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Tchernitchko, Dimitri. "Études moléculaires de DMT1, un transporteur membranaire du fer." Paris 7, 2002. http://www.theses.fr/2002PA077183.
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Rivas, Romero Daniela Paz. "Modelación molecular y estudio de la isoforma 1A/IRE(+) de la proteína DMT1 humana." Tesis, Universidad de Chile, 2015. http://repositorio.uchile.cl/handle/2250/137489.
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Ingeniera Civil en Biotecnología<br>En distintos estudios se ha determinado que mutaciones en la proteína transportadora DMT1, encargada de transportar hierro desde el lumen intestinal hacia los enterocitos, son causantes de distintos tipos de anemia, no obstante, poco se conoce sobre su estructura tridimensional y su mecanismo de transporte. Por esta razón, el objetivo del presente trabajo es obtener un modelo estructural de la isoforma 1A/IRE(+) de la proteína DMT1 humana y a partir de éste estudiar el posible comportamiento de la proteína inserta en membrana.
La predicción de dominios transmembrana para la proteína de interés estableció la presencia de 12 dominios transmembrana, 6 loops extracelulares, 5 loops intracelulares y los extremos amino y carboxilo terminales al interior del citoplasma de los enterocitos, lo cual concuerda totalmente con lo expuesto en bibliografía. Se obtuvieron 100 modelos de la proteína mediante modelamiento comparativo, utilizando el cristal de la familia de la proteína, ScaDMT, como plantilla principal. El mejor modelo se obtuvo a través de un análisis energético y estructural. Este modelo obtuvo un z-score de -4.3, dentro de la densidad de puntajes obtenidos por estructuras cristalinas, un perfil energético por residuo similar al del cristal de ScaDMT, y un gráfico de Ramachandran con tan solo 2 residuos dentro de zonas no permitidas.
Se realizaron cuatro dinámicas moleculares para estudiar el comportamiento del modelo en membrana, las cuales fueron analizadas para estudiar las características de la proteína. A partir del análisis de los modos normales, se observó un movimiento de apertura y cierre, el cual podría representar el movimiento principal de captura y liberación del ion de hierro. Por otro lado, se presentó una variación en el potencial electrostático en las regiones superior e inferior de la proteína, lo que podría estar relacionado al mecanismo de interacción de la proteína con hierro. A partir del análisis del comportamiento de las moléculas de agua en el sistema, se determinó que éstas ingresan a la proteína por la zona orientada hacia el citoplasma, posicionándose entre las hélices TM1 y TM6, donde se ubica el ion de hierro. Finalmente, en cuanto a la interacción de la proteína con hierro, se proponen los residuos Asp115, Asn118, Ala291 y Met294 como principales candidatos a interaccionar con él, y se observa un posible rol del agua en la estabilización de éste.
De esta manera, los resultados y discusiones aquí expuestos representan los primeros avances para un mejor conocimiento de la estructura y características de la proteína DMT1 humana. Se requiere profundizar y extender estos análisis para poder establecer bases más sólidas respecto a la relación estructura-función y dilucidar el mecanismo de transporte asociado a la proteína. Esto resultaría de gran utilidad para comprender la causa de las enfermedades asociadas a mutaciones en DMT1 y posteriormente proponer tratamientos más efectivos para estas enfermedades.
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Colins, Rodríguez Andrea Justina. "Determinación experimental y modelación matemática de los flujos de transporte de hierro en células Caco-2." Tesis, Universidad de Chile, 2015. http://repositorio.uchile.cl/handle/2250/135289.
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Magíster en Ciencias de la Ingeniería, Mención Química<br>Ingeniera Civil en Biotecnología<br>El hierro es un metal traza, fundamental para la existencia de la vida. Los niveles de hierro en el organismo deben ser altamente controlados ya que pequeñas variaciones desencadenan numerosas enfermedades, entre ellas la anemia y hemocromatosis. En seres humanos la presencia de este metal se controla regulando su absorción intestinal, en donde el hierro ingresa al organismo a través de la proteína DMT1, ubicada en la cara apical de los enterocitos. Luego, el hierro es transportado a la cara basolateral y finalmente, es expulsado al torrente sanguíneo mediante la proteína FPN1.
\par El objetivo de este trabajo es analizar el transporte de hierro en células Caco-2 mediante métodos experimentales y modelación matemática. Para esto se determinaron experimentalmente los flujos de hierro en el tiempo, a diferentes concentraciones iniciales en el medio apical. Se determinó la velocidad inicial de la absorción en función de la concentración apical. Y además, se midió la cantidad de hierro que ingresa a las células luego de una segunda exposición al metal. Los resultados de estos experimentos concuerdan con las magnitudes reportadas en casos similares, pero muestran un comportamiento no lineal en los flujos de absorción, lo cual no había sido observado anteriormente.
\par Para analizar matemáticamente los resultados experimentales obtenidos, se desarrolló un modelo empírico y un modelo fenomenológico. El modelo empírico se construyó utilizando un algoritmo de programación genética modificado para lograr mejores resultados. El modelo representa adecuadamente los datos experimentales utilizados en la etapa de entrenamiento, alcanzado un coeficiente de determinación de $R^2=0.85$ y un error de generalización de $MSE_{jk}=1.32$. Además, el modelo permite representar la velocidad inicial de absorción apical, es decir, datos que no fueron empleados en la etapa de entrenamiento del algoritmo. Por otro lado, el modelo exhibe características básicas del fenómeno, sin que se le entregue información a priori al respecto.
\par El modelo fenomenológico consta de un conjunto de ecuaciones diferenciales ordinarias que capturan dos fenómenos relevantes. La actividad de DMT1 y la variación de la cantidad de ésta en la membrana apical. Este modelo permite simular todos los escenarios estudiados experimentalmente, asimismo representa los flujos de absorción apical con un coeficiente de determinación de $R^2=0.867$, mientras que su error de generalización es de $MSE_{jk}=1.39$.
\par Del análisis realizado, se concluye que la endocitosis de DMT1 desde la cara apical, es un fenómeno relevante en el proceso de absorción de hierro. Este fenómeno no había sido considerado anteriormente y debe ser estudiado en detalle para poder caracterizar el sistema.
\par En el trabajo se planteó una metodología para desarrollar modelos empíricos que puede utilizarse en otros sistemas biológicos complejos. Su principal ventaja es que permite mejorar la capacidad de generalización de los modelos realizados.
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Sáez, Rojas Carla. "Modelamiento matemático del movimiento de transportadores de hierro en células caco-2." Tesis, Universidad de Chile, 2014. http://www.repositorio.uchile.cl/handle/2250/130324.
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Ingeniera Civil en Biotecnología<br>El hierro es un elemento fundamental para muchos organismos por las reacciones en las que se encuentra involucrado, y su absorción está altamente regulada por mecanismos a diferentes niveles. El transporte de hierro se realiza en el duodeno a través de proteínas transportadoras que se encuentran en la membrana apical de los enterocitos (DMT1, Divalent Metal Transporter 1). Uno de los mecanismos de regulación involucra la traslocación de estas proteínas hacia el interior de las células cuando éstas son expuestas a una cierta concentración de hierro en la cara apical. Mediante este mecanismo se disminuye la absorción del mineral minutos después de dicha exposición.
En el presente trabajo se busca proponer un modelo fenomenológico que permita representar cualitativamente los perfiles de distribución espacial de DMT1 en el interior célular. Estos perfiles han sido observados experimentalmente en la línea celular Caco-2, la cual es comúnmente utilizada para estudios de transporte de hierro debido a sus características similares con los enterocitos del intestino delgado.
El modelo propuesto consiste en un sistema de ecuaciones diferenciales parciales cuya simulación permite obtener la distribución de DMT1 en el tiempo y espacio. Se realizaron simulaciones para obtener la distribución estacionaria inicial, y la evolución del sistema desde dicho estado hasta alcanzar una nueva distribución estacionaria producto de perturbar el sistema mediante la introducción de un pulso de hierro.
Como resultado se observó que el modelo es capaz de reproducir cualitativamente el comportamiento observado experimentalmente. A través de un estudio de variación de parámetros, se verificó que el comportamiento del sistema corresponde a lo esperado biológicamente. A partir de dicho estudio se encontró un set de parámetros que permiten simular el comportamiento en el estado previo a la exposición de hierro y uno que simula el estado posterior a dicha exposición. Se concluye que este modelo propuesto representa una primera aproximación para la simulación del movimiento de DMT1 en células Caco-2.
El modelo desarrollado en este trabajo es adecuado también para la representación de otros sistemas que involucren movimiento de vesículas o elementos desde un sitio a otro de la célula, debido a que sus ecuaciones son generales y sus parámetros pueden ser variados para la simulación de diferentes escenarios tales como distintas concentraciones de proteínas motoras o distintas velocidades de transporte. Ejemplos de estos sistemas son el movimiento vesículas de las proteínas transportadoras de glucosa GLUT-4, o la transistosis de diversos elementos en células epiteliales.
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Shawki, Ali. "The Functional Properties and Intestinal Role of the H+-Coupled Divalent Metal-Ion Transporter 1, DMT1." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448037106.
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Salazar, Rivera Julio. "Altération du métabolisme du fer dans la maladie de Parkinson : participation du Transporteur 1 de Métaux Divalents (DMT1) et des Protéines Régulatrices du Fer (IRPs) dans la mort des neurones dopaminergiques de la Substantia Nigra Pars Compacta." Paris 6, 2008. http://www.theses.fr/2008PA066242.
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La maladie de Parkinson (MP) est caractérisée par la mort préférentielle et accélérée des neurones dopaminergiques de la substance noire (SN) dont la cause est inconnue. De nombreuses études ont montré une augmentation des taux de fer dans les neurones dopaminergiques mélanisés et dans les cellules gliales de cette structure. En raison de son rôle pro-oxidant, le fer pourrait être un des facteurs expliquant la mort massive des neurones dopaminergiques dans la MP. Des études post-mortem, réalisées au sein de notre laboratoire (INSERM UMR679), ont montré que les sites de liaison de la transferrine, impliqués dans une voie classique d’entrée du fer, sont diminués en numéro dans les neurones dopaminergiques de sujets parkinsoniens. Avec l’objectif d’identifier le mécanisme d’augmentation du fer dans la MP, nous avons étudié la participation d’un autre transporteur : le transporteur 1 des métaux divalents (DMT1). Nos expériences ont montré que DMT1 est exprimé préférentiellement par les neurones dopaminergiques dans la SN des humains et des rongeurs. D’autre part, le niveau d’expression d’une des isoformes de DMT1 (DMT1+IRE) est augmenté dans des modèles animaux de la MP et dans la SN de cerveaux parkinsoniens. Et enfin, des rongeurs portant une mutation dans le gène DMT1 (les souris microcytiques et les rats Belgrade) sont protégés contre les neurotoxines MPTP et 6-OHDA, utilisées comme modèles animaux de la MP. Ces observations soutiennent l’hypothèse d’un rôle de DMT1 dans l’accumulation de fer et la mort neuronale dans la MP. Par la suite, nous nous sommes focalisés à étudier la potentielle participation des protéines régulatrices du fer (IRPs) dans la neurodegeneration associée à la MP. Les IRPs contrôlent la traduction de messagers des protéines du métabolisme du fer, comme DMT1. Normalement impliquées dans homéostasie cellulaire du fer, elles peuvent être modulées par le stress oxydant et favoriser l’augmentation du fer. En cohérence avec cette hypothèse nous avons montré que la souris déficiente pour le gène IRP1 est protégée contre la toxicité du MPTP. Cette étude confirme le rôle du fer dans la neurodégénérescence associée à la MP et suggère la participation de DMT1 et IRP1 dans la neurotoxicité médiée par le fer.
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Thomas, Carla. "The validation and use of the rat intestinal epithelial cell line 6 (IEC-6) to study the role of ferroportin1 and divalent metal transporter 1 in the uptake of iron from Fe(II) and Fe(III)." University of Western Australia. Physiology Discipline Group, 2003. http://theses.library.uwa.edu.au/adt-WU2004.0019.
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[Formulae and special characters can only be approximated here. Please see the pdf version of the abstract for an accurate reproduction.] Iron is vital for almost all living organisms by participating in a wide variety of metabolic processes, including oxygen transport, DNA synthesis, and electron transport. However, iron concentrations in body tissues must be tightly regulated because excessive iron leads to tissue damage, as a result of formation of free radicals. In mammals since no controlled means of eliminating unwanted iron has evolved, body iron balance is maintained by alterations in dietary iron intake. This occurs in the duodenum where most dietary iron is absorbed. Absorption involves at least two steps, uptake of iron from the intestinal lumen and then its transport into the body, processes that occur at the apical and basal membranes of enterocytes, respectively. In chapter one of this thesis the background information relevant to iron absorption is described. Despite numerous studies, the role of these proteins in iron absorption remains unclear, partly because many studies have reported them in non-enterocyte cell lines where the expression of the proteins involved in iron absorption is unlikely and therefore the physiological significance of the findings uncertain. Therefore, the study of iron absorption would value from additional cell lines of intestinal origin being used, preferably derived from a species used to comprehensively study this process in vivo, namely the rat. Validation of such a model would enable comparisons to be made from a molecular level to its relevance in the whole organism. In chapter 3 of this thesis, the rat intestinal cell line 6 (IEC-6) was examined as a model of intestinal iron transport. IEC-6 cells expressed many of the proteins involved in iron absorption, but not the ferrireductase Dcytb, sucrase or αvβ3 integrin. In addition, in IEC-6 cells the expression of the apical transporter divalent metal transporter 1 (DMT1), the iron storage protein ferritin, the uptake of Fe(II) and Fe(III) were regulated by cellular iron stores as is seen in vivo. This suggests that IEC-6 cells are of a lower villus enterocyte phenotype. Presented in chapter 4 is the study of the uptake of iron from Fe(II):ascorbate and Fe(III):citrate by IEC-6 cells in the presence of a blocking antibody to the putative basolateral transporter ferroportin1 and of colchicine and vinblastine, different pHs, and over-expression of DMT1. It was shown that optimal Fe(II) uptake required a low extracellular pH and was dependent on DMT1. Uptake of Fe(III) functioned optimally at a neutral pH, did not require surface ferrireduction, and was increased during over-expression of DMT1. These observations suggest that intravesicular ferrireduction takes place before transport of Fe(II) to the cytoplasm by DMT1. This pathway was not blocked by a functional antibody against αvβ3 integrin but was inhibited by competition with unlabeled iron citrate or citrate alone. Surprisingly, a functional antibody against ferroportin1 had no effect on efflux but significantly reduced (p<0.05) uptake of Fe(II) by 40-50% and Fe(III) by 90%, indicating two separate pathways for the uptake of iron from Fe(II)-ascorbate and from Fe(III)-citrate in IEC-6 cells. Presented in chapter 5 is the development and validation of a technique for the removal of freshly isolated enterocytes from the rat duodenum and their use to study iron transport processes that enabled comparisons to be made between these cells, IEC-6 cells and the human enterocyte cell line Caco-2 cells. In chapter 6 a blocking antibody to ferroportin1 was shown to inhibit uptake of Fe(II) but not release of iron in freshly isolated duodenal enterocytes from rats and Caco-2 cells supporting the findings obtained with IEC-6 cells described in chapter 4. Fe(II) uptake was reduced only when the antibody was in contact with the apical membrane indicating its expression at the microvillus membrane. Confirming this, ferroportin1 was shown along the microvillus membrane of Caco-2 cells, in enriched microvillus membrane preparations and in enterocytes of duodenum tissue of rats where it co-localised with lactase. The significant findings to emerge from this thesis are that the IEC-6 cell is a valid model to study iron absorption producing results consistent with those found in freshly isolated enterocytes and in human enterocyte-like cells. In particular, ferroportin1 functions in the uptake of iron at the apical membrane possibly by modulating surface binding of Fe(II) to DMT1 or the activity of DMT1. In addition to this in Fe(II) uptake from Fe(III) ferroportin1 may also affect the number of Fe(III): citrate binding sites. Preliminary studies further characterizing the function of ferroportin1 at the apical membrane and at intracellular sites of IEC-6 cells along with integration of these data are discussed in chapter 7.
