To see the other types of publications on this topic, follow the link: CRR2.
Dissertations / Theses on the topic 'CRR2'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'CRR2.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Blömacher, Margit [Verfasser]. "Characterization of mammalian CRN5 and CRN2 / Margit Blömacher." Köln : Deutsche Zentralbibliothek für Medizin, 2013. http://d-nb.info/1052418589/34.
Full text
2
Fredriksson, Anna, and Sebastian Sporrong. "Intensivvårdssjuksköterskans vårdande av patienter med kontinuerlig njurersättningsterapi : En observationsstudie." Thesis, Högskolan i Borås, Akademin för vård, arbetsliv och välfärd, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:hb:diva-9410.
Full textAbstract:
Continuous Renal Replacement Therapy, CRRT, är idag den behandling som oftast används inom intensivvården hos patienter i behov av dialys. Ett ökande antal studier genomförs för att förbättra CRRT behandlingen för patienten, men få studier belyser intensivvårdssjuksköterskans vårdande när det gäller skötsel och att upprätthålla CRRT. Syftet med denna studie är att beskriva aspekter av betydelse för intensivvårdssjuksköterskans vårdande av patienter i behov av kontinuerlig dialys på en intensivvårdsavdelning och för att besvara syftet ligger en kvalitativ ansats till grund för uppsatsen. Som datainsamlingsmetod valdes en ostrukturerad deltagande observation. Resultatet utmynnade i tre olika kategorier. I Vårdmiljö, beskrivs hur dialysmaskinen tar upp en stor del av rummet samt avger oljud när den larmar vilket kan upplevas stressande för både sjuksköterska och patient. I Organisation och åtgärd, beskrivs hur intensivvårdssjuksköterskan organiserar och planerar sina omvårdnadsåtgärder för att effektivisera arbetet samt säkerställa att patienten får en fullgod dialysbehandling utan längre uppehåll. I Omvårdnad och information visas att intensivvårdssjuksköterskor, som vårdar patienter i CRRT, fokuserar både på patient och teknik. När den kontinuerliga dialysen inte fungerar som planerat ökas stressen och fokus riskerar att flyttas från patienten till tekniken. CRRT ställer krav på intensivvårdssjuksköterskan, organisation och medarbetarna. Resultatet skulle kunna bidra till en ökad medvetenhet kring de utmaningar som intensivvårdssjuksköterskan ställs inför vid vård av patienter med CRRT.
3
Dreßen, Jochen. "Epitaxie und Charakterisierung oxidischer Schichtsysteme: BiSrCaCuO-Hochtemperatursupraleiter und ferromagnetisches CrO2." Aachen : Shaker, 1999. http://deposit.d-nb.de/cgi-bin/dokserv?idn=970716621.
Full text
4
Brugel, D. "Theoretical studies of Cr2+(2) GaAs spectra." Thesis, University of Nottingham, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303719.
Full text
5
Ambrosino, Mariacarmela <1978>. "Ottimizzazione di un protocollo di anticoagulazione regionale con citrato in CRRT." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6516/.
Full textAbstract:
Ottimizzazione di un protocollo di anticoagulazione regionale con citrato in CRRT
Introduzione: La necessità di un'anticoagulazione continua e l'ipofosforemia in corso di trattamento sono problemi costranti in corso di CRRT. Il nostro studio ha cercato di dimostrare l'efficacia e la sicurezza dell'anticoagulazione regionale con citrato in CVVH basato sull'utilizzo di una soluzione di citrato (18 mmol/L) associata ad una soluzione di reinfusione contenente fosfato, recentemente disponibile in commercio, al fine di ridurre l'ipofosfatemia in corso di CRRT.
Metodi: Abbiamo utilizzato il nostro protocollo basato sull'utilizzo di una concentrazione di citrato contenente 18 mmol/l associata ad una soluzione di reinfusione contenente fosfato in un piccolo gruppo di pazienti ricoverati in terapia intensiva post-cardiochirurgica, sottoposti a CRRT per insufficienza renale acuta.
Risultati: Il nostro protocollo ha garantito un'adeguata durata del circuito ed un ottimo controllo dell'equilibrio acido-base in ogni paziente. E' stata necessaria solo una minima supplementazione di fosforo in alcuni dei pazienti trattati.
Conclusioni: Il nostro protocollo basato sull' utilizzo di una soluzione a concentrazione di citrato maggiore (18 mmol/l), permette un miglior controllo dell'equilibrio acido-base rispetto all'utilizzo della soluzione a più bassa concentrazione di citrato. L'uso di una minore dose di citrato ed il mantenimento di un target maggiore di calcio ionizzato all'interno del circuito sono comunque associati ad un'adeguata durata del circuito.
I livelli di fosforemia sono rimasti sostanzialmente stabili nella maggior parte dei pazienti trattati, grazie alla presenza di fosfato nella soluzione utilizzata come reinfusione in post-diluizione.Optimization of a regional citrate anticoagulation protocol in CRRT Purpose: Prolonged anticoagulation and hypophosphatemia are well known drawbacks of CRRT. The aim of our study was to show the efficacy and safety of a regional citrate anticoagulation protocol for CVVH combined with a phosphate containing replacement fluid. Methods: We used our protocol, based on a citrate solution (18 mmol/l) combined with in a phosphate containing replacement fluid, in a small cohort of heart surgery patients. Results: Our protocol provided an adequate circuit lifetime and an excellent acid-base status in every patient. A low amount of phosphorus supplememntation was required only in a very few patients. Conclusions: Our protocol based on a citrate solution (18 mmol/l) combined with a phosphate containing replacement fluid, allows a better buffer balance control than using of a lower citrate solution. Moreover, an adequate circuit lifetime was obtained. Serum phosphate was steadily maintained in all patients. Only in a very few patients a low supplementation was required.
6
Schütte, Mark [Verfasser], and Stefan [Akademischer Betreuer] Dübel. "Crf2 - Ein neues Antigen von Aspergillus fumigatus / Mark Schütte ; Betreuer: Stefan Dübel." Braunschweig : Technische Universität Braunschweig, 2009. http://d-nb.info/1175829587/34.
Full text
7
Dreßen, Jochen [Verfasser]. "Epitaxie und Charakterisierung oxidischer Schichtsysteme: BiSrCaCuO-Hochtemperatursupraleiter und ferromagnetisches CrO2 / Jochen Dreßen." Aachen : Shaker, 1999. http://d-nb.info/970716621/34.
Full text
8
Momozawa, Ai [Verfasser]. "Precipitation and Microstractural Change Mechanism in TiB2-W2B5-CrB2 Ceramics / Ai Momozawa." Aachen : Shaker, 2007. http://d-nb.info/1164341049/34.
Full text
9
Shek, Ka-wai. "DNASE2, CR2, TYK2 genes polymorphisms in systemic lupus erythematosus /." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38278765.
Full text
10
Shek, Ka-wai, and 石家偉. "DNASE2, CR2, TYK2 genes polymorphisms in systemic lupus erythematosus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B45012945.
Full text
11
Rudin, Susanne. "Mobilisering av patienter som genomgår kontinuerlig dialys på en intensivvårdsavdelning : en litteraturstudie." Thesis, Sophiahemmet Högskola, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:shh:diva-3104.
Full textAbstract:
Intensivvård är en vårdnivå som har utökade resurser att ta hand om patienter med hotande eller manifest svikt i vitala funktioner. En intensivvårdssjuksköterska är en sjuksköterska med specialistutbildning inom intensivvård vilket innebär vidareutbildning i att ha utökad förståelse för kroppens fysiologiska processer, för medicinskteknisk utrustning och för att ha utökad handlingsberedskap att hantera patienters snabbt påkomna svikt. När en patient drabbas av multiorgansvikt inkluderar det ofta akut njursvikt som kan leda till behov av kontinuerlig dialys under intensivvården. Intensivvårdens dialysbehandling har i ett historiskt perspektiv hänvisat patienter till långvarigt sängläge och immobilisering till följd av apparatens utformning och behandlingens längd men också på grund av det vårdande teamets oro för risker att mobilisera under kontinuerlig dialys. Att mobilisering inleds i ett tidigt skede av intensivvården beskrivs avgörande för patienters välbefinnande, rehabilitering och överlevnad. Syftet var att belysa faktorer som påverkar mobilisering av patienter som genomgår kontinuerlig dialys på en intensivvårdsavdelning. Metoden som användes var en allmän litteraturstudie då det är en bra metod för att kartlägga dokumenterad kunskap och skapa en överblick inom ett område. Vetenskapliga artiklar söktes i PubMed, Cinahl och Google Scholar. Fjorton vetenskapliga artiklar inkluderades i resultatet. Resultatet visade att mobilisering under kontinuerlig dialys sågs som patientsäker och genomförbar och det påverkade inte patienter hemodynamiskt negativt utan med hårdare träning vid ökad patientdelaktighet ledde det till ökad patientnöjdhet och i förlängningen till ökad överlevnad Hindrande faktorer för mobilisering under kontinuerlig dialys var när patientens fysiska och psykiska instabilitet var för svår. Personalens rädsla för att rubba dialyskateterns läge sågs inte vara befogad och inte heller rädslan att det utgjorde ökad risk att mobilisera med dialyskatetern sittande i ett kärl i ljumsken jämfört med ett på halsen. Rädslan för att dialysbehandling skulle fördröjas då filter koagulerat till följd av mobilisering sågs inte heller befogad. Personalupplevda hindrande faktorer för mobilisering under kontinuerlig dialys var rädslor för risk för patientens hälsa, personalens kunskaps- och erfarenhetsbrist, personalbrist, ogenomtänkt sederingsdjup, brist på rutiner och riktlinjer, samarbete, utrustning, samordning och gemensamma mål för verksamheten. Slutsatsen är att mobilisering under kontinuerlig dialys är motiverad, patientsäker och genomförbar men hänsyn måste tas till patientens fysiska och psykiska tillstånd. Ökad mobilisering leder till ökad patientdelaktighet och patientnöjdhet samt kan leda till ökad överlevnad. Det är viktigt att personal inom hälso-och sjukvård är medvetna om betydelsen av att mobilisera patienter som genomgår kontinuerlig dialys på en intensivvårdsavdelning.
12
Kaiser, Abigail M. "Localization of Five Target Proteins in Tachyzoites of Toxoplasma gondii." Scholar Commons, 2019. https://scholarcommons.usf.edu/etd/7820.
Full textAbstract:
Five target genes were selected in Toxoplasma gondii tachyzoites for localization studies. These five genes, detected through proteomics studies, included TgME49_227450, TgME49_223080, TgME49_262390, TgME49_230940, and TgME49_269620. Localization of these five target proteins is a first step to confirm their interaction with TgCrk2 and understand their function and role in TgCrk2 regulation of the tachyzoite cell cycle. Gene models for the targets were analyzed using ToxoDB and ApE analysis tools. Endogenous tagging constructs were created for each target. Transgenic parasites were created. Finally, localization analysis of the target proteins in tachyzoites was completed using immunofluorescent microscopy following. One protein was found to be nuclear, two were located in the cytoplasm, and two were unable to be analyzed. Future research should be completed in order to prove these putative interactors are really correlated with TgCrk2 through Co-immunoprecipitation.
13
Lott, Nikole T. "Regulation of the Histone Methyltransferase Kmt5/Set9 and its Role in Genome Stability." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1323383595.
Full text
14
Anand, Sneha Nitish. "Investigating the behavioural and molecular functions of Cry1 and Cry2 using mouse mutants." Thesis, Open University, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.551621.
Full textAbstract:
Endogenous circadian clocks generate rhythms of physiology and behaviour that are synchronised to the environment, principally through the light-dark cycle. In mammals, the circadian clock is dependent on interlocked feedback loops that involve several clock elements such as cryptochromes (Cryl and Cry2). Post-translational modifications control intracellular trafficking, functionality and degradation of CRY proteins which are keys to the functioning of the clock. CRY protein levels are dependent upon their timely degradation by F-box proteins. This has recently been shown in the afterhours (Afh) mutant carrying a mutation in the F -box gene, Fbxl3. Afh has been shown to lengthen circadian period by stabilising levels of CRY proteins across the circadian cycle. To understand the specific roles of each of the two CRY proteins in circadian regulation, we generated compound mouse mutants to investigate the behavioural and molecular consequences of stabilising either CRY1 or CRY2 protein levels in mice lacking the alternative form of Cry. The circadian wheel-running activity assessed in light:dark and constant environmental conditions for both Cryrl-;FbxI3Afh/Afh and Cry[I-;FbxI3Afh/Afh (stabilising CRY2 and CRY1 protein levels respectively); clearly show a gradual increase in period length in constant darkness as the dosage of Fbxl3Afh is increased. This would suggest that stabilisation of either CRY protein can lengthen the clock, presumably as a result of a prolonged phase of transcriptional repression by either protein. This effect seen in the compound mutants was confirmed at the gene and protein levels.
