Le canal sodique épithélial, ENaC, est une protéine hétéromérique constituée de trois sous-unités: [alpha], [bêta] et [gamma]. ENaC est exprimé au niveau de la membrane apicale des cellules épithéliales du néphron, du colon distal et des voies aériennes. Au niveau du néphron, l'activité et l'expression de ENaC sont finement régulées par deux hormones: l'aldostérone et la vasopressine, ce qui fait de ENaC un élément clé du maintient de la pression artérielle. ENaC joue également un rôle dans la régulation de la pression artérielle dans le colon distal. Il existe plusieurs mutations du canal directement liées à des troubles graves de la pression artérielle: le syndrome de Liddle et le pseudoaldostéronisme de type I (PHA I). La première pathologie est un gain de fonction du canal provoquant une hypertension précoce et sévère alors que le PHA I est une perte de fonction caractérisée par une diminution de la réabsorption sodium et une hypotension. ENaC est également une cible thérapeutique de choix dans les hypertensions de type 1. Il a récemment été démontré que la sous-unité [alpha] ENaC était impliquée dans l'augmentation de l'activité du canal de cobaye mais pas de rat par deux ligands extra-cellulaires: le cpt-cAMP un analogue perméant de l'AMPc, et le glibenclamide, un inhibiteur des canaux K[indice inférieur ATP]. Notre objectif est de déterminer les sites d'interaction des ces ligands avec ENaC ce qui permettra de mieux comprendre la relation structure/fonction de la boucle extra-cellulaire. Des techniques de biologie moléculaire nous ont permis de construire des sous-unités [alpha] chimériques contenant des séquences de rat et de cobaye. Ces chimères ont été coexprimées dans l'ovocyte de xénope avec les sous-unités [bêta] rat et [gamma] rat et les courants macroscopiques ont été enregistré en voltage clamp à deux électrodes. Nous avons ainsi déterminé que les régions centrales et terminales de la boucle extra-cellulaire de la sous-unité [alpha]gp conféraient une sensibilité partielle au cpt-cAMP. La réalisation de mutants nous a permis d'identifier cinq acides aminés dans la région terminale de la boucle dont une isoleucine en position 510 indispensable à l'activation du canal par le cpt-cAMP. Nous avons montré en patch clamp en configuration"outside out" que cette augmentation du courant macroscopique résultait d'une augmentation de la NPo du canal et non de sa conductance unitaire. Concernant l'interaction entre le glibenclamide et la sous-unité [alpha], nous avons employé la même approche que pour le cpt-cAMP. Nos résultats préliminaires indiquent que la totalité de la boucle extra-cellulaire est impliquée dans l'interaction avec le glibenclamide. Comme pour le cpt-cAMP, la région terminale de la boucle extra-cellulaire confère la plus grande sensibilité au ligand. Cependant, nous n'avons pas identifié tous les acides aminés interagissant avec le glibenclamide. Nous soupçonnons l'isoleucine 510 de jouer un rôle dans cette interaction.

Military sexual trauma (MST) has been associated with poor emotional and psychological well-being, less overall life satisfaction, and poorer health in general as well as higher rates of posttraumatic stress disorder (PTSD). The Department of Veterans Affairs provides treatment for veterans who experienced MST and recommends cognitive processing therapy (CPT) as a preferred treatment modality. Quantitative studies have shown that CPT can decrease symptoms of PTSD; however, a neglected area of study concerns the experiences of veterans who receive CPT for MST-related PTSD. In this generic qualitative study, the perceptions and experiences of female veterans who were survivors of MST and received CPT from a VA provider through a feminist lens were explored. Twenty-one female veterans who were survivors of MST and who sought treatment at the VA and received CPT were asked to complete a written questionnaire. The research questions explored the participants' experiences with CPT, changes in their symptoms, social lives and relationships, and general functioning and well-being after receiving CPT. Thematic analysis was used to identify 3 themes. Findings revealed that although participants described their experience of deciding whether to participate in CPT and receiving CPT as difficult, they reported increased quality of life and improved well-being after CPT. The results from this study will increase understanding of the experiences of veterans with CPT. Finally, scholar practitioners may be able to use findings from this study to enhance awareness of perceptions of clients, improve practice, and better serve clients who have experienced MST.