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Kirui, Joseph Kiprono. "ESR study of DMTM(TCNQ)₂." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/29191.
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The ESR g-value and susceptibility measurements for DMTM(TCNQ)₂ have been studied as a function of angle made by crystal with magnetic field and temperature. The angular dependence of g-value is fitted to g² = α+βcos2θ - γsin2θ for three orthogonal directions of crystal rotation. The principal g-values are close to those expected for TCNQ compounds: g₁ = 2.0034, g₂ = 2.0030, g₃ = 2.0024. The susceptibility as a function of temperature agrees with bulk susceptibility measurements except that the maximum position occurs at about 30 K. The results of Oostra et al. for bulk susceptibility showed a maximum at around 50 K. The phase transition
reported by Visser et al. at 272 K is observed in the ESR data as a 15% decrease in susceptibility. The linewidth is remarkably anisotropic typical of TCNQ salts. The phase transition study is done for two orientations
of the crystal with the magnet field. In one of the orientations the linewidth narrows from 0.15 to 0.11 gauss and in the other it narrows from 0.24 to 0.18 gauss. In the former case there is a growth of a second line due to the twinned stack; transformation twinning takes place at the phase transition. A small level-crossing interaction is inferred from the change in relative intensities of the lines near the crossover.<br>Science, Faculty of<br>Physics and Astronomy, Department of<br>Graduate
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Gomes, Carolina Pereira. "Reprodução em Characidium schubarti (Teleostei: Characiformes): análise da reprodução em cativeiro e de genes relacionados à diferenciação sexual (dmrt1, cyp19a1a e amh)." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/41/41131/tde-29052014-103655/.
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Os peixes teleósteos representam cerca de metade de todas as espécies de vertebrados já descritas. Esta rica diversidade reflete-se nas diferentes formas de determinação sexual, sendo as principais desencadeadas por influência ambiental e por fatores genéticos. Os genes envolvidos neste mecanismo têm sido caracterizados em diversas espécies de peixes teleósteos, como é o caso dos genes dmrt1 e amh que têm importante papel na diferenciação em machos de teleósteos e o gene cyp19a1a, que possui relação com a diferenciação sexual de fêmeas. Têm sido cada vez mais corrente na literatura, estudos envolvendo genes da via de diferenciação sexual em espécies de teleósteos, porém escassas são as informações em relação à ordem Characiformes. Além da genética, a biologia reprodutiva de peixes teleósteos engloba ainda estudos relativos ao papel dos hormônios e do ambiente na reprodução, inclusive na reprodução em cativeiro. A presente dissertação tem como principal objetivo a análise dos genes acima citados na espécie Characidium schubarti (Characiformes) - que possui pouca informação sobre sua biologia reprodutiva na literatura-; caracterizando fragmentos dos genes dmrt1 e cyp19a1a e a similaridade destes com os mesmos já descritos em outras ordens de peixes teleósteos. Além disso, foi possível no desenvolver do projeto, obter informações pertinentes em relação ao papel do ambiente e de hormônios exógenos na reprodução da espécie. Espera-se que com o aumento de pesquisas envolvendo genes relacionados ao sexo, o objetivo de controlar o gênero sexual em peixes economicamente importantes possa ser alcançado com sucesso a partir do controle da expressão de fatores da via de diferenciação<br>Teleost fishes represent about half of all vertebrate species already described. Such a rich diversity is reflected in different forms of sex determination, the main ones being triggered by environmental influences and genetic factors. Genes such as amh and dmrt1 are involved in this mechanism and have been characterized in several teleost fish species, they play an important role in the differentiation of teleost males whereas the cyp19a1a gene is related to the female sexual differentiation. Have been increasingly common in the literature, studies concerning the rule of genes in sex differentiation in teleosts, however pieces of information regarding the order Characiformes are scarce. Besides genetics, reproductive biology of teleost fishes also includes studies on the role of hormones and environment on reproduction, and also captive breeding. This thesis aims to analyze the aforementioned species in Characidium schubarti (Characiformes) genes for which little information exists on their reproductive biology literature featuring fragments of genes dmrt1 and cyp19a1a and the similarity of these with those already described in other orders of teleost fish . Moreover, it was possible to develop the project, obtaining relevant information regarding the role of the environment and exogenous hormones in reproduction of the species. It is expected that with the increase of research involving genes related to sex, in order to control the sexual gender for such an economically important fish can be successfully achieved from the control of the expression of factors of differentiation
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Xu, Yang. "Equalization algorithms for ADSL DMT system." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0004/MQ36756.pdf.
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Siyam, Arwa. "NUCLEAR LOCALIZATION OF DMP1 AND DSPP IN VARIOUS CELL LINES." Master's thesis, Temple University Libraries, 2012. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/183440.
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Oral Biology<br>M.S.<br>Objective: To examine Dentine matrix protein 1(DMP1) and Dentine sialophosphoprotein (DSPP) expression and subcellular localization in various cell lines to better understand their function. Methods: RT-PCR, immunofluorescent staining and Western-blotting analyses were used to determine the expression and subcellular localization of DMP1 and DSPP in various cell lines, including odontoblast-like (17IIA11), preosteoblast (MC3T3-E1), mesenchymal cells (C3H10T1/2), and human dental pulp stem cells (DPSC). In addition, a haemagglutinin (HA) tagged DMP1 expression construct was generated and examined for its subcellular localization in COS-7 cells. Results: Western-blot analysis showed the presence of DMP1 and DSPP in the cytoplasmic and nuclear extracts of MC3T3-E1, 17IIA11, and C3H10T1/2 cells. DMP1 and DSPP transcripts were consistently detected in all three cell lines by RT-PCR analysis. However, immunofluorescent detection of DMP1 revealed the presence of two distinct subpopulations of cells with either nuclear or cytoplasmic staining; this phenomenon was not noticed with DSPP immunofluorescence. Nuclear and cytoplasmic DMP1 was confirmed in MC3T3-E1 cells by immuofluorescent staining using a rabbit polyclonal antibody; and the staining was inhibited when the antibody was preincubated with the synthetic peptide used to generate the antibody, confirming the specificity of the antibody. Nuclear and cytoplasmic localization was also observed in COS-7 cells transfected with HA-tagged DMP1 expression construct when detected with an antibody against the HA tag. Conclusion: These findings suggest that, apart from their role as a constituent of dentin/bone matrix, both DMP1 and DSPP might play a regulatory or structural role in the nucleus that is not unique to the odontoblast/osteoblast cells.<br>Temple University--Theses
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Guan, Juan. "Investigations on natural silks using dynamic mechanical thermal analysis (DMTA)." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:c16d816c-84e3-4186-8d6d-45071b9a7067.
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This thesis examines the dynamic mechanical properties of natural silk fibres, mainly from silkworm species Bombyx mori (B. mori) and spider species Nephila edulis, using dynamic mechanical thermal analysis, DMTA. The aim is not only to provide novel data on mechanical properties of silk, but also to relate these properties to the structure and morphology of silk. A systematic approach is adopted to evaluate the effect of the three principal factors of stress, temperature and hydration on the properties and structure of silk. The methods developed in this work are then used to examine commercially important aspects of the ‘quality’ of silk. I show that the dynamic storage modulus of silks increases with loading stress in the deformation through yield to failure, whereas the conventional engineering tensile modulus decreases significantly post-yield. Analyses of the effects of temperature and thermal history show a number of important effects: (1) the loss peak at -60 °C is found to be associated the protein-water glass transition; (2) the increase in the dynamic storage modulus of native silks between temperature +25 and 100 °C is due simply to water loss; (3) a number of discrete loss peaks from +150 to +220°C are observed and attributed to the glass transition of different states of disordered structure with different intermolecular hydrogen bonding. Excess environmental humidity results in a lower effective glass transition temperature (Tg) for disordered silk fractions. Also, humidity-dynamic mechanical analysis on Nephila edulis spider dragline silks has shown that the glass transition induces a partial supercontraction, called Tg contraction. This new finding leads to the conclusion of two independent mechanisms for supercontraction in spider dragline silks. Study of three commercial B. mori cocoon silk grades and a variety of processed silks or artificial silks shows that lower grade and poorly processed silks display lower Tg values, and often have a greater loss tangent at Tg due to increased disorder. This suggests that processing contributes significantly to the differences in the structural order among natural or unnatural silks. More importantly, dynamic mechanical thermal analysis is proposed to be a potential tool for quality evaluation and control in silk production and processing. In summary, I demonstrate that DMTA is a valuable analytical tool for understanding the structure and properties of silk, and use a systematic approach to understand quantitatively the important mechanical properties of silk in terms of a generic structural framework in silk proteins.
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Hägglund, Adel, and Suan Cing Nem. "Patienters erfarenheter av egenvård vid Diabetes Mellitus Typ 2 : Literaturstudie." Thesis, Högskolan i Gävle, Avdelningen för hälso- och vårdvetenskap, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-28823.
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Bakgrund: Diabetes typ 2 (DMT2) står för majoriteten av all diabetes i Sverige som internationellt, vilket har satts i samband med vår moderna livsstil, minskad fysisk aktivitet och en tilltagande ökning av kroppsvikt. Orsaken kan t.ex. relateras till patientens ärftliga betingad eller individens levnadsvanor. Egenvård är viktig för att förebygga eller minska senkomplikationer. Syftet: Syftet med det föreliggandeexamensarbetetvar attbeskriva vuxna patienters erfarenheter av egenvård vid DMT2samt granska datainsamlingsmetoder och urvalsgrupp använts i artiklarna. Metod: Litteraturstudieutfördes med en beskrivande design där sammanfattas 12 kvalitativa artiklar. Huvudresultat:Patienter hade positiv inställning livsstilsförändringar och började ta ansvar för sin egenvård. En del patienter hade svårigheter att ta till sig kunskaper och tillämpa dessa i sin egenvård, arbetssituation påverkad, låg inkomst och en känsla av utanförskap både från hemmet och omgivningen. En del av patienter upplevde socialt stöd från familj och närstående samt hade god kontakt med vården. Slutsats:Föreliggande examenarbetevisade att patientens levnadssituation, relation till sin omgivning måste sättas i centrum. Patienten möjlighet att få en vårdkontakt förbättras, med syfte att ge individanpassad kunskap, motivera och ge mer tid. Vidare forskning bör undersöka familjens förhållningssätt till personen som har DMT2 för att få en djupare förståelse om vad familjen kan göra för att skapa en holistisk syn. Nyckelord: DMT2, Egenvård, Erfarenhet, Vuxna patienter<br>Background:Diabetes type 2 (DMT2) accounts for the majority of all diabetes in Sweden as well as global, which has been associated with our modern lifestyles, reduced physical activities and an increase in body weight. Causes can be, for example, related to the patient's hereditary condition or the individual's living habits. Self-care is important to prevent or reduces the late complications. Aim: The aim of the present thesis was to describe adult patients’ experiences of self-care with DMT2 and examine the data collection methods and sample group used of the articles. Methods: A literature study was conducted with a descriptive design summarizing 12 qualitative articles. Main result: Patients had positive attitude to lifestyle changes and began taking responsibility for their self-care. Some patients had difficulty in acquiring knowledge and applying them for their own care, affected in work situation, weak income and a sense of alienation both at home and surrounding. Some of patients experienced social support from family and close relatives and had good contact with healthcare. Conclusion: The present study shows that the patient's living situation, relationship with his surrounding, must be placed at the center. The patient possibilities for care contact should be improved in order to give him individualized knowledge, motivate and give more time. Further research should investigate the family's approach to the person with DMT2 to gain a deeper understanding of what the family can do to create holistic view. Keyword: Adult patients,DMT2, Experience, Self-care,
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Zhang, Liang. "Error control coding in ADSL DMT system." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0001/MQ36760.pdf.
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Solberg, Scott W. "Discipling Ministry Team (DMT) leadership development program /." Online full text .pdf document, available to Fuller patrons only, 2003. http://www.tren.com.
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Zhang, Liang. "Turbo coded modulation in ADSL DMT systems." Thesis, University of Ottawa (Canada), 2002. http://hdl.handle.net/10393/6308.
