1,721,952 research outputs found
Ad Watch examines television advertisements of Thomas Allen, Richard Barringe
No full textAd Watch examines television advertisements of Thomas Allen, Richard Barringer, and Susan Collins, candidates in the upcoming gubernatorial primary elections
Allen, Richard L, Ra 55855863
No full textThis record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/368304Surname: ALLEN
Given Name(s) or Initials: RICHARD L
Military Service Number or Last Known Location: RA 55855863
Missing, Wounded and Prisoner of War Enquiry Card Index Number: SEA-4298178350
Item: [2016.0049.00635] "Allen, Richard L, Ra 55855863
Allen (Richard) éd The Social Gospel in Canada
No full textBaubérot Jean. Allen (Richard) éd The Social Gospel in Canada. In: Archives de sciences sociales des religions, n°48/2, 1979. p. 246
Regulation of Vascular Smooth Muscle Cell Apoptosis by Insulin-like Growth Factor-1: Control of Apoptosis Induced by C-MYC and Protein Kinase Inhibition
No full textThe biological actions of insulin-like growth factor-1 (IGF-1) are critical from embryonic development through adulthood. IGF-1 exerts its actions almost exclusively through the IGF-1 receptor (IGF-1 R), perpetuating a receptor-tyrosine kinase signaling cascade to mediate the many pleiotropic effects of IGF-1, which include cell proliferation, differentiation and survival. Signals activated by the IGF- 1/IGF-1R system include phosphatidylinositol 3’OH-kinase (PI3-kinase) and mitogen-activated protein (MAP) kinase (ERK1/2) pathways, as well as protein kinase C (PKC) in some cells.
Following vascular interventional procedures for symptomatic occlusive arterial disease, symptomatic “restenosis” of the vessel occurs in 25-55% of patients. This arterial lumen renarrowing occurs as a result of vascular smooth muscle cell (VSMC) accumulation in the vessel intima forming a ‘neointima’, a process now believed to be due to an imbalance between cell proliferation and apoptosis. Although several factors have been implicated, IGF-1 may play an especially pivotal role. Indeed, a local IGF-1 /IGF-1 R autocrine/paracrine loop in VSMCs has been recently shown to be required for VSMC growth in vivo. In acromegalics, high levels of IGF-1 are thought to be the main contributor to the accelerated atherosclerosis seen in these patients. Moreover, IGF-1 mRNA, protein and the IGF-1 receptor are elevated in both human and animal models of atherosclerotic and post-angioplasty restenotic vascular lesions. Evidence that c-myc is involved in this process and, that IGF-1 potently inhibits c-myc-induced death, suggests that maintaining VSMC viability during cell injury may have dire consequences for the genesis of occlusive vascular diseases. However, despite our understanding of IGF-1 signals mediating growth, those signals regulating VSMC survival are mostly unknown.
In this study, we examined the pathways of staurosporine (STAU)-induced death and c-/nyc-induced death in human and rat VSMCs, respectively, and the regulation of these apoptotic pathways by IGF-1. Scanning and transmission electron microscopic studies, as well as DNA fragmentation and annexin V assays, showed that morphological and biochemical apoptosis can be induced in human VSMCs (hVSMCs) using STAU (a broad-spectrum protein kinase inhibitor). However, there was a lack of intense ‘blebbing’ in these cells relative to that observed in rat VSMCs (rVSMCs) undergoing myc-induced apoptosis. IGF-1 profoundly inhibited both STAU-induced hVSMC death and c-myc-induced apoptosis of rVSMCs. STAU also produced a 20-fold decrease in PKC-e protein over 24 h, which was partially prevented by IGF-1. Cytosolic and particulate/membrane translocation studies (for PKC activation) showed that IGF-1 activates PKC-e in hVSMCs, but not PKC-a or PKC-8. In fact, pretreatment of hVMSCs with STAU resulted in a slight increase in PKC-e activation over that with IGF-1 alone.
