Дисертації: "CDCH"

1

Dupré-Maquaire, Janine. "Spectroscopie moléculaire à 10 mu m des molécules toupies symétriques CDH et CDCl spectroscopie STRAK de CDCl avec structure hyperfine." Grenoble 2 : ANRT, 1986. http://catalogue.bnf.fr/ark:/12148/cb37597851v.

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2

CHIAPPINI, MARCO. "The construction and commissioning of the ultra low mass MEG II drift chamber for the search of the mu^+ --> e^+ gamma decay at branching ratios below 10^(−13)." Doctoral thesis, Università di Siena, 2019. http://hdl.handle.net/11365/1086892.

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The thesis work focuses on the design, construction and commissioning activities of the new cylindrical drift chamber (CDCH) of the MEG II experiment at Paul Scherrer Institut (PSI, Switzerland), in search for the lepton flavour violating mu^+ --> e^+ gamma decay. The first data taken with CDCH fully operational and integrated into the MEG II experimental apparatus are also described.

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3

CARENZA, CLAUDIA. "DENDRITIC CELL SUBSETS IN THE PATHOGENESIS OF HIGH GRADE GLIOMAS." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/844781.

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Abstract Background and aims. High grade gliomas (HGGs) are aggressive brain tumours characterized by a poor prognosis and the ability to promote an immunosuppressive tumour microenvironment that impairs anti-tumor immune responses. Therefore, there is increasing interest in developing new immunotherapeutic approaches, aimed at boosting anti-tumor immune responses in HGG patients. Because HGG has shown the highest susceptibility to dendritic cell (DC) vaccines amongst other human cancers, DC-based immunotherapeutic strategies may be particularly promising in these patients. DCs are antigen presenting cells that have the unique ability to initiate antitumor immune responses, making these cells crucial in cancer immunosurveillance. They are a rare population composed of different subsets that differ each other in origin, immunophenotype and function. The differential role of different DC subsets in HGG, and in particular the subsets specifically recruited into the tumour site and the impact of HGG on the activatory/tolerogenic properties of DCs have been poorly investigated, so far. For these reasons, in this study we performed a deep characterization of circulating and tumour-infiltrating DC subsets, and investigated possible correlations between DC parameters and histopathological and molecular HGG features, patient outcome and response to treatment. To this aim, we used multiparameter flow-cytometry and single-cell RNA sequencing (scRNAseq), which allow complex analyses on high-dimensional data. Materials and methods. In this cross-sectional study we enrolled HGG patients undergoing surgery at their first diagnosis, and we applied an 18-colour flow-cytometry panel that allows the identification of DC-lineage DCs (pDCs, cDC1s, cDC2s) and inflammatory DCs (slanDCs, moDCs), and the characterisation of their activatory/inhibitory state. This panel was applied to DC characterization in the peripheral blood (n=23) and the tumour lesion (n=10) of HGG patients. Twelve whole blood samples obtained from healthy donors (HDs) and 3 healthy brain tissue samples were included as controls. scRNAseq experiments were performed on 7 tumoral samples and 2 healthy brain tissues obtained from HGG patients, by using 10x Genomics technology. Ingenuity Pathway Analysis (IPA) software was used to investigate the pathways and functions differentially activated or inhibited in infiltrating DCs. We also performed a longitudinal study on a second cohort of patients, diagnosed with recurrent HGG and enrolled in different immunotherapeutic early clinical trials (ieCTs), mainly containing immune checkpoint inhibitors (n=17). In these patients, we assessed the count and phenotype of circulating DC subsets before and at different time points after immunotherapy, by using the same 18-colour flow-cytometry panel described above. Multivariate analyses were used to correlate DC parameters with the patient outcome. Results. In the cross-sectional study, we observed by flow-cytometry that the frequency of circulating pDCs, cDC1s, cDC2s and slanDCs was significantly lower in HGG patients than HDs. DC reduction was evident only in patients affected by the most severe form of HGGs (IDHwt IV grade gliomas). The analysis of tissue DCs revealed that DC subsets were absent in healthy brain parenchyma, whereas they infiltrated HGG tumour tissues. In particular all subsets of myeloid DCs (including cDC1s, cDC2s, slanDCs, and moDCs) were observed in the tumours, whereas pDCs were observed only in a few patients. Tumour-infiltrating DCs were markedly reduced in corticosteroid-receiving patients. By performing scRNAseq, we confirmed that DCs were mostly absent in healthy brain parenchyma whereas they were present in tumour samples and could be sub-divided in 2 sub-clusters. By IPA analysis, we observed a functional dichotomy between these clusters, with the largest one being characterised by an impaired/dormancy state, as assessed by the down-regulation of pathways and functions related to pro-inflammatory responses, cell motility and cell interactions, compared with the smallest cluster characterised, on the contrary, by a more active profile. In the longitudinal study performed on relapsed HGG patients enrolled in ieCTs, we observed that patients with a positive clinical response to immunotherapeutic agents, as assessed by an increased overall survival, showed an increase in the number of circulating cDCs. Conclusions. This study demonstrated that different subsets of DCs infiltrate human HGGs, but are mainly characterized by a transcriptomic profile suggestive of a functional impairment. These results provide novel insights into the comprehension of the molecular mechanisms of DC impairment in HGG microenvironment, and pave the way for the development of novel strategies aimed at restoring the ability of DCs to activate cytotoxic anti-tumour immune cells. Our observation in the longitudinal study that an increase of cDCs correlated with a better clinical response to immunotherapy seems to support the relevant role played by DCs in the control of HGG growth. On the other hand, our study also demonstrated that corticosteroid treatment, commonly used in HGG patients for the management of cerebral oedema, reduces the number of tumour-infiltrating DCs. Based on the above considerations, this finding may suggest a negative impact of corticosteroid treatment on anti-tumour immune responses, thus supporting the use of alternative approaches to control this clinical complication. Altogether, our results support and encourage the study of DCs in HGG, in order to improve our knowledge on the role played by DCs within the immunosuppressive tumour microenvironment that characterizes this human cancer. To this aim, in the near future we plan to apply new bioinformatic tools to the analysis of single-cell data collected in HGG tumour environment that may be particularly useful for investigating the intricate interactions occurring between DCs and other HGG-infiltrating immune cells or malignant glioma cells.

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4

Salas, Vargas Natalia E. "CDVCH Centro de difusión del vino chileno." Tesis, Universidad de Chile, 2011. http://www.repositorio.uchile.cl/handle/2250/100425.

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El estudiar el vino como tema para proyecto de titulo, hizo posible la realización de diversas visitas a varias viñas del país. Estas experiencias permitieron la observación de un fenómeno particular: La mayoría de los visitantes de las viñas eran extranjeros, aun cuando estas estuvieran ubicadas en las cercanías de Santiago. Esta inquietud fue reafirmada tiempo después a través de entrevistas realizadas a personas vinculadas al mundo del vino (sommeliers, enólogos, Viñas de Chile), concluyendo todas estas conversaciones en un mismo punto: el poco conocimiento del vino por parte de los chilenos y la disminución en el consumo de esta bebida en el mercado nacional. Al tener noción de esta realidad, el Proyecto de Titulo comenzó a configurarse con mayor claridad. Por esta razón, es que la propuesta arquitectónica de este proyecto se plantea desde la difusión del vino chileno, promoviendo conceptos tan importantes como la historia, la cultura, el territorio y el paisaje que existe entorno al vino de nuestro país. Viendo al vino no solamente como una bebida alcohólica más, sino más bien como un valor tangible que es propio de la nación.

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5

Harris, Ruth V. "Phosphorylation of linker histones by cdc2 kinase." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336626.

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6

Moyano, Rodríguez Yolanda 1992. "Mitosis exit regulation by Cdc5 and PP2A-Cdc55." Doctoral thesis, Universitat Pompeu Fabra, 2019. http://hdl.handle.net/10803/668051.