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A&barbelow;symmetric d&barbelow;igital s&barbelow;ubscriber l&barbelow;ine (ADSL) technology provides transport of high-bit-rate digital information over digital subscriber lines (i.e., common telephone lines), which were initially engineered to carry a single voice signal with a 3.4 kHz bandwidth. Sophisticated digital transmission techniques have to be utilized to overcome digital subscriber line transmission impairments due to the high signal attenuation, i&barbelow;nter-s&barbelow;ymbol i&barbelow;nterference (ISI), c&barbelow;rosst&barbelow;alk noise (XT) from the signals present on adjacent wires, signal reflections, radio-frequency noise, and impulse noise. In current ADSL standard, a multicazrier modulation technique named d&barbelow;iscrete m&barbelow;ultit&barbelow;one (DMT) is used to deal with the impairments caused by heavy ISI and signal reflections. A concatenated channel coding structure is employed to efficiently increase the transmission capability in the presence of strong additive crosstalk noise. This channel coding scheme consists of an inner 4&barbelow;-D&barbelow;imensional T&barbelow;rellis C&barbelow;oded M&barbelow;odulation (4D-TCM) and an outer R&barbelow;eed-S&barbelow;olomon (RS) code separated by an interleaver. In this thesis, we investigated the potential transmission performance improvement by using Turbo code in ADSL DMT systems. To achieve this, we first proposed a turbo coding structure that fits well in the current ADSL DMT system architecture. This structure is very similar to the existing concatenated channel coding structure, except a bandwidth efficient T&barbelow;urbo T&barbelow;rellis C&barbelow;oded M&barbelow;odulation (TTCM) is used instead of the 4D-TCM. To obtain high bandwidth efficiency, only part of the bits are turbo coded and the uncoded bits are protected by a constellation mapping similar to Ungerboeck's set partitioning in TCM. The proposed TTCM was shown to provide extremely good performance when a S&barbelow;ymbol M&barbelow;aximum a&barbelow; p&barbelow;osteriori (SMAP) decoding algorithm is employed. In spite of the good performance of this SMAP algorithm, we proposed to use a simplified TTCM decoding structure to avoid the excessive decoding complexity introduced by the possibly large number of uncoded bits. The proposed turbo coded ADSL DMT system was simulated to evaluate the achievable transmission performance in a stationary noise environment and its performance was compared to that obtained by using the 4D-TCM. Simulation results showed significant performance improvements by using turbo codes.
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Queiroz, Angela Custódia Guimarães. "Uso do DMT na avaliação de maciços compactados." reponame:Repositório Institucional da UnB, 2008. http://repositorio.unb.br/handle/10482/3649.
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Previous issue date: 2008-12-19<br>A qualidade dos maciços compactados, sejam eles de obras rodoviárias ou de barragens, é essencial para o bom funcionamento da obra como um todo. Atualmente, o controle dessa qualidade é realizado por ensaios que determinam o desvio de umidade do solo recém compactado, em relação à umidade ótima, e o grau de compactação alcançado. Com base nesses resultados características relacionadas à deformabilidade, permeabilidade e resistência são inferidas. No entanto, as informações fornecidas por esta técnica nem sempre refletem o real comportamento do solo, além de ser aplicável somente durante a fase de construção. Ensaios de campo mais elaborados são empregados, geralmente, somente quando são identificados problemas em aterros já concluídos. Todavia, estes ensaios podem ser de grande valia também durante sua execução, pois eles fornecem os parâmetros geotécnicos do solo, possibilitando assim, um controle baseado no comportamento, e não simplesmente com base em propriedades físicas. A literatura, entretanto, pouco comenta sobre investigações in situ de aterros compactados visando o desenvolvimento de uma metodologia que permita verificar os parâmetros dos solos. Todo esse contexto motivou a realização desta pesquisa, que analisou a aplicação das correlações desenvolvidas por diversos autores para a estimativa dos parâmetros geomecânicos de solos naturais via DMT em maciços compactados. As análises realizadas apontaram o ensaio dilatométrico (DMT) como uma ferramenta de controle de compactação em potencial, que deve ser melhor estudada, principalmente no que diz respeito a consideração dos efeitos da sucção em seus resultados. Estes estudos preliminares apresentaram resultados animadores. Vale ressaltar que este trabalho faz parte de um projeto de pesquisa financiado pela ANEEL, e coordenado por Furnas Centrais Elétricas S.A., em parceria com a UnB. _______________________________________________________________________________ ABSTRACT<br>The quality of compacted fill, be they of road works or dams, is essential to the smooth functioning of work as a whole. Currently, the quality control of this is done by testing that determine the diversion of moisture’s soil newly compacted, in relation to optimum moisture content, and the degree of compaction achieved. Based on these results characteristics related to the deformability, permeability and strength are inferred. However, the information provided by this technique does not always reflect the actual behavior of the soil, apart from being applicable only during the construction phase. Field tests more developed are employees, generally, only when problems are identified in fill already completed. However, these tests may be of great value also for its implementation, because they provide the geotechnical parameters of the soil, thus enabling a control based on behavior. The literature, however, little comment on investigations in situ of compacted fills to develop a methodology to assess the parameters of the soil. All this context led to the realization of this research, that examined the implementation of the correlations developed to estimate the parameters through of the DMT in compacted soil. The analysis carried out showed the dilatometer test (DMT) as a tool to control compaction in potential, that should be better studied, especially with regard to consideration of the effect of pore negative pressure in your results, but that these preliminary studies showed encouraging results.
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Silva, Fábio Krueger da. "Ensaios dilatométricos - DMT em solos de Santa Catarina." Florianópolis, SC, 2008. http://repositorio.ufsc.br/xmlui/handle/123456789/91917.
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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia Civil.<br>Made available in DSpace on 2012-10-24T03:52:29Z (GMT). No. of bitstreams: 1
254670.pdf: 15143619 bytes, checksum: b565e1d1c665e9060dfe45d0a6f696c3 (MD5)<br>É crescente a demanda mundial pela realização de ensaios geotécnicos de campo. Com os atuais avanços tecnológicos os ensaios geotécnicos têm sido rigorosamente indicados pelos projetistas para investigação do subsolo. O ensaio Dilatômetro de Marchetti (DMT) vem sendo amplamente utilizado em todo mundo, com diferentes finalidades. Neste trabalho pioneiro com o DMT em Santa Catarina foram realizadas comparações entre os resultados obtidos no DMT (Dilatometer test) com resultados de ensaios SPT (Standard Penetration Test) e CPT (Cone Penetration Test), já usuais no meio geotécnico. O DMT foi realizado em cinco locais diferentes do estado de Santa Catarina.Nas campanhas de sondagens foram realizados ensaios CPT e DMT e, quando disponível, foram obtidos laudos SPT próximos aos locais estudados. Num local existe um laudo de Sondagem Mista. As campanhas de sondagens foram realizadas nas cidades de Urussanga, Florianópolis, Tijucas e Antonio Carlos todas no Estado de Santa Catarina. Procurou-se com esta abrangência de solos analisar a consistência dos dados colhidos com a execução do Dilatômetro de Marchetti comparados com os resultados do Ensaio CPT e do Ensaio SPT. Este trabalho consiste na coleta, análise e interpretação dos dados obtidos com o ensaio DMT. Estes resultados são validados através de confrontações com resultados de ensaios SPT e CPT nos solos estudados. Ao final desta pesquisa conclui-se que o ensaio DMT é um ensaio promissor para pesquisa geotécnica em solos brasileiros, apresentando dados consistentes na avaliação de perfis estratigráficos e na busca de parâmetros geotécnicos dos solos. Busca-se introduzir comercialmente o ensaio DMT na rotina de prospecção geotécnica aliado ao ensaio CPT. A união em campo destes ensaios dispõe aos projetistas resultados mais completos, permitindo um maior entendimento das condições do maciço e assim, definir parâmetros geotécnicos mais adequados às condições impostas pelo projeto.
The world-wide demand for the accomplishment of geotechnical in situ tests is increasing. With th rigorously indicated by the designers for a subsoil identification. The testing method Marchetti Dilatometer (DMT) has being widely used in the world, with different purposes. In this pioneering work with the DMT in Santa Catarina, comparisons between (Standard Penetration Test) and CPT (Cone Penetration Test), already usual in the geotechnical area, had been carried through. The DMT was performed in five different places of Santa Catarina. In the sounding campaigns, CPT and DMT had been carried through and, when available, SPT reports were obtained near the studied places. There is a Mixed-mode Sounding in one place. The soundings campaigns had been performed in the cities of Urussanga, Florianópolis, Tijucas and Antonio Carlos, all of them in the State of Santa Catarina. The attemption of this extention of soils was to analyze the consistency of the collected data by the Marchetti Dilatometer compared with the results of CPT and SPT . This work consists of the collection, analysis and interpretation of the data obtained with the DMT . These results are validated through confrontations with results SPT and CPT in the studied soils. At the end of this research, the conclusion is that the DMT is a promising in situ method to geotechnical research in the Brazilian ground presenting consistent data in the evaluation of estratigraphic profiles and in the search for geotechnical soil parameters. It`s pursuit to introduce commercially the DMT method in the routine of the geotechnical prospection allied to the CPT. The union in field of these in situ tests assorts the devisors more complete results, allowing a bigger agreement of the bulk conditions and thus, define more adequate geotechnical parameters to the conditions
imposed by the project.
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Singh, Gunjita. "Role of recombinaison proteins in crossover formation, pairing and synapsis in Arabidopsis meiosis : Physiologie et génétique moléculaires." Thesis, Université Clermont Auvergne (2017-2020), 2017. http://www.theses.fr/2017CLFAC037/document.
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Manifestation visible des cross-overs génétiques, les chiasmata lient les paires de chromosomes homologues afin de les orienter correctement sur le fuseau méiotique en Métaphase et Anaphase I. Ils résultent d'un processus complexe et étroitement régulé impliquant l'induction de cassures double-brins et de leur réparation par l'invasion d'un duplex d'ADN homologue faisant office de modèle. La recombinaison est ainsi essentielle pour le synapsis et la ségrégation correcte des chromosomes méiotiques à la première division méiotique, et pour la génération de la variabilité génétique. Bien que les processus permettant à un chromosome de s'apparier seulement à son homologue ne soient pas complètement élucidés, l'appariement des chromosomes homologues est étroitement lié à la recombinaison catalysée par les enzymes d'échange de brins d'ADN RAD51 et DMC1. Ces deux protéines ont des capacités très similaires in vitro, mais sont fonctionnellement distinctes in vivo.La première partie de ma thèse montre l'impact de l'élimination de l'activité d'échange de brins de RAD51 dans la méiose d'Arabidopsis, tout en conservant sa fonction de facteur accessoire pour l'action de DMC1. La recombinaison peut donner lieu à des cross-over (CO) et non-cross-over (NCO) et la recombinase spécifique de la méiose DMC1 a été jugée particulièrement importante dans la production de CO interhomologue. Des résultats récents suggèrent fortement toutefois que DMC1 est la seule recombinase active dans la méiose et doit donc être responsable des résultats de CO et NCO. Etant donné qu'environ 95% de la recombinaison méiotique homologue dans Arabidopsis n'entraîne pas de cross-overs interhomologues, Arabidopsis est un modèle particulièrement sensible pour tester l'importance relative des deux protéines - même des effets mineurs sur la population d'événements non-cross-over devraient produire des effets détectables sur les cross-overs. DMC1 catalyse la réparation de toutes les cassures d'ADN méiotiques en présence d'une protéine RAD51 catalytiquement inactive (fusion RAD51-GFP), et les résultats de mon travail montrent que cela n'a pas d'effet détectable sur les taux relatifs de recombinaison de CO et de NCO : à la fois localement, à l'échelle du chromosome et du génome. Et non plus sur la progression de la division méiotique. Ce travail a abouti à une publication dans le journal PLoS One (Singh G, Da Ines O, Gallego ME & White CI (2017) Analyse de l'impact de l'absence d'activité d'échange de brins de RAD51 dans la méiose d'Arabidopsis PLoS ONE 12: e0183006- 16).Des publications antérieures montrent une synapsis homologue partielle et incomplète en l'absence de rad51 et xrcc3 dans la méiose d'Arabidopsis. Cela s'accompagne de la présence de nombreuses fibres courtes ZYP1 dans ces noyaux, ce qui pourrait indiquer de faibles longueurs de complèxe synaptonémale (SC). Ce synapsis partielle dépend à la fois de SPO11 et de DMC1 et implique des péricentromères, montrant que DMC1 est capable (au moins partiellement) d'entraîner le synapsis dans les péricentromères en l'absence de RAD51. Afin de mieux caractériser ceci et pour tester l'hypothèse que les fibres ZYP1 courtes montrent la présence d'une initiation de SC à ces sites, j'ai méné des expériences d'immunofluorescence et d'imagerie SIM. Utilisant un coloration DAPI et les antiséra ASY1, ZYP1 et CENH3, j'ai conduite des analyses cytogénétiques de le synapsis dans les mutants rad51, xrcc3 et des plantes sauvages. Ces travaux faisaient l'objet de la deuxième partie de mes travaux de thèse. Dans les plantes mutantes, j'observe effectivement des fibres courtes ZYP1 comprenant des centromères, mais elles ne sont pas la règle, ce qui signifie que le synapsis ne commence pas nécessairement à des centromères ou des péricentromères. (...)<br>The visible manifestation of genetic crossing-over, chiasmata link homologous chromosome pairs to permit them to properly orient on the meiotic Anaphase I spindle. They are the result of an intricate and tightly regulated process involving induction of DNA double- strand breaks and their repair through invasion of a homologous template DNA duplex. Recombination is thus essential for the synapsis and accurate segregation of meiotic chromosomes at the first meiotic division, and in doing so, generates genetic variation. Although the processes permitting a chromosome to pair only with its homologue are not fully understood, successful pairing of homologous chromosomes is tightly linked to recombination catalysed by the DNA strand exchange enzymes RAD51 and DMC1. Both proteins share very similar capabilities in vitro, but are functionally distinct in vivo. The first part of my thesis shows the impact of eliminating the strand exchange activity of RAD51 in Arabidopsis meiosis, while retaining its function as an accessory factor for the action of DMC1. Recombination can give rise to both crossover (CO) and non-crossover (NCO) outcomes and the meiosis-specific recombinase DMC1 has been thought to be of particular importance in the production of inter-homolog CO. Recent results however suggest strongly that that DMC1 is the only active recombinase in wild-type meiosis and thus must be responsible for both CO and NCO outcomes. Approximately 95% of meiotic homologous recombination in Arabidopsis does not result in inter-homologue crossovers and Arabidopsis is thus a particularly sensitive model for testing the relative importance of the two proteins - even minor effects on the non-crossover event population should produce detectable effects on crossing-over. DMC1 catalyses repair of all meiotic DNA breaks in the presence of the catalytically inactive RAD51 (RAD51-GFP fusion) and the results of my work show that this has no detectable effect on the relative rates of CO and NCO recombination, both locally and chromosome- and genome-wide, nor on the progression of the meiotic division. This work has resulted in a publication in the journal PLoS One (Singh G, Da Ines O, Gallego ME & White CI (2017) Analysis of the impact of the absence of RAD51 strand exchange activity in Arabidopsis meiosis. PLoS ONE 12: e0183006–16).Previous publications show partial, incomplete homolog synapsis in the absence of rad51 and xrcc3 in Arabidopsis meiosis. This is accompanied by the presence of many short ZYP1 fibres in these nuclei, possibly indicating short stretches of Synaptonemal Complex (SC). The partial synapsis is both SPO11- and DMC1-dependent and involves peri-centromeres, showing that DMC1 is able to (at least partially) drive synapsis in peri-centromeres in the absence of RAD51. In an effort to better characterize this and to test the hypothesis that the short ZYP1 fibres show the presence of initiation of SC at these sites, immunofluorescence and SIM imaging with DAPI staining and ASY1, ZYP1 and CENH3 antisera were carried out for cytogenetic analyses of synapsis in rad51 and xrcc3 mutants and the WT in the second part of my thesis work. Although I do observe short ZYP1 fibres including centromeres in the mutants, these are not the rule, so synapsis does not necessarily begin at centromeres or peri-centromeres. The superresolution imaging does confirm the presence of stretches of 4-chromatid fibres in xrcc3 plants and this approach will be extended in future work of the group to probe the nature of the RAD51-independent partial meiotic chromosome synapsis.Finally, I have designed and built CRISPR/CAS9 constructs with the aim of creating meiotic DSB hotspots at specific genomic loci. Taking advantage of single nucleotide polymorphism data, these constructs were designed to specifically cleave sites in the Arabidopsis Col-0 ecotype, and not in Ler-0 plants. (...)
