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Diseño e implementación de un sistema multiespectral en el rango ultravioleta, visible e infrarrojo. Aplicación al estudio y conservación de obras de arteHerrera Ramírez, Jorge A. 25 March 2014 (has links)
Multispectral systems have several applications and there are different possible configurations in which they can be implemented. Different characteristics make them useful, but the basic one is the access to spectral information of a scene or sample with high spatial resolution. In this thesis , the main objective has been the design and implementation of a multispectral system that covers part of the UV, the visible, and part of theIR ranges of the electromagnetic spectrum to be applied to artwork studies.
The main part of the thesis is dedicated to the design, characterization and application of a multispectral system based on
multiplexed illumination using light emitting diodes (LED). This system comprises two modules : Module 1 UV-Vis, with a CCD camera sensitive between 370nm and 930nm , coupled to a source of LEDs with 16 different channels, i.e. 16 wavelengths of emission; and Module 2 IR with an lnGaAs camera with sensitivity between 930nm and 1650nm coupled to an LED source with 7 emission wavelengths. Thus , the complete system covers from 370nm to 1650nm with a total of23 channels obtained with LED illumination.
The system elements were characterized and simulations were performed to assess their performance in the reconstruction of spectral reflectance under ideal conditions , and also under conditions of quantization noise and additive noise. Its performance was evaluated using the formula CIEDE2000 color difference, the mean square error (RMSE) and the
goodness-of-fit coefficient (GFC) . The simulation results showed a good overall system performance, but with better results for module 1 UV -Vis due to the increased amount of LED channels in its spectral range.
Computer programs with their respective graphical interfaces to control the hardware and processing the information provided by the system were implemented. For the spectral reconstruction we employed the method based on direct interpolation using splines , and the methods based on training set of samples with known digital system responses and spectral reflectances: the undetermined pseudo-inverse (PSE -1) and simple pseudo-inverse (PSE). The equipment was evaluated over real samples of the Color Checker Chart CCCR and a series of frescoes patches painted with pigments used in artworks. The results of the metrics CIEDE2000, RMSE and GFC showed that the methods ofthe PSE-1 and PSE have similar performance, with slightly better results for the second one. The interpolation method presented a slightly lower performance, but it has the practical value of not needing training. The results for the PSE method were similar to those obtained through simulation, and proved again that the module 2 IR has lower performance. lt was concluded that overall system performance was good with CIEDE2000 and RMSE average values for the methods based on PSE in the order of 1 unit.
The developed system was applied to artworks in the museum ofPedralbes Monastery in Barcelona, and the churches of Sant Pere in Terrassa. Different images of murals of the chapel of San Miguel in the Monastery of Pedralbes were captured. The evaluation of the system performance for this museum application showed similar performance to the reported one in laboratory. We also captured a painting of large format, oil on wood named: La Virgen de la Leche. For this artwork the modular design and easy movement of the system was used to generate a complete picture by composition from several smaller images. At the churches of Sant Pere, we explored wall paintings dating from the Visigoth (VI-VII) and Romance times (XII -XIII) to assess whether there were features in the paintings that were not evident in the visible range, but in other spectral ranges. Enhancement algorithms were implemented for this task. The results obtained in this thesis demonstrate the potential of the developed multispecral system for obtaining spectral information in the ultraviolet, visible and infrared regions. / Los sistemas multiespectrales tienen la caracteristica principal de proporcionar acceso a informaci6n espectral de una muestra con alta