154,545 research outputs found
Look Who's Talking
No full textAssociate Curator of UK participants in the Look Who's Talking online exhibition and information exchange
Don't look now
No full textNicolas Roeg's Don't Look Now (1973) has been called 'a ghost story for adults'. Certainly, in contrast to the more explicitly violent and bloodthirsty horror films of the 1970s, Don't Look Now seems of an entirely different order. Yet this supernaturally inflected tale of a child's accidental drowning, and her parents' desperate simultaneous recoil from her death and pursuit of her ghost, Don't Look Now is horrific at every turn. This book argues for it as a particular kind of horror film, one which depends utterly on the narrative of trauma—on the horror of unknowing, of seeing too late, and of the failures of paternal authority and responsibility. This study works to position Don't Look Now within a discourse of midcentury anxiety narratives primarily existing in literary texts. In this context, it represents a cross over or a hinge between literature and film of the 1970s, and the ways in which the women's ghost story or uncanny story turns the horror film into a cultural commentary on the failures of the modern family
Precision targeting of human iNKT cells for cancer immunotherapy
No full textInvariant natural killer T (iNKT) cells are a distinct subset of T lymphocytes that recognise lipid antigens presented by CD1d. iNKT cells have been classified into subsets based on both their TCR affinity for CD1d and coreceptor expression, such as CD4⁺ and double-negative (DN) populations, each with distinct functional properties. However, their differential roles in anti-tumour immunity remain unclear. To address this, we employed single-cell RNA sequencing to compare the gene expression and transcription factor profiles of low and high affinity iNKT cells, revealing distinct molecular signatures. TCR sequencing using Oxford Nanopore technology uncovered substantial variability,particularly within the complementarity-determining region 3 (CDR3) of both the α and βchains. Functional assays demonstrated that high affinity iNKT clones exhibit superior cytotoxicity against CD1d-expressing target cells. Additionally, we found that DN iNKT cells display greater cytotoxic potential than CD4⁺ iNKT cells, correlating with their strong expression of the activating receptor NKG2D. Blocking experiments confirmed that NKG2D mediates their enhanced tumour cell lysis. Given the importance of CD1d in iNKT cell activation, we explored strategies to enhance its expression on cancer cells. We optimised an in vitro treatment regimen combining Enhancer of Zeste Homolog 2 (EZH2) inhibitors and all-trans-retinoic acid (ATRA),demonstrating that this approach significantly increases CD1d surface expression and enhances iNKT cell-mediated lysis of acute myeloid leukaemia (AML) cells. Collectively, our findings underscore the functional and phenotypic heterogeneity of iNKT cells and their significance in cancer immunotherapy. Selectively targeting specific iNKT subsets may enhance therapeutic efficacy, while tumour micro environment modulation to upregulate CD1d could further improve direct iNKT-mediated tumour lysis. Future studies should optimise these strategies for clinical application in cancer immunotherapy
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
A new look at the pathogenesis of asthma
No full textAsthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial-mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.<br/
The 'look' and how to keep it: cinematography, postproduction and digital colour
No full textJacques Aumont has noted that, throughout screen history, filmmakers have tended to regard colour as something to be controlled.1 Between the rise of Technicolor in the mid 1930s and the emergence of digital cinema in the late 1990s, this typically involved controlling the colours that appeared in front of a film camera through techniques including production design, costume design, lens filtration and coloured lighting. Since the spread of Digital Intermediate (DI) in the early to mid 2000s, screen colour has owed at least as much to computer-based postproduction processes as it has to camera-based production processes.2 In this essay I explore colour as the focal point of a renegotiation of the historical roles of what are anachronistically still called the ‘production’ and ‘postproduction’ sectors of the film industry. I do so by means of a case study of the recent activities of the American Society of Cinematographers (ASC). Though the Society's membership numbers barely three hundred, it has for many decades been a prominent advocate of the ‘art of cinematography’ and of the interests of the cinematography profession as a whole.3 Using articles from its widely read trade journal, American Cinematographer, I explore some of the strategies used by the ASC over the last decade to preserve the privileged creative status of the Director of Photography (DoP) in the context of rapid technological and industrial change.4 These strategies have typically focused on colour. By exploring the various interactions between the ASC and the postproduction sector reported in American Cinematographer, as well as the rhetoric used to report them, I address the following question: if colour is something to be controlled, who controls it
Handwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Pelevin’s Trinity in the novel “t”: author – protagonist – reader
No full textThe article attempts to interpret Pelevin's artistic strategy in the novel "T" by exploring its subject organization and addressing the key problems of the author, the protagonist, and the reader as they are seen by the researcher. The article analyzes the peculiarities of constructing the narrative reality in the novel "T", and goes on to discuss Pelevin's philosophic models of the development of the humankind, and the emergence of his new anthropology
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