O divertículo faringo-esofágico (DFE), também conhecido como cricofaríngeo ou de Zenker (DZ), é doença rara, com prevalência estimada entre 0,01% e 0,11%, e que acomete os muito idosos, para os quais tratamentos menos invasivos podem ser úteis, destacando-se o endoscópico. A despeito das inovações com equipamentos e acessórios, hemorragias e perfurações ocorrem em até 10 e 15% dos pacientes, respectivamente. A constatação de divertículo faríngeo em porcos domésticos transformou-se em modelo experimental de grande interesse para fins didáticos e científicos. Pretendeu-se, neste sentido, introduzir inovação técnica e compará-la com o tratamento endoscópico convencional do DFE. O objetivo deste estudo foi comparar, em modelo experimental, a diérese do septo do DFE efetuada através do bisturi harmônico Ultracision &#174; (Grupo U) com a do eletrocautério monopolar (Grupo M). Foram utilizados 20 porcos domésticos com peso médio de 20,2 Kg (&#177;1,35). Os animais foram alocados entre os grupos M e U de forma não aleatorizada. Não houve diferença significativa quanto ao tamanho do divertículo (p=0,0897) ou quanto ao tempo de inserção do diverticuloscópio flexível (p=0,7387). No grupo U, o tempo médio para a incisão do septo e o tempo total do procedimento foram menores (p<0,0001) para as duas comparações. Quanto à extensão da borda seccionada, houve diferença significativa (p=0,0047) entre os grupos, com maior média de tamanho no grupo U. Em relação aos parâmetros microscópicos, apenas a extensão da lesão provocada pela corrente monopolar (Grupo M) foi maior (p<0,0001). Em relação aos parâmetros de profundidade e à presença de inflamação, não houve diferença entre os grupos. Observou-se hemorragia apenas no grupo M (p=0,01), sempre controlada endoscopicamente. Em comparação com a técnica de seção feita com uso de estilete endoscópico e corrente monopolar mista, a diverticulotomia endoscópica experimental com uso de diverticuloscópio flexível e bisturi harmônico se mostrou mais rápida e relacionada com menor dano tecidual / The pharyngoesophageal diverticulum (PED), also known as cricopharyngeal or Zenker diverticulum (ZD), is a rare disease with estimated incidence ranging from 0.01% to 0.11% and more present in elderly patients, for whom a less invasive treatment can be desirable. Despite innovations in endoscopic equipment and accessories, bleeding and perforation occur in up to 10 and 15% of the cases, respectively. The finding of pharyngeal diverticulum in domestic pigs turned into an experimental model of major interest for training and scientific purposes. For this reason, the introduction of a technical innovation and its comparison with PED conventional treatment were focused. Our aim was to compare the diaeresis of the PED septum by the harmonic scalpel Ultracision &#174; monopolar electrocautery (Group M) in an experimental model. Twenty domestic pigs (mean weight 20.2 kg; &#177;1.35) were divided into groups M and U nonrandomly. No significant differences were found related to diverticulum size (p=0.0897) or insertion time of soft diverticuloscope (p=0.7387). In group U, mean time to divide the septum and total procedure time were significantly shorter (p<0.0001) for both comparisons. Regarding incision extension, mean length was significantly higher in group U (p=0.0047). In relation to microscopic parameters, the lateral thermal spread caused by monopolar current (Group M) was found to be more intense (p<0.0001). As for depth and inflammation presence, no differences were verified between the groups. Hemorrhage was exclusively observed in group M (p=0.01) and it was endoscopically managed at all times. When compared to endoscopic incision with needle-knife and monopolar blend current, the experimental endoscopic diverticulostomy using soft diverticuloscope and harmonic scalpel demonstrated to be faster and related to less tissue damage.