15
Ostheimer, Gerard Joseph. "Proteins required for chloroplast group II intron splicing : CRS2 and its associated factors /." view abstract or download file of text, 2003. http://wwwlib.umi.com/cr/uoregon/fullcit?p3080594.
Full textAbstract:
Thesis (Ph. D.)--University of Oregon, 2003.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 111-124). Also available for download via the World Wide Web; free to University of Oregon users.
16
Lockley, Michelle. "Activity of Adenoviral E1A CR2 Deletion Mutants in Ovarian Cancer." Thesis, Queen Mary, University of London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504564.
Full textAbstract:
d1922-947 is a type 5 adenovirus deleted in a portion of its genome, EIA CR2, which releases E2F by binding retinoblastoma protein (PRb). Transactivation of E2Fresponsive genes stimulates S phase entry and viral DNA is preferentially replicated. Since over 90% of human cancers have pRb pathway abnormalities, d1922-947 replicates selectively in malignant cells. Co-immunoprecipitation in IGROVI human ovarian cancer cells and cytotoxicity in hTERT and SV 40 immortalised ovarian epithelial cells confirmed the proposed mechanism of d1922-947 activity. In IGROVI cells, d1922~947 induced S phase and viral protein expression more rapidly, and replicated more efficiently, than Ad5 WT. Cytotoxicity of d1922-947 exceeded Ad5 WT and the EIB 55K deleted adenovirus, . d11520. In female nude mice bearing intraperitoneal (IP) IGROVI xenografts, d1922- 947 increased survival above control (p<0.001), particularly when delivered in icodextrin. Hepatotoxicity, which was less severe than Ad5 WT, was seen in some nude mice treated with d1922-947 and in immunocompetent .C57B1I6 mice bearing CMT64 murine non.,.small cell lung cancer cells IP. Transformed murine ovarian epithelial cells (IDS) did not' suppoli production of late adenovirai proteins, despite efficient DNA replication, transcription and nuclear export of late viral RNAs. This could explain the .inability of IP viruses to improve survival in C57B1I6 mice bearing ID8 cells IP . . Ovarian cancer disseminates diffusely across peritoneal surfaces, so quantifying ill VIVO eIhcacy IS pro51emauc. In IllICe oeanng ll' xenograIts 01 FIreny Iucnerase expressing IGROVI cells (IGROVI-Luc), light output increased over time, whereas IP d1922-947 held bioluminescence at baseline for over two months. A Renilla relliformis luciferase expressing EIA CR2 deleted adenovirus, dlCR2 Ren, was created, which had comparable ,anti-tumour efficacy to dI922-.947. Light emission by dlCR2 Ren correlated with EIA expression and, after a single IP injection in murine models of ovarian cancer, light emission and therefore viral' persistence was demonstrated for 2 weeks.
17
Reljic, Rajko. "The interaction of CD23 and CR2 and its functional consequences." Thesis, King's College London (University of London), 1996. https://kclpure.kcl.ac.uk/portal/en/theses/the-interaction-of-cd23-and-cr2-and-its-functional-consequences(01e4a5aa-37fc-4892-8fa8-458ac1183001).html.
Full text
18
Herriot, Sandrine. "Source laser accordable pour le moyen infrarouge : Cr2+ : ZnSe polycristallin." Paris 11, 2002. http://www.theses.fr/2002PA112321.
Full textAbstract:
Le développement de nouvelles sources laser solides, compactes, émettant dans le moyen-infrarouge (MIR) a initié l'étude des matrices II-VI dopées aux ions de transitions métallique TM. Parmi ces composés, l'ion chrome inséré dans la matrice anse ressort comme un candidat idéal pour obtenir une émission radiative à température ambiante dans le domaine spectrale du 2-3 mM. Cette thèse s'inscrit dans le cadre de développement de telles sources et plus particulièrement, elle s'intéresse dans l'étude et la réalisation de source laser, accordable, à température ambiante, pour le MIR à partir de matériau Cr2+ : ZnSe polycristallin. L'intérêt des matériaux polycristallins réside sur le coût de fabrication et les dimensions réalisables comparativement aux matériaux monocristallins. Nous avons donc élaboré des matériaux Cr2+ : ZnSe par la méthode de diffusion thermique à partir de substrats de ZnSe mono et poly-cristallin. Dans le but d'obtenir un matériau approprié à l'émission laser, les différents processus intervenant lors de cette diffusion ont été analysés: insertion du chrome dans la matrice par substitution, homogénéisation du dopage et mécanisme de recristallisation. Nous avons ainsi déterminé les paramètres gouvernant le mécanisme de diffusion du chrome dans le anse et réalisé des matériaux Cr2+ : ZnSe monocristallin et poly-cristallins à différents hauteurs de dopage en chrome (de 2. 10^18 à 5. 10^19 ions. Cm^(-3)). Par la suite, ces matériaux ont été caractérisés d'un point de vu spectroscopique. Il apparaît que la forme et la largeur des bandes d'absorption (1400-2200 nm), associées à la transitions 5T-2 → 5E de l'ion Cr2+ inséré dans le ZnSe sont peu différentes pour les matrices poly ou mono-cristallines. De même, le spectre de photo-luminescence (2000-3000 nm) mesuré à 300K, ne révèle aucune différence notable sur la forme du spectre à l'émission selon le type de matériau considéré. Par ailleurs, une caractérisation dynamique de ces matériaux indique des valeurs de temps de vie de l'état excité de l'ordre de 4 à 5 ms à 300K pour des dopages de l'ordre de 5. 10^18 ions. Cm^(-3). Enfin, l'efficacité à l'émission laser de ces matériaux a été étudiée. Dans une configuration de cavité laser identique, les efficacités laser optique-optique obtenue à partir de deux types de matériaux, mono (33%) et poly (28%) cristaux de Cr2+ : ZnSe, se sont avérés être comparables. Ce résultat est lié à la qualité optique du matériau polycristallin obtenue (grains de grande dimension) selon la procédure d'élaboration employée: Diffusion thermique. Une accordabilité en longueur d'onde entre 2. 2 et 2. 7 mM à partir de ces matériaux a également été obtenue à 300K. Nous avons ainsi démontré que les matériaux polycristallins Cr2+ : ZnSe présentent les propriétés optiques adaptées pour réaliser des sources laser opérant dans le MIR à température ambiante en compétition avec les matrices monocristallinesDevelopment of efficient, compact, tunable solid state laser for the mid-infrared (MIR) at room temperature has initiated the study of transition metal ion TM doped II-VI compounds. Among those compounds, chromium ion incorporated into ZnSe host crystal represent a solid state laser material allowing radiative emission at room temperature in the spectral range of 2-3 mM. This work concern the study and realization of tunable, room temperature operating, solid state laser for MIR based on Cr2+ :ZnSe polycrystal. Advantages of polycrystals are mainly based on the elaboration cost and available dimension compared to the single crystals. We have elaborated Cr2+ :ZnSe laser materials by thermal diffusion doping method using both single and poly-crystals of ZnSe. Different process involved during the diffusion were analyzed like incorporation of chromium into substitutional site, homogenization of the doping and the recrystallization process. We have thus determined parameters governing the diffusion of chromium into the ZnSe and elaborated single and poly-crystals with different concentration on Cr (since 2. 10^18 to 5. 10^19 ions. Cm^(-3)). Then, we have proceed to spectroscopic characterization of those materials. We observed no difference in the shape and bandwidth of the absorption spectrum (1400-2200 nm) associated to the optical transition 5T-2 → 5E of Cr2+, inserted either in single or poly-crystal of ZnSe. The same observation was done concerning the shape of the room temperature photo-luminescence spectra (2000-3000 nm) obtained with either single or poly-crystal of Cr2+ :ZnSe. Furthermore, a dynamical characterization of such materials indicated an excited state lifetime at 300K in the order of 4 to 5 ms for Cr concentration of 5. 10^18 ions. Cm^(-3). Finally, laser efficiency of those materials were also studied. A comparable optical-optical laser efficiency were obtained, in a same laser cavity, with both Cr2+ :ZnSe materials : single-crystal (33%) and poly-crystal (28%). This result is deeply associated to the high optical quality of the poly-crystal (large grain size) laser material obtained using our elaboration method : Thermal diffusion doping. We have also obtained with such materials a tunability between 2. 2 to 2. 7 mM at room temperature. We have thus demonstrated that Cr2+ :ZnSe poly-crystals are highly efficiency, tunable, room temperature operating, laser materials for the MIR and are in competition with Cr2+ :ZnSe single-crystals
19
Murillo, Avecillas Marcos Fernando. "Implementación de un sistema de gestión de la calidad en las terapias continuas de depuración extrarenal (TCDE)." Doctoral thesis, Universitat Autònoma de Barcelona, 2021. http://hdl.handle.net/10803/671632.
Full textAbstract:
Entre 5-23% de pacients en UCI desenvolupen fracàs renal agut, un elevat percentatge d'aquests requereixen TCDE. La mortalitat d'aquests ronda el 60%. Les TCDE requereixen personal capacitat, el seu maneig és sofisticat i hi ha riscos que poden comprometre la seguretat de l'pacient. Anàlisi Modal de Fallades i Efectes (AMFE) és una eina per avaluar riscos, descobrir fallades proactivament i proposar accions correctives per reduir / eliminar riscos potencials.
Objectius:
Principal: aplicar l'eina AMFE a les TCDE per potenciar la seguretat de l'pacient en UCI de l'Hospital Mútua Terrassa, millorar la qualitat assistencial fent una pràctica més segura, identificant punts de major risc en la nostra activitat i introduint mesures correctores que els minimitzin, elaborant mapa de riscos de l'procés associat a les TCDE per identificar els més freqüents i greus.
Secundaris: elaborar plans d'actuació en funció dels riscos detectats i instaurar mesures correctives. Implicar els professionals en la cultura de seguretat i estimular la notificació d'efectes adversos. Finalment, mostrar el grau de satisfacció.
Materials i Mètodes:
Durant l'any 2015 descrivim tasques i procediments associades a TCDE distribuïdes en: indicació de TCDE, col·locació i maneig de l'catèter, prescripció mèdica, encebat, connexió i maneig de l'circuit extracorpori, monitorització de la teràpia, finalització i desconnexió. Calculem l'índex de prioritat de risc (IPR) que va avaluar la magnitud de cada risc relacionat amb gravetat, ocurrència i detecció. A causa de l'elevat nombre de riscos detectats i potencial gravetat (pacients crítics i puntuacions IPR elevades) vam dissenyar una matriu ocurrència / severitat i un risk rànquing table que va permetre identificar riscos d'alta prioritat sobre els que havíem de dissenyar i establir mesures correctives. Durant l'any 2016 les implementem i dotze mesos més tard vam analitzar els resultats mitjançant càlcul de l'percentatge de reducció de l'IPR (% Reducció IPR = IPRi-IPRf / IPRi) i l'impacte de les diferents mesures correctives.
Finalment vam elaborar una enquesta que mostra el grau de satisfacció.
Resultats:
Vam detectar 181 riscos, vam seleccionar 12 per puntuació IPR i matriu d'ocurrència / severitat, instaurem 14 mesures correctives relacionades amb el catèter, prescripció mèdica i monitorització de l'circuit.
A l'any de instaurades hi va haver una reducció de l'IPR mitjà de el 62%. Comparant l'any previ amb nombre similar de pacients, observem reducció de l'23,4% de disfunció de l'catèter; 36% coagulació de circuit extracorpori, calculant-118 hemofiltros no rebutjats i 5670 hores guanyades / any d'eficiència de la teràpia. Així mateix, millora en 13% d'adequació de dosi i menor diselectrolitemia. Calculant-se un estalvi de 23.375 euros respecte a l'any previ. Finalment s'ha evitat un 22,1% de transfusió d'hemoderivats imputables a pèrdua hemàtica per coagulació.