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In this thesis we studied the role of PP2ACdc55 in the cytokinesis regulation and the contribution of Cdc5 kinase in the mitosis exit using budding yeast as model. Previously, it was suggested a putative PP2ACdc55 role in cytokinesis based on the elongated phenotype in absence of Cdc55. However, the PP2ACdc55 function during cytokinesis and its direct targets were not identified. In this thesis, we demonstrated that PP2ACdc55 regulates the IPC’s phosphorylation and their residence time at the bud neck. In addition, we showed that PP2ACdc55 coordinates actomyosin ring (AMR) contraction with septa formation. As a second objective, we analyzed the Net1 residues to be phosphorylated by Cdc5 kinase contributing to the Cdc14 release from the nucleolus and mitotic exit progression.
En esta tesis hemos investigado el papel de la fosfatasa PP2ACdc55 en la regulación de la citocinesis y la contribución de la quinasa Cdc5 en la salida de mitosis en la levadura de gemación. Previamente, se había sugerido un posible papel de la PP2ACdc55 en citocinesis basándose en el fenotipo elongado en ausencia de Cdc55. Sin embargo, la función de la PP2ACdc55 durante la citocinesis y sus sustratos no han sido estudiados. En esta tesis, hemos demostrado que la PP2ACdc55 regula la desfosforilación de las proteínas de IPC que regulan la citocinesis; así como, su tiempo de localización en el cuello. Además, hemos observado como la PP2ACdc55 realiza un papel en la coordinación de la contracción del anillo de actomiosina y la formación del septo. En cuanto a Cdc5, analizamos los posibles residuos de Net1 fosforilados por Cdc5 que contribuyen a la liberación de Cdc14 en la salida de mitosis.

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7

Glasssmith, Gareth. "Characterisation of cdc2-related kinases from Trypanosoma brucei." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363169.

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8

Ko, Tun Kiat. "Characterization of Crk7-a novel Cdc2-related kinase." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621784.

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9

Leligny, Henri. "Etude des cristaux hydratés isolés dans les diagrammes CdCl-HO, CdBr-HO et CdCl-CaCl-HO structures atomiques et propriétés cristallochimiques /." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37607240v.

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10

Bahman, A. M. "Studies on the CDC7 gene product of Saccharomyces cerevisiae." Thesis, University of Manchester, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233154.

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11

Hayles, J. "Suppressor analysis of the cdc2 gene in Schizosaccharomyces pombe." Thesis, University of Sussex, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.377076.

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12

Dick, S. D. "The structural and functional characterisation of human Cdc7 kinase." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1537309/.

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Cell division cycle 7-related Ser/Thr (Cdc7) kinase is conserved and essential across eukaryotes. When bound to its activator, dumbbell-forming factor 4 (Dbf4) it phosphorylates a number of target proteins involved in various aspects of the cell cycle, including replication initiation, meiosis, the intra S-phase checkpoint, the DNA damage response and mitotic exit. Cdc7 is overexpressed in a number of cancers and expression correlates with patient prognosis. Selective inhibition of Cdc7 leads to cell death through an aberrant S-phase in transformed cells, while healthy fibroblasts are able to survive such treatments. Therefore, Cdc7 is an attractive target for cancer therapeutics, and high-resolution structural information could be very informative for the development of small molecule inhibitors. Herein, I present crystal structures of a fully active Cdc7-Dbf4 heterodimeric construct bound to a potent Cdc7 inhibitor, a non-hydrolysable ATP analogue and an Mcm2-derived substrate peptide. These structures, refined to a high resolution, reveal a previously unseen Zn-binding domain that supports a fully open conformation of the active site. The structures also reveal features required for substrate binding and phosphorylation. In vitro assays have been employed to validate the functional significance of these features, and an in cellula system developed to investigate their importance in the cell. The new structural and functional information gained from this study will inform the design of small molecule inhibitors of Cdc7 while the cell-based system opens up new ways of addressing the functions of the unique kinase insert sequences of Cdc7.

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13

Oh, Chanseok. "Improving SAT Solvers by Exploiting Empirical Characteristics of CDCL." Thesis, New York University, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10025676.

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The Boolean Satisfiability Problem (SAT) is a canonical decision problem originally shown to be NP-complete in Cook's seminal work on the theory of computational complexity. The SAT problem is one of several computational tasks identified by researchers as core problems in computer science. The existence of an efficient decision procedure for SAT would imply P = NP. However, numerous algorithms and techniques for solving the SAT problem have been proposed in various forms in practical settings. Highly efficient solvers are now actively being used, either directly or as a core engine of a larger system, to solve real-world problems that arise from many application domains. These state-of-the-art solvers use the Davis-Putnam-Logemann-Loveland (DPLL) algorithm extended with Conflict-Driven Clause Learning (CDCL). Due to the practical importance of SAT, building a fast SAT solver can have a huge impact on current and prospective applications. The ultimate contribution of this thesis is improving the state of the art of CDCL by understanding and exploiting the empirical characteristics of how CDCL works on real-world problems. The first part of the thesis shows empirically that most of the unsatisfiable real-world problems solvable by CDCL have a refutation proof with near-constant width for the great portion of the proof. Based on this observation, the thesis provides an unconventional perspective that CDCL solvers can solve real-world problems very efficiently and often more efficiently just by maintaining a small set of certain classes of learned clauses. The next part of the thesis focuses on understanding the inherently different natures of satisfiable and unsatisfiable problems and their implications on the empirical workings of CDCL. We examine the varying degree of roles and effects of crucial elements of CDCL based on the satisfiability status of a problem. Ultimately, we propose effective techniques to exploit the new insights about the different natures of proving satisfiability and unsatisfiability to improve the state of the art of CDCL. In the last part of the thesis, we present a reference solver that incorporates all the techniques described in the thesis. The design of the presented solver emphasizes minimality in implementation while guaranteeing state-of-the-art performance. Several versions of the reference solver have demonstrated top-notch performance, earning several medals in the annual SAT competitive events. The minimal spirit of the reference solver shows that a simple CDCL framework alone can still be made competitive with state-of-the-art solvers that implement sophisticated techniques outside the CDCL framework.

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14

今宿, 芳郎. "シロイヌナズナのCDC2遺伝子群の研究". 京都大学 (Kyoto University), 1997. http://hdl.handle.net/2433/202465.

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15

Shin, Kyoo-Chul. "Identification of Critical Dispute Characteristics (CDCs) during construction project operations." Diss., Georgia Institute of Technology, 2000. http://hdl.handle.net/1853/20683.

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16

Singh, Tejomayee. "Functionalization of cancer-associated mutant alleles of human CDC4 (FBXW7)." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/45351.

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Cancer is a leading cause of death worldwide. This somatic cell genetic disease is characterized by progressive accumulation of mutations in multiple genes. An important characteristic of cancer cells is an increased rate of gains and losses of chromosomes, termed Chromosomal Instability (CIN). One of the frequently mutated genes in a variety of cancers is FBXW7 (F-Box and WD repeat domain-containing 7), encoding the substrate-recognition component of a ubiquitin ligase complex. Fbxw7 targets a number of oncoproteins such as, Cyclin E, c-Myc, Notch1 and Aurora A for ubiquitin mediated degradation. Inactivation of FBXW7 has been linked to CIN in cancer cell lines. The majority of cancer-associated mutations in FBXW7 are monoallelic, missense substitutions whose phenotypic effects are difficult to predict. Interestingly, most of the mutations in FBXW7 cluster at three mutational hotspots, Arg465, Arg479 and Arg505. Located at β propeller-tip, these residues are critical for interaction with the Fbxw7 substrates. This study investigates the functional consequences of the substitutions at these residues. We individually tested the functional status of the R465C, R479Q and R505C variants of FBXW7 in three colorectal cancer cell lines in an HCT116 background. These cell lines had both, one or none of the alleles of FBXW7 inactivated by homologous recombination. Our data shows that the cell lines producing R465C, R479Q or R505C variants of FBXW7 failed to degrade Cyclin E, one of the major targets of FBXW7. These cell lines also exhibited a CIN phenotype, observed as an increase in the frequency of abnormal anaphases. These results show that mutations R465C, R479Q and R505C occurring in FBXW7 cause loss of function of the protein and act as dominant negative mutations.

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17

Scheibler, Karsten [Verfasser], and Bernd [Akademischer Betreuer] Becker. "Applying CDCL to verification and test: when laziness pays off." Freiburg : Universität, 2017. http://d-nb.info/1134967969/34.

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18

Patterson, M. N. "A molecular analysis of the yeast cell cycle gene CDC7." Thesis, University of Manchester, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370956.

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19

Hussain, Mursheda. "Vapor CdCl₂ Processing of CdTe Solar Cells." Scholar Commons, 2004. https://scholarcommons.usf.edu/etd/1088.

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Polycrystalline CdS/CdTe thin film solar cells are among the leading candidates for low-cost, large scale terrestrial photovoltaic applications. CdTe has a high absorption coefficient and it can absorb the radiant energy within less than 2 µm of thickness. This makes it suitable for thin film applications. CdTe has a band gap of 1.45 eV at room temperature, which is nearly optimum for photovoltaic conversion efficiency under the AM 1.5 solar spectrum. The theoretical maximum efficiency for CdTe solar cells is 29%. However, to-date the experimental value is in the 16 % range. In most cases CdTe cells are subjected to a post-growth heat treatment which involves annealing in the presence of CdCl2. The treatment results in significant increases in conversion efficiency (η) and all three solar cell parameters Voc, FF, and Jsc. In this work, several variations of the CdCl2 treatment were used on more than 100 samples to investigate their effects on the solar cell parameters. A vapor CdCl2 method was applied for the treatment with various source temperatures, substrate temperatures, and treatment times. The cells were characterized by dark and light J-V and spectral response (SR) measurements.

