Plusieurs travaux s’accordent sur le fait que l’analyse de l’ADN circulant (ADNcir) est un outil à fort potentiel diagnostic, pronostic, théranostic et de suivi en oncologie clinique. Cependant, le manque de standardisation des procédures pré-analytiques, des connaissances approfondies des structures des ADNcir ainsi que les facteurs influençant la dynamique de son relargage constituent des obstacles à son transfert en pratique clinique. C’est dans ce contexte que nous avons choisi d’approfondir l’étude des structures des ADNcir d’origines nucléaire et mitochondriale, évaluer leur utilité clinique en oncologie et étudier l’effet de l’hypoxie sur leur libération. A partir d’une technique de qPCR optimisée et validée cliniquement pour l’analyse des ADN circulants, nous avons quantifié les ADN extracellulaires d’origines nucléaire et mitochondriale dans des milieux de culture cellulaire et dans des plasmas humains et murins.Nos données ont révélé l’influence des procédures pré-analytiques sur la quantification de l’ADN circulant en fonction de l’origine. En effet, nous montrons que la préparation du plasma par séparation en ficoll diminue de manière significative la quantification de l’ADNcir d’origine mitochondriale sans influencer la quantification de l’ADNcir d’origine nucléaire, ce qui suggère la présence de structures de densité différente contenant de l’ADN mitochondrial dans le plasma. D’autre part, j’ai contribué à l’évaluation d’un test de dépistage du cancer basé sur l’analyse de l’ADNcir nucléaire et mitochondrial mise au point au laboratoire. Nos résultats préliminaires montrent de façon significative la capacité diagnostic de ce test sur des cohortes de patients atteints de cancers colorectal (n = 127) versus des individus sains (n = 91) (AUC = 0,8657 ; p < 0,0001).Nous montrons in vitro que l’hypoxie module de manière différente le relargage des ADN extracellulaires en fonction de leur origine, et notamment que l’ADN extracellulaire d’origine mitochondriale semble être régulé négativement en condition hypoxique. In vivo, l’hypoxie entraîne une augmentation de la libération de l’ADNcir d’origine nucléaire (p=0,002), mais pas d’origine mitochondriale, dans le plasma de souris greffées avec des cellules tumorales de cancer de poumon.Pour conclure, les travaux réalisés au cours de cette thèse mettent en lumière : (i) l’intérêt de la mise en place de procédures pré-analytiques standardisées pour la compréhension des origines et structures des ADNcir ; (ii) le fort potentiel diagnostic de l’analyse de l’ADNcir en oncologie ; (iii) et l’influence de l’hypoxie sur le relargage de l’ADN circulant. / Different studies converge on the diagnostic, theragnostic and prognostic properties of circulating DNA analysis (cirDNA) in clinical oncology. There remain various obstacles, however, to its transfer to clinical practice. These include the lack of standardization of pre-analytical procedures, and limited knowledge of cirDNA structures and of the factors influencing the dynamics of their release. In this context, we studied the structures of cirDNA of nuclear and mitochondrial origins, evaluated their diagnostic potential, and then evaluated the effect of hypoxia on their release. Using an optimized qPCR technique previously validated in clinical studies for the analysis of cirDNA, we quantified extracellular DNA of nuclear and mitochondrial origins in cell culture medium and in human and mouse plasma.Our data also revealed the influence of pre-analytical procedures on the quantification of cirDNA, depending on its origin. Indeed, we showed that plasma preparation with Ficoll separation significantly reduces the quantification of mitochondrial cirDNA without influencing the quantification of nuclear cirDNA.In addition, we evaluated the value of nuclear and mitochondrial cirDNA analysis in a cancer-screening test developed in the laboratory. Our preliminary results demonstrated a significant discrimination between colorectal cancer patients (n=127) and healthy individuals (n=91) (AUC=0.8657; p<0.0001).We demonstrated that in vitro hypoxia modulates the release of extracellular DNA in different ways, depending on its origin, and showed that extracellular DNA of mitochondrial origin is negatively regulated. By contrast, we demonstrated in vivo that hypoxia leads to a greater release of nuclear cirDNA (p=0.002), but not of mitochondrial cirDNA, as compared to normoxia. These experiments were performed using the plasma of mice grafted with lung cancer tumor cells.In conclusion, the work carried out for this thesis highlights: (i) the importance of setting up standardized pre-analytical procedures when investigating the origins and structures of cirDNA; (ii) the strong diagnostic potential of cirDNA analysis in oncology and (iii) the influence of hypoxia on the release of cirDNA.

