92 research outputs found
Rezension zu Jenny Haase und Joanna Neilly (Hgg.): „German Romanticism and Latin America. New Connections in World Literature“
No full textMiguel Gaete rezensiert Jenny Haases und Joanna Neillys (Hgg.) „German Romanticism and Latin America. New Connections in World Literature“ (Legenda 2024)
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Human rights and the limits of critical reason /
No full textThe rationalization of power has been an enduring feature of Modernity, assigning to human rights the task of subjecting the excesses of power to the scrutiny of critical reason. Gaete examines this task in the wake of the crisis of modernity, when the belief that man can draw principles out of his own ground has lost its authority and when the very possibility of an enlightened, disinterested Reason is being questioned. The aim of the book is not to offer another critique of rights but to investigate how both rights and critiques are transformed by the rhetoric of power. The author traces the discourse of judicial criticism as a series of rhetorical operations, bringing to light the paradoxes, antinomies and 'truth games' that permeate the field of human rights. He interrogates the discourse of modern humanism and investigates how its claims to being the law of the law and the metaphysics of the modern State shape the bond between State and citizen
Biopolítica, Gobierno y Salud Pública. Miradas para un diagnóstico diferencial de Tuillang Yuing y Rodrigo Karmy
No full textTuillang Yuing y Rodrigo Karmy (editores).
Participan: Rodrigo Karmy, Philippe Monti, Mariela Cecilia Ávila, Tuillang Yuing, Miguel Kotow, Jimena Carrasco, Sandra Caponi, Luis David Castiel, Yuri Carvajal, Jorge Gaete.
Escuela de Salud Pública- Ocho Libros Ediciones
Octubre 2014, 206 pp.
ISBN: 978-956-335-213-
La extensión del principialismo a la ética de la investigación con animales
No full textEl presente trabajo tiene por objetivo realizar un examen crítico del principialismo como marco de referencia ético para la investigación con animales. Encuentra su motivación en la propuesta de un enfoque principialista para la ética de la investigación con animales de laboratorio presentada el año 2020 por los filósofos Tom Beauchamp y David DeGrazia en los Principles of Animal Research Ethics. Para el propósito descrito, se analiza el estado del arte en torno a la ética de la investigación con animales, cuyo principal estándar son las 3 R´s de Russell y Burch.
Asimismo, se realiza una revisión crítica del principialismo, cuyo texto fundamental es Principles of Biomedical Ethics, escrito por Tom Beauchamp y James Childress. A partir de estas bases, se evalúa críticamente la posibilidad de aplicación del principialismo en el ámbito de la ética de la investigación con animales.
Como resultado esperado, se busca responder a la pregunta acerca de si el principialismo ofrece un marco teórico apropiado para la ética de la investigación con animales, determinando sus fortalezas y debilidades.Proyecto Fondecyt ANID No. 11200897Versión original del auto
Activación del sensor IRE1α de la Respuesta a proteínas mal plegadas (“Unfolded protein response”, UPR) en células dendríticas intratumorales
No full textDendritic cells (DCs) have emerged as attractive candidates in the cancer immunotherapy field due to their high plasticity and the capacity to regulate adaptive immunity.
As a major organelle responsible of protein synthesis, the endoplasmic reticulum (ER) represents a central hub of the immune response onset, as it contributes to key immunological processes including the regulation of the antigen presentation routes, the differentiation of secretory immune cells, and the control of inflammation, by means of cytokine production. Remarkably, tumor cells grow at expenses of the host and imposes a high degree of cellular stress. A relevant cellular stress in cancer relates to the accumulation of unfolded proteins in the ER lumen of tumor-infiltrating immune cells, causing ER stress and activating an intracellular signaling cascade known as the Unfolding Protein Response (UPR). The UPR is a three-pronged signal transduction pathway responsible to maintain protein homeostasis in the ER, and it has shown to control crucial processes in the biology of DCs including ER architecture, expression of integrins and antigen presentation. Therefore, manipulation of UPR could be a rising strategy to modulate DCs function during the activation of the antitumoral immune response.