La satisfacció amb el personal involucrat amb les TCDE a l'UCI de l'HUMT, dels canvis exercits en l'execució de les TCDE a partir dels resultats obtinguts per mitjà d'l'AMFE, ha estat mesurada a través d'una enquesta i en general han estat ben acceptats .
Conclusions
El desenvolupament de l'AMFE en TCDE és una eina útil per a la identificació i avaluació dels possibles errors i riscos associats a la teràpia. En tan sols un any d'implementar les mesures correctives s'han reduït de forma molt significativa els punts crítics de seguretat a les TCDE, permetent millora de l'eficàcia de la teràpia i una reducció de costos. S'ha estimulat el treball en equip i ha incrementat la cultura de seguretat. Els canvis efectuats han estat acceptats pel personal involucrat en les TCDE.Entre 5-23% de pacientes en UCI desarrollan fracaso renal agudo, un elevado porcentaje de éstos requieren TCDE. La mortalidad de éstos ronda el 60%. Las TCDE requieren personal capacitado, su manejo es sofisticado y existen riesgos que pueden comprometer la seguridad del paciente. Análisis Modal de Fallos y Efectos (AMFE) es una herramienta para evaluar riesgos, descubrir fallos proactivamente y proponer acciones correctivas para reducir/eliminar riesgos potenciales. Objetivos: Principal: aplicar la herramienta AMFE en las TCDE para potenciar la seguridad del paciente en UCI del Hospital Mutua Terrassa, mejorar la calidad asistencial haciendo una práctica más segura, identificando puntos de mayor riesgo en nuestra actividad e introduciendo medidas correctoras que los minimicen, elaborando mapa de riesgos del proceso asociado a las TCDE para identificar los más frecuentes y graves. Secundarios: elaborar planes de actuación en función de los riesgos detectados e instaurar medidas correctivas. Implicar a los profesionales en la cultura de seguridad y estimular la notificación de efectos adversos. Finalmente, mostrar el grado de satisfacción. Materiales y Métodos: Durante el año 2015 describimos tareas y procedimientos asociadas a TCDE distribuidas en: indicación de TCDE, colocación y manejo del catéter, prescripción médica, cebado, conexión y manejo del circuito extracorpóreo, monitorización de la terapia, finalización y desconexión. Calculamos el índice de prioridad de riesgo (IPR) que evaluó la magnitud de cada riesgo relacionado con gravedad, ocurrencia y detección. Debido al elevado número de riesgos detectados y potencial gravedad (pacientes críticos y puntuaciones IPR elevadas) diseñamos una matriz ocurrencia/severidad y un risk ranking table que permitió identificar riesgos de alta prioridad sobre los que debíamos diseñar y establecer medidas correctivas. Durante el año 2016 las implementamos y doce meses más tarde analizamos los resultados mediante cálculo del porcentaje de reducción del IPR (% Reducción IPR = IPRi-IPRf/IPRi) y el impacto de las distintas medidas correctivas. Finalmente elaboramos una encuesta que muestra el grado de satisfacción. Resultados: Detectamos 181 riesgos, seleccionamos 12 por puntuación IPR y matriz de ocurrencia/severidad, instauramos 14 medidas correctivas relacionadas con el catéter, prescripción médica y monitorización del circuito. Al año de instauradas hubo una reducción del IPR medio del 62%. Comparando el año previo con número similar de pacientes, observamos reducción del 23,4% de disfunción del catéter; 36% coagulación del circuito extracorpóreo, calculándose 118 hemofiltros no desechados y 5670 horas ganadas/año de eficiencia de la terapia. Así mismo, mejora en 13% de adecuación de dosis y menor diselectrolitemia. Calculándose un ahorro de 23375 euros con respecto al año previo. Finalmente se ha evitado un 22,1% de transfusión de hemoderivados imputables a pérdida hemática por coagulación. La satisfacción del personal involucrado con las TCDE en la UCI del HUMT, de los cambios ejercidos en la ejecución de las TCDE a partir de los resultados obtenidos por medio del AMFE, ha sido medida a través de una encuesta y en general han sido bien aceptados. Conclusiones El desarrollo del AMFE en TCDE es una herramienta útil para la identificación y evaluación de los posibles fallos y riesgos asociados a la terapia. En tan sólo un año de implementar las medidas correctivas se han reducido de forma muy significativa los puntos críticos de seguridad en las TCDE, permitiendo mejora de la eficacia de la terapia y una reducción de costes. Se ha estimulado el trabajo en equipo y ha incrementado la cultura de seguridad. Los cambios efectuados han sido aceptados por el personal involucrado en las TCDE.
Between 5-23% of Intensive Care Unit (ICU) patients develop acute renal failure and a high percentage of these require CRRT. The mortality of those who require CRRT is around 60%. CRRT are complex and require trained staff, sophisticated management, and there are risks that can compromise patient safety. Failure Mode and Effects Analysis (FMEA) is a tool to evaluate risks, proactively discover faults and propose corrective actions to reduce/eliminate potential risks. Objectives: Main: Apply FMEA tool in the CRRT to enhance patient´s safety in ICU of the Mutua Terrassa Hospital, improve the quality of care by making a safer practice, identifying points of greatest risk in our activity and introducing corrective measures that minimize them, developing risk map of the process associated with CRRT to identify the most frequent and serious adverse events. Secondary: Developing action plans based on the risks detected and establishing corrective measures. Involve ICU professionals in the safety awareness and encourage the reporting of adverse events. Finally, show the degree of satisfaction. Materials and methods: During 2015 we described tasks and procedures associated with CRRT distributed: indication of CRRT, placement and management of the catheter, medical prescription, priming, connection and management of the extracorporeal circuit, monitoring of therapy, termination and disconnection. We calculated the risk priority index (RPI) that evaluated the magnitude of each risk related to severity, occurrence and detection. Due to the high number of detected risks and potential severity (critical patients and very high RPI scores) we designed an occurrence/severity matrix and a risk ranking table that allowed us to identify high priority risks on which we should design and establish corrective measures. During 2016 we implemented them and twelve months later we analysed the results by calculating the reduction of RPI percentage (Reduction RPI% = iRPI-fRPI / iRPI) and the impact of the different corrective measures. Finally, we prepare a survey that shows the degree of satisfaction. Results: We detected 181 risks, we selected 12 by RPI score and occurrence/severity matrix, we put in place 14 corrective measures related to the catheter, medical prescription and circuit monitoring. A year of introduction, there was a reduction of the average RPI of 62%. Comparing the previous year with a similar number of patients, we observed a 23,4% reduction in catheter dysfunction; 36% coagulation of the extracorporeal circuit, calculating 118 haemofilters non-discarded and 5,670 hours gained / year of therapy efficiency. Furthermore, a 13% improvement in dose adequacy and less dyselectrolytemia were observed. All of this has meant an estimated savings of 23,375 Euros compared to the previous year. Finally, a 22.1% of blood product transfusions due to blood loss for circuit clotted has been avoided during the past year. The satisfaction of the personnel involved with the CCRT in the ICU of the HUMT, of the changes made in the execution of the CRRT from the results obtained through the FMEA, has been measured through a survey and in general they have been well accepted. Conclusions The development of FMEA in CRRT is a useful tool for the identification and evaluation of possible failures and risks associated with therapy. In just one year of implementing the corrective measures, the critical safety points in ICU CRRT has been significantly reduced, allowing an improvement in the efficacy of therapy and a reduction in costs. Teamwork has been encouraged and the safety awareness has increased. The changes made have been accepted by the staff involved in the CRRT.
20
Huitema, Edgar. "Determinants of nonhost resistance to phytophthora infestans." The Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1117038573.
Full text
21
König, Christian. "Nanomagnetismus von epitaktischen Fe(110)- und CrO2(100)-Strukturen im Hinblick auf potentielle spinelektronische Anwendungen." [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=98134495X.
Full text
22
Ducarouge, Benjamin. "Régulation des systèmes d'adhérence cellulaire par le CRF2 : un effecteur du stress dans le tube digestif." Phd thesis, Université de Grenoble, 2012. http://tel.archives-ouvertes.fr/tel-00767103.
Full textAbstract:
Le stress est impliqué dans le développement et l'exacerbation de diverses pathologies notamment au niveau intestinal. Les effets du stress dépendent de l'expression de neuromédiateurs spécifiques (CRF) et de leurs récepteurs. Notre étude porte sur la régulation et la fonction du CRF2 au niveau des entérocytes et des cellules tumorales coliques humaines. In vivo, nous avons montré que le stress et l'inflammation conduisent à l'augmentation de l'expression du CRF2 dans les colonocytes chez le rat. Dans les tumeurs, l'expression du CRF2 augmente avec le grade tumoral. In vitro, dans les cellules HT-29, l'activation du CRF2 induit une altération des jonctions adhérentes et des adhérences focales par la voie Src/ERK/FAK. Ces mécanismes sont responsables de la régulation de la perméabilité épithéliale et de l'augmentation de la migration des cellules tumorales. Ces travaux contribuent à la compréhension des mécanismes impliquant le stress dans le développement des pathologies intestinales.
23
Marks, Lori J., and M. Jernigan. "CRA2 (Concrete-Representational-Abstract and Constructed Response Assessment): Incorporating Language Skills into Math Instruction and Assessment." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/3534.
Full text
24
Pistolesi, Valentina <1979>. "CRRT nel paziente ad alto rischio emorragico: ottimizzazione di un protocollo di anticoagulazione regionale con citrato." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4493/.
Full textAbstract:
L’anticoagulazione regionale con citrato (RCA) è una valida opzione in pazienti ad alto rischio emorragico. Lo scopo del nostro studio è stato di valutare, in pazienti critici sottoposti a CRRT per insufficienza renale acuta post-cardiochirurgica, efficacia e sicurezza di un protocollo di RCA in CVVH con l’impiego di una soluzione di citrato a bassa concentrazione (12mmol/L).
Metodi: L’RCA-CVVH è stata adottata come alternativa all’eparina o alla CRRT senza anticoagulante (no-AC). Criteri per lo switch verso l’RCA: coagulazione dei circuiti entro 24h o complicanze legate all’eparina. Per facilitare l’impostazione dei parametri CVVH, abbiamo sviluppato un modello matematico per stimare il carico metabolico di citrato e la perdita di calcio.
Risultati: In 36 mesi, sono stati sottoposti a RCA-CVVH 30 pazienti. La durata dei circuiti con RCA (50.5 ± 35.8 h, mediana 41, 146 circuiti) è risultata significativamente maggiore (p<0.0001) rispetto all’eparina (29.2±22.7 h, mediana 22, 69 circuiti) o alla no-AC CRRT (24.7±20.6 h, mediana 20, 74 circuiti). Il numero di circuiti funzionanti a 24, 48, 72 h è risultato maggiore durante RCA (p<0.0001). I target di Ca++ sistemico e del circuito sono stati facilmente mantenuti (1.18±0.13 e 0.37±0.09 mmol/L). Durante l’RCA-CVVH nessun paziente ha avuto complicanze emorragiche e il fabbisogno trasfusionale si è ridotto rispetto alle altre modalità (0.29 vs 0.69 unità/die, p<0.05). Le piastrine (p=0.012) e l’AT-III (p=0.004) sono aumentate durante RCA riducendo la necessità di supplementazione. L’RCA è stata interrotta per accumulo di citrato in un solo paziente (calcemia totale/s-Ca++ >2.5).
