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1
Le, Fessant Elouan. "Etude expérimentale de la revaporisation de dépôt de produits de fission en cas d'accident grave". Electronic Thesis or Diss., Université de Lille (2022-....), 2023. https://pepite-depot.univ-lille.fr/ToutIDP/EDSMRE/2023/2023ULILR011.pdf.
Abstract (sommario):
Afin d'améliorer la prédiction de possibles relâchements tardifs de radionucléides lors d'un accident grave d'un réacteur nucléaire, les phénomènes de remobilisation de dépôt de Produits de Fission (PF) dans le circuit primaire sont étudiés. Ces phénomènes induisent un changement d'état des PF ou une réactivité chimique contribuent à la formation d'espèces gazeuses ou d'aérosols en suspension dans le flux de gaz, contribuant aux rejets atmosphériques. Ce travail, dans le cadre du projet OCDE ESTER, se concentre sur la revaporisation du césium (Cs) et de l'iode (I) en tant que principaux contributeurs aux conséquences radiologiques d'un accident grave. De plus, le tellure (Te) qui peut être une source d'I par désintégration radioactive est également étudié. Pour ce faire, deux méthodologies complémentaires sont utilisées :- Des expérimentations de revaporisation visent à évaluer le taux de revaporisation de chaque élément étudié, d'identifier les espèces revaporisées et de caractériser les espèces solides restantes.- Des simulations à l'équilibre thermodynamique visent à définir les principales réactions de revaporisation et la spéciation des espèces transportées.Différents simulants de dépôts de PF dans le circuit primaire ont été considérés : CsI, CsOH, CdI2, H2TeO4 et TeO2. Grâce au dispositif expérimental ATMIRE couvrant une large gamme de températures (de 200 à 600 °C), une large gamme de pressions partielles d'air (de 4.5.10-4 à 0.5 atm) complétée par de la vapeur d'eau et des vapeurs de bore dans le gaz porteur, la revaporisation de source de Cs, I , et Te a été étudiée. Les échantillons ont été caractérisés grâce à la combinaison d'analyses chimiques et de surfaces telles que ICP-MS, l'XPS et le ToF-SIMS. Grâce à ces techniques, l'identification et la quantification des espèces gazeuses et solides formées tout au long des essais ont été possibles. Par la suite, les résultats expérimentaux ont été comparés aux calculs à l'équilibre thermodynamique pour confirmer les principales voies de revaporisation de chaque simulant de PF.Au-dessus de 400 °C, la revaporisation du CsI entraîne à la fois sa vaporisation et sa décomposition sous atmosphère air/vapeur. La décomposition de CsI conduit à la formation d'iode gazeux (HOI, I ou I2) et d'espèces Cs telles que CsOH et CsNO3 ainsi que Cs2CrO4 (en raison de l'interaction du Cs avec l'acier oxydé) ou CsBO2 (par interaction avec le bore dans l'atmosphère de revaporisation).Sous atmosphère vapeur/air, le CdI2 est totalement décomposé au-dessus de 200 °C, entraînant la formation d'I gazeux (principalement I2) et de Cd (tel que CdO ou Cd(OH)2).Enfin, à haute température (supérieure à 400 °C), H2TeO4 est réduit et déshydraté pour former TeO2 quelle que soit la proportion d'air dans l'atmosphère (de 4.5.10-4 atm à 1 atm). Pour TeO2, la revaporisation n'est pas influencée par la proportion d'air mais est fortement augmentée en présence de CsOH avec la formation d'espèces de type Cs-Te-O (tel que Cs2TeO3 ou Cs2TeO4)In order to improve the prediction of possible delayed radioactive releases during a SA of a PWR, remobilization phenomena of Fission Product (FP) deposited in the Reactor Cooling System (RCS) have been investigated. These phenomena induce a modification of the FP state to gaseous species or aerosols suspended in the gas flow contributing to these delayed releases. This work, within the OECD ESTER project, is focusing on the revaporization of Cs and I as main contributors to radiological consequences. In addition, tellurium (Te) which may be a source of I by radioactive decay is also studied. To do so, two complementary methodologies are used:- Revaporization experiments aim at assessing the revaporization rate of each studied element, at identifying the revaporized species, and finally at characterizing the remaining solid species.- Thermodynamic simulations aim at defining the main revaporization reactions and the airborne species.Different simulants for FP deposits in the RCS were considered: CsI, CsOH, CdI2, H2TeO4 TeO2. Thanks to the ATMIRE experimental setup covering a large range of temperatures (from 200 to 600 °C), a large range of air partial pressures (from 4.5.10-4 to 0.5 atm) complemented by steam boron vapors in the carrier gas, revaporization behaviors of Cs, I, Cd and Te were characterized. The samples were characterized thanks to combined chemical and surface analyses such as ICP-MS, XPS, and ToF-SIMS. Thanks to these techniques, identification and quantification of both gaseous and solid species formed throughout the tests were possible. Then experimental results were compared to thermodynamic calculations to confirm the main revaporization paths of each FP simulant.Above 400 °C, the CsI revaporization result in both CsI vaporization and decomposition under an air/steam atmosphere. CsI decomposition leads to the formation of gaseous iodine (HOI, I, or I2) and Cs species such as CsOH and CsNO3 as well as Cs2CrO4 (due to Cs interaction with oxidized SS) or CsBO2 (by interaction with boron in the revaporization atmosphere).Under steam/air atmosphere, CdI2 is totally decomposed above 200 °C leading to the formation of gaseous I (mainly I2) and Cd (such as CdO or Cd(OH)2).Finally, at high temperatures (above 400 °C), H2TeO4 is reduced and dehydrated to form TeO2 whatever the proportion of air (from 4.5.10-4 atm to 1 atm). For TeO2, revaporization is not influenced by Pair but is strongly increased in presence of CsOH with the formation of Cs-Te-O species (such as Cs2TeO3 or Cs2TeO4)
2
Guimarães, Tathiane Barbosa. "Perfil psicossocial de portadores de CDI: COMFORT-CDI". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-24102016-154635/.
Abstract (sommario):
Introdução: Ansiedade, depressão, personalidade Tipo D e terapias de choque do cardioversor-desfibrilador implantável (CDI) são fatores de risco para pior ajuste psicossocial. Além da maior parte dos estudos serem realizados em países desenvolvidos, pouca atenção é dada a estes e outros fatores, assim como à influência na percepção de portadores de CDI quanto à sua cardiopatia de base. Estratégias de enfrentamento, diferença entre percepção do CDI e da doença, assim como percepção dos familiares também têm sido negligenciadas. Os objetivos deste estudo foram descrever o perfil psicossocial de portadores de CDI em nosso meio, avaliar a relação entre os fatores de risco supracitados, percepções do paciente quanto à doença cardíaca e CDI, a relação entre ocorrência e frequência das terapias de choque do CDI e a compreensão e percepção de familiares em relação ao CDI. Método: 250 portadores de CDI foram avaliados (54.10 ±15.15 anos, 67% sexo masculino) quanto à percepção de doença (Questionário Breve de Percepção de Doença [B-IPQ]); ansiedade, depressão, distress (Escala Hospitalar de Ansiedade e Depressão [HADS]); personalidade Tipo D (DS-14); ocorrência e frequência de choques do CDI desde implante e estratégias de enfrentamento. Representações emocionais e compressão de familiares dos pacientes também foram medidas. A análise estatística utilizou os métodos de Mann-Whitney, Wilcoxon e X2. Resultados: Noventa e nove pacientes (39,6%) apresentaram ansiedade, 62 (24.8%) depressão; 85(34%) distress, 84(34%) personalidade Tipo D e 72(29%) perceberam a doença cardíaca como ameaça. Ansiedade, distress, depressão e personalidade Tipo D foram associadas à percepção de cardiopatia como ameaçadora, OR=11 (p= <. 0001); 7.4 (p= <. 0001); 5.3 p= <. 0001); e 2.9 (p= 0.0001), respectivamente. A percepção da doença cardíaca como ameaça também foi influenciada pela presença de choques do CDI desde o implante, com OR= 2.2 (p= 0.007), 2.1 para >=3 choques em 24 horas (p= 0.03) e 2.4 para >= 5 choques desde o implante (p= 0.008). Pacientes ansiosos e Tipo D foram associados a pior percepção de doença, considerando: 1 - fortes crenças sobre consequências mais graves da doença; 2 - não serem capazes de controlar a doença; 3 - atribuem maior número de sintomas à doença; 4 - são mais preocupados e apresentam mais emoções negativas. As percepções de pacientes com distress ou depressivos são mais negativas em todas as subescalas, exceto compreensão. A maioria dos pacientes (68%) utilizou estratégias de enfrentamento focadas na emoção. Vinte e cinco por cento dos pacientes reportaram limitação imposta pela doença, enquanto 75% se sentiram limitados pelo CDI. Pacientes perceberam mais consequências negativas da doença que do CDI. Familiares apresentaram desgaste emocional e baixa compreensão quanto o uso e funcionamento do CDI. Conclusões: Portadores de CDI assistidos em hospital terciário de atenção cardiológica apresentaram: Elevada taxa de ocorrência de ansiedade; depressão, distress, personalidade Tipo D e percepção de doença como ameaça; Limitação das atividades da vida diária como a maior demanda vivenciada; Cardiopatia de