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AMIN, AHMED. "Implementation and Investigation of VDSL2 Signal Modulation/Demodulation Functions for FDM Solution via POF Channel." Thesis, Högskolan i Gävle, Avdelningen för elektronik, matematik och naturvetenskap, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-10766.
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For higher data rate and attractive price level internet service Very High Data rate Subscriber Line 2 (VDSL2) is a perfect option. VDSL2 is a great achievement in Digital Subscriber Line (DSL) technology. It has a good impact in modern triple play (Voice, Data and Video) Internet service but for modern world applications required more data rate than the VDSL2 system can provide but it should be inexpensive and easy to install. So the desired goal of this thesis work is to achieve higher bitrates for VDSL2 system, by transmitting multiple VDSL2 signal using Plastic Optical Fiber (POF) channel instead of copper channel. POF channel is a suitable solution for high data rate application. Moreover POF is very rugged and suitable for high data rate application because of optical based transmission and it’s also very easy to implement into the interior networking. Moreover POF doesn’t have any impact of Electro Magnetic Interference because of optical transmission. So several VDSL2 signals are amplitude modulated to allocate specific frequency band and combined together which can be called as frequency division multiplexing and POF is used as channel to carry the combined signal which provide much higher bit rate than single signal and efficiently utilize the bandwidth of the channel. Then at the receiver end the combined signals are split and amplitude demodulate at the respective receiver to recover the expected frequency band for the receiver.
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Istanbulluoglu, Ipek. "A Novel Modeling Methodology And Performance Improvement Technique For Dmtl Phase Shifters." Master's thesis, METU, 2006. http://etd.lib.metu.edu.tr/upload/2/12607522/index.pdf.
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This thesis presents distributed MEMS transmission line (DMTL) phase shifters, emphasizing the circuit modeling and design as well as the performance improvement. A novel modeling methodology is introduced for DMTL unit sections, with bridge widths larger than 50 &<br>#956<br>m. The introduced model is compared with EM simulation results and the CLR modeling results. For structures with bridge widths larger than 50 &<br>#956<br>m, the introduced model fits the simulation results much better than the CLR model. The simulated structures are fabricated in METU micro-electronics facilities on glass substrates using gold structural layers. 1-20 GHz S-parameter measurement results of various DMTL structures are compared with the introduced model. It is observed that the S-parameters match except for a scaling need in the insertion loss. The measurement results give 2 dB insertion and 15 dB isolation at 20 GHz.
The ABCD parameters of the introduced model are converted into S-parameters. Loss and the phase shift of the DMTL structures are expressed in terms of these S-parameters. These expressions are re-written as MATLAB code, from which the phase shift/loss (degree/dB) performance is evaluated. Therefore degree/dB plots with respect to bridge widths and center CPW conductor widths are obtained. From these plots the optimum DMTL phase shifters, which give maximum phase shift for minimum loss are determined for a pre-defined DMTL structure.
To increase the degree/dB performance of a DMTL phase shifter, a change in the geometry of the DMTL phase shifters is proposed. The geometry change is based on inserting an open-ended stub through the signal line and connecting one side of the stub to the bridge. By this way, the stub capacitance is added to the shunt capacitance of the bridge satisfying a larger phase shift. The simulations point out a performance of 217 degree/dB at 20 GHz with a 15 % change in the 25 &<br>#956<br>m wide bridge height ratio.
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George, Susan. "The distribution of DMC1 epitopes in lilies with normal and aberrant meioses." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ58737.pdf.
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Lu, Yongbo Feng Jian Q. "Studies of dentin matrix protein 1 (DMP1) regulation and function in vivo." Diss., UMK access, 2007.
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Thesis (Ph. D.)--School of Dentistry. University of Missouri--Kansas City, 2003.<br>"A dissertation in oral biology and molecular biology and biochemistry." Advisor: Jian Q. Feng. Typescript. Vita. Title from "catalog record" of the print edition Description based on contents viewed July 16, 2008. Includes bibliographical references (leaves 109-121). Online version of the print edition.
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Fullerton, Donna Lynn. "Investigation of the expression of DMC1, a meiotic gene, in trichomonas vaginalis." Scholarly Commons, 2007. https://scholarlycommons.pacific.edu/uop_etds/664.
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T. vaginalis is a protozoan parasite without an observed sexual stage in its life cycle. However, T. vaginalis has genes, such as Dmc1, known to be involved in meiosis in other organisms. In order to look at the expression of these genes in T. vaginalis, RT-PCR was done using purified mRNA. It shows that Dmc1 is expressed in both normal and drug treated cells. However, relative levels are unclear. Localization studies were done in T. vaginalis using immunofluorescence against Dmc1 protein with an HA tag. These studies showed that recombinant Dmc1 remained in the cytoplasm upon treatment with DNA damaging drugs. Additionally, T.vaginalis Dmc1 protein was expressed and purified from E.coli to have polyclonal antibodies made to use in further immunofluorescence studies.
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Belloli, Marcus Vinicius Alves. "Interpretação de ensaios DMT em solos com drenagem parcial." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2018. http://hdl.handle.net/10183/181399.
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Entre os objetivos da engenharia geotécnica está a busca pelo entendimento e previsão do comportamento mecânico dos solos. Para isso, existem basicamente duas abordagens: ensaios de laboratório ou ensaios de campo. Em cada obra o Engenheiro Geotécnico deve julgar quais são os métodos e procedimentos mais indicados de investigação, que resultarão em parâmetros confiáveis de projeto. Os ensaios de campo foram desenvolvidos baseados nos solos argilosos e arenosos em virtude dos comportamentos distintamente bem definidos, especialmente em termos de drenagem. O mesmo ocorre para o ensaio DMT, cuja execução e interpretação são influenciadas pelo tipo de solo e pelas condições de drenagem. O grande desafio, neste caso, está na interpretação dos ensaios em solos cuja solicitação ocorre sob condição de drenagem parcial, como nos casos de barragens de rejeito de mineração, ou em depósitos naturais de solos siltosos, onde esta condição pode levar a erros de interpretação. No DMT, a ocorrência de drenagem parcial influencia tanto na etapa de cravação da lâmina, quanto na etapa de expansão da membrana. Neste sentido, o foco deste trabalho está no problema da dissipação de poropressão durante a expansão da membrana, apresentando procedimentos especiais para realização do ensaio DMT. Serão apresentados dois métodos de interpretação de resultados, visando compensar os erros de interpretação causados pela dissipação parcial de poropressão: Método de Dissipação Completa e, Método de Dissipação Incompleta. Este trabalho foi desenvolvido baseado na realização de ensaios de campo, com uma campanha executada em solo brasileiro argiloso, que serviu de base à interpretação, sendo complementada por 6 ensaios realizados em diferentes sítios na Itália. Os resultados dos ensaios realizados pelo Método de Dissipação Completa foram interpretados através de duas abordagens: Método da Igualdade (analítico) e Método Simplificado. Enquanto a interpretação do Método de Dissipação Incompleta é permitida apenas através de procedimento simplificado. A análise paramétrica apresentou comportamentos similares entre ambas abordagens, demonstrando que a taxa de dissipação é o fator que mais influencia nos resultados. Ao final, os métodos foram aplicados e validados em diferentes locais, apresentando resultados adequados e compatíveis com o comportamento previamente definido através de outros ensaios.<br>Among the geotechnical engineering goals are the understanding and prediction of soil behavior. For this, there are basically two approaches: laboratory or in situ tests. In this case, the Geotechnical Engineer must judge the most appropriate investigation methods and procedures that will result in reliable design parameters. In situ tests were developed for clay and sand given to the fact that the behavior of these soils is well-defined and drainage conditions are properly controlled. The DMT is no exception, with test and interpretation methods influenced by the drainage conditions. The challenge resides in the interpretation of tests carried out in soils under partial-drainage conditions, such as tailings dams or natural deposits of silty soils, where partial-drainage conditions are taking place around the DMT blade leading to errors on its interpretation. The partial drainage condition influences both the DMT blade penetration phase and the membrane expansion phase. In this sense, this work focus on the problem of the pore pressure dissipation taking place simultaneously to membrane expansion. A non-standard procedure is proposed to sounding the DMT in silts that include two methods for DMT interpretation in order to compensate the errors caused by the partial pore pressure dissipation: Method of Complete Dissipation Curve and Method of Incomplete Dissipation Curve. This work was developed based on tests carried out in Brazilian clay soils to develop the proposed approach that was validated latter in non-standard tests carried out in different Italian sites. The results of the tests performed by the complete dissipation method were interpreted through two approaches: Equality Method (analytical) and Simplified Method, while the interpretation of the incomplete dissipation method is possible only through simplified procedure. The parametric analysis showed that these approaches yield similar results, demonstrating that the dissipation rate is the most important factor in the analysis. At the end, the methods were applied and validated at different sites, showing results that are compatible to previously defined behavior of the soils.
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Mateus, Cárin Cristina de Almeida. "Determinação dos erros de medição associados ao ensaio DMT." Master's thesis, Universidade de Aveiro, 2008. http://hdl.handle.net/10773/2716.
Full textAbstract:
Mestrado em Engenharia Geológica<br>A evolução tecnológica verificada sobretudo nos últimos 20 anos revolucionou de forma drástica o contexto da prática da engenharia, nomeadamente pelo desenvolvimento de modelos numéricos de elevada precisão e fiabilidade, que facilitam a simulação de comportamentos e de soluções de engenharia. A eficiência e a qualidade dos resultados desses modelos estão intrinsecamente relacionadas com a selecção dos parâmetros de entrada, os quais dependem sobretudo da qualidade dos equipamentos de medição, da sua
adequabilidade a cada situação particular e dos erros associados a cada um dos parâmetros medidos.
No presente trabalho, apresenta-se uma análise de
sensibilidade paramétrica a fim de verificar a precisão associada e as respectivas implicações na parametrização física e mecânica dos maciços terrosos caracterizados com base no ensaio com Dilatómetro de Marchetti, DMT.
ABSTRACT: In the last two decades, the practice of engineering has immensely benefitted from technological evolution.
Namely, the development of models and numerical
methods with very high precision and efficiency, made it possible to simulate quite accurately the behaviour of engineering problems. Nevertheless, the efficiency and quality of the results obtained from such models, strongly depend on the selection of the input parameters and also on the quality of the equipment used to measure them.
In particular, the adequacy of the equipment to a
particular situation and the inherent errors associated to any measurement, have an important role in this process.
In this work we present an analysis of parametric
sensitivity to the Marchetti Dilatometer Test, DMT, with the aim of checking its precision and the respective implications on the physical and mechanical parametrization of soils.
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Santos, Neife Aparecida Guinaim dos. "Efeito da cisplatina na função, estresse oxidativo e estado redox mitocondrial renal em ratos: efeito protetor da dimetiltiouréia." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/60/60134/tde-22052007-091457/.
