417 research outputs found

    Rapamycin perfluorocarbon nanoparticle mitigates cisplatin-induced acute kidney injury

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    For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10-20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and no specific mechanism-based prophylactic approach is available to date. Here, we postulated that systemically delivered rapamycin perfluorocarbon nanoparticles (PFC NP) could reach the injured kidneys at sufficient and sustained concentrations to mitigate cisplatin-induced acute kidney injury and preserve renal function. Using fluorescence microscopic imaging and fluorine magnetic resonance imaging/spectroscopy, we illustrated that rapamycin-loaded PFC NP permeated and were retained in injured kidneys. Histologic evaluation and blood urea nitrogen (BUN) confirmed that renal structure and function were preserved 48 h after cisplatin injury. Similarly, weight loss was slowed down. Using western blotting and immunofluorescence staining, mechanistic studies revealed that rapamycin PFC NP significantly enhanced autophagy in the kidney, reduced the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as decreased the expression of the apoptotic protein Bax, all of which contributed to the suppression of apoptosis that was confirmed with TUNEL staining. In summary, the delivery of an approved agent such as rapamycin in a PFC NP format enhances local delivery and offers a novel mechanism-based prophylactic therapy for cisplatin-induced acute kidney injury

    Radio Astronomy

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    Contains reports on five research projects.National Aeronautics and Space Administration (Grant NsG-419)National Aeronautics and Space Administration (Contract NSR-22-009-120)Lincoln Laboratory Purchase Order No. 74

    Radio Astronomy

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    Contains research objectives and reports on six research projects.National Aeronautics and Space Administration (Contract NSR-22-009-120)National Aeronautics and Space Administration (Grant NsG-419)Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U.S. Air Force) under Contract DA 36-039-AMC-03200(E

    Silly Questions and Arguments for the Implicit, Cinematic Narrator

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    My chapter aims to advance the debate on a problem often raised by philosophers who are skeptical of implied narrators in movies. This is the concern that positing such elusive narrators gives rise to absurd imaginings (Gaut 2004: 242; Carroll 2006: 179-180). Friends of the implied cinematic narrator reply that the questions critics raise about the workings of the implied cinematic narrator are "silly ones" to ask. I examine how the "absurd imaginings" problem arises for all the central arguments for the elusive cinematic narrator and discuss why the questions critics pose about this narrator are legitimate ones to ask

    Imagination and Film

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    This chapter addresses the application of contemporary theories of the imagination—largely drawn from cognitive psychology—to our understanding of film. Topics include the role of the imagination in our learning what facts hold within a fictional film, including what characters’ motivations, beliefs, and feelings are; how our perceptual experience of a film explains our imaginative visualizing of its contents; how fictional scenarios in films generate certain affective and evaluative responses; and how such responses compare to those we have toward analogous circumstances in real life
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