293 resultados para Xeroderma pigmentoso (XP)


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Abstract This work is a contribution to the research and development of the intermediate band solar cell (IBSC), a high efficiency photovoltaic concept that features the advantages of both low and high bandgap solar cells. The resemblance with a low bandgap solar cell comes from the fact that the IBSC hosts an electronic energy band -the intermediate band (IB)- within the semiconductor bandgap. This IB allows the collection of sub-bandgap energy photons by means of two-step photon absorption processes, from the valence band (VB) to the IB and from there to the conduction band (CB). The exploitation of these low energy photons implies a more efficient use of the solar spectrum. The resemblance of the IBSC with a high bandgap solar cell is related to the preservation of the voltage: the open-circuit voltage (VOC) of an IBSC is not limited by any of the sub-bandgaps (involving the IB), but only by the fundamental bandgap (defined from the VB to the CB). Nevertheless, the presence of the IB allows new paths for electronic recombination and the performance of the IBSC is degraded at 1 sun operation conditions. A theoretical argument is presented regarding the need for the use of concentrated illumination in order to circumvent the degradation of the voltage derived from the increase in the recombi¬nation. This theory is supported by the experimental verification carried out with our novel characterization technique consisting of the acquisition of photogenerated current (IL)-VOC pairs under low temperature and concentrated light. Besides, at this stage of the IBSC research, several new IB materials are being engineered and our novel character¬ization tool can be very useful to provide feedback on their capability to perform as real IBSCs, verifying or disregarding the fulfillment of the “voltage preservation” principle. An analytical model has also been developed to assess the potential of quantum-dot (QD)-IBSCs. It is based on the calculation of band alignment of III-V alloyed heterojunc-tions, the estimation of the confined energy levels in a QD and the calculation of the de¬tailed balance efficiency. Several potentially useful QD materials have been identified, such as InAs/AlxGa1-xAs, InAs/GaxIn1-xP, InAs1-yNy/AlAsxSb1-x or InAs1-zNz/Alx[GayIn1-y]1-xP. Finally, a model for the analysis of the series resistance of a concentrator solar cell has also been developed to design and fabricate IBSCs adapted to 1,000 suns. Resumen Este trabajo contribuye a la investigación y al desarrollo de la célula solar de banda intermedia (IBSC), un concepto fotovoltaico de alta eficiencia que auna las ventajas de una célula solar de bajo y de alto gap. La IBSC se parece a una célula solar de bajo gap (o banda prohibida) en que la IBSC alberga una banda de energía -la banda intermedia (IB)-en el seno de la banda prohibida. Esta IB permite colectar fotones de energía inferior a la banda prohibida por medio de procesos de absorción de fotones en dos pasos, de la banda de valencia (VB) a la IB y de allí a la banda de conducción (CB). El aprovechamiento de estos fotones de baja energía conlleva un empleo más eficiente del espectro solar. La semejanza antre la IBSC y una célula solar de alto gap está relacionada con la preservación del voltaje: la tensión de circuito abierto (Vbc) de una IBSC no está limitada por ninguna de las fracciones en las que la IB divide a la banda prohibida, sino que está únicamente limitada por el ancho de banda fundamental del semiconductor (definido entre VB y CB). No obstante, la presencia de la IB posibilita nuevos caminos de recombinación electrónica, lo cual degrada el rendimiento de la IBSC a 1 sol. Este trabajo argumenta de forma teórica la necesidad de emplear luz concentrada para evitar compensar el aumento de la recom¬binación de la IBSC y evitar la degradación del voltage. Lo anterior se ha verificado experimentalmente por medio de nuestra novedosa técnica de caracterización consistente en la adquisicin de pares de corriente fotogenerada (IL)-VOG en concentración y a baja temperatura. En esta etapa de la investigación, se están desarrollando nuevos materiales de IB y nuestra herramienta de caracterizacin está siendo empleada para realimentar el proceso de fabricación, comprobando si los materiales tienen capacidad para operar como verdaderas IBSCs por medio de la verificación del principio de preservación del voltaje. También se ha desarrollado un modelo analítico para evaluar el potencial de IBSCs de puntos cuánticos. Dicho modelo está basado en el cálculo del alineamiento de bandas de energía en heterouniones de aleaciones de materiales III-V, en la estimación de la energía de los niveles confinados en un QD y en el cálculo de la eficiencia de balance detallado. Este modelo ha permitido identificar varios materiales de QDs potencialmente útiles como InAs/AlxGai_xAs, InAs/GaxIni_xP, InAsi_yNy/AlAsxSbi_x ó InAsi_zNz/Alx[GayIni_y]i_xP. Finalmente, también se ha desarrollado un modelado teórico para el análisis de la resistencia serie de una célula solar de concentración. Gracias a dicho modelo se han diseñado y fabricado IBSCs adaptadas a 1.000 soles.

