1,003 research outputs found

    Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene

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    G protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH beta-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH2-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH beta-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH2-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH beta-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression

    Development and validation of safety practices, perceived risk, risk coping and stigma questionnaire among frontline healthcare workers dealing with covid-19 pandemic in Hospital Universiti Sains Malaysia

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    Background: Healthcare workers (HCWs) are at higher risk of contracting COVID-19 infection compared to the general population. Safety practices, perceived risk, risk coping strategies and stigma faced by HCWs are important aspects to be investigated to ensure their wellbeing. This study aims to develop and validate Safety Practices, Perceived Risk, Risk Coping and Stigma Questionnaire among HCWs in Hospital Universiti Sains Malaysia (Hospital USM), Malaysia. Methods: The questionnaire was generated after an extensive literature review. Content validity was done by six experts, followed by face validity with eight HCWs from the Emergency Department, Hospital USM. A cross-sectional study was done among 213 frontline HCWs directly or indirectly involved in managing COVID-19 patients in Hospital USM. Exploratory factor analysis (EFA) and reliability analysis were done. Findings: Content validity was acceptable with item-level content validity index (I-CVI) ranging from 0.83 to 1.00 and scale-level content validity index (S-CVI) ranging from 0.85 to 1.00. Face validity was acceptable with item-level face validity index (I-FVI) ranging from 0.88 to 1.00 and scale-level face validity index (S-FVI) ranging from 0.85 to 1.00. For EFA, all factor loadings were more than 0.30. The safety practices domain was divided into three subdomains. The perceived risk domain showed three factors, the risk coping domain showed four factors, while the stigma domain revealed two factors. Cronbach’s alpha was acceptable (0.714-0.970) except for the factor dietary change under the risk coping domain which scored 0.479. Conclusions: The Safety Practices, Perceived Risk, Risk Coping and Stigma Questionnaire is valid. All domains of this questionnaire have good reliability, except for the factor dietary change under the risk coping domain. This validated questionnaire will thoroughly assess HCWs during the COVID-19 pandemic and guide policymakers to plan appropriate interventions if required

    Learning how to learn

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    This lightning talk presents some learning concepts that could be useful for researchers wanting to learn a new skill or a new tool, and trainers who wants to create effective training programmes.Jun will explain some learning related concepts including but not limited to: • The mastery curve • Chunking • Categorising what to understand vs memorise vs practiceABOUT THE AUTHOR(S) Jun Huh comes from a start-up background with focus around providing genuine value to the users and steering organisations to be more user driven.</div

    On the Possession of Truth in Fiction: A.S. Byatt's Confrontation with the Role of the Author

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    When Possession’s protagonist, a post-structuralist/deconstructionist scholar named Roland Michell, finds and takes drafts of a letter written by Victorian poet Randolph Henry Ash, A.S. Byatt re-opens the longstanding debate concerning the ownership of truth and an author’s role in textual interpretation, ultimately asking: Who owns the meaning of a text? And even more so, why? The act of theft from the private world of an author (and the journey it spurs) allows Possession to coincide with pre-formalist notions about the author—that the author and their life is central to the meaning of their work—despite a dominant knowledge of formalism, new criticism, structuralism, poststructuralism, and deconstruction in the contemporary timeline. However, Possession’s three-and-a-half-page postscript chapter unravels a novel-length endorsement of pre-formalist notions, affording the novel a neutral existence that does not condemn nor encourage reliance on the biography of the author. As a result, this essay finds that the novel acts as a means for readers to identify two fundamental ideas about authorship and to witness a regressive transition from a post- to pre-formalist literary approach. In fact, by depicting the common occurrence of exchange to curate an author’s belongings (despite their passing), Possession even suggests that the reconfiguration of the author is a response to capitalist commodification. And so, by utilizing the theories of Roland Barthes and Michel Foucault, this essay argues how Possession shows the role of capitalism and consumerism in the contemporary approach to literature