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20

Hansson, Alexander, and Andreas Petersson. "Mappningsstrategi på IKEA:s CDC-lager i Torsvik." Thesis, Jönköping University, JTH, Industrial Engineering and Management, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-939.

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This study has been assigned by Bengt Hellman who works at the logistic department at IKEA Torsvik just outside of Jönköping. The task has been to develop a new picking strategy for the Oversize area in the CDC-Warehouse. The reason why IKEA wants a new strategy is because they want to minimize the route length for the forklifts when collecting the orders.

By evaluating the current strategies on other areas in the CDC-storehouse, study literature within this subject and look at restrictions for the storing of goods, we have analyzed how the Oversize area works today. We compared the gathered information, to how it should be done according to the literature to be able to work out a new functional strategy.

Today, IKEA does not have a working strategy for the oversize area because of lack of time and because all the power has been put on other areas were sales rates are currently higher. This have led to lack of organisation at the Oversize area and items are just put were there is space without first analysing were it should be placed.

The strategy that we have worked out and introduced to IKEA builds on easiness of understanding the layout, the employees shall know why an item is placed where it is. We have also analyzed which items that are frequently ordered with each other. We have put weight on trying to keep those items as close as we can to minimize the route length for the forklifts. To help IKEA with reorganizations in the future we have made it as easy as we could to move high- and low frequently items around and also introducing new articles in the storehouse, this by the reason that sales rate can change drastically when a new sales campaign is initiated by IKEA

Detta examensarbete är utfört på önskemål av Bengt Hellman som arbetar på logistikavdelningen på IKEA Torsvik utanför Jönköping. Arbetet har gått ut på att ta fram ett nytt förslag på hur de skall placera sina artiklar på plocknivå (vad IKEA kallar för mappning) inne på Oversize avdelningen på IKEA:s CDC-lager. Anledningen till detta är att IKEA vill minska sina körsträckor för plockarna inne på lagret och därmed öka effektiviteten.

Genom att studera befintliga mappningsstrategier som redan finns på övriga avdelningar på CDC-lagret, litteraturstudier och titta på vilka begränsningar som finns inne på lagret så har vi analyserat nuläget mot teori för att sedan kunna ta fram en ny strategi för hur en fungerande mappning skulle kunna se ut.

I dag så finns det inte någon väl utarbetat strategi för mappningen på Oversize avdelningen, detta på grund av att andra avdelningar prioriterats på grund av att de säljer mycket mer i dagsläget. Detta har även medfört att den huvudsakliga uppdelning som fanns tidigare på Oversize avdelningen med affärsområden har fått stå åt sidan på grund av tidsbrist och artiklar har placerats in där det finns plats istället för att analysera var de kan placeras bäst.

Det nya förslaget som vi presenterar för IKEA bygger på att det skall vara enkelt att förstå layouten, plockarna skall veta varför en artikel finns där den finns. Vi har även tagit stor hänsyn till vad som säljs med vad och försökt placera dessa artiklar i närheten av varandra för att på så sätt minska körsträckorna. Vi har även haft i åtanke att det skall vara enkelt att placera om hög och lågfrekventa artiklar samt nyheter inne på lagret då försäljningsvolym påverkas väldigt mycket utav olika kampanjer som IKEA har.

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21

Engemann, Harald Gotthard. "Charakterisierung der Dlk/CDC5-Interaktion und der Genstruktur des Dlk-Gens." [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=981418090.

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22

Petersen, Birgit Otzen. "Regulation of mammalian CDC6 by CDK phosphorylation and proteasome dependent degradation." Thesis, Open University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298212.

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23

Smedt-Peyrusse, Véronique de. "Activation du MPF dans l'ovocyte de Xénope : rôle du Cdc2 monomérique." Paris 6, 2002. http://www.theses.fr/2002PA066340.

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24

Carr, A. M. "Analysis and characterisation of the cdc2 gene region of fission yeast." Thesis, University of Sussex, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.375854.

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25

Lindblad, Johan. "On the Structure of Resolution Refutations Generated by Modern CDCL Solvers." Thesis, KTH, Skolan för elektroteknik och datavetenskap (EECS), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-252732.

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Анотація:

Modern solvers for the Boolean satisfiability problem (SAT) that are based on conflict-driven clause learning (CDCL) are known to be able to solve some instances significantly more efficiently than older kinds of solvers such as ones using the Davis-Putnam-Logemann-Loveland (DPLL) algorithm. In addition to solving instances that can be satisfied, SAT solvers will implicitly generate proofs of unsatisfiability for formulae that are unsatisfiable. Theoretical models of CDCL based solvers are known to have access to more powerful forms of reasoning compared to their DPLL counterparts and as a result, are able to generate proofs that are significantly shorter for certain kinds of formulae. Additionally, certain characteristics are expected when representing these proofs as graphs, such as them not being strictly tree-like in shape. It is however less well known if these theoretical justifications are indeed the reason CDCL solvers are so successful in practice. This project attempts to answer this question by modifying a modern CDCL solver to output the proof and comparing these proofs to what theoretical results would predict. Firstly, the results indicate that CDCL solvers generate significantly shorter proofs for all kinds of formulae that were investigated as compared to a DPLL solver. Furthermore, it appears that this is in large part due to the proof not being tree-like. Secondly, utilizing restarts was found to make for significantly shorter proofs for most families of formulae but the effect was the opposite for formulas representing the relativized pigeonhole principle. The explanation for this is seemingly not clear. Lastly, it appears that the Tseitin formulae used do not exhibit timespace trade-offs but instead simply require a large amount of space. This is indicated by the run time being significantly greater if clause erasure if more aggressive but the refutation being similar in both length and number of learned clauses. To summarize, it has been found that modern CDCL solvers appear to result in significantly different proofs that largely mirror what one would expect. However, the results are unclear on the role of restarts and how their effect on the proof best can be explained.
Moderna lösare för Boolean satisfiability problem (SAT) baserade på konfliktdriven klausulinlärning (CDCL) har visats prestera väl och lösa vissa typer av formler mer effektivt än äldre varianter såsom Davis-Putnam-Logemann-Loveland-algoritmen (DPLL). Förutom att lösa instanser som är lösbara så producerar SAT-lösare implicit bevis på olösbarhet för formler som är olösbara. Teoretiska modeller över CDCL-baserade lösare har visat på att mer kraftfulla former av resonemang är tillgängliga jämfört med DPLL-baserade motsvarigheter; som ett resultat kan CDCL-baserade lösare enligt dessa modeller producera kortare bevis. Vidare väntas dessa bevis ha vissa karaktärsdrag när de representeras som grafer som exempelvis att de inte är strikt trädformade. Dock är det inte känt om dessa teoretiska förklaringar faktiskt korrekt beskriver anledningarna att CDCL-baserade lösare är så framgångsrika i praktiken. Detta projekt ämnar klargöra denna fråga genom att modifiera en CDCL-baserad lösare så att den producerar bevisen explicit och sedan jämföra dessa bevis med vad teoretiska resultat skulle förutspå. För det första så visar resultaten att CDCL-baserade lösare genererar betydligt kortare bevis för alla sorters formler som undersöktes. Studier av småskaliga probleminstanser visar att en del av förklaringen till detta är att beviset inte är strikt trädformat. För det andra visar resultaten att omstarter gör bevisen betydligt kortare för nästan alla formler men att det motsatta är sant för så kallade relativized pigeonhole principle-formler. Förklaringen till detta är inte helt tydlig. För det tredje sågs tendenser till tid-utrymmes-avvägningar för formler som var inspirerade av så kallade Tseitin-formler där dessa avvägningar är bevisade. Det antyder att även dessa inspirerade formler ger dessa avvägningar i praktiska implementationer av CDCL-lösare. För att summera så visar resultaten att moderna CDCL-baserade lösare till stor del uppnår vad teoretiska modeller förutspår i termer av formen på deras bevis. Dock är resultaten mindre tydliga vad gäller omstarter och hur deras påverkan på bevisen bäst förklaras.

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Roccuzzo, M. "REGULATION OF CHROMOSOME SEGREGATION BY CONSERVED PHOSPHATASE CDC14 AND KINASE CDC5." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/234144.

