5,325 research outputs found
Customizing the therapeutic response of signaling networks to promote antitumor responses by drug combinations
No full textThis work was supported by grants from Breakthrough Breast Cancer and Scottish Funding Council (SRDG), and personal support to Alexey Goltsov from Scottish Informatics and Computer Science Alliance (SICSA) and to James Bown from The Northwood Trust.Drug resistance, de novo and acquired, pervades cellular signaling networks (SNs) from one signaling motif to another as a result of cancer progression and/or drug intervention. This resistance is one of the key determinants of efficacy in targeted anti-cancer drug therapy. Although poorly understood, drug resistance is already being addressed in combination therapy by selecting drug targets where SN sensitivity increases due to combination components or as a result of de novo or acquired mutations. Additionally, successive drug combinations have shown low resistance potential. To promote a rational, systematic development of combination therapies, it is necessary to establish the underlying mechanisms that drive the advantages of combination therapies, and design methods to determine drug targets for combination regimens. Based on a joint systems analysis of cellular SN response and its sensitivity to drug action and oncogenic mutations, we describe an in silico method to analyze the targets of drug combinations. Our method explores mechanisms of sensitizing the SN through a combination of two drugs targeting vertical signaling pathways. We propose a paradigm of SN response customization by one drug to both maximize the effect of another drug in combination and promote a robust therapeutic response against oncogenic mutations. The method was applied to customize the response of the ErbB/PI3K/PTEN/AKT pathway by combination of drugs targeting HER2 receptors and proteins in the down-stream pathway. The results of a computational experiment showed that the modification of the SN response from hyperbolic to smooth sigmoid response by manipulation of two drugs in combination leads to greater robustness in therapeutic response against oncogenic mutations determining cancer heterogeneity. The application of this method in drug combination co-development suggests a combined evaluation of inhibition effects together with the capability of drug combinations to suppress resistance mechanisms before they become clinically manifest.Peer reviewe
The Rhetoric of Landscape in Gregory of Nyssa’s Homilies on the Song of Songs
No full textThis is the author accepted manuscript. The final version is available from Brill via the ISBN in this recordAnalytical and Supporting Studies. Proceedings of the 13th International Colloquium on Gregory of Nyssa (Rome, 17-20 September 2014)Series:
Vigiliae Christianae, Supplements, Volume: 150In this paper I want to take you on a walk through a garden. It is, to be sure, an imaginary garden; nevertheless, it bears a significance which extends beyond itself. Some of this significance concerns words and texts: for as we shall see, the garden is, amongst other things, a ‘garden of rhetoric’. The garden in question appears in the Gregory of Nyssa’s Homilies on the Song of Songs.[...
An Evening with Richard Claxton “Dick” Gregory, Civil Rights Activist, Nutritionist, Comedian, and Author
No full textGregory, Richard Claxton “Dick” (Born, October 12, 1932, St. Louis, Mo.), African American comedian and civil rights activist whose social satire changed the way white Americans perceived African American comedians since he first performed in public. Gregory’s autobiography, Nigger, was published in 1963 prior to The assassination of President Kennedy, and became the number one best-selling book in America. Over the decades it has sold in excess of seven million copies. His choice for the title was explained in the forward, where Dick Gregory wrote a note to his mother. “Whenever you hear the word ‘Nigger’,” he said, “you’ll know their advertising my book.” In 1984 he founded Health Enterprises, Inc., a company that distributed weight loss products. In 1987 Gregory introduced the Slim-Safe Bahamian Diet, a powdered diet mix, which was immensely profitable. Economic losses caused in part by conflicts with his business partners led to his eviction from his home in 1992. Gregory remained active, however, and in 1996 returned to the stage in his critically acclaimed one-man show, Dick Gregory Live! The reviews of Gregory’s show compared him to the greatest stand-ups in the history of Broadway
“Judge Me Gently”: Reflections on the Religious Life of John Milton Gregory, 1822–1898
No full text John Milton Gregory is familiar to many Christian educators through his 19th-century publication, The Seven Laws of Teaching. For most readers of this important book, little is known about the author himself. This article explores the religious life and theological foundations of John Milton Gregory, who was both author of The Seven Laws of Teaching and founding president of the University of Illinois. Utilizing his spiritual diaries preserved in his daughter's biography of her father and archival sources from the University of Illinois, this essay offers a theological and spiritual understanding of this important historical figure. </jats:p
David Gregory
No full textPhotograph - David Gregory, member of the Book Sub-Committee, part of the Town of Athabasca 75th Anniversary Committee, Athabasca, Alberta. The Book Sub Committee produced the book "Athabasca Landing: An Illustrated History
Improved Balloon
No full textLetter to the editor by J. Gregory describing his improved gas balloon, with an accompanying labeled mechanical illustration.For more information about this item, visit https://archivesspace.mit.edu/repositories/2/digital_objects/71
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Homeric Echoes in Posidippus
No full textLabored in Papyrus Leaves: Perspectives on an Epigram Collection Attributed to Posidippus (P.Mil.Vogl. VIII 309) is a Center for Hellenic Studies publication, specifically Hellenic Studies Series 2. Since Gregory Nagy is both article author and Director of the Center for Hellenic Studies, no special permission needed for online submission.The ClassicsAuthor's Origina
Columbus\u27s Ghost: Tourism, Art and National Identity in the Bahamas
No full textIan Gregory Strachan (1969-), Bahamian writer, Chair of English Studies at College of the Bahamas, author of God\u27s Angry Babies (1997) and Paradise and Plantation (2002)
Gregory Grosvenor
No full textPublicity photo submitted by author/presenter for ODU\u27s Annual Literary Festival 2025.https://digitalcommons.odu.edu/litfest_images/1006/thumbnail.jp
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