resoluci6n espacial. En esta tesis, como principal objetivo, se ha disefiado e implementado un sistema multiespectral para aplicarlo al estudio de obras de arte. Este sistema comprende dos m6dulos: el m6dulo 1 UV-Vis, con una camara CCD con sensibilidad entre 370nm y930nm, acoplada a una fuente de diodos emisores de luz(LED) con 16 canales diferentes, es decir 16 1ongitudes de onda de emisi6n; yel m6dulo 2 IR, con una camara lnGaAs con sensibilidad entre 930nm y 1650nm, acoplada a una fuente LED con 71ongitudes de onda de emisi6n. Por tanto, el sistema completo abarca desde 370nm a 1650nm con un total de 23 canales. Se caracterizaron Ios elementos del sistema y se han realizado simulaciones para evaluar su rendimiento en la reconstrucci6n de reflectancias espectrales bajo condiciones ideales, condiciones de ruido de cuantificaci6n y aditivo. Su rendimiento se evalu6 empleando la formula de diferencia de color CIEDE2000,el error cuadratico medio (RMSE) y el coeficiente de bondad del ajuste (GFC). Los resultados de las simulaciones mostraron un buen rendimiento general del sistema, aunque con mejores resultados para el m6dulo 1 UV-Vis debido a la mayor cantidad de canales LED en su rango espectral. Paralelamente se implementaron Ios programas computacionales con sus respectivas interfaces graficas necesarias para el control del hardware usado y para el procesamiento de la informaci6n proporcionada por el sistema. Para la reconstrucci6n espectral empleamos un metodo de interpolaci6n directa basado en splines, y Ios metodos de pseudoinversa indeterminada (PSE-l) y pseudoinversa simple (PSE) que necesitan de un entrenamiento con un conjunto de muestras con respuestas digitales del sistema y reflectancias espectrales conocidas. El equipo se evalu6 sobre muestras reales de la carta de colores Color Checker CCCR y sobre un conjunto de pinturas alfresco realizadas con pigmentos comunmente presentas en obras de arte. Los resultados de las metricas CIEDE2000,RMSE yGFC mostraron que Ios metodos de la PSE-1 y PSE tienen desempefios similares,con resultados ligeramente mejores para el segundo metodo. El metodo de interpolaci6n present6 un rendimiento ligeramente menor, aunque tiene el valor practico de no necesitar entrenamiento. Los resultados reales para el metodo del PSE fueron similares a Ios obtenidos mediante simulaci6n, y se mostr6 una vez m as que el m6dulo 2 IR tiene un rendimiento inferior. Se concluy6 que en general el desempefio del sistema era bueno, con valores CIEDE2000 y RMSE promedio para Ios metodos basados en PSE del orden de 1 unidad en ambos casos. El sistema desarrollado fue aplicado a obras de arte en elmuseo de Monasterio de Pedralbes, en Barcelona, y Ias lglesias de Sant Pere, en Terrassa.En el Monasterio de Pedralbes se capturaron diferentes imagenes de pinturas murales de la capilla de San Miguel y se evalu6 el desempefio del sistema para esta aplicaci6n de museo, mostrando un desempeno similar al reportado en las pruebas de laboratorio. Tambien se accedi6 a la obra Virgen de la Leche que es un 61eo en tabla de gran formato. En esta obra se aprovech6 el diseno modular y de facil movimiento del sistema para generar por composici6n una imagen completa a partir de varias imagenes menores.En las iglesias de Sant Pere se exploraron pinturas murales que se estima datan de las epocas visigoda (siglos VI-VII) y romanica (siglos XII-XIII) para evaluar si existian caracteristicas en Ias pinturas que no fueran evidentes en el rango visible y que silo fueran en otros rangos espectrales. Para ello se implementaron algoritmos de realce de la informaci6n. Los resultados obtenidos en esta tesis doctoral ponen de manifiesto las potencialidades del sistema multiespecral desarrollado para la obtenci6n de informaci6n espectral en las regiones ultravioleta, visible e infrarrojo
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Jämförbarhet och harmonisering i riskupplysningar enligt kraven från IFRS 7 : En studie om svenska bankmarknaden åren 2007 och 2012Svensson, Gustav, Larsson, Christofer January 2014 (has links)