O divertículo faringo-esofágico (DFE), também conhecido como cricofaríngeo ou de Zenker (DZ), é doença rara, com prevalência estimada entre 0,01% e 0,11%, e que acomete os muito idosos, para os quais tratamentos menos invasivos podem ser úteis, destacando-se o endoscópico. A despeito das inovações com equipamentos e acessórios, hemorragias e perfurações ocorrem em até 10 e 15% dos pacientes, respectivamente. A constatação de divertículo faríngeo em porcos domésticos transformou-se em modelo experimental de grande interesse para fins didáticos e científicos. Pretendeu-se, neste sentido, introduzir inovação técnica e compará-la com o tratamento endoscópico convencional do DFE. O objetivo deste estudo foi comparar, em modelo experimental, a diérese do septo do DFE efetuada através do bisturi harmônico Ultracision &#174; (Grupo U) com a do eletrocautério monopolar (Grupo M). Foram utilizados 20 porcos domésticos com peso médio de 20,2 Kg (&#177;1,35). Os animais foram alocados entre os grupos M e U de forma não aleatorizada. Não houve diferença significativa quanto ao tamanho do divertículo (p=0,0897) ou quanto ao tempo de inserção do diverticuloscópio flexível (p=0,7387). No grupo U, o tempo médio para a incisão do septo e o tempo total do procedimento foram menores (p<0,0001) para as duas comparações. Quanto à extensão da borda seccionada, houve diferença significativa (p=0,0047) entre os grupos, com maior média de tamanho no grupo U. Em relação aos parâmetros microscópicos, apenas a extensão da lesão provocada pela corrente monopolar (Grupo M) foi maior (p<0,0001). Em relação aos parâmetros de profundidade e à presença de inflamação, não houve diferença entre os grupos. Observou-se hemorragia apenas no grupo M (p=0,01), sempre controlada endoscopicamente. Em comparação com a técnica de seção feita com uso de estilete endoscópico e corrente monopolar mista, a diverticulotomia endoscópica experimental com uso de diverticuloscópio flexível e bisturi harmônico se mostrou mais rápida e relacionada com menor dano tecidual / The pharyngoesophageal diverticulum (PED), also known as cricopharyngeal or Zenker diverticulum (ZD), is a rare disease with estimated incidence ranging from 0.01% to 0.11% and more present in elderly patients, for whom a less invasive treatment can be desirable. Despite innovations in endoscopic equipment and accessories, bleeding and perforation occur in up to 10 and 15% of the cases, respectively. The finding of pharyngeal diverticulum in domestic pigs turned into an experimental model of major interest for training and scientific purposes. For this reason, the introduction of a technical innovation and its comparison with PED conventional treatment were focused. Our aim was to compare the diaeresis of the PED septum by the harmonic scalpel Ultracision &#174; monopolar electrocautery (Group M) in an experimental model. Twenty domestic pigs (mean weight 20.2 kg; &#177;1.35) were divided into groups M and U nonrandomly. No significant differences were found related to diverticulum size (p=0.0897) or insertion time of soft diverticuloscope (p=0.7387). In group U, mean time to divide the septum and total procedure time were significantly shorter (p<0.0001) for both comparisons. Regarding incision extension, mean length was significantly higher in group U (p=0.0047). In relation to microscopic parameters, the lateral thermal spread caused by monopolar current (Group M) was found to be more intense (p<0.0001). As for depth and inflammation presence, no differences were verified between the groups. Hemorrhage was exclusively observed in group M (p=0.01) and it was endoscopically managed at all times. When compared to endoscopic incision with needle-knife and monopolar blend current, the experimental endoscopic diverticulostomy using soft diverticuloscope and harmonic scalpel demonstrated to be faster and related to less tissue damage.

Las técnicas ablativas basadas en energía por radiofrecuencia (RF) se emplean con el fin de lograr un calentamiento seguro y localizado en el tejido biológico. En los últimos años ha habido un rápido crecimiento en el número de nuevos procedimientos médicos que hacen uso de dichas técnicas, lo cual ha ido acompañado de la aparición de nuevos diseños de electrodos y protocolos de aplicación de energía. Sin embargo, existen todavía muchas incógnitas sobre el verdadero comportamiento electro-térmico de los aplicadores de energía, así como de la interacción energía-tejido en aplicaciones concretas. El principal propósito de esta Tesis Doctoral es adquirir un mejor conocimiento de los fenómenos eléctricos y térmicos involucrados en los procesos de calentamiento de tejidos biológicos mediante corrientes de RF. Esto permitirá, por un lado, mejorar la eficacia y seguridad de las técnicas actualmente empleadas en la clínica en campos tan diferentes como la cirugía cardiaca, oncológica o dermatológica; y por otro, sugerir mejoras tecnológicas para el diseño de nuevos aplicadores. La Tesis Doctoral combina dos metodologías ampliamente utilizadas en el campo de la Ingeniería Biomédica, como son el modelado computacional (matemático) y la experimentación (ex vivo e in vivo). En cuanto al área cardiaca, la investigación se ha centrado, por una parte, en mejorar la ablación intraoperatoria de la fibrilación auricular por aproximación epicárdica, es decir, susceptible de ser realizada de forma mínimamente invasiva. Para ello, se ha estudiado mediante modelos matemáticos un sistema de medida de la impedancia epicárdica como método de valoración de la cantidad de grasa previo a la ablación. Por otra parte, se ha estudiado cómo mejorar la ablación de la pared ventricular por aproximación endocárdica-endocárdica (septo interventricular) y endocárdica-epicárdica (pared libre del ventrículo). Con este objetivo, se han comparado mediante