The nm23 gene, a putative metastasis suppressor gene, was originally identified by its reduced expression in highly metastatic K‐1735 murine melanoma cell lines, as compared to related, low metastatic melanoma cell lines. Transfection of nm23 cDNA has been reported to suppress malignant progression in Drosophila and mammalian cells. Highly conserved homologues of nm23 have been found in organisms ranging from the prokaryote Myxococcus xanthus to Drosophila, where the gene is involved in normal development and differentiation. The product of the nm23 (...) gene exhibits a nucleoside diphosphate kinase activity, yet the nucleoside diphosphate kinase activity of Nm23 does not correlate with its apparent biological functions. We review recent cellular, genetic, biochemical and X‐ray crystallographic data to formulate and evaluate hypotheses concerning the molecular mechanism of nm23 action. (shrink)

Despite the prodigious inventiveness of the Middle Ages, the era is often characterized as deeply suspicious of novelty. But if poets and philosophers urged caution about the new, Patricia Clare Ingham contends, their apprehension was less the result of a blind devotion to tradition than a response to radical expansions of possibility in diverse realms of art and science. Discovery and invention provoked moral questions in the Middle Ages, serving as a means to adjudicate the ethics of invention and (...) opening thorny questions of creativity and desire. The Medieval New concentrates on the preoccupation with newness and novelty in literary, scientific, and religious discourses of the twelfth through sixteenth centuries. Examining a range of evidence, from the writings of Roger Bacon and Geoffrey Chaucer to the letters of Christopher Columbus, and attending to histories of children's toys, the man-made marvels of romance, the utopian aims of alchemists, and the definitional precision of the scholastics, Ingham analyzes the ethical ambivalence with which medieval thinkers approached the category of the new. With its broad reconsideration of what the "newfangled" meant in the Middle Ages, The Medieval New offers an alternative to histories that continue to associate the medieval era with conservation rather than with novelty, its benefits and liabilities. Calling into question present-day assumptions about newness, Ingham's study demonstrates the continued relevance of humanistic inquiry in the so-called traditional disciplines of contemporary scholarship. (shrink)

Using the Godel incompleteness result for leverage, Roger Penrose has argued that the mechanism for consciousness involves quantum gravitational phenomena, acting through microtubules in neurons. We show that this hypothesis is implausible. First the Godel result does not imply that human thought is in fact non-algorithmic. Second, whether or not non-algorithmic quantum gravitational phenomena actually exist, and if they did how that could conceivably implicate microtubules, and if microtubules were involved, how that could conceivably implicate consciousness, is entirely speculative. Third, (...) cytoplasmic ions such as calcium and sodium are almost certainly present in the microtubule pore, barring the quantum-mechanical effects Penrose envisages. Finally, physiological evidence indicates that consciousness does not directly depend on microtubule properties in any case, rendering doubtful any theory according to which consciousness is generated in the microtubules. (shrink)

It is a commonplace to observe that we have been living through an extraordinary pan-European and trans-Atlantic populist moment. But do the heterogeneous phenomena lumped under the rubric “populist” in fact belong together? Or is “populism” just a journalistic cliché and political epithet? In the first part of the article, I defend the use of “populism” as an analytic category and the characterization of the last few years as a “populist moment,” and I propose an account of populism as a (...) discursive and stylistic repertoire. In the second part, I specify the structural trends and the conjunctural convergence of a series of crises that jointly explain the clustering in space and time that constitutes the populist moment. The question in my title is thus twofold: it is a question about populism as a term or concept and a question about populism as a phenomenon in the world. The article addresses both the conceptual and the explanatory question, limiting the scope of the explanatory argument to the pan-European and trans-Atlantic populist conjuncture of the last few years. (shrink)

In this paper we consider the use of cases in medical ethics research and teaching. To date, there has been little discussion about the consent or confidentiality requirements that ought to govern the use of cases in these areas. This is in marked contrast to the requirements for consent to publish cases in clinical journals, or to use personal information in research. There are a number of reasons why it might be difficult to obtain consent to use cases in ethics. (...) Many cases concern people who are incompetent, and thus unable to give consent. Often the material is of a sensitive nature, it is not clear who should give consent, or the ethicist has no access to those involved. We argue that the use of cases in ethics research and teaching can be justified by appeal to the public interest argument, and suggest a number of areas for discussion and clarification. (shrink)

Populist protests against Coronavirus-related restrictions in the US appear paradoxical in three respects. Populism is generally hostile to expertise, yet it has flourished at a moment when expertise has seemed more indispensable than ever. Populism thrives on crisis and indeed often depends on fabricating a sense of crisis, yet it has accused mainstream politicians and media of overblowing and even inventing the Corona crisis. Populism, finally, is ordinarily protectionist, yet it has turned anti-protectionist during the pandemic and challenged the allegedly (...) overprotective restrictions of the nanny-state. I address each apparent paradox in turn before speculating in conclusion about how populist distrust of expertise, antipathy to government regulation, and skepticism toward elite overprotectiveness may come together – in the context of intersecting medical, economic, political, and epistemic crises – in a potent and potentially dangerous mix. (shrink)

An international legal agreement governing the global antimicrobial commons would represent the strongest commitment mechanism for achieving collective action on antimicrobial resistance (AMR). Since AMR has important similarities to climate change—both are common pool resource challenges that require massive, long-term political commitments—the first article in this special issue draws lessons from various climate agreements that could be applicable for developing a grand bargain on AMR. We consider the similarities and differences between the Paris Climate Agreement and current governance structures for (...) AMR, and identify the merits and challenges associated with different international forums for developing a long-term international agreement on AMR. To be effective, fair, and feasible, an enduring legal agreement on AMR will require a combination of universal, differentiated, and individualized requirements, nationally determined contributions that are regularly reviewed and ratcheted up in level of ambition, a regular independent scientific stocktake to support evidence informed policymaking, and a concrete global goal to rally support. (shrink)

