Mad Men, The Sopranos and The American Way of Life. The history of the capital in two times

Don Draper (Mad Men, Matthew Weiner, AMC: 2007-2015) actively colaborates in the birth and consolidationof a model of consumer society without realizing the enormous lie he is telling himself. Tony Soprano(The Sopranos, David Chase, HBO: 1999-2007) desperately grasps the wreckage of that ideal imageof effort and self-improvement which is not only disappearing but was actually never coherent or real.This article does a comparative textual, sociological, and discursive analysis these two characters as arepresentation of the evolution of the discourse of capitalism in the second half of the 20th century, that is,the artificiality of the hegemonic discourse of “pursuit of happiness” as the main myth in post-war NorthAmerican neoliberalism.

El papel de los museos en la sociedad actual: discurso institucional o museo participativo

Desde hace ya varias décadas se ha extendido un lema convertido en habitual año tras año: que los museos necesitan cambios y que, éstos, deben seguir produciéndose en el futuro para que estas instituciones sigan siendo significativas en la sociedad, es decir, para los ciudadanos a quienes representan y sirven. La cuestión de cómo afrontan los cambios es lo que verdaderamente ha dado lugar a reflexiones interesantes en el campo de la museología. No existe un enfoque único para una cuestión tan compleja, ya que está compuesta de múltiples capas que, en muchas ocasiones, son difícilmente acoplables. Sin embargo, en términos generales, podemos apuntar que va a ser en la exposición donde los nuevos planteamientos tendrán su desarrollo.

Is Experts' Knowledge Modular?

This paper explores, both with empirical data and with computer simulations, the extent to which modularity characterises experts' knowledge. We discuss a replication of Chase and Simon's (1973) classic method of identifying 'chunks', i.e., perceptual patterns stored in memory and used as units. This method uses data about the placement of pairs of items in a memory task and consists of comparing latencies between these items and the number and type of relations they share. We then compare the human data with simulations carried out with CHREST, a computer model of perception and memory. We show that the model, based upon the acquisition of a large number of chunks, accounts for the human data well. This is taken as evidence that human knowledge is organised in a modular fashion.

Three Essays in Empirical Asset Pricing

The financial crisis of 2007-2008 led to extraordinary government intervention in firms and markets. The scope and depth of government action rivaled that of the Great Depression. Many traded markets experienced dramatic declines in liquidity leading to the existence of conditions normally assumed to be promptly removed via the actions of profit seeking arbitrageurs. These extreme events motivate the three essays in this work. The first essay seeks and fails to find evidence of investor behavior consistent with the broad 'Too Big To Fail' policies enacted during the crisis by government agents. Only in limited circumstances, where government guarantees such as deposit insurance or U.S. Treasury lending lines already existed, did investors impart a premium to the debt security prices of firms under stress. The second essay introduces the Inflation Indexed Swap Basis (IIS Basis) in examining the large differences between cash and derivative markets based upon future U.S. inflation as measured by the Consumer Price Index (CPI). It reports the consistent positive value of this measure as well as the very large positive values it reached in the fourth quarter of 2008 after Lehman Brothers went bankrupt. It concludes that the IIS Basis continues to exist due to limitations in market liquidity and hedging alternatives. The third essay explores the methodology of performing debt based event studies utilizing credit default swaps (CDS). It provides practical implementation advice to researchers to address limited source data and/or small target firm sample size.