modelado por computador la eficacia de los modos de ablación bipolar y unipolar en términos de la transmuralidad de la lesión en la pared ventricular. En lo que respecta al área de cirugía oncológica, la investigación se ha centrado en la resección hepática asistida por RF. Las técnicas de calentamiento por RF deberían ser capaces de minimizar el sangrado intraoperatorio y sellar vasos y ductos mediante la creación de una necrosis coagulativa por calentamiento. Si este calentamiento se produce en las cercanías de grandes vasos, existe un problema potencial de daño a la pared de dicho vaso. En este sentido, se ha evaluado con modelos matemáticos y experimentación in vivo si el efecto del flujo de sangre dentro de un gran vaso es capaz de proteger térmicamente su pared cuando se realiza una resección asistida por RF en sus cercanías. Además, se ha realizado un estudio computacional y experimental ex vivo e in vivo del comportamiento electro-térmico de aplicadores de RF bipolares internamente refrigerados, puesto que representan una opción más segura frente a los monopolares en la medida en que las corrientes de RF fluyen casi exclusivamente por el tejido biológico situado entre ambos electrodos. Respecto al área dermatológica, la investigación se ha centrado en mejorar el tratamiento de enfermedades o desórdenes del tejido subcutáneo (tales como lipomatosis, lipedema, enfermedad de Madelung y celulitis) mediante el estudio teórico de la dosimetría correcta en cada caso. Para ello, se han evaluado los efectos eléctricos, térmicos y termo-elásticos de dos estructuras diferentes de tejido subcutáneo durante el calentamiento por RF, y se ha cuantificado el daño térmico producido en ambas estructuras tras dicho calentamiento / González Suárez, A. (2014). Computational Models and Experimentation for Radiofrequency-based Ablative Techniques [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/36502 / TESIS

A Sindrome do Desconforto Respiratório Agudo (SDRA) apresenta alta taxa de mortalidade em UTI. Sua principal característica é alteração da permeabilidade da membrana alvéolo capilar, com liberação de agentes inflamatórios, disfunção de surfactantes e da aeração pulmonar, queda da complacência e dos níveis de oxigenação. Frequentemente evolui com necessidade de suporte ventilatório. Vários modelos experimentais foram propostos na tentativa de reproduzir as mesmas característica da SDRA encontradas em pacientes, porém com pouco sucesso. Tem sido difícil reproduzir modelos estáveis, e por períodos prolongados. Assim, o nosso objetivo foi validar um novo modelo de SDRA, submetido a um período de observação e estabilização de 40 horas de ventilação mecânica protetora, testando a reprodutibilidade das principais características da apresentação clínica da SDRA. Realizamos o estudo em suínos, divididos em 3 grupos : SHAM (não submetido a Lesão), LESÃO (submetido a lavagem total pulmonar e ventilação lesiva por 3 horas) e VMP40 (submetido a Lesão e 40hs de ventilação protetora segundo a estratégia ARDSNET). Observamos que os níveis de PaO2 e complacência tiveram queda significativa após a lesão mantendo esta queda ao final de 40 horas. Os níveis de citocinas IL1, IL8 e IL6 tiveram um aumento significativa logo após a lesão, mantendo aumento significativo de IL1 e IL8 nas 40 horas de observação. Os níveis de polimorfonuclear no bal também tiveram um aumento significante, mantido nas 40 horas. Uma significativa alteração da permeabilidade alveolo-capilar foi demonstrada pelo aumento de proteínas no lavado broncoalveolar, aumento da água extravascular pulmonar, e aumento da relação peso seco/úmido que foram persistentes após 40hs da estratégia protetora ARDSnet. A lesão histológica foi evindenciada pela presença de todos os componentes clássicos: membrana hialina, hemorragia alveolar, infiltrado inflamatório e edema alveolar, também mantidos por 40hs. Conclusão: O modelo desenvolvido apresentou características clínicas e fisiopatológicas similares a pacientes com SDRA grave, mantidas por um período de 40 horas de ventilação protetora, mostrando assim que este modelo pode ser utilizado para estudos de SDRA e estratégias de ventilação mecânica protetora por período prolongado / The Acute Respiratory Distress Syndrome (ARDS) has high mortality in the ICU. Its main features comprise the disruption of the alveolo-capillary membrane with permeability alterations, release of inflammatory agents, and physiological dysfunctions like surfactant function degradation, loss of compliance and reduced PaO2 levels demanding ventilatory support. Several experimental models were developed in an attempt to simulate the same characteristics of ARDS in patients, but could not reproduce the complex, florid characteristics or the persistent damage for long periods. This study aimed to validate a new ARDS model in our laboratory, submited to an stabilization/observation period of 40 hours period of protective mechanical ventilation (according to the protective ARDSnet strategy), during which we tested the persistence of the main physiopathological characteristics of ARDS. We conducted the study in pigs divided into 3 groups : SHAM (not injured), INJURY (total lung lavage and injurious mechanical ventilation for 3hs) and MVP40 (injury protective mechanical ventilation for aditional 40hs-ARDSNET strategy). Respiratory-system compliance and PaO2 significantly decreased after injury, with a persistent drop till the end of 40hs. The levels of IL1, IL6 and IL8 cytokines presented a significant increase immediately after injury, with persistent levels of IL1 and IL8 after 40hs. Polymorphonuclear cells in the BAL were also increased after injury, with persistent levels after 40 hours. Gross alterations in the alveolo-capillary permeability were demonstrated by increased levels of proteins in the bronchoalveolar lavage, increased extravascular lung water and an increased wet/dry lung-weight ratio that remained elevated after 40hs of protective strategy. Histological injury was confirmed by visualization of hyaline membranes, frequent alveolar hemorrhage, alveolar edema and massive inflammatory infiltration. Conclusion: The proposed model reproduced the clinical and phisiopathological alterations found in patients with ARDS. The alterations persisted for at least 40hs of protective ventilation strategy. Thus, this model can be used for long term studies of ARDS and protective ventilation strategies