I takt med ökad globalisering och ökat ekonomiskt utbyte mellan länder världen över blir det allt viktigare att kunna jämföra information i företagens finansiella rapporter. I Europa har ett led mot ökad jämförbarhet varit krav på börsnoterade företag att följa IFRS, vars målsättning är att skapa en redovisning som är jämförbar och harmoniserad på global nivå. 2007 infördes IFRS 7 Finansiella instrument: Upplysningar, som utvecklades då krav på riskupplysningar inte var tillräckliga i tidigare regelverk. Vid införandet fick regelverket större effekt på banksektorn än andra branscher, då bankernas totala tillgångar och skulder i genomsnitt 90 % utgörs av finansiella instrument. Banker har en central roll i samhället och en koppling till alla individer på ett eller annat sätt. Vår studie syftar till att undersöka hur banker på den svenska bankmarknaden lämnar riskupplysningar enligt kraven från IFRS 7, samt hur svenska banker riskupplyser i jämförelse med de utländska bankerna. Vidare syftar studien till att undersöka om det går att jämföra riskupplysningar och om de har harmoniserat i enlighet med IFRS målsättning. Slutligen, syftar studien till att förstå vad som kan påverka riskupplysningarna som bankerna lämnar. Studien är en kvalitativ undersökning med ett mindre urval banker från den svenska bankmarknaden, baserad på åren 2007 och 2012. Studien går på djupet och undersöker variabler framtagna med hjälp av IFRS 7, med fokus på de vanligt förekommande riskerna kredit-, likviditets- och marknadsrisk. Vi har mätt riskupplysningarna och jämförbarheten genom att räkna antal sidor, antal ord, diagram/tabeller och studera presentationstekniken i bankernas årsredovisningar. Studiens resultat och slutsatser visar på att mängden riskupplysningar generellt ökat från 2007 då IFRS 7 infördes till 2012. IFRS närmar sig målsättningen med jämförbarhet i riskupplysningar, men är än idag inte perfekt. 2007 gick det att jämföra bankernas riskupplysningar vid 21 av totalt 49 tillfällen, vilket blev bättre 2012 då det gick vid 31 tillfällen. Det som kan påverka riskupplysningar är viljan från ledningen att lämna riskupplysningar och påtryckningar från bankernas omgivning. En händelse som kan påverkat utvecklingen av riskupplysningarna är den senaste finanskrisen där banksektorn hade en central roll. / With increased globalization and increased economic exchange between countries around the world, it becomes increasingly important to be able to compare information in corporate financial statements. In Europe, a step towards increased comparability has been the requirement for listed companies to follow IFRS. IFRS objective is to become an accounting standard that is comparable and harmonized at a global level. 2007, IFRS 7 Financial Instruments: Disclosures was introduced, because the requirements for risk disclosures in previous regulations were not adequate. When IFRS 7 was introduced it got greater impact on the banking industry than other industries, because the banks' total assets and liabilities on average consist of 90% financial instruments. Banks has a central role in the community and has a connection to all individuals in one way or another. Our study aims to examine how banks in the Swedish banking market risk disclosures as required by IFRS 7, and how Swedish banks risk disclosures in comparison with the foreign banks. Furthermore, the study aims to examine whether it is possible to compare the risk disclosures and if they have harmonized in accordance with IFRS objective. Finally, the study aims to understand what can affect the risk disclosures by banks. The study is a qualitative study with a smaller sample banks from the Swedish banking market, based on the years 2007 and 2012. Study examines using variables produced from IFRS 7, with a focus on the most common risks of credit, liquidity and market risk. We have measured the risk disclosures and comparability by counting the number of pages, number of words, graphs / tables and study presentation methods in the banks' annual reports. The study's results and conclusions show that the amount of risk disclosures generally increased from 2007 to 2012. IFRS is getting close to the objective of comparability of risk disclosures, but is still not perfect. In 2007 it was possible to compare banks' risk disclosures at 21 of a total of 49 occasions, which increased to 31 occasions in 2012. What may have affected risk discolsures is the willingness of management to provide risk disclosures and pressure from the banks surroundings. The recent financial crisis, where the banking sector had a central role, may have influenced the development of risk disclosures.