In this thesis work, we studied how the tumor niche activates the UPR branch controlled by the sensor IRE1α and its transcription factor XBP-1s, in DCs infiltrating tumors and tumor draining lymph nodes (TdLNs), in a murine model of melanoma induced by inoculation of B16-OVA cells. For this purpose, we used two approaches: First we identified cDC1 and cDC2 cell subtypes with an active IRE1α RNAse activity at the tumor and TdLNs of mice, by an strategy of multiparametric 14-colors flow cytometry and the use of a transgenic mice line, ERAI (ER stress Activated Indicator[1]). ERAI mice carry the mRNA sequence of XBP-1s, which is spliced by IRE1α, fused to Venus FP, allowing the quantification of the activation of IRE1α in vivo. Second, we quantified the expression of XBP-1s and RIDD target genes in sorted intratumoral DCs, which allowed the quantification of the activation of the IRE1α-XBP-1s and the IRE1α-RIDD axis.
Our results indicate that high levels of IRE1a RNase activity is selectively induced in the intratumoral cDC1s lineage of DCs. The outcome of this activation was evidenced by enhanced ERAI signal, high amounts of XBP-1s mRNA and decreased expression of RIDD targets, which was selectively noticed in the tumor site compared to the draining lymph node. These data indicate that the tumor site elicit strong activation of IRE1a RNase activity in cDC1, which is the most immunogenic antigen presenting cell type infiltrating Tumors. Current work is focused on unveiling which branch of IRE1 RNase regulates the acquisition of an immunogenic profile in tumor cDC1.Las células dendríticas (DCs) han surgido como atractivas candidatas en inmunoterapia del cáncer, debido su alta plasticidad y a su capacidad de regular la inmunidad adaptativa.
Siendo el principal organelo responsable de la síntesis de proteínas, el retículo endoplasmático (RE) es un foco central en el inicio de la respuesta inmune, ya que contribuye a procesos inmunológicos claves que incluyen la regulación de rutas de presentación de antígenos, la diferenciación de células inmunes de naturaleza secretora, y el control de la inflamación mediante la producción de citoquinas. Notablemente, el crecimiento de diversos tipos de tumores expone señales capaces de inducir la acumulación de proteínas mal plegadas en el lumen del RE de células inmunes, lo que origina estrés de RE, activando una cascada de señalización intracelular conocida como respuesta a proteínas mal plegadas o UPR por su sigla en inglés “Unfolded Protein Response”. La UPR es una vía transducción de señales de tres ejes responsable de mantener la homeostasis proteica en el RE, ya que ha demostrado controlar procesos cruciales en la biología de las DCs tales como la arquitectura del RE, expresión de integrinas y presentación antigénica. Por esta razón, la manipulación de la UPR podría ser una estrategia prometedora para modular la función de DCs durante la activación de la respuesta inmune anti-tumoral.
En este trabajo, se estudió cómo el nicho del tumor activa el eje de la UPR controlado por el sensor IRE1α y su factor de transcripción XBP-1s, en DCs infiltrantes de tumor y linfonodo drenante de tumor (TdLN) en un modelo murino de melanoma inducido vía inoculación de células B16-OVA de melanoma. Para ello, el trabajo se centró en dos enfoques: Primero se identificaron los subtipos cDC1 y cDC2 que presentaron una activación de la actividad RNasa de IRE1α en el tumor y TdLN mediante citometría de flujo multiparamétrica de 14 colores empleando los ratones transgénicos, ERAI (ER stress Activated Indicator[1]). Los ratones ERAI contienen la secuencia de XBP-1s, la cual es cortada por IRE1α, fusionada a Venus FP, permitiendo la cuantificación de la activación de la enzima in vivo. Segundo, se cuantificó la expresión de genes blanco de XBP-1s y de RIDD en DCs sorteadas de tumor y TdLN, lo cual permitió la cuantificación de la activación de los ejes IRE1α-XBP-1s y IRE1α-RIDD.