<p>In order to maximize operating time of an industrial machine and minimize stand-by time, service time and operating costs, a diagnostic system can be a useful tool. Diagnostic systems employ information already available in a machine’s control system (such as control signals, system state, sensor readings and so forth) to perform intelligent fault detection and localisation, and predict future faults and service needs.</p><p>CC Systems develops advanced electronics and control systems for industrial machines and vehicles operating in rough environments. One of their products is a diagnostic platform called Diagnostic Runtime Engine (DRE), supplying the customer with a tool for building a diagnostic system. The platform offers supervision of the control system. Actions are performed when it detects a possible fault or indication of a potential future fault. An action could be for example the creation of an alarm.</p><p>The DRE, as designed today, only works together with a control system running in an environment called CoDeSys. In this master thesis a new architecture of the platform is presented, with the objective to make the platform compatible with an arbitrary control system. A prototype is implemented to prove the concept of the suggested architecture model. A number of different standard diagnostic blocks, used for building the diagnostic system, are also suggested with the objective to make it easier for the user to employ the DRE. A proposition of how development with the diagnostic platform can proceed beyond this thesis is also presented.</p> / <p>För att maximera drifttid hos en industriell maskin och minimera driftskostnader samt standby- och service-tid, kan ett diagnostiksystem användas. Ett sådant system använder sig av information som redan finns tillgänglig i maskinens styrsystem (så som styrsignaler, tillstånd, sensorvärden och så vidare) för att utföra feldetektering och fellokalisering samt analys av möjliga framtida feltillstånd och servicebehov.</p><p>CC Systems utvecklar avancerade elektronikkomponenter och styrsystem för industriella maskiner och fordon. En av deras produkter är en diagnostikplattform, Diagnostic Runtime Engine (DRE), som erbjuder ett verktyg för att bygga upp ett diagnostiksystem. Plattformen möjliggör övervakning av styrsystemet, och detektion av ett nuvarande feltillstånd eller möjligt framtida feltillstånd leder till att en handling utförs. En handling kan till exempel vara att ett alarm skapas.</p><p>Diagnostikplattformen, som den är gjord idag, fungerar bara tillsammans med ett styrsystem som är implementerat i utvecklingsmiljön CoDeSys. I detta examensarbete presenteras en ny arkitektur på plattformen som möjliggör användande tillsammans med ett godtyckligt styrsystem. En prototyp är implementerad för att visa att den föreslagna arkitekturmodellen fungerar i praktiken. Dessutom är ett antal standard-diagnostikblock, som används då ett diagnostiksystem byggs upp, föreslagna. Standardblocken har till syfte att underlätta användandet av diagnostikplattformen. Ett förslag för hur DRE kan byggas om och utvecklas i framtiden är också presenterat.</p>

Thèse d'exercice : Médecine. Médecine générale : Paris 12 : 2006. / Titre provenant de l'écran-titre. Bibliogr. f. 80-85.

Reproduction de : Thèse d'exercice : Médecine : Nancy 1 : 2006. / Titre provenant de l'écran-titre.

