Lysophosphatidic acid (LPA) is a lipid mediator with a wide variety of biological actions, particularly as an inducer of cell proliferation, migration and survival. LPA binds to specific G‐protein‐coupled receptors and thereby activates multiple signal transduction pathways, including those initiated by the small GTPases Ras, Rho, and Rac. LPA signaling has been implicated in such diverse processes as wound healing, brain development, vascular remodeling and tumor progression. Knowledge of precisely how and where LPA is produced has long proved elusive. Excitingly, (...) it has recently been discovered that LPA is generated from precursors by ‘autotaxin’, a once enigmatic exo‐phosphodiesterase implicated in tumor cell motility. Exogenous phospholipases D can also produce LPA, which may contribute to their toxicity. Here we review recent progress in our understanding of LPA bioactivity, signaling and synthesis. BioEssays 26:870–881, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Recent findings necessitate revision of the traditional view of G protein‐coupled receptor (GPCR) signaling and expand the diversity of mechanisms by which receptor signaling influences cell behavior in general. GPCRs elicit signals at the plasma membrane and are then rapidly removed from the cell surface by endocytosis. Internalization of GPCRs has long been thought to serve as a mechanism to terminate the production of second messengers such as cAMP. However, recent studies show that internalized GPCRs can continue to either stimulate (...) or inhibit cAMP production in a sustained manner. They do so by remaining associated with their cognate G protein subunit and adenylyl cyclase at endosomal compartments. Once internalized, the GPCRs produce cellular responses distinct from those elicited at the cell surface. (shrink)

Deductivism is not merely a logical technique, but also a theory of normativity: it provides an objective and universal standard of evaluation. Contemporary dialectical logic rejects deductive normativity, replacing its universal standard by an intersubjective standard. It is argued in this paper that dialectical normativity does not improve upon deductive normativity. A dialogico-rhetorical alternative is proposed.

The introduction of novel diagnostic techniques in clinical domains such as genomics and radiology has led to a rich ethical debate on how to handle unsolicited findings that result from these innovations. Yet while unsolicited findings arise in both genomics and radiology, most of the relevant literature to date has tended to focus on only one of these domains. In this article, we synthesize and critically assess similarities and differences between “scanning the body” and “sequencing the genome” from an ethical (...) perspective. After briefly describing the novel diagnostic contexts leading to unsolicited findings, we synthesize and reflect on six core ethical issues that relate to both specialties: terminology; benefits and risks; autonomy; disclosure of unsolicited findings to children; uncertainty; and filters and routine screening. We identify ethical rationales that pertain to both fields and may contribute to more ethically sound policies. Considerations of preserving public trust and ensuring that people perceive healthcare policies as fair also support the need for a combined debate. (shrink)

If climate change represents a severe threat to humankind, why then is response to it characterized by inaction at all levels? The authors argue there are two complementary explanations for the lack of motivation. First, our moral judgment system appears to be unable to identify climate change as an important moral problem and there are pervasive doubts about the agency of individuals. This explanation, however, is incomplete: Individual emitters can effectively be held morally responsible for their luxury emissions. Second, doubts (...) about individual agency have become overly emphasized and fail to convincingly exonerate individuals from responsibility. This book extends the second explanation for the motivational gap, namely that the arguments for the lack of individual agency do in fact correspond to mechanisms of moral disengagement. The use of these mechanisms enables consumption elites to maintain their consumptive lifestyles without having to accept moral responsibility for their luxury emissions. (shrink)

The Random Number Generation task has a long history in neuropsychology as an assessment procedure for executive functioning. In recent years, understanding of human behavior has gradually changed from reflecting a static to a dynamic process and this shift in thinking about behavior gives a new angle to interpret test results. However, this shift also asks for different methods to process random number sequences. The RNG task is suited for applying non-linear methods needed to uncover the underlying dynamics of random (...) number generation. In the current article we present RandseqR: an R-package that combines the calculation of classic randomization measures and Recurrence Quantification Analysis. RandseqR is an easy to use, flexible and fast way to process random number sequences and readies the RNG task for current scientific and clinical use. (shrink)

ion is instrumental for our understanding of how numbers are cognitively represented. We propose that the notion of abstraction becomes testable from within the framework of simulated cognition. We describe mental simulation as embodied, grounded, and situated cognition, and report evidence for number representation at each of these levels of abstraction.

The expression that professionals should be led by their moral or ethical compass is increasingly used by academics, policy makers, professionals, and educational institutes. Dutch universities of applied sciences (UAS), for example, explicitly aim to educate their students to become professionals equipped with a moral compass. This moral or ethical compass is a metaphor of which people intuitively grasp its meaning, but our literature review also shows that various interpretations are possible. We found three clusters of proposed ethical compasses expressing (...) its a) content, b) form, or c) use, which we present in this article. Thereafter, we evaluate which compass can meaningfully assist (young) professionals and, therefore, should be part of the aims and content of education provided by UAS. Based on this evaluation, we describe the possibilities and boundaries of UAS’ contribution to the development of their students’ ethical compass. (shrink)

An English language translation accompanies the original Greek text of Aristotle's book about the nature of the state, constitutions, revolutions, democracy, and oligarchy.