Full textAbstract:
Embora a cisplatina (cis-diaminocloroplatina II) seja um efetivo agente anticâncer, seu uso clínico é altamente limitado, predominantemente devido ao seu potencial nefrotóxico. Muitos estudos têm demonstrado que a cisplatina causa disfunção mitocondrial em células epiteliais renais e danos ao DNA nuclear devido à ação de espécies reativas de oxigênio tais como superóxido e radicais hidroxila. O aumento na produção destas espécies de oxigênio causa liberação de citocromo c no citosol, iniciando uma cascata de eventos que leva à morte celular por apoptose. A proteção seletiva da mitocôndria contra espécies reativas de oxigênio geradas pela cisplatina nos tecidos intactos tais como os rins, é fundamental na quimioterapia de pacientes com câncer. O presente estudo investigou os efeitos da cisplatina na bioenergética, no estado redox e no estresse oxidativo mitocondrial renal, bem como o potencial protetor da dimetiltiouréia (DMTU), um antioxidante seqüestrador de radicais hidroxila, com relação à toxicidade renal induzida pela cisplatina. Método: Ratos Wistar machos adultos pesando de 200 a 220 g foram divididos em quatro grupos de 8 animais cada. Ao primeiro grupo foi administrada cisplatina (10 mg/ kg) por via intra peritonial (i.p.). O segundo grupo recebeu somente injeções de DMTU (500 mg/kg, i.p., seguida de 2 injeções diárias de 125 mg/Kg, i.p). O terceiro grupo de animais foi tratado com DMTU (500 mg/kg, i.p.), imediatamente antes da injeção de cisplatina (10 mg/kg, i.p.), seguida de 2 injeções diárias de DMTU (125 mg/Kg, i.p.). O grupo controle recebeu somente solução salina (1ml/200g, i.p.). Os animais foram sacrificados 72 horas após a injeção de cisplatina (ou salina). Resultados: O tratamento com a cisplatina resultou em uma marcante diminuição da função renal demonstrada pela elevação dos níveis plasmáticos de uréia e de creatinina, concomitante a uma significativa alteração nos parâmetros relacionados à função Resumo ix mitocondrial (síntese de ATP, estado 3 da respiração, RCR, ADP/O, potencial de membrana e transporte de cálcio); ao estresse oxidativo mitocondrial (oxidação da cardiolipina, atividade da aconitase, lipoperoxidação, níveis de proteína carbonila e proteína sulfidrila); ao estado redox mitocondrial (oxidação do NAD(P)H, relação glutationa reduzida e glutationa oxidada) e à apoptose (atividade da caspase 3). O pré-tratamento dos animais com DMTU preveniu a falência renal aguda e as alterações dos parâmetros mitocondriais , sendo capaz de inibir a morte celular por apoptose. Conclusão: Os resultados demonstram o papel central da mitocôndria na falência renal aguda induzida pela cisplatina, bem como o efeito protetor do DMTU e sugerem que o desenvolvimento de potentes seqüestradores de radicais hidroxila, passíveis de uso clínico, poderia contribuir de forma marcante na prevenção dos danos renais resultantes da quimioterapia com este fármaco.<br>Although cis-diamminedichloroplatinum (II) (cisplatin) is an effective anticancer agent, its clinical use is highly limited predominantly due to its adverse effects on renal functions. Many studies have shown that cisplatin causes mitochondrial dysfunction and direct injury to nuclear DNA by generating reactive oxygen species such as superoxide and hydroxyl radicals. Overproduction of reactive oxygen species causes the release of cytochrome c into cytosol, thereby triggering the sequence of events leading to cell death via apoptosis. The selective protection of mitochondria against reactive oxygen species generated by cisplatin in intact tissues, such as kidney, is of critical importance in the chemotherapy of patients with cancer. The present study examined the effects of cisplatin on renal mitochondrial bioenergetics, redox state and oxidative stress as well as the protective potential of dimethylthiourea (DMTU), a hydroxyl radical scavenger, against the cisplatin-induced nephrotoxicity. Methods: Adult male Wistar rats weighing 200 to 220g were divided into 4 groups with 8 animals each.. The first group was given a single intraperitoneal (i.p.) injection of cisplatin (10 mg/kg). The second group was given only DMTU (500 mg/kg body weight, i.p, followed by intraperitoneal injections of 125 mg/Kg twice a day until sacrifice). A third group of animals was given DMTU (500 mg/kg body weight, i.p.), just before cisplatin injection (10 mg/kg body weight, i.p.), followed by intraperitoneal injections of DMTU (125 mg/Kg body weight) twice a day until sacrifice. The control group was treated only with saline solution (1ml/200g body weight, i.p.). Animals were sacrificed 72 hours after the treatment. Results: Cisplatin treated animals presented a marked impairment of the renal function evidenced by the elevation of plasmatic creatinine and urea levels simultaneously to a significant alteration of the parameters related to: (a) the mitochondrial function assessed by ATP synthesis, Summary xi state 3 respiration, RCR, ADP/O ratio, membrane potential, calcium uptake; (b) the mitochondrial oxidative stress assessed by cardiolipin oxidation, aconitase activity, lipid peroxidation, protein carbonyls and protein sulphydryl; (c) the mitochondrial redox state assessed by NADPH/NADP+ ratio, GSH/GSSG ratio and (d) apoptosis assessed by caspase-3 activity. DMTU substantially inhibited cisplatin-induced mitochondrial injury and cellular death by apoptosis, thereby suppressing the occurrence of acute renal failure. Conclusions: Results show the central role of the mitochondria in the cisplatin-induced renal acute failure, the protective potential of DMTU and suggest that the development of potent hydroxyl radical scavengers suitable for use in man could minimize the adverse effects of cisplatin in the kidney of patients under chemotherapy.
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Yadav, Pankaj. "Time and thermo-mechanical coupling effects in polymers." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTS061.
Full textAbstract:
L'étude du comportement mécanique et thermique des polymères est d'une importance capitale pour les applications techniques. Par conséquent, la capacité de prédire ces propriétés pour des plages étendues de fréquences de sollicitation et de température, est une forte motivation. Sur la base d'une combinaison expérimentale d'analyses rhéologiques mécaniques et thermiques (DMTA), des modèles phénoménologiques sont ainsi développés pour prédire le comportement viscoélastique linéaire des polymères avec l'utilisation traditionnelle du principe dit de "superposition temps-température (TTSP)". Lors de la mise en œuvre de ces modèles, la prise en compte (i) des effets liés à la température réelle de l'échantillon ou (ii) des effets induits par les couplages thermomécaniques n'est pas prise en compte. Cependant, les matériaux polymères sont très sensibles aux variations de température et même de faibles variations de température peuvent engendrées des sources de couplage thermomécanique ou de dissipation non négligeables dans le bilan d’énergie. L'applicabilité du TTSP dans ce contexte mérite d’être revisitée. Ainsi, une connaissance précise du comportement mécanique et thermique de cette classe de matériaux, dans le cadre de la thermodynamique des processus irréversibles, en tenant compte de l'effet dissipatif et du couplage thermomécanique, est nécessaire.Pour atteindre ces objectifs, la présente étude a été réalisée à partir d'une revue de la littérature sur le comportement thermomécanique des polymères vitreux et amorphes et du TTSP. Ensuite, nous avons rappelé le cadre théorique de la thermodynamique des processus irréversibles et sa mise en œuvre dans le formalisme des matériaux standards généralisés (GSM). Ainsi la température pu être considérée comme une variable d'état et les équations comportementales constitutives ont pu être dérivées d'un potentiel thermodynamique et de dissipation. Ce formalisme a également permis de définir puis de calculer les différentes sources de chaleur et la forme globale du bilan d’énergie.Deuxièmement, des mesures ont été effectuées pour caractériser les propriétés viscoélastiques linéaires en dessous de la température de transition vitreuse de certains polymères amorphes et rhéologiquement simples (PS, PMMA et PA-6.6). On a ensuite appliqué un TTSP classique utilisant une loi d'Arrhenius pour prédire le comportement viscoélastique linéaire sur une très large plage de température/fréquence, qui ne peut être atteinte expérimentalement. Une première série de mesures a été effectuée sur PS dans plusieurs laboratoires pour vérifier la réponse monochromatique à une charge monochromatique et construire une base de données de référence pour l'étalonnage et la validation des différentes procédures de correction (rigidité machine et déphasage électronique) de notre DMTA. Par la suite, des mesures thermographiques synchronisées ont été effectuées pour mesurer les variations de température de l'échantillon pendant les mesures DMTA. Ceci permet d'estimer l'énergie mécanique moyenne dissipée pendant un cycle ainsi que les pertes de chaleur et le couplage thermoélastique.Enfin, ces résultats expérimentaux ont été utilisés pour identifier les branches d'un modèle de Maxwell généralisé (MGM) en utilisant la méthode des moindres carrés non négatifs pour les 3 polymères différents. Dans chaque branche de ce modèle, la constante de temps viscoélastique et le module d'élasticité associé dépendent de la température (par une loi d'Arrhenius et une énergie d'activation préalablement déterminée expérimentalement). En utilisant le formalisme GSM, les différentes sources de chaleur (couplages thermomécaniques, dissipation) ont également été calculées. Le bilan énergétique a montré la prédominance des sources de couplages thermomécaniques. Pour conclure cette étude, nous avons montré qu'un MGM supposant l'hypothèse de matériau rhéologiquement simple est compatible avec le TTSP<br>The study of the mechanical and thermal behaviour of polymers is of prime importance for engineering applications. Therefore, the ability of predicting these properties for several decades of loading frequencies and/or several tens of degree Celsius, is a strong motivation. Based on experimental combination of mechanical and thermal rheological-analysis (DMTA), phenomenological models are thus developed to predict the linear viscoelastic behaviour of polymers with the traditional use of the so-called “time-temperature superposition principle (TTSP)”. While implementing these models, the consideration of (i) effects linked to the real temperature of the sample or of (ii) the time effects induced by thermo-mechanical couplings are not taken into account. However, polymer materials are very sensitive to temperature variations and even slight temperature variations can be due to thermo-mechanical coupling or dissipation sources. The TTSP applicability in such a context is thus not straightforward. Therefore, an accurate knowledge of the mechanical and thermal behaviour of this class of materials, under the Thermodynamics of Irreversible processes, taking into account the dissipative effect and thermo-mechanical coupling, can become of prime importance.To achieve these objectives, the present study was performed starting from a literature review on the thermo-mechanical behaviour of vitreous and amorphous polymers and the TTSP. This was followed by understanding the theoretical framework of thermodynamics of irreversible processes and its implementation in the Generalized Standard Material (GSM) formalism. The theoretical framework of GSM allowed us to consider the temperature as an internal state variable and to derive the constitutive behavioural equations from a thermodynamic and a dissipation potential. This formalism also induced the possibilities to define and then compute the different heat sources involved in the heat diffusion equation.Second, measurements were performed to characterize the linear viscoelastic properties below the glass transition temperature of selected amorphous and rheologically simple polymers (PS, PMMA and PA-6.6). This was followed by the application of a classical TTSP using an Arrhenius law to predict the linear viscoelastic behaviour on a very large temperature/frequency range, which cannot be experimentally reachable. A first set of measurements was performed on PS in several laboratories to check for its monochromatic response to a monochromatic loading and build a reference database for the calibration and validation of different correction procedures (machine stiffness and electronic phase shift) of our DMTA. Later, synchronized thermography measurements were performed to measure the temperature variations of the sample during DMTA measurements. This allows for the estimation of the average mechanical energy dissipated during one cycle together with the heat losses and thermoelastic coupling.Finally, these experimental results were used to identify the optimum branches of a generalized Maxwell model (GMM) using non negative least squares method for the 3 different polymers. In each branch of this model, the viscoelastic time constant and the associated elastic modulus depend on the temperature (through an Arrhenius law and an activation energy determined previously experimentally). Using the GSM formalism, the different heat sources (thermomechanical couplings, dissipation) were also computed. The energy rate balance showed the predominance of the thermomechanical couplings sources. To conclude this study, we stressed that a GMM assuming the rheological simple material hypothesis is TTSP compatible
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Banville, Isabelle. "Étude des caractéristiques biochimiques et structurales de la protéine DMC1 de Schizosaccharomyces pombe." Thesis, Université Laval, 2004. http://www.theses.ulaval.ca/2004/22203/22203.pdf.
Full textAbstract:
Peu de données sont connues à savoir comment des protéines méiotiques régulent la recombinaison homologue de façon biochimique. Lors d'études effectuées chez l'humain, il a été démontré que hRad51 se comporte sensiblement comme le fait son homologue bactérien, RecA. Malgré que hDmc1 possède une séquence d’acides aminés possédant 52% d’identité à celle de hRad51, ses caractéristiques et ses capacités sont différentes.
Afin d’étudier si cette disparité est conservée chez l'organisme Schizosaccharomyces pombe nous avons purifié et étudié biochimiquement la protéine Dmc1 de cet organisme. Nous montrons que spDmc1 lie préférentiellement l'ADN simple brin et protubérant à l'ADN double brin, une propriété similaire à son homologue bactérien RecA. SpDmc1 purifiée est capable de catalyser des réactions d’échange de brins, telles que rencontrées durant la recombinaison homologue. Contrairement à la protéine humaine, spDmc1 a la capacité de lier l'ADN et d'y former un filament hélicoïdal, la signature des recombinases classiques.
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Marceau, Jean-François. "Low-complexity echo cancellers for DMT-based asymmetric DSL transceivers." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=83875.
Full textAbstract:
In the past years, a number of researchers have investigated the use of digital echo cancellation systems for transmission technologies based on discrete multi-tone (DMT) modulation, such as that used in asymmetrical digital subscriber lines (ADSL) and the likes. Almost all the existing papers report on equal transmission rate systems, while little attention has been given to the multi-rate case. In fact, the first multi-rate echo canceller structure was developed by Ho et al., and has always been referred since.<br>In this thesis, two sets of simplified techniques are developed. The first one reports on a fast initialization technique of the echo canceller. The method consists of replacing the first least mean square (LMS) iteration of the echo channel estimate by the solution of a system cost function in which circular convolution is assumed. The simplification of the method resides in the fact that no known sequence is used, and thus, no protocol is required.<br>The second simplified technique developed aims to reduce the computational complexity of the multi-rate echo canceller structure at the lower transmit rate side of the link, e.g. the line terminal side in ADSL. In this case, the echo canceller located in the terminal, processes the signals in the entire frequency bandwidth (higher rate). During the processing, the echo channel that is estimated corresponds in fact to the imperfect hybrid channel combined with the lowpass filtering action of the digital-to-analog converter (DAC) and the time-domain equalizer(TEQ). In such a situation, the frequency taps representing the estimated echo channel decay rapidly above the cutoff frequency of the DAC filter. In this work, we exploit this specific structure of the echo channel to reduce the computational complexity of the echo cancellation processing by setting a portion of the high frequency echo tap coefficients to zero, and by exploiting certain properties of the inverse Fast Fourier Transform (IFFT) algorithm.<br>Experimental simulations for an ADSL-like configuration involving 32 tones on the upstream and 256 tones on the downstream, showed that by employing the new proposed approach, the computational complexity can be reduced by a factor of as much as 53% while at the same time improving the achievable bitrate by 35 kbps. Furthermore, in regards of the initialization technique, the echo channel estimate convergence can be reached after around 6 iterations as compared to 15 for usual LMS algorithm.
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Zhang, Junjie. "Mechanisms of resistance toT-DM1 in HER2-positive breast cancer." Doctoral thesis, Universitat Autònoma de Barcelona, 2018. http://hdl.handle.net/10803/650489.