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Usability is a critical quality factor. Therefore, like traditional software teams, agile teams have to address usability to properly catch their users experience. There exists an interesting debate in the agile and usability communities about how to achieve this integration. Our aim is to contribute to this debate by discussing the incorporation of particular usability recommendations into user stories, one of the most popular artifacts for communicating agile requirements. In this paper, we explore the implications of usability for both the structure of and the process for defining user stories. We discuss what changes the incorporation of particular usability issues may introduce in a user story. Although our findings require more empirical validation, we think that they are a good starting point for further research on this line.

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In this dissertation, after testing that neither the definition of Agile methodologies, nor the current tools that support them, such as Scrum or XP, gave guidance for stages of software development prior to the definition of the first interaction of development; we proceeded to study the state of the art of Inception techniques, that is, techniques to deal with this early phase of the project, that would help guide its development. From the analysis of these Inception techniques, we defined what we considered as the essential properties of an Inception framework. With that list at hand, it was found that no current Inception framework supported all the features, also, we found that it did not exist, either, any software application on the market that did it. Finally, after checking the above gaps, we defined the Inception framework "Agile Incepti-ON", with all the practices necessary to meet the requirements specified above. In addition to this, a software application was developed to support the practices defined in the Inception framework, called "Agile Dojo".

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Este proyecto ha sido estructurado en tres bloques diferenciados que tiene como objetivo analizar el presente, pasado y futuro de la gestión de proyectos con una orientación clara a ofrecer apoyo a aquellas empresas que planeen realizar un giro en sus estructura de organización de trabajo hacia filosofías ágiles. La gestión de proyectos a acompañado al hombre desde el inicio de los tiempos, pero sin embargo no fue hasta nuestra historia más cercana cuando se comienza a tener conciencia de la necesidad de establecer aplicar métodos generales a la hora de afrontar proyectos de ingeniería. Pioneros fueron en este sentido personajes como Taylor, Fayol o Gantt, cuyas aportaciones iniciales posibilitaron el nacimiento de la gestión de proyectos a mediados del siglo XX. En las década sucesivas hasta nuestros días han aparecido un número considerable de metodologías, perfeccionando elementos anteriormente asimilados y adaptándose a la realidad tecnológica y social del momento. Este recorrido histórico se aborda en el primer bloque de este proyecto. Los puntos revisados en la introducción histórica proporcionan las bases de conocimiento para entender las principales características entre las grandes familias de metodologías que actualmente son implantadas en el mundo empresarial. Es precisamente este punto, el de la exposición y análisis de las metodologías más extendidas y contemporáneas a la elaboración de este proyecto, lo que se aborda en el segundo bloque. En él se desarrolla con intenso detalle dos metodologías de la familia de filosofías ágiles, elegidas entre las más extendidas en la industria: Scrum, eXtreme Programming (XP) y un híbrido de ambas. Para entender la dimensión del cambio filosófico en cuanto a la gestión de proyectos que emprenden estas metodologías, se hace necesario repasar cuales son las metodologías no ágiles más extendidas actualmente. Para ello se introducen metodologías como la llamada tradicional o PRINCE2, principalmente, ya que también