Approximately two-thirds of US adults are overweight or obese, and obesity is also becoming more prevalent in children and adolescents. Similar to adults, obese children are at a higher risk of developing health problems due in part to dysfunctional immune surveillance. Obesity has been shown reduce the generation of new T-cells by accelerating thymic aging in an adult mouse. This study therefore aimed at determining whether similar diet induced obesity (DIO) changes can be induced in a young mouse. Comparisons made between lean and DIO C57Bl/6 mice showed a significant increase in thymic weight, decrease in thymic cellularity and thymic output, and impaired T-cell development at the double negative stage. We associate these alterations with changes in thymic architecture and accumulation of lipid droplets within the thymic cortex and medulla of the obese mice. The above observations indicate that DIO can induce fat accumulation and reduce thymic function at a young age. Resveratrol, a natural polyphenolic compound, was then used to regulate fat metabolism in an attempt to reduce these DIO changes we observed. Resveratrol induces fat oxidation via 5' adenosine monophosphate-activated protein kinase (AMPK), and its reciprocal regulation of glycerol-3-phosphate acyltransferase-1 (GPAT-1) and carnitine palmitoyltransferase-1 (CPT-1), the rate-limiting enzymes required for glycerophospholipid biosynthesis and oxidation, respectively. Through resveratrol feeding, we were able to prevent the effects of DIO on thymic architecture and thymic T-cell proliferation. This was achieved by manipulating AMPK into inhibiting GPAT-1 and enhancing CPT-1 activity. Since the expression of GPAT-1 was upregulated in the obese mice, we investigated whether deleting GPAT-1 altogether might prevent the thymic involution, by inhibiting synthesis of glycerophospholipids and triacylglycerol. Instead, we found that GPAT-1 deletion slowed thymic growth and reduced cellularity in young mice, which we associated with impaired thymic T-cell function and development, suggesting that the deleterious effects of GPAT-1 deficiency may be due to perturbations in thymic T-cell activation and signaling. These data provide a novel link between lipid metabolism and T-cell development, and identify the use of the naturally-occurring resveratrol to reduce lipid accumulation within the involution-prone thymus, thus providing a useful approach to preventing a decline in thymic function in childhood. / text

Στην παρούσα εργασία μελετάμε την κυκλική μεταφορά πληθυσμών σε κβαντικά συστήματα με σπασμένη συμμετρία μέσω εξαναγκασμένης αδιαβατικής μετάβασης Raman (STIRAP) στην οποία προσθέτουμε μια διαδικασία ενός φωτονίου που κλείνει τον κύκλο μετάβασης. Αρχικά μελετάμε το σύστημα θεωρητικά για καθαρούς παλμούς ενώ στη συνέχεια προσθέτουμε όρους θορύβου και αποσβεσης (decay) προσεγγίζοντας, έτσι, περισσότερο ένα ρεαλιστικό σύστημα. Η μελέτη του δεύτερου μέρους βασίζεται στη λύση των εξισώσεων του συστήματος με αριθμητικές μεθόδους. / We study cyclic population transfer in quantum systems with broken symmetry through stimulated Raman adiabatic passage (STIRAP) in which we add a one-photon process that closes the STIRAP two-photon process. After the initial theoretical treatment of the problem, for simple Gaussian pulses, we later add noise and decay terms in the Hamiltonian of the system, rendering a more realistic approach. On the second part of this study we use numerical methods to solve the equations found.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / Correlations between the results from cone and SPT in sands are established in the present research for different sand densities. Such proposition is based on the experience obtained with the use of piezocone whose penetration in sands occurs commonly in drained condition. The SPT penetration, on the other hand, is much faster, occurring in a partially drained condition. The results confirm distinct correlations for different sand densities. The qc/NSPT ratio of 0,6MPa for sands, obtained from Danziger and Velloso (1986, 1995), for the whole data, is consistent with the value obtained in the present research if no distinction of density is made. If distinct density range is considered, the qc/NSPT ratio was found to be 1,1; 0,8; 0,6 and 0,5MPa, respectively for very loose, loose, medium and dense sands. Such results have repercussion on foundation design, as long as the most common methods applied in design make use of correlations between the CPT and SPT results. While the traditional correlations depend only on soil granulometry, the results presented in this research show that the relative density is of fundamental importance and must be also considered. In relation to the friction ratio, no tendency of variation with the relative density of sand has been observed, as expected, as long as both fs and qc are obtained from the cone. The results obtained with Palacios (1977) data, with liner removal, and also the comparison between the resistance mobilized during the SPT sampler penetration evaluated by Schmertmann (1979) and Aoki et al. (2004) show that sampler plugging in sand probably does not occur. / Nesta pesquisa são estabelecidas correlações entre os resultados de ensaios de cone (CPT) e de SPT em areias, para diferentes faixas de compacidade. A proposta se fundamenta em experiência com o ensaio de piezocone, que ocorre quase sempre nas areias em condições drenadas. A realização do SPT se dá a maiores velocidades, em condição parcialmente drenada. Os resultados confirmam diferentes correlações para diferentes compacidades. Verificou-se que o valor 0,6MPa da relação qc/NSPT para areias, indicado por Danziger e Velloso (1986,1995), para os dados globais, é consistente com a média da faixa indicada nesta dissertação. Considerando-se as diferentes faixas de compacidade os valores encontrados de qc/NSPT foram de 1,1; 0,8; 0,6; 0,5MPa, respectivamente para areias fofas, pouco compactas, medianamente compactas e compactas. Tais resultados têm repercussão no projeto de fundações, em que métodos de projeto utilizam correlações entre os resultados de SPT e CPT. Enquanto nas correlações tradicionais os valores de qc/NSPT são função apenas da granulometria, os resultados apresentados mostram que a compacidade relativa tem importância fundamental, devendo ser também considerada. Em relação à razão de atrito, não se observou tendência de variação com a compacidade, conforme esperado, pois tanto fs como qc são obtidos do cone. Os resultados obtidos com os dados de Palacios (1977), com a remoção do liner, bem como a comparação entre os valores da força resistente à penetração do amostrador, a partir da interpretação de Schmertmann (1979) e Aoki et al. (2004), sinalizam para o não embuchamento do amostrador quando da sua penetração em areias.

