B cell development is a highly organized process, which commences in the fetal liver during embryogenesis and in the bone marrow (BM) after birth. Surface IgM+ immature B cells emigrate from the BM via the blood stream to the spleen and finally differentiate into conventional mature follicular B (FoB) cells and marginal zone (MZ) B cells. Conversely, some sIgM+ immature B cells can also mature into IgD+ FoB cells in the BM. The ubiquitously expressed cell surface glycoprotein CD47 and its receptor signal regulatory protein α (SIRPα) are members of the immunoglobulin superfamily. Both individually and upon their interaction, CD47 and SIRPα have been found to play important role in the homeostasis of T lymphocytes or CD8­ conventional dendritic cells (cDCs) in secondary lymphoid organs. However, their role in regulating B cell homeostasis has remained unknown. The present study describes important roles of CD47 and SIRPα in B cell homeostasis. Lack of SIRPα signaling in adult SIRPα mutant (MT - cytoplasmic domain deletion) mice resulted in an impaired B cell maturation in the BM and spleen, which was also reflected in the blood. In the BM and spleen of SIRPα MT mice, reduced numbers of semi-mature IgD+IgMhi follicular type-II (F-II) and mature IgD+IgMlo follicular type-I (F-I) B cells were observed, while earlier BM B cell progenitors or splenic transitional B cells remained unaltered. In SIRPα MT mice, maturing B cells in BM and spleen were found to express higher levels of the pro-apoptotic protein BIM and contained an increased level of apoptotic cells. In contrast to that for FoB cells, the splenic MZ B cell population was increased with age in SIRPα MT mice without showing an increased level of activation markers. Immunohistochemical analysis revealed an increased follicular localization of MZ B cells in the spleens of SIRPα MT mice. In addition, MZ macrophages and marginal metallophilic macrophages were not restricted to their normal position in SIRPα MT spleens. Interestingly, CD47-deficient (CD47-/-) mice mimicked the FoB cell phenotype observed in SIRPα MT mice and had a reduced number of  FoB cells in the BM, blood and the spleen at 5­6 months of age, but not in younger mice. Similar to SIRPα MT mice, CD47-/- mice also displayed an increased number of splenic MZ B cells. Sera form both mouse strains did not show any signs of an increased production of autoantibodies or antinuclear antigens. BM reconstitution experiments identified a requirement for non-hematopoietic SIRPα signaling for normal B cell maturation in the BM and to maintain normal numbers and retention of MZ B cells in the splenic MZ. On the contrary, hematopoietic SIRPα signaling appeared to be important for FoB cell maturation in the spleen. Interestingly, hematopoietic SIRPα was required for normal MZ retention of MZ macrophages while normal distribution of metallophilic macrophages required non­hematopoietic SIRPα signaling.  Collectively, these findings revealed an important role of CD47 and of SIRPα signaling in B cell homeostasis in different lymphoid organs.

This thesis is an investigation into the possible genetic background underlying the liability of Standardbred racehorses (Std) to atrial fibrillation (AF). Pedigrees of 204 affected Std admitted to the Ontario Veterinary College Teaching Hospital (OVCTH) for treatment of AF born from 1978 to 2007 and of 1,017 randomly selected racing contemporaries (5 for each Std admitted). Estimates of heritability of AF were obtained using a linear threshold animal model. Marginal genetic contributions of ancestors to affected and control cohorts were determined and differences were tested. The estimate of heritability of AF in the Std was 14% on the observed scale. Eleven ancestors had significantly higher contributions to affected cohorts than to controls. Many of these ancestors appeared multiple times in the five-generation pedigrees of affected horses. Results strongly indicate a genetic predisposition to AF in the Std, with the arrhythmia particularly prevalent in one popular sire line.

No description available.