Conclusioni: L’RCA ha consentito di prolungare la durata dei circuiti riducendo il fabbisogno trasfusionale e la necessità di supplementazione di AT-III e piastrine. L’utilizzo di un modello matematico ha facilitato l’impostazione dei parametri CVVH. L’RCA appare meritevole di maggiore considerazione come metodica di anticoagulazione di prima scelta in pazienti ad alto rischio emorragico sottoposti a CRRT.Regional citrate anticoagulation (RCA) is a valid option in patients at high risk of bleeding. The aim was to evaluate the efficacy and safety of RCA-CVVH using a low concentration citrate solution in critically ill patients at high risk of bleeding undergoing Continuous Renal Replacement Therapies (CRRT) for Acute Kidney Injury (AKI) following cardiac surgery. Methods: In cardiac surgery patients we adopted, as alternative to heparin or no anticoagulation (no-AC), RCA-CVVH using a 12 mmol/L citrate solution. Criteria for switching to RCA: early circuit clotting or heparin related complications. To facilitate CVVH settings, we developed a mathematical model to estimate metabolic citrate load and calcium loss. Results: Thirty patients were switched to RCA-CVVH from no-AC or heparin. RCA-CVVH filter life (50.5 ± 35.8 hrs, median 41, 146 circuits) was significantly longer (p<0.0001) if compared to heparin (29.2±22.7 hrs, median 22, 69 circuits) or no-AC (24.7±20.6 hrs, median 20, 74 circuits). Probability of circuit running at 24, 48, 72 hrs was higher during RCA-CVVH (p<0.0001). Targets circuit and systemic Ca++ were easily maintained inside the target range (0.37±0.09 and 1.18±0.13 mmol/L). During RCA-CVVH no patients had bleeding complications and transfusion rate was lower if compared to other AC modalities (0.29 vs 0.69 blood units/day, p<0.05). PLT count (p=0.012) and AT-III activity (p=0.004) increased throughout days of RCA reducing supplementation needs. RCA has been stopped for citrate accumulation in one patient (total calcemia/s-Ca++ >2.5). Conclusions: In this study, RCA allowed to safely prolong filter life decreasing transfusion rate and supplementation needs for AT-III and PLT. The use of a mathematical model allowed to simplify CVVH settings. Therefore, RCA should be worthy of more consideration as first choice CRRT anticoagulation modality in patients at high risk of bleeding.
25
江刺, 史子. "DNA損傷チェックポイントに必須な分裂酵母Crb2の研究." 京都大学 (Kyoto University), 2000. http://hdl.handle.net/2433/181155.
Full text
26
Frigerio, Mark. "Synthetic studies on novel bryostatin analogues and their interaction with the CRD2 of protein kinase C." Thesis, University College London (University of London), 2004. http://discovery.ucl.ac.uk/1446848/.
Full textAbstract:
A fully stereocontrolled asymmetric synthesis of the Southern Hemisphere intermediate 426 for the bryostatin family of antitumour agents is described in this thesis. It details how the strategy evolved from (E)-1,4-hexadiene 450 including a Roush-Masamune coupling between 462 and 507, cyclisation to glycal 505, selective epoxidation and in-situ Fischer glycosidation to 503 and an aldol / dehydration sequence to establish the (E)-exocyclic olefin. We also document a rare example of slow bond rotation in the C(18)- C(19)-bond of 426 and provide an explanation of this phenomenon. In addition, the synthesis of two truncated bryostatin analogs 525 and 526 is described, and the interaction of 525 with the CRD2 of human PKC-α discussed.
27
Moitrier, Sarah. "Compétition entre populations de cellules normales et transformées." Thesis, Paris Sciences et Lettres (ComUE), 2017. http://www.theses.fr/2017PSLET027/document.
Full textAbstract:
Lors du développement d’une tumeur au sein d’un tissu, les cellules cancéreuses se retrouvent entourées par les cellules saines. Les interactions entre ces deux types cellulaires, transformé et normal, jouent un rôle important dans le devenir de la tumeur, mais restent à ce jour mal comprises. L’objectif de cette thèse a été de mettre en place des systèmes in vitro qui permettent d’étudier les interactions entre une population de cellules normales et une population de cellules transformées.Nous avons tiré profit d’une lignée de cellules épithéliales sensibles à la lumière, élaborée par Olivier Destaing (IAB, Grenoble). Lorsqu’elles sont exposées à la lumière bleue, ces cellules suractivent la protéine Src, connue pour être surexprimée dans de nombreux cancers. Sinon, elles gardent un phénotype normal. L’utilisation de ces cellules, appelées « OptoSrc », combinée à un dispositif optique, permet de créer des tissus mosaïques dans lesquels le motif des cellules mutées est déterminé par le motif d’illumination bleue. Notre système présente plusieurs avantages : le contrôle dans le temps et dans l’espace du motif de cellules transformées, mais aussi l’activation graduelle et réversible de l’oncoprotéine.Nous avons montré qu’en illuminant dans le bleu un îlot circulaire de cellules au sein d’une monocouche OptoSrc, les cellules activées s’extrudent collectivement, donnant naissance à un agrégat tri-dimensionnel cohésif surplombant la monocouche. Nous pouvons contrôler la taille et le temps d’apparition de ce sphéroïde en ajustant respectivement l’aire éclairée et la fréquence d’illumination. De plus, ce phénomène d’extrusion collective est réversible lorsque le stimulus de lumière bleue s’arrête. Finalement, nous avons montré que la formation de cet agrégat s’accompagne d’une diminution des E-cadhérines à la membrane, et de l’apparition de la vimentine, pour les cellules éclairées. Nos résultats suggèrent qu'un groupe de cellules surexprimant la protéine Src, au sein d’une monocouche de cellules normales, subit une transition epithéliale- mesenchymateuse partielleDuring the development of a tumour in a tissue, the cancer cells are surrounded by healthy cells. The interactions between these two cell types, transformed and normal, play an important role in the tumour stability, but remain to this day poorly understood. The aim of this thesis was to establish in vitro assays to study the interactions between populations of normal and transformed cells.We benefited from a light-sensitive cell line, constructed by Olivier Destaing (IAB, Grenoble). When they are exposed to blue light, these cells overactivate the protein Src, which is known to be overexpressed in many cancers. Otherwise, they keep a normal phenotype. Using these cells, called “OptoSrc”, in combination with an optical setup, we are able to create mosaic tissues in which the pattern of mutated cells is determined by the blue illumination pattern. Our system has several advantages: a selective control in time and space of the group of transformed cells, and a gradual and reversible activation of the oncoprotein.We have shown that when we illuminate a circular islet of cells from a monolayer of OptoSrc cells, the activated cells were collectively extruded, resulting in a cohesive three-dimensional aggregate on top of the monolayer. We can control the size and appearance time of this spheroid by tuning, respectively, the area and frequency of illumination. Besides, this collective extrusion is reversible when the blue light stimulation is stopped. Finally, we have shown that the formation of this three-dimensional aggregate coincides with the loss of E-cadherin at the membrane, as well as the apparition of vimentin, for the illuminated OptoSrc cells. Our results suggest that a group of cells overexpressing the protein Src, in a monolayer of normal cells, undergoes a partial epithelial-to-mesenchymal transition
28
Collura, Ada. "Rôle de la protéine Crb2 dans les systèmes de surveillance de l'intégrité du génome chez Schizosaccharomyces pombe." Paris 11, 2005. http://www.theses.fr/2005PA112104.
Full textAbstract:
En présence de lésions de l'ADN ou de perturbations dans la phase de réplication ou encore dans l'attachement des microtubules aux centromères pendant la mitose, les cellules de S. Pombe comme toutes les cellules eucaryotes, induisent l'activation du système de surveillance de la réparation, de la réplication et du fuseau mitotique. La fonction de ces systèmes de surveillance est d'inhiber ou de ralentir la progression du cycle cellulaire si une anomalie dans un de ces processus cellulaires est détectée. Ceci permettra à la cellule de résoudre le problème rencontré sans que la transmission de l'information génétique d'une cellule mère aux cellules filles soit mise en péril. . Au cours de mon travail de thèse, j'ai étudié, d'une part l'allèle Dset1 de S. Pombe, déficient dans la méthyltransferase spécifique de la lysine 4 de l'histone H3, en analysant l'effet de mutations des gènes checkpoint en réponse à différents traitements génotoxiques de la souche Dset1. D'autre part, je me suis intéressée à la caractérisation d'une nouvelle fonction de la protéine Crb2 de S. Pombe. La protéine Crb2 est la protéine nécessaire pour l'activation de la kinase Chk1 en réponse à l'activation du checkpoint de la réparation. Dans cette activation elle joue le rôle de protéine adaptatrice, permettant le recrutement de Chk1 à proximité de la kinase Rad3 afin que la phosphorylation de Chk1 par Rad3 soit efficace. Crb2 est aussi nécessaire pour la survie cellulaire en réponse à l'exposition chronique à l'hydroxyurée ou en cas d'inhibition des ADN polymérasesThe appearance of DNA lesions or problems during the replicative phase or during microtubule attachment to centromeres during mitosis in Schizosacharomyces pombe, like in all other eucaryotes, all result in the activation of checkpoint systems responsible for DNA repair, and for correct DNA replication and mitotic spindle assembly. When anomalies in one of these cellular processes are detected, the different checkpoint systems can nhibit or retard cell cycle progression, thus allowing the cell machinery to repair the problem encountered without affecting the transmission of genetic information to the daughter cells. During my PhD, I have studied, on one hand, the Dset1 allele of S. Pombe, an allele which is deficient in methyltransferase activity towards lysine 4 of the histone H3. More specifically, I have studied the effect of mutations in checkpoint genes on the response of the Dset1 strain to different genotoxic treatments. I have also investigated a new function assigned to the Crb2 protein of S. Pombe. This protein is essential for the activation of the Chk1 kinase after induction of the DNA repair checkpoint. In this pathway Crb2 plays the role of an adapter, recruiting Chk1 to the vicinity of the Rad3 kinase, thus enhancing Chk1 phosphorylation by Rad3. The Crb2 protein is also necessary for cell survival in response to chronic exposure to hydroxyurea or to DNA polymerase inhibition
29
Bowen, Galo Emilio. "Service and Ultimate Limit State Flexural Behavior of One-Way Concrete Slabs Reinforced with Corrosion-Resistant Reinforcing Bars." Thesis, Virginia Tech, 2013. http://hdl.handle.net/10919/23205.
Full textAbstract:
This paper presents results of an experimental investigation to study the structural performance and deformability of a concrete bridge deck reinforced with corrosion resistant reinforcing (CRR) bars, i.e., bars that exhibit improved corrosion resistance when embedded in concrete as compared to traditional black steel. Flexural tests of one-way slabs were conducted to simulate negative transverse flexure over a bridge girder as assumed in the commonly employed strip design method. The bar types studied were Grade 60 (uncoated), epoxy-coated reinforcing (ECR, Grade 60), Enduramet 32 stainless steel, 2304 stainless steel, MMFX2, and glass fiber reinforced polymer (GFRP). The experimental program was designed to evaluate how a one-to-one replacement of the Grade 60 with CRR, a reduction of concrete top clear cover, and a reduction in bar quantities in the bridge deck top mat influences flexural performance at service and ultimate limit states. Moment-curvature predictions from the computer-based sectional analysis program Response 2000 were consistent with the tested results, demonstrating its viability for use with high strength and non-metallic bar without a defined yield plateau. Deformability of the concrete slab-strip specimens was defined with ultimate-to-service level ratios of midspan deflection and curvature. The MMFX2 and Enduramet 32 one-to-one replacement specimens had deformability consistent with the Grade 60 controls, demonstrating that bridge deck slabs employing high strength reinforcement without a defined yield plateau can still provide sufficient ductility at an ultimate limit state. A reduction in bar quantity and cover provided acceptable levels of ductility for the 2304 specimens and MMFX2 reinforced slabs.
Master of Science
30
BOUILLIE, SYLVIE. "Contribution a l'analyse moleculaire du role du recepteur pour le virus d'epstein-barr et pour le c3d (cr2, cd21) : identification des voies intracellulaires de signalisation regulees par le cr2 dans les lymphocytes b humains." Paris 6, 1998. http://www.theses.fr/1998PA066426.
Full textAbstract:
Le cr2, recepteur pour le c3d et le virus d'epstein-barr, est implique dans la regulation de la proliferation et de la transformation des lymphocytes b humains. Nous avons precedemment demontre que le c3d humain et le pep16 induisent dans les lymphocytes b humains la phosphorylation d'une proteine intracellulaire d'un poids moleculaire apparent de 105 kda. En etudiant l'effet de ses autres ligands (la proteine de l'enveloppe virale, gp350 ou l'anticorps monoclonal anti-cr2, okb-7) et le role du complexe cr2/cd19/tapa-1 dans la regulation de la phosphorylation de pp105, nous montrons que la phosphorylation de pp105 est induite uniquement par les ligands du cr2 qui controlent positivement la proliferation des lymphocytes b. De plus, la phosphorylation de pp105 induite lors de l'activation du cr2 est regulee selon deux voies distinctes : la premiere necessite la presence de cd19 non active, la seconde est independante de cd19. Les deux voies sont independantes de tapa-1. En utilisant un peptide synthetique dont la sequence est issue du domaine intracellulaire du cr2, nous avons mis en evidence que le domaine intracellulaire du cr2 est implique dans la regulation de la proliferation des lymphocytes b induite par l'ebv et par le c3d. Par ailleurs, nous avons montre que l'activation du cr2 regule l'activite catalytique de la pi 3-kinase ainsi que l'association de la sous-unite regulatrice de la pi 3-kinase, p85, avec un proteine phosphorylee sur tyrosine d'une masse moleculaire apparente de 95 kda, p95. L'utilisation de proteines de fusion nous a permis de montrer que p95 interagit directement avec le domaine sh2 de p85 pi 3-kinase. La cinetique de la phosphorylation de p95 est parallele a la cinetique d'activation de la pi 3-kinase. En depit d'une masse moleculaire apparente identique, p95 n'est pas l'antigene cd19 ou le proto-oncogene vav. L'ensemble de ces resultats demontre que la signalisation intracellulaire regulee par le cr2 est differente de celle du cd19.