Made available in DSpace on 2014-06-11T19:22:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-08-19Bitstream added on 2014-06-13T20:48:01Z : No. of bitstreams: 1 arbex_cjn_me_bauru.pdf: 913801 bytes, checksum: d07afb491bb762699a6e8c708405c758 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Este trabalho apresenta um estudo de aplicação da Teoria de Potência Conservativa (CPT) na geração da referência para um filtro ativo de potência paralelo (FAP), a fim de promover a compensação de distúrbios de corrente em um sistema elétrico trifásico a três fios. Apresenta, também, um resumo de algumas das principais teorias de potência utilizadas na análise de sistemas elétricos com formas de onda não senoidais e desequilibradas, especialmente aquelas úteis para o controle de filtros ativos. Atenção especial foi dada para a teoria CPT que, além de ser uma proposta recente, permite selecionar o distúrbio a ser compensado pelo filtro ativo paralelo, bastando definir sua referência a partir das parcelas de corrente da CPT. Neste trabalho também foi proposta uma metodologia de projeto para filtros ativos paralelo, a qual é baseada na análise da carga através da CPT e em função da compensação seletiva de distúrbios. Dessa forma é possível estudar a viabilidade econômica de um dado filtro ativo paralelo escolhendo a parcela de corrente mais adequada a ser compensada, obviamente, dentro de uma determinada configuração de carga. Outro ponto destacado no trabalho foi a introdução de uma nova definição de fator de potência, proposta pela CPT e que, além de reativos, também considera os efeitos dos desequilíbrios e das distorções no sistema elétrico. Com base nesta nova definição, percebe-se a necessidade de uma revisão dos valores de referência definidos pelas normas atuais para o fator de potência. A validação dos estudos e do uso da CPT no controle do filtro ativo paralelo foi feita através de simulações computacionais no software PSIM / This work presents an application study of the Conservative Power Theory (CPT) in the generation of control reference for a Parallel Active Power Filter (PAF), in order to compensate current disturbances in a Three-phase three-wite electrical power system. Some of the most important power teories find in literature have also been summarized, especially those related to active filter controlling techniques. Special attention was given for the CPT, since is a recent proposal and it allows the selection of the disturbance to be compensated through the definition of different control references using different CPT current parcels. An alternative methodology has also been proposed tot the design of the parallel active power filter, which is based on the analysis of the load by means of the CPT current decomposition and according to a previously defined selective compensating strategy. Therefore, it is possible to analyze the economic viability of the active power filter implementation if choosing the most important disturbance to be compensated, obvioulsly assuming a specific load configuration. Other important contribution was the discussion of a new power factor definition (proposed by the CPT), which considers not only the load reactive behavior, but also the effects of current unbalances and distortions on the efficiency of the power circuit. Based on this new definition, we observe the necessity of revising the normalized referential values in order to ensure a proper accountability or revenue metering methodology. Finally, the theoretical studies and the CPT application for controlling a parallel active filter were validated by means of computational simulations using PSIM software

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / Correlations between the results from cone and SPT in sands are established in the present research for different sand densities. Such proposition is based on the experience obtained with the use of piezocone whose penetration in sands occurs commonly in drained condition. The SPT penetration, on the other hand, is much faster, occurring in a partially drained condition. The results confirm distinct correlations for different sand densities. The qc/NSPT ratio of 0,6MPa for sands, obtained from Danziger and Velloso (1986, 1995), for the whole data, is consistent with the value obtained in the present research if no distinction of density is made. If distinct density range is considered, the qc/NSPT ratio was found to be 1,1; 0,8; 0,6 and 0,5MPa, respectively for very loose, loose, medium and dense sands. Such results have repercussion on foundation design, as long as the most common methods applied in design make use of correlations between