se realiza un repaso más superficial por otras aproximaciones notables. El último bloque que construye el desenlace del proyecto, intenta responder a las cuestiones futuras relacionadas con la adopción de metodologías ágiles. Para ello se revisa los puntos más conflictivos a señalar en este proceso y se ofrecerán soluciones teóricas y prácticas para ayudar a las empresas en su fase de migración hacia filosofías de organización ágiles. Ya que toda empresa hoy en día debería tener un soporte tecnológico que ofrezca apoyo a su desarrollo empresarial, gran parte de la elaboración de este proyecto se ha dedicado a hacer un estudio comparativo de las actuales herramientas Open Source. Se han instalado y probado 25 herramientas para posteriormente seleccionar 3 que han sido analizadas en profundidad. Así mismo, se enumeran pros y contras de estas herramientas, aportando ideas de mejoras y trazando cuál debería ser su evolución para ofrecer una alternativa real a las herramientas comerciales orientadas a esta labor. Las empresas pueden utilizar este índice de herramientas de software para decidir si pueden sustentar su proceso de migración en una herramienta Open Source o si deben orientarse a herramientas comerciales o de creación propias. ABSTRACT. This project has been divided into three different blocks that aims to analyze the past, present and future of project management with a clear focus on providing support to those companies that are planning to make a shift in its organizational structure working towards agile philosophies . The project management has walked together with the humanity since the beginning of time , but it was on our recent history when it begins to become aware of the need to establish general methods to apply to engineering projects. There was pioneers like Taylor , Fayol or Gantt, whose contributions made possible the birth of project management in the mid- twentieth century. In the following decades, there was a considerable number of new methodologies, improving concepts and adapting then to the technological and social reality of the moment . This historical journey is addressed in the first block of this project. The different facts reviewed at the first block provide the knowledge to understand the key features among the most important families of methodologies that nowadays are implemented in the business world. It is precisely this point, the presentation and analysis of the most widespread methodologies what is addressed in the second block. Two of the most widespread agile methodologies are detailed: Scrum , eXtreme Programming ( XP ) and a hybrid of both . In order to understand the philosophical shift in terms of project management performed by these methodologies , it is necessary to review what are the most widespread no agile methodologies currently. For this purpose, methodologies like Waterfall or PRINCE2 are explained. Other no agile methodologies are explained as well, but not so deeply in comparison with them. The last section of this project is the conclusion, it tries to answer future questions related to the adoption of agile methodologies. For that reason, the most important milestones are reviewed to provide theoretical and practical solutions and answers to help companies in this migration process toward agile methodologies. Since every company should has a solid technical support for its business development, a considerably part of the time has been applied to make a comparative study of the existing Open Source tools. 25 tools have been installed and tested. Then, 3 tools has been selected to be analyzed deeply. Also, pros and cons of these tools have been exposed in order to suggest a roadmap to offer a real alternative to the existing commercial tools in this business area. The companies that are involved in a migration progress toward a agile methodology can used this study about the available Open Source tools to decide if they can afford the migration process based on one of them or if they should use a commercial tool or a tailor-made software.