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Prácticas artísticas ecológicas relativas al agua en un contexto de cambio climático. Estrategias y procesos de aprendizajeGarcía Cano, Antonio José 12 June 2014 (has links)
Son numerosas y diversas las iniciativas artísticas que abordan aspectos relativos a la ecología. En esta tesis proponemos una definición de arte ecológico y describimos sus propiedades principales. Dada la gran diversidad de trabajos, establecemos un criterio de selección que nos permite delimitar el área de estudio. De esta manera, la presente investigación se centra en proyectos de arte ecológico que se realizan en ecosistemas acuáticos, que conciben la ecología como el conjunto de relaciones complejas entre los seres vivos y de éstos con su entorno, y que tienen como aspiración la mejora del estado ecológico del ecosistema en el que se trabaja. Por otra parte, dado que el Cambio Climático está alterando las relaciones ecológicas a nivel global, analizamos aquellos proyectos que asumen este fenómeno. La pregunta de investigación principal es: ¿Cómo pueden las prácticas artísticas ecológicas contribuir a mejorar la situación ecológica? La metodología utilizada para contestar esta pregunta queda configurada por tres elementos principales. En primer lugar, la revisión bibliográfica tanto de publicaciones relativas a un arte preocupado por el entorno como por otras de diferentes disciplinas como la Ecología o la Hidrología. En segundo lugar, hemos tenido la oportunidad de entrevistar a la mayoría de artistas que analizamos, así como a personas de otras disciplinas con las que han colaborado. Por otra parte, a la vez que realizábamos este estudio, estábamos desarrollando un proyecto artístico relativo a la memoria ecológica de la pedanía murciana de Rincón de Beniscornia. Los tres casos de estudio seleccionados son el colectivo artístico formado por Helen Mayer y Newton Harrison, el artista David Haley y la artista Aviva Rahmani. Sus planteamientos se basan en el conocimiento de los procesos ecológicos y de los efectos del Cambio Climático sobre los mismos. Además, en estos trabajos suelen participar expertos de disciplinas científicas. Helen Mayer y Newton Harrison buscan cómo poder adaptarse al nuevo contexto que el Cambio Climático está provocando con fenómenos como la subida de los niveles del mar o el aumento de las temperaturas. David Haley también defiende la necesidad de aprender de lo que está sucediendo y de imaginar distintos futuros de adaptación. Finalmente, Aviva Rahmani propone actuar en lugares clave que pueden desencadenar la mejora ecológica de áreas mucho mayores. También presentamos otras prácticas artísticas en ecosistemas acuáticos que no se centran directamente en el Cambio Climático pero que sí consideramos que pueden ser muy útiles para la mitigación de sus consecuencias. Organizamos estos trabajos en cinco grupos en función de sus características más destacables, tales como el carácter activista o la capacidad de promover la colaboración comunitaria, o de crear sistemas de depuración de agua. Observamos que los artistas desarrollan procesos de aprendizaje para conocer mejor las situaciones a las que se enfrentan. Se valen de las siguientes herramientas: de la colaboración con la comunidad que habita un lugar, del diálogo con otras disciplinas, de la recuperación de la memoria ecológica del ecosistema en el que se quiere intervenir y de la propia práctica artística que les proporciona un punto de vista distinto. También proponemos la posibilidad de aprender de las propiedades del agua y de cómo se relaciona con el entorno. Por último, esta tesis recoge una descripción de la parte práctica de la investigación, el Proyecto Iskurna, el cual nos permite explorar las diferentes estrategias de aprendizaje en un entorno real. En definitiva, esta tesis tiene como objetivo presentar una serie de prácticas artísticas que abordan el Cambio Climático y se preguntan cómo pueden contribuir a la mejora de la situación ecológica. Esta investigación muestra cómo lo hacen y cómo el arte aprende de la ecología. / This thesis proposes a specific definition of ecological art and describes the main properties of this genre. Considering the diversity of such artworks, a selection of criteria was established to delimit the field of study. Therefore, the research focused on ecological art projects that address aquatic ecosystems. These projects conceptualize ecology as a set of complex relationships between living beings and their environment and aspire to improve the ecological status in which they work. They consider Climate Change to be an ecologically modifying phenomenon at the global level. The main research question is: how can ecological art practices contribute to improving the ecological situation? The methodology used to answer this question includes three elements. Firstly, a review of publications regarding environmental art as well as other publications from different disciplines like Ecology and Hydrology. Secondly, interviews were conducted with most of the featured artists, as well as people from other disciplines with whom they worked. And finally, the author of this research includes the development of his own artistic project related to the ecological memory of Rincón de Beniscornia, a borough of Murcia. This thesis analyses different projects by the artists Helen Mayer Harrison and Newton Harrison, David Haley, and Aviva Rahmani. This research presents the artists’ different approaches to ecological processes and their ways of learning. The Harrisons’ projects focus on adaptation to Climate Change and the phenomena it provokes, like ocean level rise and temperature increase. David Haley also promotes the need to learn from Global Warming, and imagines diverse practical adaptations for various potential future scenarios. Finally, Aviva Rahmani proposes acting in key places that can trigger the ecological improvement of large areas. Other art practices are also presented, including those that address aquatic ecosystems. They are not focused on Climate Change directly but they can be very useful to mitigate its consequences. These initiatives have been organised into five groups, depending on their most prominent characteristics, such as the level of activism, or the capacity to promote community collaboration, or the ability to create water treatment systems. This research has shown that most ecological artists develop learning processes to better understand the situation that they face. They often deploy the following strategies: collaboration with the local community, dialogue with other disciplines, recovery of ecological memory of the ecosystem where they want to intervene, and an art practice that allows them a different point of view. Given the properties of water and how water is related to the environment, another kind of learning is proposed. Finally, this thesis includes a description of the practical part of the research, the Iskurna Project, which allows us to explore the different learning strategies in a real-world environment. This thesis critically analyses a series of art projects that address Climate Change and contribute to the improvement of the related ecological situation. It questions how they do this and how art learns from ecology.