Stabilising suppressor of cytokine signalling 3 (SOCS3) protein levels to limit neointimal hyperplasia

Suppressor of cytokine signalling 3 (SOCS3) is a potent inhibitor of the mitogenic, migratory and pro-inflammatory pathways responsible for the development of neointimal hyperplasia (NIH), a key contributor to the failure of vascular reconstructive procedures. However, the protein levels of SOCS3, and therefore its potential to reduce NIH, is limited by its ubiquitylation and high turnover by the proteasome. I hypothesised that stabilisation of endogenous SOCS3 by inhibiting its ubiquitylation has the potential to limit vascular inflammation and NIH. Consequently, the aim of this PhD was to identify the mechanisms promoting the rapid turnover of SOCS3. Initial experiments involved the identification of residues involved in regulating the turnover of SOCS3 at the proteasome. I assessed the ubiquitylation status of a panel of FLAG tagged SOCS3 truncation mutants and identified a C-terminal 44 amino acid region required for SOCS3 ubiquitylation. This region localised to the SOCS box which is involved in binding Elongin B/C and the formation of a functional E3 ubiquitin ligase complex. However, the single lysine residue at position 173, located within this 44 amino acid region, was not required for ubiquitylation. Moreover, Emetine chase assays revealed that loss of either Lys173 or Lys6 (as documented in the literature) had no significant effect on SOCS3 stability 8 hrs post emetine treatment. As mutagenesis studies failed to identify key sites of ubiquitylation responsible for targeting SOCS3 to the proteasome, LC-MS-MS analysis of a SOCS3 co-immunoprecipitate was employed. These data were searched for the presence of a Gly-Gly doublet (+114 Da mass shift) and revealed 8 distinct sites of ubiquitylation (Lys23, Lys28, Lys40, Lys85, Lys91, Lys173, Lys195, Lys206) on SOCS3 however Lys6 ubiquitylation was not detected. As multiple Lys residues were ubiquitylated, I hypothesised that only a Lys-less SOCS3, in which all 8 Lys residues were mutated to Arg, would be resistant to ubiquitylation. Compared to WT SOCS3, Lys-less SOCS3 was indeed found to be completely resistant to ubiquitylation, and significantly more stable than WT SOCS3. These changes occurred in the absence of any detrimental effect on the ability of Lys-less SOCS3 to interact with the Elongin B/C components required to generate a functional E3 ligase complex. In addition, both WT and Lys-less SOCS3 were equally capable of inhibiting cytokine-stimulated STAT3 phosphorylation upon co-expression with a chimeric EpoR-gp130 receptor. To assess whether SOCS3 auto-ubiquitylates I generated an L189A SOCS3 mutant that could no longer bind the Elongins and therefore form the E3 ligase complex required for ubiquitylation. A denaturing IP to assess the ubiquitylation status of this mutant was performed and revealed that, despite an inability to bind the Elongins, the L189A mutant was poly-ubiquitylated similar to WT SOCS3. Together these data suggested that SOCS3 does not auto-ubiquitylate and that a separate E3 ligase must regulate SOCS3 ubiquitylation. This study sought to identify the E3 ligase and deubiquitylating (DUB) enzymes controlling the ubiquitylation of SOCS3. Our initial strategy was to develop a tool to screen an E3 ligase/DUB library, using an siARRAY, to sequentially knockdown all known E3 ligases in the presence of a SOCS3-luciferase fusion protein or endogenous SOCS3 in a high content imaging screening platform. However, due to a poor assay window (<2) and non-specific immunoreactivity of SOCS3 antibodies available, these methods were deemed unsuitable for screening purposes. In the absence of a suitable tool to screen the si-ARRAY, LC-MS-MS analysis of a SOCS3 co-immunoprecipitate (co-IP) was investigated. I performed a SOCS3 under conditions which preserved protein-protein interactions, with the aim of identifying novel E3 ligase and/or DUBs that could potentially interact with SOCS3. These data were searched for E3 ligase or DUB enzymes that may interact with SOCS3 in HEK293 cells and identified two promising candidates i) an E3 ligase known as HectD1 and ii) a DUB known as USP15. This thesis has demonstrated that in the presence of HectD1 overexpression, a slight increase in K63-linked polyubiquitylation of SOCS3 was observed. Mutagenesis also revealed that an N-terminal region of SOCS3 may act as a repressor of this interaction with HectD1. Additionally, USP15 was shown to reduce SOCS3 polyubiquitylation in a HEK293 overexpression system suggesting this may act as a DUB for SOCS3. The C-terminal region of SOCS3 was also shown to play a major role in the interaction with USP15. The original hypothesis of this thesis was that stabilisation of endogenous SOCS3 by inhibiting its ubiquitylation has the potential to limit vascular inflammation and NIH. Consistent with this hypothesis, immunohistochemistry visualisation of SOCS3, in human saphenous vein tissue derived from CABG patients, revealed that while SOCS3 was present throughout the media of these vessels the levels of SOCS3 within the neointima was reduced. Finally, preliminary data supporting the hypothesis that SOCS3 overexpression may limit the proliferation, but not migration, of human saphenous vein smooth muscle cells (HSVSMCs) is presented. It is expected that multiple E3 ligases and DUBs will contribute to the regulation of SOCS3 turnover. However, the identification of candidate E3 ligases or DUBs that play a significant role in SOCS3 turnover may facilitate the development of peptide disruptors or gene therapy targets to attenuate pathological SMC proliferation. A targeted approach, inhibiting the interaction between SOCS3 and identified E3 ligase, that controls the levels of SOCS3, would be expected to reduce the undesirable effects associated with global inhibition of the E3 ligase involved.