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El cáncer de mama HER2-positivo representa alrededor del 15-30% del total de pacientes con cáncer de mama. Este subtipo tiene un mal pronóstico, seguido del subtipo Triple-negativo (TNBC), que lo tiene aún peor. Actualmente, varios medicamentos están aprobados para las pacientes HER2-positivo, como Trastuzumab, Lapatinib y T-DM1. Sin embargo, a menudo éstas adquieren resistencia a estas terapias en un período de 1 a 2 años. El objetivo principal de este estudio es definir los mecanismos de resistencia a T-DM1. Durante mi tesis, generé líneas celulares resistentes a T-DM1 y exploré diferentes posibilidades in vitro que pudieran explicar cómo estas células escapan de la terapia contra HER2. Obtuve células resistentes a T-DM1 usando una línea celular derivada de un tumor primario de una paciente (PDX, Patient-derived xenograft) tratándolas con dosis crecientes de T-DM1. Comprobé los niveles de HER2 por mRNA y proteína, número de copias, efectores de señalización, analicé la región citotóxica de T-DM1 y su actividad lisosómica diferencial comparando la línea parental y las células resistentes. Esta tesis describe punto por punto todos los posibles mecanismos de resistencia que investigamos y cuales resultaron ser los responsables de la resistencia a T-DM1.<br>HER2-positive breast cancer represents around 15-30% of the breast cancer patients. This breast cancer subtype has poor prognosis, followed by the triple negative subtype, which has the worse. Several drugs are currently approved for HER2-positive breast cancer, such as Trastuzumab, Lapatinib and T-DM1. However, often these patients acquire resistance to these therapies in a period of 1 - 2 years. The main goal of this study is defining mechanisms of resistance to T-DM1. First, I have generated T-DM1 resistant cell lines, and I explored in vitro different possibilities to explain how these cells escape from HER2-target therapy. I obtained T-DM1 resistant cells using a PDX-derived cell line (PDX118) through continuous treatment of increasing doses of T-DM1. These cells were tested of resistance to T-DM1 in the presence of this HER2 target drugs. I have tested whether the levels of HER2 by mRNA and protein, copy number, downstream signaling effectors, cytotoxic part of T-DM1 or differential lysosome activity might justify the differences between parental and resistant cells. No differences in copy number, neither at transcript or total protein levels of HER2 was observed in parental versus resistant cells. However, in two of three T-DM1 resistant cultures, the protein levels at the surface of the resistant cells were significantly lower, although the downstream signaling activity remained similar. A HER2 rescue experiment resulted in a partial recovery of the sensibility. HER2 protein levels at the surface of the tumor cells is the main mechanism of resistance to T-DM1 therapy, and also, abnormal function of lysosomes maybe a reason to escape this treatment.
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Sauveur, Juliette. "Development and characterization of models of resistance to T-DM1." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1266/document.
Full textAbstract:
Le T-DM1 est un immunoconjugué composé de l'anticorps trastuzumab qui cible HER2 lié au DM1, un agent anti-tubuline dérivé de la maytansine. Malgré son efficacité, la résistance acquise au T-DM1 a été démontré lors des tests précliniques et chez certains patients. Nous avons développé des lignées résistantes à partir de la lignée de cancer du sein MDA-MB-361 et de la lignée de cancer de l'œsophage OE-19, que nous avons exposées au T-DM1 à doses croissantes pendant une longue durée en absence ou en présence de ciclosporine A (CsA). A partir de ces conditions nous avons obtenus les lignées “TR” qui ont été exposées uniquement au T-DM1 et “TCR” qui ont été exposées au T-DM1 et CsA. Nous avons observé une augmentation de la vitesse de migration et une diminution de la force d'adhésion chez OE-19 TCR associées à une sensibilité accrue à un inhibiteur de RHOA. Aussi, la voie des prostaglandines était dérégulée chez OE-19 TR et TCR, avec une forte augmentation de l'expression de COX-2 et de prostaglandine E2 dans la lignée OE-19 TR. La sensibilité à l'aspirine, un inhibiteur des cyclooxygenases 1-2, était accrue chez les deux lignées OE-19 résistantes par rapport à la lignée parentale. En conclusion nous avons démontré que différentes voies de signalisation peuvent être impliquées dans la résistance au T-DM1. Nos résultats restent à être validés chez les patients. Nous suggérons que cibler la voie de régulation de la composition du cytosquelette ou la voie des prostaglandines pourrait permettre d'obtenir un effet thérapeutique dans le cas de cancers résistants au T-DM1<br>T-DM1 is an antibody-drug conjugate composed of the monoclonal antibody trastuzumab linked to DM1, a potent tubulin binding agent. Despite its efficacy in the treatment of HER2-positive breast cancer patients, acquired resistance to T-DM1 was observed during clinical trials. In order to study resistance mechanisms to T-DM1, we developed resistance models using OE-19 (esophageal) and MDA-MB-361 (breast) cancer cell lines in the absence or presence of ciclosporin A (CsA), an inhibitor of MDR1 mediated efflux. Resistant cells selected with T-DM1 alone are named “TR” and cells selected in the presence of T-DM1 and CsA are called “TCR”. OE-19 TCR cells showed modifications in adhesion gene expression, migration and adhesion strength, combined with an increased sensitivity to a RHOA inhibitor. Also, OE-19 TR cells presented an overexpression of COX-2 associated with an increased amount of PGE2 in the supernatant. A deregulation of the genes involved in the prostaglandin pathways was found in OE-19 TR and TCR cells, associated with increased sensitivity to aspirin. In conclusion, we found two signaling pathways deregulated in cell lines resistant to T-DM1. These results need to be validated using samples from patients resistant to T-DM1. Targeting the adhesion or the prostaglandin pathway could be of benefit for patients with T-DM1 resistant cancers
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Průša, Jaromír. "Využití DMT při návrhu ochrany a organizace povodí Děrenského potoka." Master's thesis, Vysoké učení technické v Brně. Fakulta stavební, 2012. http://www.nusl.cz/ntk/nusl-225393.
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The theme of the work is the creation of the characteristics of the erozních and drainage conditions in the cadastral territory of the commune and the subsequent proposal Kujavy erosion control measures. Analysis of erozion ratios was processed using GIS method of the grid. Characteristics of runoff ratios was carried out for major service area of the critical points (SPKB) using model DesQ and numbers of the CN. In the design of erosion control measures was drawn up in the economic evaluation.
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Moran, Lopez Natalia Isabel. "Effects of Ethinylestradiol, EE2, exposure on Poecilia reticulta male specific genes, DMRT1 and CYP11b." Thesis, Södertörns högskola, Institutionen för livsvetenskaper, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-12356.
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Endocrine disrupting chemicals (EDCs) found in every day product, can either be natural or man-made and usually exists in a concerning concentration in our aquatic environment which in turn could affect teleost reproduction. EDCs exposure in fishes may result in changes in their reproductive physiology and morphology resulting in for example induction in gonopodia in female fish when exposed to androgens and in males exposed to female estrogen a reduced sperm count and skewed sex ration. Exposures during development have effects on organisms that are permanent and irreversible. Exogenous estrogens are known to direct gonadal in male fish into differentiation of functional ovary while androgens in the other hand can masculine female fish. The contraceptive pills, ethinylestradiol (EE2), secreted by women, is one of those chemicals that affects organisms by demasculizing or feminizing it. One of the most useful biomarkers in distinguishing male fish that are feminized or desmaskuliniseras is the detection of vitellogenin, VTG a female yolk protein in samples. For this study Poecilia reticulata, guppy, is chosen since they are live bearers, reproduce readily and one can easily distinguish the male from the female and they grow quickly. The most significant hormone in fish, were outstanding secondary sexual characterization, is 11-ketotestosterone whose production starts in Leydig cells. The biosynthesis of these potent 11-oxygenated androgens includes a first enzyme, 11-β hydroxylase cytochrome P45011β(CYP11b), involved from precursors such as testosterone (T) or androtestedione (AT). Another important protein involved in the role of sex determination is Double sex and map-3 related transcription factor 1, a gene that is essential for the testicular differentiation. Main objective of this study is to study the effects of administration of estrogen in male fish that has been exposed during the two week period at different levels of estrogen; 0 ng / L, 3 ng / L and 10ng / L, where the expected results should show that these fishes becomes feminized or demaskuliniserade, because the masculine genes such as CYP11b and DMRT-1 will decreases in gene expression or result in no expression at all. A molecular approach in the manner of RNA isolation by TRIZOL protocols, obtaining cDNA, PCR with RNA/ cDNA and semi-quantitive PCR with cDNA will be performed. Results in the study does not correlate with the expected results, which meant that of the fishes that are exposed to maximum dose of estrogen still gave transcription of CYP11b and DMRT1. Although this was a declining pattern discern in some cases. Despite that results were not as expected these genes are definitely good biomarkers for indentifying males and for the use of identifying desmasculinization in male. Considering the ecological disturbance these EDCs are having, they are for certain affecting aquatic organisms due to the huge amount of pollution that are being released in their environment. It is therefore important to continue already proceed studies.
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Devisetty, Upendra Kumar. "Molecular investigation of RAD51 and DMC1 homoeologous genes of hexaploid wheat (Triticum aetivum L.)." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/13340/.
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Meiotic recombination in eukaryotes requires two orthologues of the E. coli RecA proteins, Rad51 and Dmc1. Both genes play an important role in the binding of single strand DNA, homology search, strand invasion and strand exchange resulting in Holliday junctions which are resolved into crossovers or non-crossovers events. Even though both genes are well characterized in a variety of organisms including plants, very little information is available from hexaploid wheat. In most diploid plant species, deletion of either the RAD51 or DMC1 orthologues leads to sterility but wheat being a polyploid, offers a unique opportunity to examine the effects of the deletion of specific homoeologue, while maintaining a degree of fertility. The transcript expression profiling of RAD51 and DMC1 genes in Arabidopsis, rice and wheat using available microarray databases indicated higher levels of expression in mitotically and meiotically active tissues compared to other tissues. However, the possible function of the DMC1 gene in mitotic-active tissues needs to be investigated further. Previously cDNA sequences of TaRAD51 and TaDMCl of hexaploid wheat were cloned and reported. In this study, it has been demonstrated that the reported TaRAD51A1 and TaRAD51A2 cDNA sequences are (D) and (A) homoeologues of TaRAD51 respectively and TaDMCl cDNA sequence is (D) homoeologue of the TaDMC1. This study also found that the amino acid sequences and evolutionary relationships of RAD51 and DMC1 cDNA homoeologues are highly conserved across eukaryotes. Functional characterization of TaRAD51 and TaDMCl gene homoeologues was undertaken in planta using Forward Genetics, Reverse Genetics and Complementation methods. Forward and Reverse Genetic screening of a subset of a Highbury mutant population could not identify any mutants that have deletions in TaRAD51 and TaDMC1 genes. However, Reverse Genetics screening of Paragon mutant population identified mutant lines that tested as having deletions for all the three homoeologues of TaRAD51 and TaDMCl. However, most likely due to high mutational load and a deleterious phenotype, only a few mutant lines survived. Phenotypic and cytogenetic analysis indicated the probable functional redundancy of TaRAD51 (B) homoeologue in meiosis, although the unknown size of the deletion and limited phenotype makes it impossible to completely certain of this. The single mutants for TaDMC1 (B) and (D) indicated a reduction in pollen viability and ear fertility compared to wild-type. The cytological examination of these mutants indicated low levels of abnormal diakinesis, resulting in the formation of dyads. However, the single mutants were still able to produce normal tetrads. This suggests that there is a possible dosage effect of these homoeologues in hexaploid wheat. Unless deletion lines for the (A) and (D) homoeologues of TaRAD51 and (B) homoeologue of TaDMC1 can be recovered and characterized the above assumptions will remain inconclusive. The results of complementation assays using over-expressing CaMV35S::TaRAD51(D)±GFP constructs demonstrated a very low (-14% and -2%, respectively, with +GFP and -OFP constructs) functional complementation in terms of seed set compared to 0% in homozygous Atrad51 mutants. One explanation of these results is that the wheat genes are not complete functional orthologues for the inactivated Arabidopsis genes. The functional complementation experiments could not be performed for TaDMC1 gene because of time limitation, although the transformants were produced in AtDMC1/atdmc1 background. Finally, overexpression of the TaRAD51 gene suggests 2-fold increase in genetic distances in Arabidopsis using CaMV35S::TaRAD51(D) construct. This was done by crossing the appropriate transformant with fluorescent tetrad lines. However the results need to be confirmed by a large scale analysis.
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Polley, Shamik. "The genetic structure, function and relevance to disease of the salivary agglutinin gene (DMBT1)." Thesis, University of Leicester, 2015. http://hdl.handle.net/2381/31400.
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Salivary agglutinin, encoded by the gene DMBT1, is a multifunctional high molecular mass glycoprotein (340 kDa) that acts as a pattern recognition receptor (PRRs) in innate immunity and mediates epithelial differentiation. The central region of the protein contains 13 tandemly-repeated scavenger receptor cysteine-rich (SRCR) domains that are copy number variable and bind to bacteria and viruses. The paralogue ratio test (PRT) was used to estimate the exact copy number of two distinct CNV (1 & 2) regions of DMBT1 gene and results were compared with other CNV estimation assays. Both CNV1 and CNV2 at DMBT1 were multiple allelic CNVs and diploid copy number varied in different populations. The de novo mutation rate at CNV1 and CNV2 of DMBT1 was estimated using a segregation study of 520 samples from 40 multigenerational CEPH families; a high mutation rate was found at both loci of DMBT1 (CNV1 - 1.4% and CNV2 - 3.3% per generation). The evolutionary basis of CNV at DMBT1 was examined using 971 samples from 52 populations from the Human Genome Diversity Panel (HGDP-CEPH). The study found that the subsistence history of human populations affected the frequency distribution of both CNVs at DMBT1. The increase in dental caries following the development of agriculture, and the likely causative role played by an increase in Streptococcus mutans following transition to a starch-rich diet, the present study suggests that this has favoured CNV1 and CNV2 alleles at DMBT1 with more S. mutans-binding SRCR domains in agricultural populations. Due to the functional importance of DMBT1, the study analysed association of DMBT1 copy number in different disease cohorts. The study found no evidence of the association between DMBT1 copy number with Crohn’s disease (n=2900), Urinary tract infection (UTI; n=405), vesicoureteral reflux (VUR; n=625), Chronic obstructive pulmonary disease (COPD; n=241) and Asthma cohorts (n=850). A significant association was found between CNV2 copy number and base-line HIV (n=987) viral load just before anti-retroviral therapy.
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Tavares, Lidiane Silva. "Investigação de alcaloides ß-carbolinas, Triptaminas presentes na Ayahuasca (Santo Daime) em amostras de suor." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/60/60134/tde-30102014-162441/.