El presente trabajo, realiza ejercicios de incidencia distributiva en Ecuador para el periodo 2004-2012, para ello se efectúa análisis de incidencia media e incidencia marginal. En los ejercicios de incidencia media se utiliza la metodología tradicional Demery, (2003), para determinar quiénes fueron los beneficiarios de los servicios de salud pública en cada uno de los periodos bajo estudio. Además, se realiza ejercicios de incidencia marginal siguiendo la metodología propuesta por Younger (2000) y Glick y Razakamanantsoa (2002), que permiten saber cómo ha cambiado la estructura de beneficiarios a lo largo del tiempo; teniendo en cuenta que durante el periodo de estudio, se produjo una reforma sanitaria que incrementó el financiamiento y la cobertura del sistema de salud público ecuatoriano. Para el caso de los ejercicios de incidencia media se observa que para ambos años la mayoría de servicios de salud pública son progresivos y pro-pobres y en lo que concierne al análisis de incidencia marginal, se determinó que los servicios de salud pública se volvieron más progresivos durante el periodo 2004-2012.

上市公司邊際債務策略之探討 / This thesis aims at understanding the corporate finance strategy of companies which have no or an extremely low debt to equity ratio. For this thesis, companies that have a debt-to-equity ratio less than 5% are defined as “marginal-debt” companies. We identify 167 U.S. public companies which could easily access to the financial market for debt. In order to find some explanations for the phenomenon of marginal-debt, we first examine the trade-off theory. According to the theory, it can be hypothesized that an extremely low corporate tax rate or a high marginal cost of bankruptcy could explain the minimal presence of debt for those marginal-debt companies. However, we find no evidence to accept this hypothesis. Marginal-debt companies have an average tax rate of 31.4%, compared to 29.8% for our sample of indebted companies. They also have a generally better financial health, even when deleveraging their financial ratios. Owing to that, neither bankruptcy cost explains the financial management strategy of marginal-debt. Hence, we expect this phenomenon to be purely behavioral. We therefore propose a survey questionnaire to better analyze the incentives for managers to adopt a marginal-debt strategy.. Keywords: Marginal-debt, Capital structure, Low leverage, Trade-off theory, Debt aversion