the CPT and SPT results. While the traditional correlations depend only on soil granulometry, the results presented in this research show that the relative density is of fundamental importance and must be also considered. In relation to the friction ratio, no tendency of variation with the relative density of sand has been observed, as expected, as long as both fs and qc are obtained from the cone. The results obtained with Palacios (1977) data, with liner removal, and also the comparison between the resistance mobilized during the SPT sampler penetration evaluated by Schmertmann (1979) and Aoki et al. (2004) show that sampler plugging in sand probably does not occur. / Nesta pesquisa são estabelecidas correlações entre os resultados de ensaios de cone (CPT) e de SPT em areias, para diferentes faixas de compacidade. A proposta se fundamenta em experiência com o ensaio de piezocone, que ocorre quase sempre nas areias em condições drenadas. A realização do SPT se dá a maiores velocidades, em condição parcialmente drenada. Os resultados confirmam diferentes correlações para diferentes compacidades. Verificou-se que o valor 0,6MPa da relação qc/NSPT para areias, indicado por Danziger e Velloso (1986,1995), para os dados globais, é consistente com a média da faixa indicada nesta dissertação. Considerando-se as diferentes faixas de compacidade os valores encontrados de qc/NSPT foram de 1,1; 0,8; 0,6; 0,5MPa, respectivamente para areias fofas, pouco compactas, medianamente compactas e compactas. Tais resultados têm repercussão no projeto de fundações, em que métodos de projeto utilizam correlações entre os resultados de SPT e CPT. Enquanto nas correlações tradicionais os valores de qc/NSPT são função apenas da granulometria, os resultados apresentados mostram que a compacidade relativa tem importância fundamental, devendo ser também considerada. Em relação à razão de atrito, não se observou tendência de variação com a compacidade, conforme esperado, pois tanto fs como qc são obtidos do cone. Os resultados obtidos com os dados de Palacios (1977), com a remoção do liner, bem como a comparação entre os valores da força resistente à penetração do amostrador, a partir da interpretação de Schmertmann (1979) e Aoki et al. (2004), sinalizam para o não embuchamento do amostrador quando da sua penetração em areias.

Vid geotekniska fältundersökningar används ofta ”Cone Penetration Test” (CPT-sondering). Denna metod ger en bedömning av jordlagerföljd samt en uppskattning av de geotekniska egenskaperna. Metoden används i lösa till fast lagrade jordar med kornstorlekar upp till grusfraktion, alltså jordar där en sond kan tryckas ned utan slag eller rotation.  När en CPT-spets penetrerar en vattenmättad tät jord sker en omlagring av jorden varvid en lokal ökning av portrycket sker. När ett portrycksutjämningstest utförs, stoppas den nedåtgående rörelsen av sonderingen under en viss tid och portrycket tillåts att klinga av.  Det portryck som sedan uppmäts förväntas motsvara det rådande porvattentrycket på nivån. Syftet med denna studie är att utreda om metoden är lämplig att använda vid mätning av portryck samt om den kan ersätta portrycksspetsar i vissa fall, exempelvis vid tidiga skeden av projekt etc. Studien utfördes för att bedöma hur lång tid portrycksutjämningsförsök tar beroende på jordens permeabilitet, om resultatet blir annorlunda om artesiskt portryck råder, hur resultatet skiljer sig beroende på vilken jordtyp försöket utförs i, om resultatet blir liknande som vid mätning med BAT-portrycksspets samt om det går att hitta samband mellan resultat för försök som är utförda i liknande jord. Den geotekniska fältundersökningen genomfördes i Röbäck som är beläget sydväst om Umeå centrum. Fältundersökningen var tidsmässigt begränsat till 3 dagar. Portrycksutjämnings-försöken tilläts pågå under maximalt 2 timmar per nivå eller till dess att portrycksutjämningen klingat av. Undersökningarna är huvudsakligen utförda i sulfidhaltig jord och endast en typ av CPT-utrustning har använts. Inga portryck som uppmättes vid portrycksutjämningsförsöken var lägre än de som mättes i de installerade portrycksspetsarna för samma nivå. Det tog längre tid för portrycket att klinga av där försöket utfördes på större djup under markytan. Resultatet blev inte annorlunda på de platser där artesiskt portryck uppmätts. Denna studie indikerar att en väntetid på 2 timmar i denna typ av jord endast var tillräckligt lång tid för portrycksutjämningstest ned till ca 7 meter under markytan. I jord med låg permeabilitet, så som i denna fallstudie, blir väntetiderna vid varje stopp väldigt långa. Detta försvårar det praktiska utförandet i fält.