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Os alcaloides ß-carbolinas, Harmina e Harmalina, e o potente alucinógeno N, N-dimetiltriptamina são os principais componentes da Ayahuasca, uma bebida típica, utilizada na forma de chá e amplamente empregada em rituais religiosos na América do Sul. Embora seu uso ocorra desde períodos pré-colombianos ainda são poucas as informações sobre suas possíveis aplicações clínicas, assim como seus efeitos toxicológicos. Nos últimos anos, o uso da Ayahuasca se difundiu para vários países: Estados Unidos, Alemanha, Inglaterra, França e Espanha, com isso houve o aumento do interesse em estudos científicos acerca do chá. Em decorrência do aumento no consumo do chá, é importante o desenvolvimento e aplicação de métodos analíticos validados na rotina laboratorial e a utilização de uma matriz biológica que seja de fácil coleta e possibilite um número representativo de amostras. No presente trabalho, o suor foi utilizado como uma amostra biológica não convencional, pois possui algumas vantagens em relação às amostras convencionais como, por exemplo, o sangue; possui uma coleta não invasiva, indolor e sem constrangimentos para o voluntário, fácil aquisição de um registro cumulativo da exposição de substâncias, e janela de detecção mais longa, tornando-se uma ferramenta útil, pois permite a realização de uma coleta com maior frequência e sem atrapalhar o ritual religioso do voluntário. Embora vários métodos já tenham sido publicados para determinação de diferentes substâncias utilizando o suor como matriz biológica, tais como: ecstasy, cocaína, anfetamina, codeína, MDMA e ?9-Tetrahidrocannabinol, até a presente data, não foram encontrados métodos descritos na literatura utilizando o suor como matriz biológica para identificação de DMT, HRM e HRL em voluntários usuários da bebida. O método desenvolvido apresentou linearidade de 50 a 1500 ng/adesivo e o limite de detecção encontrado foi de 15 ng/adesivo para Harmina, 15 ng/adesivo para Harmalina e 10 ng/adesivo para o DMT. O ceficiente de variação intra-ensaio variou de 3,92% a 9,06% e o inter-ensaio variou entre 3,34% a 9,85%; a exatidão variou entre 87,5% a 105%. A recuperação encontrada foi superior a 70%.<br>The ß carbolines alkaloids, and Harmina Harmalina, and the potent hallucinogen N, N - dimethyltryptamine are the main components of Ayahuasca, a typical drink used in tea form widely used in religious rituals in South America. Although its use occurs from preoperative - Colombians are still little information about their possible clinical applications, as well as their toxicological effects. In recent years, the use of Ayahuasca has spread to many countries: United States, Germany, England, France and Spain, it was the increased interest in scientific studies about tea. Due to the increase in the consumption of tea, it is important the development and application of validated analytical methods for routine monitoring and the use of a biological matrix that is easily collected and allow a representative number of samples. In the present work , sweat was used as a biological sample unconventional because it has some advantages as compared to conventional samples, such as blood; have a non-invasive, painless and without constraints for voluntary, easy acquisition of a cumulative record of exposure of substances, and longer detection window, making it a useful tool collects as it allows the realization of a collection more frequently and without disturbing the religious ritual of voluntary. Although several methods have been published for the determination of different substances using sweat as a biological matrix, such as ecstasy, cocaine, amphetamine, codeine, MDMA and ?9 - Tetrahidrocannabinol, to date, no methods have been described in the literature using the sweat as a biological matrix for identification of DMT, HRL and HRM in volunteer users of the drink. The developed method was linear 50-1500 ng / patch and the limit of detection was 15 ng / patch Harmina, 15 ng / patch Harmalina and 10 ng / patch for DMT. The ceficiente intra -assay variation ranged from 3.92 % to 9.06 % and inter -assay ranged from 3.34 % to 9.85%; the accuracy ranged from 87.5 % to 105 %. The recovery was found to exceed 70%.
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Conde, Marcus Cristian Muniz. "Obtenção de RNA odontoblástico de alta qualidade após o armazenamento de dentes em diferentes condições de temperatura." Universidade Federal de Pelotas, 2010. http://repositorio.ufpel.edu.br/handle/ri/2277.
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Previous issue date: 2010-04-30<br>Isolate high quality RNA form dental tissues is a most critical step to perform gene expression analysis. In some situations it is impossible to achieve the RNA isolation after tooth extraction, which leads to tooth discarding. Since, the aim of this experiment was to verify the effect of different teeth storage methods in the quality of RNA obtained from freshly extracted third molars. The teeth were randomly divided in five groups according to the temperature and storage time conditions. In control group RNA was isolated immediately after tooth extraction in room temperature. Experimental storage conditions evaluated were: liquid nitrogen, -80°C, -20°C (24h) and 4°C (6h). To RNA isolation, teeth were longitudinally sectioned and then pulp and pre-dentin were submerged in TRIzol®. Semi-quantitative RT-PCR was used to analyze the expression of odontoblast makers (DSPP, DMP1, and MEPE), which were normalized against the GAPDH gene. DSPP, DMP1 and MEPE were amplified in all storage conditions evaluated, regardless of storage method or tissue analyzed. Was possible to obtaining high quality RNA from pulp and dentin in all storage conditions appraised, increasing the RNA available to be used as positive control in cell differentiation studies<br>Extrair RNA de qualidade dos tecidos dentais é um passo crítico para a realização da análise de expressão gênica. Em algumas situações não é possível realizar o isolamento do material genético dos tecidos dentários logo após a exodontia, o que conduz ao descarte do dente. Assim, o objetivo desse estudo foi avaliar o efeito de diferentes formas de armazenamento dos dentes na qualidade do RNA odontoblástico isolado de
terceiros molares recém extraídos. Os dentes foram separados de forma aleatória em cinco grupos de acordo com o tempo e a temperatura de armazenamento. No grupo controle o RNA foi isolado imediatamente após o procedimento cirúrgico em temperatura ambiente.As condições experimentais avaliadas foram: armazenamento dos dentes em nitrogênio líquido, -80°C e -20°C durante 24h e armazenamento 4°C durante 6h. Para
a extração do RNA os dentes foram seccionados e então o tecido pulpar e a pré-dentina foram imersos, separadamente, em TRIzol. RT-PCR foi utilizado para analisar a efetividade dos métodos de armazenamento através da amplificação dos marcadores da diferenciação odontoblástica (DSPP, DMP1, e MEPE), que foram normalizados contra o gene constitutivo GAPDH. DSPP, DMP1, e MEPE foram amplificados de forma
clara em todas as condições avaliadas, independentente do método de armazenamento, ou do tecido avaliado. Foi possível obter RNA de qualidade em polpa e dentina, em todas as condições de armazenamento avaliadas, aumentando assim a disponibilidade de RNA para ser utilizado como controle positivo em estudos de diferenciação celular
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Gasnier, Erwan. "Expansion de triplets CTG et arrêt prolifératif précoce des myoblastes DM1." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00829312.
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La dystrophie myotonique de type I est la pathologie neuromusculaire la plus répandue chez l'adulte. Elle est caractérisée par une atteinte multisystémique plus ou moins prononcée en fonction de l'extension des répétitions CTG, mutation à l'origine de l'atteinte. Le muscle squelettique est particulièrement touché avec un phénomène de myotonie ainsi qu'une atrophie. Les myoblastes, à l'origine de la formation des muscles et de leur régénération potentielle, présentent, chez les patients DM1, une capacité proliférative limitée par rapport à des myoblastes issus d'individus sains. C'est l'activation précoce de la voie p16 qui est à l'origine de cette sénescence prématurée des cellules DM1. Les mécanismes conduisant à ce phénotype sont néanmoins inconnus. Au cours de cette étude, nous avons tenté de décrypter une partie de ces mécanismes et notamment les liens potentiels entre les expansions CTG, la sensibilité au stress oxydatif et l'activation précoce de la voie p16 conduisant à la sénescence des myoblastes DM1
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Zimmermann, Eva. "Assoziation von funktionell wirksamen Polymorphismen im humanen DMBT1-Gen mit der Pathogenese der chronischen Parodontitis." Diss., Ludwig-Maximilians-Universität München, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-158507.
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Le, Bras Emanuelle. "Die Rolle von DMBT1-Polymorphismen auf die Suszeptibilität und den Phänotyp von chronisch entzündlichen Darmerkrankungen." Diss., Ludwig-Maximilians-Universität München, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-161747.
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El, Zaiat Maëva. "Cibles et voies de signalisation régulées par FOXL2 au cours de la morphogenèse ovarienne." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS035/document.
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FOXL2 est un facteur de transcription crucial pour la fonction ovarienne. Dans l'espèce humaine, des mutations hétérozygotes de ce gène sont responsables de la survenue d'un syndrome associant des malformations des paupières à une insuffisance ovarienne prématurée. De même chez la souris, l'invalidation totale de Foxl2 conduit à un blocage de la folliculogenèse et donc à une infertilité femelle. Chez la chèvre, la mutation Polled Intersex Syndrome (PIS) engendre le silence transcriptionnel de FOXL2 dans les gonades XX PIS-/- ce qui conduit à une inversion sexuelle et à la différenciation de testicules à la place d'ovaires chez les animaux génétiquement femelles homozygotes pour la mutation (inversion sexuelle de type mâle XX). FOXL2 est donc déterminant pour la différenciation ovarienne très précocement au cours du développement dans l'espèce caprine, alors qu'il ne semble impliqué que plus tardivement dans l'établissement de la fertilité chez la souris et la femme. Afin de comprendre ces différences entre espèces, nous avons recherché quels étaient les gènes et les voies de signalisation régulés par FOXL2 dans l'ovaire de chèvre au début de sa différenciation. Grâce à un séquençage à haut-débit des transcrits présents dans trois types de gonades caprines (testicules XY, ovaires XX et gonades XX PIS-/- (qui n'expriment pas FOXL2)) au début de leur différenciation, nous avons pu (i) mieux caractériser le rôle de FOXL2 dans l'ovaire caprin et montrer qu'il y agit avant tout comme un facteur anti-testiculaire, et (ii) mettre en évidence de nouveaux gènes pro-ovariens comme DMXL2 et étudier son rôle putatif dans la fonction ovarienne grâce à des expériences fonctionnelles chez la souris<br>FOXL2 is a transcription factor which is crucial for the ovary. In humans, heterozygous mutations are responsible for the BPES syndrome characterized by eyelid anomalies and premature ovarian failure. Similarly in mice, Foxl2 invalidation leads to complete folliculogenesis disruption and female infertility. In the goat, the Polled Intersex Syndrome mutation is responsible for the transcriptional silencing of FOXL2 in XX PIS-/- gonads that leads to female-to-male sex reversal and the differentiation of testes instead of ovaries in genetically female animals homozygous for the mutation. Thus, FOXL2 is determining for ovarian differentiation early during development in goats, whereas it is involved in fertility tardily in mice and women. In order to understand these species-specific differences, we searched for the genes and pathways regulated by FOXL2 in early goat ovaries. Thanks to RNA-sequencing of goat XY testes, XX ovaries and XX PIS-/- gonads (lacking FOXL2) at the beginning of their differentiation, we were able to (i) better characterize the role of FOXL2 in goat ovaries and show that it acts mainly as an anti-testis factor, and (ii) highlight new pro-ovarian genes like DMXL2, and study its putative role during ovarian development using functional experiments in the mouse
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Sosnoski, Jonatas. "Interpretação de ensaios de CPTU e DMT em solos com permeabilidade intermediária." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/156352.
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A indústria mineradora do país sofre constantemente com problemas ambientais devido à qualidade e volume de rejeitos gerados durante o processo de extração do minério. Os volumes gerados demandam grandes áreas para armazenagem e consequentemente obras complexas de contenção dos rejeitos. A engenharia geotécnica busca entender o comportamento mecânico de depósitos destes rejeitos através do uso de ensaios tanto de campo como de laboratório. Para isso utiliza ferramentas e procedimentos consagrados no meio técnico seguindo normas e procedimentos estabelecidos e consagrados mundialmente. No entendimento do comportamento mecânico dos solos argilosos, as análises são desenvolvidas em termos de tensões totais, já para os solos arenosos em termos de tensões efetivas. Todavia, para solos com granulometria intermediária, não se tem um consenso no que se refere à interpretação do comportamento mecânicos a partir de ensaios de campo Este trabalho apresenta resultados de ensaios de DMT e CPTU conduzidos em diferentes velocidades de penetração no intervalo de aproximadamente 1 e 57 mm/s, em depósito de rejeito de mineração, para avaliar tanto a influência da velocidade sobre as medidas do ensaio, quanto a transição das condições de fluxo ao redor do piezocone e durante a expansão da membrana do dilatômetro. Um equipamento simples e de baixo custo foi desenvolvido para monitorar a poropressão no centro da lâmina do DMT e dados são interpretados à luz das condições de drenagem impostas durante a execução do ensaio. Resultados indicam que as leituras e os valores de P0 e P1 são medidas de tensão total e por este motivo influenciadas pela magnitude da poropressão gerada durante a penetração da lâmina. Um novo Fator de Velocidade adimensional “Vt” é proposto para identificar possíveis efeitos de consolidação que ocorrem durante a penetração do piezocone e orientações são dadas para utilização de CPTU e DMT em solos de permeabilidade dentro do intervalo de 10-6 a 10-3 cm/s.<br>The mining industry of the country constantly suffers from environmental problems due to the quality and volume of waste generated during the mineral extraction process. Volumes generated require large areas for storage and consequently complex works of tailings. The geotechnical engineering seeks to understand the mechanical behavior of deposits of this waste by using assays well as laboratory and field. To this end tools and procedures laid down in the technical means following established rules and procedures consecrated worldwide. In the understanding of the mechanical behavior of clay soils, the analyzes are developed in terms of total stresses and for sandy soils in terms of effective stress. However, in soils with intermediate particle size, there is no consensus concerning the interpretation of the mechanical behavior from field trials. This paper presents the results of DMT and CPTU test conducted at different penetration rates in the range of about 1 to 57 mm / s in mining waste deposit to evaluate both the effect of speed on the measurements of the test, as the transition the flow conditions around the piezocone and during the expansion of the dilatometer membrane. A simple and inexpensive equipment has been developed to monitor the pore pressure in the center of the DMT blade and data are interpreted in the light of the imposed drainage conditions during the test. Results indicate that the readings that the P0 and P1 are total stress measurements and for this reason influenced by the magnitude of pore pressure generated during penetration of DMT blade. A new dimensionless Velocity Factor "Vt" is proposed to identify potential consolidation effects occurring during the penetration of piezocone and guidance is provided for use CPTU and DMT in soil permeability in the range 10-6 to 10-3 cm/s.