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The faithful transmission of the replicated genome from the mother to the daughter cell requires the correct establishment of linkages between the duplicated chromosomes (sister chromatids) and their bi-orientation on the mitotic spindle. Chromosome segregation initiates only after each sisters pair is correctly aligned onto the microtubules emanating from the spindle poles. Next, Esp1-mediated cleavage of cohesin is required to trigger anaphase onset while the physical segregation of the separated sisters is next driven by spindle activity. However, this scenario appears to be more complicated involving additional factors driving the sister chromatid segregation process (i.e. the Top2-mediated resolution of replication catenates). In budding yeast, anaphase progression and exit from mitosis require the protein phosphatase Cdc14 whose activation relies on two consecutive protein pathways, the FEAR network and the MEN. As the polo-like kinase Cdc5 is a component of both pathways its activity is essential to Cdc14 release and in its absence Cdc14 is never released. By combining loss-of-function alleles of Cdc5 and Cdc14 we obtained double mutant cells that had cohesin cleaved but still arrested with undivided nuclei and short bipolar spindles. Anaphase spindle elongation initiates quickly after cohesin removal (anaphase A) and then switches to a slower elongation rate (anaphase B) due to changes in spindle behaviour mediated by motor proteins and microtubule-associated enzymes. Although some residual cohesion between sister chromatids seems to contribute to the terminal phenotype of cdc14 cdc5 cells, our data indicate that anaphase B is the main mitotic defect of these cells. We conclude that Cdc5 and Cdc14 are redundantly involved in activating spindle activity following cohesion resolution, suggesting the existence of a regulatory network that coordinates sister chromatid separation with spindle elongation after cohesin cleavage. Importantly, we identified the motor protein Cin8 as a (direct or indirect) target of Cdc5 in the regulation of spindle elongation.

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27

Massey, Jack. "The dynamics and demography of socially structured carnivores : badgers, lions and wolves." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:49e1063c-cdc5-4865-a931-5da91f4556c5.

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Sociality in carnivores is theoretically expected to produce quantitatively different dynamics compared to solitary species, exhibiting Allee effects, increasing extinction risk and limiting population growth. There is also evidence in social species that demographic stochasticity can impact the population when densities are high. Empirical support for these processes is lacking and the effects of socio-spatial structure on population dynamics is now widely debated. The roles of social structure, reproductive suppression, communal predator vigilance, communal hunting and babysitting on population responses to perturbations away from carrying capacity have important implications for species management. Social systems also possess inherent spatial structure. Such structure is known to influence dynamics in solitary species. This thesis investigates the relative contributions of spatial and social structure on population dynamics in three contrasting carnivores, from three different families; badgers (Meles meles), lions (Panthera leo) and grey wolves (Canis lupus), that each demonstrate comparable and different life history strategies with one another. Simple and complex structured population models are used to demonstrate how intra-group processes interact within inter-group process and habitat features to produce population wide dynamics. The models are used to investigate whether general rules governing the dynamics of social species can be drawn across species.

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28

Lazzaro-Albert, Maribeth A. "Characterization of a novel cdc2-related kinase expressed in the nervous system." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0015/NQ36997.pdf.

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29

Ongkeko, Weg M. "The role of Cdc2 and p53 in cell cycle checkpoints and apoptosis." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244848.

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30

Das, Neves Henrique Coutinho Póvoas Esteves. "MCM10, CDT1 and CDC6 as prognostic biomakers and drivers of breast cancer." Thesis, University of Macau, 2018. http://umaclib3.umac.mo/record=b3953629.

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31

Paolinelli, Roberta. "Roles for ORC1 and CDC6 in the regulation of human DNA replication." Doctoral thesis, Scuola Normale Superiore, 2007. http://hdl.handle.net/11384/85991.

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32

Ni, Tao. "Structural and functional study of MACPF/CDC superfamily proteins." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:50793dea-6aa6-4922-b7d8-43c50079639b.

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The thesis mainly focuses on structural study of proteins in membrane attack complex- perforin/cholesterol-dependent cytolysins (MACPF/CDC) superfamily, in particular, Astrotactins from human and perforin-like proteins (PLPs) from Toxoplasma and Plasmodium. Both of these subfamily proteins are implicated in human diseases and structurally uncharacterised before. Astrotactins (ASTNs) have been shown to play a crucial role in enabling neural migration along glial fibres. While ASTN1 directly forms contacts between the neuron and the fibre, ASTN2 is responsible for extracting ASTN1 from contacts at the lagging edge of the cell and recycling them to the leading edge. ASTN2 is associated with endosomes, with the majority of its structure (at the C-terminus) projecting into their lumen, anchored by a pair of transmembrane â-helices. Here we present the structure of this "endodomain" region of ASTN2, and find it to consist of a unique combination of polypeptide folds comprising a membrane attack com- plex/perforin (MACPF) domain, an EGF-like domain, a previously-unobserved form of fibronectin type III (Fn(III)) domain and an annexin-like domain. Taken together, the structural characterisation provides a framework for better understanding the mechanism of the ASTNs and related proteins in neural and other forms of vertebrate development. Perforin-like proteins from Toxoplasma and Plasmodium (TgPLP1 and PPLPs) are critical for normal life cycle progression of these parasites, and knockout out of any of them results in significant defects in their life cycle, entrapping the parasites within the host cells and thus limiting their ability to egress. Here we present the crystal structures of TgPLP1 MACPF domain and C-terminal domain at 2.0 Å and 1.1 Å, respectively. We also presents the MACPF domain assembled in helical and hexameric ring form, which indicates the possibility of pore-formation by 6 subunits. This is the first structure of perforin-like protein from Apicomplexan parasites and provides a structural basis to elucidate the function of PLPs in toxoplasmosis and malaria pathogenesis. The final section is a continuation of a previous study in our lab on pleckstrin homology (PH) domain of kindlins. We determined the crystal structure of kindlin-3 PH domain and characterised its lipid and membrane binding properties. Using nanodiscs incorporated with different lipids as model membrane system to study the interaction between inositol phosphate lipids and kindlin-3 PH domain, together with molecular dynamic simulation studies (in collaboration with Mark Sansom's group, University of Oxford), we propose that a subset of PH domains is able to bind to multiple inositol phosphates simultaneously and so via an avidity effect have its interaction with target membranes strengthened.

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Canales, Renata Pereira. "O Centro de Divulgação Científica Cultural da Univerisdade de São Paulo, campus São Carlos: um projeto de extensão universitária." Universidade Federal de São Carlos, 2006. https://repositorio.ufscar.br/handle/ufscar/2395.

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Анотація:

