thermodynamic and numerical investigation of a novel sorption cycle for application in adsorption heat pumps and chillers / Valentin Schwamberger ; Betreuer: M. Gabi." Karlsruhe : KIT-Bibliothek, 2016. http://d-nb.info/1116427583/34.

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Johan, Åckander, and Rygert Pontus. "Avyttringars inverkan på säljande bolags aktiekurs : En studie på den svenska marknaden med hänsyn till branschtillhörighet, finansieringsalternativ och konjunkturläge." Thesis, Linköpings universitet, Företagsekonomi, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-148976.

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Background: Previous studies on the subject, contrary to corresponding studies on mergers and acquisitions, have shown significant positive market reactions from all over the world on the announcements of divestitures. However, similar studies have not been done on the Swedish market. There are split opinions on the origin of the abnormal returns from the announcements of divestitures, but the economic cycle, choice of payment method and industry affiliation are recurring explaining variables in event studies. Aim: The aim of the study is to investigate the effect on shareholder wealth from the announcements of a divestiture on the Swedish market during the period from 1997-2017, as well as investigating how the abnormal returns are affected by the economic cycle, choice of payment method and industry affiliation. Completion: The study is conducted using the event study methodology and a deductive approach. Historical time series from divesting companies share prices are used to estimate expected returns which are then compared to actual returns to decide whether the announcement of a divestiture has an impact on shareholder wealth. Results: The study finds significant results that divesting companies’ shareholder wealth are positively affected by the announcement of a divestiture for both event windows (-3, +3) and (-1, +1). For each separate day within the event window the authors find statistically significant returns for day T-2 and T0. The authors find no statistically significant differences between the returns regarding the economic cycle. Regarding the choice of method of payment, it is concluded that payment through stock generates excess returns when compared to other financing alternatives. No differences could be found between different industry affiliations.
Bakgrund: Tidigare studier inom ämnet har, till skillnad från motsvarande forskning om företagsförvärv, påvisat signifikanta positiva reaktioner från marknader över hela världen vid tillkännagivandet av en avyttring. Däremot saknas studier om avyttringars effekt på den svenska marknaden. Det råder delade meningar om varför abnormal avkastning uppstår vid tillkännagivandet, där konjunkturläge, finansieringsalternativ och branschtillhörighet är vanligt förekommande förklarande variabler i eventstudier. Syfte: Studiens syfte är att undersöka hur tillkännagivandet av en avyttring påverkar säljande bolags aktiekurs på den svenska marknaden under tidsperioden 1997–2017, samt att undersöka hur rådande konjunkturläge, valt finansieringsalternativ och branschtillhörighet påverkar avkastningen Genomförande: Studien genomförs genom eventstudiemetodologin med en deduktiv ansats. Empirin utgår från historisk tidsseriedata från avyttrande bolags aktiekurser för att bestämma förväntad avkastning som sedan jämförs med faktiskt avkastning för att urskilja om tillkännagivandet påverkar kursutvecklingen. Resultat: Studien visar statistiskt signifikanta resultat för att avyttrande bolags aktiekurs påverkas positivt av tillkännagivandet av en avyttring både för eventfönstret (-3, +3) och (-1, +1). För de enskilda dagarna i eventfönstret finner författarna statistiskt signifikanta avkastningar för dag T-2 och T0. Författarna finner inga statistiskt säkerställda skillnader i avkastning beroende på rådande konjunkturläge. Gällande val av finansieringsalternativ visas att betalning genom aktier genererar signifikant högre avkastning än övriga alternativ. Inga samband kunde säkerställas beroende på företagens branschtillhörighet.

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Sigglekow, Nicholas David Garvan Institute of Medical Research Faculty of Medicine UNSW. "Mutated in colorectal cancer (MCC): a putative tumour suppressor gene in colorectal cancer." Publisher:University of New South Wales. Garvan Institute of Medical Research, 2009. http://handle.unsw.edu.au/1959.4/43617.

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Colorectal cancer (CRC) remains a significant burden in contemporary society due to an aging population, unhealthy dietary choices and an increasingly sedentary lifestyle. While the underlying defects for many hereditary forms of CRC have been determined, many genetic and epigenetic changes promoting common sporadic CRCs have yet to be identified. The Mutated in Colorectal Cancer (MCC) gene, identified in 1991, was initially thought to be responsible for the hereditary form of CRC, familial adenomatous polyposis, before the discovery of the susceptibility gene Adenomatous Polyposis Coli (APC), which then became the focus of intense research. Recent data, however, suggests that MCC may also be important in the development of CRC. I have investigated the mechanism of MCC gene silencing, the putative structure, and multiple functions of MCC. MCC was frequently silenced by promoter hypermethylation in CRC cell lines and primary tumours. MCC methylation showed strong molecular and clinicopathological associations with hallmarks of the serrated neoplasia pathway. Furthermore, MCC methylation was more frequent in serrated precursor lesions compared with adenomas, thus occurring early during carcinogenesis. MCC is highly conserved in complex multicellular organisms. Re-introduction of MCC in CRC cell lines resulted in partial G1 to S phase, and G2/M phase cell cycle blocks, potentially by upregulating cell cycle inhibitor gene transcription and interfering with the process of mitotic checkpoints and division, respectively. Changes in MCC levels also modulated NF?B pathway signalling, the pathway required for maintaining cell viability and proliferation in colonic epithelial cells. In particular, MCC overexpression suppressed both TNF? and LPS-induced NF?B activation, decreasing both the magnitude and rate of cellular responses. Overexpression also resulted in downregulation of proteins involved in canonical NF?B pathway signalling, while increasing the transcription of non-canonical NF?B genes. Therefore, MCC may direct activation of this pathway to a specific subset of NF?B-regulated genes. These data provide a molecular basis for the role of MCC as a tumour suppressor gene in CRC. MCC may have multiple functions, regulating cell cycle progression and modulating NF?B pathway signalling, either through direct involvement in pathway signalling cascades, or by providing a scaffold on which signalling events can occur.