A Sindrome do Desconforto Respiratório Agudo (SDRA) apresenta alta taxa de mortalidade em UTI. Sua principal característica é alteração da permeabilidade da membrana alvéolo capilar, com liberação de agentes inflamatórios, disfunção de surfactantes e da aeração pulmonar, queda da complacência e dos níveis de oxigenação. Frequentemente evolui com necessidade de suporte ventilatório. Vários modelos experimentais foram propostos na tentativa de reproduzir as mesmas característica da SDRA encontradas em pacientes, porém com pouco sucesso. Tem sido difícil reproduzir modelos estáveis, e por períodos prolongados. Assim, o nosso objetivo foi validar um novo modelo de SDRA, submetido a um período de observação e estabilização de 40 horas de ventilação mecânica protetora, testando a reprodutibilidade das principais características da apresentação clínica da SDRA. Realizamos o estudo em suínos, divididos em 3 grupos : SHAM (não submetido a Lesão), LESÃO (submetido a lavagem total pulmonar e ventilação lesiva por 3 horas) e VMP40 (submetido a Lesão e 40hs de ventilação protetora segundo a estratégia ARDSNET). Observamos que os níveis de PaO2 e complacência tiveram queda significativa após a lesão mantendo esta queda ao final de 40 horas. Os níveis de citocinas IL1, IL8 e IL6 tiveram um aumento significativa logo após a lesão, mantendo aumento significativo de IL1 e IL8 nas 40 horas de observação. Os níveis de polimorfonuclear no bal também tiveram um aumento significante, mantido nas 40 horas. Uma significativa alteração da permeabilidade alveolo-capilar foi demonstrada pelo aumento de proteínas no lavado broncoalveolar, aumento da água extravascular pulmonar, e aumento da relação peso seco/úmido que foram persistentes após 40hs da estratégia protetora ARDSnet. A lesão histológica foi evindenciada pela presença de todos os componentes clássicos: membrana hialina, hemorragia alveolar, infiltrado inflamatório e edema alveolar, também mantidos por 40hs. Conclusão: O modelo desenvolvido apresentou características clínicas e fisiopatológicas similares a pacientes com SDRA grave, mantidas por um período de 40 horas de ventilação protetora, mostrando assim que este modelo pode ser utilizado para estudos de SDRA e estratégias de ventilação mecânica protetora por período prolongado / The Acute Respiratory Distress Syndrome (ARDS) has high mortality in the ICU. Its main features comprise the disruption of the alveolo-capillary membrane with permeability alterations, release of inflammatory agents, and physiological dysfunctions like surfactant function degradation, loss of compliance and reduced PaO2 levels demanding ventilatory support. Several experimental models were developed in an attempt to simulate the same characteristics of ARDS in patients, but could not reproduce the complex, florid characteristics or the persistent damage for long periods. This study aimed to validate a new ARDS model in our laboratory, submited to an stabilization/observation period of 40 hours period of protective mechanical ventilation (according to the protective ARDSnet strategy), during which we tested the persistence of the main physiopathological characteristics of ARDS. We conducted the study in pigs divided into 3 groups : SHAM (not injured), INJURY (total lung lavage and injurious mechanical ventilation for 3hs) and MVP40 (injury protective mechanical ventilation for aditional 40hs-ARDSNET strategy). Respiratory-system compliance and PaO2 significantly decreased after injury, with a persistent drop till the end of 40hs. The levels of IL1, IL6 and IL8 cytokines presented a significant increase immediately after injury, with persistent levels of IL1 and IL8 after 40hs. Polymorphonuclear cells in the BAL were also increased after injury, with persistent levels after 40 hours. Gross alterations in the alveolo-capillary permeability were demonstrated by increased levels of proteins in the bronchoalveolar lavage, increased extravascular lung water and an increased wet/dry lung-weight ratio that remained elevated after 40hs of protective strategy. Histological injury was confirmed by visualization of hyaline membranes, frequent alveolar hemorrhage, alveolar edema and massive inflammatory infiltration. Conclusion: The proposed model reproduced the clinical and phisiopathological alterations found in patients with ARDS. The alterations persisted for at least 40hs of protective ventilation strategy. Thus, this model can be used for long term studies of ARDS and protective ventilation strategies

The diploma thesis describes non-destructive methods for diagnostics of reinforcement. It is focused on the method of electromagnetic indicators. In the first part the methods are described and compared. The profometer PM-630 is also described. The second part describes experimental measurements with profometer on reinforced concrete structures. The results are described and interpreted. The effects, which have influence on measurement, are described. The recommendations for practical measurement with profometer are described. The experimental models were created for calibration of profometer. The part of this thesis is also the determination of load bearing capacity of reinforced concrete bridge in Nosislav.