Made available in DSpace on 2016-06-02T19:38:45Z (GMT). No. of bitstreams: 1 DissRPC.pdf: 4541699 bytes, checksum: 0a15e746cc62d592608bcad54351b1db (MD5) Previous issue date: 2006-08-08
The present study endeavours to contribute to a better understanding of the education in this country by means of a case study of the Centro de Divulgação Científica e Cultural CDCC (Centre for Scientific and Cultural Promotion). This centre was established in 1980 by the São Carlos campus of the University of São Paulo and since then put under the care of the Institute of Physics and Chemistry. The CDCC operates educational projects aimed at fostering scientific curiosity in basic educational level students. The investigation covers the process of CDCC s creation and seeks comprehension of its first motivation and objectives as well as peruses into the history of its building, which once hosted the Engineering School of USP-São Carlos. It does also investigate the services offered to the community, analyses CDCC administrative rules, and more incisively, reasons out the role of the Experimentoteca , the initial project that begot the Centre itself, and whose scope is to provide means of empirical experience of scientific theories for children at the basic level of education. The Experimentoteca is a portable laboratory of sciences that, under request, is taken to schools for classroom demonstrations. This project, initially restricted to São Carlos City and region, is currently extended to 31 cities of 13 different states. Following the steps of Buffa and Nosella, an epistemological frame of reference is taken from work and educational relations as well as from the relations of general overview and singular descriptions, as established by the New History, along with analysis of documents and facts under the educational viewpoint of the country. The sources are both the literature concerning community roles of the university, defined as one of the corners of the university s triple mainstay in the 5,540/68 Bill and the 1988 Constitution, and yet the literature concerning the history of Brazilian education, chiefly after the 5,692/71 Bill, which was in force when the CDCC was created. Additional research sources are magazines, books, scientific articles concerning the CDCC and its building, as well as CDCC s reports and governance rules. Interviews with CDCC s workers and founders and questionnaires applied to students using the Experimentoteca are yet complementary sources. Data analyses avail a conclusion that CDCC orientation differs from the patronizing stance that pervades most of community services. Indeed, evidence was produced as to suggest that CDCC s intervention fosters reflection and responsibility among students. Nevertheless, the scientific curiosity does not seem to blossom as expected. School and social-family adverse environments do not make room for such: these are children of low income working class parents, who are educationally deprived and subjected by a neglected educational policy that includes deteriorated buildings, unhealthy classrooms, and teachers discouraged by low wages and bad working conditions. The CDCC s work stands alike a clean drop over a polluted river but its initiative is not useless, and does meet its best meaning in the respect to citizenship and in the interchange of lay and academic wisdom provided by the collaboration between university and community. There remains a hope that such values that exceed school limits be dully appreciated by the country politicians.
A presente dissertação busca contribuir para o entendimento da educação no país através do estudo de caso do Centro de Divulgação Científica e Cultural (CDCC), um trabalho de extensão realizado, desde 1980, pela Universidade de São Paulo, câmpus São Carlos, sob responsabilidade do Instituto de Física e Química. Este Centro realiza projetos educacionais voltados a alunos do ensino básico com o intuito de desenvolver o interesse pelas ciências. A pesquisa percorre o processo de criação deste Centro e busca entender suas motivações e objetivos iniciais; resgatar o histórico do prédio no qual se instala, que foi a primeira sede da Escola de Engenharia da USP-São Carlos; analisar as atividades oferecidas à população; apreciar o seu regimento administrativo; e, de forma mais aprofundada, estudar o desenvolvimento do projeto Experimentoteca, mola propulsora para o nascimento do Centro, cujo objetivo é instrumentalizar o aluno do ensino básico para que ele entenda, através da prática, as teorias científicas aprendidas em sala de aula. A Experimentoteca é um laboratório de ciências circulante e os experimentos são levados às escolas que os solicitam para serem realizados em sala de aula. O projeto, que se iniciou em São Carlos e região, atualmente, é usado em 31 cidades de 13 Estados do país. Seguindo os passos de Buffa e Nosella, usam-se como referências teóricometodológicas as relações de trabalho e educação, as relações das visões gerais e descrições do singular estabelecidas na chamada Nova História, além da análise de documentos e fatos sob a ótica educacional do país. As fontes são tanto a bibliografia que se refere ao trabalho de extensão universitária, definido como um dos elementos do tripé de sustentação da universidade na Lei n° 5.540/68 e ratificado na Constituição de 1988, quanto a que analisa a história da educação brasileira, principalmente depois da Lei n° 5.692/71, que se encontrava em vigência no país à época da criação do CDCC. Também são fontes documentais da pesquisa: revistas, livros, artigos científicos sobre o CDCC e sobre prédio onde atua, relatórios das atividades, projetos e regimentos do Centro. Entrevistas gentilmente cedidas por funcionários e participantes da criação do CDCC são fontes orais fundamentais para a análise assim como entrevistas e questionários respondidos por alunos que utilizam a Experimentoteca. Da análise dos dados e informações obtidos pôde-se concluir que a orientação do Centro de Divulgação Científica e Cultural distingue-se da visão assistencialista que guia a maioria dos trabalhos de extensão. De fato, reuniram-se evidências que sugerem que a intervenção do CDCC promova reflexão e responsabilidade entre os alunos que seu trabalho alcança. No entanto, o esperado interesse pelas ciências é diluído em meio aos problemas que os estudantes da rede pública enfrentam em seu cotidiano tanto escolar quanto sócio-familiar. Eles são filhos de trabalhadores de renda modesta, de limitado capital cultural e ainda vítimas de uma política educacional deficiente que proporciona ensino em prédios mal cuidados, em salas mal ventiladas e com professores desmotivados por baixos salários e más condições de trabalho. O trabalho do CDCC acaba sendo uma gota de água limpa em um rio sujo, porém a iniciativa não é inócua e encontra seu maior significado no respeito ao cidadão, na troca entre os saberes popular e acadêmico, na abertura da comunicação da universidade com a população. Permanece a expectativa de que esta compreensão de que a educação excede os muros da escola ganhe o respeito que reclama dos governantes do país.

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34

Patala, Anne Havilah. "Discordance of Drug Susceptibility Test Data between the CDC Mycobacteriology Laboratory and Local Public Health Laboratories Participating in Tuberculosis Clinical Trials, TBTC, CDC." Digital Archive @ GSU, 2011. http://digitalarchive.gsu.edu/iph_theses/171.

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BACKGROUND: Multi drug resistant Tuberculosis (MDR-TB) is a serious public health concern in many parts of the world. As per the WHO- 2010 global report on Surveillance and response 3.6% of all incident TB cases globally are multidrug resistant. In this regard, there is an increasing demand for timely, reliable and comprehensive drug susceptibility testing (DST) as MDR-TB surveillance is being geared up. The intent of this analysis is to determine whether there is a need to continue routine confirmatory DST testing at CDC in addition to just sending the isolates for genotyping. Analysis is done by measuring the discordance between the results of laboratory DST at CDC and the local labs drug type, drug testing concentrations, and study sites. METHODS: The data for this analysis was provided by the Tuberculosis Trials Consortium (TBTC), CDC. Data for this analysis was collected over nearly two decades (1993-2011), gathered from 7 clinical trials. Discordance between the local and CDC lab DST results was measured using Kappa statistic. Sensitivity and specificity analysis was done by taking the CDC DST lab results as the gold standard. Discordance levels were calculated by local sites and baseline drug resistance for each antibiotic in each study was measured. RESULTS: Average Kappa values for inter rater agreement for all the studies was 0.6444 whereas the overall level of discordance across all studies is 7.786%. Drug resistance at baseline was highest for Isoniazid and Streptomycin (except Study 23 and 22). CONCLUSION: Though the current results show few DST result discordances between local and CDC labs, it is better to continue to send isolates to the centralized lab (CDC) in view of the worldwide threat of drug resistant TB epidemic, the recommendations of the current literature and the benefits of reliable confirmatory testing services and availability of other molecular diagnostic methods.

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35

Lee, Brian H. (Brian Han) 1976. "Regulation of meiosis I chromosome segregation by Spol3 and Cdc5 in Saccharomyces cerevisiae." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/32257.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2004.
Includes bibliographical references.
Meiosis is a specialized cell cycle that generates gametes for the purpose of disseminating genetic material to the next generation. The reduction of chromosome number by half is brought about two chromosome segregation phases following a single DNA replication phase. In the first division, homologs segregate away from each other and in the second division the sister chromatids separate. These two consecutive meiotic divisions necessitate innovations in chromosome dynamics and hence the involvement of both meiosis-specific modulators and regulators of the mitotic cell cycle. The work described herein characterizes the roles of two essential meiosis I regulators, a mitotic protein kinase, Cdc5 and a meiosis-specific gene, Spol 3. The conserved polo-like kinase Cdc5 regulates many essential aspects of meiosis I including the removal of cohesion between sister chromatids for homolog segregation, sister-kinetochore co-orientation and exit from meiosis I. Spol3 likely cooperates with Cdc5 to regulate some of these processes. SpoI3 controls kinetochore co-orientation and the retention of centromeric cohesion which is essential for accurate sister chromatid segregation in meiosis II. In sum, this work elucidated the roles of two important regulators of the meiotic cell cycle and defines a component of the complex regulatory circuit necessary for the specialized meiotic divisions.
by Brian H. Lee.
Ph.D.

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36

Hong, H. K. "Cdc7/ASK kinase as a novel target for anti-cancer drug development programmes." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1324534/.

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Targeting Cdc7, a kinase essential for DNA replication initiation, results in potent cancer cell killing. Cancer cells in which CDC7 is silenced by RNAi enter an abortive S phase followed by apoptosis due to loss of a functioning DNA replication origin activation checkpoint. This checkpoint prevents normal cells from entering S phase (reversible G1 arrest) if the DNA replication initiation machinery is perturbed. The pre-clinical anti-cancer effects of CDC7 silencing have highlighted this kinase as an important target for new drug development. Expanding on published reports, I performed further target validation using molecular tools generated in the work of this thesis, including an affinity-purified antibody to the Cdc7 regulator ASK and functional recombinant Cdc7/ASK kinase complex. Making use of fibroblast and HL60 tissue culture model systems, I show that Cdc7 and ASK are amongst a group of essential replication initiation factors that are tightly downregulated to suppress proliferative capacity during exit from cycle into quiescent and differentiated states. This finding is further supported by low expression levels in normal liver and oral squamous epithelium and the lack of Mcm2 phosphorylation at serine 53, a well known Cdc7 target. In liver carcinoma and oral squamous cell carcinoma, on the contrary, the majority of cancer cells are expressing Cdc7 and ASK and show Mcm2 phosphorylation at Ser-53. Thus it can be postulated that Cdc7 inhibitors should selectively kill cancer cells, while normal proliferating cells are reversibly arresting in G1 and quiescent and differentiated cell populations are not affected due to downregulation of the target protein. To screen for compounds that selectively inhibit Cdc7, I developed a sensitive in vitro kinase assay and contributed to the successful transfer of this assay to a high-throughput screening platform and the generation of a structural model of the Cdc7 kinase domain allowing in silico predictions of the most potent inhibitors. On completion of the work for this thesis, the HTS assay and structural model fromed the core of an ongoing drug discovery programme run by Cancer Research Technology. Two series of novel, selective small molecule inhibitors which exhibit low nM activity against Cdc7 and cellular efficacy (apoptosis) have been developed and are currently being tested in mouse xenograft models. The work presented in this thesis provides a strong rationale for targeting the DNA replication initiation pathway, and in particular Cdc7. Future intend to treat clinical trials will establish the potential of pharmacological Cdc7 inhibitors for selective cancer cell killing in patients.