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Chiri, Sandrine. "Rôles de MAP kinase et de PI 3-kinase dans le contrôle des premières divisions de l'œuf d'oursin." Paris 6, 2002. http://www.theses.fr/2002PA066077.

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Hargreaves, Michael. "Innovation, Collaboration, and the International Firm." Thesis, Queensland University of Technology, 2004. https://eprints.qut.edu.au/15928/1/Michael_Hargreaves_Thesis.pdf.

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In the lead up to the Year 2000 dot.com crash of publicly traded high-technology equities, Information Communication Technology (ICT) Companies proudly displayed inter-firm allegiances on their newly created websites. These collaborative relationships were in reality licensing agreements to develop or market new products internationally. Phenomena associated with ICT product development - collaboration, innovation, and internationalisation - are the core tenets of the accompanying dissertation. Leading scholars have suggested these phenomena challenge conventional economic theories of the firm. This study commences with tracing the evolution of trade and production theories from absolute advantage through to competitive advantage and introduces the concepts of non-adversarial collaborative advantage. Within the framework of the technology cycle, this dissertation then seeks to answer why firms engage in international collaborative innovation. The cycle of technological innovation is investigated and this leads to postulating a period of technological overlap and its implications for collaboration. One of the shortcomings acknowledged in the literature is the generic application of the term collaboration to cover a wide scope of inter-firm agreements. Within the literature this is referred to as a problem of multidimensionality. A model is developed in this dissertation that identifies the choices available to the firm and addresses the problem of defining collaboration. The choices provided in the developed model are more complex than simply choosing between external and internal intermediate markets. As a separable form of industry organisation, the success rates of alliance collaboration are compared to Mergers and Acquisitions (M&As) to validate issues of sustainability before examining the impact of location on innovation and collaboration. Again, theory is tested by recent events that require explanation. These events include the relocation of early stage foreign R&D to both developed and lesser-developed nations. The final chapter assesses the findings throughout this study and identifies separate and distinct roles for large and small firms in the international and collaborative commercialisation of new innovations. This central conclusion requires empirical validation and suggests the need investigate how firms shape the cycle of innovation from a reflected vantage point to the evolutionary perspective taken in this study. Further research is warranted because the literature on international innovation and collaboration is at an early stage and gaps in understanding remain.

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Hargreaves, Michael. "Innovation, Collaboration, and the International Firm." Queensland University of Technology, 2004. http://eprints.qut.edu.au/15928/.

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Анотація:

In the lead up to the Year 2000 dot.com crash of publicly traded high-technology equities, Information Communication Technology (ICT) Companies proudly displayed inter-firm allegiances on their newly created websites. These collaborative relationships were in reality licensing agreements to develop or market new products internationally. Phenomena associated with ICT product development - collaboration, innovation, and internationalisation - are the core tenets of the accompanying dissertation. Leading scholars have suggested these phenomena challenge conventional economic theories of the firm. This study commences with tracing the evolution of trade and production theories from absolute advantage through to competitive advantage and introduces the concepts of non-adversarial collaborative advantage. Within the framework of the technology cycle, this dissertation then seeks to answer why firms engage in international collaborative innovation. The cycle of technological innovation is investigated and this leads to postulating a period of technological overlap and its implications for collaboration. One of the shortcomings acknowledged in the literature is the generic application of the term collaboration to cover a wide scope of inter-firm agreements. Within the literature this is referred to as a problem of multidimensionality. A model is developed in this dissertation that identifies the choices available to the firm and addresses the problem of defining collaboration. The choices provided in the developed model are more complex than simply choosing between external and internal intermediate markets. As a separable form of industry organisation, the success rates of alliance collaboration are compared to Mergers and Acquisitions (M&As) to validate issues of sustainability before examining the impact of location on innovation and collaboration. Again, theory is tested by recent events that require explanation. These events include the relocation of early stage foreign R&D to both developed and lesser-developed nations. The final chapter assesses the findings throughout this study and identifies separate and distinct roles for large and small firms in the international and collaborative commercialisation of new innovations. This central conclusion requires empirical validation and suggests the need investigate how firms shape the cycle of innovation from a reflected vantage point to the evolutionary perspective taken in this study. Further research is warranted because the literature on international innovation and collaboration is at an early stage and gaps in understanding remain.