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Sabor, Software de Análisis de BOcinas y Reflectores, es una herramienta didáctica la cual es utilizada en los laboratorios de la escuela para realizar prácticas de la asignatura Antenas y Compatibilidad Electromagnética, esta herramienta da a los alumnos una visión gráfica de lo que se enseña en clase de teoría de lo que son los campos en las aperturas de los reflectores. El proyector pretende sustituir al primer Sabor , ya que se queda obsoleto debido al sistema operativo, ya que funciona solo para Windows XP y con ordenadores de 32 bits, y también realizar mejoras y corregir errores de la versión anterior. El proyecto se ha desarrollado en Matlab que es un software matemático con grandes ventajas en cuanto a cálculo, desarrollo gráfico, y a la creación de nuevos algoritmos en su propio lenguaje y además está disponible para las plataformas Unix, Windows, Mac OSX y GNU/Linux. El objetivo del proyecto ha sido implementar, al igual que las versiones anteriores, cinco tipos de reflectores, como son: Parabólico, Offset, Cassegrain y los dos Dobles Offset, Cassegrain y Gregorian, y han sido analizados con un alimentador ideal ,cos-q, y por último los resultados obtenidos se han comparado con las versiones anteriores de Sabor, como son Sabor 3.0 y el primer Sabor. El proyecto consta de partes muy bien diferencias como son :  La interpretación correctas de las formulas que se han utilizado para la realización de este proyecto ,dichas formulas han sido las dadas por el proyecto fin de carrera titulado Sabor3.0 de Francisco Egea Castejón.  GUIDE, the graphical user interface development environment, con el que se creó: GUI, graphical user interface, que es la parte de Matlab dedicada a crear interfaces de usuario , herramienta utilizada para crear nuestras distintas ventanas dedicadas para la obtención de datos para analizar los distintos reflectores y para mostrar por pantalla los distintos resultados.  Programación Orientada a Objetos de Matlab y sus distintas propiedades como son la herencia lo cual es muy útil para ocupar menos memoria ya que con un único método podemos realizar distintos cálculos con los distintos reflectores, objetos, solo cambiando las propiedades de cada objeto  Y por último ha sido la realización de validación de los resultados con la ayuda de las versiones anteriores de Sabor, que están detallados en el capítulo 5 y la unión con bocinas del proyecto fin de carrera Análisis de Bocinas en Matlab de Javier Montero. Por otra parte tenemos las mejoras realizadas a las antiguas versiones como son: realización de registros que el usuario puede guardar y cargar con las distintas variables, también se ha realizado un fichero .txt en el que consta la amplitud del campo con su respectiva theta para que el usuario pueda visualizarlo en cualquier plataforma gráfica de datos como por ejemplo exel. ABSTRACT. Sabor, Software de Análisis de BOcinas y Reflectores, is a teaching tool, which is used to do laboratory practice in the subject of Antennas y Compatibilidad Electromagnética, this tool gives students a graphic view of the knowledge that are given in theory class in regard to aperture field of reflectors. This project intend to replace the first Sabor, because it is outdated, due to the operating system, because Sabor works only with Widows XP and computer with 32 bits, and to make improves and correct errors that were detected in the last version of Sabor too. This project has been carried out in Matlab, which is a mathematical software with high-level language for numerical computation, visualization and application development, and furthermore it is available to different platforms such as Unix, Windows ,Mac OSX and GNU/Linux This project has focused on implementing, the same as last versions, five kind of reflectors, such as : Parabolic, Offset, Cassegrain and two offset dual reflector Cassegrain y Gregorian ,and these were analysed with a cos-q ideal feed, and finally the results were checked with the versions of Sabor, as well as Sabor 3.0 and the first Sabor. This project consist of four parts:  The correct interpretation of the formulas , which were used to do this project, from the final project Sabor3.0 by Francisco Egea Castejón.  GUIDE, the graphical user interface development environment, tool that was used to create : GUI, graphical user interface, part of Matlab dedicated to create user interface.  Object Oriented Programming of Matlab and different properties like inheritance, that is very useful for saving memory space because with only one method we can analyse different kind of reflectors, object, only change the properties of the object.  At finally, the results were contrasted with the results from the previous versions and the link reflectors with horns from the final project Análisis de Bocinas en Matlab by Javier Montero. On the other hand, we have the improvements such as: registers and .txt file. The registers are used by user to save and load different variables and .txt file is useful because it allows to the user plotting in different platforms for example exel.