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37

Pearson, Neil Joseph. "Genetic dissection of acentrosomal spindle formation : the role of the Cdc2 kinase pathway." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/15619.

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In many animals female meiotic spindles lack centrosomes. In the absence of centrosomes the chromosomes drive spindle formation. This process is not well understood so I examined two mutants from a screen for female sterile mutations with acentrosomal spindle defects. I found that the first mutant, remnants (rem), disrupted spindle morphology, chromosome alignment and microtubule dynamics in non-activated oocytes. rem encodes Cks30A a conserved subunit of Cdc2. Essential pole proteins, msps and D-TACC were often mislocalised to the equator and Cks30A is involved in modification of D-TACC. The second mutant, msps-like, had tripolar spindles in non-activated oocytes. I found that msps-like encodes Weel, a negative regulator of Cdc2 activity. Wee1 is also required for modification of D-TACC in a Cdc2 dependent manner. Twine, the positive regulator of Cdc2, is essential for spindle unification/metaphase arrest of non-activated oocytes and Cdc2 itself is required for correct spindle morphology in female meiosis. Cdc2, its subunit, Cks30A, and its regulators, Weel and Twine, are all required for ancentrosomal spindle formation. Cdc2 is a central figure in a kinase pathway required for multiple facets of acentrosomal spindle formation. To gain new insights in the formation of female meiotic spindles I took part in a screen for metaphase I arrested spindle mutants in female meiosis on the X chromosome of Drosophila. I found mutants defective in chromosome alignment, spindle morphology, spindle unification and spindle formation around individual chromosomes. I characterised several of the mutants found in this screen as well as established complementation groups for all of the mutants discovered to aid in future studies.

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Soares, Daiane da Rocha. "Modulação de Orc1/Cdc6 de Trypanosoma brucei pela ligação e hidrólise de ATP." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42135/tde-13082014-184135/.

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O Complexo de pré-replicação em T.brucei é composto por Orc1/Cdc6 e as helicases MCMs. Em um trabalho anterior mostramos que TbOrc1/Cdc6 pode ligar e hidrolisar ATP in vitro. Neste sentido, o objetivo deste trabalho é avaliar a importância da hidrólise e ligação de ATP para a formação e estabilidade do complexo pré-replicação de T.brucei. Para tanto, foram geradas proteínas recombinantes Orc1/Cdc6 de T. brucei mutadas nas regiões Walker A (TbOrc1/Cdc6K79T) ou sensor 2 (TbOrc1/Cdc6R251,252E) incapazes de ligar ou hidrolisar ATP, respectivamente. Finalmente, as células expressando TbOrc1/Cdc6K79T ou TbOrc1/Cdc6R251,252E foram avaliadas quanto a (i ) estabilidade da interação Orc1/Cdc6 -DNA, (ii) capacidade de estabilizar MCM no DNA, (iii) capacidade de replicar seu DNA. A mutação na região sensor 2 de T.brucei (TbOrc1/Cdc6R251,252E) reduziu drasticamente a atividade de ATPase em comparação com a proteína selvagem . TbOrc1/Cdc6 mutado no sitio de ligação ao ATP perdeu a capacidade de interagir com o ATP (TbOrc1/Cdc6K79T). A super expressão desses genes inibiu de forma significativa a proliferação celular, causou ineficiência no carregamento de MCM para o DNA e ocasionou falhas na progressão do ciclo celular, atrasando a fase S.
The pre-replication complex in T.brucei is composed of at Orc1/Cdc6 and MCMs helicases. In a previous paper we showed that TbOrc1/Cdc6 can bind and hydrolyze ATP in vitro. Based on that, the objective of this study is to evaluate the importance of ATP binding and hydrolysis to the formation and stability of the pre - replication complex in T.brucei. For this purpose, T. brucei Orc1/Cdc6 recombinant proteins were generated mutated at regions on Walker A (TbOrc1/Cdc6K79T) and sensor 2 (TbOrc1/Cdc6R251 , 252E) in order to unable the ATP binding and hydrolyzation respectively . Finally , cells expressing TbOrc1/Cdc6K79T or TbOrc1/Cdc6R251 , 252E were evaluated for (i) stability of Orc1/Cdc6 - DNA interaction , (ii) ability to stabilize MCM in DNA , (iii) ability to replicate its DNA . The mutation in the sensor 2 region of T.brucei (TbOrc1/Cdc6R251 , 252E) drastically reduced the ATPase activity compared to the wild-type protein. TbOrc1/Cdc6 mutated in the ATP binding site has lost the ability to interact with ATP (TbOrc1/Cdc6K79T). The overexpression of these genes significantly inhibited cell proliferation causing inefficient loading of MCM DNA and led to failure in cell cycle progression by delaying the phase S.

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39

Godoy, Patricia Diogo de Melo. "Estudos sobre o componente ORC1/CDC6 da maquinaria de pré-replicação dos tripanossomas." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/42/42135/tde-18102010-112445/.

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Em eucariotos, a origem de replicação é reconhecida por um complexo ORC, a proteína Cdc6 e outras proteínas. Nos tripanossomas, encontramos somente uma proteína similar a Orc1 e Cdc6, que chamaremos de Orc1/Cdc6. Nesta tese serão descritos os estudos realizados sobre Orc1/Cdc6 do Trypanosoma cruzi e do Trypanosoma brucei. As proteínas recombinantes dos tripanossomas apresentam atividade de ATPase e são capazes de substituir Cdc6 em ensaio de complementação em leveduras. A indução do silenciamento do gene de Orc1/Cdc6 por RNAi resulta em células anucleadas. Orc1/Cdc6 é expressa durante todo o ciclo celular das formas replicativas, permanecendo associada à cromatina. No caso do T.cruzi, Orc1/Cdc6 é expressa não só nas formas replicativas, mas também nas formas não replicativas. Nestas últimas, a proteína expressa não interage com o DNA, este resultado sugere que a ausência desta interação deve contribuir para ausência da duplicação do DNA nas formas infectivas do T. cruzi.
In eukaryotes, the replication origin is recognized by a complex ORC, Cdc6 and other proteins. The trypanosomes contain only one protein, we named it Orc1/Cdc6. Here we show that the recombinant Orc1/Cdc6 from T.cruzi (TcOrc1/Cdc6) and from T.brucei (TbOrc1/Cdc6) present ATPase activity, replaced yeast Cdc6 in a phenotypic complementation assay. The induction of Orc1/Cdc6 silencing by RNA interference in T.brucei resulted in enucleated cells. Orc1/Cdc6 is expressed during the entire cell cycle and in all stages of the life cycle of trypanosomes, remaining associated with chromatin in all stages of the cell cycle. This association is different among the stages from T. cruzi life cycle. In the non replicative ones, Orc1/Cdc6 does not interact with DNA. The lack of pre-replication machinery-DNA interaction in T. cruzi non-replicative stages might contribute to the absence of DNA replication in these stages.

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40

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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41

Daldello, Enrico Maria. "Arpp19 et Cdc6, deux régulateurs majeurs des divisions méiotiques de l'ovocyte de Xénope." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066116/document.