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Marti, Cécile. "Seven towers : an orchestral cycle focused on different musical temporalities." Thesis, City, University of London, 2017. http://openaccess.city.ac.uk/17282/.

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This dissertation examines formal aspects of a seven work orchestral cycle. The composition is structured as a series of distinct pieces which can be played either independently or as one uninterrupted musical performance lasting 78 minutes. The temporal dimension of music is a determining factor in both the composition of music and its perception by the listener. This issue is particularly acute in the case of such a substantial, uninterrupted musical statement; therefore I have had to examine questions of temporality in some detail whilst composing this cycle. In the following research I try to distinguish different temporal structures from each other and show how they can shape music differently. Temporality will be first discussed in a wider context within the field of music generally. This is followed by a discussion of the seven different types of time exemplified in the seven pieces of the orchestral cycle. To achieve coherence throughout a cycle of 78 minutes’ duration, one needs some linking elements. Some of these elements will be illustrated in the musical analysis of the cycle itself. This research aspires towards a deeper understanding of musical development in time. It is possible that the typologies might have a wider applicability and assist other composers to shape music over longer durations such as those I have employed in this cycle. This research can possibly also give some further indications as to how the listener might follow music over large spans of time.

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Doumont, Gilles. "Identification et caractérisation de nouveaux médiateurs de l'activité biologique de la protéine suppresseur de tumeur p53." Doctoral thesis, Universite Libre de Bruxelles, 2005. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211022.

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Le suppresseur de tumeur p53 permet à la cellule de se défendre contre différentes formes de stress. Il joue un rôle de barrière s'opposant à la tumorigenèse: en effet la perte de p53 chez la souris prédispose grandement ces animaux à développer des tumeurs; de même le locus p53 est inactivé dans près de 50% des tumeurs humaines.

p53 constitue un facteur de transcription qui se lie à des séquences particulières de l'ADN et active l'expression des gènes adjacents. L'expression orchestrée de ces gènes conduit, directement ou indirectement et suivant le contexte cellulaire, soit à la mort de la cellule soit à l'inhibition de la division cellulaire.

Les mécanismes moléculaires médiant ces deux activités biologiques essentielles de p53, de même que les mécanismes influençant le choix de la réponse cellulaire, sont encore mal compris. L'importance de p53 dans ce choix reste également à démontrer.

Afin de contribuer à la compréhension de ces mécanismes, le modèle murin déficient pour Mdm4, un régulateur négatif de l'activité de p53, a été choisi. L'inactivation de Mdm4 chez la souris conduit en effet à l'activation ectopique de p53 in vivo et l'induction de deux types de réponse: apoptose dans le neuroépithélium et arrêt de la prolifération cellulaire dans les tissus non neuronaux. Le profil d'expression des gènes dans les tissus neuronaux et non neuronaux a donc été comparé entre embryons de souris sauvage et mdm4-/- par la technique d'hybridation de biopuces à ADN. Les résultats obtenus suggèrent que le type de réponse dépend du type cellulaire et non de p53 lui-même. En effet les profils d'expression des gènes dans les tissus neuronaux (conditions d'apoptose) et non neuronaux (conditions d'arrêt de la prolifération cellulaire) chez l'embryon de souris mdm4-/- sont comparables.

Nous nous sommes ensuite particulièrement intéressés à deux nouveaux gènes dont l'expression est augmentée dans les embryons mdm4-/-. Dans un premier temps, leur induction transcriptionnelle chez l'embryon de souris mdm4-/- a été confirmée par différentes techniques et il a été vérifié qu'ils constituaient tous deux des cibles directes de p53 induites suite à un stress génotoxique.

Le premier gène code Dapk1, une protéine suppresseur de tumeur pro-apoptotique présentant une activité de type sérine/thréonine kinase. Ce travail a permis d'établir que Dapk1 participait à une boucle de rétroaction du contrôle de l'activité de p53.

Le deuxième gène identifié code la protéine Ptprv, un récepteur transmembranaire présentant une activité de type tyrosine phosphatase. En vue d'étudier la signification physiologique de l'induction transcriptionnelle de ptprv suite à l'activation de p53, des expériences effectuées à partir de matériel biologique issu de souris déficientes pour Ptprv ont été réalisées. Ces expériences confirment le rôle essentiel de Ptprv comme médiateur de l'arrêt du cycle cellulaire en phase G1 induit par p53 suite à un stress génotoxique, à la fois in vitro et in vivo. Par contre, Ptprv ne semble pas influencer l'apoptose induite suite à l'activation de p53. Ce travail a également permis d'établir le rôle essentiel de Ptprv dans la suppression de tumeurs induites chez la souris par activation constitutive de l'oncogène Ras.

Doctorat en sciences, Spécialisation biologie moléculaire
info:eu-repo/semantics/nonPublished

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