base afetando mais a vida que o CDI, mas a maioria considerando o choque do CDI aversivo. Implicação: Intervenções psicossociais específicas são essenciais para melhor ajustamento de portadores de CDI e seus familiaresIntroduction: Anxiety, depression, Type D personality, and implantable cardioverter-defibrillator (ICD) shocks are well-known risk factors for psychosocial maladjustment. Despite the fact that most of the studies were conducted in well-developed countries, little attention has been given to these and others factors and their influence on ICD patients\' perceptions of their heart disease. Coping strategies, the differences between ICD patient and heart disease patient perceptions, and the perception of family members has also been neglected. This project was aimed at describing the psychosocial profile of Brazilian ICD patients and evaluating the relationship between the aforementioned risk factors and patient perceptions about their heart disease and ICD, the temporal relation between occurrence and frequency of ICD shocks, and the understanding and perception of family members regarding the ICD. Methods: 250 ICD patients were evaluated (54.10 ±15.15 years, 67% male) regarding illness perception (Brief Illness Perception Questionnaire [B-IPQ]); anxiety, depression, distress (Hospital Anxiety and Depression Scale [HADS]); Type D personality (DS-14); occurrence and frequency of ICD shocks since implantation; and coping. Family members\' comprehension and emotional representations of the ICD were also assessed. Mann-Whitney, Wilcoxon and X2 were used for statistical analysis. Results: Ninety-nine patients (40%) had anxiety, 62 (25%) depression; 85 (34%) distress, 84 (34%) Type D personality, and 72 (29%) perceived the heart disease as a threat. Anxiety, distress, depression, and Type D personality were associated with perceiving heart disease as a health threat with odds ratios of 11 (p= <.0001); 7.4 (p= <.0001); 5.3 (p= <.0001); and 2.9 (p= 0.0001), respectively. Patients\' perceptions of their heart disease as a threat were also influenced by ICD shocks since implantation with odds ratios of 2.1 (p= 0.007), of 2.1 for >=3 shocks in 24 hours (p= 0.045) and of 2.4 for >= 5 shocks since implantation (p= 0.043). Anxious and Type D patients were also associated with poorer illness perceptions regarding: 1 - strong beliefs about more serious consequences of the illness; 2 - not being capable of controlling the disease on their own; 3 - a greater number of symptoms attributed to the illness; 4 - more concerns and negative reactions. Distressed or depressive patients\' perceptions are more negative on every item of the scale except for understanding. The majority of patients (68%) used emotion focused coping mechanisms. Twenty-five percent of the patients reported feeling limited by heart disease, while 75% reported feeling limited by having the ICD in place. Patients perceived more negative consequences with heart disease than with ICD placement. Family members manifested distress about the ICD and misunderstanding regarding its purpose and function. Conclusions: ICD patients treated in a tertiary heart center presented with incresead frequency of anxiety, depression, distress, Type D personality, and perception of their illness as threat. Limitation of activities of daily living was the most common complaint. Heart disease was reported as more debilitating than the ICD itself, but most patients still considered the device\'s shock aversive. Implication: Specific psychosocial interventions are essential for better adjustment of ICD patients and their families after ICD placement
3
Burman, Per. "Extending CDIF to support Enterprise Modeling". Thesis, University of Skövde, Department of Computer Science, 1997. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-287.
Abstract (sommario):
In recent years organizations developing information systems have started to demand that there should be an explicit connection between the rationale of the system developed and the system itself. In the "From Fuzzy to Formal" project an attempt to develop a methodology supporting this was made. Within the project a method called Enterprise Modeling was developed, aiming at creating this connection. This method contains five different sub-models. The sub-models are connected to each other by inter-model links. The models developed using EM are of high complexity. Therefore tool and repository support should be provided. To be flexible and extendible, such a tool set should be based upon a standardized meta-model. CDIF is an example of such a standard.
In this dissertation we develop a meta-model capable of capturing the information that is created using the Enterprise Modeling technique. We use the extensibility mechanism that is provided with the CDIF standard to extend the existing CDIF Integrated meta-model to support the models used in this work. We also develop a procedure supporting the mapping between the representations. Finally we discuss the functionality of a tool capable of supporting the work with the models.
4
Duncan, Tod. "Identifying substrates of CDK2:cyclin A". Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396250.
5
Walker, Jennifer Anne. "CD22, autoimmunity and the B cell". Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612192.
6
Feliciano, Lisa. "Clostridium difficile Infection (CDI): Use of Preventive Bundle to Decrease CDI Incidences". ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/5188.
Abstract (sommario):
The challenge of combating Clostridium difficile infections (CDI) is a major problem within many health care organizations as CDI adds to the cost of care and is an uncomfortable and sometimes fatal complication of hospitalization for the patient. The practice-focused question for this doctoral project was targeted at patients in hospital settings on a medical surgical floor and asked if clostridium difficile preventive bundles reduce the incidence of CDI compared with nonstandardized preventative methods. Using the plan-do-study-act framework, the purpose of this DNP project was to use a clostridium difficile bundle approach to study the effects of clostridium difficile incidence (CDI) decrease on a medical-surgical unit with high CDI incidences. Standardized environmental cleaning practices resulted in improvement of the patient environment. High-touch cleaning improved from 43.7% to 83.3%. Time between CDI events lengthened from 19.9 days to 30.2, environmental cleaning with the use of Dazo auditing improved from 33.4% to 81.6%, isolation practices improved from 62.7% to 90%, and with the implementation of the nurse-driven CD testing protocol, unnecessary testing improved. Results showed that the CDI incidence on an acute care medical surgical unit was reduced through the use of a clostridium difficile preventive bundle in this DNP project. Reducing the incidence of CDI is a significant contribution to social change as this unwanted complication of hospitalization causes discomfort and pain and adds unnecessary cost to health care.
7
Lam, Jennifer. "Dll1 is a Potential CDX2 Target Gene". Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28896.
Abstract (sommario):
The functional redundancy and peri-implantation lethality inherent to members of the CDX family has traditionally limited their investigation. As such, the development by our lab of a conditional null mutant, obliterating CDX activity in the mouse, has opened up an exploration of their additional roles. Along with the loss of caudal tissue and failure of neural tube closure, Cdx1/2 null mutants exhibit abnormal somites, an observation which is echoed by the misregulation of many somitic players including members of the Wnt and Notch signaling pathways upon microarray analysis. The replication of altered expression patterns in situ and identification of consensus CDX response elements (CDRE) in the proximal promoter regions validated many of these genes as potential CDX targets. Characterization of one candidate in particular, DIl1, revealed reduced expression in the absence of CDX and overlapping expression domains with CDX members as well as somitic anomalies in Dil1 null mutants. The identification of two highly conserved putative CDRE in the proximal promoter region, in addition to the ability of CDX2 to occupy the promoter in the vicinity of these sites in vivo and specifically bind the identified motifs in vitro, was consistent with direct regulation. Functional analysis of CDX2 in association with the Dll1 promoter has so far proven inconclusive, but synergistic induction of the wildtype promoter in the presence of TBX6 supports a potential co-regulation. Overall, this thesis presents evidence for delta-like 1(Dll1) as a potential direct target of CDX2. Moreover, these findings support the possibility that CDX may regulate players in the Notch and Wnt signaling pathways and thereby play an important role in somitogenesis.
8
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.
9
Colleypriest, Benjamin John. "The role of Cdx2 in Barrett's metaplasia". Thesis, University of Bath, 2010. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.524136.
