25 research outputs found

    Notes on sexuality and space

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    Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Architecture, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (p. 87).Very little has been written on sexuality in architectural scholarship. Sexuality & Space (Princeton Architectural Press, 1992) contains the proceedings of an eponymous 1990 conference at Princeton University, and was both the first and last book-length publication dedicated to a comprehensive discourse on sexual identity within the discipline of architecture. While symposium organizer and proceedings editor Beatriz Colomina writes in the proceedings' introduction that the occasion's effort to "raise the question of 'Sexuality and Space'" was but "one small event" in an ongoing discourse, that discourse failed to materialize. To the extent that feminist theorists conspicuously ignored in architectural discourse and practice are addressed by Sexuality & Space, the "interdisciplinary exchange in which theories of sexuality are reread in architectural terms and architecture is reread in sexual terms," by its essays, asserts the very silence that its inquiry ostensibly alleviated. By carefully examining the constative impact of literary style within the publication Sexuality & Space-that is, by looking at how the use of language, therein, impacts that document's inscription of its intellectual and historical context-I have come to a better understanding of how that publication was both the beginning and end of the conversation it sought to inaugurate. "Notes on Sexuality and Space" investigates three related essays from that publication: Laura Mulvey's "Pandora: Topographies of the Mask and Curiosity," Beatriz Colomina's "The Split Wall: Domestic Voyeurism," and Mark Wigley's "Untitled: The Housing of Gender." Each investigated essay has been given a corresponding chapter. My method has been close reading, or the sustained interpretation of brief passages of text. Paying close attention to individual words, syntax, and the order in which ideas unfold as they are read, I have developed a comprehensive narrative of how these three essays, together, both instantiate and negate a shared discourse. To these ends, this thesis raises serious questions about what it means to have historiography after silence, and what it means to re-open an already closed discourse.by Samuel Ray Jacobson.S.M

    Act now against new NHS competition regulations: an open letter to the BMA and the Academy of Medical Royal Colleges calls on them to make a joint public statement of opposition to the amended section 75 regulations.

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    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Cholesterol affects spectrin-phospholipid interactions in a manner different from changes resulting from alterations in membrane fluidity due to fatty acyl chain composition

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    AbstractWe previously showed that erythrocyte and brain spectrins bind phospholipid vesicles and monolayers prepared from phosphatidylethanolamine and phosphatidylserine and their mixtures with phosphatidylcholine (Review: A.F. Sikorski, B. Hanus-Lorenz, A. Jezierski, A. R. Dluzewski, Interaction of membrane skeletal proteins with membrane lipid domain, Acta Biochim. Polon. 47 (2000) 565). Here, we show how changes in the fluidity of the phospholipid monolayer affect spectrin–phospholipid interaction. The presence of up to 10%–20% cholesterol in the PE/PC monolayer facilitates the penetration of the monolayer by both types of spectrin. For monolayers constructed from mixtures of PI/PC and cholesterol, the effect of spectrins was characterised by the presence of two maxima (at 5 and 30% cholesterol) of surface pressure for erythroid spectrin, and a single maximum (at 20% cholesterol) for brain spectrin. The binding assay results indicated a small but easily detectable decrease in the affinity of erythrocyte spectrin for FAT-liposomes prepared from a PE/PC mixture containing cholesterol, and a 2- to 5-fold increase in maximal binding capacity (Bmax) depending on the cholesterol content. On the other hand, the results from experiments with a monolayer constructed from homogenous synthetic phospholipids indicated an increase in Δπ change with the increase in the fatty acyl chain length of the phospholipids used to prepare the monolayer. This was confirmed by the results of a pelleting experiment. Adding spectrins into the subphase of raft-like monolayers constructed from DOPC, SM and cholesterol (1/1/1) induced an increase in surface pressure. The Δπ change values were, however, much smaller than those observed in the case of a natural PE/PC (6/4) monolayer. An increased binding capacity for spectrins of liposomes prepared from a “raft-like” mixture of lipids could also be concluded from the pelleting assay. In conclusion, we suggest that the effect of membrane lipid fluidity on spectrin–phospholipid interactions is not simple but depends on how it is regulated, i.e., by cholesterol content or by the chemical structure of the membrane lipids

    Analogue Gravity

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    Analogue models of (and for) gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing) and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity)
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