Η παρούσα έρευνα πραγματοποιήθηκε στο Εργαστήριο Ρευστομηχανικής και Εφαρμογών Αυτής του Τμήματος Μηχανολόγων και Αεροναυπηγών Μηχανικών του Πανεπιστημίου Πατρών και χρηματοδοτήθηκε από το πρόγραμμα «Ηράκλειτος ΙΙ» στα πλαίσια του Επιχειρησιακού Προγράμματος Εκπαίδευση και Δια Βίου Μάθησης, Επένδυση στη κοινωνία της γνώσης. Ο έλεγχος του θερμικού φορτίου στη λειτουργία διαφόρων μηχανολογικών ή ηλεκτρολογικών συστημάτων από συστήματα ψύξης, γίνεται όλο και πιο αναγκαίος στη σημερινή εποχή. Τα συστήματα ψύξης κατηγοριοποιούνται σε ενεργά, που μεταφέρουν ενέργεια υπό μορφή αισθητής θερμότητας μέσω ενός υγρού και σε παθητικά συστήματα ψύξης που χρησιμοποιούν τη λανθάνουσα θερμότητα εξάτμισης του ρευστού λειτουργίας που κυκλοφορεί στην εγκατάσταση, εξαιτίας των τριχοειδών δυνάμεων που αναπτύσσονται από την ύπαρξη πορώδους υλικού. Τα παθητικά συστήματα ψύξης προτιμώνται έναντι των ενεργών, καθώς έχουν τη δυνατότητα να απάγουν περισσότερη θερμότητα, παρουσιάζουν πιο αξιόπιστη λειτουργία, εξαιτίας της έλλειψης κινητών μερών και τέλος, εμφανίζουν μεγαλύτερη διάρκεια ζωής. Μία διάταξη που προσφέρει δυνατότητες ελέγχου του θερμικού φορτίου είναι το κύκλωμα τριχοειδούς αντλίας, Capillary Pump Loop (CPL), που αποτέλεσε και το αντικείμενο μελέτης στην παρούσα διδακτορική διατριβή. Αξιοποιεί τις τριχοειδείς δυνάμεις που αναπτύσσονται στη διεπιφάνεια υγρής-αέριας φάσης του ρευστού λειτουργίας στο πορώδες υλικό που περικλείει ο εξατμιστής στο εσωτερικό του, καθώς και τη λανθάνουσα θερμότητα εξάτμισης και συμπύκνωσης του ρευστού. Με τον τρόπο αυτό, επιτυγχάνει την κυκλοφορία του ρευστού λειτουργίας στην εγκατάσταση, χωρίς την παρουσία μηχανικής αντλίας, και τη μεταφορά των απαιτούμενων θερμικών φορτίων σε μεγάλες αποστάσεις. Ένα κύκλωμα τριχοειδούς αντλίας αποτελείται από έναν εξατμιστή, ένα συμπυκνωτή, τις γραμμές υγρού και ατμού καθώς και ένα ρεζερβουάρ. Από τη μέχρι τώρα έρευνα είχαν μελετηθεί πειραματικά αρκετά μοντέλα CPL, δίνοντας ιδιαίτερη έμφαση στη διαδικασία εκκίνησης της διάταξης καθώς και στις συνθήκες μόνιμης λειτουργίας. Σε όλα αυτά τα μοντέλα το θερμικό φορτίο επιβάλλονταν μέσω ηλεκτρικών αντιστάσεων. Στην παρούσα διερεύνηση η διάταξη ενσωμάτωσε τη δυνατότητα η προσφερόμενη θερμότητα να παρέχεται και από την ηλιακή ακτινοβολία αναπτύσσοντας έναν εργαστηριακό ηλιακό προσομοιωτή. Προκειμένου να βελτιώσουμε τη συγκέντρωση της ακτινοβολίας και να επιτύχουμε υψηλότερη θερμοκρασία στον εξατμιστή του CPL χρησιμοποιήθηκε παραβολικό κάτοπτρο σε συνδυασμό με συγκεντρωτικό συλλέκτη. Η πειραματική εγκατάσταση που σχεδιάσθηκε και κατασκευάστηκε είχε ως στόχο τη μελέτη της συμπεριφοράς του CPL σε θερμικά φορτία υπό μεταβλητές συνθήκες πλήρωσης της εγκατάστασης, ενώ εξετάστηκε και η συμπεριφορά της τριχοειδούς αντλίας όταν ο εξατμιστής βρίσκονταν υπό κλίση ως προς το επίπεδο, και έγινε σύγκριση των πειραματικών αποτελεσμάτων που προέκυψαν με τα αντίστοιχα για λειτουργία σε οριζόντιο επίπεδο. Η παραμετροποίηση της πειραματικής διερεύνησης του CPL αφορούσε τέσσερις τιμές θερμοκρασίας εισόδου του ρευστού, 15, 25, 35 και 45 οC, τρεις τιμές πίεσης πλήρωσης του κυκλώματος, 0,05, 0,15 και 0,25 bar, και, τέλος, τρεις γωνίες κλίσης, 8ο, 16ο και 23ο. Η διάρκεια των πειραμάτων ήταν αρχικά δέκα ώρες, ώστε να προσομοιώνει τη λειτουργία της εγκατάστασης σε διάστημα ηλιοφάνειας κατά τη διάρκεια της καλοκαιρινής περιόδου, αλλά και εικοσιτέσσερις, ώστε να αποτυπωθεί η απρόσκοπτη διατήρηση της κατάστασης σταθερής λειτουργίας του κυκλώματος. Στο δεύτερο μέρος της διατριβής παρουσιάζονται τα υπολογιστικά μοντέλα δύο και τριών διαστάσεων, 2Δ και 3Δ, όπως σχεδιάστηκαν στο λογισμικό GAMBIT της Fluent Inc., βάση των διαστάσεων του εξατμιστή της πειραματικής εγκατάστασης. Τα αποτελέσματα της διερεύνησης που πραγματοποιήθηκε αφορούσαν το νερό, την ακετόνη, την αμμωνία σαν ρευστά λειτουργίας, τόσο στο επίπεδο όσο και υπό γωνίες κλίσης, παραμετροποιώντας τόσο το θερμαινόμενο μήκος πορώδους επί του συνολικού μήκους του πορώδους του εξατμιστή, όσο και τη θερμοκρασία κορεσμού. Τα δεδομένα για όλα τα ρευστά συγκεντρώθηκαν σε συγκριτικά διαγράμματα, ώστε να εξαχθούν συμπεράσματα για τα περιθώρια αξιοποίησης αυτών, είτε υπάρχει κλίση είτε όχι. Επιπλέον, τεκμηριώθηκε η επιλογή του νερού σαν καταλληλότερο ρευστό λειτουργίας κάτω από δεδομένες συνθήκες. Στο τρίτο μέρος παρουσιάζεται ο αριθμητικός κώδικας που δημιουργήθηκε για τη μοντελοποίηση ολόκληρης της εγκατάστασης του CPL και παραθέτουμε