Abstract (sommario):
Barrett's metaplasia describes a condition in which the stratified squamous epithelium of the oesophagus switches to intestinal type columnar epithelium. The molecular mechanisms underlying the switch to intestinal epithelium is poorly understood but the transcription factor CDX2 has been implicated in the pathogenesis of Barrett's metaplasia and is sufficient to provoke an intestinal metaplasia in the stomach of transgenic mice. To address the molecular basis of Barrett’s, I developed an innovative explant system for adult mouse oesophageal epithelium in which the full repertoire of stratified squamous cell types is maintained for prolonged culture periods. In adult oesophageal cultures, cells expressing p63, K14, K4 and loricrin were detected. The ability of Cdx2 to induce intestinal genes in this model as well as in a human oesophageal cell line and foetal mouse oesophageal cultures was assessed. Cdx2 was sufficient to induce intestinal markers in Het-1A cells and foetal oesophageal epithelium but not in adult oesophageal explants. Following infection with Cdx2, Het-1A cells expressed four intestinal genes, Cdx1, Muc2, villin and K20. Embryonic oesophagus responds similarly and Muc2 and villin mRNA and Muc2 protein were detected. In contrast, infection of adult oesophageal explants did not provoke the expression of intestinal genes. These data suggest that additional factor(s) to Cdx2 are required in the conversion of adult oesophagus towards an intestinal phenotype as seen in Barrett's metaplasia. HNF4α is a candidate factor to cooperate with Cdx2 in intestinal development and therefore Barrett's metaplasia. Herein I demonstrate that HNF4α is sufficient to induce a columnar phenotype and the expression of intestinal genes within adult squamous oesophageal cells. The resultant phenotype is consistent with that seen in Barrett's metaplasia. Furthermore HNF4α and Cdx2 synergise to further enhance intestinalisation. This data suggests a hitherto unknown potential role for HNF4a in Barrett’s metaplasia.
10
LEBEL-BINAY, SOPHIE. "Caracterisation fonctionnelle d'une nouvelle proteine transmembranaire : cd82". Paris 7, 1995. http://www.theses.fr/1995PA077277.
Abstract (sommario):
La glycoproteine cd82 a ete identifiee et clonee dans notre laboratoire pour son expression preferentielle sur les lignees cellulaires sensibles a la lyse par les effecteurs nk/lak. Cette molecule de 267 acides amines (35 a 100 kda) est une proteine de type iii avec 4 segments transmembranaires, des extremites nh2 et cooh intracytoplasmiques et un grand domaine extracellulaire. Elle appartient a la famille des proteines tetra span transmembranaires (tst) qui comprend cd9, cd37, cd53, cd63 et cd81. Cd82. Elle est exprimee a la surface de nombreux types cellulaires. Son expression est augmentee apres activation ou differenciation des cellules mononuclees (lymphocytes, monocytes). Cd82 possede des proprietes de transduction sur la lignee monocytaire u937 (mobilisation de calcium intracellulaire). Cd82 est une molecule de costimulation de l'activation des lymphocytes t. Les lymphocytes t stimules in vitro par des acs anti-cd3 et anti-cd82 immobilises, se differencient et produisent de l'il-2 et de l'ifng
11
Palmquist, Kristian. "Extending CDIF to support Business Rules targeting SQL3". Thesis, University of Skövde, Department of Computer Science, 1997. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-298.
Abstract (sommario):
Business Rules have gained attention in recent years and are now considered to be important organizational elements. Several sources in the literature argue that there are major achievements to be made with an explicit business rule focus in software engineering, e.g. promoting communication between analysts and users and accounting for changeability and maintenance aspects. However, to fully take advantage of an explicit rule focus in software engineering requires the ability to create business rule models. The problem is that business rule models of realistic size quickly become extensive and complex, hence there is a need for CASE tool support.
We choose a modeling technique from the literature which is suited to express business rules. Basec on this modeling technique we propose an extension to the Case Data Interchange Format standard (CDIF), thereby allowing the standard to express and support the transfer of business rule models. In addition, we define a mapping procedure that which maps business rules from the conceptual modeling level via CDIF (using the proposed extensions) to SQL3 triggers. The main idea is that the mapping algorithms could be used by a CDIF conformant CASE tool which allows traditional database design, together with extended modeling constructs for expressign business rules.
12
Meschini, Elisa. "Purine-based dual inhibitors of CDK2 and CDK7". Thesis, University of Newcastle Upon Tyne, 2011. http://hdl.handle.net/10443/1363.
Abstract (sommario):
Cyclin-Dependent Kinases (CDKs) play a fundamental role in eukaryotic cell cycle progression, particularly at cell cycle checkpoints, and are therefore important targets for anticancer drug discovery. Activation of CDK2 in complex with Cyclin A regulates entry into S phase of the eukaryotic cell cycle. CDK7, a dual-function enzyme, acts both as a CDK-Activating Kinase (CAK) and as a component of the general transcription factor TFIIH. However, experiments with MAT1-knockdown mice have shown that cell cycle arrest by CAK inhibition would not be detrimental for transcriptional activity in non-dividing cells, as CDK9 in complex with Cyclin T can perform transcriptional duties in the absence of TFIIH. Previous studies have resulted in the identification of NU6102 (1, IC50 mM = 0.005 (CDK2), 4.4 (CDK7)) as a potent and selective CDK2 inhibitor, and NU6247 (2, IC50 mM = 0.12 (CDK2), 0.23 (CDK7)) as an equipotent CDK2/7 inhibitor. It was shown that the sulfonamide group of 1 confers potency and selectivity for CDK2, whereas the pendant piperazinyl substituent of 2 diminishes CDK2 actvity whilst improving activity versus CDK7. S NH N N NH N O O O 2 N N AccordinglyAs part of the work described in the present thesis, sulfonamide 3 (IC50 mM = 0.012 (CDK2), 0.67 (CDK7)) was synthesised and found to be is a potent CDK2 inhibitor, but with some CDK7-inhibitory activity (IC50 mM = 0.012 (CDK2), 0.67 (CDK7)). Further elaboration of the side-chain function has enabled the development of structure-activity relationships (SARs), and the identification of purines (e.g. 4, IC50 mM = 2.6 (CDK2), 0.56 (CDK7)) exhibiting some selectivity for CDK7, albeit with a loss of potency. 4 Subsequent SAR studies conducted on 2 have enabled the following observations to be made: firstly, the purine 6-cyclohexylmethoxy substituent is necessary for activity, with the corresponding 6-unsubstituted purine (5, IC50 mM = 46.9 (CDK2), 20.8 (CDK7)) exhibiting a 100-fold loss of potency against both CDK2 and CDK7. A terminal basic group (e.g. piperazinyl in 2) is required for activity, as replacement by a cyclohexyl substituent results in loss of activity against both kinases (6, 11% inhibition at 10 mM (CDK2), 13% inhibition at 100 mM (CDK7)). The sulfone linker is not a prerequisite for CDK7 activity, with the simple alkylpiperazine derivative (7, IC50 mM = 0.48 (CDK2), 0.51 (CDK7)) exhibiting comparable potency and selectivity. Finally, there appears to be some opportunity for expansion into the gatekeeper pocket of CDK7 by introducing small substituents at the purine C-8 position, with the potential for selectivity over CDK2 (8, 47% inhibition at 100 mM (CDK2), IC50 = 5 mM (CDK7)). Isolation and biological evaluation of the vinyl sulfone 9, an intermediate in the synthesis of 2, indicated a time-dependent inhibition of CDK2, suggesting that 9 is an irreversible inhibitor of CDK2. This would be the first reported irreversible inhibitor of a cyclin-dependent kinase, and therefore the activity of the compound against CDK2 was investigated using protein crystallography and site-directed mutagenesis 5 techniques. From these studies, encouraging evidence has emerged that 9 acts as an irreversible inhibitor of CDK2, covalently binding to a lysine residue within the ATP-binding pocket.
13
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.
14
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.
15
LAGAUDRIERE, GESBERT CECILE. "Caracterisation biochimique et fonctionnelle de la tetraspanine cd82". Paris 11, 1997. http://www.theses.fr/1997PA112138.
Abstract (sommario):
La proteine membranaire cd82 a ete identifiee a l'aide d'un anticorps monoclonal dirige contre les molecules de surface exprimees a la surface des cellules sensibles a la lyse par les effecteurs natural killer. L'adnc correspondant code pour une proteine de 267 acides amines appartenant a la famille des tetraspanines. Cette famille comprend des marqueurs leucocytaires, des antigenes tumoraux, et des proteines de schistosomes et drosophile. Le but de ce travail etait de caracteriser la proteine cd82 sur le plan biochimique et fonctionnel. Cette molecule est constituee d'une chaine proteique de 28 kda et de residus n-glycosyles de taille heterogene. Faible sur les cellules immunitaires au repos, son expression augmente apres activation ou differenciation. Sur le plan fonctionnel, l'engagement de la proteine cd82 par des anticorps specifiques renforce et amplifie les signaux transmis par diverses molecules d'activation : recepteur fc sur les cellules monocytaires (augmentation du calcium cytosolique), recepteur t sur les lymphocytes t (production de cytokines). Dans les lymphocytes t, un evenement precoce induit par l'engagement de la proteine cd82 est son association au cytosquelette qui s'accompagne de changements morphologiques. De plus, les anticorps anti-cd82 ont la capacite d'induire une agregation homotypique et une inhibition de la migration cellulaire. Ces fonctions sont communes a d'autres tetraspanines (cd9, cd81, cd53). Sur le plan biochimique, une caracteristique majeure des tetraspanines est leur capacite a former des complexes. Ainsi, la proteine cd82 est associee aux tetraspanines leucocytaires (cd9, cd63, cd81), aux molecules du complexe majeur d'histocompatibilite de classe i et ii et aux integrines vla. L'ensemble de ces resultats suggere que la proteine cd82 est une molecule adaptatrice membranaire permettant le recrutement et la stabilisation de complexes de signalisation impliques dans les contacts et l'activation cellulaires.
