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

The Amplifier - v. 12, no. 6

In this issue...Archaeology, Walkerville, Mardi Gras, Selective Service, Copper Guards, Virginia City, Sheriff Henry Plummer, Civil Rights, Montana Power Company

Navigating equality:religious young women's perceptions of gender and sexuality equality

Equality has become an important concept within secular-liberal societies (Perrons 2005), with white, secular Western women interpellated as quintessentially embodying this equality (Gill and Scharff 2011; McRobbie 2011; Nayak and Kehily 2008). For religious organizations, the interacting spaces of gender and sexuality constitute two of the most contested terrains in rights-giving, and many religions are seen as less progressive regarding equality vis-à-vis other social institutions (Plummer 2003; Tosh and Keenan 2003; Weeks2007). Young religious women have to articulate how they fit into the contours of secular-liberal equality norms as religious subjects. This chapter will focus on how young religious women living in the UK made sense of equality in the context of their religion, focusing on attitudes to gender equality and sexuality equality.

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.

Iberian and Latin American Music Scholarship on the Ascent: Reflections from the United States

In the early twentieth century, musicology was established as an academic discipline in the United States. Nonetheless, with the exception of Iberian medieval and Renaissance repertories, U.S. scholars largely overlooked the music of the Spanish- and Portuguese- speaking world. Why should this have been the case, especially in light of Spain’s strong historical presence in the United States? This autobiographical essay examines this question by tracing the career of an individual musicologist, the Hispanist musicologist Carol A. Hess. Evaluated here are disciplinary shifts in U.S. musicology —methodological, philosophical, and ideological— over the past thirty years. These transformations have combined to make this repertory a viable field of study today. Musicologists in the United States can now make their careers by specializing in Iberian and Latin American music, as well as the music of the Hispanic diaspora. They research topics ranging from the avant-garde composer Llorenç Barber to the rapper Nach Scratch or the popular bandleader Xavier Cugat and his U.S. audiences of the 1940s, while others also pursue the time-tested areas of medieval and Renaissance music. Iberian and Latin American music is regularly offered in postsecondary institutions while instructors now have a variety of textbooks and other pedagogical resources from which to choose. All add up to a disciplinary freedom that would have been unthinkable only a few decades ago.

Print versus digital texts: understanding the experimental research and challenging the dichotomies

This article presents the results of a systematic critical review of interdisciplinary literature concerned with digital text (or e-text) uses in education and proposes recommendations for how e-texts can be implemented for impactful learning. A variety of e-texts can be found in the repertoire of educational resources accessible to students, and in the constantly changing terrain of educational technologies, they are rapidly evolving, presenting new opportunities and affordances for student learning. We highlight some of the ways in which academic studies have examined e-texts as part of teaching and learning practices, placing a particular emphasis on aspects of learning such as recall, comprehension, retention of information and feedback. We also review diverse practices associated with uses of e-text tools such as note-taking, annotation, bookmarking, hypertexts and highlighting. We argue that evidence-based studies into e-texts are overwhelmingly structured around reinforcing the existing dichotomy pitting print-based (‘traditional’) texts against e-texts. In this article, we query this approach and instead propose to focus on factors such as students’ level of awareness of their options in accessing learning materials and whether they are instructed and trained in how to take full advantage of the capabilities of e-texts, both of which have been found to affect learning performance.

The space for social media in structured online learning

In this paper, we explore the benefits of using social media in an online educational setting, with a particular focus on the use of Facebook and Twitter by participants in a Massive Open Online Course (MOOC) developed to enable educators to learn about the Carpe Diem learning design process. We define social media as digital social tools and environments located outside of the provision of a formal university-provided Learning Management System. We use data collected via interviews and surveys with the MOOC participants as well as social media postings made by the participants throughout the MOOC to offer insights into how participants’ usage and perception of social media in their online learning experiences differed and why. We identified that, although some participants benefitted from social media by crediting it, for example, with networking and knowledge-sharing opportunities, others objected or refused to engage with social media, perceiving it as a waste of their time. We make recommendations for the usage of social media for educational purposes within MOOCs and formal digital learning environments.