Nuestros resultados indican altos niveles de actividad RNasa de IRE1a selectivamente en el linaje cDC1s de DCs intratumorales. La consecuencia de esta activación fue evidenciada en una señal ERAI aumentada, cantidades elevadas de ARNm de XBP-1s y disminuida expresión de mRNAs blanco de RIDD, lo cual fue observado de manera selectiva en tumor en comparación a linfonodo drenante. Estos datos indican que el nicho tumoral induce una fuerte activación de la actividad RNasa de IRE1a en cDC1, la cual corresponde a la célula presentadora de antígenos más eficiente de las infiltrantes de tumores. Nuestro trabajo actual está focalizado en identificar cuál rama de la actividad RNasa de IRE1 regula la adquisición de un perfil inmunogénico en las cDC1 de tumor cDC1.Versión original del autor30-Junio-202
Interface Agents' Design for a DRT Transportation System using PASSI
No full textAbstract. The present work continues a longer research in the field of flexible transportation services and the design of an agent system devoted to the planning, scheduling and control of trips under such a domain. In particular, this paper focuses in the design and development of the interface agents present in the system by following an agent development methodology named PASSI. The interface agent devoted to interaction with the customers is explained in detail and its prototype is shown
Planning support systems for implementing blue-green infrastructure: Multi-functional spatial planning strategies in Amsterdam
No full textCities are facing more extreme climates and weather events. This requires changes in the way cities are planned and designed. Blue-Green Infrastructure (BGI) is increasingly recognized to guide the transition to climate resilient cities. BGI is founded in urban water management but has emerged as a complementary type of infrastructure because it can provide multiple benefits. To advance the integration of BGI in the urban landscape, Planning Support Systems (PSS) have proven their merit. PSS are any kind of digital tool for support in planning processes. However, PSS are not used much in urban planning. This could have multiple reasons, but it referred to the implementation gap. The gap suggests a mismatch between PSS supply and demand. The demand is set by the practitioners of PSSs, the urban planners. Most effort in closing the gap is with research on improving the technical specifications of PSS. The challenges urban planners are facing in implementing BGI hasn’t been carefully studied. To improve the uptake of PSS for BGI implementation, this thesis evaluated a prototype PSS, studied on the case of the municipality of Amsterdam. Next to the conceptualization of BGI and PSS, the objectives were: to understand urban planning processes; to determine the challenges for BGI implementation; and to find opportunities for PSS to address these challenges. This thesis conceptualizes BGI and PSS in the perspective socio-technical solutions in the transition to sustainable urban development. The planning processes and related challenges are studied by means of semi-structured in-depth interviews with 9 urban planners of the municipality of Amsterdam. Five of them participated in a focus group in which the prototype PSS was evaluated. Amsterdam constructed four main planning processes with which it aims to apply an integrated approach to the implementation of BGI. The main challenges urban planners are struggling with multi-objective planning required in the increasingly complex urban landscape; translating abstract and contradictory policy into practice without classification and standardized BGI measures; and collaborating to obtain the integrated approach. During the focus group, the participants listed multi-objective planning and supporting collaborative processes as most appropriate opportunities for the protype PSS. The use of PSS is highly dependent on the balance of technical and supportive functions. This thesis provides insights for PSS-developers on how to meet the demand of urban planners. With more useful PSS the transition for sustainable urban development can be accelerated.Metropolitan Analysis, Design and Engineering (MADE
Social-Ecological Knowledge Integration in Co-Design Processes: Lessons From Two Resilient Urban Parks in Chile
No full textCities worldwide face multiple social and ecological challenges, such as climate change and its impacts. Adapting and transforming our urban environments is urgent to improve their resilience to uncertain scenarios. These challenges require renewed urban solutions and force us to rethink their design processes. Multiple actors are involved in such processes, coming from different sectors, and sometimes having conflicting agendas and knowledge backgrounds. Many of these processes can be considered co‐design processes, with actors interacting to improve the design quality, legitimacy, and feasibil-ity. Many conceptualise cities as social‐ecological systems and public spaces are their subsystems. A collaborative approach to designing public spaces contributes to integrating the social‐ecological knowledge from the public, private, and citizen act-ors. The question remains: How is sometimes conflicting social‐ecological knowledge integrated into public space co‐design processes? We study two large‐scale urban parks in Chile. We framed them as social‐ecological systems and analysed their co‐design processes. This study aims to provide insights into the difficult‐to‐grasp phenomena of knowledge integration in co‐design processes. We analysed these cases in previous studies. Now we provide insights into social‐ecological knowledge integration in co‐design processes. Although framed in Latin America, the findings may be helpful elsewhere.Urban Development Managemen
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