16
Strömsten, Eva-Lotta. "CDIO-modellen som stöd för teknikundervisning på gymnasiet". Thesis, Luleå tekniska universitet, Pedagogik, språk och Ämnesdidaktik, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-78905.
Abstract (sommario):
Syftet med detta utvecklingsarbete har varit att utveckla och testa en arbetsmetod som baserar sig på CDIO-modellen, vilket är en modell för att utveckla tekniska utbildningar. Namnet CDIO står för: Conceive, Design, Implement och Operate. CDIO-modellen innebär att inte bara elevernas ämneskunskap ska utvecklas, utan även deras färdigheter och förmågor, vilket dem kommer ha nytta utav i sina framtida yrkesroller. Med stöd av CDIO-modellen har en hel lektionsserie i kursen Teknik 2 på gymnasiet genomförts. Det är framförallt vid planering och framtagande av lärandemålen för lektionsserien som CDIO-modellen har varit till stort stöd. Resultatet från lektionsserien visade på att majoriteten av eleverna utvecklade sina tekniska ämneskunskaper, samt sina färdigheter och förmågor. De praktiska färdigheterna testades även vid den slutliga examinationen där alla elever utom en uppvisade goda praktiska kunskaper. Den stora utmaningen vid arbetet enligt CDIO-modellen är att det kräver mycket planering och förberedelse, vilket kan tänkas innebära att det är svårt att applicera den fullt ut om ej tillräckligt med tid finns. När väl arbetet för ett kursmoment är genomfört finns det dock goda möjligheter att återanvända och förbättra det vid planering av kommande lektionsmoment.
17
Oakes, Vanessa Louise. "Cyclin A/CDK2 regulates multiple G2 phase pathways". Thesis, Queensland University of Technology, 2012. https://eprints.qut.edu.au/63534/1/Vanessa_Oakes_Thesis.pdf.
Abstract (sommario):
The cell cycle is a carefully choreographed series of phases that when executed successfully will allow the complete replication of the genome and the equal division of the genome and other cellular content into two independent daughter cells. The inability of the cell to execute cell division successfully can result in either checkpoint activation to allow repair and/or apoptosis and/or mutations/errors that may or may not lead to tumourgenesis.
Cyclin A/CDK2 is the primary cyclin/CDK regulating G2 phase progression of the cell cycle. Cyclin A/CDK2 activity peaks in G2 phase and its inhibition causes a G2 phase delay that we have termed 'the cyclin A/CDK2 dependent G2 delay'. Understanding the key pathways that are involved in the cyclin A/CDK2 dependent G2 delay has been the primary focus of this study.
Characterising the cyclin A/CDK2 dependent G2 delay revealed accumulated levels of the inactive form of the mitotic regulator, cyclin B/CDK1. Surprisingly, there was also increased microtubule nucleation at the centrosomes, and the centrosomes stained for markers of cyclin B/CDK1 activity. Both microtubule nucleation at the centrosomes and phosphoprotein markers were lost with short-term treatment of CDK1/2 inhibition. Cyclin A/CDK2 localised at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase. Thus G2 phase cyclin A/CDK2 controls the timing of entry into mitosis by controlling the subsequent activation of cyclin B/CDK1, but also has an unexpected role in coordinating the activation of cyclin B/CDK1 at the centrosome and in the nucleus. In addition to regulating the timing of cyclin B/CDK1 activation and entry into mitosis in the unperturbed cell cycle, cyclin A/CDK2 also was shown to have a role in G2 phase checkpoint recovery.
Known G2 phase regulators were investigated to determine whether they had a role in imposing the cyclin A/ CDK2 dependent G2 delay. Examination of the critical G2 checkpoint arrest protein, Chk1, which also has a role during unperturbed G2/M phases revealed the presence of activated Chk1 in G2 phase, in a range of cell lines. Activated Chk1 levels were shown to accumulate in cyclin A/CDK2 depleted/inhibited cells. Further investigations revealed that Chk1, but not Chk2, depletion could reverse the cyclin A/CDK2 dependent G2 delay. It was confirmed that the accumulative activation of Chk1 was not a consequence of DNA damage induced by cyclin A depletion. The potential of cyclin A/CDK2 to regulate Chk1 revealed that the inhibitory phosphorylations, Ser286 and Ser301, were not directly catalysed by cyclin A/CDK2 in G2 phase to regulate mitotic entry. It appeared that the ability of cyclin A/CDK2 to regulate cyclin B/CDK1 activation impacted cyclin B/CDK1s phosphorylation of Chk1 on Ser286 and Ser301, thereby contributing to the delay in G2/M phase progression.
Chk1 inhibition/depletion partially abrogated the cyclin A/CDK2 dependent G2 delay, and was less effective in abrogating G2 phase checkpoint suggesting that other cyclin A/CDK2 dependent mechanisms contributed to these roles of cyclin A/CDK2. In an attempt to identify these other contributing factors another G2/M phase regulator known to be regulated by cyclin A/CDK2, Cdh1 and its substrates Plk1 and Claspin were examined. Cdh1 levels were reduced in cyclin A/CDK2 depleted/inhibited cells although this had little effect on Plk1, a known Cdh1 substrate. However, the level of another substrate, Claspin, was increased. Cdh1 depletion mimicked the effect of cyclin A depletion but to a weaker extent and was sufficient at increasing Claspin levels similar to the increase caused by cyclin A depletion. Co-depletion of cyclin A and Claspin blocked the accumulation of activated Chk1 normally seen with cyclin A depletion alone. However Claspin depletion alone did not reduce the cyclin A/CDK2 dependent G2 delay but this is likely to be a result of inhibition of S phase roles of Claspin.
Together, these data suggest that cyclin A/CDK2 regulates a number of different mechanisms that contribute to G2/M phase progression. Here it has been demonstrated that in normal G2/M progression and possibly to a lesser extent in G2 phase checkpoint recovery, cyclin A/CDK2 regulates the level of Cdh1 which in turn affects at least one of its substrates, Claspin, and consequently results in the increased level of activated Chk1 observed. However, the involvement of Cdh1 and Claspin alone does not explain the G2 phase delay observed with cyclin A/CDK2 depletion/inhibition. It is likely that other mechanisms, possibly including cyclin A/CDK2 regulation of Wee1 and FoxM1, as reported by others, combine with the mechanism described here to regulate normal G2/M phase progression and G2 phase checkpoint recovery. These findings support the critical role for cyclin A/CDK2 in regulating progression into mitosis and suggest that upstream regulators of cyclin A/CDK2 activation will also be critical controllers of this cell cycle transition.
The pathways that work to co-ordinate cell cycle progression are very intricate and deciphering these pathways, required for normal cell cycle progression, is key to understanding tumour development. By understanding cell cycle regulatory pathways it will allow the identification of the pathway/s and their mechanism/s that become affected in tumourgenesis. This will lead to the development of better targeted therapies, inferring better efficacy with fewer side effects than commonly seen with the use of traditional therapies, such as chemotherapy. Furthermore, this has the potential to positively impact the development of personalised medicines and the customisation of healthcare.
18
Wöhner, Miriam [Verfasser], e Lars [Akademischer Betreuer] Nitschke. "Entwicklung einer knockin Mauslinie mit Expression von humanem CD22 zum Test therapeutischer Anwendungen künstlicher CD22-Liganden / Miriam Wöhner. Betreuer: Lars Nitschke". Erlangen : Universitätsbibliothek der Universität Erlangen-Nürnberg, 2012. http://d-nb.info/1024608700/34.
19
Greenberg, David. "An analysis of CD2 expression and the use of CD2 sequences for thymus directed oncogenesis". Thesis, University College London (University of London), 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315354.
20
Mateo, González Francesca. "Regulació del complex ciclina A-CDK2 per l'acetilasa PCAF". Doctoral thesis, Universitat de Barcelona, 2009. http://hdl.handle.net/10803/914.