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Mutational Analysis of the HIV-1 Tat Protein and its Role in Downregulating CD127 on CD8 T CellsSugden, Scott M. 15 April 2013 (has links)
HIV Tat protein downregulates surface expression of the interleukin-7 receptor alpha-chain (CD127) on CD8 T cells resulting in impaired T cell proliferation and cytolytic capacity. Once taken up by CD8 T cells, Tat binds directly to the cytoplasmic tail of CD127 inducing receptor internalization and degradation. Given the important roles of CD127 in proper immune function, the Tat/CD127 interactions were characterized and the mechanisms required to induce receptor loss from the surface of CD8 T cells were investigated.
Tat deletion mutants were generated each sequentially lacking a region of the protein. CD8 T cells isolated from HIV negative volunteers were exposed to exogenous or intracellular Tat proteins before surface CD127 expression was analyzed by flow cytometry. To characterize Tat/CD127 physical interactions, wild type Tat and Tat mutants were incubated with lysates from a CD127+ Jurkat cell line followed by CD127/Tat co-immunoprecipitation. The effect of Tat on CD127 post-translational modifications was also investigated.
Removal of the N-terminus of Tat (aa 1-10 or aa 17-21) prevented Tat from downregulating CD127 and prevented Tat from binding CD127 as assessed by co-immunoprecipitation. Deletion of the basic region (aa 48-59) also prevented Tat from downregulating CD127 but did not prevent Tat from interacting physically as demonstrated by co-immunoprecipitation. Strikingly, endogenously expressed Basic Tat acted as a dominant negative mutant, causing an accumulation of CD127 at the cell surface. These observations suggest that Tat may bind CD127 via its N-terminus to disrupt the normal recycling of the receptor, and then recruit cellular endocytic machinery to the receptor via it’s basic region, to remove the receptor from the cell surface and target it for degradation. Furthermore, Tat encourages the ubiquitination of CD127 by recruiting the cytokine-inducible SH2 containing (CIS) protein to the receptor, possibly leading to accelerated CD127 internalization and proteasomal degradation. I propose a model whereby Tat binds CD127 via its N-terminal region then recruits CIS via its basic region. CIS in turn recruits a cellular E3 ubiquitin ligase to ubiquitin tag the receptor for internalization and proteasome degradation. This research may lead to novel treatments designed to maintain IL-7 signalling and strengthen CD8 T cell function in HIV+ persons.
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Effects Of Guided Reading On Upper-intermediate Level English Langauge Learners' / Writing Outcome At The Turkish Prime MinistryOrgun, Firat 01 August 2004 (has links) (PDF)
This study aims at finding whether reading about a specific topic/genre affects the writing outcome on the same topic/genre and the general writing performance positively in terms of content, organization, grammar, vocabulary and mechanics. This study was conducted with two upper-intermediate level EFL classes. Both groups were given a sample KPDS and a pre-test of writing at the beginning of the study. For five weeks, one of the groups received extra reading instruction with the usual writing instruction while the other group followed usual writing instruction only. Both groups&rsquo / performance was tested with a writing test at the end of each week and a post-test at the end of the treatment. The analyses of the data collected through these tests indicated that there were not significant differences between the mean scores of the two groups (p& / #61502 / 0.05). Hence it was found that the different treatments applied to the groups proved no difference in terms of improving students writing ability.
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An Evaluation Of The In-service Teacher Training Program For The Newly Hired Instructors In The School Of Foreign Languages At Middle East Technical UniversityUcar Duzan, Canan 01 February 2006 (has links) (PDF)
The purpose of this study was to evaluate the effectiveness of the in-service teacher training program implemented for the newly hired teachers in the School of Foreign Languages (SFL) at Middle East Technical University. The study was conducted with the help of three groups of participants who were the trainees who participated in the training program in the 2004-2005 academic year, the experienced teachers who were current members of the SFL and the teacher trainers. Data from the 12 trainees were collected through two questionnaires which were developed to identify the needs of the trainees at the start of the program and their degree of satisfaction at the end. Moreover, an interview was conducted with the trainees. Data from the 4 teacher trainers were collected through a questionnaire and it aimed to identify their expectations from and satisfaction with the program. 45 experienced teachers, on the other hand, were involved in the study to understand whether they need in-service training. The questionnaires included both Likert scale and open-ended items.