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L’objectif de cette thèse a été de comprendre deux caractéristiques majeures des divisions méiotiques chez la femelle: le blocage en prophase de 1ère division méiotique qui permet à l’ovocyte d’accumuler des réserves énergétiques et des déterminants nécessaires au développement embryonnaire ; et l’absence de phase-S entre les deux divisions méiotiques ce qui permet de former des cellules haploïdes aptes à la fécondation. Pour cela, j’ai choisi comme modèle d’étude l’ovocyte de Xénope qui permet de suivre ces processus in vitro en réponse à la progestérone. L’ovocyte subit les deux divisions méiotiques grâce à l’activation du facteur universel de la division cellulaire, le MPF, et se bloque en métaphase de 2ème division méiotique dans l’attente d’être fécondé. Chez tous les vertébrés, le 1er arrêt en prophase dépend de l’activité de la protéine kinase dépendante de l’AMPc, PKA, dont l’inactivation est nécessaire pour la reprise de la méiose. Le substrat de PKA dans l’ovocyte était resté inconnu. Nous avons découvert que la protéine Arpp19, jusqu’alors connue pour son rôle positif dans l’activation du MPF, est phosphorylée par PKA de cette phosphorylation bloque l’activation du MPF nécessaire pour la levée du blocage en prophase. ARPP19 possède donc un double rôle, le 1er exercé comme substrat de PKA et responsable de l’arrêt en prophase, le second dans l’activation du MPF suite à un changement dans sa phosphorylation. Dans un second temps, nous avons étudié la protéine Cdc6, un acteur majeur de la réplication de l’ADN. Absente en prophase, Cdc6 s’accumule entre les deux divisions méiotiques ce qui permet à l’ovocyte d’acquérir la compétence à répliquer l’ADN. Cette compétence ne s’exprime pas ce qui permet de réduire de moitié la ploïdie. Nous avons montré que Cdc6 est un inhibiteur puissant du MPF capable de bloquer les divisions méiotiques et d’induire la réplication de l’ADN. Pour éviter ces effets délétères l’accumulation de Cdc6 est strictement régulée lors des deux divisions méiotiques, ce qui est absolument requis pour assurer l’enchainement des deux divisions cellulaires sans phase-S intercalaire
The goal of my PhD project was to understand two main features of the female meiotic division: the arrest in prophase of the 1st meiotic division that allows the accumulation of nutrients and determinants necessary for the embryonic cell cycles; and the absence of S-phase between the two meiotic divisions in order to produce haploid gametes. For this purpose, I studied Xenopus oocytes, a powerful model system that allows the biochemical analysis of these two processes in vitro. In ovary, oocytes are arrested in prophase I and resume meiosis in response to progesterone. The oocytes then proceed through the 1st and the 2nd meiotic divisions and halt at metaphase II, awaiting for fertilization. These two consecutive divisions are controlled by two waves of Cdk1 activation, the universal factor responsible for the entry into mitosis. I analysed the mechanisms responsible for arresting the oocyte in prophase I. In all vertebrates, this arrest depends on a high activity of the cAMP-dependent protein kinase, PKA, whose downregulation is required for the release of the prophase block. The substrate of PKA had never been identified up to date. I discovered that the small protein Arpp19, already known for positively regulating entry into M-phase, is phosphorylated by PKA in prophase I and is dephosphorylated upon progesterone addition, an event required for Cdk1 activation. Hence, Arpp19 has a dual function, responsible of the prophase arrest as a PKA substrate, and then converted into an activator of Cdk1 by changes of its phosphorylation pattern. The second part of my thesis has been dedicated to understanding the role and the regulation of the Cdc6 protein during meiotic divisions. This protein is essential for DNA replication in somatic cells. It is accumulated between the two oocyte meiotic divisions and restores the competence to replicate DNA in oocyte. However, this competence is repressed before fertilization, allowing formation of haploid cells. I found that the accumulation of Cdc6 is tightly controlled during meiotic maturation by the Cyclin B accumulation and the Mos/MAPK pathway. I further demonstrated that Cdc6 is a strong inhibitor of Cdk1 in Xenopus oocytes and that the timely accumulation of Cdc6 is required to coordinate the two meiotic divisions with no intercaling S-phase

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42

Jensen, Bryan. "Regulation of the G1 to S-phase transition in S. cerevisiae by CDC4 /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/10257.

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43

Quaresma, Paula Gabriele Fernandes 1987. "Estudo da regulação da proteína CDC2-Like Kinase (Clk2) em hipotálamo e fígado de camundongos controles e obesos = CDC2-Like Kinase (Clk2) hypothalamic and hepatic regulation in lean and obese mice." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311558.

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Orientador: Patrícia de Oliveira Prada
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-21T14:12:45Z (GMT). No. of bitstreams: 1 Quaresma_PaulaGabrieleFernandes_M.pdf: 949361 bytes, checksum: 237d0acc0b5bc5358adba045381b4a92 (MD5) Previous issue date: 2012
Resumo: O hipotálamo é um órgão crucial na regulação do balanço energético por integrar sinais hormonais e nutricionais de órgão periféricos. O hormônio produzido pelo pâncreas - insulina - e o hormônio derivado de células adiposas - leptina- reconhecidamente, agem no SNC controlando a ingestão alimentar e o gasto energético. Recentemente foi demonstrado que a fosforilação em treonina 343 da proteina Cdc2-like kinase 2 (Clk2) é induzida pela sinalização de PI3-q/Akt no fígado. Esta regulação envolve a repressão de genes que controlam a gliconeogênese e produção de glicose hepática, levando a hipoglicemia. Porém, não há informações de que a insulina ou a leptina podem regular a Clk2 no hipotálamo in vivo. Camundongos das linhagens Swiss, db/db e C57/BL6J com oito semanas de idade foram utilizados nos experimentos. Nossos resultados mostraram que a Clk2 é expressa e regulada por insulina e leptina em hipotálamo e também que a inibição da Clk2 causou aumento da adiposidade e ingestão alimentar, diminuição do gasto energético e alterações na expressão de neuropeptídeos e do metabolismo de glicose. Além disso, a fosforilação no sítio treonina 343 da Clk2 está diminuída em animais com obesidade induzida por dieta e geneticamente obesos (db/db). A avaliação da gliconeogênese hepática em animais com a proteína Clk2 inibida via ICV mostrou uma tendência ao aumento da produção hepática de glicose, revelando uma possível participação da proteína Clk2 no controle hipotalâmico da gliconeogênese hepática. Sendo assim, podemos sugerir que a Clk2 hipotalâmica é importante no controle do balanço energético pois sua inibição acarreta obesidade acompanhada por aumento da ingestão alimentar e diminuição do gasto energético, e também podemos sugerir um papel no controle hipotalâmico da produção hepática de glicose
Abstract: The hypothalamus plays an important role in the regulation of whole-body energy balance by integrating nutrients and hormones signals from peripheral inputs. The pancreatic hormone - insulin - and the adipocyte hormone - leptin - are known to act in the CNS controlling food intake and energy expenditure. Leptin and insulin signaling regulate anorexigenic neuropeptide expression. Recently, it was shown that Cdc2-like kinase 2 (Clk2) threonine 343 phosphorylation is induced by PI3K/Akt signaling in the liver. This regulation is involved in the repression of gluconeogenic gene expression and hepatic glucose output leading to hypoglycemia. Thus, it was not shown if insulin or leptin are able to regulate Clk2 threonine 343 phosphorylation in the hypothalamus in vivo. Swiss, db/db and C57/BL6J mice eight-weeks-old were used to proceed the experiments. Our data show that Clk2 is expressed and regulated by insulin and leptin in hypothalamus and hypothalamic Clk2 inhibition increased adiposity and food intake, decreased energy expenditure and disrupted neuropeptides expressions and glucose metabolism. Indeed, Clk2 threonine 343 phosphorylation is impaired in the hypothalamus of DIO and db/db mice. Hepatic gluconeogenesis was evaluated and showed increase in ICV inhibited Clk2 mice, it is plausible that Clk2 participates of hypothalamic control of hepatic gluconeogenesis. We suggest that hypothalamic Clk2 is crucial to control energy balance because its inhibition triggers obesity accompanied by increased food intake, decreased energy expenditure and increased hepatic gluconeogenesis
Mestrado
Clinica Medica
Mestra em Ciências

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44

Leligny, Henri. "Etude des cristaux hydrates isoles dans les diagrammes cdcl::(2)-h::(2)o, cdbr::(2)-h::(2)o et cdcl::(2)-cacl::(2)-h::(2)o : structures atomiques et proprietes cristallochimiques." Caen, 1987. http://www.theses.fr/1987CAEN2022.

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Determination par diffraction rx des arrangements atomiques de neuf phases cristallines hydratees. Les polyedres de coordination des cations s'organisent en trois types structuraux : chaines simples (cd); empilement en couches (cd); chaines mixtes (cd,ca). Quatre phases possedent des structures caracterisees par une pseudo-symetrie marquee. Les macles et les transformations orientees, observees sur certains cristaux, sont interpretees par l'existence de pseudo-symetrie locale et de parentes structurales entre blocs atomiques des hydrates concernes

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45

Gordon, Colin B. "Molecular genetics of the cdc 22 gene of Schizosaccharomyces pombe." Thesis, University of Edinburgh, 1985. http://hdl.handle.net/1842/14920.