Abstract (sommario):
Els complexes ciclina-CDK són elements clau perquè el cicle cel·lular es doni de manera ordenada. Estan regulats a diferents nivells ja que les seves funcions són essencials per a la correcta progressió del cicle. El primer nivell de regulació és la interacció entre la ciclina i la CDK. En segon lloc, aquestes proteïnes poden experimentar fosforilacions i defosforilacions activadores i inhibidores. En tercer lloc, aquests complexes poden ser inhibits per la interacció amb CKIs (CDK Inhibitors). Finalment, la localització subcel·lular també és una manera de regular l'activitat d'aquests complexes, ja que només són actius al nucli de la cèl·lula.En aquest treball presentem un nou mecanisme de regulació dels complexes ciclina-CDK. Concretament hem observat que els membres del complex ciclina A-CDK2 interaccionen amb l'acetilasa PCAF. Aquesta proteïna ha estat generalment considerada com a un co-activador transcripcional gràcies a la seva capacitat d'acetilar histones i activar la transcripció gènica. Tanmateix, també s'ha vist que és capaç d'acetilar proteïnes no-histones com ara p53 o MyoD, i com a conseqüència està implicada en altres funcions cel·lulars com la diferenciació o la resposta a dany al DNA. L'acetilasa PCAF s'uneix al complex ciclina A-CDK2 tot inhibint la seva activitat quinasa. A més, acetila la ciclina A, cosa que comporta la seva degradació pel sistema ubiquitina-proteasoma. PCAF també acetila CDK2 a la lisina 33, la qual es troba molt conservada a la família de les CDKs, ja que és un aminoàcid crucial per a la interacció amb l'ATP. L'acetilació de CDK2 a la lisina 33 comporta la inhibició de la seva activitat quinasa i la seva separació de la ciclina A.
En conclusió, els resultats d'aquesta tesi aporten un nou nivell de regulació dels complexes ciclina-CDK desconegut fins ara, i que cal tenir en compte com a possible mecanisme d'acció dels fàrmacs basats en compostos inhibidors de deacetilases els quals, d'altra banda, estan donant bons resultats en el tractament de malalties hematològiques i tumors sòlids.
"REGULATION OF CYCLIN A-CDK2 COMPLEX BY ACETYLATION"
TEXT:
Cell cycle proteins are regulated in different ways, being phosphorylation one of the most important and more studied mechanisms of regulation. On the other hand, acetylation is another kind of post-translational modification that was discovered in histones and initially it was associated with transcriptionally active chromatin. However, different studies indicate that acetylation can also play a role in the regulation of non-histone proteins and it has been linked to oncogenesis and cardiovascular and neurodegenerative diseases.
In this work we report that cyclin A/cdk2 complex, which is crucial for cell cycle progression during S phase, is acetylated by the acetyltransferase P/CAF. Cyclin A directly interacts with P/CAF and is acetylated at lysines 54, 68, 95 and 112. Maximal acetylation occurs simultaneously to ubiquitylation at mitosis, indicating a role of acetylation on cyclin A stability. A non-acetylatable mutant in which these lysines were substituted by arginines (cycA 4R) cannot be ubiquitylated, is more stable than cycA wild-type and arrests cell cycle at mitosis.
Increased expression of cyclin A has been detected in many types of cancers and it has a prognostic value to predict survival or early relapse. Our results indicate that acetylation is able to cause a decrease in the levels of cyclin A, suggesting that treatment with HDAC inhibitors (which potentiate acetylation in the cell) could be considered to treat this kind of tumors.
21
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.
22
Brown, Marion Hanbury. "Physical interactions of the CD2 antigen". Thesis, Open University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.277634.
23
Mongrain, Sébastien. "Caractérisation du mécanisme de régulation de Cdx2 par la MAP kinase p38 et implication de Cdx2 dans la différenciation des cellules épithéliales intestinales". Mémoire, Université de Sherbrooke, 2006. http://savoirs.usherbrooke.ca/handle/11143/3855.
Abstract (sommario):
Les gènes Cdx encodent des facteurs de transcription possédant un rôle très important dans le développement et le maintien de l'épithélium intestinal. Cdx2 joue un rôle central dans la différenciation des cellules épithéliales intestinales. Celui-ci permet d'activer l'expression de plusieurs enzymes digestifs et d'induire l'expression de protéines de jonctions cellulaires. Nous avons démontré que la MAP kinase p38 est impliquée dans le processus de différenciation, entre autres, en activant le facteur de transcription Cdx2. La MAP kinase p38 retrouvée dans le noyau des cellules différenciées lie et phosphoryle Cdx2. Un des objectifs de mon projet de recherche consistait à identifier le site de liaison de la MAP kinase p38 sur Cdx2 ainsi que son ou ses site(s) de phosphorylation. Premièrement, par la création de mutations site-spécifiques, nous avons identifié un site de phosphorylation par la MAP kinase p38 sur Cdx2 au niveau de la sérine 156. Deuxièmement, nous avons déterminé, par la création de mutants de délétion, que le site de liaison de la MAP kinase p38 sur Cdx2 se trouve entre les acides aminés 61 et 76 dans la portion N-terminale. Dans le but de mieux comprendre le rôle de Cdx2 dans la différenciation épithéliale intestinale, nous avons surexprimé de manière stable Cdx3 dans la lignée cellulaire épithéliale intestinale IEC-6. La surexpression de Cdx3 mène à une meilleure adhésion cellulaire. Nous avons identifié plusieurs cibles de Cdx2 par analyse de micropuces d'ADN, entre autres, le gène de la galectine-4 qui est induit de 34.5 fois par Cdx2. La galectine-4 est une lectine capable de lier le [bêta]-lactose et de favoriser l'adhésion cellulaire puisqu'elle possède deux domaines CRD (carbohydrate recognition domain). Une autre caractéristique de la galectine-4 est qu'elle est retrouvée au niveau des radeaux lipidiques de la bordure en brosse dans les entérocytes, où elle permet leur stabilisation ainsi que le ciblage des radeaux lipidiques au niveau de la membrane apicale. Nous avons démontré que la cinétique d'expression de la galectine-4 suit parfaitement celle de Cdx2 dans la lignée Caco2/15 provenant d'un adénocarcinome de côlon humain, et dans la lignée IEC-6 surexprimant Cdx3. Nous avons identifié la galectine-4 comme faisant partie des radeaux lipidiques des cellules surexprimant Cdx3, et que ces radeaux lipidiques contenant la galectine-4 sont plus spécialisés, avec la présence de la phosphatase alcaline. Ces résultats montrent que Cdx2 pourrait favoriser deux processus importants de la différenciation intestinale épithéliale, soit l'adhésion cellulaire et le développement de radeaux lipidiques spécialisés comme ceux retrouvés à la portion apicale des cellules différenciées par l'expression de la galectine-4.
24
Mongrain, Sébastien. "Caractérisation du mécanisme de régulation de Cdx2 par la MAP kinase p38 et implication de Cdx2 dans la différenciation des cellules épithéliales intestinales". [S.l. : s.n.], 2006.
25
Nair, Asmaa. "Expression ectopique du gène homéotique Cdx2 dans les pathologies du système digestif". Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ003/document.
Abstract (sommario):
Le facteur de transcription homéotique CDX2 est spécifiquement exprimé dans l’épithélium intestinal où il maintient l’identité, contrôle l’homéostasie et exerce une fonction suppresseur de tumeurs. Chez l’homme, une expression ectopique (hors de l’intestin) de CDX2 peut survenir, dans les métaplasies intestinales d’organes digestifs, considérées comme pré-cancéreuses. Ce travail de thèse visait à étudier les conséquences physiopathologiques de l’expression ectopique de CDX2. Nous avons développé et validé un modèle murin d’induction conditionnelle de CDX2 dans plusieurs organes digestifs. Nos résultats montrent que cette expression est dépendante du contexte cellulaire, et induit des métaplasies intestinales seulement dans l’estomac et le pancréas. Ces métaplasies n’évoluent pas spontanément en cancer. Cependant, CDX2 sensibilise ces lésions métaplasiques à l’apparition de tumeurs intestinales dans l’estomac placé dans un contexte où le gène Apc est muté. Globalement, ces résultats montrent que CDX2 est essentiel au développement de métaplasies intestinales mais n’exercerait pas de fonction oncogénique en situation ectopiqueThe intestine-specific homeotic transcription factor CDX2 is required throughout life for intestinal homeostasis, the maintenance of intestinal identity and has tumor suppressor activity. In Human, ectopic expression of the gene Cdx2 is observed in several digestive organs as in intestinal metaplasia which is considered as pre-cancerous lesion. This work aimed to investigate the pathophysiological consequences and molecular mechanisms of ectopic expression of CDX2. We created and validated a conditional murine model of CDX2 induction in several digestive organs. Ectopic CDX2 causes intestinal metaplasias only in the stomach and the pancreas which do not spontaneously evolve to cancer, depending on cellular context. However, CDX2 promotes intestinal carcinogenesis in complete intestinal metaplasia of the stomach. Collectively, these results show that CDX2 is essential for the development of intestinal metaplasia but has no oncogenic function in ectopic situation
26
Delhorme, Jean-Baptiste. "Etude des mécanismes de chimiorésistance dans les cancers digestifs : impact de CDX2 et des transporteurs ABC". Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ119.