En México, el crecimiento urbano descontrolado y la falta de planificación, generó importantes desequilibrios territoriales. En ese sentido son muchos los desafíos, uno de los más preocupantes es el de la vivienda, la falta de infraestructura y acceso a servicios básicos para los pobres que habitan en los asentamientos urbanos precarios. Son muchas las características de la pobreza en aglomeraciones urbanas, el interés de esta investigación es la vivienda marginal ubicada en la periferia de los tiraderos a cielo abierto.La tesis se estructura de dos partes: la primera presenta los fundamentos de la investigación, la segunda es la presentación del ámbito estudiado y el estudio de caso. Cada parte está integrada por tres capítulos.El capítulo primero contextualiza el crecimiento urbano en América Latina y México, así como los problemas generados por este crecimiento, desarrollando un marco de referencia de la pobreza, a partir de los enfoques teóricos existentes para medirla, finalizando con el tema de los asentamientos humanos marginales, su formación y características, los pronunciamientos internacionales y el marco jurídico en México sobre el tema.En el segundo capítulo se presentan los fundamentos teóricocontextuales de la vivienda, abordando la definición que se le da a esta, se revisan los pronunciamientos internacionales que sobre el derecho a la vivienda se han emitido y las políticas habitacionales en América Latina y se presenta el panorama de la vivienda en México y una breve aproximación a los estudios sobre el tema.El tercer capítulo trata el tema de la vivienda marginal y su relación con la sustentabilidad urbana. Se presentan reflexiones sobre el problema de la vivienda marginal en México y América Latina, y sus diferentes características y patologías, centrándonos en el caso de la vivienda marginal ubicada en la periferia de los tiraderos a cielo abierto de la zona sur de Tamaulipas.En el capítulo cuarto, se describe la zona metropolitana del sur de Tamaulipas, así como los antecedentes sobre la vivienda en la zona y el caso particular de los asentamientos marginales. Se describe el problema de los vertidos de basura en los tiraderos a cielo abierto en la zona de estudio.En el quinto capítulo se reseña la metodología aplicada al estudio, se describen las técnicas e instrumentos utilizados y los asentamientos objeto de nuestro estudio. También se explica el desarrollo del trabajo de campo, y se presentan los resultados.En el capítulo sexto, se expone el análisis e interpretación de los resultados y se intenta interpretar el fenómeno en base a los datos obtenidos a partir de los cuales se concluye que, los barrios marginales en México en su mayoría se originan en asentamientos irregulares o ilegales y éstos son un problema arraigado que ha sido construido y fomentado por las mismas autoridades.Se concluye que mientras no existan esfuerzos integrados que trabajen de manera continua para abatir la marginalidad, la formación de asentamientos irregulares seguirá dándose como consecuencia del dinámico crecimiento urbano en las ciudades, además de que las urbanizaciones ofertan vivienda con infraestructura y servicios a un costo inalcanzable para los pobres y marginados de esa población, por lo que para sobrevivir, recurren a otras alternativas como habitar terrenos baratos en las periferias de las ciudades, en sitios de riesgo y vulnerabilidad y en la periferia de basureros.Se proponen dos aspectos para el mejoramiento de las condiciones de las familias que habitan en estos asentamientos marginales. Uno es el de sanear de manera completa los ex basureros a cielo abierto en la zona Sur de Tamaulipas, mediante las normas oficiales mexicanas. Otro es diseñar un proyecto integral de desarrollo social y urbano sustentable. / In Mexico, urban growth and lack of planning caused large territorial imbalances. In that sense there are many challenges; one of the most troubling is the housing, lack of infrastructure and access to basic services for poor people living in precarious urban settlements. There are many characteristics of poverty in urban areas, the interest of this research is the marginal housing located on the periphery of the open air dumps.The thesis is structured in two parts: the first presents the basics of research. The second part is the presentation of the area studied and the case study. Each part consists of three chapters. The first chapter contextualizes the urban growth in Latin America and Mexico as well as the problems generated by this growth. In the second chapter presents the theoretical-context of housing. The third chapter addresses the issue of marginal housing and its relationship to urban sustainability, focusing on the marginal case of housing located on the periphery of the open-air dumps in the south of Tamaulipas. The fourth chapter describes the metropolitan area of southern Tamaulipas and the background on housing in the area and the particular case of squatter settlements. In the fifth chapter outlines the methodology applied to the study, describes the techniques and tools used and the object of our study settlements. In the sixth chapter, setting out the analysis and interpretation of results and tries to interpret the phenomenon is based on the data obtained.Finally it was concluded that slums in Mexico originate mostly in informal settlements or illegal and they are an entrenched problem that has been built and promoted by the authorities themselves. Two aspects are proposed to improve the conditions of families living in these squatter settlements.

A work of architecture holds the observations of the architect, an accumulation of images, feelings and sensations. These remain largely detached and invisible to the casual observer, occasionally becoming apparent as an idea is glimpsed through an external point of observation. The research has looked to redefine the paradigms of observation, that define the way architecture is seen and interpreted, by exploring attachments to places and belief systems. It has followed a journey within practice. Part of this journey has been about locating the aesthetic and metaphysical experience of architecture within its physical and operational realities. The research is an observation of the architect experiencing, as an observer, himself, his place in the world, and of the cities and spaces that occupy his imagination. By observing the interface between things that have defined career and identity, an architectural narrative has been developed to describe how an architect' s persona, what he lives through and the memories that he carries with him have been and can continue to be condensed into his work. Beauty resides in the interface between these things and ultimately, the fixed reality of the work. The search is characterised by the appearance of The Blue Room. It is a metaphorical place representing both the present and the un-created future. The Blue Room is a metaphor for all of the emotions that rest behind the evolution of an architectural idea and which remain embedded within it as a finished work. It is a metaphor for beauty and a metaphor for loss and sadness, all of the things that exist in-between the idea and the representation of that idea; between the visible and the invisible. It also represents the inherent paradox of the architectural work in that the idea is never the same as it is first imagined; in its finished form it is both the space of the architect and the client.