Data collected through the instruments were analyzed both quantitatively and qualitatively. Closed-ended items were analyzed via the SPSS program and mean scores for each item were calculated. To identify if there is any statistically significant difference between the mean scores, a paired-sample t-test was calculated. The qualitative data were analyzed through content analysis.
The results of the study revealed that the trainees especially need to improve their practical teaching skills which are immediately necessary in the new setting. Their degree of satisfaction was also found to be high. The results about the experienced teachers showed that they did not feel the need to enroll in an in-service training program. The findings about the teacher trainers revealed that they are generally happy with the program although they listed some suggestions for improvement.
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La Nominació de l'artefacte en el procés de Disseny.Mallol Esquefa, Miquel 14 September 2001 (has links)
La investigación estética filosófica también se puede ocupar de las artes aplicadas. La íntima relación de estas artes con el contexto de producción aporta contenidos de gran interés para la investigación crítica de la autonomía del arte.
La actualidad de esta relación se concentra en el diseño. Y, por otro lado, la actividad teórica i práctica del diseño también necesita hoy de una mirada más atenta y crítica de los principios que pretende aplicar.Las investigaciones de más interés en este sentido se han centrado en la confrontación entre las aplicaciones del tipo y del ornamento. Pero el diseño es una actividad colectiva y, por este motivo, la expresión verbal de sus resultados también es uno de los momentos fundamentales de su proceso. El tratamiento conceptual de los artefactos de diseño es también un contenido indispensable para la estética filosófica y para el mismo diseño.
La nominación del artefacto en el proceso de diseño es el ámbito de estudio crítico de todas las formas de tratamiento conceptual en esta actividad colectiva. La presente tesis desarrolla una investigación crítica sobre cuatro formas de tratamiento conceptual: teoría, metodología, concepto de una particularidad y nombre.
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The role of neuropeptides in inflammatory disease / by Andrzej Wozniak.Wozniak, Andrzej, 1956- January 1992 (has links)
Copies of author's previously published articles inserted. / Amendments (2 leaves) in front cover pocket. / Bibliography: leaves 227-259. / xiii, 259 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the contribution of tachykinins, in particular Substance P (SP), to the processes of inflammation. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1993
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Critical roles for the transcription factor c-Myb in early B cell developmentGreig, K. T. January 2009 (has links)
B cell development is a carefully orchestrated process involving many transcription factors acting in concert with cytokine signals, particularly IL-7. The transcription factor c-Myb has long been implicated in B cell development, however surprisingly little is known about the function of c-Myb in B cell progenitors. I have used several mouse models of c-Myb deficiency to investigate the role of c-Myb in the B cell lineage. Conditional deletion of c-Myb in early B cell progenitors using mb-1Cre (c MybΔmb1/Δmb1) leads to a striking lack of B cells from the pre-pro-B cell stage onwards, demonstrating that c-Myb is absolutely required for B cell development. Mice homozygous for a hypomorphic allele of c-Myb (c MybPlt4/Plt4) also display a severe reduction in B cells; in these mice, defects in lymphoid development can be detected within the multipotent progenitor compartment of bone marrow. c-Myb activates transcription via coactivator proteins, particularly CBP and p300. Mice bearing a point mutation in p300 (p300Plt6/Plt6) that inhibits the interaction of p300 with c Myb display a partial block in B cell development, highlighting the importance of the c Myb-p300 complex for B cell development. Together, these mice demonstrate that c-Myb regulates B cell development by functioning both in multipotent progenitor cells and directly in B cell progenitors. In addition, I show that the B-lymphopenia in c-Myb deficient mice is related to a profound defect in IL-7 signalling. IL-7 normally stimulates the proliferation, survival and differentiation of B cell progenitors, however pro-B cells from c-MybPlt4/Plt4 and c MybΔmb1/Δmb1 mice fail to respond to IL 7. Expression of the IL-7Rα chain is reduced on pro-B cells from c MybPlt4/Plt4 and c-MybΔmb1/Δmb1 mice, suggesting that Il7r may be a c-Myb target gene in B cells. Reporter gene assays show that c-Myb can activate the Il7r promoter in synergy with the transcription factor Pu.1. Overall, this work demonstrates that c-Myb is essential for early B cell development and plays a critical role in linking cytokine signals to the transcription factor networks in B cell progenitors.