31
Mond, Michael [Verfasser]. "Cr2+-dotierte Chalkogenide - Neue durchstimmbare Festkörperlaser und passive Güteschalter im mittleren infraroten Spektralbereich / Michael Mond." Aachen : Shaker, 2003. http://d-nb.info/1172611653/34.
Full text
32
Figueiredo, Camila Soares. "Interação das proteínas CRY1, CRY2 E VIP3 de Bacillus thuringiensis no controle de Anticarsia gemmatalis, Chrysodeixis includens e Spodoptera frugiperda /." Jaboticabal, 2017. http://hdl.handle.net/11449/149877.
Full textAbstract:
Orientador: Janete Apparecida DesidérioBanca: Vivian Boter Bergamasco
Banca: Sonia Marli Zingaretti
Banca: Odair Aprecido Fernandes
Banca: Ana Maria Guidelli Thuler
Resumo: Este trabalho teve como objetivo estudar a toxicidade e a interação entre proteínas Cry1Ab, Cry1Ac, Cry2Aa, Cry2Ab e Vip3Aa em lagartas neonatas de Anticarsia gemmatalis, Chrysodeixis includens e Spodoptera frugiperda. Lisados das proteínas foram utilizados em bioensaios com lagartas neonatas para determinar a CL50 e CL90 das proteínas Cry1Ab, Cry1Ac, Cry2Aa, Cry2Ab e Vip3Aa e realizar experimentos histopatológicos. Ensaios de competição, entre as proteínas Cry1, Cry2 e Vip3 biotiniladas, foram realizados com as proteínas das vesículas de membrana da microvilosidade apical do intestino médio ("Brush Border Membrane Vesicles" - BBMV) das lagartas. Foi feita a purificação de receptores para toxina Cry1Ac a partir da BBMV de A. gemmatalis e C. includens por afinidade seguida da identificação das proteínas ligantes. As toxinas Cry1A e Cry2A demonstraram maior toxicidade para A. gemmatalis e C. includens que a proteína Vip3Aa, porém o inverso foi observado em S. frugiperda. As lagartas da espécie A. gemmatalis se mostraram mais suscetíveis as proteínas testadas do que as de S. frugiperda e C. includens. As espécies diferiram também quanto ao tipo de interação entre as toxinas. Enquanto para S. frugiperda e C. includens, as interações foram sinérgicas, para A. gemmatalis foram predominantemente antagônicas. As proteínas se uniram aos receptores presentes nas BBMV de S. frugiperda, A. gemmatalis e C. includens, permitindo inferir sobre a presença e ausência de comp... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: This work aimed to study the toxicity and interaction between Cry1Ab, Cry1Ac, Cry2Aa, Cry2Ab and Vip3Aa proteins in neonate larvae of Spodoptera frugiperda, Anticarsia gemmatalis and Chrysodeixis includens. Lysates containing proteins were used in bioassays for the determination of LC50 and LC90 of the Cry1Ab, Cry1Ac, Cry2Aa, Cry2Ab and Vip3Aa proteins. Histopathological experiments were realized with A. gemmatalis, C. includens (fed with Cry1Ac and Vip3Aa) and S frugiperda (fed with Cry1Ab and Vip3Aa). Competition assays, among biotinylated Cry1, Cry2 and Vip3 proteins, were performed with brush border membrane vesicles (BBMV) proteins from A. gemmatalis, C. includens and S. frugiperda. Purification of Cry1Ac receptors from A. gemmatalis and C. includens BBMV was performed by affinity followed by identification of binding proteins. The Cry1A and Cry2A toxins demonstrated higher toxicity to A. gemmatalis and C. includens than the Vip3Aa protein, but the inverse was observed to S. frugiperda. A. gemmatalis larvae were more susceptible as Cry and Vip proteins than as S. frugiperda and C. includens. Species differed about type of protoxins interaction. While for S. frugiperda and C. includens, the protoxins showed as synergistic interactions, for A. gemmatalis they were predominantly antagonistic. It was possible to infer about presence and absence of competition of the receptors in the BBMV from S. frugiperda, A. gemmatalis and C. includens. Histopathological changes as vacuolization and disruption were observed in the intestine from S. frugiperda larvae, fed with Cry1Ab and Vip3Aa and A. gemmatalis and C. includens, fed with Cry1Ac and Vip3Aa. Putative receptors were to identified from A. gemmatalis and C. includens to Cry1Ac toxin. The combination of Cry and Vip proteins, as well as helping to manage resistance and can increase toxicity through synergistic acti... (Complete abstract electronic access below)
Doutor
33
Powell, Rebecca. "Synaptotoxicité dans la maladie d'Alzheimer : Influence du processing d'APP sur les synapses excitatrices Involvement of CRF2 signaling in enterocyte Differentiation." Thesis, Université Grenoble Alpes (ComUE), 2019. http://www.theses.fr/2019GREAV051.
Full textAbstract:
La maladie d’Alzheimer (MA) est définie comme une maladie neurodégénérative où des altérations synaptiques mènent à la perte neuronale parallèlement à des défauts de mémoire et d’apprentissage. Il est établi que les dysfonctions synaptiques observées dans la MA sont initiées par les formes oligomériques du peptide β-amyloïde (Aβ), un dérivé protéolytique de l’Amyloid Precursor Protein (APP). Cependant, le chemin qu’empreinte Aβ, selon son origine intra- ou extracellulaire, afin d’induire ces effets délétères et la façon dont ses effets sont maintenus et se propagent dans le cerveau restent encore à définir.Dans cette étude, nous avons utilisé plusieurs formes mutées de l’APP qui conduisent à des peptides Aβ avec des signatures moléculaires uniques, tel que : la mutation Swedish (K670M/N671L) (APPswe) qui augmentent la sécrétion (extracellulaire) d’Aβ; la mutation Osaka (E693Δ) (APPosa) qui cause une accumulation intraneuronale (intracellulaire) d’Aβ; ainsi que la mutation Icelandic (A673T) (APPice) qui a été établi comme diminuant la production d’Aβ et protégeant contre la MA. Ces formes mutées d’APP ont été surexprimées dans des cultures de neurones corticaux murins et on permit : i) d’étudier la morphologie et fonction des épines dendritiques, l’élément post-synaptique, par microscopie confocale; ii) de tenter de mieux comprendre comment la pathologie se développe et se propage dans le cerveau et iii) d’identifier un nouveau partenaire d’intéraction avec l’Aβ faisant la lumière sur un possible rôle physiologique de ce peptide dans les neurones.Nous montrons qu’une accumulation pathologique d’Aβ, due à la surexpression d’APPwt, APPswe et APPosa mais pas APPice, induit une diminution significative de la densité synaptique particulièrement celle des épines les plus fonctionnelles, dites « mushroom ». Ses épines mushroom restantes présentent également une augmentation significative de leur volume et il semblerait que l’Aβ intracellulaire soit suffisant pour induire ses effets. Ses épines mushroom élargies présentent également une plasticité structurale altérée puisqu’elles n’ont pas augmenté d’avantage de volume à la suite d’une activation synaptique. Il semblerait que ceci soit la résultante d’un défaut de la dynamique activité-dépendante du cytosquelette d’actine dans les épines. Ces altérations de la morphologie, structure et plasticité synaptique serait dû à une intéraction, nouvellement identifiée, de l’Aβ avec l’actine et pourrait faire lumière sur un possible rôle physiologique de l’Aβ dans la plasticité synaptique activité-dépendante. De plus, nous montrons que le clivage amyloïde de l’APP est aussi activité-dépendant et que la séquence du peptide Aβ généré est aussi importante, dans l’induction de la synaptotoxicité, que sa concentration. En effet, car nous montrons que des concentrations pathologiques du peptide Aβice n’engendrent pas de perte ou de gonflement des épines mushroom. Enfin, nous mettons en lumière que l’Aβ sécrété dans le milieu extracellulaire affecte, non seulement le neurone sécrétant lui-même, mais aussi la densité synaptique des neurones sains avoisinant (qui ne surexpriment pas d’APP) d’une manière APP-dépendante, rappelant un mécanisme de propagation du type prion. L’ensemble de ces données démontrent que le clivage protéolytique de l’APP et la production d’Aβ qui en découle est un processus finement accordé, impliqué dans le remodelage de l’actine dans la plasticité synaptique activité-dépendante et ouvre de nouvelles voies pour le développement de stratégies thérapeutiques contre la MAAlzheimer’s disease (AD) is defined as a neurodegenerative disorder where synaptic defects lead to neuronal loss and concurrent memory impairments. It is now well-established that synaptic dysfunction in AD is initiated by oligomeric forms of the amyloid-β peptide (Aβ), a proteolytic derivative of Amyloid Precursor Protein (APP). However, the pathway by which Aβ induces its deleterious effects, whether it is due to intra- and/or extracellular Aβ pools, and how these effects are sustained and propagated throughout the brain, are still unclear.In this study, we used several mutated forms of APP which give rise to Aβ peptides with unique molecular signatures, such as: the Swedish mutation (K670M/N671L) (APPswe) which increases secreted (extracellular) Aβ; the Osaka mutation (E693Δ) (APPosa) which causes intraneuronal (intracellular) accumulation of Aβ; and the Icelandic mutation (A673T) (APPice) which has been reported to decrease Aβ production and protect against AD. These mutated forms of APP were overexpressed in cultured mouse cortical neurons in order to: i) study the morphology and function of dendritic spines, the post-synaptic element of synapses, by confocal microscopy, ii) get a better insight into pathology development and propagation and iii) identify a novel interacting partner bringing to light the possible physiologic role of Aβ in neurons.We report that pathological Aβ accumulation, due to APPwt, APPswe and APPosa overexpression but not APPice overexpression induces a significant decrease in spine density especially mushroom spines, accompanied by a significantly increased volume of the remaining mushroom spines, and that intracellular Aβ is sufficient to induce these effects. These enlarged mushroom spines have impaired structural plasticity as they did not increase in volume following synaptic activation seemingly as a result of defective activity-dependent actin dynamics in the spines. This alteration of synaptic morphology, structure and plasticity seems to be due to a newly-identified interaction between actin and Aβ, hinting a possible physiological role for Aβ in activity-dependent synaptic plasticity. We also show that synaptic activity modulates amyloïdogenic APP processing which, in pathological conditions, further exacerbates these synaptic defects. Furthermore, we show that Aβ sequence is as important as Aβ concentration in inducing synaptic alterations since pathological concentrations of Aβ harbouring the Icelandic mutation had no effect on spine density or volume. Lastly, we bring to light that secreted Aβ, not only affects the Aβ-secreting neuron itself, but also affects spine density of nearby neurons in an APP-dependent manner, reminiscent of a prion-like mechanism. Together these results demonstrate that APP processing is a finely tuned equilibrium involved in actin-remodelling during activity-dependent synaptic plasticity and opens a new route for AD therapeutic strategies
34
持田, 悟. "DNA損傷チェックポイントの二つのキナーゼと相互作用するCrb2の研究." 京都大学 (Kyoto University), 2004. http://hdl.handle.net/2433/147896.
Full text
35
Regnat, Alexander [Verfasser], Christian [Akademischer Betreuer] Pfleiderer, Christian [Gutachter] Pfleiderer, and Christian [Gutachter] Back. "Low-temperature properties and magnetic structure of CrB2, MnB2, and CuMnSb / Alexander Regnat ; Gutachter: Christian Pfleiderer, Christian Back ; Betreuer: Christian Pfleiderer." München : Universitätsbibliothek der TU München, 2019. http://d-nb.info/1214368506/34.