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46

Vendrell, Arasa Alexandre. "SCF cdc4 regulates msn2 and msn4 dependent gene expression to counteract hog1 induced lethality." Doctoral thesis, Universitat Pompeu Fabra, 2009. http://hdl.handle.net/10803/7153.

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L'activació sostinguda de Hog1 porta a una inhibició del creixement cel·lular. En aquest treball, hem observat que el fenotip de letalitat causat per l'activació sostinguda de Hog1 és parcialment inhibida per la mutació del complexe SCFCDC4. La inhibició de la mort causada per l'activació sostinguda de Hog1 depèn de la via d'extensió de la vida. Quan Hog1 s'activa de manera sostinguda, la mutació al complexe SCFCDC4 fa que augmenti l'expressió gènica depenent de Msn2 i Msn4 que condueix a una sobreexpressió del gen PNC1 i a una hiperactivació de la deacetilassa Sir2. La hiperactivació de Sir2 és capaç d'inhibir la mort causada per l'activació sostinguda de Hog1.
També hem observat que la mort cel·lular causada per l'activació sostinguda de Hog1 és deguda a una inducció d'apoptosi. L'apoptosi induïda per Hog1 és inhibida per la mutació al complexe SCFCDC4. Per tant, la via d'extensió de la vida és capaç de prevenir l'apoptosi a través d'un mecanisme desconegut.
Sustained Hog1 activation leads to an inhibition of cell growth. In this work, we have observed that the lethal phenotype caused by sustained Hog1 activation is prevented by SCFCDC4 mutants. The prevention of Hog1-induced cell death by SCFCDC4 mutation depends on the lifespan extension pathway. Upon sustained Hog1 activation, SCFCDC4 mutation increases Msn2 and Msn4 dependent gene expression that leads to a PNC1 overexpression and a Sir2 deacetylase hyperactivation. Then, hyperactivation of Sir2 is able to prevent cell death caused by sustained Hog1 activation.
We have also observed that cell death upon sustained Hog1 activation is due to an induction of apoptosis. The apoptosis induced by Hog1 is decreased by SCFCDC4 mutation. Therefore, lifespan extension pathway is able to prevent apoptosis by an unknown mechanism.

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47

Silva, Silvia Roberta de Oliveira e. "Economia solidÃria e sustentabilidade: o caso do centro de desenvolvimento comunitÃrio das TimbÃubas - CDCT." Universidade Federal do CearÃ, 2013. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=10362.

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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
O presente trabalho se concentra no estudo detalhado da AssociaÃÃo Centro de Desenvolvimento ComunitÃrio das TimbaÃbas â CDCT, localizada no bairro das TimbaÃbas em Juazeiro do Norte/CE. Ao se instalar numa nova sede, os associados que a compunham, foram inseridos em uma comunidade onde havia muito mais do que apenas escassez de recursos materiais. Foi quando alguns deles sentiram a necessidade de mudanÃa de ideal que os mantinham unidos. A realidade com que se depararam, foi suficiente para entenderem que uma mudanÃa de comportamento por parte de todos se fazia necessÃria. ComeÃaram a pensar em aÃÃes, onde aquela comunidade carente de tantos serviÃos pudesse usufruir do espaÃo comum da sede da associaÃÃo, alÃm de se beneficiar de projetos que ela mesma viesse a desenvolver. A pesquisa tem como objetivo geral o processo de analisar esta associaÃÃo na perspectiva de um empreendimento econÃmico e solidÃrio (EES) e Ã luz do marco analÃtico de sustentabilidade, com intuito de saber em que medida esta, enquanto EES tem desenvolvido as dimensÃes da sustentabilidade. Para tanto Ã feita uma anÃlise a partir de um quadro analÃtico da sustentabilidade. Como objetivos especÃficos buscou-se identificar os referenciais ligados Ã economia solidÃria, empreendimentos econÃmicos e solidÃrios e seus panoramas atuais no Brasil e na regiÃo do Cariri, alÃm de um levantamento teÃrico sobre sustentabilidade. Foi tambÃm realizada uma caracterizaÃÃo profunda e uma analise do CDCT a partir do quadro analÃtico apresentado. Como pressuposto, considerou-se que o CDCT articula as diversas dimensÃes de sustentabilidade e pode desenvolver aÃÃes capazes de contribuir para um desenvolvimento sustentÃvel. A pesquisa foi do tipo exploratÃria e utilizou como mÃtodo o estudo de caso com coleta de dados por meio de pesquisa bibliogrÃfica e da observaÃÃo participante, bem como entrevista focalizada e anÃlises documentais. Como resultado, observou-se que a associaÃÃo se enquadra no perfil de empreendimento econÃmico e solidÃrio, articulando diversas lÃgicas econÃmicas e desenvolve atividades que estimulam uma participaÃÃo da comunidade envolvida capaz de promover transformaÃÃes sociais, polÃticas, culturais e ambientais.

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48

Poh, Wei Theng. "The role of Cdc7 and cyclin-dependent kinases in DNA replication and S phase." Thesis, University of Dundee, 2012. https://discovery.dundee.ac.uk/en/studentTheses/a5399a6d-9aef-4152-9a13-222dcf27aa55.

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The cell cycle is a highly orchestrated developmental process that eventually leads to the reproduction of a cell. In metazoans, it is driven by the successive activation of cyclin-dependent kinases (Cdk) and proper coordination of cell cycle transitions and processes ensure genomic stability. DNA replication takes place during S phase to faithfully duplicate a cell’s genetic material. In eukaryotes, S phase onset involves the initiation of numerous licensed replication origins across the genome and requires the activities of two protein kinases, S phase-Cdk and Cdc7. In this thesis, I present work relating to the role of the S phase-promoting kinases in DNA replication and S phase regulation. Using the cell-free system of Xenopus egg extracts, a small molecule inhibitor of Cdc7, PHA-767491, was characterised. PHA-767491 was then used to demonstrate that Cdc7 executes its activity early in S phase before the Cdk-dependent step. Cdc7 is not rate limiting for the progression of the replication timing programme once its essential function has been executed, unlike S-Cdk whose activity is required throughout S phase. Protein Phosphatase 1 (PP1) was identified as a modulator of Cdc7 activity in egg extracts, which rapidly reverses Cdc7-dependent phosphorylation of chromatin-bound Mcm4 and likely functionally lowers Cdc7 activity during an etoposide-induced checkpoint response. This provides a novel mechanism for regulating Cdc7 by counteracting its activity on essential replication substrates in the event of replicative stress. In the second part of the thesis, the design strategy for generating a Cdc7-conditional knockout mouse (cko) is outlined and results from the screen for a transgenic founder are presented. A Cdc7-cko mouse will be a valuable tool to further dissect Cdc7 function and regulation in mammalian cells. In the final section, S phase entry and progression in mouse embryonic fibroblasts lacking both Cdk1 and Cdk2 was examined. Contrary to expectations, Cdk1/Cdk2 double knockout cells can enter S phase in the absence of detectable S phase-Cdk activity. S phase progression, however, was inefficient. Cdc6 and cyclin E1 proteins were found to accumulate in high levels in these cells. The exact function(s) and mechanism(s) for these observations remain to be discovered. With this work, I hope to provide additional insight into the roles and regulation of S phase kinases in eukaryotic DNA replication.

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49

Fisher, Daniel Leslie. "Molecular characterization of the fission yeast cyclin B homologue, cdc 13." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308658.

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50

Moissenet, Didier. "Bacille CDC GROUP IVc-2 : caractérisation, phylogénie, épidémiologie, sensibilité aux antibiotiques." Paris 5, 2006. http://www.theses.fr/2006PA05N05S.

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CDC Group IVc-2 est un bacille à Gram négatif, aérobie strict, mobile grâce à une ciliature péritriche, oxydase et catalase positives et non fermentant. Connu depuis les années 80, il a d'abord été rapproché de Bordetella bronchiseptica puis parfaitement différencié biochimiquement de cette espèce en 1986 par Pickett (87). Sa position taxonomique longtemps indéterminée a été précisée en 1999 (74, 83, 116) et nous y avons contribué (74). Bactérie de l'environnement hydrique (7, 63, 82). .
Our study of CDC Group IVc-2 began in 1995 with the report of five bacteriema at Trousseau hospital (APHP). Genotyping with RAPD, used for the first time for this species, showed a single pattern. Pulsed field gel electrophoresis, applied to Trousseau isolates and other French isolates, was unsuccessful since DNA was degraded. These isolates remained undistinguished after genotyping with PCR-ribotyping, PCR-RFLP, IRS-PCR. Surprisingly, all the strains obtained from American (ATCC) and Belgian (LMG) collections were easily distinguished by RAPD. We contributed to the taxonomic study of CDC Group IVc-2 named Ralstonia paucula in. .

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