An investigation into the folding and assembly of engineered antibodies and novel antibody formats

Monoclonal antibodies and novel antibody formats are currently one of the principal therapeutic in the biopharmaceutical industry worldwide and are widely used in the treatment of autoimmune diseases and cancer. It is for this reason that the productivity and quality of antibody production requires improvement; specifically investigations into the engineering of antibodies and any issues that may arise from the production of these therapeutics. The work presented in this thesis describes an investigation into the folding and assembly of seven antibodies plus the novel antibody format FabFv. IgG is comprised of two identical HCs and two identical LCs. The folding process of immunoglobulin is controlled by the CH1 domain within the HC. The CH1 domain remains in a disordered state and is sequestered by BiP in the endoplasmic reticulum. Upon the addition of a folded CL domain, BiP is displaced, the CH1 domain is able to fold and the complete IgG protein can then be secreted from the cell. The results presented in this thesis however, have outlined an additional mechanism for the folding of the CH1 domain. We have shown that the CH1 domain is able to fold in the absence of LC resulting in the secretion of HC dimers in a VH dependent manner. The proposed mechanism for the secretion of HC dimers suggests that some VH domains can interact with each other in order to bring the CH1 domains in close proximity to enable folding to occur. As HC dimer secretion is a hindrance in antibody production, this result has highlighted an engineering target to improve antibody yield. Examination of the folding of IgG4 with the variable region A33 has revealed the inability to secrete LC dimers, cleavage of the HC during expression and secretion of HC dimers in the Fab, FabFv and full length forms. The attributes described have also been shown to be variable region dependent. This has introduced a new concept that the variable domain is important in determining the expression and secretion of antibodies and their individual chains. Pulse chase and 2D gel electrophoresis analysis of the novel antibody format FabFv has revealed that the folding and expression of the LC and HC causes multimeric species of FabFv to be secreted, as opposed to the monomeric form which is the desired therapeutic. Our hypothesis is that this process occurs via a LC dependent mechanism. The proposed hypothesis suggests that further engineering to the LC could diminish the formation and secretion of FabFv multimers. The results from these investigations can be applied to increase the productivity of therapeutics and increase the biological understanding of the domain interactions of IgG during folding, assembly and secretion.