συγκριτικά διαγράμματα, για τις ίδιες συνθήκες λειτουργίας, με τα πειραματικά, τα αριθμητικά και τα υπολογιστικά αποτελέσματα. Στο τελευταίο μέρος έχουμε σχεδιάσει κυκλώματα, αξιοποιώντας την τριχοειδή αντλία, για τη ψύξη/θέρμανση των χώρων μιας κατοικίας για ολόκληρο το έτος. Μια πρόταση που βασίζεται στην αξιοποίηση της ηλιακής ενέργειας και ανταποκρίνεται στην επιτακτική ανάγκη για εκμετάλλευση των ανανεώσιμων πηγών ενέργειας και τη μείωση της χρήσης ηλεκτρικής ενέργειας, εξοικονομώντας χρήματα και προστατεύοντας το περιβάλλον / Present research was conducted in Fluid Mechanics Laboratory of the Mechanical Engineering and Aeronautics Department, University of Patras, and was financed by the operational programme «Herakleitos II», Education and Lifelong Learning Investing in knowledge society. Modern demands in controlling heating load of the cooling systems of mechanical or electrical components are increasing. Cooling systems are divided in active and passive systems. In active systems energy is transported due to sensual heat. While in passive systems due to working fluid latent heat of evaporation because of capillary forces developed in the porous wick inside the evaporator. Passive systems are preferred compared to active systems because they can transfer larger amount of heat, are more reliable, since there are no moving parts, and, finally, lifetime period is longer. The Capillary Pumped Loop (CPL) is a device proper for thermal management control, and was investigated in the present PhD study. The CPL operating principle is based on capillary action, developed in the liquid-vapor phase interface of the working liquid in the porous wick inside the evaporator, and working fluid evaporation and condensation latent heat. The result is that the working fluid is displaced inside the loop without any mechanical pump and heat load is transported in large distances. CPL main components are an evaporator, a condenser, a liquid line, a vapor line and a reservoir. Research regarding the CPL experimental models so far concentrated in the evaporator start-up and steady working state conditions. For all those cases heat load was applied through electric resistances. In the present study heat load was alternatively applied through solar radiation using a solar simulator, designed for this purpose. In order to achieve higher temperature in the evaporator external wall and increase solar radiation exploited, a parabolic mirror was used in combination with a solar collector. The experimental installation was designed in such a way to study the behavior of a CPL when heat load was imposed under different loop charging pressures and for several evaporator inclination angles. Experimental results where compared to the results acquired for evaporator operating at zero inclination angle. The initial values of the working fluid temperature were 15, 25, 35 and 45 oC, of the charging pressure 0,05, 0,15, 0,25 bar and of the inclination angle 8, 16 and 23o. The duration of the experiments was initially ten hours, in order to simulate CPL operating during a typical summer day, and then increased to twenty four hours to investigate continuous operation during all day. In the second section of this study two and three dimensions, 2D and 3D, computational models are presented designed in Gambit, Fluent Inc., based on the exact dimensions of the experimental ones. Computational results were derived for water, acetone and ammonia, as working fluid, for zero inclination and the three values of angles mentioned above. Models were customized for different porous wick heated length and working liquid of different saturation temperature. Comparative figures for all working fluids are presented whether evaporator was under inclination angle or not. Moreover, those comparative figures reviled that water was more suitable as working fluid under steady operating state. In the third section the numerical model simulating the overall CPL function is presented and comparative figures between experimental, computational and numerical results are given, for the same operating conditions. In the last section a potential solar CPL heating/cooling system for domestic use is presented. This potential system could meet the demands for using renewable energy sources in order to reduce electrical energy consumption, save money and protect the environment at the same time.