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In females, most genes on the X chromosome are generally assumed to be transcriptionally silenced on the inactive X as a result of X inactivation. However, particularly in humans, an increasing number of genes are known to “escape” X inactivation and are expressed from both the active (Xa) and inactive (Xi) X chromosomes; such genes reflect different molecular and epigenetic responses to X inactivation and are candidates for phenotypes associated with X aneuploidy. To identify genes that escape X inactivation and to generate a first-generation X-inactivation profile of the X, we have evaluated the expression of 224 X-linked genes and expressed sequence tags by reverse-transcription–PCR analysis of a panel of multiple independent mouse/human somatic cell hybrids containing a normal human Xi but no Xa. The resulting survey yields an initial X-inactivation profile that is estimated to represent ≈10% of all X-linked transcripts. Of the 224 transcripts tested here, 34 (three of which are pseudoautosomal) were expressed in as many as nine Xi hybrids and thus appear to escape inactivation. The genes that escape inactivation are distributed nonrandomly along the X; 31 of 34 such transcripts map to Xp, implying that the two arms of the X are epigenetically and/or evolutionarily distinct and suggesting that genetic imbalance of Xp may be more severe clinically than imbalance of Xq. A complete X-inactivation profile will provide information relevant to clinical genetics and genetic counseling and should yield insight into the genomic and epigenetic organization of the X chromosome.

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Nondistorting C4′ backbone adducts serve as molecular tools to analyze the strategy by which a limited number of human nucleotide excision repair (NER) factors recognize an infinite variety of DNA lesions. We have constructed composite DNA substrates containing a noncomplementary site adjacent to a nondistorting C4′ adduct to show that the loss of hydrogen bonding contacts between partner strands is an essential signal for the recruitment of NER enzymes. This specific conformational requirement for excision is mediated by the affinity of xeroderma pigmentosum group A (XPA) protein for nonhybridizing sites in duplex DNA. XPA recognizes defective Watson–Crick base pair conformations even in the absence of DNA adducts or other covalent modifications, apparently through detection of hydrophobic base components that are abnormally exposed to the double helical surface. This recognition function of XPA is enhanced by replication protein A (RPA) such that, in combination, XPA and RPA constitute a potent molecular sensor of denatured base pairs. Our results indicate that the XPA–RPA complex may promote damage recognition by monitoring Watson–Crick base pair integrity, thereby recruiting the human NER system preferentially to sites where hybridization between complementary strands is weakened or entirely disrupted.

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Transcription-coupled repair (TCR) plays an important role in removing DNA damage from actively transcribed genes. It has been speculated that TCR is the most important mechanism for repairing DNA damage in non-dividing cells such as neurons. Therefore, abnormal TCR may contribute to the development of many age-related and neurodegenerative diseases. However, the molecular mechanism of TCR is not well understood. Oligonucleotide DNA triplex formation provides an ideal system to dissect the molecular mechanism of TCR since triplexes can be formed in a sequence-specific manner to inhibit transcription of target genes. We have recently studied the molecular mechanism of triplex-forming oligonucleotide (TFO)-mediated TCR in HeLa nuclear extracts. Using plasmid constructs we demonstrate that the level of TFO-mediated DNA repair activity is directly correlated with the level of transcription of the plasmid in HeLa nuclear extracts. TFO-mediated DNA repair activity was further linked with transcription since the presence of rNTPs in the reaction was essential for AG30-mediated DNA repair activity in HeLa nuclear extracts. The involvement of individual components, including TFIID, TFIIH, RNA polymerase II and xeroderma pigmentosum group A (XPA), in the triplex-mediated TCR process was demonstrated in HeLa nuclear extracts using immunodepletion assays. Importantly, our studies also demonstrated that XPC, a component involved in global genome DNA repair, is involved in the AG30-mediated DNA repair process. The results obtained in this study provide an important new understanding of the molecular mechanisms involved in the TCR process in mammalian cells.