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Tarsounas, Madalina Cecilia. "Synaptonemal complex proteins, post-translational modifications, protein-protein interactions and interaction with the rad51/dmc1 recombinases." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0007/NQ39313.pdf.
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Diogenes, Adriana de Holanda Mafaldo. "Capilaroscopia na DMTC: um processo dinâmico associado ao envolvimento intersticial pulmonar e à gravidade de doença." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5145/tde-22112006-093814/.
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Selecionamos consecutivamente 63 pacientes com doença mista do tecido conectivo (DMTC) (Kasukawa, 87) para determinar a relevância do padrão SD. Ter uma capilaroscopia periungueal (CPU) até cinco anos antes do início do estudo foi o principal critério de inclusão. Na entrada, avaliamos o envolvimento de órgãos e os auto-anticorpos. A idade média e o tempo de doença foram 45,3 + 10 e 8,45 + 5,42 anos, respectivamente. O padrão SD foi observado em 41 pacientes na entrada (65%) e em 45 na CPU prévia (71,5%), p = 0,20. Dez pacientes (16%) alteraram a CPU, 7 normalizaram e 3 desenvolveram padrão SD. O tempo de doença, número e freqüência de órgãos envolvidos foram semelhantes em pacientes com e sem padrão SD. Em contraste, a análise de cada parâmetro do padrão SD mostrou uma freqüência significativamente menor de áreas avasculares (AA) moderadas/graves na entrada, comparada com a CPU anterior (26,5 e 53%, p = 0,013). Além disto, 76% dos pacientes com doença intersticial pulmonar (TCAR) tiveram AA na entrada, enquanto apenas 24% dos pacientes com esta alteração não apresentavam este achado à CPU (p = 0,017). Adicionalmente, reduzida densidade capilar foi freqüentemente observada em pacientes submetidos à terapia imunossupressora, quando comparados com o grupo sem este tratamento (66,7 e 33,3%, p = 0,001). A CPU na DMTC é um processo dinâmico e a análise de cada parâmetro do padrão SD parece ser um bom indicador de doença intersticial pulmonar e gravidade de doença.<br>For determining the clinical relevance of SD-pattern in MCTD, sixty-three MCTD patients (Kasukawa´s criteria) were consecutively selected. The main inclusion criterion was availability of previous nailfold capillaroscopy (NC) 5 years before inclusion. At entry, organ involvement and autoantibody evaluation were performed. The mean age and disease duration were 45.3 + 10 and 8.45 + 5.42 years, respectively. SD-pattern was observed in 41 patients at entry (65%) and in 45 at previous NC (71.5%), p = 0.20. Ten patients (16%) changed NC, 7 normalized, and 3 developed SD-pattern. Disease duration, number and frequency of organ involvement were similar in patients with and without SD-pattern. In contrast, analysis of each SD-pattern parameter revealed a significant lower frequency of moderate/severe avascular areas (AA) at entry compared to previous examination (26.5 vs. 53%, p = 0.013). Moreover, 76% of patients with interstitial lung disease (HRCT) had AA at entry, whereas only 24% of patients with this alteration did not have this NC finding (p = 0.017). Furthermore, reduced capillary density was frequently observed in patients taking immunosuppressive therapy than those without (66.7 vs. 33.3%, p = 0.001). NC in MCTD is a dynamic process and analysis of each SD-pattern parameter seems to be a good indicator of lung involvement and disease severity
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Rodgers, Edmund William. "Sexual Plasticity in a Marine Goby (Lythrypnus dalli): Social, Endocrine, and Genetic Influences on Functional Sex." Digital Archive @ GSU, 2007. http://digitalarchive.gsu.edu/biology_diss/34.
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Sex determination occurs early in development for most animals, at which time sex is fixed for life. Many teleost fishes, however, exhibit remarkable sexual plasticity throughout their life history, ranging from multiple morphs within a sex to functional adult sex reversal. To understand the development and evolution of adult sex reversal, I examined behavioral, endocrine, and genetic contributions to the regulation of functional sex in adult animals, using the bluebanded goby (Lythrypnus dalli) as an experimental model. This species was found to be equally capable of sexual transitions from female to male (protogyny) as from male to female (protandry). Throughout adult life, sexual phenotype is determined by social status, an emergent property of agonistic behavioral interactions that follows a relatively simple social convention: if dominant become or remain male, or if subordinate, become or remain female. The translation of social status into a change in sexual phenotype in the protogynous direction requires a rapid drop in circulating estrogens and an increase in the gonadal expression of a testis differentiating gene dmrt1. Steroid hormones do not play a significant role in modulating status, but the androgen 11-ketotestosterone does positively correlate with the expression of paternal behavior. Taken together, these findings suggest an evolutionary mechanism in sexually plastic species that has linked the conserved molecular cascades of sexual differentiation to a novel signal that varies over life history, social status, thereby allowing for lifelong phenotypic plasticity.
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Nilsson, Kristian. "Film formation of latex in dry coating films." Thesis, Karlstad University, Faculty of Technology and Science, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-1048.
Full textAbstract:
<p>The objective of this master thesis was to investigate the possibility to measure the gain in stiffness of the dry coating due to film formation of latex with a Dynamic Mechanic Thermal Analyzer (DMTA). This could tell when and to which extent the latex forms a film after the drying process.</p><p>Two latices with different Tg was used for the experiments, one with a Tg of 36°C, denoted hard, and the one with a Tg of 8°C, denoted soft. The hard latex was used to make coating samples that would not form a film when dried at room temperature and the soft latex was used as a reference to the coating with hard latex since it would form a film at room temperature.</p><p>It was shown that a gain in stiffness due to film formation of latex in coating can be measured with a DMTA. It was also shown that that the film forming of latex in coatings depend on time, temperature and the history of the sample. Further investigations were carried out to try to determine the time for film formation to be completed at a certain temperature.. These investigations showed that this type of trials cannot be carried out in a DMTA directly since the stiffness seemed to increase monotonically during a very ling time. This might be due to the rearrangements in the pigment structure that might affect the gain in stiffness. Therefore, a method involving oven curing was developed. Only one series of test were performed with this method due to lack of time but the method showed promising results.</p><br><p>Syftet med detta examensarbete var att undersöka möjligheten att använda en Dynamic Mechanic Thermal Analyzer (DMTA) för att mäta ökningen av styvhet som följd av filmbildning av latex i en torr bestrykning.</p><p>Två olika latexer användes för experimenten, en med Tg = 36°C (hård) och en med Tg = 8°C (mjuk). Den hårda latexen användes för att kunna göra tester på prover som ännu inte filmbildat när de torkat vid rumstemperatur och den mjuka latexen användes för att göra referens prover mot bestrykningen med hård latex.</p><p>Resultaten visade att det går att mäta styvhetsökning i bestrykningen som en följd av filmformation med DMTA och filmformation av latex i bestrykningen troligtvis beror på både tid, temperatur och provets historia. Ett försök att mäta vilken uppehålls tid vid en specifik temperatur som krävs för att filmbildningen skall fulländas genomfördes. Dessa försök visade att DMTA:n inte var en lämplig metod för att mäta denna tid då styvheten verkade öka under en längre tid. Detta kan bero på att pigment partiklarna packade sig tätare och på så sätt orsakade en ökning av styvheten. Därför gjordes ett annat försök som involverar ugns härdning, men på grund av tidsbrist blev det bara en mätserie utförd. Den sist nämnda metoden visade dock goda resultat och måste därför bedömas ha en potential.</p>
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Haridas, Nakul Raghavanand. "Parylene based low actuation MEMS phase shifters for reconfigurable antenna applications." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/17079.
Full textAbstract:
Wireless networks face ever-changing demands on their spectrum and infrastructure resources such as, increased communication bands, capacity-intensive data applications, and the steady growth of worldwide wireless subscribers. This rapid increase in the use of wireless communication and the dependence on a reliable connectivity leads manufacturers to seek systems which are ever smaller, low power, provide long range, and high bandwidth, whilst giving higher reliable technologies. In modern communication systems MEMS is now finding its way, replacing older more high power and non-linear systems. One of the important components of RF MEMS technology is the implementation of MEMS phase shifters for phased array applications that require better performance than arrays of conventional phase shifters. An important example is where RF MEMS devices can be applied to vary the characteristics of an antenna, such as beam steering or tuning in a multiband antenna. The core of this thesis is the development and fabrication of a novel Parylene based MEMS phase shifter. This is the first novel application of Parylene as the strength member of the MEMS bridge. The implementation provided MEMS devices with lower actuation voltage of < 25 V. The fabricated phases shifters provide higher RF performance such as < 1 dB insertion loss, linearity of > 65 dBm, and return loss of < -15 dB. The reliability of the fabricated devices were tested beyond 2 billion switching cycles. This is higher than competing MEMS capacitive devices with a maximum lifetime of 500 million cycles. The fabricated device provides a maximum phase shift of 16.82° at 2.5 GHz, whilst the nominal value of phase shift was 5.4° at 2.5 GHz within the stable region of operation. The fabricated device provides comparable results with respect to reference DMTL designs. The research carried out in this thesis has lead to a number of international publications and four granted patents. The generic nature of this technology can open new opportunities in the conception and application of new MEMS devices in communication and sensing applications. The ability to deliver miniature, low power and high efficiency MEMS capacitive devices, will revolutionise the next generation of tuneable RF components suitable for mobile and handheld devices of the future.
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Pightling, Arthur William. "The evolutionary history of meiotic genes: early origins by duplication and subsequent losses." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/2960.
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Meiosis is necessary for sexual reproduction in eukaryotes. Genetic recombination between non-sister homologous chromosomes is needed in most organisms for successful completion of the first meiotic division. Proteins that function during meiotic recombination have been studied extensively in model organisms. However, less is known about the evolution of these proteins, especially among protists. We searched the genomes of diverse eukaryotes, representing all currently recognized supergroups, for 26 genes encoding proteins important for different stages of interhomolog recombination. We also performed phylogenetic analyses to determine the evolutionary relationships of gene homologs. At least 23 of the genes tested (nine that are known to function only during meiosis in model organisms) are likely to have been present in the Last Eukaryotic Common Ancestor (LECA). These genes encode products that function during: i) synaptonemal complex formation; ii) interhomolog DNA strand exchange; iii) Holliday junction resolution; and iv) sister-chromatid cohesion. These data strongly suggest that the LECA was capable of these distinct and important functions during meiosis. We also determined that several genes whose products function during both mitosis and meiosis are paralogs of genes whose products are known to function only during meiosis. Therefore, these meiotic genes likely arose by duplication events that occurred prior to the LECA. The Rad51 protein catalyzes DNA strand exchange during both mitosis and meiosis, while Dmc1 catalyzes interhomolog DNA strand exchange only during meiosis. To study the evolution of these important proteins, we performed degenerate PCR and extensive nucleotide and protein sequence database searches to obtain data from representatives of all available eukaryotic supergroups. We also performed phylogenetic analyses on the Rad51 and Dmc1 protein sequence data obtained to evaluate their utility as phylogenetic markers. We determined that evolutionary relationships of five of the six currently recognized eukaryotic supergroups are supported with Bayesian phylogenetic analyses. Using this dataset, we also identified ten amino acid residues that are highly conserved among Rad51 and Dmc1 protein sequences and, therefore, are likely to confer protein-specific functions. Due to the distributions of these residues, they are likely to have been present in the Rad51 and Dmc1 proteins of the LECA.
To address an important issue with the gene inventory method of scientific inquiry, we developed a heuristic metric for determining whether apparent gene absences are due to limitations of the sequence search regimen or represent true losses of genes from genomes. We collected RNA polymerase I (Pol I), Replication Protein A (RPA), and DNA strand exchange (SE) sequence data from 47 diverse eukaryotes. We then compared the numbers of apparent absences to a single measure of protein sequence length and sequence conservation (Smith-Waterman pairwise alignment (S-W) scores) obtained by comparing yeast and human protein sequence data. Using Poisson correlation regression to analyze the Pol I and RPA subunit datasets, we confirmed that S-W scores and apparent gene absences are correlated. We also determined that genes encoding products that are critical for interhomolog SE in model organisms (Rad52, Rad51, Dmc1, Rad54, and Rdh54) have been lost frequently during eukaryotic evolution. Saccharomyces cerevisiae null rad52, dmc1, rad54, and rdh54 mutant phenotypes are suppressed by rad51 overexpression or mutation. If rad51 overexpression or mutation affects other eukaryotes in a similar fashion, this phenomenon may account for frequent losses of genes whose products are critical for the completion of meiosis in model organisms. Finally, we place this work into greater context with a review of hypotheses for the selective forces and mechanisms that resulted in the origin of meiosis. The review and the data presented in this thesis provide the basis for a model of the origin of meiotic genes in which meiosis arose from mitosis by large-scale gene duplication, following a preadaptation that served to reduce increased numbers of chromosomes (from diploid to haploid) caused by erroneous eukaryotic cell-cell fusions.
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Chmelíková, Jitka. "Stanovení exprese molekul transportu a metabolismu železa u vybraných chronických onemocnění." Master's thesis, 2010. http://www.nusl.cz/ntk/nusl-295879.
Full textAbstract:
Iron is an essential element for human organism, because it cooperates as a cofactor of enzymes in many metabolic pathways. Iron is a component of hemoglobin, and thus it is indispensable for the oxygen transport to tissues. It can exist as a ferrous or ferric form. However, ferrous iron paticipates in reactions in which highly reactive hydroxyl group can be formed. This product is harmful for the organism. Non-heme iron is taken up to the circulation through duodenal enterocyte. Iron excretion is carried out only by desquamation of the enterocytes or by bleeding. Therefore, iron intake must be strictly regulated. Iron overloading is observed in some chronic diseases (hereditary hemochromatosis, alcohol liver disease). In contrary, iron depletion can be a case of iron deficiency anemia. The aim of this master thesis is to determine the expression of iron transport molecules in duodenum in chronic diseases which originate due to disturbances of iron intake regulation. We determine the expression of molecules of iron transport (DMT1, Dcytb, ferroportin, hephaestin) on mRNA level by qPCR and on protein level by western blot. The level of serum hepcidin was determined by ELISA. Our results show an increased expression of mRNA of transporters DMT1 and ferroportin as well as ferrireductase Dcytb and ferroxidase...