5 research outputs found

    Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids.

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    Protein kinase C iota (PKCĪ¹), a serine/threonine kinase required for cell polarity, proliferation and migration, is commonly up- or downregulated in cancer. PKCĪ¹ is a human oncogene but whether this is related to its role in cell polarity and what repertoire of oncogenes acts in concert with PKCĪ¹ is not known. We developed a panel of candidate oncogene expressing Madin-Darby canine kidney (MDCK) cells and demonstrated that H-Ras, ErbB2 and phosphatidylinositol 3-kinase transformation led to non-polar spheroid morphogenesis (dysplasia), whereas MDCK spheroids expressing c-Raf or v-Src were largely polarized. We show that small interfering RNA (siRNA)-targeting PKCĪ¹ decreased the size of all spheroids tested and partially reversed the aberrant polarity phenotype in H-Ras and ErbB2 spheroids only. This indicates distinct requirements for PKCĪ¹ and moreover that different thresholds of PKCĪ¹ activity are required for these phenotypes. By manipulating PKCĪ¹ function using mutant constructs, siRNA depletion or chemical inhibition, we have demonstrated that PKCĪ¹ is required for polarization of parental MDCK epithelial cysts in a 3D matrix and that there is a threshold of PKCĪ¹ activity above and below which, disorganized epithelial morphogenesis results. Furthermore, treatment with a novel PKCĪ¹ inhibitor, CRT0066854, was able to restore polarized morphogenesis in the dysplastic H-Ras spheroids. These results show that tightly regulated PKCĪ¹ is required for normal-polarized morphogenesis in mammalian cells and that H-Ras and ErbB2 cooperate with PKCĪ¹ for loss of polarization and dysplasia. The identification of a PKCĪ¹ inhibitor that can restore polarized morphogenesis has implications for the treatment of Ras and ErbB2 driven malignancies.Cancer Research UK; Royal Marsden/Institute of Cancer Research National Institute for Health Research Biomedical Research Centre (M.L.)

    Concert recording 2016-11-15

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    [Track 1]. Subjugation. Connection [Track 2]. Captivation / Durgan Maxey -- [Track 3]. Fight / Bryce Owens -- [Track 4]. Overture to Stay / Joshua Bland -- [Track 5]. A cellist\u27s legacy. Part I [Track 6]. Part II / Eric Dreggors -- [Track 7]. Evening prayer / Robbie Baker -- [Track 8]. Elegy / Brandon Wade -- [Track 9]. The grotesques trio. Gargoyles [Track 10]. Chimera [Track 11]. Grotesques / Marissa Johnson -- [Track 12]. Crosshair / Joshua Bland -- [Track 13]. Nightwind sings / L. Coley Pitchford -- [Track 14]. Six reflections through poetry. Memories (Walt Whitman) [Track 15]. The musician\u27s wife (Weldon Kees) [Track 16]. The road not taken (Robert Frost) [Track 17]. Lessons (Whitman) [Track 18]. Stronger lessons (Whitman) [Track 19]. O me! O life! (Whitman) / Nick Vecchio -- [Tracks 20-21]. String quartet #1 / Jeremiah Flannery -- [Track 22]. Tides. Morning tide [Track 23]. Bore tide / Elizabeth Greener -- [Track 24]. Shepherd\u27s contemplation / Robbie Baker -- Green grass / arranged by Eva Martin -- [Track 25]. Urbe fracta est II. A prayer for Jerusalem / Joshua Bland

    MI 48084-5353 (formerly Technical Fellow at General Motors Research), [email protected]. John R. Hauser is the Kirin Professor of Marketing

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    Abstract Researchers and practitioners devote substantial effort to targeting banner advertisements, but less effort on how to communicate with consumers once targeted. Morphing enables a website to learn (actively and near optimally) which banner advertisements to serve to each cognitive-style segment in order to maximize click-through, brand consideration, and purchase. Cognitive-style segments are identified automatically from consumers' clickstreams. This paper describes the first large-sample random-assignment field-test of banner morphing -over 100,000 consumers viewing over 450,000 banners on CNET.com. On relevant webpages, CNET's click-through rates almost doubled relative to control banners. We supplement the CNET field test with a focused experiment on an automotive information-andrecommendation website. The focused experiment replaces automated learning with a longitudinal design to test the premise of morph-to-segment matching. Banners matched to cognitive styles, as well as the stage of the consumer's buying process and body-type preference, significantly increase click-through rates, brand consideration, and purchase likelihood relative to a control. Together the field and the focused experiments demonstrate that matching cognitive styles provide significant benefits above and beyond more-traditional targeting. Such improved banner effectiveness has strategic implications for allocations among media

    MI 48084-5353 (formerly Technical Fellow at General Motors Research), [email protected]. John R. Hauser is the Kirin Professor of Marketing

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    Abstract Morphing enables a website to learn (actively and near optimally) which banner advertisements to serve to each cognitive-style segment in order to maximize outcome measures such as click-through, brand consideration, or purchase. Consumer segments are identified automatically from consumers' clickstream choices. Morphing works best on high-traffic websites with tens of thousands of visitors because large samples are necessary to reach steady state optimally. This paper describes the first large-sample random-assignment field test of banner morphing -over 100,000 consumers viewing over 450,000 banners on CNET.com. (Previously published morphing evaluations evaluated morphing website characteristics and were based on predictive simulations using only priming-study data.) On relevant webpages, CNET's clickthrough rates almost double relative to control banners. We supplement the CNET field test with a focused experiment on an automotive information-and-recommendation website. The focused experiment replaces automated learning with a longitudinal design which tests the premise of morph-to-segment matching. Banners matched to cognitive styles, as well as the stage of the consumer's buying process and body-type preference, significantly increase click-through rates, brand consideration, and purchase likelihood relative to a control
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