A Modeling-Derived Hypothesis on Chronicity in Respiratory Diseases: Desensitized Pathogen Recognition Secondary to Hyperactive IRAK/TRAF6 Signaling

Several chronic respiratory diseases exhibit hyperactive immune responses in the lung: abundant inflammatory mediators; infiltrating neutrophils, macrophages, lymphocytes and other immune cells; and increased level of proteases. Such diseases include cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and severe/neutrophilic asthma. Paradoxically, patients with these diseases are also susceptible to detrimental bacterial infection and colonization. In this paper, we seek to explain how a positive feedback mechanism via IL-8 could lead to desensitization of epithelial cells to pathogen recognition thus perpetuating bacterial colonization and chronic disease states in the lung. Such insight was obtained from mathematical modeling of the IRAK/TRAF6 signaling module, and is consistent with existing clinical evidence. The potential implications for targeted treatment regimes for these persistent respiratory diseases are explored

"Outside, it is snowing": Experience and finitude in the nonrepresentational landscapes of Alain Robbe-Grillet

Copyright © 2008 PionRomanillos J L, 2008. The definitive, peer-reviewed and edited version of this article is published in Environment and Planning D: Society and Space 26(5) 795 – 822 DOI: 10.1068/d6207This paper presents and explicates the anonymous and impersonal spatialities tentatively mapped in the novels of Alain Robbe-Grillet. Emerging from the kinds of landscapes and visualities articulated, these spatialities are at odds with the kind of anthropocentrism characteristic of phenomenological narratives of spatial experience that would start from an apparently stable human-subject position. It is argued that his body of literature dismantles the anthropocentric narratives and biographies that would produce in both the space of the world and the ‘phenomenological subject’ an unwarranted depth and naturalism. Importantly, and reflecting the theoretical turn towards the being of language, Robbe-Grillet questions the legitimacy of linguistic subjects to capture the spaces of the visible. As such, it is argued that his literature reflects an experience of the critiques of phenomenology. Importantly, this ‘critique’ goes hand in hand with the kinds of spatialities and landscapes that are rendered in the novels—the indefinite perspectives they open up, the paradoxical visualities they sustain or deny, and the disorientation they inject into the heart of spatial experience. These literary effects produce a nonanthropocentric and nonpersonal spatiality which, although contributing to an erasure of the ‘subject’, at the same time expose and open up a sociospatiality based on singularities, intensities, and finitude