Full text
36
Spinieli, Richard Leandro. "Avaliação do envolvimento de receptores específicos para o fator liberador de corticotropina CRF1 e CRF2 dos núcleos basolateral e central da amígdala no comportamento de imobilidade tônica em cobaias (Cavia porcellus)." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/59/59134/tde-26062014-140049/.
Full textAbstract:
A resposta comportamental de Imobilidade Tônica (IT) ocorre em situações de perigo intenso, e em situações inescapáveis, como por exemplo,o ataque de um predador. Esta resposta caracteriza-se por perda do reflexo de endireitamento e relativa falta de responsividade aos estímulos ambientais. Estudos consistentes tem demonstrado o envolvimento de distintas áreas encefálicas na modulação desta resposta, entre elas a substância cinzenta periaquedutal, o hipotálamo e a amígdala. Considerando a amígdala em particular, estudos mostraram o envolvimento dos receptores para o fator liberador de corticotropina (CRF) dos núcleos basolateral (BLA) e central (CeA) na modulação da resposta de IT em cobaias. De fato, nas últimas décadas, várias evidências sugerem que o CRF está intimamente correlacionado com comportamento emocional associado ao medo e à ansiedade. Embora seja claro o envolvimento de receptores CRF na modulação do medo, e especificamente na modulação da IT em cobaias, ainda não está esclarecido o envolvimento dos diferentes subtipos de receptores para CRF na modulação emocional. Desta forma, o objetivo deste trabalho foi investigar o envolvimento dos receptores específicos para o fator liberador de corticotropina, CRF1 e CRF2 dos núcleos basolateral (BLA) e central da amígdala (CeA) na modulação da resposta de IT em cobaias.Para atingir estes objetivos, grupos independentes de cobaias, com implante de cânulas-guias dirigidas para o BLA ou para o CeA foram avaliadas no teste de imobilidade tônica, antes e depois da administração dos antagonistas específicos para receptores CRF1 (CP-376395) ou para receptores CRF2 (Astressin 2B), ou depois da administração de CRF precedido ou não dos antagonistas CRF1 ou CRF2. Em adição, para avaliar se as drogas utilizadas alteraram a atividade locomotora, foi realizado o teste do campo aberto, por 5 minutos, após a administração dos antagonistas para receptores CRF1 (CP-376395) e CRF2 (Astressin 2B), em doses capazes de alterar a resposta de IT em cobaias, e de CRF precedido por antagonista CRF1 ou CRF2. Os resultados deste trabalho mostram que o bloqueio dos receptores CRF1 e CRF2 no BLA e no CeA reduziram a duração da resposta defensiva de imobilidade tônica (IT) em cobaias. Inversamente, a ativação destes receptores no BLA e no CeA aumentou o tempo de IT, demonstrado pela administração de CRF nestas regiões amigdalóides. Ainda, os antagonistas específicos para receptores CRF1 e CRF2 foram capazes de bloquear o aumento da duração da IT induzida pelo CRF administrado no mesmo sítio. Estes resultados sugerem que o efeito promovido pelo CRF no BLA e no CeA ocorre por atuação conjunta em receptores CRF1 e CRF2. Em adição, é importante ressaltar que as drogas, nas doses utilizadas neste estudo, não promoveram alteração da resposta motora, desde que não alteraram a atividade no teste do campo aberto, o que por si só, poderia alterar a resposta de IT. Assim, é possível que sugerir que o bloqueio específico de receptores CRF1 e CRF2 do BLA e do CeA promovem redução do medo e/ou da ansiedade, resultando em redução da resposta de IT em cobaias.The tonic immobility response (TI ) occurs in inescapable situations of intense danger, such as the predator attack. This response is characterized by loss of righting reflex and the relative lack of responsiveness to environmental stimuli. Consistent studies have demonstrated the involvement of different brain areas to modulate this defensive behavior, including the periaqueductal gray matter, hypothalamus and amygdala. Whereas the amygdala in particular, studies have shown the involvement of receptors for corticotropin-releasing factor (CRF) of the central (CeA) and basolateral (BLA) nuclei os amygdala in TI modulating in guinea pigs. Indeed, in recent decades, several evidences suggest that CRF is closely correlated with emotional behavior associated with fear and anxiety. While it is clear the involvement of CRF receptors in the modulation of fear, and specifically in the modulation of TI, it is still unclear the involvement of different subtypes of CRF receptors in the emotional modulation. Thus, the aim of this study was to investigate the involvement of specific receptors for corticotropin-releasing factor, CRF1 and CRF2of BLA and of CeA in modulating the TI response in guinea pigs. To achieve these objectives, independent groups of guinea pigs were implanted with guide cannulae aimed for BLA or CeA were evaluated in the test of tonic immobility before and after the administration of specific antagonists of CRF1 receptors (CP- 376395) or CRF2 receptors (Astressin 2B), or after the administration of CRF preceded by CRF1or CRF2 antagonists, or CRF per se. In addition, to assess whether the drugs used altered locomotor activity, the open field test, for 5 minutes was performed after administration of antagonists for CRF1 receptors (CP- 376395) and CRF2 (Astressin 2B), at doses that alter the TI response in guinea pigs, and the CRF agonist preceded by CRF1 or CRF2. These results show that blockade of CRF1 and CRF2 receptors in the BLA and CeA reduced the duration of the defensive response of tonic immobility (TI) in guinea pigs. In contrast, activation of these receptors in the BLA and CeA increased the TI duration, demonstrated by administration of CRF in these amygdaloid regions. Also, specific antagonists for CRF1 and CRF2 receptors were able to block the increase in the TI response induced by CRF administered in the same structure. These results suggest that the effect promoted by CRF in the BLA and CeA is by joint performance of CRF1 and CRF2 receptors. Additionally, it is important to note that the drugs, in the doses used in this study, did not promote change in the motor response, since it did not alter the activity in the open field test, which by itself could alter the TI response. Thus, it is possible to suggest that the specific blockade of CRF1 and CRF2 receptors in the BLA and CeA promote reduction of fear and/or anxiety, resulting in reduced TI response in guinea pigs.
37
Masilamani, Madhan. "Immunological investigation of human complement receptor type II (CR2/CD21) : serum soluble CD21 in health and disease /." Konstanz, 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=967076668.
Full text
38
Cruickshank, Mark. "Analysis of CR2/CD21 transcriptional regulation by chromatin structural variation and notch activity in human cell models." University of Western Australia. School of Biomedical, Biomolecular and Chemical Sciences, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0115.
Full textAbstract:
[Truncated abstract] Human complement receptor 2 (CR2/CD21) is a cell surface glycoprotein detected on specific cells involved in immunity, which binds complement C3 cleavage fragments, cellular ligands IFN-? and CD23 as well as the EBV coat protein, gp350/220. During the early stages of B-cell development CR2/CD21 is silenced. Expression is initiated on immature B-cells escaping negative selection. During peripheral maturation CR2/CD21 is up-regulated with B-cell sub-populations showing distinctive surface levels (comparatively low, intermediate or high). CR2/CD21 is silenced upon terminal plasmacytic differentiation. Appropriate timing and expression level of CR2/CD21 is important for the development of a healthy B-cell repertoire. Previous studies have identified sequences within the proximal promoter and first intron of CR2/CD21 that cooperate within native chromatin to control cell-specific silencing. Further, analysis of cultured human cells has revealed chromatin structural variation causing DNase I hypersensitivity at these regulatory sites in a CR2/CD21-expressing mature B-cell line (Raji) which are absent in a non-lymphoid cell type (K562). The primary focus of the present study involved characterising chromatin structural variation over previously recognized DNase I hypersensitive regions at the CR2/CD21 locus in human cells to understand how chromatin structure might regulate developmental expression of CR2/CD21. ... These studies provide evidence that notch signaling influences CR2/CD21 expression in human cell lines. First, in vivo binding of CBF1 to CR2/CD21 sequences in the proximal promoter and CRS implies that CR2/CD21 is a direct target of notch activation. Second, the effect of exogenous notch signalling molecules on CR2/CD21 proximal promoter activity was modulated by factors binding tandem E-boxes near the transcriptional start site suggesting that the notch pathway may also influence CR2/CD21 expression via control of HLH molecules. Third, initiation of CR2/CD21 expression was observed in a nonexpressing pre-B cell line (Reh) by co-culture with stromal cells expressing a notch ligand (OP9-DL) but not control stroma (OP9-GFP). Together, these findings support a role for notch regulation of B-cell maturation and invite speculation that initiation of CR2/CD21 expression following negative selection of immature B-cells involves crosstalk between HLH transcriptional regulators and the notch pathway. Furthermore, the Reh/OP9-DL co-culture system may provide a model to directly study the relationship between cell signalling molecules, transcription factor regulation, chromatin structural variation and differentiation of B-cells.
39
Måssebäck, Simon. "A comparison of the IRB approach and the Standard Approach under CRR for purchased defaulted retail exposures." Thesis, KTH, Matematisk statistik, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-150546.
Full textAbstract:
We investigate under what circumstances the IRB approach under Regulation (EU) no 575/2013 (Capital Requirements Regulation) renders a lower capital requirement for purchased defaulted retail exposures than under the Standard Approach of the same regulation. We also discuss some alternative approaches to calculating the capital requirement for the mentioned exposures. The results show that it is only beneficial in a few cases to use the IRB approach compared to the Standard Approach. We can also see that the IRB approach in some cases renders a capital requirement that is clearly not reflecting the actual risk. Of the alternative approaches investigated, a Value-at-Risk approach seems most promising for further development.Vi undersöker under vilka omständigheter Internmetoden enligt Förordning (EU) nr 575/2013 (tillsynsförordningen) ger ett lägre kapitalkrav för förvärvade fallerande hushållsexponeringar än Schablonmetoden enligt samma förordning. Vi diskuterar också några alternativa metoder för att beräkna kapitalkravet för de nämnda exponeringarna. Resultaten visar att det bara är fördelaktigt i ett fåtal fall att använda Internmetoden jämfört med Schablonmetoden. Vi kan också se att Internmetoden ger ett kapitalkrav i vissa fall som tydligt inte återspeglar den faktiska risken. Av de alternativa metoder som undersökts ser en Value-at-Risk-metod mest lovande ut för fortsatt utveckling.
40
Thorel, Nathalie. "Rôle du complément dans la réaction inflammatoire gliale : contribution à l'étude du CR2/CD21 et du GPR176." Rouen, 2009. http://www.theses.fr/2009ROUES041.
Full textAbstract:
Dans le but d'approfondir le rôle des anaphylatoxines dans le système nerveux central, nous avons stimulé des cellules T98G par le C3a ce qui a conduit à la découverte de deux molécules. Le CR2 est présent sur les astrocytes mais sa fonction est inconnue. Nous avons produit un anticorps monoclonal capable d'activer le CR2 astrocytaire qui s'associe à TAPA-1 et à la caldesmone qui sont connus pour arrêter la prolifération cellulaire. Ensuite, nous avons étudié le GPR176 dont le ligand est inconnu. Des animaux ont été immunisés selon quatre protocoles mais nous n'avons pas pu obtenir d'anticorps. Le GPR176 est principalement exprimé au niveau du système nerveux. Nous avons produit une lignée stable qui permettra de découvrir son ligand. L'ensemble de ces résultats ne nous a pas permis de corréler le complexe CR2/TAPA-1 et le GPR176 avec la réaction inflammatoire gliale mais les résultats obtenus sur le CR2 supposent une action de ce récepteur dans la formation de la cicatrice glialeIn order to decipher the function of anaphylatoxins in the central nervous system, we stimulated glioblastomas cells with C3a which leads us to the discovery of two molecules induced by C3a. CR2 is expressed on astrocytes but its function is unknown. We produced a monoclonal antibody which can activate astrocytic CR2 which translocates with TAPA-1 and with the non-muscle caldesmon. These proteins are known to arrest cell migration. In a second part, we study the GPR176 whose ligand is unknown. We immunized rabbits and mice with four protocols but we failed to obtain an antibody. We localized GPR176 in the central nervous system and particularly in the lombar spinal cord and in locus coeruleus. We produced a stable cell line which will be used in ligand finding. These results don't show an interaction between the complex TAPA-1/CR2 and GPR176 with glial inflammation but findings obtained with CR2 suppose a role of this receptor in promoting glial scar formation
41
Rouibi, Khalil Adnane. "Dépendance aux drogues opiacées : focus sur le système corticotropin-releasing factor." Thesis, Bordeaux 1, 2011. http://www.theses.fr/2011BOR14434/document.