El desarrollo de nanofármacos aplicados en terapias frente al cáncer es un prometedor campo de la biomedicina en el cual se entrecruzan diferentes disciplinas científicas como la biología, la ciencia de los materiales, química, medicina y farmacia. Con la aplicación clínica de este tipo de materiales se pretende superar los inconvenientes que presentan los actuales tratamientos contra el cáncer, como una limitada efectividad terapéutica y un gran número de efectos secundarios. La presente tesis doctoral se ha enfocado en la síntesis de nanofármacos basados en sílice para la difusión intracelular y liberación controlada del agente antineoplásico camptotecina. En primer lugar, se llevó a cabo la síntesis de diversos nanomateriales aplicando el método sol-gel. En paralelo, se obtuvieron diferentes profármacos para su posterior incorporación a los materiales mediante enlace covalente. Tras una completa caracterización, se comprobó la estabilidad de los nanofármacos en medio fisiológico y, una vez demostrada su robustez, se procedió al estudio del mecanismo de liberación del principio activo a partir del nanofármaco, realizando experimentos de liberación mediante la aplicación de diferentes estímulos. Sobre los datos experimentales obtenidos se aplicaron varios modelos cinéticos de liberación de fármacos, observando que la difusión en matrices granulares es el fenómeno físico-químico de mayor influencia. Posteriormente, se evaluó la actividad antineoplásica in vitro de los nanofármacos mediante ensayos de viabilidad celular, apreciando una toxicidad similar a la del fármaco libre. Por otro lado, también se realizaron experimentos para determinar los principales factores que influyen en la internalización de los materiales por parte de las células, siendo estos el diámetro hidrodinámico y la hidrofobicidad del material. Finalmente, se investigó la biodistribución, tolerabilidad y eficacia terapéutica in vivo en un modelo de xenoinjerto de cáncer colorectal humano en ratones. A pesar de observarse una importante captación del nanofármaco por células del sistema retículoendotelial, la acumulación del sistema terapéutico en el tumor mejoró la efectividad del fármaco libre, a la vez que se minimizaron los efectos secundarios del agente antitumoral. Los resultados obtenidos apuntan al desarrollo de una nueva generación de fármacos basados en nanomateriales híbridos orgánicoinorgánicos, capaces de llevar a cabo terapias anticancerígenas con un elevado grado de eficacia y selectividad. / Muniesa Lajara, C. (2013). Materiales nanoestructurados biocompatibles basados en sílice. Preparación y aplicaciones en terapia anticancerígena [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/29691 / TESIS

Soil liquefaction, or loss of strength due to excess pore water pressures generated during dynamic loading, is a main cause of damage during earthquakes. When a soil liquefies (referred to as triggering), it may lose its ability to support overlying structures, deform vertically or laterally, or cause buoyant uplift of buried utilities. Empirical liquefaction models, used to predict liquefaction potential based upon in-situ soil index property measurements and anticipated level of seismic loading, are the standard of practice for assessing liquefaction triggering. However, many current models do not incorporate predictor variable uncertainty or do so in a limited fashion. Additionally, past model creation and validation lacks the same rigor found in predictive modeling in other fields. This study examines the details of creating and validating an empirical liquefaction model, using the existing worldwide cone penetration test liquefaction database. Our study implements a logistic regression within a Bayesian measurement error framework to incorporate uncertainty in predictor variables and allow for a probabilistic interpretation of model parameters. Our model is built using a hierarchal approach account for intra-event correlation in loading variables and differences in event sample sizes that mirrors the random/mixed effects models used in ground motion prediction equation development. The model is tested using an independent set of case histories from recent New Zealand earthquakes, and performance metrics are reported. We found that a Bayesian measurement error model considering two predictor variables, qc,1 and CSR, decreases model uncertainty while maintaining predictive utility for new data. Two forms of model uncertainty were considered – the spread of probabilities predicted by mean values of regression coefficients (apparent uncertainty) and the standard deviations of the predictive distributions from fully probabilistic inference. Additionally, we found models considering friction ratio as a predictor variable performed worse than the two variable case and will require more data or informative priors to be adequately estimated.