Abstract (sommario):
La chimiorésistance est un enjeu majeur dans la prise en charge des patients atteints de cancers digestifs et peut se manifester par l’efflux de molécules cytotoxiques via la surexpression des transporteurs ABC. Le facteur de transcription CDX2 est un régulateur important de l’identité intestinale et agit comme gène suppresseur de tumeur dans le côlon. Il pourrait être impliqué dans des phénomènes de chimiorésistance des cancers colorectaux (CCR) car le transporteur MDR1/ABCB1 correspond à un de ses gènes cibles. Nous avons confirmé le rôle de CDX2 dans la chimiorésistance des CCR. Nous avons montré par une approche translationnelle, que la surexpression de CDX2 était impliquée dans la résistance au 5-fluorouracile (5-FU) dans les CCR. Le transporteur du 5-FU ABCC11 a été identifié comme gène cible de CDX2 dont l’activité contribue à la résistance au 5-FU des cellules cancéreuses coliques. L’expression d’ABCC11 corrèle avec celle de CDX2 dans les CCR humains mais également avec celle de la DYPD, enzyme impliquée dans le catabolisme du 5-FU. Cette étude montre pour la première fois que CDX2 contribue à la chimiorésistance au 5-FU en impliquant des mécanismes régulant son métabolismeChemoresistance represents a major drawback in digestive cancers’ management and may be achieved particularly through active efflux of the drug through overexpression of ABC transporters The transcription factor CDX2 is a master regulator of intestinal identity that acts as a tumor suppressor in the colon and may be important for drug resistance in colorectal cancer (CRC) as MDR1/ABCB1 was recently identified as one of its target genes. Here, we confirmed the role of CDX2 in the chemoresistance of CRC. We showed through a translational approach that CDX2 overexpression is implicated in 5-fluorouracil (5-FU) chemoresistance in CRC and described the molecular mechanisms implicated in this finding. We identified the 5-FU transporter ABCC11 as a new transcriptional target of CDX2 whose activity contributes to the 5-FU-chemoresistance of colon cancer cells. Remarkably, CDX2 expression correlates with the expression of ABCC11 in human colon tumors, but also with the one of the DPYD, enzyme involved in the 5-FU break down. Thus, our study links for the first time CDX2 to the 5-FU metabolism and provides a molecular mechanism for its impact on 5-FU-based chemotherapy
27
Michet, Florence. "Du CDI physique au CDI numérique : articulation des espaces documentaires réels et de l'offre numérique aux usagers". Thesis, Bordeaux 3, 2020. http://www.theses.fr/2020BOR30016.
Abstract (sommario):
Ce travail de réflexion a pour objectif d’appréhender les pratiques managériales, pédagogiques et communicationnelles mises en place par les professeurs documentalistes afin de créer des liens entre CDI physique et CDI numérique. Pour cela, nous avons procédé à une enquête de terrain, sur la Région PACA, auprès de 41 professeurs documentalistes, soit 39 CDI de collège ou lycée général. Notre investigation est structurée en deux phases successives : un questionnaire exploratoire suivi d’un entretien semi-directif. Le matériau ainsi constitué a été analysé « épisode par épisode », relatant les moments importants pour les acteurs : ceux qui relèvent de la routine et ceux qui apparaissent inhabituels. Nous avons comparé le sens des paroles relavant les logiques récurrentes pour isoler les tendances conjoncturelles spécifiques à certains établissements procédant donc à un double niveau. Les professeurs documentalistes s’approprient le numérique en fonction de leurs envies, leurs possibilités et les moyens à leur disposition en l’absence de réelles prescriptions. Ils sont aussi contraints par le CDI, espace physique dont ils dépendent. Les études actuelles s’intéressent à l’espace documentaire scolaire dans ses aspects purement pédagogiques ou numériques mais peu relient directement les deux. Par conséquent, comment le professeur documentaliste tiraillé entre injonctions institutionnelles et besoins professionnels spécifiques peut-il proposer un service qui réponde réellement et efficacement aux usagers dans son organisation globale ?This thinking process aims at perceiving the managerial, pedagogical and communication practices introduced by the school librarians in order to create links between the material and the digital school libraries. To the end, we have proceeded with a field survey in the south east of France : 41 school librarians (39 secondary school librarians and 2 high school librarians). Our investigation is organized in two successive periods : an exporatory study followed by a semi-structured interview. The established data has been analysed « step by step », relating the important moments of the participants : those which prove the routine and those which seem unusual. We have compared the words meaning, selecting the reccuring rationales in order to define the conjonctural and particular trends in some schools, leading to a double level. The school librarians appropriate digital tools according to their needs, possibilities and resources in absence of regulatory requirements. They are also constrainted by the school libraries, real documentary spaces they depend on. The current studies are interested in the purely pedagogical or digital aspects but they rarely connect the two facets. Therefore, how may the school librarian, torn between the institutional ordinances and the particular professional necessity, offer a service that could really and efficiently respond to the needs of the users considering its general management ?
28
Sundareshan, Padma. "Clostridium difficile Infection (CDI) Incidence Rate and CDI-Associated Length of Stay, Total Hospital Charges and Mortality". The University of Arizona, 2009. http://hdl.handle.net/10150/623982.
Abstract (sommario):
Class of 2009 AbstractOBJECTIVES: The purpose of the study was to determine the rate of Clostridium difficile infections (CDI) in hospitalized patients and the various factors that were associated with the risk of developing CDI by examining patient discharge data for hospitals in 37 states in the United States using Healthcare Cost and Utilization Project (HCUP). METHODS: Patient discharge information for all patients obtained using HCUP census for the years 2002-2005, either for primary or secondary (all-listed) occurrences of CDI using the ICD-9-CM code (008.45) specific for intestinal infections due to C. difficile, were included in the study. Regression analysis, either Generalized Linear Model log-link or power-link, or a logistic regression was employed to control for the multiple independent variables. RESULTS: The incidence rate for CDI was 9.4% for the years 2002-2005. Among the concomitant diagnoses and procedures, essential hypertension, volume depletion, congestive heart failure, urinary tract infection and venous catheterization were the top 5. The length of stay (LOS) for CDI was associated with being Black, Hispanic or Other race category, number of diagnoses and procedures, primary expected payer of Medicaid, private insurance and other (including worker’s compensation, CHAMPUS,CHAMPVA etc), and all groups classified based on median household income category for patient’s zip code. Predictors of CDI related to inpatient total hospital charges were being female, race (other than black), number of diagnoses and procedures, Death, LOS, patient location and with self-pay and no charge categories as primary expected payer. Predictors of higher CDI related inpatient hospital deaths were age, female sex, Hispanic race, number of diagnoses and procedures, LOS and having Medicaid, self-pay or other as primary expected payer. CONCLUSIONS: LOS, inpatient total hospital charges, and inpatient mortality were dependent on several patient and other characteristics.
29
Hecker, Kim Ione. "Bleach-It-Away Clostridium difficile". ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/5471.
Abstract (sommario):
Hospital-associated infections (HAIs) are infections patients contract as a result of being hospitalized. HAI rates decreased for almost all pathogens in the past few years, with the exception of Clostridium difficile infections (CDIs), which have been steadily climbing, placing hospital-acquired CDI at the top of the HAI list. The Center for Disease Control and Prevention reported in 2010 almost a half a million people were infected with CDIs yearly in the United States, and CDIs claimed the lives of approximately 29,000 people, representing a 4-fold increase from 1993. To address the problem in the local hospital, a quality improvement initiative called Bleach-It-Away was initiated. The initiative involved nurses wiping down the high touch areas in the patient's medical intensive care (MICU) rooms once every shift. The purpose of this quantitative research project was to evaluate the effectiveness of the Bleach-It-Away practice. The project question asked if the Bleach-It-Away practice was effective in reducing CDI rates. Deidentified CDI rates were provided by the clinical practice site covering a period of 12 months prior to implementation and 12 months after implementation of the practice. An independent t-test was used to determine whether there were significant improvements in CDI rates in the MICU. No significant improvement was seen in the postimplementation total CDI rates (p=.07) compared to the preimplementation rates. While the process did not demonstrate a significant improvement, positive social change is possible as hospitals recognize the many factors contributing to CDIs and the need for collaboration from various disciplines to control the problem.
30
Balbinot, Camille. "Fonction et mode d'action du gène homéotique intestinal Cdx2 dans les cancers de l'intestin". Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ006/document.