Full textAbstract:
La prise illicite de drogues opiacées est un problème majeur de santé publique dans le monde. L’apparition du syndrome de sevrage aux opiacés (SAO) suite à l’arrêt de prise d’opiacés est considérée comme élément clef dans la vulnérabilité associée à la rechute de prise d’opiacés. En effet le syndrome de SAO est caractérisé par des altérations comportementales et neurobiologiques en réponse au stress qui sont déterminantes dans le phénomène de dépendance aux opiacés. Le système corticotropin-releasing factor (CRF) est un coordinateur central des circuits de réponse au stress par l’intermédiaire de ses deux récepteurs le: CRF1 et CRF2. L’objectif de cette thèse est de déterminer le rôle du récepteur CRF2 dans l’apparition des états affectifs négatifs et des désordres motivationnels impliqués dans la rechute de la consommation de drogues opioïdes lors du SAO.Nous avons démontré par une série d’expériences conduite chez des souris invalidées au récepteur CRF2 (CRF2-/-), que la délétion génétique du récepteur CRF2-/- éliminait les états dysphoriques ainsi que les altérations moléculaires induites par le SAO sans détériorer les réponses neuroendocriniennes qui sont primordiales lors des adaptations aux stress associées au sevrage. De surcroît, nous avons trouvé que les souris CRF2-/- entrainées dans une procédure de tâche opérante dirigée vers l’obtention d’une nourriture palatable, montraient une diminution des troubles motivationnels induits par le SAO. Plusieurs rapports montrent que chez l’Homme, les évènements stressants apparaissant lors d’une période de sevrage provoquent une rechute de la consommation d’alcool ou de drogues. Nous avons développé un modèle murin qui montrait un rétablissement de recherche de nourriture palatable suite à une procédure de stress appliquée pendant une période de SAO. Par ailleurs, nous avons observé un dimorphisme sexuel du rôle du récepteur CRF2 dans le rétablissement de recherche de nourriture palatable, suite au stress, longtemps après un SAO.Les résultats de ce travail de thèse nous permettent de mettre en avant le récepteur CRF2 comme possible cible thérapeutique dans le traitement de la dépendance aux opiacésOpiate illicit use represents one of the most severe sanitary problems throughout the world. Among humans, the emergence of the opiate withdrawal (OW) syndrome after cessation of opiate intake is considered as one of the key motivational elements that lead to the vulnerability to opiates relapse. Therefore, the OW is characterized by a various alterations of the behavioral and neurobiological homeostasis responses to stress which are determinants in opiate dependence. The Corticotropin-releasing factor (CRF) system is the major coordinator of stress-responsive circuitry. Through its two receptors CRF1 and CRF2, the CRF system has recently emerged as major contributor in the development of components of the OW syndrome. The aim of this thesis is to determine the role of CRF2 receptor in the negative affective states and motivational disorders implicated in opiate relapse during OW.Behavioral and biological experiments were conducted in CRF2 receptor-deficient mice (CRF2-/-). We reported that genetic deletion of the CRF2 receptor eliminates dysphoria and molecular alterations elicited by OW without impairing brain, neuroendocrine and autonomic stress-coping responses to withdrawal. Using behavioral approaches of operant responding to highly palatable food (HPF) we found that CRF2-/- reduces motivational disorders induced by intermittent morphine injections and withdrawal. Finally, we described a mouse model of stress-induced food reinstatement seeking behavior during prolonged OW. Furthermore, we reported a gender dimorphism in the role of the CRF2 receptor in the stress-induced reinstatement of HPF seeking behavior long-lasing after opiate treatment.These findings underscore the importance of CRF2 receptor as possible effective treatment of the critical problem of opiate dependence
42
Vivet, Nicolas. "Elaboration et caractérisation de films minces Cr2+:ZnSe nanostructurés pour la fabrication de microlasers émettant dans le moyen infrarouge." Phd thesis, Université de Caen, 2008. http://tel.archives-ouvertes.fr/tel-00347093.
Full textAbstract:
Il existe une demande de plus en plus importante pour des sources laser bon marché émettant dans le moyen infrarouge (MIR) à température ambiante pour différentes applications incluant la détection des constituants atmosphériques, la communication optique et le domaine de la médecine. De part ses propriétés optiques et structurales, le Cr2+: ZnSe est devenu le candidat idéal pour une émission largement accordable dans la région 2-3 µm. Dans l'objectif de développer un laser compact pompé électriquement, des films minces de Cr2+:ZnSe ont été élaborés à température ambiante par pulvérisation magnétron radiofréquence d'une cible de SiO2 recouverte de morceaux de ZnSe et de chrome sous plasma d'argon pur, sur des substrats de verre, Si et GaAs.
Quelque soit le substrat, les films déposés sont constitués de ZnSe cubique quasi-stoechiométrique et présentent une structure colonnaire avec une forte orientation préférentielle dans la direction 111. Le recours à l'analyse combinée par diffraction X a permis de résoudre simultanément la texture, la structure et la microstructure d'un des films déposés. Le spectre de PL des films à température ambiante dans le domaine 2-3 µm, comparable à celui des cristaux de référence de Cr2+ :ZnSe, a été obtenu d'une part par excitation directe des ions Cr2+ (1.85 µm) et d'autre part par excitation indirecte en utilisant un laser visible. Les paramètres de dépôt (puissance radiofréquence, pression d'argon, quantité de chrome) ont été optimisés pour obtenir des films présentant une intensité de PL maximum dans le MIR.
43
MOUHOUB, AMAL. "Expression et fonction des recepteurs du complement cr1/cd35 et cr2/cd21 au cours de la maturation des lymphocytes t chez l'homme. Role de cr1 et cr2 dans l'induction de la replication virale dans les thymocytes et les lymphocytes t infectes par le vih." Paris 11, 1996. http://www.theses.fr/1996PA112334.
Full textAbstract:
Les recepteurs du complement cr1 (cd35, recepteur c3b) et cr2 (cd21, recepteur c3dg/ebv/cd23s/ifn-) permettent l'infection par le vih, de lignees lymphocytaires b et t, et des monocytes humains. Nous avons mis en evidence l'expression de cr1 et cr2 a la membrane des thymocytes humains. Le recepteur cr1 est exprime par 15% des thymocytes et le recepteur cr2 par 70% des thymocytes. Une sous-population de thymocytes (10 a 15%) exprime cr2 avec une intensite 10 fois superieure au reste des thymocytes, equivalente a celle des lymphocytes b. Etant donne toutes les caracteristiques fonctionnelles des recepteurs du complement a la membrane des lymphocytes b et des monocytes, cette donnee justifiait l'etude des proprietes fonctionnelles et immunoregulatrices de la molecule cd21 exprimee par les thymocytes humains. Nous avons caracterise les cellules exprimant cr2 dans le thymus: cr2 est exprime par les thymocytes a tous les stades de maturation, toutefois son expression diminue au fur et a mesure que les cellules se differencient. Les cellules exprimant cr2 sont des cellules de grande taille, incorporant le brdurd. L'expression de cr2 est plus forte a la membrane des cellules exprimant cd45ra qu'a la membrane des cellules exprimant cd45ro. Ces trois observations suggerent que, l'expression de cr2 serait liee a un etat d'activation de cellules quelque soit leur stade de maturation, et ouvrent des perspectives interessantes concernant le role de cr2 dans les phenomenes de selection. La capacite de cr2 a transmettre des signaux de phosphorylation et son eventuelle association a d'autres molecules membranaires, ont ete etudiees et ont montre que cr2 phosphoryle deux proteines de 50 et 18 kda, et pourrait etre associe a une proteine membranaire de 50 kda. Ces proprietes de cr2, si elles se confirment, pourraient indiquer que cr2 a un role dans la signalisation et par consequent dans la maturation des thymocytes humains. Cr1 et cr2 permettent l'infection par le vih-1 (rf) opsonise par les fragments de c3. L'infection est totalement bloquee par les recepteurs recombinants solubles cr1 et cr2, indiquant que l'infection serait independante de cd4. Leurs recepteurs ont un role dans l'entree du virus dans les cellules et pourraient jouer un role dans la pathogenese du sida. La stimulation du recepteur cr1 a la membrane des lymphocytes t cd4#+ peripheriques, infectes par le vih in vitro ou in vivo, entraine une augmentation de la replication virale. Le recepteur cr1 n'est pas modifie au cours de l'infection par le vih. Au cours du sida, l'interaction de cr1 avec les complexes immuns pourrait constituer un mecanisme supplementaire de reactivation virale
44
Morisot, Nadège. "La délétion génétique du récepteur corticotropin-releasing factor de type 2 réduit les déficits mnésiques et sociaux induits par la cocaïne." Thesis, Bordeaux 1, 2013. http://www.theses.fr/2013BOR15220.
Full textAbstract:
Les travaux de cette thèse visent à étudier le role du système corticotropin-releasing factor (CRF) dans les dysfonctions cognitives, les altérations du comportement social et la vulnérabilité au stress associées à l’addiction aux drogues. Les effets de la délétion génétique du récepteur CRF1 ou CRF2 sont examinés dans les tests de reconnaissance d’objet et de préférence sociale après une exposition chronique et pendant le sevrage à la cocaine. Le rôle du récepteur CRF2 dans la vulnérabilité au stress qui pourrait précipiter l’apparition de déficits cognitifs et sociaux pendant le sevrage prolongé à la cocaine est également étudiéStimulant-related disorders are characterized by emotional-like, cognitive and social dysfunction that may contribute to the maintenance of the disease. In addition, stimulant use and withdrawal may alter brain stress systems. The corticotropin-releasing factor (CRF) system is a major stress coordinator hypothesized to contribute to substance-related disorders. CRF signalling is mediated by two receptor types, named CRF1 and CRF2. The specific role of each of the CRF receptors in negative affective-like, cognitive and social dysfunction associated with stimulant administration and withdrawal remains largely unknown. The present study demonstrates that the CRF1 receptor-deficiency increases the anxiety-like behaviour induced by intermittent administration of escalating doses of cocaine (5-20 mg/kg, i.p.), as assessed by the elevated plus maze. In addition, the same cocaine regimen induces novel object recognition (NOR) and sociability deficits, which are unaffected by CRF2 receptor-deficiency. However, CRF2 receptor-deficiency effectively shortens the duration of the NOR and sociability deficit induced by cocaine withdrawal. Furthermore, following the apparent recovery of NOR and sociability performances during relative long-term (42 days) cocaine withdrawal, CRF2 receptor-deficiency eliminates the stress-induced re-emergence of NOR and sociability deficit. Stressed cocaine-withdrawn mice show a genotype-independent higher c-fos mRNA expression in the perirhinal cortex, a brain region mediating NOR performance, than stressed drug-naïve mice. However, neither genotype nor drug withdrawal affects the expression of tyrosine hydroxylase in the ventral tegmentale area and the locus coeruleus, CRF in the amygdala and the paraventricular nucleus of the hypothalamus and dynorphin in the nucleus accumbens shell. The latter results suggest that stress vulnerability during long-term cocaine withdrawal is not due to alterations in stress-coping mechanisms. The present study provides initial evidence of a critical role for the CRF system in cognitive and sociability deficits and vulnerability induced by stimulant administration and withdrawal, suggesting new therapeutic strategies for substance-related disorders
45
Souza, Priscila Queiroz Pires de. "Relógios biológicos e padrões de alimentação em camundongos normais e com sobrepeso." Universidade do Estado do Rio de Janeiro, 2011. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=3472.
