Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

Isolation in the back-country: George Chamier, G.B. Lancaster, Katherine Mansfield, John Mulgan, and Graham Billing -- Outsiders and misfits in fragmented social milieux: William Satchell, Vincent Pyke, John A. Lee, Robin Hyde, Frank Sargeson, and others -- The lonely and the alone in the fiction of Janet Frame -- Maurice Gee and postmodern isolation -- Women, isolation, and history: Fiona Kidman, Noel Hilliard, and Patricia Grace -- Cultural deracination and isolation : Witi Ihimaera, Keri Hulme, and Alan Duff.

In recent years important contributions to the interpretation of the eighth book of Lucan have been made by Professor Postgate , and by Mr.J.D.Duff .The following notes make a further attempt to solve some of the many problems presented by the book.

This essay reviews six different approaches to intellectual property. It and argues that none of these accounts provide an adequate justification of intellectual property laws and policies because (1) there are many different types of intellectual property, and (2) a variety of incommensurable values play a role in the justification of intellectual property. The best approach to intellectual property is to assess and balance competing moral values in light of the particular facts and circumstances.

The phrase “minimal risk,” as defined in the United States’ federal research regulations, is ambiguous and poorly defined. This article argues that most of the ambiguity that one finds in the phrase stems from the “daily life risks” standard in the definition of minimal risk. In this article, the author argues that the daily life risks standard should be dropped and that “minimal risk” should be defined as simply “the probability and magnitude of the harm or discomfort anticipated in research (...) are not greater than those encountered during the performance of routine physical or psychological examinations or tests”. (shrink)

This essay develops a framework for thinking about the moral basis for the commodification of human reproductive materials. It argues that selling and buying gametes and genes is morally acceptable although there should not be a market for zygotes, embryos, or genomes. Also a market in gametes and genes should be regulated in order to address concerns about the adverse social consequences of commodification.

Inappropriate authorship is a common problem in biomedical research and may be becoming one in bioethics, due to the increase in multiple authorship. This paper investigates the authorship policies of bioethics journals to determine whether they provide adequate guidance for researchers who submit articles for publication, which can help deter inappropriate authorship. It was found that 63.3% of bioethics journals provide no guidance on authorship; 36.7% provide guidance on which contributions merit authorship, 23.3% provide guidance on which contributions do not (...) merit authorship, 23.3% require authors to take responsibility for their contributions or for the article as a whole, 20% provide guidance on which contributions merit an acknowledgement but not authorship, 6.7% require authors to describe their contributions, and only 3.3% distinguish between authorship in empirical and conceptual research. To provide authors with effective guidance and promote integrity in bioethics research, bioethics journals should adopt authorship policies that address several important topics, such as the qualifications for authorship, describing authorship contributions, taking responsibility for the research and the difference between authorship in empirical and conceptual research. (shrink)

We construct all cosmic field tensors which are symmetric rank-two tensor concomitants of a metric and a background metric and which have zero divergence when the background metric satisfies the generalized De Donder condition. The resulting background cosmic field represents an Einstein space-time.

This book focuses on the mind and its ability to seek answers to unknown or unanswered questions. The theory of educating provides the grounding for using V diagrams by students, educators, researchers, and parents. Teachers make lesson plans using V diagrams and concept maps. They become expert coaches in guiding student performances. Students learn to construct their own knowledge. They change from question-answerers to question-askers. Parents share meaning with their children and their children's teachers and administrators. Administrators monitor programs and (...) are in touch with all participants in schools and universities. Researchers and evaluators can share records of events and facts. With this theory working in the classrooms and laboratories of many practical places of educating plus extending into the world of technology literacy, The Art of Educating with V Diagrams explains how educating works. (shrink)

Mr. Kubat attributes much of the misinformation about Brentano's theories to the lack of an edition of Brentano's collected writing. If anyone should wish to know more about Brentano's doctrines, he may have been led by this remark to despair of finding them anywhere in print. The three works which Mr. Kubat mentions, Grundlegung und Aufbau der Ethik, Religion und Philosophie, and Die Lehre vom richtigen Urteil, all edited by F. Mayer-Hillebrand and published by A. Francke in Bern, represent no (...) more than a continuation of the Gesamtausgabe of Brentano's writings which was begun by Oskar Kraus and Alfred Kastil after Brentano's death. The volumes in the Gesamtausgabe represent ten numbers in Meiner's Philosophische Bibliothek and are listed under the heading, "Gesammelte philosophische Schriften." They contain not only new editions of much of the work which Brentano published during his lifetime, but a large amount of material which Kraus and Kastil selected from his enormous Nachlass as well. I am sure that Mrs. Mayer-Hillebrand herself would be the first to recognize that the three published volumes she has edited, and the one on esthetics which is soon to appear in print, are part of a whole which also includes the volumes edited by Kraus and Kastil. Taken altogether, the thirteen volumes that have been published by Meiner and by Francke can well be viewed as at least an adequate substitute for a collected edition. Surely they include everything which is necessary to dispel the common misinformation which Mr. Kubat tries to explain by denying their existence. The trouble has not been the lack of a collected edition, but the lack of readers. (shrink)

On the vedantic philosophy of Śaṅkaracarya.