New technologies to probe the global output of the normal and cancer genomes have recently reached widespread use. The resulting genomewide gene expression profiles, e.g, a gene expression measurement per gene and per tissue sample, remain challenging to analyze and interpret, but have already provided new insights into the pathophysiology of cancer and towards personalized care.<p><p><p>In vitro cell culture-based experimental models are used to elucidate cancer onset and progression because experimentation in humans is difficult practically and ethically unacceptable, and because they provide simplified, reproducible and controlled systems to test hypotheses. The thyroid tumors and their in vitro experimental models are particularly suited to compare the molecular phenotypes of experimental models and tumors. From one type of cell, the thyrocyte, at least five distinct benign and malignant tumors can arise. In addition, many immortalized tumor-derived cell lines and primary cultures models of these cells exist.<p><p><p>This thesis has focused on the bioinformatic comparison of these in vitro models to the in vivo tumors, from the point of view of their gene expression profiles, to gain insight into the pathogenesis of thyroid tumors, and of tumors in general.<p><p><p>In a first study, we showed that primary cultures of freshly isolated normal thyroid cells where proliferation and differentiation through the TSHR/cAMP pathway was chronically activated experimentally resemble specifically the autonomous thyroid adenomas, a type of benign thyroid tumor, and provide insight into a general mechanism of tumor progression: the suppression of negative feedbacks that normally restrain excessive cell division.<p><p><p>Subsequently, we found that immortalized thyroid tumor-derived cell lines have converged to a common phenotype regardless of their tumor subtype of origin. A TSHR/cAMP thyroid cell differentiation signature, derived from data obtained for the first study, was used to show that the cell lines were dedifferentiated. Accordingly, we showed that the cell lines resemble most the phenotype of the more dedifferentiated, clinically aggressive anaplastic thyroid cancers.<p><p><p>Finally, using large databases of gene expression profiles publicly available, we extended the comparison of cell lines and tumors to cancers of five other organs: breast, colon, kidney, ovary and lung. We discuss the correct use of these models and advance an hypothesis regarding the nature of the state to which these cells have converged: they could represent a surviving subpopulation of tumors cells, cancer stem cells, capable of initiating and maintaining tumor growth.<p><p><p>As other technologies designed to perturb the genome in experimental models are emerging, careful characterization and validation of the experimental models are needed to extrapolate the results in vivo.<p> / Doctorat en sciences biomédicales / info:eu-repo/semantics/nonPublished

La démyélinisation et la mort oligodendrocytaire sont bien connues dans la sclérose en plaques (SEP). Au cours de ces dernières années, plusieurs études ont également décrit ce type de lésion après un traumatisme crânien (TC), participant à l’aggravation des lésions de la substance blanche, responsables des dysfonctionnements cognitifs et moteurs. Malgré de nombreux efforts, aucune thérapie efficace n’est disponible à ce jour pour traiter les lésions de la substance blanche. Dans ce contexte, une stratégie thérapeutique prometteuse serait de freiner la neuro-inflammation et la démyélinisation, en plus de promouvoir la maturation des oligodendrocytes afin de favoriser la remyélinisation des axones et de limiter ainsi leur dégénérescence. Notre choix de stratégie porte sur la stimulation des processus de réparation endogène via la protéine neuroprotectrice et neurotrophique sAPPα, forme soluble de la protéine βAPP libérée par l’action des α-sécrétases (ADAM10). Dans ce contexte, l’objectif de mes travaux de thèse était d’étudier l’intérêt thérapeutique de l’étazolate, un activateur desα-sécrétases, sur les conséquences biochimiques, histologiques et fonctionnelles, dans différents modèles de TC et de SEP in vivo chez la souris, et ex vivo sur des tranches organotypiques de cervelet. Les résultats obtenus sur le modèle de TC par percussion mécanique chez la souris ont montré pour la première fois le potentiel anti-inflammatoire de l’étazolate, associé à la restauration du taux de la sAPPα. De plus, l’étazolate s’est également opposé aux troubles fonctionnels post-TC tels que l’hyperactivité locomotrice et le déficit cognitif à court et à long terme. Par la suite, j’ai développé un nouveau modèle