Abstract (sommario):
Chez l’adulte, le facteur de transcription homéotique Cdx2 est spécifiquement exprimé dans l’intestin dont il maintient l’identité et contrôle l’homéostasie. Des études récentes menées chez l’homme ont identifié des formes de cancer colorectal de mauvais pronostic dans lesquelles l’expression de Cdx2 est très fortement réduite. Ce travail de thèse visait à étudier les conséquences physiopathologiques de la perte de fonction de Cdx2 dans l’intestin adulte. A partir d’un modèle murin d’invalidation conditionnelle et mosaïque de Cdx2, nos résultats montrent que la perte de Cdx2 conduit au développement de lésions caecales de type gastrique qui n’évoluent pas spontanément en cancer. Ces lésions créent cependant un microenvironnement inflammatoire qui favorise la transformation maligne de cellules épithéliales voisines intactes pour Cdx2 et prédisposées à la tumorigénèse. Globalement, ces résultats montrent que Cdx2 exerce une fonction suppresseur de tumeurs « cellule non-autonome » dans l’intestinThe intestine-specific transcription factor Cdx2 is required throughout life for intestinal homeostasis and for the maintenance of intestinal identity. Several recent studies showed that Cdx2 expression is dramatically reduced in some human colon cancers of poor prognosis. This work aimed to investigate the pathophysiological consequences of the loss of Cdx2 in the adult gut. Conditional mosaic ablation of Cdx2 in mice causes gastric-type metaplasia in the cecum which do not spontaneously evolve to cancer. However, these lesions strongly modify the inflammatory microenvironment which facilitates the malignant transformation of adjacent Cdx2-intact and cancer-prone epithelial cells. Collectively, these results unravel a novel and original function of Cdx2, namely its non-cell autonomous tumor suppressor activity in the gut
31
Klein, Jörg. "Verwendung von Gene-Targeting-Techniken zur Etablierung neuer Mauslinien mit Mutationen in B-Zell-Signalwegen". [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=976107953.
32
Widström, Stefan. "Teknikämnets utveckling i GY11 : En analys av läromedel och lärares planering av den nya kursen Teknik 1 utifrån kursmålen". Thesis, Uppsala universitet, Institutionen för pedagogik, didaktik och utbildningsstudier, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-170617.
Abstract (sommario):
Kursplanering är en av lärarens viktigaste arbetsuppgifter. Uppsatsen har undersökt hur fem olika lärare har planerat kursen Teknik 1 som är ny i och med GY11. Uppsatsen utgår och analyserar ingående läroplanen och de nya läroböcker som kommit ut anpassade för kursen. Studien visar att det är svårt att få med alla moment som ska ingå i kursen. Studien definierar också elva kunskapsområden och fem förhållningssätt som ingår i målen för kursen. Dessa kan användas vid kursplanering för att se till att alla moment inkluderas. Uppsatsen ger slutligen ett förslag på kursplanering som kan användas i kursen.
33
Tschannen, Dominique. "Erlebensmodi und Soziale Arbeit : Erläuterungen zu den Erlebensmodi - Überlegungen zur Relevanz für die Soziale Arbeit - handlungstheoretische Folgerungen /". Zürich, 2007. http://www.infostelle.ch/filedownload.html?cdid=3654&file=0.
34
Schönfeld, Nicole. "Isolation und molekulare Charakterisierung des Apoptose-induzierenden Metastasensuppressors C33/CD82". Diss., lmu, 2003. http://nbn-resolving.de/urn:nbn:de:bvb:19-8675.
35
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.
36
Jean, Bruno. "Propriétés électriques, optiques et électro-optiques du semiconducteur CdIn2 Te4". Bordeaux 1, 1994. http://www.theses.fr/1994BOR10553.
Abstract (sommario):
Cette these est consacree aux proprietes electriques, optiques et electro-optiques du semiconducteur ternaire cdin#2te#4. La premiere partie de la these est consacree a l'etude des proprietes optiques et de transport par absorption optique, photoluminescence, photoconductivite et effet hall. La compensation du materiau, due a des defauts antisites dans le sous reseau cationique, a ete mise en evidence par effet hall. Un niveau accepteur situe a environ 40 mev de la bande de valence a ete observe en photoconductivite. D'autre part, l'asymetrie des mesures de conductivite par la methode de van der pauw et aussi des spectres dlts (deep level transient spectroscopy) dont la forme depend de la tension de polarisation ont montre la presence d'un desordre a moyenne distance. Les fluctuations spatiales des bords de bandes qui en resultent permettent d'expliquer la plupart des resultats experimentaux. Enfin, un niveau donneur profond, situe a 0. 5 ev environ sous la bande de conduction, a ete observe par luminescence sur les echantillons presentant un ecart a la stchiometrie important. La seconde partie de ce travail est consacree au reexamen de la mesure du coefficient electro-optique r#4#1 en mode longitudinal. Nous montrons que les classiques mesures en detection synchrone peuvent conduire a des resultats errones si les electrodes transparentes n'ont pas un caractere ohmique. Un modele theorique est ensuite developpe pour rendre compte de la distribution particuliere du champ electrique due au caractere schottky des contacts. Les resultats de diverses mesures en champ electrique continu sont en bon accord avec le modele et nous permettent alors de proposer une nouvelle valeur du coefficient r#4#1, proche de 3pmv##1
37
Soffar, Ahmed. "The Role of CDK2 and CDK9 in the Radiation Response of human HNSCC Cancer Cells". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-119407.
Abstract (sommario):
The radiosensitivity of tumour cells depends mainly on their capacity to maintain genomic integrity. This requires efficient repair of radiation-induced DNA double strand breaks, a process governed by the cell cycle.
Based on their functions in cell cycle regulation and DNA damage repair, we hypothesised that targeting of CDK2 and CDK9 modifies cancer cell response to radiotherapy. Therefore, we evaluated the significance of CDK2 and CDK9 for the cellular radiation response in a panel of human head and neck squamous cell carcinoma (HNSCC) cell lines. In order to achieve our goal, we performed a series of experiments to measure several key parameters such as clonogenic radiation survival, cell cycling, DNA damage repair and apoptosis.
We found that loss of CDK2 radiosensitises mouse embryonic fibroblasts (MEFs) as well as HNSCC two dimensional (2D) cell cultures. However, under more physiological three dimensional (3D) growth conditions in laminin-rich extracellular matrix, targeting of CDK2 failed to modulate the radiosensitivity of HNSCC cells. Moreover, CDK2 attenuated the repair of radiogenic double strand breaks (DSBs) in MEFs as well as SAS and FaDu HNSCC cells indicating a possible role of CDK2 in DNA damage repair. However, we found that CDK2 is dispensable for cell cycle and checkpoint regulation in response to irradiation in SAS and FaDu cells. Taken together, our results suggest that targeting of CDK2 may not provide a therapeutic benefit to overcome HNSCC cell resistance to radiotherapy.
We also showed that depletion of CDK9 clearly enhances the radiosensitivity of HNSCC cultures. In addition, the ectopic expression of CDK9 has a radioprotective effect. These findings suggest a potential role of CDK9 in the radiation response of HNSCC cells. Moreover, our study indicates a possible role of CDK9 in the DNA damage repair response and cell cycling of HNSCC cells. Conclusively, on the basis of these data, targeting of CDK9 in addition to conventional radiotherapy might be a viable strategy to overcome cancer cell resistance.
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Жиляк, Іван Дмитрович. "Акваамінодифосфати Co2+, Ni2+, Cu2+, Zn2+ та Cd2". Dissertazione di Candidato in Scienze Chimiche, Нац. аграрний ун-т, 2006.
39
Stell, David Andrew. "Anti-CD2 mediated prolongation of allograft survival". Thesis, University of Glasgow, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340254.
40
Chen, Ho Ann. "Biophysical characterisation of rat CD2 domain 1". Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.392332.
41
Соловйов, М. В., В. А. Франів, О. В. Футей, О. В. Бовгира e А. І. Кашуба. "Динаміка гратки кристалу TI[4]CdI[6]". Thesis, Сумський державний університет, 2016. http://essuir.sumdu.edu.ua/handle/123456789/45757.
42
Ravindranath, Priya. "Förmågor utvecklade genom projektarbete inom Teknik1 i förhållande till CDIO : Förmågor och färdigheter som utvecklas i förhållande till CDIO-modellen, genom projektarbete i gymnasiekursen Teknik1". Thesis, KTH, Lärande, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-293164.