Social epistemologists should be well-equipped to explain and evaluate the growing vulnerabilities associated with filter bubbles, echo chambers, and group polarization in social media. However, almost all social epistemology has been built for social contexts that involve merely a speaker-hearer dyad. Filter bubbles, echo chambers, and group polarization all presuppose much larger and more complex network structures. In this paper, we lay the groundwork for a properly social epistemology that gives the role and structure of networks their due. In particular, (...) we formally define epistemic constructs that quantify the structural epistemic position of each node within an interconnected network. We argue for the epistemic value of a structure that we call the (m,k)-observer. We then present empirical evidence that (m,k)-observers are rare in social media discussions of controversial topics, which suggests that people suffer from serious problems of epistemic vulnerability. We conclude by arguing that social epistemologists and computer scientists should work together to develop minimal interventions that improve the structure of epistemic networks. (shrink)

In this paper, we explain and showcase the promising methodology of testimonial network analysis and visualization for experimental epistemology, arguing that it can be used to gain insights and answer philosophical questions in social epistemology. Our use case is the epistemic community that discusses vaccine safety primarily in English on Twitter. In two studies, we show, using both statistical analysis and exploratory data visualization, that there is almost no neutral or ambivalent discussion of vaccine safety on Twitter. Roughly half the (...) accounts engaging with this topic are pro-vaccine, while the other half are con-vaccine. We also show that these two camps rarely engage with one another, and that the con-vaccine camp has greater epistemic reach and receptivity than the pro-vaccine camp. In light of these findings, we question whether testimonial networks as they are currently constituted on popular fora such as Twitter are living up to their promise of delivering the wisdom of crowds. We conclude by pointing to directions for further research in digital social epistemology. (shrink)

Artificial intelligence (AI) and machine learning (ML) are increasingly integrated into the functioning of physical and digital products, creating unprecedented opportunities for interaction and functionality. However, there is a challenge for designers to ideate within this creative landscape, balancing the possibilities of technology with human interactional concerns. We investigate techniques for exploring and reflecting on the interactional affordances, the unique relational possibilities, and the wider social implications of AI systems. We introduced into an interaction design course (_n_ = 100) nine (...) ‘AI exercises’ that draw on more than human design, responsible AI, and speculative enactment to create experiential engagements around AI interaction design. We find that exercises around metaphors and enactments make questions of training and learning, privacy and consent, autonomy and agency more tangible, and thereby help students be more reflective and responsible on how to design with AI and its complex properties in both their design process and outcomes. (shrink)

Man (Islam); Islamic philosophy; Islamic ethics.

What responsibilities does each of us have to reduce or limit our greenhouse gas emissions? Advocates of individual emissions reductions acknowledge that there are limits to what we can reasonably demand from individuals. Climate ethics has not yet systematically explored those limits. Instead, it has become popular to suggest that such judgements should be ‘context-sensitive’ but this does not tell us what role different contextual factors should play in our moral thinking. The current approach to theory development in climate ethics (...) is not likely to be the most effective way to fill this gap. In existing work, climate ethicists use hypothetical cases to consider what can be reasonably demanded of individuals in particular situations. In contrast, ‘climate ethics with an ethnographic sensibility’ uses qualitative social science methods to collect original data in which real individuals describe their own situations. These real-life cases are more realistic, more detailed and cover a broader range of circumstances than hypothetical cases. Normative analysis of real-life cases can help us to develop a more systematic understanding of the role that different contextual factors should play in determining individual climate responsibilities. It can also help us to avoid the twin dangers of ‘idealization’ and ‘special pleading’. (shrink)

Philosophy; philosophical theology; philosophical anthropology; history.

In this paper, we introduce the Societal Readiness Thinking Tool to aid researchers and innovators in developing research projects with greater responsiveness to societal values, needs, and expectations. The need for societally-focused approaches to research and innovation—complementary to Technology Readiness frameworks—is presented. Insights from responsible research and innovation concepts and practice, organized across critical stages of project-life cycles are discussed with reference to the development of the SR Thinking Tool. The tool is designed to complement not only shortfalls in TR (...) approaches, but also improve upon other efforts to integrate RRI, sustainability, and design thinking in research and innovation cycles. Operationalization and early-stage user tests of the Tool are reported, along with discussion of potential future iterations and applications. (shrink)

al-majmūʻah 1. Kayfa naʻmal lil-Islām -- Muqawwimāt shakhṣīyat al-Muslim -- al-Tawāzun wa-al-iʻtidāl fī ḥayāt al-Muslim.

Epistemologists have not usually had much to say about believing ‘in’, though ever since Plato's time they have been interested in believing ‘that’. Students of religion, on the other hand, have been greatly concerned with belief ‘in’, and many of them, I think, would maintain that it is something quite different from belief ‘that’. Surely belief ‘in’ is an attitude to a person, whether human or divine, while belief ‘that’ is just an attitude to a proposition? Could any difference be (...) more obvious than this? And if we over-look it, shall we not be led into a quite mistaken analysis of religious belief, at any rate if it is religious belief of the theistic sort? On this view belief ‘in’ is not a propositional attitude at all. (shrink)

The book called 'The Consolation of Philosophy' was throughout the Middle Ages, and down to the beginnings of the modern epoch in the sixteenth century, the scholar's familiar companion. Few books have exercised a wider influence in their time. It has been translated into every European tongue, and into English nearly a dozen times, from King Alfred's paraphrase to the translations of Lord Preston, Causton, Ridpath, and Duncan, in the eighteenth century.

Healing Emotions is the record of an extraordinary series of encounters between the Dalai Lama and prominent Western psychologists, physicians, and meditation teachers that sheds new light on the mind-body connection. Edited by Pulitzer Prize nominee and best-selling author Daniel Goleman.

This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact, and remains as true to the original work as possible. Therefore, you will see the original copyright references, library stamps (as most of these works have been housed in our most important libraries around the world), and other notations in the work. This work is in the public domain (...) in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. As a reproduction of a historical artifact, this work may contain missing or blurred pages, poor pictures, errant marks, etc. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

Collected sayings of Muslim Caliphs and saints.