In regards to apoptosis, inhibition of PI3-kinase by wortmannin and LY294002 showed that PI3-kinase (and the downstream survival-related enzyme, Akt/PKB) were required for greater than 60% of the survival effects of IGF-1 in human and rat VSMCs. Moreover, exposure of cells to the MEK inhibitors PD098059 or U0126 showed that IGF-1 also required the MEK-ERK1/2 MAP kinase pathway for preventing STAU- and c-myc-induced human and rat VSMC apoptosis. In addition, IGF-1 produced a strong activation of the PI3-kinase downstream survival enzyme Akt/PKB in hVSMCs. Interestingly, Akt activation peaked at 2 h but returned to near baseline at 6 h using IGF-1 alone, while in the presence of the death stimulus STAU, IGF-1 produced a sustained and greater than 10-fold increase in Akt/PKB activation at 6 h. Sustained Akt/PKB activation for at least 12 h also occurred by IGF-1 during myc-induced apoptosis inhibition. Indeed, IGF-1 sustained the activation of Akt for the duration of apoptosis inhibition. Use of phosphorothioate antisense oligonucleotides, designed to hybridize to PKC-e mRNA, leading to its degradation and thereby specifically inhibiting PKC-e expression, reversed the survival effects of IGF-1 on hVSMCs during STAU-induced apoptosis by about 50%.
Further stress/death pathway studies led to the findings that both STAU and c- Myc, during their respective apoptosis induction programs, induce a strong and sustained activation of the stress kinase family member, JNK/SAPK. This activity was strongly inhibited by IGF-1 at 1 h during either death stimulus, whereas at 2 h inhibition was lost and at 4 and 6 h, the presence of IGF-1 led to a significant augmentation of JNK activity in hVSMCs. Studies on the phosphorylation status of c-Jun, the downstream transcriptional-regulatory target of JNK/SAPK, showed that both apoptosis and activating c-Jun phosphorylations paralleled increases in JNK activity during both apoptotic stimuli. As with JNK, c-Jun phosphorylation at 1 h was only transiently inhibited by IGF-1. Use of selective enzyme inhibitors showed that the transient inhibition of JNK activity and c-Jun phosphorylation (at 1 h) by IGF-1 was dependent on PI3-kinase and ERK1/2 MAP kinase pathways, but not on PKC.
Importantly, studies on MAP kinases revealed that IGF-1 produced a relatively small, but sustained activation of ERK1/2 for up to 2 h in human VSMCs.
To explore the link between the survival abilities of PI3-kinase, Akt/PKB and PKC-e, constitutively active and dominant negative expression vectors for Akt/PKB, PDK1, and PKC-e and PKC-^ were transiently transfected into cells and apoptosis assessed in the absence or presence of IGF-1. These data showed not only that Akt/PKB was important and itself sufficient to inhibit c-myc-induced apoptosis, but also that active PKC-e could partially prevent this form of death. Further, dominant negative PDK1 partially reversed the ability of IGF-1 to prevent myc-induced death. The VSMC survival functions of both PKC-e and PDK1, especially in response to IGF-1, were previously unknown. Taken together, these data suggest that a preferential activation by IGF-1 of all the characterized survival substrates, including Akt/PKB, PKC-e and ERK1/2, occurred when apoptotic stimuli were present. This appears to be highly responsive and benefits the cell by allowing its survival during stress-inducing, death-promoting stimuli. Moreover, multiple pathways previously uncharacterized in human and rat VSMCs, such as ERK1/2, PDK1, Akt and PKC-e, create this environment in response to IGF-1, some in a sustained fashion (ERKs, Akt), while PKC-e does so within about 30 minutes or less. As a consequence of these studies, it is hoped that understanding this signaling tapestry will culminate in a greater diversity of cellular targets for therapeutic intervention. Ultimately, inhibition of gene expression, which is/are regulated by these IGF-1-induced signaling cascades, will likely provide the best targets for disease modification.ProQuest Traditional Publishing Optionxvii, 381 leave
Encountering Anthropomorphism: Editorial
Full text linkThe term ‘anthropomorphism’ relates to a complex of interesting and mutually contradictory ideas, which this issue aims to explore. On the one hand, it is used to refer to something that resembles a human, and, on the other hand, it refers to our natural tendency to read human characteristics in the non-human object or animal. Bruno Latour complicates things further when he insists that ‘anthropos and morphos together mean either that which has human shape or that which gives shape to humans’ (Latour 2009: 237). The articles in this issue address the subject of anthropomorphism in its multiplicity, with different conceptions of the term coexisting in the same volume, and we hope that the tensions between them will make the issue more than the sum of its parts. The purpose of this introduction, then, is not to argue for one conception of anthropomorphism over another, but to present a series of encounters with it and to tease out conceptual threads that connect the varying contributions
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
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