Digital hyperconnectivity is a defining fact of our time. In addition to recasting social interaction, culture, economics, and politics, it has profoundly transformed the self. It has created new ways of being and constructing a self, but also new ways of being constructed as a self from the outside, new ways of being configured, represented, and governed as a self by sociotechnical systems. Rather than analyze theories of the self, I focus on practices of the self, using this expression in (...) a looser, more general sense than that used by Foucault. I begin by considering and reformulating two early lines of argument about the web as a medium for exploring and emancipating the self. Subsequent sections show how digital hyperconnectivity has engendered new ways of objectifying, quantifying, producing, and regulating the self—considered both as active, reflexive practices and as systemic, data- and algorithm-driven processes. I conclude by reflecting on the broader implications of contemporary modes of governing the self and by underscoring the ways in which hyperconnectivity has colonized the territories of the self, conscripting the self into the service of techno-social systems. (shrink)

This paper argues that, in addition to humanitarian concerns, policies toward immigrants should also be shaped by recognition of special responsibilities toward some populations of noncitizens. National governments acquire such responsibilities in part through their histories of coercive impositions on those populations. Former imperial powers, in particular, often possess special obligations toward the inhabitants of their foreign colonies that go beyond their general humanitarian responsibilities. Those obligations might be met in various ways; but if national governments of wealthy, formerly imperial (...) states granted greater access for immigration to the poor of their former colonies, migration flows might significantly contribute to reductions in global levels of inequality. (shrink)

Antimicrobial resistance (AMR) is an urgent threat to global public health and development. Mitigating this threat requires substantial short-term action on key AMR priorities. While international legal agreements are the strongest mechanism for ensuring collaboration among countries, negotiating new international agreements can be a slow process. In the second article in this special issue, we consider whether harnessing existing international legal agreements offers an opportunity to increase collective action on AMR goals in the short-term. We highlight ten AMR priorities and (...) several strategies for achieving these goals using existing “legal hooks” that draw on elements of international environmental, trade and health laws governing related matters that could be used as they exist or revised to include AMR. We also consider the institutional mandates of international authorities to highlight areas where additional steps could be taken on AMR without constitutional changes. Overall, we identify 37 possible mechanisms to strengthen AMR governance using the International Health Regulations, the Agreement on the Application of Sanitary and Phytosanitary Measures, the Agreement on Trade-Related Aspects of Intellectual Property Rights, the Agreement on Technical Barriers to Trade, the International Convention on the Harmonized Commodity Description and Coding System, and the Basel, Rotterdam, and Stockholm conventions. Although we identify many shorter-term opportunities for addressing AMR using existing legal hooks, none of these options are capable of comprehensively addressing all global governance challenges related to AMR, such that they should be pursued simultaneously with longer-term approaches including a dedicated international legal agreement on AMR. (shrink)

Americans have always been divided over whether to welcome or to discourage immigration. But virtually all American leaders have rested their views on notions that the United States has unique providential or world-historical significance-as an asylum for the world's oppressed, as a model to the world, or even as the world's leader. Today, it is normatively desirable for the U.S. to view itself not as the world's "city on a hill" but simply as one worthy political society among many others. (...) Whether such a view can be made politically appealing to most Americans, however, remains in doubt. (shrink)

ABSTRACT Few denials of tolerance are more severe than rejection of the moral worth of another’s way of life. In the U.S. today, many traditional religious believers, especially fundamentalist Christians, and many LGBQT+ persons see each other’s ways of life as deeply evil in important respects. These gulfs probably cannot be bridged; but public policies can and should seek to accommodate all claims of conscience as far as this can be done without denying anyone meaningful possession of basic rights. By (...) placing religious and moral consciences equally in a constitutionally “preferred position,” governments can foster a wider sense that citizens are engaged in a shared enterprise of helping everyone to pursue their distinctive forms of happiness. (shrink)

If within the borders of human life the truth is, as Vico has said, what is made, then the task of a student of human life can be and should be to find out from what human beings have made what manner of makers they are and what sorts of production their circumstance allows.

This paper takes a critical look at the rise of the practice of philosophy in the market place in late modernity. Two main forms of such practice are identified: the practice of Socratic Dialogue in small groups in organisations and one-to-one philosophical counselling of individual 'clients'. The relevance of professionalism for commercialised applied practical philosophy is discussed. Philosophical counsellors in particular may be at risk of engaging with vulnerable individuals who are in need of protection from practitioners who are not (...) trained to deal with their problems. Psychology is the discipline which is most related to practical philosophy and it is growing in ethical awareness. This paper emphasises the importance of ethics for philosophy in practice. There is a pressing need for eternal vigilance by practitioners from such disciplines, whether professionalised or not, in the complex modern'runaway world'. (shrink)

This paper takes a critical look at the rise of the practice of philosophy in the market place in late modernity. Two main forms of such practice are identified: the practice of Socratic Dialogue in small groups in organisations and one-to-one philosophical counselling of individual 'clients'. The relevance of professionalism for commercialised applied practical philosophy is discussed. Philosophical counsellors in particular may be at risk of engaging with vulnerable individuals who are in need of protection from practitioners who are not (...) trained to deal with their problems. Psychology is the discipline which is most related to practical philosophy and it is growing in ethical awareness. This paper emphasises the importance of ethics for philosophy in practice. There is a pressing need for eternal vigilance by practitioners from such disciplines, whether professionalised or not, in the complex modern'runaway world'. (shrink)