    Japanese foreign direct investment : recent trends, determinants, and prospects

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    In the late 1980s, Japan became the biggest source of foreign direct investment (FDI) in the world. The main beneficiaries of the rapid increase in investment flows were industrial countries, but the developing world (especially East Asia and Latin America) also received substantial inflows. In East Asia, the newly industrial economies (NIEs) of Hong Kong, Republic of Korea, Singapore, and Taiwan (China) were, at first, production bases for Japanese manufacturing in the 1970s and early 1980s. But in the late 1980s, these countries became new, expanding consumer markets, attracting huge Japanese investments in the tertiary (service) sector, while investments in manufacturing shrank rapidly because of rising labor costs. The Association of Southeast Nations (ASEAN) and China became Japan's new production base. In Latin America (mostly small Caribbean countries) Japan's focus is almost exclusively on tax havens. Globally, Japan's investments in the secondary (manufacturing) and service sectors of the major Latin American nations are only marginal. Japanese investment flows declined drastically after 1989, mostly because of the depressed global and domestic economy, after rapid asset price deflation in Japan. Hardest hit by the decline were the United States and Europe. Japanese FDI flows to developing countries also declined, but less. The biggest losers were the NIEs and the Caribbean tax havens. The biggest losers were the NIEs and the Caribbean tax havens. Japanese investments continued to grow in other Latin American countries and, even more, in the ASEAN and China. Japanese investors sharply reduced tertiary sector investments, primarily geared to maintaining or expanding markets. Investments in the secondary sector, making use of low-cost production, continued to expand. This trend is expected to continue in the near future, with FDI flows declining further, albeit more slowly. Low-wage production countries such as China and Indonesia will attract an increasing share. Investment to expand markets in the industrial countries and the NIEs are likely to decline. But medium-term prospects for Japanese FDI in developing countries are brighter, as economic recovery and continuing current account surpluses in Japan will lead to a resumption of active foreign investment by Japanese multinational corporations.Foreign Direct Investment,Environmental Economics&Policies,International Terrorism&Counterterrorism,Economic Theory&Research,Trade and Regional Integration

    User journey-driven product management

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    NeSI was facing challenges around user onboarding. We built a journey map for NeSI researchers to gain better understanding of the extent of the problem, and focus on where the biggest issue was. As an organisation, we are striving to be more metric driven, and using this user journey as a reference for the team members to see things from researchers’ perspective.Jun will share the process NeSI went through, along with the user journey and service blueprint that maps the journey to internal processes, how looking at the numbers in the context of the user journey helped us identify problem areas. The process led us to achieve improvements in the account setup process, and have given us a useful reference point to understand what to focus on next.ABOUT THE AUTHOR(S)Jun Huh, Innovation and Growth at NeSI. Jun comes from a start-up background with focus around providing genuine value to the users and steering organisations to be more user driven. </div

    Big Data, Big Libraries, Big Problems?: the 2014 LibTech Anti-talk?

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    The desire to create automatons is a familiar theme in human history, and during the age of the Enlightenment mechanical automatons became not only an “emblem of the cosmos”, but a symbol of man’s confidence that he would unlock nature’s greatest mysteries and fully harness her power. And yet only a century later, automatons had begun to represent human repression and servitude, a theme later picked up by writers of science fiction. Man’s confidence undeterred, the endgame of the modern scientific and technological mindset, or MSTM, seems to be increasingly coming into view with the rise of “information technology” in general and “Big data” in particular. Along with those who wield them, these can be seen as functioning together as a “mechanical muse” of sorts – surprisingly alluring – and, like a physical automaton can serve as a symbol – a microcosm – of what the MSTM sees (at the very least in practice) as the cosmic machine, our “final frontier”. And yet, individuals who unreflectively participate in these things – giving themselves over to them and seeking the powers afforded by the technology apart from technology’s rightful purposes – in fact yield to the same pragmatism and reductionism those wielding them are captive to. Thus, they ultimately nullify themselves philosophically, politically, and economically – their value increasingly being only the data concerning their persons, and its perceived usefulness. Likewise libraries, the time-honored place of, and symbol for, the intellectual flowering of the individual, will, insofar as they spurn the classical liberal arts (with the idea that things are intrinsically good, and in the case of humans, special as well) in favor of the alluring embrace of MSTM-driven “information technology” and Big data - unwittingly contribute to their irrelevance and demise as they find themselves increasingly less needed, valued, wanted. Likewise for the liberal arts as a whole, and in fact history itself, if the acid of a “science” untethered from what is, in fact, good (intrinsically), continues to gain strengt