Jeux de séduction dans la comédie de la Restauration : pratique sociale, expérience théâtrale

Colloque tenu en Sorbonne les 17-19 janvier 2008

La actualización del modelo socialista y sus efectos en el Partido Comunista Cubano

El VI Congreso del Partido Comunista de Cuba introdujo una nueva agenda económica que el Gobierno llama la actualización del modelo socialista. Muchos piensan que en esencia se trata de una serie de reformas y reducen su importancia a su dimensión económica. Esta monografía busca explicar la actualización aplicando el análisis de sistemas-mundo de Immanuel Wallerstein, aportando una interpretación no convencional del fenómeno. Se puntualizará en las variables de poder y en los actores políticos que han determinado la nueva política económica: el Partido Comunista de Cuba (PCC) y las Fuerzas Armadas Revolucionarias (FAR). Ambos conforman lo que Wallerstein denomina un movimiento antisitémico. El argumento principal es que el movimiento ha puesto en marcha las reformas buscando fortalecer el Estado y así garantizar su supervivencia al consolidar su posición como el competidor único del poder estatal. Como se verá, estas metas han llevado al movimiento a sacrificar parte de su naturaleza antisistémica.

The significant role of third-party logistics (3pl) operators as fosterers of organizational performance in colombian companies

La eliminación de barreras entre países es una consecuencia que llega con la globalización y con los acuerdos de TLC firmados en los últimos años. Esto implica un crecimiento significativo del comercio exterior, lo cual se ve reflejado en un aumento de la complejidad de la cadena de suministro de las empresas. Debido a lo anterior, se hace necesaria la búsqueda de alternativas para obtener altos niveles de productividad y competitividad dentro de las empresas en Colombia, ya que el entorno se ha vuelto cada vez más complejo, saturado de competencia no sólo nacional, sino también internacional. Para mantenerse en una posición competitiva favorable, las compañías deben enfocarse en las actividades que le agregan valor a su negocio, por lo cual una de las alternativas que se están adoptando hoy en día es la tercerización de funciones logísticas a empresas especializadas en el manejo de estos servicios. Tales empresas son los Proveedores de servicios logísticos (LSP), quienes actúan como agentes externos a la organización al gestionar, controlar y proporcionar actividades logísticas en nombre de un contratante. Las actividades realizadas pueden incluir todas o parte de las actividades logísticas, pero como mínimo la gestión y ejecución del transporte y almacenamiento deben estar incluidos (Berglund, 2000). El propósito del documento es analizar el papel de los Operadores Logísticos de Tercer nivel (3PL) como promotores del desempeño organizacional en las empresas colombianas, con el fin de informar a las MIPYMES acerca de los beneficios que se obtienen al trabajar con LSP como un medio para mejorar la posición competitiva del país.

Perfil logístico de Volkswagen desde la producción

Este análisis muestra detalladamente la línea de producción de la planta de Volkswagen, ubicada en México en el estado de Puebla. Se describe la capacidad operativa utilizada para satisfacer la demanda de la planta de producción de automóviles más grande de Latinoamérica, siendo clave para mantenerse en el mercado con estándares de calidad altos y contribuir al desarrollo de la economía del país. Asimismo, a nivel regional, esta planta se abastece de proveedores estratégicos ubicados en una zona cercana, ayudando a disminuir costos de transporte de piezas y tiempos de respuesta. Inicialmente se realiza una breve descripción del entorno económico de la empresa a nivel regional y del sector a nivel global para hacer énfasis en lo competitivo que es el mercado de la producción de automóviles. Posteriormente se describe la finalidad que tiene esta misión empresarial soportada por la Universidad del Rosario, donde se afianzan conocimientos importantes sobre un mercado de talla mundial. El siguiente aspecto es un diagnóstico de la empresa, donde se dan a conocer las marcas que hacen parte del grupo Volkswagen y la situación financiera que refleja la marca desde el 2012, revelando los ingresos obtenidos durante el período 2012-2014, gastos operacionales y factores que no se destacan positivamente como un flujo de caja negativo para el 2014. Posteriormente se plasman los conceptos teóricos necesarios para que el lector comprenda las variables inmersas en una planta de producción, destacando la teoría de colas y el diseño del layout de la empresa. Finalmente, se da una descripción detallada del proceso de producción en esta planta, donde se muestra la línea de producción, el ensamble y la importancia de un sistema operativo interno que depende principalmente de una alta inversión de tecnología e ingeniería que permite obtener un mayor beneficio en cada etapa del proceso.