Full textAbstract:
Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de JaneiroA saudável interação entre o indivíduo e o meio depende do alinhamento entre a dinâmica fisiológica do primeiro e os periódicos movimentos da natureza. A interação entre tais ritmos por sua vez constitui-se em base e derivação do processo de evolução. O comprometimento de tal alinhamento representa um risco para a sobrevivência das espécies. Neste contexto, os organismos alinham seus ritmos fisiológicos a diferentes ciclos externos. Desta forma, ciclos endógenos são coordenados por relógios biológicos que determinam em nosso organismo, específicos ritmos em fase com a natureza, tais como ritmos circadianos (RC), cujo período aproxima-se de 24 horas. O peso corporal, a ingestão de alimentos e o consumo de energia são processos caracterizados pelo RC e a obesidade está associada a uma dessincronização deste processo. A modulação do RC é resultado da expressão dos clock gens CLOCK e BMAL1 que formam um heterodímero responsável pela transcrição gênica de Per1, Per2, Per3, Cry1 e Cry2. As proteínas codificadas por estes genes, uma vez sintetizadas, formam dímeros (PER-CRY) no citoplasma que, a partir de determinada concentração, retornam ao núcleo, bloqueando a ação do heterodímero CLOCK/BMAL1 na transcrição dos próprios genes, formando assim uma alça de retroalimentação negativa de transcrição e tradução. Estes genes asseguram a periodicidade e são significativamente expressos no núcleo supraquiasmático (SCN) do hipotálamo. Para estudar esse processo em camundongos normais e hiperalimentados, saciados e em estado de fome, foi utilizado um método de registro do comportamento alimentar baseado no som produzido pela alimentação dos animais, e a correlação destes estados metabólicos com a expressão de CLOCK, BMAL1, Per1, Per2, Per3, bem como das proteínas Cry1 e Cry2 no SCN, por análise de imagens obtidas em microscopia confocal. Camundongos suíços controle em estado de fome (CF) e saciados (CS) foram comparados com animais hiperalimentados com fome (HF) e saciados (HS). Nenhum grupo demonstrou diferença nos conteúdos CLOCK e BMAL1, indicando capacidade potencial para modular os ritmos biológicos. No entanto, as proteínas Per1, Per2, Per3 e Cry1 apresentaram menor expressão no grupo CS, mostrando uma diferença significativa quando comparados com o grupo CF (P<0,05), diferença esta não encontrada na comparação entre os grupos HF e HS. A quantidade de proteína Cry2 não foi diferente na mesma comparação. Os resultados do estudo indicaram que as alterações dos ritmos endógenos e exógenos, refletido pelo comportamento hiperfágico observado em camundongos hiperalimentados, pode ser devido a um defeito no mecanismo de feedback negativo associado ao dímero Cry-Per, que não bloqueia a transcrição de Per1 Per2, Per3 e Cry1 pelo heterodímero CLOCK-BMAL1.
The healthy interaction between the subject and the environment depends on the alignment between the physiological dynamics of the first one and the periodical movements of nature. The interaction between these rhythms in turn is based on the derivation and evolution process. The involvement of such an alignment is a risk to the survival of species. In this context the bodies line up their physiological rhythms to different external cycles. Thus, endogenous cycles are coordinated by biological clocks which determine in our organism specific rhythms in phase with the nature, such as Circadian Rhythms (CR) whose period is close to 24 hours. The body weight, the food intake and the energy consumption are processes characterized by the CR and the obesity is associated with a different timing of this process. The CR modulation is a result of the formulation of clock-gens CLOCK and BMAL1 who form an heterodimer responsible for the gene transcription of Per1, Per2, Per3, Cry1 e Cry2. The proteins encoded by these genes, once synthesized, form dimers (PER-CRY) in the cytoplasm that, depending on a given concentration, return to the core blocking the action of the CLOCK/BMAL1 heterodimer in the transcription of its own genes, thus forming a negative feedback loop of transcription and translation. These genes secure the periodicity and are significantly expressed in the hypothalamus suprachiasmatic nucleus. In order to study this process in regular, hyper-fed, hungry and satiated mice, we used a registration method of feeding behavior based on the sound produced by animal feeding and the relation between the metabolic states with the expression CLOCK, BMAL1, Per1, Per2, Per3, as well as the Cry1 and Cry2 proteins in the SCN, by analysis of images obtained in confocal microscopy. Control Swiss mice in state of hunger/ satiated were compared to hyper-fed animals in the same conditions. None of them showed difference in the CLOCK and BMAL1 contents, showing a potential capacity to modulate the biological rhythms. However, the Per1, Per2, Per3 and Cry1 proteins showed a minor expression in the CS group and a significant difference when compared to the CF group (P<0,05). This difference cant be found in the HF and HS groups. The results of the studies indicated that the endogenous and exogenous changes, reflected by the hyperphagic behavior observed in hyper-fed mice, may be due to a defect in the mechanism of negative feedback associated to the Cry-Per dimer, which has abolished the blocking mechanism of Per1 Per2, Per3 and Cry1 by the CLOCK-BMAL1 heterodimer.
46
Penkhues, Manfred. "Fulvenkomplexe des Typs Cp2Zr(j6-C5H4=CR2) [Cp 2 Zr (eta 6 C 5 H 4 CR 2)] neuartige Elektronenüberschussverbindungen /." [S.l. : s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=962077038.
Full text
47
DELIBRIAS, CATHERINE. "Etude phenotypique et fonctionnelle des recepteurs pour les fragments de c3, cr1 (cd35) et cr2 (cd21), des lymphocytes t humains." Paris 7, 1993. http://www.theses.fr/1993PA077245.
Full textAbstract:
Le composant c3 du complement est implique dans le controle de la reponse immunitaire specifique par l'intermediaire d'interactions avec des recepteurs pour les fragments de c3 exprimes a la surface des cellules immunocompetences. Seul, le recepteur cr1 (cd35, recepteur c3b) avait ete decrit a la surface de 15% des lymphocytes t humains. Nous avons montre que la molecule cr2 (cd21, recepteur c3dg/ebv) est exprimee par 40% des lymphocytes t humains, alors que cette molecule etait classiquement consideree comme un marqueur des lymphocytes b. La caracterisation fonctionnelle et physicochimique des recepteurs cr1 et cr2 exprimes par les cellules de la lignee t hpb-all indique que ces recepteurs sont identiques aux molecules exprimees par les lymphocytes b et sont capables de s'internaliser. La stimulation de cr2, mais pas celle de cr1, induit une elevation de la concentration de calcium intracellulaire. Cr1 est physiquement associe a cr2 dans la membrane cellulaire. Ce complexe pourrait permettre la captation des virus opsonises et renforcer l'adhesion des lymphocytes t aux cellules presentatrices de l'antigene. Cr2 est de plus associe a une proteine membranaire de 185 kda qui pourrait exercer une fonction de molecule transductrice de signaux. L'opsonisation du vih par des fragments de c3 facilite l'infection des cellules t cd4-positives hpb-all et des cellules b csd4-negatives raji. Les recepteurs cr1 et cr2 a la surface des lymphocytes constituent une voie d'entree pour le virus opsonise par le complement et contribuent a l'infection par le vih
48
Kolarz, Adam [Verfasser], Wolfgang [Akademischer Betreuer] [Gutachter] Wurst, and Carsten T. [Gutachter] Wotjak. "Genetically dissecting the role of CRHR2 and UCN2 in the control of emotional behavior / Adam Kolarz. Betreuer: Wolfgang Wurst. Gutachter: Wolfgang Wurst ; Carsten T. Wotjak." München : Universitätsbibliothek der TU München, 2015. http://d-nb.info/1107543509/34.
Full text
49
Labeur, Carole. "Intégration de signaux peptidiques et hormonaux régulant l’architecture du système racinaire des légumineuses Different Pathways Act Downstream of the CEP Peptide Receptor CRA2 to Regulate Lateral Root and Nodule Development Independent Regulation of Symbiotic Nodulation by the SUNN Negative and CRA2 Positive Systemic Pathways The NIN transcription factor coordinates CEP and CLE signaling peptides that regulate nodulation antagonistically." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASB009.
Full textAbstract:
Les légumineuses adaptent l’architecture de leur système racinaire aux conditions environnementales en modifiant la croissance et le nombre de leurs racines latérales mais aussi en développant des nodosités fixatrices d’azote en condition de carence azotée et en présence de bactéries symbiotiques (rhizobia). Des voies de régulation systémique impliquant des peptides de signalisation perçus par des récepteurs kinases permettent la coordination du développement de ces organes racinaires en fonction de la disponibilité en azote dans le sol et des besoins de la plante. Les objectifs de cette thèse était d’une part d’identifier quel signal peptidique agit via l’un de ces récepteurs, appelé CRA2, pour induire la nodulation et réprimer la formation des racines latérales ; et d’autre part de déterminer comment cette voie s’intègre avec d’autres voies de signalisation régulant l’architecture racinaire, ie (i) la voie systémique impliquant des peptides de signalisation CLE et le récepteur SUNN régulant négativement la nodulation et (ii) la voie des phytohormones cytokinines régulant l’architecture racinaire de manière similaire à CRA2 .Nous avons montré que le récepteur CRA2 est requis pour l’action du peptide de signalisation MtCEP1, et que les deux voies systémiques régulant de manière antagoniste la nodulation agissaient de manière indépendante Enfin, nous avons montré que le gène MtCEP7, induit par rhizobium et les cytokinines, favorise les infections rhizobiennes, et sa production est coordonnée avec celle d’un peptide CLE régulant négativement la nodulation, via les cytokinines et le facteur de transcription NINLegumes adapt their root architecture to environmental conditions by modifying the growth and number of their lateral roots, but also by developing nitrogen-fixing nodules in nitrogen-deficient conditions and in the presence of symbiotic bacteria (rhizobia). Systemic regulatory pathways involving signaling peptides perceived by receptors kinase allow the coordination of the development of these root organs according to the availability of nitrogen in the soil and the needs of the plant. The objectives of this thesis were, on the one hand, to identify which peptide signal acts via one of these receptors, namely CRA2, to induce nodulation and suppress the formation of lateral roots; and secondly to determine how this pathway integrates with other signaling pathways regulating the root architecture, ie (i) the systemic pathway involving CLE signaling peptides and the SUNN receptor negatively regulating nodulation and (ii) the pathway of cytokinin phytohormones regulating root architecture similarly to CRA2. We have shown that the CRA2 receptor is required for the action of the signaling peptide MtCEP1, and that the two systemic pathways antagonistically regulating nodulation act independently. Finally, we have shown that the MtCEP7 gene, induced by rhizobium and cytokinins, promotes rhizobial infections, and its production is coordinated with that of a CLE peptide that negatively regulates nodulation, via cytokinins and the NIN transcription factor
50
GRENON, MURIEL. "Analyse genetique et moleculaire des genes chk1#+ et crb2#+ impliques dans les voies de surveillance de la reparation et de la replication de l'adn chez schizosaccharomyces pombe." Paris 11, 1998. http://www.theses.fr/1998PA112385.
Full textAbstract:
La replication de l'adn pendant la phase s et la segregation des chromosomes a la mitose sont les deux evenements majeurs du cycle cellulaire eucaryote. La progression du cycle cellulaire, en particulier l'interdependance entre ces deux phases, est strictement regulee par l'activite de proteines kinases dependantes des cyclines. En plus de ce controle intrinseque, des systemes de surveillance, nommes checkpoints, arretent le cycle cellulaire lorsque celui-ci est perturbe afin de permettre a la cellule de resoudre le probleme rencontre. En particulier, les systemes de surveillance de la replication et de la reparation de l'adn bloquent l'entree en mitose lorsque la replication de l'adn est arretee ou lorsque l'adn est endommage. Ce mode de controle aboutit a la regulation de l'activite de la proteine kinase cdc2 et est extremement conserve des eucaryotes inferieurs a l'homme. Afin d'isoler plusieurs elements impliques dans le systeme de surveillance de la replication de l'adn de schizosaccharomyces pombe, nous avons recherche des mutations qui abolissent l'arret specifique en phase s d'un mutant conditionnel de l'adn polymerase delta. Nous avons isole deux alleles du gene chk1#+, considere jusqu'alors comme uniquement implique dans le systeme de surveillance de la reparation de l'adn. Grace a l'etude de ces alleles, nous avons demontre que chk1 est impliquee dans le systeme de surveillance de la replication de l'adn. Par la meme approche, nous avons isole une nouvelle proteine checkpoint, la proteine crb2. Nous avons montre que crb2 agit en amont de chk1 dans les systemes de surveillance de la replication et de la reparation de l'adn. Crb2 est egalement impliquee dans une voie d'inhibition de la mitose independante de la voie de chk1. Finalement, nous avons montre que crb2 est necessaire au maintien de la survie cellulaire dans certaines conditions. Cette fonction est independante du role de cette proteine dans les systemes de surveillance.