    Adoption of management innovation: an organizational learning perspective

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    Institutional theorists have generally focused on the role of social and cultural characteristics of the external environment that motivate and facilitate the diffusion of management innovations (MIs). However, most studies have treated innovation as a discrete phenomenon and have not examined the variability of innovation adoption over time. MI, characterized by flexibility, variability, and continuity, necessitates probing into the “Iron Cage” to describe a more complete image of institutional change. Based on insights from the behavioral theory of the firm (Cyert & March, 1963), this dissertation focuses on the dynamic process that determines organizational responses to institutional pressure. It is composed of three studies which deal with the population-level diffusion, individual-level adoption, and field-level isomorphism of MI practices respectively. The empirical setting is the adoption of alternative types of public service delivery in U.S. local governments. Information on service delivery was obtained from the International City/County Management Association’s (ICMA) surveys of local governments’ service delivery choices in 1982, 1987, 1992, 1997, 2002, and 2007. The ICMA data were supplemented by the data from censuses of governments and other sources. The primary method of implementing the New Public Management (NPM) movement has been the use of contractual or cooperative agreements between local governments and private sector businesses or non-profit organizations to deliver public services. Whereas the outsourcing of government services has its advocates and critics, this study posits that accompanying the NPM movement has been an institutional change from traditional to market-driven public management, where conflicting institutional models coexist. This dissertation hopes to make several contributions. First, it depicts how organizational heterogeneity is generated through path dependence, even in dealing with identical institutional change. Second, it provides a more dynamic process of institutional change by borrowing insights from the behavior theory of the firm (Cyert & March, 1963). Third, it offers a new approach to understanding the nature and process of institutional isomorphism. Demonstrating the impact of variability and flexibility pertaining to MI, this dissertation calls for holistic, balanced interpretations and applications of structuralistic, deterministic theories.  Ph. D.Includes bibliographical referencesIncludes vitaby Jun L

    Cult: A Composite Novel

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    Cult (redacted) The first component of the thesis is a composite novel called Cult which falls into two parts with seven narratives in each. Part 1 tracks the protagonist, Ellen, from her first involvement with the cult through to her eventually leaving it. Although fiction, the first half of the book answers the kinds of questions the author is asked when people discover that she was once a sannyasin (a follower of the guru Bhagwan Shree Rajneesh). While the experiences of meditation, group therapy and communal living are all faithfully rendered within the stories, the need for strong characters, narrative drive and a lightness of touch takes precedence. Part 2 picks up Ellen’s story some twenty or so years later and explores what becomes of her in middle age. It also looks at other groups in society, such as academia, the law and the internet dating community which each have their own jargon, hierarchies, rituals and rules but are not considered to be cults. The book examines the question raised in the Epigraph, ‘how do we be together when we feel so alone’ with a focus on relationships other than the familial and the romantic. Collisions, Chasms and Connections: a Performative Exploration of the Composite Novel Form The second part of the thesis is both a critical and creative response to three contemporary American books: Olive Kitteridge by Elizabeth Strout; A Visit from the Goon Squad by Jennifer Egan; and Legend of a Suicide by David Vann. The critical element comprises a close reading of the three books; a chronological reconstruction of their overarching storylines; and a consideration of what their authors have said about writing the books. It concludes that, in the composite novel, the simultaneous presentation of multiple views and storylines operate much like a 3D image to give the impression of depth to the characters and situations rendered. The creative element of the essay is a playful and personal response to the texts
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