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7,8-Dihydroneopterin-mediated protection of low density lipoprotein, but not human macrophages, from oxidative stressFirth, Carole Anne January 2006 (has links)
Any lipoproteins and cells present in the inflammatory environment of atherosclerotic plaques are likely to be exposed to high levels of oxidative stress. As 7,8-dihydroneopterin (7,8-NP) is synthesized by interferon-γ (IFN-γ)-activated macrophages, this pteridine is also thought to exist at sites of inflammation. 7,8-NP s in vivo role remains controversial, but numerous in vitro studies have identified a radical scavenging activity. The possibility of 7,8-NP protecting against oxidative damage in inflammatory environments like plaque was investigated in this thesis. Both human monocyte-derived macrophages (HMDMs) and low density lipoprotein (LDL) were used as substrates. The extent of protein hydroperoxide formation in each model, and 7,8-NP s effect on this process, were specifically studied since most previous research has focussed on lipid rather than protein peroxidation. For the first time, neopterin (including oxidized 7,8-NP) was also directly detected by high performance liquid chromatography in the inflammatory environments of 19 pus and two atherosclerotic plaque samples. Peak concentrations even reached the low micromolar range. The positive correlation identified in the pus between neopterin and a well known antioxidant, vitamin E, further hinted at a potential antioxidant function. However, no significant association was noted between neopterin and markers of protein or lipid oxidation. Exposure of HMDMs to the AAPH peroxyl radical generator resulted in significant quantities of lipid hydroperoxides but not protein hydroperoxides, as detected by the FOX assays. This is likely due to the large accumulation of polyunsaturated fatty acidrich lipid in the primary HMDMs during differentiation in 10% human serum and is of relevance to atherosclerotic plaque, where macrophages also become lipid-loaded. The addition of up to 200μM 7,8-NP failed to prevent AAPH-induced lipid peroxidation and was also unable to inhibit a loss of cellular thiols or viability. This lack of effect suggests the damaging peroxyl radicals are not being scavenged by 7,8-NP. The high lipid content of HMDM cells appears to cause the AAPH and/or 7,8-NP to localize to a cellular site, where they are unable to interact. Macrophage-mediated oxidation of LDL in iron(II)-supplemented Hams F10 was associated with the formation of 30-40 moles of protein hydroperoxides per mole of LDL. The close parallel between protein and lipid peroxidation supports the theory that lipid-derived radicals are involved in protein hydroperoxide formation on LDL and indicates that protein hydroperoxides are an early product of LDL oxidation. Their detection during exposure of LDL to both the THP-1 macrophage cell line and primary HMDM cells confirms that protein hydroperoxides are also a normal consequence of macrophage-mediated LDL oxidation. Incubation of LDL with micromolar 7,8-NP prevented macrophage-mediated protein hydroperoxide formation in a concentration-dependent manner. Lipid oxidation and vitamin E loss were similarly inhibited by 7,8-NP during the cell-mediated attack of LDL. Kinetic analysis revealed protection due to extension of the lag phase, with 7,8-NP depletion and initiation of the propagation phase coinciding. This supports a radical scavenging activity for 7,8-NP, resulting in protection of the entire LDL particle. By contrast, the release of nanomolar quantities of 7,8-NP by IFN-γ-stimulated THP-1 macrophages failed to prevent LDL oxidation. HMDMs activated by IFN-γ did significantly inhibit LDL oxidation, including protein hydroperoxide formation, for up to 48 hours but this antioxidant effect was not due to the de novo synthesis of 7,8-NP. These results indicate that both the prevalence of protein hydroperoxides, and the ability of 7,8-NP to act as an antioxidant, depend on the system under investigation. Neopterin exists in inflammatory environments but, considering the lack of protection against AAPH-mediated HMDM oxidation and the 7,8-NP concentration required to inhibit macrophage-mediated LDL oxidation, strong evidence for an antioxidant activity of 7,8-NP in atherosclerotic plaque is currently lacking.
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