Classical immunoglobulin transgenic (Ig-Tg) mouse models such as the MD4 anti-hen egg lysozyme (-HEL) Ig-Tg line have been used extensively to study B cell responses in tolerance and immunity. This thesis describes a new generation of gene-targeted mice (designated SWHEL mice) whereby the VH10 Ig variable gene encoding the HyHEL-10 specificity of the original anti-HEL Ig-Tg mouse was targeted to the Ig heavy chain locus. B cells in the SWHEL mouse are therefore capable of undergoing class switch recombination (CSR) and somatic hypermutation (SHM), representing a major advance on the original MD4 mouse model. SWHEL mice were found to not only contain a large population of HEL-specific (HEL+) B cells but also a significant population of non-HEL-binding (HEL-) B cells generated by VH gene replacement. HEL+ SWHEL B cells were found to belong to the B2 lineage and displayed high levels of surface IgM. Nevertheless, they matured normally and colonised the primary B cell follicle and marginal zone (MZ) of the spleen. The SWHEL model thus provided an opportunity to re-examine some of the original observations made in the MD4 system and also to extend these observations, particularly with regard to the regulation of CSR by self-reactive B cells. As expected, analysis of SWHEL B cells exposed to high avidity membrane-bound HEL revealed that they underwent clonal deletion in the bone marrow (BM). More interestingly, analysis of HEL+ B cells exposed to low avidity soluble HEL revealed that they were able to emigrate from the BM to the spleen as anergic B cells. However, unlike anergic MD4 B cells, anergic SWHEL B cells were reduced in frequency, displayed an immature B cell phenotype, were excluded from the follicle and had a reduced lifespan. Direct measurement of B cell antigen receptor (BCR) occupancy by HEL and the frequency of HEL- competitor B cells was combined with mixed BM irradiation chimeras to demonstrate unequivocally that the difference in phenotype and fate of HEL+ B cells in the two systems was due solely to competition from HEL- B cells. In addition, the SWHEL model of B cell self-tolerance was used to show that while self-reactive B cells were hypo-responsive to BCR stimulation, BCR-independent signals delivered via anti-CD40 plus IL-4 or lipopolysaccharide could trigger them to undergo CSR and secretion of potentially pathogenic isotype-switched autoantibodies. Finally, the SWHEL model was used to study the responses of adoptively transferred follicular (Fo) and MZ B cells to in vivo activation with HEL conjugated to sheep red blood cells (HEL-SRBC). These studies revealed that both HEL+ MZ and Fo B cells were capable of mounting a robust T cell-dependent IgG1 antibody response to HEL-SRBC. However, HEL+ MZ B cells did not efficiently localise to the T cell-B cell border following antigen engagement and preferentially migrated to the bridging channels and red pulp. In contrast, HEL+ Fo B cells rapidly localised to the T cell-B cell border and subsequently colonised numerous germinal centres. As a result, the rate and pattern of SHM by HEL+ Fo and MZ B cells was shown to be distinct, with preferential targeting of mutations to the second complementarity-determining region in the former and to the second framework region in the latter. Together these data indicate illustrate the value of the SWHEL model and its potential to greatly advance the current understanding of B cell responses in tolerance and immunity.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

The National Basketball Association (NBA) generated well over $4 billion in revenues during the 2014-15 season. I analyze the value of a win to a team in terms of revenue and examine the potential underpayment or overpayment of players and superstars throughout the league relative to their marginal revenue product (MRP). My findings suggest that players are overpaid, especially superstars. However, it is important to consider the fixed-revenue streams a team receives before assuming a player is simply overpaid compared to his MRP. In congruence with previous literature, I find that veterans are overpaid at the expense of younger players’ lower salaries. I also look at the drivers of a player’s salary and find that general managers tend to overpay for points relative to other statistics.