Abstract (sommario):
I dagens värld har samhället blivit beroende av teknik och de flesta yrken använder teknik iolika konstellationer. Med alltmer teknisk utveckling har kompetenskraven och arbetsmetoderna förändrats. Det som tidigare upplevdes som ett ingenjörsmässigt sätt att arbeta har nu blivit ett allmänt sätt att arbeta. Det vill säga - att arbeta i grupper och projekt är sättet att arbeta för de flesta yrken. I en teambaserad miljö behövs förutom utvecklad teknisk kompetens även icke-tekniska (mjuka) färdigheter, såsom interaktion och samarbete med andra människor. Teknik 1, som är en introduktionskurs till teknik i gymnasiet, kan ses som det allra första steget mot en ingenjörsutbildning som är organiserad enligt CDIO (Conceive, Design,Implement, Operate). CDIO är en modell som används i stor utsträckning inom ingenjörsutbildningen för att förbättra sättet att undervisa i teknik och för att förbättra de blivande ingenjörernas kunskaper. Ur detta perspektiv är det intressant att se om teknikundervisningsmetoderna på gymnasienivån - särskilt arbetet i grupper och projekt -utvecklar vissa förmågor och färdigheter som är gemensamma med de som beskrivs i CDIO-modellen. Denna studie kommer att hjälpa oss att bättre förstå om Skolverkets val att basera teknikundervisning med inspiration från CDIO introducerar eleverna till ett ingenjörsmässigt sätt att arbeta och de färdigheter som behövs inom ingenjörsutbildning, som bygger på CDIO-modellen. I denna studie intervjuades tre tekniklärare och sex elever på olika gymnasieskolor i Sverige för att ta reda på deras perspektiv på förmågor och färdigheter enligt ämnets syfte och examensmål som de uppfattar att de uppnår / utvecklar genom grupp- och projektarbete. Vidare studerades om det finns enighet mellan elevernas och lärarnas svar och de lärandemål som anges i CDIO-kursplanen. Resultaten av denna studie visar att det finns många likheter mellan lärandemål skrivna i CDIO-kursplanen i förhållande till de förmågor som lärare och elever nämnde att de utvecklade genom att arbeta i projekt- och grupparbete. Mestadels utvecklades färdigheter relaterade till individuell och yrkesmässig utveckling, såsom ansvarstagande, kreativ problemlösning och analytiska färdigheter, men även kommunikation, systemtänkande och samarbete, samt arbete i grupper av olika konstellationer.In today's world, society has become dependent on technology and most professions use technology in various constellations. With increasing technical development, the competence requirements and working methods have changed. What was previously perceived as an engineer’s way of working has now become a general way of working. That is - working in groups and projects is the way to work in most professions. In a team-based environment, in addition to developed technical competence, a range of non-technical (soft) skills - such as interaction and collaboration with other people, are also required. Technology 1, which is an introductory course to technology in upper secondary schools in Sweden, can be seen as the very first step towards engineering studies - which are at the university level organized and driven according to the CDIO (Conceive, Design, Implement,Operate). CDIO is a model that is widely used in engineering education to improve the way technology is taught and to improve the quality of the workforce. From this perspective, it is interesting to see if the teaching methods of technology 1 at the upper secondary schools - especially group and project work - develop certain abilities and skills that are common to those described in the CDIO-Syllabus. This study will help us better understand whether the National Agency for Education's choice to base technology education with the inspiration from CDIO, introduces students to an engineering way of working and the skills needed for engineering studies that is based on the CDIO-concept. In this study, three technology teachers and six Technology 1 students from different upper secondary schools in Sweden were interviewed, in order to find out their perspectives on abilities and skills - according to the subject's purpose and degree goals - that they perceive that they achieve / develop through group and project work. Furthermore, it was studied whether there is agreement between the students' and the teachers' answers and the learning objectives stated in the CDIO-syllabus. The results of this study show that there are many similarities between learning objectives written in the CDIO-syllabus in relation to the abilities that teachers and students mentioned that they developed by working in project and group work. Mostly, skills related to individual and professional development were developed that include taking responsibility, creative problem solving and analytical skills, communication, systems thinking and collaboration and work in groups of different constellations are a few of them.
43
Saandi, Thoueiba. "Le gène homéotique Cdx2 : fonctions in-vivo et régulation dans les pathologies intestinales". Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAJ030.
Abstract (sommario):
Le gène Cdx2 exerce de nombreuses fonctions au cours du développement embryonnaire. Son expression est maintenue spécifiquement dans l’épithélium intestinal adulte. Cdx2 est diminué dans les cancers colorectaux (CCR), favorisant la migration et la dissémination des cellules tumorales. Cette diminution de Cdx2 est réversible, suggérant une dérégulation du gène. Nous avons étudié d’une part les fonctions intestinales de Cdx2 au cours du développement et surtout chez l’adulte, et d’autre part les mécanismes moléculaires associés à la dérégulation de Cdx2 dans les CCR.Une approche d’invalidation conditionnelle de Cdx2 chez la souris a été choisie. Nous montrons que Cdx2 est nécessaire pour l’établissement de l’identité intestinale au cours du développement. De plus, dans l’intestin adulte il contribue au maintien de l’identité des cellules souches et intervient dans la différenciation terminale des cellules épithéliales. Le croisement du modèle murin transgénique pCdx2-9LacZ avec le modèle de cancérogénèse colique spontanée Apc∆14/+ indique que les éléments nécessaires à la diminution d’expression de Cdx2 dans les CCR sont sur le promoteur de 9kb de Cdx2. Par ailleurs, nous montrons une corrélation d’expression entre les protéines HNF4α, régulateur transcriptionnel de Cdx2, et Cdx2 dans des échantillons de tumeurs intestinales humaines et murines. L’invalidation conditionnelle de Hnf4α dans l’intestin est associée à une réduction d’expression de Cdx2 et à une plus grande susceptibilité des animaux à la tumorigenèse colique chimio-induite. HNF4α constitue un facteur important de la dérégulation de Cdx2 dans les CCR et exerce une fonction suppresseur de tumeur dans l’intestinThe Cdx2 gene exerts many functions during embryonic development. Its expression is maintained specifically in the adult intestinal epithelium. Cdx2 expression is reduced in colorectal cancers (CRC); moreover, this reduction promotes migration and the spread of colon tumor cells. The alteration of Cdx2 in CRC is reversible, suggesting a deregulation of the gene. The objectives of my project were to study the functions of Cdx2 during intestinal development and in adults and to study the molecular mechanisms associated with the deregulation of Cdx2 in CRC. An approach of conditional invalidation of Cdx2 in mice has been used. We show that Cdx2 plays a key role in establishing the intestinal identity during development. In addition, at the adult stage Cdx2 is involved in the maintaining of the intestinal stem cells identity and in the control of terminal differentiation of intestinal epithelial cells. Crossing the transgenic mouse model pCdx2-9LacZ with spontaneous colon carcinogenesis model ApcΔ14/+ indicates that the elements necessary for the decrease of Cdx2 expression are located on the Cdx2 promoter of 9kb. Earlier team works have highlighted HNF4α as a transcriptional regulator of Cdx2 expression. In this work, we have demonstrated a correlation between HNF4α and Cdx2 protein expression in samples of human and mouse intestinal tumors. The conditional invalidation of Hnf4α in the intestine is associated with a reduction of Cdx2 expression, and a greater susceptibility for mice to chemo-induced colonic tumorigenesis. HNF4α is an important factor in the deregulation of Cdx2 in CRC and it exerts itself a tumor suppressor function in the gut
44
Lundin, Jeanette. "Targeted CD52 therapy in lymphoid malignancies : a clinical and immunological study /". Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-441-0/.
45
Taylor, Vanessa Claire. "Biology of the CD52 antigen, a major glycoprotein of human lymphocytes". Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242883.
46
Piperi, Christina. "Structural and functional studies on the B cell surface molecule CD22". Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299109.
47
Hinkel, Isabelle. "Plasticité des cellules cancéreuses coliques : impact du facteur d'identité tissulaire Cdx2". Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-00871086.
Abstract (sommario):
Le facteur de transcription homéotique Cdx2 est un suppresseur de tumeurs et son expression est réduite de manière hétérogène dans les tumeurs coliques. Or, le cancer colorectal demeure un problème de santé publique par sa fréquence et sa gravité. Au travers de 3 sous-projets, cette thèse visait à comprendre le mode d'action de Cdx2. Premièrement, la cadhérine Mucdhl a été identifiée et caractérisée en tant que nouvelle cible de Cdx2 : Mucdhl inhibe la croissance des cellules cancéreuses coliques et s'oppose à l'activité de la -caténine. Deuxièmement, un effet inattendu de Cdx2 sur le cytosquelette et la rigidité cellulaire a été montré. Ceci pourrait expliquer comment Cdx2 intervient dans l'organisation structurale des entérocytes ou la migration. En parallèle, une lignée cellulaire rapportrice de l'expression de Cdx2 a été créé qui, après validation, sera un outil précieux pour l'étude des mécanismes moléculaires qui conditionnent l'hétérogénéité tumorale. Par la mise en évidence de nouvelles fonctions et cibles de Cdx2, cette thèse permet de mieux appréhender son rôle physiologique et son action de suppresseur de tumeurs dans l'intestin.
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Heady, Lucy Clare. "Inhibiting CDK2 : a computational study with ab-initio and classical methods". Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613729.
49
Barros, Rita Henriques Pinto de. "Identification of signalling pathways involved in CDX2 regulation in metaplastic lesions". Doctoral thesis, Faculdade de Medicina da Universidade do Porto, 2009. http://hdl.handle.net/10216/55321.
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Lajaunias, Frédéric. "Rôle de CD22 et son ligand dans le lupus érythémateux disséminé". Paris 7, 2002. http://www.theses.fr/2002PA077214.