ex vivo de TC par percussion mécanique sur des tranches organotypiques de cervelet. Nous avons montré pour la première fois que l’étazolate était neuroprotecteur dans le tissu cérébelleux, et qu’il s’opposait à la démyélinisation post-traumatique. Par ailleurs, les effets bénéfiques de l’étazolate sur les gaines de myéline ont été reproduits dans un modèle ex vivo de démyélinisation induite par la lysolécithine, modèle ex vivo de SEP. De façon intéressante nous avons montré que l’étazolate exerçait un effet remyélinisant en stimulant la différenciation des oligodendrocytes. Cet effet a été reproduit in vitro dans des cultures primaires mixtes de cellules gliales issues de souris PLP-eGFP, où la maturation morphologique des oligodendrocytes a été favorisée en présence d’étazolate. L’ensemble des effets bénéfiques exercés par l’étazolate a été inhibé en présence d’un inhibiteur pharmacologique spécifique d’ADAM10, le GI254023X, suggérant que l’effet remyélinisant de l’étazolate dépend, au moins en partie, d’ADAM10. Par la suite, l’effet remyélinisant de l’étazolate a été étudié dans un modèle in vivo de démyélinisation chronique induite par la cuprizone. Dans ce modèle, l’étazolate a été capable de promouvoir la remyélinisation en stimulant la différenciation des oligodendrocytes, confirmant nos résultats in vitro et ex vivo. L’ensemble de mon travail permet de considérer le potentiel thérapeutique de l’étazolate, en visant l’ADAM10 comme nouvelle cible thérapeutique neuroprotectrice et remyélinisante. Cela aura pour intérêt de limiter la neuro-inflammation, la démyélinisation, ainsi que de promouvoir la différenciation des oligodendrocytes et la remyélinisation, afin de favoriser la récupération fonctionnelle suite aux lésions de la substance blanche survenant après un TC ou la SEP chez l’homme. / Demyelination and oligodendrocyte cell death are well established in multiple sclerosis (MS) and are increasingly described after traumatic brain injury (TBI), participating in the aggravation of white matter injury responsible of motor and cognitive deficits. Despite many efforts in clinical research, no efficient therapy against white matter injury progression is available nowadays. Thus, promoting remyelination and counteracting neuroinflammation and demyelination are major therapeutic strategies in order to restore white matter integrity. Here, we studied the stimulation of endogenous repair mechanisms through the neuroprotective and neurotrophic protein sAPPα, the soluble form of βAPP protein released by the α-secretases (ADAM10). In this context, the aim of this work was to evaluate the therapeutic potential of etazolate, an α-secretase activator on short- and long-term biochemical, histological and functional outcome in different mouse models of TBI and MS in vivo, and ex vivo on organotypic cerebellar slices. The results obtained from the TBI mouse model by mechanical percussion showed for the first time the anti-inflammatory effect of etazolate associated to a restoration of sAPPα levels. The same treatment was able to attenuate functional deficits (hyperactivity, cognitive deficit). We also developed a new ex vivo model of TBI by mechanical percussion on organotypic cerebellar slices. We confirmed the neuroprotective effect of etazolate on cerebellar tissue reducing the lesion size. Interestingly, etazolate treatment attenuated post-traumatic ex vivo demyelination. Moreover, the beneficial effect of etazolate on myelin sheaths have been well reproduced after lysolecithin-induced demyelination, an ex vivo model of MS. Interestingly, etazolate was able to enhance remyelination promoting oligodendrocyte differentiation. This effect has been reproduced in the primary mixed glial culture from PLP-eGFP mice, enhancing oligodendrocyte morphological maturation. However, etazolate failed to promote its beneficial effects in the presence of GI254023X, a specific ADAM10 (α-secretase) inhibitor, suggesting that the mechanism of action of etazolate is partly through the activation of ADAM10. Furthermore, etazolate reproduced in vivo the oligodendrocyte differentiation, accompanied by an increase of the myelinated axons, observed by electron microscopy in a mouse model of cuprizone-induced chronic demyelination. Taken together, the findings of this work provide a first evidence for the therapeutic potential of etazolate, with ADAM10 as new therapeutic target in white matter repair. The interest of this approach is to attenuate neuroinflammation and demyelination and to enhance oligodendrocyte differentiation and thus remyelination, in order to promote functional recovery following white matter lesions arising after TBI or MS.