Most of the discussion in bioethics and health policy concerning social responsibility for health has focused on society’s obligation to provide access to healthcare. While ensuring access to healthcare is an important social responsibility, societies can promote health in many other ways, such as through sanitation, pollution control, food and drug safety, health education, disease surveillance, urban planning and occupational health. Greater attention should be paid to strategies for health promotion other than access to healthcare, such as environmental and public (...) health and health research.Lifestyle plays a major role in most of the illnesses in industrialised nations.1 Six of the 10 leading factors contributing to the global burden of disease are lifestyle related: unsafe sex, high blood pressure, tobacco use, alcohol use, high cholesterol and obesity.2 Lifestyle-related illnesses also contribute to the rising costs of healthcare. Spending on healthcare accounts for about 16% of the gross domestic product in the USA, or US$1.9 trillion.3 Although smoking has declined steadily there since the 1960s, smoking-related medical expenses are still about US$75.5 billion per year.4 Obesity, which has been climbing in the past two decades, accounts for about US$75 billion in healthcare costs there each year.5 Alcoholism and drug addiction in the USA account for annual healthcare costs of about US$22.5 billion and US$12 billion, respectively.6,7 Federal government spending on healthcare relating to HIV/AIDS is over US$13 billion per year.8Given the well-documented relationship between lifestyle, disease burden and healthcare costs, it makes economic and medical sense to hold individuals morally responsible for their health-related choices. While this view has a great deal of intuitive appeal, it also faces numerous objections.9–12 First, holding individuals entirely responsible for their own health conflicts with medicine’s obligation to treat the sick and society’s obligation …. (shrink)

Susan Schneider (2019) has proposed two new tests for consciousness in AI (artificial intelligence) systems, the AI Consciousness Test and the Chip Test. On their face, the two tests seem to have the virtue of proving satisfactory to a wide range of consciousness theorists holding divergent theoretical positions, rather than narrowly relying on the truth of any particular theory of consciousness. Unfortunately, both tests are undermined in having an ‘audience problem’: Those theorists with the kind of architectural worries that motivate (...) the need for such tests should, on similar grounds, doubt that the tests establish the existence of genuine consciousness in the AI in question. Nonetheless, the proposed tests constitute progress, as they could find use by some theorists holding fitting views about consciousness and perhaps in conjunction with other tests for AI consciousness. (shrink)

Purpose. The aim of the article is to clarify the content of the concept of culture as an explication of vitality within the philosophy of life and its further modifications in current problems of contemporary. The analysis performed standing from the point, that contrasting of nature and culture is irrelevant, since culture does not contradict natural determinants and patterns, but rather qualitatively alters them. So, are justified the idea of culture as a phenomenon that exist accordingly and in proportion to (...) nature, need to form its potential and content and not contradict the axioms and values of life. Theoretical basis. In the theoretical field of philosophy of life, the local development of the problem of culture as an explication of vitality produces grounds for analytical and prognostic activity concerning meaningful transformations in a separate historical and social horizon. The fundamental categories of culture: spirit, value, symbol, freedom, justice and harmony receive the requested content and meaning. The idea of the constancy and super-naturality of cultural universals is illusory and dangerous. The consequences of such a "non-cosmological" justification of freedom and will, and the assertion of values, that contradict the logic of life, are the global environmental, economic and social crisis of our time. Originality. The originality of the authors’ thought lies in the interpretation of the essence of culture as an explication of vitality, as a logical and natural extension of life. In this formulation of the problem of culture, the possibility of reconciling the natural, social and value determinants of human life is formed. Theorists of the philosophy of life substantiated the primacy and supremacy of the values of life over the values and meanings of culture. The position of authors position consists in the need to understand culture as an environmentally appropriate and dimensional phenomenon, the content and strategies of which are determined by a single ontology. Conclusions. The analysis let authors understand the voluntarily chaotic element of life. Culture in its philosophical analysis took on a clearer anthropomorphic dimension: the immanent logic of being in substantiating the essence and purpose of man and the value of his being localized the universe of transcendence in the concept of "living world", "inhabited space", "human, too human". Accordingly, the range of cultural evaluations has been polarized: from the approving statement of its vital essence, to the disparaging calls for its reform. The chaotic state of voluntarily acts is transformed into cultural codes and stereotypes by rationalization. The modern global nature of crisis phenomena, both in the worldview, in the social, and in the ecological dimension, requires reformatting the understanding of culture as a continuation of nature, and not its antipode. (shrink)