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TFIIH is a multifunctional RNA polymerase II general initiation factor that includes two DNA helicases encoded by the Xeroderma pigmentosum complementation group B (XPB) and D (XPD) genes and a cyclin-dependent protein kinase encoded by the CDK7 gene. Previous studies have shown that the TFIIH XPB DNA helicase plays critical roles not only in transcription initiation, where it catalyzes ATP-dependent formation of the open complex, but also in efficient promoter escape, where it suppresses arrest of very early RNA polymerase II elongation intermediates. In this report, we present evidence that ATP-dependent TFIIH action in transcription initiation and promoter escape requires distinct regions of the DNA template; these regions are well separated from the promoter region unwound by the XPB DNA helicase and extend, respectively, ≈23–39 and ≈39–50 bp downstream from the transcriptional start site. Taken together, our findings bring to light a role for promoter DNA in TFIIH action and are consistent with the model that TFIIH translocates along promoter DNA ahead of the RNA polymerase II elongation complex until polymerase has escaped the promoter.

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With assays of hormone-sensitive behaviors, it is possible to demonstrate both direct and indirect actions of genes on mammalian social behaviors. Direct effects of estrogen receptor gene expression and progesterone receptor gene expression figure prominently in well analyzed neuroendocrine mechanisms for sex behavior, operating through a neural circuit that has been delineated. Indirect effects, notably the consequences of sexual differentiation, display complex dependencies. In a human condition, Kallmann syndrome, the data show a clear, indirect genetic influence on an important human social behavior, in which damage at chromosome Xp-22.3 works through at least six discrete steps to affect libido. Altogether, simplistic extrapolations from lower animals, especially during brief summaries for nonscientists, do not appear justified as we discover and conceptualize genetic influences on mammalian brain and behavior.

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DNA polymerase η (Polη) functions in the error-free bypass of UV-induced DNA lesions, and a defect in Polη in humans causes the cancer-prone syndrome, the variant form of xeroderma pigmentosum. Both yeast and human Polη replicate through a cis-syn thymine-thymine dimer (TT dimer) by inserting two As opposite the two Ts of the dimer. Polη, however, is a low-fidelity enzyme, and it misinserts nucleotides with a frequency of ≈ 10−2 to 10−3 opposite the two Ts of the TT dimer as well as opposite the undamaged template bases. This low fidelity of nucleotide insertion seems to conflict with the role of Polη in the error-free bypass of UV lesions. To resolve this issue, we have examined the ability of human and yeast Polη to extend from paired and mispaired primer termini opposite a TT dimer by using steady-state kinetic assays. We find that Polη extends from mispaired primer termini on damaged and undamaged DNAs with a frequency of ≈ 10−2 to 10−3 relative to paired primer termini. Thus, after the incorporation of an incorrect nucleotide, Polη would dissociate from the DNA rather than extend from the mispair. The resulting primer-terminal mispair then could be subject to proofreading by a 3′→5′ exonuclease. Replication through a TT dimer by Polη then would be more accurate than that predicted from the fidelity of nucleotide incorporation alone.

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We describe a novel DNA damage binding activity in nuclear extracts from a normal human fibroblast cell strain. This protein was identified using electrophoretic mobility shift assays of immunopurified UV-irradiated oligonucleotide substrates containing a single, site-specific cyclobutane pyrimidine dimer or a pyrimidine (6-4) pyrimidinone photoproduct. Compared with the (6-4) photoproduct, which displayed similar levels of binding in double and single-stranded substrates, the protein showed somewhat lower affinity for the cyclobutane dimer in a single-stranded oligonucleotide and negligible binding in double-stranded DNA. The specificity and magnitude of binding was similar in cells with normal excision repair (GM637) and repair-deficient cells from xeroderma pigmentosum groups A (XP12RO) and E (XP2RO). An apparent molecular mass of 66 kDa consisting of two subunits of approximately 22 and approximately 44 kDa was determined by Southwestern analysis. Cell cycle studies using centrifugal cell elutriation indicated that the binding activity was significantly greater in G1 phase compared with S phase in a human lymphoblast cell line. Gel supershift analysis using an anti-replication protein A antibody showed that the binding protein was not antigenically related to the human single-stranded binding protein. Taken together, these data suggest that this activity represents a novel DNA damage binding protein that, in addition to a putative role in excision repair, may also function in cell cycle or gene regulation.