In order to maximize operating time of an industrial machine and minimize stand-by time, service time and operating costs, a diagnostic system can be a useful tool. Diagnostic systems employ information already available in a machine’s control system (such as control signals, system state, sensor readings and so forth) to perform intelligent fault detection and localisation, and predict future faults and service needs. CC Systems develops advanced electronics and control systems for industrial machines and vehicles operating in rough environments. One of their products is a diagnostic platform called Diagnostic Runtime Engine (DRE), supplying the customer with a tool for building a diagnostic system. The platform offers supervision of the control system. Actions are performed when it detects a possible fault or indication of a potential future fault. An action could be for example the creation of an alarm. The DRE, as designed today, only works together with a control system running in an environment called CoDeSys. In this master thesis a new architecture of the platform is presented, with the objective to make the platform compatible with an arbitrary control system. A prototype is implemented to prove the concept of the suggested architecture model. A number of different standard diagnostic blocks, used for building the diagnostic system, are also suggested with the objective to make it easier for the user to employ the DRE. A proposition of how development with the diagnostic platform can proceed beyond this thesis is also presented. / För att maximera drifttid hos en industriell maskin och minimera driftskostnader samt standby- och service-tid, kan ett diagnostiksystem användas. Ett sådant system använder sig av information som redan finns tillgänglig i maskinens styrsystem (så som styrsignaler, tillstånd, sensorvärden och så vidare) för att utföra feldetektering och fellokalisering samt analys av möjliga framtida feltillstånd och servicebehov. CC Systems utvecklar avancerade elektronikkomponenter och styrsystem för industriella maskiner och fordon. En av deras produkter är en diagnostikplattform, Diagnostic Runtime Engine (DRE), som erbjuder ett verktyg för att bygga upp ett diagnostiksystem. Plattformen möjliggör övervakning av styrsystemet, och detektion av ett nuvarande feltillstånd eller möjligt framtida feltillstånd leder till att en handling utförs. En handling kan till exempel vara att ett alarm skapas. Diagnostikplattformen, som den är gjord idag, fungerar bara tillsammans med ett styrsystem som är implementerat i utvecklingsmiljön CoDeSys. I detta examensarbete presenteras en ny arkitektur på plattformen som möjliggör användande tillsammans med ett godtyckligt styrsystem. En prototyp är implementerad för att visa att den föreslagna arkitekturmodellen fungerar i praktiken. Dessutom är ett antal standard-diagnostikblock, som används då ett diagnostiksystem byggs upp, föreslagna. Standardblocken har till syfte att underlätta användandet av diagnostikplattformen. Ett förslag för hur DRE kan byggas om och utvecklas i framtiden är också presenterat.

Thesis (M.H.A.)--University of Michigan, 1974. / "Program in Hospital Administration."

Thesis (M.H.A.)--University of Michigan, 1974. / "Program in Hospital Administration."

Thesis (M.S.)--University of Wisconsin--Madison, 1982. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 88-101).

Les piles à combustible constituent une alternative aux moteurs thermiques utilisés dans le cadre d’applications transport ou dans le cadre d’applications stationnaires. Cependant, il existe encore aujourd’hui des verrous technologiques limitant leur développement à l’échelle industrielle. Un des verrous importants est la détermination de leur état de santé en temps réel permettant un diagnostic voire un pronostic de leurs dysfonctionnements ou de leur temps de bon fonctionnement. Dans ce travail, deux approches différentes ont été abordées en vue de proposer des outils de diagnostic pour des empilements de taille industrielle : une approche électrochimique et une approche acoustique. Dans un premier temps, un modèle simple de spectroscopie d’impédance électrochimique et un algorithme d’identification des paramètres ont été développés dans l’optique de proposer un outil de diagnostic rapide et facile à implémenter. Dans un second temps, deux méthodes basées sur la propagation des ondes sonores (l’émission acoustique et les acousto-ultrasons) ont été testées et évaluées dans des conditions de fonctionnement optimales et dégradées. / Fuel cells are a promising alternative to classical fossil energy based engines used in transport applications and electro-generators. However, there still exist limitations preventing it to be used at an industrial scale. In particular, the real-time determination of the cell’s state of health, allowing one to establish a diagnosis or a prognosis of the malfunctions and failures In this document, two different approaches are tested in order to propose real-diagnostic tools for industrial scale stacks. First, a simple electrochemical impedance spectroscopy model is developed in order to create a fast and easily embeddable diagnostic tool. Finally, two techniques based on ultrasound propagation (acoustic emission and acousto-ultrasound).are tested and evaluated in optimal and degraded conditions.

The increasing incidence of disseminated (invasive) candidiasis is probably attributable to iatrogenic factors and to improved pre and postmortem evaluation. Premortem diagnosis of such infections have seldom been made early enough for successful treatment. In order to increase the likelihood of successful antifungal chemotherapy, rapid diagnosis of such infections is vital. However, present diagnostic procedures for invasive candidiasis are insensitive and often do not reliably differentiate superficial from invasive infections. This study was undertaken to produce DNA probes and to optimize conditions for rapid and efficient detection of Candida DNA. Seven random Candida albicans DNA fragments (2-7 kbp) were cloned into plasmid pACYC 184. These recombinant plasmids were labeled with either ³²p or biotin and used as probes. Two of the four recombinant plasmids tested were genus specific. The other two were slightly cross reactive with other yeasts (Saccharomyces cerevisiae and Hansenula anomala). Probes labeled with ³²p were twice as sensitive as the biotin probes. One ³²p labelled recombinant (#66) detected 7 Pg of target DNA , which corresponds to approximately 2 X 10⁵ C.albicans cells. With refined simple DNA extraction procedures for C.albicans (in serum), these recombinant probes could possibly be suitable for clinical application. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate